Methicillin-resistant Staphylococcus aureus (MRSA) infections, in particular biofilm-organized bacteria, remain a clinical challenge and a serious health problem. Rifabutin (RFB), an antibiotic of the rifamycins class, has shown in previous work excellent anti-staphylococcal activity. Here, we proposed to load RFB in liposomes aiming to promote the accumulation of RFB at infected sites and consequently enhancing the therapeutic potency. Two clinical isolates of MRSA, MRSA-C1 and MRSA-C2, were used to test the developed formulations, as well as the positive control, vancomycin (VCM). RFB in free and liposomal forms displayed high antibacterial activity, with minimal inhibitory concentrations (MIC) ranging from 0.009-0.013 μg/mL and MBIC50 values ranging from 0.008-0.012 μg/mL, in planktonic and biofilm bacteria, respectively. Confocal microscopy studies demonstrated the rapid internalization of unloaded and RFB-loaded liposomes in the bacterial biofilm matrix. In murine models of systemic MRSA-C1 infection, Balb/c mice were treated with RFB formulations and VCM at 20 and 40 mg/kg of body weight, respectively. Obtained data proved the superior therapeutic effectiveness of RFB formulations compared to Control and VCM groups even using a two-fold lower therapeutic dose as demonstrated by significantly reduced bacterial burden and growth index values in major organs. In addition, RFB formulations were the only formulations associated with 100% survival. Globally, this study emphasizes the potential of RFB nanoformulations as an effective and safe approach against MRSA infections.

Antimicrobial resistance (AMR) is a worsening global health crisis that has arisen due to antibiotic overuse and misuse. Antibiotic resistance renders standard treatments less effective, making it difficult to control some infections, thereby increasing morbidity and mortality. Medicinal plants are sustainable treatment options that are becoming increasingly important as antibiotics lose their efficacies. The present study evaluates the antibacterial activity of aqueous, methanolic and ethyl acetate extracts prepared using Terminalia bellirica and Terminalia chebula fruit against six bacterial pathogens using disc diffusion and broth microdilution assays. The aqueous and methanol extracts of T. bellirica and T. chebula showed substantial zones of inhibition (ZOIs) against S. aureus and MRSA. The activity against those bacteria was determined to be strong, with minimum inhibitory concentrations (MIC) ranging from 94 µg/mL to 392 µg/mL. Additionally, the T. bellirica methanolic extract showed noteworthy antibacterial activity against E. coli and an ESBL E. coli strain (MIC values of 755 µg/mL for both). The aqueous T. bellirica and T. chebula extracts also inhibited K. pneumoniae growth (MIC values of 784 µg/mL and 556 µg/mL respectively), whilst the methanolic extracts of these plants also inhibited ESBL K. pneumoniae growth (MIC values of 755 µg/mL and 1509 µg/mL respectively). Eighteen additive interactions were observed when extracts were combined with reference antibiotics. Notably, strong antagonistic interactions occurred when any of the extracts were mixed with polymyxin B. All extracts were subjected to LC-MS analysis, revealing several interesting flavonoids and tannins, including 6-galloylglucose, 1,2,6-trigalloyl-β-D-glucopyranose, 6-O-[(2E)-3-phenyl-2-propenoyl]-1-O-(3,4,5-trihydroxybenzoyl)-β-D-glucopyranose, propyl gallate, methyl gallate, sanguiin H4, hamamelitannin, pyrogallol, gallic acid, ellagic acid, chebulic acid, and chebuloside II. All extracts were nontoxic when tested in brine shrimp assays. This lack of toxicity, combined with their antibacterial activities suggests that these plant species may be promising sources of antibacterial compound(s) that warrant further study.

Medicinal activities carried out within hospitals lead to a high consumption of antibiotics and subsequently result in a high excretion rate of antibiotic residues. These antibiotics consumed in human medicine are not fully absorbed by the body and are often discharged into the environment as biological waste from infected human patients. The significant water consumption in hospitals and the pharmaceutical impact on wastewater from healthcare facilities facilitate the emergence and spread of antibiotic-resistant bacteria and antibiotic-resistant genes in the environment. Hospital effluents could be doubly involved in the dissemination of antibiotic molecules and multidrug-resistant bacteria in various ecosystems. The objective of this study is to characterize hospital effluents by assessing antibiotic concentrations and the diversity of antibiotic-resistant bacteria in these hospital wastewaters and within the environment (aquatic environments; rivers), as well as to inventory the bacteria present and those carrying antibiotic resistance in both hospital wastewater and the environment.

This study aimed to isolate, identify enteric bacterial species from the migratory seagulls migrated to Libyan cost and to assess the antibiotic resistance of these bacteria. A total of 50 fecal samples were collected from slender-billed gulls in January, 2023 at Farwa Island near the city of Zwara. Bacteria were isolated by conventional culturing method, identified by using the Enterosystem 18R, and antibiotic susceptibility testing was conducted on the isolated bacteria. Only 32 of 46 bacteria were identified using biochemical tests. These identified bacteria belong to six species of Enterobacteriacae namely Citrobacter freundii, Pantoea agglomerans, E. coli, Enterobacter cloacae, Serratia liquifaciens, and Proteus mirabilis, with percentages of (17) 53.125%, (10) 31.25%, (2) 6.25%, (1) 3.125%, (1) 3.125%, and (1) 3.125%, respectively. All isolated bacterial species in this study were 100% sensitive to gentamicin and ciprofloxacin. The highest resistance rate was observed against the antibiotic cefoxitin. The results indicated that C. freundii was the most antibiotic-resistant bacterial species isolated in this study. In conclusion, slender-billed gulls carry multi-drug resistant bacteria. The study recommends implementation of a national program to survey antibiotic-resistant bacteria and expanding scientific research on migratory birds.

(1) Background: Health Care-Associated Infections (HAIs)are a significant public health problem worldwide favoring multidrug-resistant (MDR) microorganisms. The SARS-CoV-2 infection had a negative association with the increase in antimicrobial resistance, and the ESKAPE group had the most significant impact on HAIs. The study aimed to evaluate the bactericidal effect of high concentration O3 gas on some reference and ESKAPE bacteria. (2) Material and Methods: Four standard strains and four clinical or environmental MDR strains were exposed to high ozone doses at different concentrations and times. Bacterial inactivation (growth and cultivability) was investigated using colony counts and resazurin as a metabolic indicator. Scanning electron microscopy (SEM) was performed. (3) Results: The culture exposure to a high level of O3 inhibited the growth of all bacterial strains tested with a statistically significant reduction in colony count compared to the control group. The cell viability of S. aureus (MRSA) (99,6%) and P. aeruginosa (XDR) (29,2%) was reduced considerably, and SEM showed damage on bacteria after O3 treatment (4) Conclusion: High doses of ozone were able to interfere in the growth of all strains studied, evidencing that ozone-based decontamination approaches may represent the future of hospital cleaning methods.

Antibiotics are released into the environment either directly in an unchanged form or in a partially metabolized form. The discharge is usually through untreated waste or industrial treatment effluents. The potential concern is the uptake of these antibiotics by crops irrigated by treated wastewater. This study collected wastewater from eight points at the Pagla, Kadamtali, Dhaka treatment plant. Here we consider three crucial antibiotics, Doxycycline, Ciprofloxacin, and Tetracycline, used mainly during the last two years of the pandemic. A PDA detector was used in high-performance liquid chromatography (HPLC) analysis to determine the raw and processed effluent antibiotics. The most frequently seen antibiotics in natural wastewater were Doxycycline and Ciprofloxacin, with the highest concentration of 0.23µgL-1and 0.20 µgL-1(raw water), respectively. Tetracycline was not detected in natural water. Contrarily, Doxycycline was discovered in the Pagla plant's completed water and had the highest concentration (0.12 gL-1), whereas Ciprofloxacin and Tetracycline were not found in the dead water. The findings of this study showed that Doxycycline was still present in both the raw and processed effluent. Both natural and finished wastewater was subjected to a microbial-resistant test in the presence of all three antibiotics. The results revealed that the samples detected both heterotrophic bacteria and total coliform. The viable aerobic heterotrophic bacteria ranged between 5.421 and 4.754 log cfu/ml. Total bacteria load gradually decreased in the finished wastewater.

Bacterial resistance to antibiotics is a growing global concern, threatening human and environ-mental health, particularly among urban populations. Wastewater treatment plants (WWTPs) are thought to be “hotspots” for antibiotic resistance dissemination. The conditions of WWTPs, in conjunction with the persistence of commonly used antibiotics, may favor the selection and trans-fer of resistance genes among bacterial populations. WWTPs provide an important ecological niche to examine the spread of antibiotic resistance. We used heterotrophic plate count methods to identify phenotypically resistant cultivable portions of these bacterial communities and charac-terized the composition of the culturable subset of these populations. Resistant taxa were more abundant in raw sewage and wastewater before the biological aeration treatment stage. While some antibiotic resistant bacteria (ARB) were detectable downstream of treated wastewater re-lease, these organisms are not enriched relative to effluent-free upstream water, indicating effi-cient removal during treatment. Combined culture-dependent and culture-independent analyses revealed a stark difference in community composition between culturable fractions and the envi-ronmental source material, irrespective of culturing conditions. Higher proportions of the envi-ronmental populations were recovered than predicted by the widely accepted 1% culturability paradigm. These results represent baseline abundance and compositional data for ARB commu-nities for reference in future studies addressing the dissemination of antibiotic resistance associ-ated with urban wastewater treatment ecosystems.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. In this narrative review we focused the antibiotic treatment of CRAB infections in view of newly β-lactam agents (NBLs) like sulbactam/durlobactam and cefiderocol, discussing the main hot points such as the superiority of combination treatment over monotherapy and the best antibiotic partner to use in combination. Sulbactam/durlobactam seems to be the best candi-date to replace current back-bone agents. Cefiderocol, could play a crucial role in combina-tion-regimen. Due to toxicity and the PK/PD limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the ef-ficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with lung im-proved activity, as well as on the i.v. rifabutin formulation.

Background: Most drug-resistant Escherichia coli isolates in dogs come from diseased dogs. Prior to this study, the prevalence and risk factors of fecal carriage drug-resistant E. coli and epidemic clone sequence type (ST) 131 (including subtypes) isolates in dogs were unknown. Methods: Rectal swabs were used for E. coli isolation from 299 dogs in a veterinary teaching hospital in Taiwan. Antibiotic resistance and multiplex PCR analyses of E. coli for major STs were performed. Result: There were 43.1% cefazolin-resistant, 22.1% fluoroquinolone-resistant, and 9.4% extended-spectrum beta-lactamase-producing E. coli in our cohort. In the phylogenetic study, B2 was the predominant group (30.1%). The cefazolin-resistant group and ciprofloxacin-resistant group had greater antibiotic exposure in the last 14 days (P < 0.05). The age, sex, and dietary habits of the antibiotic-resistant and -susceptible groups were similar. In the seven isolates of ST131 in fecal colonization, the most predominant subtypes were FimH41 and FimH22. Conclusion: Recent antibiotic exposure was related to the fecal carriage of antibiotic-resistant E. coli isolates. Three major subtypes (FimH41, H22, and H30) of ST131 can thus be found in fecal carriage in dogs in Taiwan.

The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, which is one of the most common skin diseases. Acne vulgaris often associates with acne-related bacteria such as <i>Propionibacterium acnes</i>, <i>Staphylococcus epidermidis</i>, <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>, some of which exhibit a resistant against commercial antibiotics used in the treatment of acne vulgaris (tetracycline, erythromycin, and lincomycin). In the current study, we evaluated <i>in vitro</i> antibacterial activity of chitosan-phytochemical conjugates against acne-related bacteria. Three of chitosan-phytochemical conjugates used in this study showed stronger antibacterial activity than that of chitosan (unmodified control). Chitosan-caffeic acid conjugate (CCA) exhibited the highest antibacterial activity against acne-related bacteria with minimum inhibitory concentration values of 8 μg/mL to 256 μg/mL. In addition, the MICs of antibiotics against antibiotic resistant <i>P. acnes</i> and <i>P. aeruginosa</i> strains were dramatically reduced in the combination with CCA, suggesting that CCA would restore the antibacterial activity of the antibiotics. The analysis of fractional inhibitory concentration indices clearly revealed a synergistic antibacterial effect between CCA and the antibiotics. Thus, the median ∑FIC values against the antibiotic resistant bacterial strains were ranged from 0.375 to 0.533 in the combination mode of CCA and antibiotics.

Developing new antibiotics poses a significant challenge in the fight against antimicrobial resistance (AMR), a critical global health threat responsible for approximately 5 million deaths annually. Finding new classes of antibiotics that are safe, have acceptable pharmacokinetic properties, and are appropriately active against pathogens is a lengthy and expensive process. Therefore, high-throughput platforms are needed to screen large libraries of synthetic and natural compounds. In this review, we present bacterial cytological profiling (BCP) as a rapid, scalable, and cost-effective method for identifying the mechanisms of action of antibiotics, offering a promising tool for combating AMR and drug discovery. We present the application of BCP for different bacterial organisms and different classes of antibiotics and discuss BCP's advantages, limitations, and potential improvements. Furthermore, we highlight the studies that have utilized BCP to investigate pathogens listed in the Bacterial Priority Pathogens List 2024 and we identify the pathogens whose cytological profiles are missing. Lastly, we explore the most recent artificial intelligence and deep learning techniques that could enhance the analysis of data generated by BCP, potentially advancing our understanding of antibiotic resistance mechanisms and the discovery of novel druggable pathways.

