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[Resistance to antibiotic treatment produced in a model of experimental Pseudomonas aeruginosa peritonitis]
S Froidefond1, S Saivin, J Lemozy
1Laboratoire Central de Microbiologie, Hôpital Purpån, Toulouse.
Abstract:
A mouse model of experimental Pseudomonas aeruginosa peritonitis was used to evaluate the emergence of resistant mutants during antimicrobial therapy. Mice were infected intraperitoneally with a large inoculum (10(8) CFU + 125 mg talcum) of one of eight strains of Pseudomonas aeruginosa and treated for eight hours with imipenem (IPM) (2 mg/kg/60 min), ciprofloxacin (CIP) (5 mg/kg/45 min), ceftazidime (CAZ) (2 mg/kg/45 min), and amikacin (AN) (2 mg/kg/45 min), alone or in combination. Dosages were selected to achieve and maintain for 8 hours intraperitoneal concentrations similar to those seen in human bronchial secretions. Emergence of resistant strains occurred in 88% of mice after IPM, 29% after CIP, and 31% after CAZ. MICs for resistant strains were increased 8-fold to 512-fold above baseline. Given in combination, IPM and CIP use was followed with lower rates of resistance to each drug (6% and 2% respectively) than use of each antimicrobial alone (p less than 0.001). Combination with amikacin reduced resistance rates for all the antimicrobials studied. No resistant strains occurred with the CIP-CAZ combination. Under the experimental conditions used, the CIP-CAZ combination provided the best results, although the difference with the CIP-IPM combination was not statistically significant.
Insights
Antimicrobial resistance emerged frequently in Pseudomonas aeruginosa peritonitis treated with imipenem, ciprofloxacin, or ceftazidime alone. Combinations like ciprofloxacin-ceftazidime significantly reduced resistance development.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Pseudomonas aeruginosa is a significant opportunistic pathogen.
- Antimicrobial resistance is a growing global health concern.
- Understanding resistance emergence during therapy is crucial for effective treatment.
Purpose of the Study:
- To evaluate the emergence of resistant Pseudomonas aeruginosa mutants during antimicrobial therapy.
- To compare the efficacy of different antimicrobial agents and combinations in preventing resistance.
- To identify optimal treatment strategies against Pseudomonas aeruginosa peritonitis.
Main Methods:
- A mouse model of experimental Pseudomonas aeruginosa peritonitis was utilized.
- Mice were infected and treated with imipenem, ciprofloxacin, ceftazidime, or amikacin, alone and in combination.
- Antimicrobial concentrations were maintained to mimic human bronchial secretions.
- Emergence of resistant strains and Minimum Inhibitory Concentrations (MICs) were assessed.
Main Results:
- High rates of resistance emerged with monotherapy: 88% with imipenem, 29% with ciprofloxacin, and 31% with ceftazidime.
- Combination therapy significantly reduced resistance rates (e.g., 6% for imipenem and 2% for ciprofloxacin).
- The ciprofloxacin-ceftazidime combination resulted in no resistant strains, showing superior efficacy.
Conclusions:
- Monotherapy with imipenem, ciprofloxacin, or ceftazidime leads to significant emergence of Pseudomonas aeruginosa resistance.
- Combination antimicrobial therapy, particularly ciprofloxacin-ceftazidime, is highly effective in preventing resistance development.
- These findings support the use of combination therapy to combat antimicrobial resistance in Pseudomonas aeruginosa infections.