Synergy between polyethylenimine and different families of antibiotics against a resistant clinical isolate of Pseudomonas aeruginosa - PubMed (original) (raw)

Synergy between polyethylenimine and different families of antibiotics against a resistant clinical isolate of Pseudomonas aeruginosa

Hayssam Khalil et al. Antimicrob Agents Chemother. 2008 May.

Abstract

The in vitro activities of 10 families of antimicrobial agents alone and in combination with a synthetic polycationic polymer, polyethylenimine (PEI), against a resistant clinical isolate of Pseudomonas aeruginosa were investigated by MIC assays, checkerboard testing, and killing curve studies. At a concentration of 250 nM, PEI (10 kDa) was not directly bactericidal or bacteriostatic; but when it was used in combination with novobiocin, ceftazidime, ampicillin, ticarcillin, carbenicillin, piperacillin, cefotaxime, chloramphenicol, rifampin, or norfloxacin, it significantly reduced the MICs of these antibiotics by 1.5- to 56-fold. However, the MICs of aminoglycosides, polymyxins, and vancomycins were increased by 1.2- to 5-fold when these drugs were combined with PEI; and the MICs of tetracycline, erythromycin, ciprofloxacin, and ofloxacin were not affected when these drugs were combined with PEI. In the killing curve studies, combinations of PEI with novobiocin, ceftazidime, chloramphenicol, or rifampin resulted in 5- to 8-log(10) CFU/ml reductions in bacterial counts when 25% of the MIC of each antibiotic was used. These results indicate that infections due to resistant Pseudomonas strains could be treated by the use of a synergistic combination of PEI and antimicrobial drugs.

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Figures

FIG. 1.

FIG. 1.

Chemical structures of the hydrophilic (A) and the hydrophobic (B) drugs tested in this study.

FIG. 2.

FIG. 2.

In vitro growth and killing curves of Pseudomonas aeruginosa 100609 exposed to four hydrophobic antibiotics whose activities are synergistic with PEI. •, control growth curve of the strain in the absence of antibiotics and PEI; ▪, growth curve with PEI (250 μg/ml); ▴, growth curve with antibiotic (25% of the MIC); and ⋄, growth curve with antibiotic (25% of MIC) and PEI (250 μg/ml). Data are the means ± standard deviations of an experiment performed in triplicate.

FIG. 3.

FIG. 3.

In vitro growth and killing curves of Pseudomonas aeruginosa 100609 exposed to three antibiotics antagonized or not affected by PEI. •, control growth curve of the strain in the absence of antibiotics and PEI; ▪, growth curve with PEI (250 μg/ml); ▴, growth curve with antibiotic (25% of the MIC); and ⋄, growth curve with antibiotic (25% of MIC) and PEI (250 μg/ml). Data are the means ± standard deviations of an experiment performed in triplicate.

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