In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associate with the use of small molecule antibiotics and AMPs is the combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review is intended to cover and critically analyze the design, synthetic strategies, antibacterial activity and, when possible, the cytotoxicity of antibiotic-AMPs conjugates.

Skin wounds and their infections by antibiotic resistant bacteria (ARB)are very common in small animals, posing the risk of acquiring ARB by pet owners or antibiotic resistance gene (ARG) transfer to the owners’ microbiota. The aim of this study was to identify the most common pathogens infecting wounds of companion animals, assess their antibiotic resistance and determine the ARGs using culture-based, molecular and proteomic methods. A total of 136 bacterial strains were isolated from wound swabs. Their species was identified using chromogenic media, followed by MALDI-TOF spectrometry. Disk diffusion was used to test the antibiotic resistance and twelve ARGs were detected using PCRs. The dominant species included Staphylococcus pseudintermedius (9.56%), E. coli and E. faecalis (both n=11, 8.09%). Enterobacterales were mostly resistant to amoxicillin/clavulanic acid (68.3% strains), all Pseudomonas were resistant to ceftazidime, piperacillin/tazobactam, imipenem and tylosin, Acinetobacter was mostly resistant to tylosin (55.5%), all Enterococcus were resistant to imipenem, 39.2% of Staphylococci were resistant to clindamycin. Among ARGs, strA (streptomycin resistance), sul3 (sulfonamide resistance) and blaTEM, an ESBL determinant, were the most frequent. The risk of ARB and ARD transfer between animals and humans causes the need to search for new antimicrobial therapies in the future veterinary medicine.

Nocardia is an emerging bacterial disease that often affects patients with compromised immune systems. As survival increases, more and more patients are receiving solid organ transplantations, and more patients are cancer survivors and receiving long-term immune system modifying agents or corticotherapy and immunosuppressive agents, organisms that are not harmful in usual circumstances become a public health problem. Carbapenems are usually a second-line therapy in the setting of Nocardia infections. We present the case of a patient who had an immunocompromised status and was diagnosed with Nocardia farcinica, which showed in vitro resistance to carbapenems. The symptoms were non-specific and had a common presentation, although the infection was disseminated and had severe CNS and ocular involvement. The clinical course was more severe when the carbapenem was withdrawn based on the provided antibiogram and markedly improved when clinical judgment considered it might be beneficial. The first case in our region to describe an „in vitro” carbapenem-resistant Nocardia species, that responded „in vivo” differently and we believe it is important to remind clinicians of this potentially severe disease in difficult cases.

Copper-containing materials are attracting attention as self-desinfecting surfaces, suitable for helping healthcare settings in reducing healthcare associated infections. However, the impact of repeated exposure to disinfectants frequently used in biocleaning protocols on their antibacterial activity remains insufficiently characterized. This study aimed at evaluating the antibacterial effi-ciency of copper (positive control), a brass alloy (AB+®) and stainless steel (negative control) after repeated exposure to a quaternary ammonium compound and/or a mix of peracetic acid/hydrogen peroxide routinely used in healthcare settings. A panel of 6 antibiotic-resistant strains (clinical isolates) was selected for this assessment. After a short (5 min) exposure time, the copper and brass materials retained significantly better antibacterial efficiencies than stainless steel, whatever the bacterial strain or disinfectant treatment considered. Moreover, post-treatment with both disinfectant products, copper-containing materials still reached similar levels of antibacterial efficiency as those obtained before treatment. Antibiotic resistance mechanisms such as efflux pump overexpression did not impair the antibacterial efficiency of copper-containing materials, neither did the presence of one or several genes related to copper homeostasis/resistance. In light of those results, surfaces made out of copper and brass remain interesting tools in the fight against dissemination of antibiotic-resistant strains that might cause healthcare associated infections.

Acid stress poses a common challenge for bacteria in diverse environments by the presence of inorganic (e.g., mammals’ stomach) or organic acids (e.g., feed additives; acid-based disinfectants). Limited knowledge exists regarding acid-tolerant strains of specific serotypes, clonal lineages, or sources in human/animal pathogens, namely non-typhoidal Salmonella enterica (NTS) and Enterococcus faecium (Efm). This study evaluated acidic pH and peracetic acid (PAA) susceptibility of Efm (n=72) and NTS (n=60) from diverse epidemiological/genetic backgrounds, and with multiple antibiotic resistance profiles. Efm minimum growth/survival-pH was 4,5-5/3-4 and for NTS 4,0-4,5/3,5-4,0. Among Efm, only those of clade-non-A1 (non-hospital associated) or food chain demonstrated greater tolerance to acidic pH compared to clade-A1 (hospital-associated clones) or clinical isolates (P<0.05). MDR (multidrug-resistant) NTS survived better to acidic pH (P<0.05). The MICPAA/MBCPAA was 70-120/80-150mg/L for Efm and 50-70/60-100mg/L for NTS. Efm-clade-A1 or MDR strains exhibited higher PAA tolerance than clade-non-A1 or non-MDR ones (P<0.05). Higher tolerance was found in non-MDR and clinical NTS than in food chain isolates (P<0.05), but not between different serogroups. This unique study identifies specific NTS or Efm populations more tolerant to acidic pH or PAA, emphasizing the need for further research to tailor control measures of public health and food safety within a One Health framework.

Developing countries are confronted with general issues of municipal wastewater management and treatment. Untreated faecal sludges and wastewaters from septic tanks and traditional toilet are rejected into rivers and sometimes using for urban agriculture without any treatment to reduce the biorisk. Consequently, there are potential environmental and public health risks. In this study, a wastewater treatment plant prototype coupled with Moringa Oleifera seeds treatment was developed to evaluate their effectiveness for the reduction of faecal indicator bacteria and antibiotics resistant bacteria in domestic wastewater. Results indicate that our performed prototype system presents high capacity to reduce bacteria with abatements up to 99.34%. High reductions of bacteria load were obtained after add of Moringa Oleifera seeds into waters, with reductions varied from 36.6-78.8% for E. coli, 28.3-84.6% for Faecal coliform, 35.3-95.6% for Vibrio cholerae and 32.1-92.4% for total flora. Same effects of Moringa Oleifera seeds were noted for reducing antibiotic resistant bacteria, Extended Spectrum Beta-lactamases and Carbapenem-Resistant Enterobacteriaceae with abatements up to 98% for E. coli and faecal coliform, 100% for Vibrio cholerae and 91.96% for total flora. Our results supported high capacity of Moringa Oleifera seeds as an excellent alternative for pathogens and antibiotics resistant bacteria reduction/purification from domestic wastewater

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

The COVID-19 pandemic has underscored the intricate interplay between viral infections and opportunistic bacterial pathogens such as Klebsiella pneumoniae. K. pneumoniae harbors various antibiotic resistance determinants like extended-spectrum and plasmid-mediated AmpC β-lactamases and carbapenemases. In the two years following the pandemic, carbapenemase producing K. pneumoniae isolates obtained routinely in outpatient and inpatient setting demonstrated similar resistance patterns which prompted research. The aim was to compare and subsequently analyze carbapenem-resistant hospital and outpatient’s K. pneumoniae isolates’ resistance mechanisms, traits and molecular epidemiology, following the COVID-19 pandemic. Disk diffusion and broth dilution method were the methods of choice to determine antibiotic susceptibility. β-lactamases were screened by phenotypic methods and confirmed with PCR. In total 113 isolates were analysed. Resistance to amoxicillin-clavulanate and ertapenem was confirmed in all strains. High resistance rates (over 90%) were observed for extended-spectrum cephalosporins, and ciprofloxacin. OKNV testing and PCR detected OXA-48 in 106, NDM in 7 and KPC in only one isolate. ESBLs accompanied carbapenemases in 103 isolates. Carbapenem resistance in K. pneumoniae is becoming a global problem, hence careful monitoring of its resistance traits is of utmost importance in order to combat the arising threat. OXA-48 seems to continue predominating in the turbulent period after pandemic.

Acetic acid bacteria (AAB) are major contributors to the production of fermented vinegar, offering various cultural, culinary, and health benefits. Although the residual unpasteurized AAB after vinegar production are not pathogens, these are necessary the safety evaluations including antibiotic resistance for the use as starters. In this research, we investigated the antibiotics resistance profiles of 26 AAB strains, including various species of Komagataeibacter and Acetobacter, against ten different antibiotics using the E-test method. All strains exhibited resistance to aztreonam and clindamycin. Komagataeibacter species demonstrated a 50% resistance rate to ciprofloxacin, analogous to Acetobacter species, but showed twice the resistance rates to chloramphenicol and erythromycin. Genomic analysis of K. saccharivorans CV1 identified intrinsic resistance mechanisms, such as multidrug efflux pumps, thereby enhancing our understanding of antibiotic resistance in acetic acid-producing bacteria. These findings enhance understanding of antibiotic resistance in AAB for food safety and new antimicrobial strategies, suggesting the need for standardized testing methods and molecular genetic study.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as the Broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml. In contrast, it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. The maximum concentration was 7-8 mcg/ ml at a maximum time of 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the bactericidal antibiotic Myxopyronin A production from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

The emergence of antimicrobial resistance have represented a serious threats for public health and infections due to multidrug-resistant (MDR) microorganisms represent one of the most important causes of death worldwide. The renew of old antimicrobials, such as colistin, have been proposed as valuable therapeutic alternative to the emergence of the MDR microorganisms. Although colistin is well known to presents several adverse toxic effect, its usage in clinical practice have been reconsidered due to the broad spectrum of activity to gram-negative (GN) bacteria and to the important role of “last resort” agent against MDR-GN. Despite the revolutionary prospective of treatment of this old antimicrobial molecule, many questions remain open regarding the emergence of novel phenotypic traits of resistance and the optimal usage of the colistin in clinical practice. In the last years, several forward steps have been done in the understanding of resistance determinants, clinical usage and pharmacological dosage of this molecule, however, different points regarding the role of colistin in clinical practice and the optimal pharmacokinetic/pharmacodynamic targets are not well defined yet. In this review, we summarize the mode of action, the emerging resistance determinants and its optimal administration in the treatment of difficult-to-treat infections due to MDR Gram-negative bacteria.

Background: Across the world, antibiotic resistance is a critical challenge. To address such a problem, it has to be done to investigate new antibiotic sources. Aim of the study: Study of the antibacterial activity of Corallopyronin A in preclinical animal testing and randomized human clinical trials stages 1/2, as well as investigating the purification of Corallopyronin A from different soil conditions in Egypt. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were tested to develop bacterial isolates that produced the antibiotic compound Corallopyronin A. Reversed phase HPLC was used to purify Myxopyronin A. The broth microdilution method and the paper disc diffusion assay determined the test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in phases 1/2 of randomized clinical studies involving humans and animal models. Results: Corallopyronin A was generated from the culture supernatant of the soil bacterial isolate Corallococcus coralloides M2, cultivated on a Casein yeast peptone( CYP) plate. The test antibiotic prevented the growth of several Gram-ve bacteria, including Escherichia coli, at MICs higher than 100 mcg/ ml; while blocking the development of many Gram +ve bacteria, with MICs ranging from 3 to 15 mcg/ ml. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. A bactericidal consequence of the test antibiotic was detected in the inhibition of prokaryotic DNA-dependent RNA polymerase( RNLP). Conclusion: The synthesis of the bactericidal antibiotic Corallopyronin A from Corallococcus coralloides M2 isolated from different soil settings in Egypt intrigued the current investigation.

Background: Across the world, antibiotic resistance is a critical challenge. To address such a problem, it has to be done to investigate new antibiotic sources. Aim of the study: Study of the antibacterial activity of Corallopyronin A in preclinical animal testing and randomized human clinical trials stages 1/2, as well as investigating the purification of Corallopyronin A from different soil conditions in Egypt. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were tested to develop bacterial isolates that produced the antibiotic compound Corallopyronin A. Reversed phase HPLC was used to purify Myxopyronin A. The broth microdilution method and the paper disc diffusion assay determined the test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in phases 1/2 of randomized clinical studies involving humans and animal models. Results: Corallopyronin A was generated from the culture supernatant of the soil bacterial isolate Corallococcus coralloides M2, cultivated on a Casein yeast peptone( CYP) plate. The test antibiotic prevented the growth of several Gram-ve bacteria, including Escherichia coli, at MICs higher than 100 mcg/ ml; while blocking the development of many Gram +ve bacteria, with MICs ranging from 3 to 15 mcg/ ml. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. A bactericidal consequence of the test antibiotic was detected in the inhibition of prokaryotic DNA-dependent RNA polymerase( RNLP). Conclusion: The synthesis of the bactericidal antibiotic Corallopyronin A from Corallococcus coralloides M2 isolated from different soil settings in Egypt intrigued the current investigation.

Fires constitute a significant threat due to the pollutants emitted and the destruction they cause. People who take part in fire-fighting operations must be equipped with appropriate tools, including special clothing that will allow them to work and guarantee safety. One of the threats are compounds from the PAH group, which are characterized by high toxicity and carcinogenicity. Therefore, it is important that the materials used constitute a barrier to contamination. Various materials from which individual elements of special firefighter's clothing are made were tested. Additionally, the importance of height on the possibility of sorption of PAH compounds on a given type of material was analyzed. Based on the results obtained, it was found that the type of material and the zone in which the clothing items are used are important in the sorption processes of pollutants. Data in this area may be important for taking further actions regarding the modification of materials used in special fire brigade clothing and in their cleaning processes.

The first half of the 20th century was noteworthy for the introduction of a unique group of drugs – antibiotics. It drastically changed concepts of infectious diseases treatment, which for centuries remained a scourge of the human population. With improvement of the antibiotic treatment efficacy, humanity has faced the problem of a dramatic increase in antibiotic resistance in bacteria. The COVID-19 pandemic has only exacerbated the problem and posed a new challenge to the medical community in finding solutions, both clinical and organizational and methodological, to fight antibiotic resistance widespread all over the globe. This publication covers some aspects of evolutionary processes in either pathogens or diseases, including ethical perspective.

The global usage of veterinary antibiotics is significant. These antibiotics can be released into the aquatic environment and exert toxic effects on non-target organisms. To explore the physiological effects of tetracycline antibiotics on aquatic life, the growth characteristics of and toxin release from the cyanobacterium Microcystis aeruginosa (M. aeruginosa) were studied. Results showed that the toxicity order of the three target antibiotics was TC (tetracycline) > CTC (chlortetracycline hydrochloride) > OTC (oxytetracycline) in terms of inhibition occurrence time and the EC₁₀ and EC₂₅ values. Further, the target antibiotics regulated the production of MC-LR (microcystin-LR) to different degrees. CTC destroyed the M. aeruginosa cells and resulted in a decreased MC-LR release but stimulated the ability to synthesise MC-LR. OTC had a relatively weaker toxicity compared with CTC, while TC was the most toxic among the three antibiotics. Therefore, TC is friendly to the aquatic environment because it simultaneously reduced the intracellular and extracellular MC-LR content. These results aid our understanding of the effects of tetracycline antibiotics on Microcystis aeruginosa, which is important for environmental evaluation and protection. These results are also helpful for guiding the application of veterinary antibiotics in agricultural settings.

This study aimed to evaluate if the change of vehicle for CTZ (chloramphenicol, tetracycline, zinc oxide, and eugenol) paste improves the inhibition of Enterococcus faecalis in vitro. The vehicles evaluated alone and mixed with CTZ were eugenol, propylene glycol (PG), chitosan, su-per-oxidized solution (SOS), grapefruit-seed extract (GSE), and as a negative control, 0.9% saline solution. A clinical isolated of E. faecalis was morphological and biochemical characterized, in-cluding antimicrobial susceptibility was tested using 20 antimicrobial agents. Once character-ized, the clinical isolated was cultivated to performed Kirby–Bauer disc diffusion method with paper discs embedded with the different vehicles mixed or used alone, incubating at 37 ºC for 24 h. Data were analyzed by One-way ANOVA and the means were compared using Tukey test with a significance level of p<0.05. For vehicles used alone, GSE presented the greatest inhibition showing a statistically significant difference with the rest of the vehicles. When vehicles were mixed with the CTZ paste, PG showed a greater inhibition with a statistically significant differ-ence from the rest of the vehicles. In conclusion, the vehicle used to mix the CTZ paste plays an im-portant role in the inhibition of E. faecalis in vitro, therefore we consider that this can be an im-portant factor to achieve success in the use of this technique.

The rapid evolution of drug resistance is one of the greatest health issues of the 21st century. There is an alarming situation to find new therapeutic strategies or candidate drugs to tackle ongoing multi-drug resistance development. The marine environment is one of the prime natural ecosystems on Earth, the majority of which is still unexplored, especially when it comes to the microbes. A wide variety of bioactive compounds have been obtained from a varied range of marine organisms, however, marine bacteria-produced bacteriocins are still undermined. Owing to the distinct environmental stresses that marine bacterial communities encounter, their bioactive compounds frequently undergo distinct adaptations that confer on them a variety of shapes and functions, setting them apart from their terrestrial counterparts. The ribosomally-synthesized and posttranslationally modified peptides (RiPPs), bacteriocins are of special interest because of their variety in structure and diverse potential biological activities. Additionally, the gut microbiome of marine creatures are largely unexplored source of new bacteriocins with promising activities. There is a huge possibility of novel bacteriocins from marine bacterial communities that might come out as efficient candidates to fight against antibiotic resistance, especially in light of the growing pressure from antibiotic-resistant diseases and industrial desire for innovative treatments. The present review summarizes known bacteriocins from marine bacteria, evolutionary aspects, challenges, and huge possibilities of unexplored bacteriocins from marine bacterial communities.

Clostridioides difficile is a Gram-positive pathogen known for its toxin production and spore formation. It is primarily responsible for most cases of antibiotic-associated diarrhea. Bacterial persisters are a small subset of the population that exhibits transient tolerance to bactericidal substances, and they are of significant medical concern due to their association with the emergence of antibiotic resistance and difficult-to-treat chronic or recurrent infections. Vancomycin, the predominant antibiotic utilized in the management of C. difficile infection, is extensively applied in the realm of clinical practice. Previous studies have demonstrated a persister-like phenotype with treatments involving this antibiotic. However, the mechanism in C. difficile remains largely unknown, primarily due to the challenge of isolating this small population at any given time. To better characterize C. difficile persister cells, we present a study that enables the enrichment and characterization of persister cells from bacterial cultures in both exponential and stationary phases. Moreover, we could differentiate between triggered (induced by antibiotics, such as vancomycin) and spontaneous (stochastic) persister cells. Additionally, we observed the involvement of toxin-antitoxin systems and Clp proteases in persister cell formation.

Bacteria that have become resistant to antibiotics, also known as superbugs,pose a huge threat to the human population. This is because these developed resistance to antibiotics. Antibiotics are a type of medicine that fights bacteria by either killing it or preventing it from growing. Although antibiotics make the once deadly now easily treatable, they can become ineffective as bacteria develop resistance to the antibiotic, causing diseases to become potentially fatal once more. Thus, scientists are rushing to find solutions in this arms race against evolving bacteria by either evolving current antibiotics or discovering new stands to fight evolving bacteria. In order to discover whether bacteria can develop resistance to household antibiotics, a controlled experiment was conducted. This was done by growing bacteria on agar plates with antibiotic ointments applied (in dilution series) to see if antibiotic resistance could build. Theorizing that by lowering the concentration of over the counter antibiotics, resistant bacteria would be selected and my bacterial population would evolve antibiotic resistance.In conclusion of the experiment antibiotic resistance did appear as a trait, but the level of it was inconsistent across the different bacteria populations.

In the process of oil and gas development and production, when the flow rate in the wellbore is large, the materials underground will be eroded, causing the operation to be unable to proceed smoothly and reducing the efficiency of oil and gas production. Therefore, optimizing the anti-erosion coating under high-speed flow conditions in wellbore is a very interesting thing. It can greatly improve operational efficiency. In this paper, laser cladding was used to prepare the new coating used in the PDC drill bit. Then, the effects of tungsten carbide and multi-layer graphene on the microstructure and properties of the tungsten carbide coating were studied. The research results indicate that, for new coatings, 60% tungsten carbide and 0.3% graphene are the optimal ratios. After adding WC, the hardness has significantly improved. However, when the WC content further increases more than 30%, the increase in hardness is relatively small. In addition, when the content of graphene is more than 0.3%, the branched structure became thicker, and not only the segregation of Cr, Si and W became very obvious again, but also the segregation of Fe occurred at the Ni enrichment site. The research results contribute to improving oil and gas production and operational efficiency under high-speed fluid flow conditions in the wellbore.

In this review we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml; whereas it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. Cmax was 7-8 mcg/ ml at Tmax 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2; as well as T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin A from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

Background: Bacteria can survive antibiotic exposure by mechanisms like tolerance without a shift in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone (CRO), azithromycin (AZM), and ciprofloxacin (CIP), in clinical isolates and WHO reference panel of N. gonorrhoeae and explored the prevalence between urogenital and anorectal infection sites. Methods: We examined 66 N. gonorrhoeae clinical isolates, evenly divided between anorectal and urogenital infection sites, using a modified tolerance disk (TD test) for three antibiotics. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disc for 20 hours of incubation (Step I), followed by the replacement of the antibiotic disc with a nutrient disc for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III). Results: Four isolates were lost due to contamination. Of 62 clinical isolates, 7 exhibited tolerance to AZM, with 6 from anorectal and 1 from urogenital sites (p = 0.0496). Tolerance to CRO was observed in 11 isolates, which was significantly associated with the infection site, with 9 from the anorectum, and 2 from the urogenital site being tolerant (p = 0.02). Tolerance to CIP was found in 11 isolates, but was not significantly associated with the infection site. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO (World Health Organization) reference strains, with varying patterns of tolerance to CRO (n=8), CIP (n=2) and AZM (n=1). Conclusion: This study identified CRO, AZM, and CIP tolerance in clinical Neisseria gonorrhoeae isolates. Significant variations in tolerance proportions between anorectal and urogenital infection sites, particularly for CRO, were observed. Additionally, tolerance was detected in WHO reference strains.

The over use of pharmaceutical compounds, essentially antibiotics, led to an increase of their concentrations in aquatic ecosystems. In this study, the white-rot fungus Coriolopsis gallica (high-laccase-producing fungus) was investigated for the biodegradation of ampicillin (AMP) under different cultivation conditions. The biotransformation of the antibiotic was confirmed by means of high-performance liquid chromatography (HPLC), and the antibacterial activity was evaluated via the bacterial growth inhibition agar well diffusion method using Escherichia coli as an ampicillin-sensitive test strain. The results showed that AMP (50 mg L-1) was totally removed by C. gallica after 6 days of incubation in a liquid medium. The antibiotic removal rate was maximal with a fungal culture aged 9 days. Such a culture achieved the removal of a higher concentration of up to 500 mg L-1 of ampicillin in 3 days. This higher antibiotic removal rate was concomitant with the maximal laccase production in culture supernatant. In addition, four consecutive doses of 500 mg L-1 of ampicillin were transformed by the same fungal culture in 24 days. After that, the fungus was unable to remove the antibiotic. The measurement of ligninolytic enzyme activity showed that laccase of C. gallica might participate in the biotransformation of AMP.

This paper explores various aspects of microbiology and immunology, focusing on the epidemiology and molecular characterisation of infectious diseases in the Caribbean and South America. Key areas of investigation include tuberculosis (TB), nosocomial infections, Salmonella infections, and bloodborne pathogens. A retrospective study in Jamaica underscores the high mortality rates in HIV-positive TB patients and the need for early HIV diagnosis and integrated care. Research in Trinidad and Tobago reveals the genetic diversity of Mycobacterium tuberculosis strains, highlighting high HIV-TB co-infection rates. The paper also examines the challenges posed by nosocomial infections, particularly those caused by antibiotic-resistant Gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA), and emphasises the importance of infection control. In addition, the study investigates Salmonella prevalence in poultry in Jamaica and the risks associated with foodborne infections. The paper further explores transfusion-transmitted infections and the development of IgM antibodies in egg whites for bacterial antigen detection. Lastly, it addresses immune responses in patients with immunodeficiency disorders, such as severe combined immunodeficiency (SCID) and chronic granulomatous disease (CGD), highlighting their susceptibility to a wide range of infections.

Successful translation of biofortified orange maize (BOM) to a household staple food is dependent on farmers’ ability to cultivate the maize and it subsequent utilization. In this study, we assessed farmers ‘allocation of their land to cultivation of BOM and con-ventional white maize (CWM) varieties in districts where AFI-KEPO Nutrition Program is implemented in Malawi. Results show farmers were skeptical of allocating more land to cultivation of BOM. CWM was allocated significantly more land (1.75 ± 0.51 acres) than BOM (1.12 ± 0.32 acres) (p

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

The emergence of antibiotic-resistant Campylobacter jejuni, a leading cause of gastroenteritis worldwide, presents a significant public health challenge requiring vigilant surveillance and disease control. This study aimed to characterize C. jejuni strains isolated in Romania from 2017-2020, focusing on genetic diversity, virulence, and antibiotic resistance determinants. The isolates underwent phenotypical testing, PCR, and antibiotic resistance assessment using Disc Diffusion Kirby–Bauer for ciprofloxacin, nalidixic acid, erythromycin, and tetracycline. Genetic analysis identified resistance and virulence genes, point mutations, and performed sequence typing (7-gene MLST) to determine genetic relatedness. Results indicated substitutions at position 86 in the amino acid sequence or position 257 in the nucleotide sequence of the gyrA gene in 47 fluoroquinolone-resistant isolates. Additionally, mutations in the rRNA23S gene at positions 2074 and 2075, associated with macrolide resistance, were found in 12 of the 66 isolates. Allelic profiles generated 38 sequence types (STs), including three new STs not present in the reference database. The sequence data analysis revealed a genetically diverse C. jejuni population with a weak clonal structure. This study provides crucial insights into the genetic diversity and antibiotic resistance of C. jejuni strains in Romania, highlighting the need for ongoing surveillance and control measures.

