title: Enhancement of leucocyte killing of resistant bacteria selected during exposure to aminoglycosides or quinolones.
abstract: In vitro exposure to aminoglycosides and quinolones may select resistant subpopulations, although this is not a common clinical problem. This study was designed to determine whether aminoglycoside and quinolone resistant bacteria are more susceptible to leucocyte (WBC) killing. Cultures of Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus were pretreated with aminoglycosides (netilmicin, amikacin) and quinolones (enoxacin, ciprofloxacin) at 1/2 MIC for 24 h. The median susceptibility of bacteria selected during antibiotic exposure was reduced four-fold. These resistant subpopulations (10(6) cfu/ml) were exposed to 10(7) human WBC/ml for 6 h in antibiotic free cell culture media with 10% fresh human serum. Enhanced WBC activity was observed against all antibiotic pretreated bacteria in comparison with untreated controls (P less than 0.01). After 4 h of exposure to WBC, aminoglycoside or quinolone pretreated cultures of P. aeruginosa were reduced by 1.3-1.7 log, in comparison with a reduction of only 0.5 log in control cultures. These observations may explain in part the infrequent therapeutic failure with these drugs in hosts with competent neutrophils despite the potential of these drugs to select resistant strains in vitro.
authors.affiliation: Department of Medicine, Brown University, Roger Williams General Hospital, Providence, R.I. 02908.
authors.forename: F
authors.initials: F
authors.lastname: Schlaeffer
authors.forename: J
authors.initials: J
authors.lastname: Blaser
authors.forename: J
authors.initials: J
authors.lastname: Laxon
authors.forename: S
authors.initials: S
authors.lastname: Zinner
mesh_terms: D042462:4-Quinolones; D000328:Adult; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010587:Phagocytosis / Q000187:drug effects*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D042462:4-Quinolones; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents