Colistin

Patients undergoing intensive chemotherapy for acute myeloid leukemia are at high risk for bacterial infections during therapy-related neutropenia. However, the use of specific antibiotic regimens for prophylaxis in afebrile neutropenic acute myeloid leukemia patients is controversial. This was a retrospective evaluation of 172 acute myeloid leukemia patients who received 322 courses of myelosuppressive chemotherapy and had an expected duration of neutropenia of >7 days. The patients were allocated to antibiotic prophylaxis groups and treated with colistin or ciprofloxacin through 2 different hematological services at our hospital as available. The infection rate was reduced from 88.6% to 74.2% through antibiotic prophylaxis (vs. without prophylaxis, p=0.04). A comparison of both antibiotic drugs revealed a trend towards fewer infections associated with ciprofloxacin prophylaxis (69.2% vs. 79.5% in the colistin group, p=0.07), as determined by univariate analysis. This result was...

Background: Multidrug-resistant strains of Acinetobacter baumannii have been reported increasingly around the world. The administration of an association of antibiotics has been proposed to create an active combination and to prevent the emergence of resistance. Methodology: The activity of colistin, rifampicin, gentamicin, imipenem and their associations was evaluated by means of killing curves in fourteen isolates belonging to three endemic PFGE types, in a university hospital of Buenos Aires city. The 14 isolates were selected on the basis of different mechanisms responsible for resistance to carbapenems and different susceptibility to colistin. Results: The mechanism responsible for the resistance to imipenem was the production of OXA-23 and OXA-58 carbapenemases. Heteroresistance to colistin was observed in six isolates. The associations colistin-rifampicin and colistin-imipenem were synergistic in heteroresistant isolates and prevented the development of colistin-resistant mut...

The molecular characterization of 37 clinical isolates of P. aeruginosa obtained during September 2013 and September 2014 was conducted based on the 16S rDNA and oprL genes. The genetic diversity among isolates was determined with ERIC-pcr. The segments of the opr L and 16s rDNA genes were used to detect all P. aeruginosa isolates. The ERIC-PCR bands generated patterns that allowed the separation of isolates into different groups or clades and classify them into different genotypes. The susceptibility pattern of the isolated strains against ceftazidime, imipenem, gentamicin and amikin was assessed by a disk diffusion method. The percentage of isolates resistant to ceftazidime, imipenem, gentamicin and amikin was 14%, 16%, 16% and 24% respectively. In general these percentages are relatively low compared to those reported in other countries and only one of the isolates (64113) showed multidrug resistance.

Acinetobacter baumannii has successfully developed resistance against all common antibiotics, including colistin (polymyxin E), the last universally active drug against this pathogen. The possible widespread distribution of colistin-resistant A. baumannii strains ...

The aim of this study was to determine the impact of carbapenemase-producingEnterobacteriaceae(CPE) in Spain in 2013 by describing the prevalence, dissemination, and geographic distribution of CPE clones, and their population structure and antibiotic susceptibility. From February 2013 to May 2013, 83 hospitals (about 40,000 hospital beds) prospectively collected nonduplicateEnterobacteriaceaeusing the screening cutoff recommended by EUCAST. Carbapenemase characterization was performed by phenotypic methods and confirmed by PCR and sequencing. Multilocus sequencing types (MLST) were determined forKlebsiella pneumoniaeandEscherichia coli. A total of 702Enterobacteriaceaeisolates met the inclusion criteria; 379 (54%) were CPE. OXA-48 (71.5%) and VIM-1 (25.3%) were the most frequent carbapenemases, andK. pneumoniae(74.4%),Enterobacter cloacae(10.3%), andE. coli(8.4%) were the species most affected. Susceptibility to colistin, amikacin, and meropenem was 95.5%, 81.3%, and 74.7%, respecti...

Background: Colistin is one of the oldest antibiotics in the polymyxin group, and is used mostly against gram-negative bacteria. Because of developing resistance among clinical isolates colistin has become an alternative drug for multidrug resistant bacteria. Objectives: To determine colistin resistance among isolates from Tamil Nadu, India. Methods: We included 94 gram-negative isolates from two centers in Tamil Nadu in the present study. Isolates were identified by 16S rRNA sequencing. Minimal inhibitory concentrations (MICs) were determined by agar dilution. Results: The isolates identified at species level included 48 Escherichia coli, 9 Klebsiella pneumoniae, 10 Pseudomonas aeruginosa, 5 Proteus mirabilis, 4 Salmonella enterica, 3 Enterobacter hormaechei, 3 Enterobacter cloacae, 2 Achromobacter xylosoxidans, 2 Acinetobacter baumannii, 1 Providencia vermicola, 1 Acinetobacter towneri, 1 Enterobacter gergoviae, 2 Providencia rettgeri, 1 Enterobacter asburiae, 1 Pseudomonas stutzeri, and 1 Salmonella typhi. The MIC of colistin ranged from 0.12 μg/ml to 128 μg/ml. The MIC 50 was 1 μg/mL and MIC 90 was >128 μg/ml. The MIC ≥ 8 μg/mL was resistant breakpoint for all the species. A total of 27 isolates were resistant to colistin. Colistin resistant isolates included E. coli (9/48), K. pneumoniae (6/9), P. aeruginosa (3/10), A. baumannii (1/2), P. mirabilis (4/5), E. cloacae (1/3), P. rettgeri (2/2), and S. enterica (1/4). Carbapenem susceptibility of colistin resistant isolates was tested and 14 were found to be resistant to meropenem. Conclusions: Our study indicates the emergence of colistin resistant isolates from clinical samples among different groups of gram-negative organisms. Resistance to both carbapenem and colistin occurs. Developing new antibiotics and programs to reduce nosocomial infections is necessary especially for multidrug resistant isolates.

We report the whole genome sequence analysis of Chryseobacterium oranimense G311, a multidrug resistant bacterium, including resistance to colistin, for the first time from a cystic fibrosis patient in France. Whole genome sequencing of C. oranimense G311 was performed using Ion Torrent PGM and RAST, EMBL-EBI server and ARG-ANNOT (Antibiotic Resistance Gene-ANNOTation) database were used for annotation of all genes including antibiotic resistance genes. General features of C. oranimense G311 draft genome were compared to the other available genomes of Chryseobacterium gleum and Chryseobacterium sp. CF 314. C. oranimense G311 was found to be resistant to all β-lactams, including imipenem and to colistin. The genome size of C. oranimense G311 is 4,457,049 bp in length, with 37.70% GC content. We found 27 AR genes in the genome, including β-lactamases which showed less identity with the known β-lactamase genes and could likely be novel. We found type I polyketide synthase operon follow...

The impact of under-acylation of lipid A on the interaction between Klebsiella pneumoniae LPS and polymyxins B and E was examined with fluorometric and calorimetric methods, and by (1)H NMR, using a paired wild type (WT) and the ΔlpxM mutant strains B5055 and B5055ΔlpxM, which predominantly express LPS with hexa- and penta-acylated lipid A structures respectively. LPS from B5055ΔlpxM displayed a fourfold increased binding affinity for polymyxins B and E compared with the B5055 WT LPS. EC50 values were consistent with polymyxin minimum inhibitory concentration (MIC) values for each strain. Accordingly, polymyxin exposure considerably enhanced the permeability of the B5055ΔlpxM OM. Analysis of the melting profiles of isolated LPS aggregates suggested that bactericidal polymyxin activity may relate to the acyl chains' phase of the outer membrane (OM). The enhanced polymyxin susceptibility of B5055ΔlpxM may be attributable to the favorable insertion of polymyxins into the more fluid...