[Resistance to antibiotic treatment produced in a model of experimental Pseudomonas aeruginosa peritonitis].
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.
Froidefond
S
S
Laboratoire Central de Microbiologie, Hôpital Purpån, Toulouse.
Saivin
S
S
Lemozy
J
J
Marchou
B
B
Auvergnat
J C
JC
Dabernat
H
H
D000583:Amikacin / Q000627:therapeutic use; D000818:Animals; D002442:Ceftazidime / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D015378:Imipenem / Q000627:therapeutic use*; D051379:Mice; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*
D002939:Ciprofloxacin; D015378:Imipenem; D000583:Amikacin; D002442:Ceftazidime
Emergence de résistance au cours de traitements antibiotiques dans un modèle de péritonite expérimentale à Pseudomonas aeruginosa.