Internet of thing (IoT) has been used in different aspect of life as industry, and daily life. Aligned with IoT, Quantum computers have been generated with high features that can accomplish complicated tasks with high speed. IoT and Quantum computers don’t match in resources and due to this collaboration between the two terms, it was found there are many challenges with quantum computers brought some security concerns. This paper will examine all challenges and future direction that face the use of IoT through using different quantum cryptograph methods. The first part on the paper discussed the vulnerabilities of existing cryptographic methods like RSA and ECC. these two methods were used as basic level for IoT security protocols. These cryptographic algorithms could be easily attacked by quantum computers so to ensure that IoT devices are secure must develop quantum resistant cryptographic algorithms. Next this paper will examine the challenges in implementing quantum resistant cryptographic algorithm in any IoT device through quantum resistant cryptographic algorithms such as lattice-based cryptography, code-based cryptography, multivariate cryptography, and hash-based signatures. Then, the paper discussed the future direction of securing IoT in quantum computing. In conclusion, securing IoT devices in quantum presents many challenges that require to be addressed where quantum resistant algorithms can be a solution that mitigate threats.

Background/Objectives: The global push to eliminate tuberculosis (TB) as a public health threat is in-creasingly urgent, particularly in high-burden areas like O.R. Tambo District Municipality, South Africa. Drug-resistant TB (DR-TB) poses a significant challenge to TB control efforts and is a leading cause of TB-related deaths. This study aimed to assess DR-TB transmission patterns and predict future cases using geospatial and predictive modeling techniques. Methods: A retrospective cohort study was conducted across five decentralized DR-TB facilities in O.R. Tambo District Municipality from January 2018 to De-cember 2020. Data were obtained from Statistics South Africa, and patient GPS coordinates were used to identify clusters of DR-TB cases via DBSCAN clustering. Hot Spot Analysis (Getis-Ord Gi) was performed, and two predictive models (Linear Regression and Random Forest) were developed to estimate future DR-TB cases. Analyses were conducted using Python 3.8 and R 4.1.1, with significance set at p < 0.05. Results: A total of 456 DR-TB patients were enrolled, with 56.1% males and 43.9% females. The mean age was 37.5 (±14.9) years. The incidence of DR-TB was 11.89 cases per 100,000 population, with males dispropor-tionately affected. Key risk factors included poverty, lack of education, and occupational exposure. DR-TB types included RR-TB (60%), MDR-TB (30%), Pre-XDR-TB (5%), XDR-TB (3%), and INHR-TB (2%). Spatial analysis revealed significant clustering in socioeconomically disadvantaged areas. A major cluster was identified, along with a distinct outlier. Predictive models indicated differing trends, with the Random Forest model predicting stabilization at 30 cases per year by 2022, while the Linear Regression model projected a decline to zero by 2026. Conclusions: The study highlights the need for targeted interventions in vulnerable populations to curb DR-TB transmission and improve treatment outcomes.

Several studies have shown that antibiotics, analgesic – sedative, and antiseizure medications are among the most commonly used medications in preterm and sick neonates. These infants are at high risk of developing nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe, potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. Previous studies and reviews have revealed significant variability in medications used in neonatal intensive care units (NICUs) worldwide, especially concerning the indications and dosages of first-line medications. This variability indicates the lack of adequate studies regarding the effectiveness and safety of these medications in neonates, especially the preterm ones. Important obstacles contributing to inadequate studies in preterm infants include difficulties in obtaining parental consent, physicians’ unwillingness to recruit preterm infants, the lack of license for use in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials – antifungals, analgesics – sedatives, and antiseizure medications used in neonates, focusing on existing evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage regimen (dose, dosing interval, route of administration), and evidence-based guidelines for the optimal use in neonates.

Background: Previous studies have found variable impact of the coronavirus disease 2019 (COVID-19) pandem-ic on the consumption of antimicrobial drugs in human medicine, with trends in several European countries differing between community and inpatient prescribing. Aim: This study analysed changes in the volumes and use density of antibacterial and antifungal drugs dis-pensed in acute care hospitals in Germany between 2019 and 2022. Methods: Surveillance data for the four years available from 279 hospitals, among them 272 for antifungals, were expressed as the total volumes of daily doses or as use density (daily doses per 100 patient/occupied bed days) per year and analysed descriptively, using recommended hospital-adapted daily dose definitions (RDD) and (as sensitivity analysis) WHO/ATC-defined daily dose definitions (DDD). Hospitals were stratified according to size (number of beds) and university affiliation, and location (East, West, South). Results: There were significant decreases both in the total number of patient days and antibacterial drug vol-umes in 2020 through 2022 compared with 2019. The relative changes between 2019 and 2020, 2021 and 2022 were -12.8%, -13.5%, and -13.3% for patient days, and -9.7%, -11.0%, and -10.1% for antibacterial RDD, respec-tively. Broad-spectrum betalactams, notably piperacillin-tazobactam and carbapenems, increased in volume unlike most other drug classes. The resulting antibacterial drug use density was slightly but significantly increas-ing with pooled means (and medians) of 43.3 (40.0) RDD/100 in 2019 compared to 44.8 (41.7), 44.5 (40.80), and 44.9 (41.7) RDD/100 in the years 2020 through 2022, respectively. Antifungal drug volumes and use density increased after 2019 and peaked 2021 (differences between 2019 and 2021 for total volumes +6.4%, and for pooled mean use density values +22.9%, respectively). These trends were similar in the different hospital strata and comparable when DDD instead of RDD were used. Conclusions: Similar to what has been observed in a majority of European countries the total volume of antibac-terial drug use in German acute care hospitals decreased with the pandemic without a rebound phenomenon in 2022. In association with restricted hospital capacities and presumably more immunocompromised general medi-cine patients, however, inpatient prescribing of (primarily broad-spectrum) antibacterials and of antifungal drugs increased.

Calcium sulphate (CS) is currently used as a bioabsorbable, completely synthetic and sterile material in the management of infected tissues and dead spaces (DS) mainly resulting from surgical procedures. Residual DS in the postoperative, may create an environment where hematomas fill up and bacteria can proliferate, leading to a high incidence of postoperative infections. Considering the available reviews in the literature, CS has been mainly studied in orthopedic surgery mostly giving brilliant results and low complication rates. Nowadays, orthopedists avail it in the form of pearls both as a bone void filler and as an “off-label” delivery agent for antibiotics in arthroplasty, chronic osteomyelitis and open fractures, paving the way of its application in many other contexts given its natural dis-position to biodegradation. In the last years, CS beads have been gaining ground in the general, vascular and endocrinological surgical specialties. Despite its clear potential and the increasing number of scientific evidences on the safety and effectiveness of CS application in the prophylaxis and treatment of infections, there are not many studies reporting on its application in fields other than orthopedics, with a substantial paucity in plastic and reconstructive surgery literature. This is some-how surprising, since reconstructive surgery often deals with complex wounds secondary to bone and soft tissue exposure, suture dehiscence, trauma, and surgical site infections. As far as we know this is the first updated systematic review assessing the state of the art, indications and new perspectives on the application of CS beads in plastic and reconstructive surgery.

Background Cervical insufficiency, marked by recurrent painless cervix dilation leading to second-trimester pregnancy losses, is traditionally managed through cerclage placement and vaginal progesterone administration. However, a recent experimental approach targeted intra-amniotic inflammation or infection in a selected group of women with cervical dilation over 1 cm, intact membranes, and no uterine contractions in the second or third trimester. Case presentation We report a case of a 21 year old primigravid woman who experienced resolution of mid-trimester cervical insufficiency after the administration of triple antibiotic therapy, as confirmed by ultrasound monitoring. Remarkably, the patient successfully carried the pregnancy to term and delivered a healthy baby. Conclusions This case highlights the potential effectiveness of a novel combination of antibiotics, even in the presence of several high-risk pregnancy conditions, and underscores the possibility of a favorable outcome.

Urethral catheterization, a common procedure in canine patients, often compromises urinary tract defenses, leading to bacterial colonization and potential systemic infection. Despite posi-tive urine cultures, clinical signs of urinary tract infection (UTI) may be absent in catheterized dogs. This study evaluated the correlation between urinalysis results and catheter-associated UTIs in hospitalized dogs, considering prior antibiotic treatment and antibiotic resistance. Twen-ty-eight dogs at Kasetsart University Veterinary Teaching Hospital were included. Urine cul-tures and antibiotic sensitivity tests were performed on days 0, 3, and 7 and prior to catheter re-moval, with a positive urine culture defined at ≥104 CFU/mL. Instances of pyuria (>5 WBCs/HPF), hematuria (>5 RBCs/HPF), and bacteriuria were recorded. A statistical analysis showed no significant association between the urine culture results and urinalysis parameters, catheterization duration, breed, sex, neutering status, or age. Dogs with prior antibiotic treat-ments exhibited UTI-free periods after catheter placement that were longer than those previous-ly reported. A Kaplan–Meier analysis showed a probability of being UTI-free of 92.8% at 3 days, declining to 60.7% by 7 days and 53.6% by 10 days. Alarmingly, eighty percent of the isolates (12/15) were multidrug-resistant organisms (MDROs), resistant to ≥3 antimicrobials. Routine urinalysis cannot reliably predict catheter-associated UTI, and the high rate of MDROs under-scores the need for judicious antibiotic use and improved diagnostic tools.

In this work, the resistance/susceptibility (R/S) profile of Staphylococcus equorum strains (n=30) from cheese to 16 antibiotics was determined by broth microdilution. The minimum inhibitory concentration (MIC) for all antibiotics was low in most strains, although higher MICs compatible with acquired genes were also noted. Genome analysis of 13 strains showed the S. equorum resistome to be composed of intrinsic mechanisms, acquired mutations, and acquired genes. However, the genetic data did not always correlate with the phenotype. As such, a cat gene providing resistance to chloramphenicol was found on a plasmid in one strain; this was able to provide resistance to Staphylococcus aureus after electroporation. An msr(A) polymorphic gene was identified in five strains. The Mrs(A) variants were associated with variable resistance to erythromycin. All strains harboured a polymorphic fosB/fosD gene, although only one acquired copy was associated with strong resistance to fosfomycin. Similarly, a plasmid-associated blaR1-blaZI operon encoding a penicillinase was identified in five ampicillin- and penicillin G-susceptible strains. Identified genes not associated with resistance further included mph(C) in two strains and norA in all strains. The antibiotic R/S status and gene content of S. equorum strains intended to be employed in food systems should be carefully determined.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

Public restrooms are often a hub of microbial contamination, and the examination of bacterial contamination in these facilities can serve as an important indicator of the transmission of infectious diseases. This study was conducted to determine the prevalence of bacterial contamination in public restrooms based on the economic class of the building. Samples were collected from various spots in 32 restrooms found in 10 shopping malls, classifying them into two categories: upper-end restrooms and lower-end restrooms. The findings showed that the level of contamination was higher in the lower-end restrooms, with the seat being the most contaminated area. The most dominant Gram-positive bacteria were coagulase-negative staphylococci species, making up 86% of the identified Gram-positive isolates. The most dominant Gram-negative bacteria identified were Klebsiella pneumoniae and Pseudomonas aeruginosa. The antibiotic sensitivity test results revealed the presence of multi-drug resistant bacteria among the Gram-positive and negative isolates, including Staphylococcus haemolyticus, Staphylococcus kloosi, Acinetobacter baumanii, and Pseudomonas aeruginosa. In conclusion, the study underscores the significance of monitoring bacterial contamination in public restrooms and the need for measures to reduce the spread of infectious diseases. Further research is crucial to gain a complete understanding of the bacterial contamination in public restrooms and their resistance patterns, to ensure the safety and health of the public. The implementation of improved cleaning practices and hands-free designs in restrooms can help reduce the risk of cross-contamination and prevent the spread of diseases.

The exponential rise of bacterial resistance poses a threat to antibiotic efficacy, with a great impact on public health. This study aims to analyze the correlation between antibiotic consumption and the emergence of bacterial resistance. Conducted retrospectively at Charles Nicolle Hospital in Tunis, Tunisia from 2010 to 2022, this study was based on STKMED® software for antibiotic consumption data, hospital administrative records for the number of hospitalization days, and SIRSCAN® software for bacteriological data. Data processing was performed using Excel® software, and analysis was conducted using SPSS23®. In 2022, Consumption was almost evenly split between the two major “AWaRe” groups, with 49.33% for "Access" and 46.89% for "Watch", and the consumption of the "Reserve" group also increased, accounting for 3.77% of the total. Bacterial resistances, notably carbapenem-resistant Klebsiella pneumoniae, increased. Seventy-four significant correlations were identified, including those be-tween carbapenem consumption and resistance in Escherichia coli and Klebsiella pneumoniae strains. However, no significant corre-lation was observed with imipenem-resistant Pseudomonas aeruginosa strains. The significant correlations between the emergence of bacterial resistance and antibiotic use, particularly with antibiotics in the "Watch" and "Reserve" groups, underscore the urgent need to continue efforts to combat this threat through rational antibiotic use.

