Pseudomonas peritonitis in neutropenic rats treated with amikacin, ceftazidime and ticarcillin, alone and in combination.
Peritonitis in neutropenic rats, caused by a strain of Pseudomonas aeruginosa resistant to amikacin and ticarcillin alone but susceptible to ceftazidime and combinations of amikacin with ticarcillin, amikacin with ceftazidime and ticarcillin with ceftazidime, was investigated. Four hours after a bacterial challenge with a LD70 intraperitoneal dose of P. aeruginosa (1.5 X 10(8) cfu/ml), either amikacin, ticarcillin, ceftazidime, amikacin-ticarcillin, amikacin-ceftazidime, or ticarcillin-ceftazidime was administered at dosing intervals that mimicked the serum concentrations of the drugs found in humans after therapeutic doses. When the serum concentrations did not exceed the MIC, as occurred with amikacin, no difference in survival was observed compared with controls. All other regimens resulted in animal survival during the treatment. When therapy was stopped only those regimens resulting in serum concentrations above the MBC were effective (amikacin-ticarcillin, amikacin-ceftazidime, ticarcillin-ceftazidime). The recovery of viable bacteria from the peritoneum agreed well with mortality.
D000380:Agranulocytosis / Q000150:complications*; D000583:Amikacin / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D002442:Ceftazidime / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D009503:Neutropenia / Q000150:complications*; D010406:Penicillins / Q000627:therapeutic use*; D010529:Peritoneal Cavity / Q000382:microbiology; D010538:Peritonitis / Q000188:drug therapy*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D013982:Ticarcillin / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*
D010406:Penicillins; D000583:Amikacin; D002442:Ceftazidime; D013982:Ticarcillin