Emergence of resistance after therapy with antibiotics used alone or combined in a murine model.
A murine model of peritonitis allowing detection and quantification of in-vivo acquired resistance during short term therapy has been used in order to evaluate the capacity of antimicrobial combinations to limit emergence of resistance, as compared to individual components of the regimens. Mice were challenged intraperitoneally with 10(8) cfu of bacteria. Two hours later, a single antibiotic dose was injected subcutaneously: amikacin (15 mg/kg), ceftriaxone (50 mg/kg), pefloxacin (25 mg/kg), amikacin + ceftriaxone, amikacin + pefloxacin or ceftriaxone + pefloxacin. Escherichia coli and Staphylococcus aureus never became resistant. Single drug therapy yielded resistant mutants in Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae and Pseudomonas aeruginosa as follows: 74% of ceftriaxone-treated animals, 57% of pefloxacin treated animals and 27% of amikacin treated animals. All the tested combinations reduced the frequency of in-vivo acquired resistance produced by single drugs, and no combination selected resistance when the separate agents of the combination did not. Combining antimicrobial agents limits the risk of emergence of resistance during antibiotic therapy.
D000583:Amikacin / Q000494:pharmacology*; D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D002443:Ceftriaxone / Q000494:pharmacology* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D004754:Enterobacter / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D007612:Kanamycin / Q000031:analogs & derivatives*; D007711:Klebsiella pneumoniae / Q000187:drug effects; D051379:Mice; D009643:Norfloxacin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015366:Pefloxacin; D010538:Peritonitis / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012706:Serratia marcescens / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
D015366:Pefloxacin; D007612:Kanamycin; D002443:Ceftriaxone; D000583:Amikacin; D009643:Norfloxacin