The growing threat of antibiotic pollution in water systems demands innovative and sustainable remediation strategies. Nanocellulose-based magnetic metal-organic frameworks (MOFs) represent a cutting-edge solution for the adsorption and removal of antibiotics, leveraging their high porosity, magnetic properties, and environmentally friendly nature. This paper provides an in-depth review of recent advancements in nanocellulose-based MOFs, focusing on their synthesis, adsorption mechanisms, and applications in environmental remediation between 2020 and 2024. By summarizing key studies, we highlight their performance in targeting widely used antibiotics such as tetracyclines and fluoroquinolones. The integration of nanocellulose with MOFs not only enhances adsorption capacity but also offers easy recovery, recyclability, and environmental compatibility. This review explores their adsorption mechanisms, practical applications, and future research directions, contributing to the advancement of scalable and sustainable water treatment technologies.

Correlations among estrus cycle, pyometra, and canine diabetes mellitus (CDM) have been described since the late 1950s, and substantial progress in understanding mechanisms beyond was achieved nowadays. Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. Thus, a deep understanding of the physiopathological aspects involved is crucial to postulate treatment guidelines to improve the PRDM remission rate, as well as to inform preventive measures. This narrative review aims to provide relevant detailed information on 1) canine estrus cycle and its impact on CDM etiology and management, 2) the role of pyometra as a further cause of insulin resistance, and 3) useful individual therapeutic and preventive strategies. Pharmacological annulment of progesterone effects, as well as inflammatory and progesterone-related conditions resolution in association with adequate exogenous insulin therapy, and residual beta cell function, are key aspects to achieve remission, or at least to improve diabetic clinical control. In this way, spaying should be considered mandatory in most PRDM cases. Preventive measures against CDM can include spaying recommendations; however, individual-based recommendations should be considered since castration may be associated with some long-term health issues.

Under the increasingly severe global heat threat, continuous high temperature has far-reaching effects on plant growth and development and become a major constraint to crop production. The development of heat-resistant varieties has become research hotspot in many fields, and it is also necessary to establish effective identification methods. In this study, twenty Brassica rapa varieties were selected to to investigate the physiological and biochemical characteristics under heat stress, explore the relationship between physiological response and the heat resistance mechanism, select some typical heat-resistant and heat-sensitive varieties. The effects of photosynthetic electron transfer and antioxidant pathway on heat resistance of Brassica rapa were identified. These findings will providing an important reference for the physiological regulation and identification method of high-temperature stress in plants.

In this study, global response analysis was performed to explore the mechanism of action of Usnic acid and its synergy with Norfloxacin, a well-known quinolone antibiotic to which MRSA clinical isolates showed resistance (MIC, 500 µg/mL). Microdilution assay, growth kinetics, microscopic analysis, and cell-based assays consistently showed that Usnic acid possess strong anti-staphylococcal activity (MIC, 7.8 µg/ml), causes cell leakage, modulates efflux pump activity, and synergizes with Norfloxacin against multi-drug resistant clinical isolate MRSA 2071. Whole cell proteome profiling using gel-free based nano-LC-ESI-QTOF-MS/MS revealed several proteins whose expression was significantly modulated by Usnic acid and Norfloxacin alone or in combination. Usnic acid downregulated the abundance of RNA polymerase subunits (RpoB, RpoC), carbamoyl phosphate synthase large subunit (PyrAB), chaperone (GroEL), and adenylosuccinate synthetase (PurA). Interestingly, proteins found to be upregulated in the presence of Usnic acid and Norfloxacin included oxidative stress-related proteins such as peroxidase (Tpx), alkyl hydroperoxide reductase (AphC), and general stress protein (UspA). This study clearly showed that Usnic acid affects numerous cellular targets and can potentiate the action of Norfloxacin. Furthermore, an in-vivo study emphasized the use of Usnic acid to develop as a safe phytopharmaceutical to repurpose old antibiotics through combination therapy against MRSA infections.

Diarrhea remains one of the leading causes of mortality worldwide, especially among children. Recent epidemiological studies conducted in developing countries identified Shigella species as the most predominant pathogenic bacteria responsible for diarrhea. Antimicrobial therapy is necessary for Shigella infections; however, the rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. To identify alternative antimicrobial compounds with activity against Shigella species, the pathogens responsible for bacterial diarrhea. In this study, we have applied antibacterial phenotypic screening to identify potent anti-Shigella compounds across a broad chemical diversity, including selected acetaminophen derivatives containing benzothiazoles backbone, and their combination with certain antibiotics. In continuation to our effort in searching potent antimicrobial compounds, we have found this time around that two acetaminophen derivatives containing benzothiazoles backbone (4a and 4b) could inhibit the growth of Shigella flexneri with common MIC value of 12.5 µg/ml. These compounds were established through a time-kill kinetics’ study to be bactericidal. Meanwhile, the 2-aminobenzothiazoles (1a and 1b) used for the synthesis of compounds 4 (a & b) were found to be poorly active (MIC: 100 µg/ml) against this pathogen. Combination studies of 4a and 4b with the least susceptible antibiotics (ceftriaxone and cotrimoxazole) demonstrated synergistic anti-Shigella activity. The present study demonstrates that the azobenzothiazole dyes 4 (a & b) can be repurposed as potential anti-Shigella compounds, which can serve as scaffolds for the development of new agents against infectious diarrhea caused by Shigella and other enteric pathogens, especially in developing countries.

The genus Aeromonas is widely distributed in aquatic environments. It is frequent as a fish pathogen, but has also been described associated to human infections. Most human cases are caused by A. caviae, A. veronii biovar sobria, and A. hydrophila, though A. dhakensis is becoming increasingly important. Transmission happens primarily by ingestion or contact with aquatic collections, or by consumption of contaminated food, especially of aquatic origin. Increasing resistance has been described in Aeromonas to penicillins, including their combinations with classical b-lactamase inhibitors, cephalosporins and carbapenems. Among the b-lactam antibiotics, only the 4th generation cephalosporins remain almost uniformly active. In addition, the simultaneous presence of resistance genes to 3rd generation cephalosporins and carbapenems in the same isolates is increasing. Recently, the presence of mobile genes linked to colistin resistance has also been described, in some cases with resistance percentages higher than 30%. Most likely, this evolution of colistin resistance is linked to its use in aquaculture, and, together with the evolution of b-lactam resistance, may be turning this genus into a reservoir of resistance genes that may affect other species much more frequently linked to human infections, such as Enterobacterales.

Background: Public misconception and demand for the indication of antibiotics could lead to inappropriate prescribing and consumption. Successful treatment can only be achieved when the public and industrial users have knowledge on antibiotic use and resistance. This survey is aimed to assess antibiotic usage and knowledge regarding antibiotics and antimicrobial resistance (AMR) among undergraduate students of Universiti Brunei Darussalam (UBD), public university located in Brunei Darussalam. Methods: A cross-sectional study was performed using a self-administered questionnaire. The questionnaire was adapted from the World Health Organization (WHO) Antibiotic Resistance, Multi-country public awareness survey distributed online. Students at UBD were invited to participate in the online survey through internal email. The questionnaire consisted of 5 sections: demographic information, antibiotic usage, knowledge on antibiotics, antibiotic resistance (AMR) and use of antibiotics in agriculture. Data were analyzed descriptively and appropriate inferential statistics was used accordingly. Cronbach’s alpha was also done to determine the internal consistency. The section on antibiotic use and knowledge showed good internal consistency of Cronbach’s alpha 0.66 and 0.86 respectively. Research ethics approval was obtained from the PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam (UBD). Results: A total of 145 students returned the complete questionnaire. The result of the study found that 50% of the students had good level of knowledge of antibiotic and antimicrobial resistance with a mean total knowledge score of 11.4 out of 14. Respondents reported the use of antibiotic in the past (69%). Many of the students could identify the use of antibiotics for the treatment of bacterial infection. However, there were also students who incorrectly thought that antibiotics can be used for cold and flu (43%) and fever (41%). Moreover, 76% of the respondents mistakenly believed that antibiotic resistance is the result of the body becoming resistant to antibiotics. Only 12% of the respondents were found to have poor knowledge in the study. Conclusions: Misconceptions in regards to the use of antibiotics for conditions related to viral illnesses was noticed among the respondents in our study. Thus, improving knowledge on antibiotics is crucial to address those beliefs.

Acute and chronic graft versus host disease (a/cGVHD) are major complications of allogeneic stem cell transplantation and a frequent cause of non relapse-mortality. The treatment of a/cGVHD consists of steroid administration at full dose. In the case of aGVHD, around 60 % of patients with grade III/IV fails to respond (steroid-resistant, SR), requiring a second line therapy. Extracorporeal photopheresis (ECP) represents a good option for second line treatment, leading to multiorgan response in several patients. Here, we have evaluated the performances of a cytofluorimetric quality control of the first ECP procedure in 29 patients with severe SR aGVHD who underwent ECP. The quality control represents a check control of in vitro cell apoptosis/death induction in collected and irradiated CD3+ cells by ECP. Our analysis shows that in more than 70 % quality controls a relevant apoptotosis/death of CD3+ cells was observed after cell irradiation, as compared to non-irradiated controls. Albeit observed in a small patients’ series, the occurrence of relevant in vitro effect after ECP relates to less procedures and/or to a better survival on ECP. Age, disease, gender, aGVHD grade and time from transplant to the first ECP had not impact on ECP efficacy in this patients’ series.

The injury causes resistance in human gastric cancer (GC). This Adverse Outcome Pathway (AOP) entitled “Increases in cellular reactive oxygen species (ROS) and chronic ROS leading to human treatment-resistant gastric cancer (GC)” consists of molecular initiating event (MIE) as “Increases in cellular ROS” and “Chronic ROS”, followed by series of key events (KEs); “porcupine-induced Wnt secretion and Wnt signaling activation”, “beta-catenin activation”, “epithelial-mesenchymal transition (EMT), and adverse outcome (AO) as “human treatment-resistant GC” in the sequence. ROS has multiple roles in disease such as development and progression of cancer, or apoptotic induction causing anti-tumor effects. In this AOP, we focus on the role of sustained levels of chronic ROS to induce the therapy-resistance in human GC. EMT, which is cellular phenotypic change from epithelial to mesenchymal-like features, demonstrates cancer stem cell (CSC)-like characteristics in human GC. EMT is induced by Wnt/beta-catenin signaling, providing the rationale to have Wnt secretion and beta-catenin activation as KEs in the AOP.

The global antibiotic resistance crisis, driven by antibiotic overuse and misuse, is multifaceted. This study aimed to assess the microbiological and genetic characteristics of raw retail pork meat, including the isolation, antibiotic susceptibility testing (AST), whole genome sequencing (WGS) of selected indicator bacteria, antibiotic residue testing, and metagenomic sequencing. Samples were purchased from 10 randomly selected retail stores in Gauteng, South Africa. Samples were aseptically separated, with a portion sent to an external laboratory for isolating indicator bacteria and antibiotic residue testing. Identification of the isolated bacteria was reconfirmed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). AST was performed using the Microscan Walkaway system. WGS and metagenomic sequencing were performed using the Illumina NextSeq 550 instrument. The isolated E. coli and enterococci exhibited little phenotypic resistance, with WGS revealing tetracycline resistance genes. Isolated bacteria and meat samples all harboured tetracycline resistance genes, and the antibiotic residue concentrations were within acceptable limits for human consumption. In the metagenomic context, most identified bacteria were of food/meat spoilage and environmental origin, with the resistome analysis primarily indicating beta-lactam, tetracycline and multidrug resistance genes. Further research is needed to understand the broader implications of these findings on environmental health and antibiotic resistance.

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeted resistance to β-lactams including carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones.

Probiotics are microorganisms infused in products for health benefits including acceleration of nutrient digestion, however, it is also important to ensure the safety prior to incorporation. Here, we present evidence of the ability of two probiotic isolates,Lacticaseibacillus paracasei BCRC-16100 and Lacticaseibacillus paracasei ZFM54, in the (1) enhancement of carbohydrate digestion, (2) tolerance to stress, and (3) antibiotic resistance. Approaches include whole genome sequence (WGS) analysis and bioactivity assays. WGS revealed genes suggesting the ability of the two isolates to promote carbohydrate digestion, tolerance to stress and antibiotic resistance. Carbohydrate digestive ability was confirmed through a biochemical assay where the two isolates cause glucose release from starch. The two isolates also showed versatility in a range of temperature and alcohol concentration. For antibiotic resistance particularly on vancomycin, there are three mechanisms namely transporter control, transcriptional regulation, and efflux pump. Furthermore, promoter and transposable element analysis showed that some of the active antibiotic resistant (AbR) genes can be laterally transferred. Altogether, we show the potential of two probiotic isolates to be incorporated in products for improved carbohydrate digestion and the need to address the removal of active and mobile antibiotic resistance genes that may compromise safety.

Shigella and Salmonella have been implicated in neonatal sepsis, food poisoning, and bacteremia. Their increasing resistance to antibiotics has undermined treatment options, constituting a public health crisis. Also, the scarcity of new antibiotics in the development pipeline compounds multidrug-resistance (MDR). Hence, there is a need to potentiate antibiotics to mitigate resistance. This study leveraged riboflavin to re-sensitize fluoroquinolones and carbapenems against MDR Shigella and Salmonella spp. Disk diffusion, microbroth-dilution, chequerboard, and time-kill assays were used to determine resistance profiles and riboflavin-antibiotic activity. Biofilm-formation and bacterial viability (after riboflavin-antibiotic challenge) was determined with crystal-violet and Macrophage infection assays, respectively. Strains exhibited &gt;80% resistance to fluoroquinolones and carbapenems, with 160–320 µg MIC ranges and 0.5–2 FIC, indicating no synergy. At 40–80 µg riboflavin, there was two-fold reduction in bacterial survival, with meropenem-riboflavin exhibiting significant reduction and FIC of 0.075 indicating high synergistic activity. Biofilm-formation was altered (from strong to weak phenotype) with 40 µg riboflavin-antibiotic treatment. There was a 40–70% reduction in bacterial survival in THP-1 cells treated with meropenem-riboflavin after 3 hours, and complete clearance between 24-48 hpi. Riboflavin potentiated fluoroquinolones and meropenem, leading to modulation of the host immune response for the clearance of the strains.

The eutrophication of open water bodies, especially in coastal water area, has received intensive public focuses in recent years. Biological treatment of organic pollutants in industrial and domestic wastewater requires microbial flora to participate. The environmental impact of these microbes, particularly in regard to the spread of antibiotic resistance genes and pathogenicity in coastal water, remains largely unknown. We initiate studies to examine antibiotic resistance genes (ARGs) in microbial flora and study the mode of antibiotic spread in the coastal waters of Bohai Bay, North China by using high performance liquid chromatography-mass spectrum analysis and quantitative polymerase chain reaction. The metabolic features of bacteria related to the presence of ARGs in the coastal area showed the enrichment of Pseudomonadale species with triple resistance properties (ampicillin, kanamycin and gentamycin) at the estuary site locating adjacent to a coastal sewage treatment plant where both type I and type II polyketide synthase genes and b-lactam type antibiotics are detected. Pseudomonadale order is phylogenetically belonged to Proteobacteria Phylum, Gamma-proteobacteria Class and contains Pseudomonadaceae family and Pseudomonas genus. QPCR analysis suggests that the percent occupation of Pseudomonadale species to total Proteobacteria in the examined stations is close to several sampling stations close to sewage treatment plants, where consistent release of organic wastes occurred.

Enterococcus faecalis is a growing cause of nosocomial and antibiotic-resistant infections. Treating drug-resistant E. faecalis requires novel approaches. The use of bacteriophages (phages) against multidrug-resistant (MDR) bacteria has recently garnered global attention. Biofilms play a vital role in E. faecalis pathogenesis as they enhance antibiotic resistance. Phages eliminate biofilms by producing lytic enzymes, including depolymerases. In this study, Enterococcus phage vB_Efs8_KEN04 (ФKEN04), isolated from a sewage treatment plant in Nairobi, Kenya, was tested against clinical strains of MDR Enterococcus faecalis. This phage had a broad host range against 100% (26/26) of MDR E. faecalis clinical isolates and cross-species activity against Enterococcus faecium. It was able to withstand acidic and alkaline conditions, from pH 3 to 11, as well as temperatures between -80ᵒC and 37ᵒC. It could inhibit and disrupt the biofilms of MDR E. faecalis. Its linear double-stranded DNA genome of 142,402 bp contains 238 coding sequences with a G+C content and coding gene density of 36.01% and 91.46%, respectively. Genomic analyses showed that ФKEN04 belongs to the genus Kochikohdavirus in the family Herelleviridae. It lacked antimicrobial resistance, virulence, and lysogeny genes, and its stability, broad host range, and cross-species lysis indicate strong potential for the treatment of Enterococcus infections.

The $k$-means problem is to compute a set of $k$ centers (points) that minimizes the sum of squared distances to a given set of $n$ points in a metric space. Arguably, the most common algorithm to solve it is $k$-means++ which is easy to implement, and provides a provably small approximation factor in time that is linear in $n$. We generalize $k$-means++ to support: (i) non-metric spaces and any pseudo-distance function. In particular, it supports M-estimators functions that handle outliers, e.g. where the distance $\mathrm{dist}(p,x)$ between a pair of points is replaced by $\min {\mathrm{dist}(p,x),1}$. (ii) $k$-means clustering with $m\geq 1$ outliers, i.e., where the $m$ farthest points from the $k$ centers are excluded from the total sum of distances. This is the first algorithm whose running time is linear in $n$ and polynomial in $k$ and $m$.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

Antibiotic resistance is a persistent and growing concern. Our objective was to analyze antibiotic prescribing in the United States (US) in the Medical Expenditure Panel System (MEPS) and to Medicaid patients. We obtained total MEPS prescriptions for eight antibiotics from 2013 to 2020. We extracted prescribing rates per 1,000 Medicaid enrollees for two years, 2018 and 2019, for four broad spectrum (azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin) and four narrow spectrum (amoxicillin, cephalexin, doxycycline, and trimethoprim/sulfamethoxazole) antibiotics. Antibiotics in MEPS decreased from 2013 to 2020 by -38.7% with a larger decline for broad (-53.7%) than narrow (-23.5%) spectrum. Antibiotic prescriptions in Medicaid decreased by -6.7%. Amoxicillin was the predominant antibiotic followed by azithromycin, cephalexin, trimethoprim/sulfamethoxazole, doxycycline, ciprofloxacin, levofloxacin, and moxifloxacin. Substantial geographic variation in antibiotic prescribing existed with 2.8-fold between the highest (Kentucky = 855/1,000) and lowest (Oregon = 299) states. The South prescribed 52.2% more antibiotics (580/1,000) than the West (381/1,000). There were significant correlations across states in antibiotic prescribing. This study identified sizable disparities by geography in prescribing rates of eight antibiotics with over three-fold state level differences. Areas with high antibiotic prescribing rates, particularly for outpatients, may benefit from stewardship programs to reduce potentially unnecessary prescribing.

The mosquito microbiota reduces the vector competence of Anopheles to Plasmodium and affects host fitness, it is therefore considered as a potential target to reduce malaria transmission. While immune induction, secretion of antimicrobials and metabolic competition are three typical mechanisms of microbiota-mediated protection against invasive pathogens in mammals, the involvement of metabolic competition or mutualism in mosquito-microbiota and microbiota-Plasmodium interactions has not been investigated. Here, we describe a metabolome analysis of the midgut of An. coluzzii provided with a sugar-meal or a blood-meal, under conventional or antibiotic-treated conditions. We observed that the antibiotic treatment affects the tricarboxylic acid cycle and nitrogen metabolism, notably resulting in decreased abundance of free amino acids. Linking our results with published data, we identified candidate pathways which may participate in microbiota/Plasmodium interactions via metabolic interactions or immune modulation.

Predictive studies are essential to establish fundamental data for monitoring and controlling Xylella fastidiosa infections in our country. Limited knowledge exists about how Xylella fastidiosa interacts with the plant host's immune system, leaving numerous unanswered questions regarding Xylella fastidiosa biology and its interactions with national plant hosts. Key inquiries include understanding of how the plant immune system interfaces with Xylella fastidiosa in the xylem and identifying the specific or shared mechanisms underlying the susceptibility of different hosts. Factors such as the presence of insect vectors, abundance of host plants, and climate suitability play pivotal roles in Xylella fastidiosa dispersal. We recommend that countries identified with relatively high risk, like Portugal, undertake thorough individual risk analyses. The implementation of preventive measures and, if necessary, the enhancement of surveillance systems for early detection of Xylella fastidiosa in plants and insect vectors are crucial steps. Additionally, raising awareness is of equal importance to mitigate socioeconomic and ecological impacts on their ecosystems.

Around the world, there is no population clear from urinary tract infection (UTI), particularly among women. UTI is considered the most predominant bacterial infection. This study aimed to detect the incidence of the most common major uropathogens in patients severe from urinary tract infection with antibiotic sensitivity tests that assist urologist doctors for appropriate antimicrobial empirical therapy.Methods: This study was carried in a private laboratory in Babil city, Iraq from May 2019 to May 2020. Totally 70 individuals suffering from clear symptoms of UTI, as well as, 20 healthy persons participated in this study as a control group. Then, the standard microbiological methods carried out to isolate and identify bacterial species. Antimicrobial susceptibility tests were performed using different antimicrobial discs by applying the Kirby–Bauer disc diffusion method.Results: Totally, 90 specimens were obtained from them 20 control group, 19 with no growth, and 51 patients with bacterial growth distributed as 43 (83%) females and 8 (17%) males. E. coli were the most common predominant organisms. All isolates were showed a high rate of resistance to evaluated cephalosporins 100% and 82% to cefotaxime and ceftriaxone respectively, while very low resistance recorded in Aminoglycosides 20% and 13% to Gentamicin and amikacin respectively. Most age group infected with UTI was 21-40 years old.Conclusion: The current study showed an increasing burden of urinary tract infection caused by various bacteria implicated in UTI that causes changeable sensitivity to various antimicrobial agents. Therefore, in clinical use appropriate medications should be selected based on the data obtained from antimicrobial susceptibility tests.

Gender and biological sex have distinct impacts on the pathogenesis of type 2 diabetes (T2D). Estrogen deficiency is known to predispose female mice to T2D. In our previous study, we found that high-fat, high-sucrose diet (HFHSD) induces T2D in male mice through the miR-10b-5p/KLF11/KIT pathway, but not in females, highlighting hormonal disparities in T2D susceptibility. However, the underlying molecular mechanisms of this hormonal protection in females remain elusive. To address this knowledge gap, we utilized ovariectomized, estrogen-deficient female mice, fed them a HFHSD to induce T2D, and investigated the molecular mechanisms pathway in estrogen-deficient diabetic female mice, cell lines, and patients with T2D in female. Initially, female mice fed a HFHSD exhibited delayed onset of T2D, but ovariectomy-induced estrogen deficiency promptly precipitated T2D without delay. Intriguingly, insulin (INS) was upregulated, while insulin receptor (INSR) and protein kinase B (AKT) were downregulated in these estrogen-deficient diabetic female mice, indicating insulin-resistant T2D. These dysregulations of INS, INSR, and AKT were mediated by a miR-10a/b-5p-NCOR2 axis. Treatment of miR-10a/b-5p effectively alleviated hyperglycemia in estrogen-deficient T2D female mice, while β-estradiol temporarily reduced hyperglycemia. Consistent with the murine findings, plasma samples from female T2D patients exhibited significant reductions in miR-10a/b-5p, estrogen, and INSR, but increased insulin levels. Our findings suggest that estrogen protect against insulin-resistant T2D in females through miR-10a/b-5p/NCOR2 pathway, indicating the potential therapeutic benefits of miR-10a/b-5p restoration in female T2D management.

Background/objectives: The health benefits of resistant starch are well known, but there have not been many studies available documenting the effect of basmati rice products containg resistant starch upon blood glucose level and lipid profile in vivo efficacy. Methods: Common cooking methods were used to prepare basmati rice products including two boiling methods viz. boiling 1 (boiling by absorption), boiling 2 (boiling in extra amount of water), frying and pressure cooking. The cooked rice were held at various temperatures and times: it was made fresh (T1), kept at room temperature (20–22°C) for 24 h (T2), kept at 4°C for 24 h (T3), and then reheated after being kept at 4°C for 24 h(T4). Next, the products' proximate composition, total dietary fibre (soluble and insoluble), resistant starch (RS), and In vitro starch digestion rate (rapidly and slowly digested starch) were examined. The effect of RS on blood glucose and lipid profile were measured in humans and rats. Histopathological study of liver and pancreas in rats were also observed. Results: The basmati rice prepared by boiling 1 and stored with T3 was found more effective to control blood glucose and lipid profile. Similarly in rats, the blood glucose level, cholesterol, triglycerides and LDL were reduced about 29.7, 37.9, 31.3 and 30.5% respectively, after consumption of basmsti rice prepared by boiling 1 and stored at T3. Conclusion: Rice products stored at 4⁰C have a high amount of resistant starh, insoluble dietary fibre, slowly digestible starch and low glycemic index. Thus helps to inhibit glycogen and lipid synthesis.

Candida glabrata is a yeast of increasing medical relevance, particularly in critically ill patients. It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans. The attributed higher incidence is primarily due to an increase in the acquired immunodeficiency syndrome (AIDS) population, cancer, and diabetes patients. The elderly population and the frequent use of indwelling medical devices are also predisposing factors. The work aimed to review various virulence factors that facilitate the survival of pathogenic C. glabrata in IC. The available published research articles related to the pathogenicity of C. glabrata were retrieved and reviewed from four credible databases, mainly Google Scholar, ScienceDirect, PubMed, and Scopus. The articles highlighted many virulence factors associated with pathogenicity in C. glabrata, including adherence to a susceptible host surface, evading host defences, and producing hydrolytic enzymes (e.g., phospholipases, proteases, and haemolysins). The factors facilitate infection initiation. Other virulent factors include iron regulation and genetic mutations. Accordingly, biofilm production, tolerance to high-stress environments, and development of resistance to the antifungal drug, notably to fluconazole and other azole derivatives, were reported. The review provided evident pathogenic mechanisms and antifungal resistance associated with C. glabrata in ensuring its sustenance and survival.

Multidrug resistant organisms (MDROs) outbreaks have been steadilyincreasing in Intensive care units (ICUs). Still, healthcare institutions and workers (HCW) reached no unanimity on how and when implementing infection prevention and control (IPC) strategies. We aimed to provide a pragmatic, physician practice-oriented, resume of strategies towards different MRDOs outbreaks in ICU. We performed a narrative review on IPC in ICUs, investigating patient-to-staff ratios, education, isolation, decolonization, screening and hygiene practices, outbreak reporting, cost-effectiveness, reproduction-number(R0), and future perspectives. The most effective IPC strategy remains unknown. Most studies focus on a specific pathogen or disease, making the clinician losing the big picture. IPC strategies proved their cost-effectiveness regardless typology, country, or pathogen. A standardized, universal, pragmatic protocol for HCW education should be elaborated. Likewise, a rapid outbreak recognition tool elaboration (i.e., an easy-to-use mathematical model) would improve early diagnosis and spreading prevention. Further studies are needed to express in favor or against MDROs decolonization. New promising strategies are emerging and need to be tested in the field. The lack of IPC strategies application has made, and still makes ICUs a major MDROs reservoir into the community. In a not-too-distant future genetic engineering and phage therapies could represent a plot-twist in MDROs IPC strategies.

Abstract: Colistin is a last-resort antimicrobial for treating multidrug-resistant Gram-negative bacteria. Phe-notypic colistin resistance is highly associated with plasmid-mediated mobile colistin resistance (mcr) genes. mcr-bearing Enterobacteriaceae have been detected in many countries, with the emergence of colistin-resistant pathogens a global concern. This study assessed the distribution of mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes with the phenotypic colistin resistance in isolates from diarrheal infants and children in Bangladesh. Bacteria were identified using the API-20E biochemical panel and 16s rDNA gene sequencing. Polymerase chain reac-tions detected mcr gene variants in the isolates. Their susceptibilities to colistin were determined by agar dilu-tion and E-test by minimal inhibitory concentration (MIC) measurements. Over 30.0% (69/225) of isolates showed colistin resistance by agar dilution assessment (MIC> 2.0 μg/mL). Overall, 15.5% of isolates carried mcr genes (7, mcr-1; 17, mcr-2; 13, mcr-3; and co-occurrence occurred in 2 isolates). Clinical breakout MIC val-ues (≥ 4 μg/mL) were associated with 91.3% of mcr-positive isolates. The mcr-positive pathogens include twenty Escherichia spp., five Shigella flexneri, five Citrobacter spp., two Klebsiella pneumoniae, and three Pseudo-monas parafulva. mcr-genes appeared to be significantly associated with phenotypic colistin resistance phe-nomena (p=0.000), with 100% colistin-resistant isolates showing MDR phenomena. Age and sex of patients showed no significant association with detected mcr variants. Overall, mcr-associated colistin-resistant bacte-ria have emerged in Bangladesh, which warrants further research to determine their spread and instigate ac-tivities to reduce resistance.

Staphylococcus aureus (S. aureus), particularly Methicillin-resistant S. aureus (MRSA), is a life-threatening pathogen that causes a variety of infections in hospital and community settings. It poses a significant risk and challenge for global health that hinders our ability to control and treat bacterial infections. Recently, the emergence and spread of variant strains of bacteria, misuse of the limited available options of effective antibiotics, spread of fake drugs, and climate change that increased the contact between humans and animals’ populations carrying different bacterial has significantly increased the incidence of Multi-Drug Resistance strains (MDR). This in turn, has created a severe problem in the infection control treatment of S. aureus infected patients. Treatment options for MRSA infection are increasingly limited and complicated. Unfortunately, different strains of MRSA are showing tolerance and resistance toward vancomycin, which is the standard of care for complicated MRSA. Therefore, it is crucial now to invest developing new effective anti-biotics and synergies, develop and implement national action plans for the management of an-tibiotic resistance, as well as improving our understanding of the antimicrobial resistance mechanisms. Here, in this review we explain the main mechanisms of antibiotic resistance in MRSA and describes different approaches to manipulate it in MRSA, providing a basis for de-signing effective drugs, and shedding some light on the evolution of S. aureus.

The development of antimicrobial resistance to conventional antibiotics is a major global health challenge. Infections caused by multidrug-resistant gram-negative bacteria have been named one of the most urgent global health threats. Considerable efforts are devoted to developing new antibiotic drugs and investigating the mechanism of antibiotic resistance. Recently, Anti-Microbial Peptides (AMPs) have emerged as a new platform for the target and design of novel drug resistant anti-microbial agents promising a new therapeutic strategy. AMPs are rapid, potent, possess an unusually broad spectrum of activity, and have shown efficacy as topical agents. Unlike traditional therapeutics that interfere with essential bacterial enzymes, AMPs interact with microbial membranes through electrostatic interactions and physically damage cell integrity. However, naturally occurring AMPs have limited selectivity and modest efficacy. Therefore, recent efforts have focused on the development of synthetic AMP analogs as suitable drug targets. This work explores the development of novel antimicrobial agents which mimic the structure of graft-copolymers and mirror the mode of action of an AMP. Chitosan-graft-polypeptide side chains are synthesized by the ring-opening polymerization of N-carboxyanhydrides of L-lysine and L-leucine initiated from the functional groups of chitosan. The derivatives with random- and block-copolymer side chains are explored as drug targets. These graft copolymer systems exhibit activity against clinically significant pathogens and disrupt biofilm formation. This work highlights the potential of chitosan-graft-polypeptide structures in biomedical applications.

The world faces two seemingly unrelated challenges—a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.

The antibiotic or antimicrobial resistance is rapidly spreading in microbes relevant to human health. Two visible major contributory factors have been the indiscriminate overuse of antimicrobials for preventing diseases in human and to enhance the productivity in agriculture sector. To mitigate the potential threat posed by post-antibiotic era, the global health stakeholders have been making extra efforts at a war footing to formulate and implement global and national plans of action. In the current article, an endeavour is made to provide a perspective to look beyond the current focus on just use of the antimicrobials. Attention has been drawn towards various obvious and not-so-obvious self-preservation infection-prevention practices in vogue from the pre-antibiotic era whose usage has been on decline in the antibiotic era for various reasons. Particularly, the practices with a clear potential to effectively decrease the spread of pathogens through contact, curtail the evolution and dissemination of the antimicrobial resistance in local environment and its introduction into the global community, should be Identified and strengthened to make them part of comprehensive hygiene and quarantine practices. Broadly, the suggestions pertaining to the personal and community hygiene including bereavement practices, isolation and quarantine of suspected pathogen carriers, and water and environment security have been made to invoke a constructive debate and discussion among various stakeholders for their evaluation and implementation to effectively delay the development of antimicrobial resistance wherever possible and disrupt its spread to pathogens.

The emergence of antimicrobial resistance (AMR) Candida auris presents a formidable global health challenge, causing severe healthcare-associated infections with high mortality rates. Its ability to colonize surfaces and resist standard disinfectants undermines traditional hygiene practices, prompting an urgent need for novel strategies. Ultraviolet C (UVC) light offers a promising approach due to its rapid and broad-spectrum germicidal efficacy. This review comprehensively examines the current knowledge of UVC LED technology in combating C. auris, highlighting its effectiveness, limitations, and potential applications in healthcare hygiene. UVC light has potent activity against C. auris, including multidrug-resistant (MDR) strains. UVC can reduce C. auris on contaminated surfaces, aiding in transmission prevention. This review explores implementation strategies, including mobile UVC systems for targeted disinfection of high-risk areas and equipment, integration into air handling units (AHUs) to continuously disinfect recirculating air, and incorporation into water treatment systems. Current limitations in our understanding of UVC safety and effectiveness necessitate further research to optimize application protocols and ensure treatment safety while maintaining efficacy against C. auris. Integrating UVC disinfection technology into infection control programs holds promise for strengthening hygiene practices that will curb the global spread of C. auris and improve patient outcomes.

Multidrug resistant extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is considered a serious concern to public health worldwide including Bangladesh, and chicken meat is recognized as an important reservoir of ESBL-Ec dissemination to humans. Therefore, this study aimed to determine the prevalence, and phenotypic and genotypic antimicrobial resistance pattern of ESBL-producing Escherichia coli (ESBL-Ec) in frozen chicken meat. A total of 113 frozen chicken meat samples were purchased from 40 outlets of 9 branded supershops in five megacities in Bangladesh. Isolation and identification of Escherichia coli were done based on cultural, biochemical properties and PCR assay. The resistance pattern was determined by disk diffusion method. ESBL-encoding genes were determined by multiplex PCR. The results showed that 76.1% samples were positive for Escherichia coli, of which 86% were ESBL producers. All the isolates were multidrug-resistant (MDR). Resistance to 9–11 and 12–13 antimicrobial classes was observed in 38.4% and 17.4% isolates, respectively while only 11.6% were resistant to 3–5 classes. The possible extensively drug resistance (pXDR) was found in 2.3% isolates. The high single resistance was observed for oxytetracycline (93%) and amoxicillin (91.9%), followed by ampicillin (89.5%), trimethoprim-sulphamethoxazole and pefloxacin (88.4%), and tetracycline (84.9%). Most importantly, 89.6% of isolates were resistant to carbapenems. All the isolates were positive for blaTEM gene. However, the blaSHV and blaCTX-M-2 genes were identified in two ESBL-non producer isolates. None of the isolates were carried blaCTX-M-1 gene. This study provided evidence of wide dissemination of MDR and existence of pXDR ESBL-Ec in frozen chicken meat in Bangladesh. Our data clearly indicated that frozen chicken meat is, at the present time, the most significant known food source of ESBL-Ec to which peoples are regularly exposed.

Research is scarce regarding antimicrobial use and antimicrobial resistance (AMR) for specific localities in Northern Ireland (NI). Additionally, the effects of COVID-19 on antimicrobial pre-scribing patterns and AMR are unknown. Between the European Union (EU) and United States (US), AMR causes approximately 68,000 deaths annually. This study will provide a better understanding of antimicrobial use and prescribing patterns in Belfast and link with AMR. An electronic survey was developed and distributed to eighty-five community pharmacists in Belfast. Yearly and monthly prescription data was gathered from the Business Services Organisation and COVID-19 statistics from Gov.uk. All data was analysed on Microsoft Office Excel® and IBM® SPSS® Statistics 25. Overall response rate was 46%. Most pharmacists (82%) failed to address prescriber non-compliance with guidelines and antimicrobial dosing errors (59%). The most common in-dication for antibiotics was upper respiratory tract infections (URTIs). Overprescribing of anti-biotics was perceived as the leading cause of AMR, therefore 69% of pharmacists indicated in-creased General Practitioner (GP) compliance with guidelines would reduce AMR. Pharmacists’ are in an ideal position to reduce AMR through patient education however, it is demonstrated that pharmacists failed to adequately counsel patients on antibiotic use. All GP practices demonstrated inappropriate antibiotic use, especially for URTIs which suggests antibiotic appropriateness should be reviewed. Many patients avoided contact with GP’s during COVID-19 which may have resulted in reduced antibiotic use. This research established amoxicillin as the most commonly prescribed antibiotic, which is contributing to increased AMR with its broad-spectrum activity and has recognised a decrease in antibiotic prescribing during COVID-19. Based on the results found and a critical review of the literature it is recommended antimicrobial guidelines should be re-viewed and improved, enhanced training should be provided to pharmacists and the antibiotic guardian (AG) campaign should be reenergised.

Antibiotic resistance and accordingly their pollution because of uncontrolled usage has emerged as a serious problem in recent years. Hence, there is an increased demand to develope robust, easy, and sensitive methods for rapid evaluation of antibiotic and their residues. Among different analytical methods, the aptamer-based biosensors (aptasensors) have attracted considerable attention because of good selectivity, specificity, and sensitivity. This review gives an overview about recent developed aptasensors for antibiotic detection. The use of various aptamer assays to determine different groups of antibiotics like β-lactams, Aminoglycosides, Anthracyclines, Chloramphenicol, (Fluoro)Quinolones, Lincosamide, Tetracyclines and Sulfonamides are presented in this paper.

Antimicrobial resistance (AMR) is a major global concern; antibiotics and other regular treatment methods have failed to overcome the increasing number of infectious diseases. Bacteriophages (phages) are viruses that specifically target/ kill bacterial hosts without affecting other human microbiome. Phage therapy provides optimism in the current global healthcare scenario with a long history of its applications in humans that has now reached various clinical trials. Phages in clinical trials have specific requirements of being exclusively lytic, free from toxic genes with an enhanced host range that adds an advantage to this requisite. This review explains in detail the various phage engineering methods and their potential applications in therapy. To make phages more efficient, engineering has been attempted using techniques like conventional homologous recombination, Bacteriophage Recombineering of Electroporated DNA (BRED), clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, CRISPY-BRED/Bacteriophage Recombineering with Infectious Particles (BRIP), chemically accelerated viral evolution (CAVE), and phage genome rebooting. Phages are administered in cocktail form in combination with antibiotics, vaccines, and purified proteins, such as endolysins. Thus, phage therapy is proving to be a better alternative for treating life-threatening infections, with more specificity and fewer detrimental consequences.

With the increasing use of genome sequencing as a surveillance tool for molecular epidemiology of antimicrobial resistance (AMR), databases and clear nomenclature for AMR gene families are critical. Due to the convoluted nomenclatural history of the integron-associated trimethoprim-resistant dihydrofolatereductase (dfr) gene family, we decided to conduct a literature review, comparative sequence analysis, and phylogenetic investigation of the dfr family, the results of which are presented here and available at the Comprehensive Antibiotic Resistance Database (CARD). Overall, literature review and phylogenetic analysis resolved gene name synonyms based on sequence. We recommend adoption of phylogenetic methods to help guide AMR gene naming efforts and relegation of misleading names to synonyms.

Beetles are by far one of the most successful and diverse insect species. A part of this success is attributed to their elytra which provide various functions such as protection to their bodies from mechanical forces and the harmful environmental factors. In this study, Stag beetle (Lucanus cervus) elytra were first examined for their overall flexural properties and were observed to have a localized shape retaining snap-through mechanism which could play a crucial role in energy absorption, e.g. during battles and falls from heights. The snap-through mechanism was validated using theoretical calculations and also finite element simulations. Elytra were also characterized to examine their puncture and wear resistance. Our results show that elytra resisted puncture up to a force of 1.8±0.4 N and have puncture resistance compared to that of commercially available puncture resistant gloves. The measured values of modulus and hardness of elytra exocuticle were 10.3±0.8 GPa and 0.7±0.1 GPa. Using the hardness to modulus ratio as an indicator of wear resistance, the estimated value was observed to be in the range of wear resistant biological materials. Thus, our study demonstrates different mechanical properties of the stag beetle elytra which can be explored to design shape retaining bio-inspired composites with enhanced puncture and wear resistance.

Background: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers’ (HCWs) knowledge, attitudes and behaviours on antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented. Methods: A 43-item questionnaire was developed through a two-round modified Delphi consensus process. The UK target quota was 1,315 respondents. Results: 2,404 participants responded. The highest proportion were nursing and midwifery professionals (42%), pharmacists (23%) and medical doctors (18%). HCWs correctly answered that antibiotics are not effective against viruses (97%), they have associated side effects (97%), unnecessary use makes antibiotics ineffective (97%) and healthy people can carry antibiotic resistant bacteria (90%). However, fewer than 80% correctly answered that using antibiotics increases a patient’s risk of antimicrobial resistant infection or that resistant bacteria can spread from person to person. Whilst the majority of HCWs (81%) agreed there is a connection between their antibiotic prescribing behaviour and the spread of antibiotic resistant bacteria, only 64% felt that they have a key role in controlling antibiotic resistance. The top three barriers to providing advice or resources were lack of resources (19%), insufficient time (11%) and the patient being uninterested in the information (7%). Approximately 35% of UK respondents who were prescribers prescribed an antibiotic at least once in the last week due to fear of patient deterioration or complications. Conclusion: These findings highlight that a multifaceted approach to tackling the barriers to prudent antibiotic use in the UK is required and provides evidence for guiding targeted policy, intervention development and future research. Education and training should focus on patient communication, information on spreading resistant bacteria and increased risk for individuals.

: Crohn’s disease (CD) is a multifactorial chronic disorder that involves a combination of factors as genetic, immune response and gut microbiota. Actually, the therapy comprises salicylates, immunosuppressive agents, corticosteroids, biologic drugs. International guidelines don’t recommend the use of antibiotics except for septic complications of CD patients. The increased evidence of the implication of gut bacteria in this chronic disease support the rationale for using antibiotics as primary treatment of active CD. In the last decades several pathogens have been reported to be involved in the development of CD, but only Escherichia coli (E.coli) species and Mycobacterium avium paratubercolosis (MAP), aroused the interest due to their strong association with CD pathogenesis. Several meta-analyses have been published concerning antibiotic treatment in CD patients but randomized trials of antibiotic treatments against E.coli and MAP did not show prolonged benefits, and only generated conflicting results so much so that several questions are still unresolved regarding trial design, antibiotic dosing, the formulation used, the treatment course and the outcome measures. In this article we attempted to provide an overview and update of the trials on antibiotic treatment in active CD patients taking into account the role of pathogens, the mechanism by which the different antibiotics act on harmful pathogens, and antibiotic resistance. Finally, we also tried to draw new lines for future studies to use antibiotics to treat active CD patients

Staphylococcus spp. are among the main pathogens responsible for important infections worldwide, both in humans and in domestic or wild animals. Chiropterans, popularly known as bats, inhabit natural environments and human constructions, and have been considered potential disseminators of several pathogens. Studies have shown the expression of the mecA gene in these animals, being a significant threat to One Health. The objective of this study was to determine antibiotic resistance and the presence of the mecA gene in Staphylococcus spp. isolates from bats from forest areas in the municipalities of Paraná, Brazil. A total of 87 frugivorous chiropterans belonging to the family Phyllostomidae were captured. Of these, 87 rectal and 87 oral swabs samples were collected, re-sulting in 32 Staphylococcus spp. isolates. Twenty-four isolates were characterized as coagu-lase-negative, and 8 coagulase-positive Staphylococcus spp. (STACP), which showed notable re-sistance to oxacillin (78.12%), penicillin G (65.62%) and to other antimicrobials as well. One STACP isolate was mecA-positive. Therefore, further studies are needed to elucidate the mechanisms of contamination and dissemination of these pathogens, emphasizing that anthropic actions in na-tural environments, especially those related to the use of antimicrobials, pesticides may be the main reasons for the presence of resistant bacteria in bats.

Epithelial surfaces in humans are home to symbiotic microbes (i.e., microbiota) that influence the defensive function against pathogens depending on the health of the microbiota. Healthy microbiota contribute to the well-being of their host in general (e.g., via the gut-brain-axis), and their respective anatomical site in particular (e.g., oral, urogenital, skin or respiratory microbiota). Despite efforts towards a more responsible use of antibiotics, they are often prescribed for uncomplicated, self-limiting infections and can have a substantial negative impact on the gut microbiota. Treatment alternatives such as non-steroidal anti-inflammatory drugs may also influence the microbiota and thus can have lasting adverse effects. Herbal drugs offer a generally safe treatment option for uncomplicated infections of the urinary or respiratory tract. Additionally, their microbiota preserving properties allow for a more appropriate therapy of uncomplicated infections without contributing to an increase in antibiotic resistance or disturbing the gut microbiota. Here, herbal treatments may be a more appropriate therapy with a generally favorable safety profile.

Lemonomycin (1) was first isolated from the fermentation broth of Streptomyces candidus in 1964. The complete chemical structure was not elucidated until 2000 with extensive spectroscopic analysis. Lemonomycin is currently known as the only glycosylated tetrahydroisoquinoline antibiotic. Its potent antibacterial activity against Staphylococcus aureus and Bacillus subtilis and complex architecture make it an ideal target for total synthesis. In this short review, we summarize the research status of lemonomycin for biological activity, biosynthesis and chemical synthesis. The unique deoxy aminosugar-lemonose was proposed to play a crucial role in biological activity, as shown in other antibiotics, such as arimetamycin A, nocathiacin I, glycothiohexide α, and thiazamycins. Given the self-resistance of the original bacterial host, the integration of biosynthesis and chemical synthesis to pursue efficient synthesis and further derivatization is in high demand for the development of novel antibiotics to combat antibiotic-resistant infections.

Diversity as well as temporal and spatial changes of the proportional abundances of different antibiotics (cycling, mixing or combinations thereof) have been hypothesised to be an effective administrative control strategy in hospitals to reduce the prevalence of antibiotic-resistant pathogens in nosocomial or community-acquired infections. However, a rigorous assessment of the efficacy of these control strategies is lacking. The main purpose here is to present a mathematical framework for the assessment of control stategies from a processual stance. To this end, we adopt diverse measures of heterogeneity and diversity of proportional abundances based on the concept of entropy from other fields and adapt them to the needs in assessing the impact of variations in antibiotic consumption on antibiotic resistance. Thereby, we derive a family of diversity measures whose members exhibit different degrees of complexity. Most important, we extent these measures such that they account for the assessment of temporal changes in heterogeneity including otherwise undetected diversity-invariant permutations of antibiotics consumption and prevalence of resistant pathogens. We apply a correlation analysis for the assessment of associations between changes of heterogeneities on the antibiotics and on the pathogen side. As a showcase, which serves as a proof-of-principle, we apply the derived methods to records of antibiotic consumption and prevalence of antibiotic-resistant germs from University Hospital Dresden. Besides the quantification of heterogeneities of antibiotics consumption and antibiotic resistance, we show that a reduction of prevalence of antibiotic-resistant germs correlates with a temporal change of similarity with respect to the first observation of antibiotics consumption, although heterogeneity remains approximately constant. Although an interventional study is pending, our mathematical framework turns out to be a viable concept for the assessment and optimisation of control strategies intended to reduce antibiotic resistance.

Antibiotic Resistance (ABR) is increasing the mortality and morbidity associated with infectious diseases, besides increasing the cost of healthcare, saturating health-system capacity, and adversely affecting food security. Framing an appropriate narrative and engaging local communities through ‘One Health’ approach is essential to complement the top down measures. However, the absence of objective criteria to measure the performance of ABR interventions at community settings make it difficult to mobilize interest and investment for such interventions. An exercise was therefore done to develop an indicator framework for this purpose. An exhaustive list of indicators was developed from experiences gathered through community engagement work in a local panchayat (small administrative area) in Kerala, India, and a consultative process with health, veterinary, environment, and development experts. A prioritization exercise was done, looking at appropriateness, feasibility and validity, by global experts on ABR. A 15-point indicator framework was designed based on the prioritization process. The final set of indicators covers human health, animal health, environment management and Water Sanitation and hygiene (WASH) domains. The indicator framework was piloted in the panchayat(located in Kerala), which attained a score of 34 (maximum 45). The score increased when interventions were implemented to mitigate the ABR drives, indicating the framework is sensitive to change. Simultaneously, the indicator framework was tested in four sites from three other Indian states with different socioeconomic and health profiles, yielding different scores. Those collecting the field data were able to use it with minimal training. To conclude, this indicator framework can help policymakers broadly understand the factors contributing to ABR and measure the performance of interventions they choose to implement in the community

Background: Although rarely indicated, antibiotics are commonly used for acute diarrhoea in China. We conducted a randomized, double blind exploratory clinical trial of loperamide, berberine and turmeric for treatment of acute diarrhoea. Methods: Adults with acute uncomplicated diarrhoea were randomized to 4 groups: (A) loperamide; (B) loperamide and berberine; (C) loperamide and turmeric; (D) loperamide, berberine and turmeric. All participants were given rescue ciprofloxacin for use after 48 hours if symptoms worsened or were unimproved. Primary endpoints were feasibility and ciprofloxacin use during the 2 week follow-up period. Semi-structured interviews were conducted following recruitment. Results: Only 21.5% (278/1295) of patients screened were deemed eligible, and 49% (136/278) of these consented and entered into the final analysis. Most participants had mild symptoms, because most patients with moderate or severe symptoms wanted to be given antibiotics. Follow-up was good (94% at 2 weeks). Only two participants used rescue antibiotics compared to 65% of acute diarrhoea patients in the hospital during the recruitment period. The median symptom duration was: 14 hours in group B (IQR 10-22), 16 hours in group D (IQR 10-22), 18 hours in group A (IQR 10-33), 20 hours in group C (IQR 16-54). Re-consultation rates were low. There were no serious treatment-related adverse events. Most interviewed participants said the treatment was effective. Conclusion: Although recruitment was challenging because of widespread expectations for antibiotics, patients with mild diarrhoea accepted to try an alternative. This therapy requires further evaluation in a fully powered, randomised controlled trial among a broader sample.

Helicobacter pylori (H. pylori) is a global health concern, particularly in regions with a high incidence of stomach cancer. The effective eradication of this bacteria is essential for the prevention and treatment of related gastrointestinal disorders. However, antibiotic resistance has emerged as a significant challenge to effective treatment. This review examines antibiotic resistance among H. pylori populations in Central Asia, a region with limited data on this topic. We critically analyze the available literature, exploring the mechanisms behind resistance and highlighting implications for clinical practice and future research. Despite the lack of studies in the region, data suggest alarming levels of resistance to two common antibiotics, clarithromycin and metronidazole. These results underscore the need for enhanced surveillance and personalized treatment strategies to combat H. pylori infections and reduce the risk of stomach cancer in Central Asian populations.