Reference

The in vivo postantibiotic effect of imipenem and other new antimicrobials

The in vivo postantibiotic effect of imipenem and other new antimicrobials. Gudmundsson, S.; Vogelman, B.; Craig, W. A. (Wm. S. Middleton Mem. V. A. Hosp., Univ. Wisconsin, Madison, WI, USA). J. Antimicrob. Chemother., 18(Suppl. E), 67-73 (English) 1986. CODEN: JACHDX. ISSN: 0305-7453. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The postantibiotic effect (PAE; the suppression of bacterial growth that persists after short exposure of a microorganism to an antimicrobial) in vivo of imipenem [64221-86-9], cefoperazone [62893-19-0] and latamoxef [64952-97-2] was investigated in a neutropenic mouse thigh model. Two hours after inoculation of 106 colony-forming units of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa into each thigh, the neutropenic mice were treated with single doses of 50-200 mg/kg imipenem, 40-1200 mg/kg cefoperazone and 50-100 mg/kg latamoxef. Serum levels exceeded the min. inhibitory concn. for 1.1-2.9 h. Cefoperazone and latamoxef induced PAEs of 2.1-5.6 h for S. aureus, but no significant PAEs were induced for the Gram-neg. bacilli. In contrast imipenem produced PAE of 0.9-4.6 h with P. aeruginosa. However, strain variation was obsd. in the duration of the PAE after imipenem. These data are in concordance with the PAEs of the antimicrobials under study when these are detd. in vitro.

Evaluation of aztreonam, cefoperazone, latamoxef and ceftazidime in the hamster colitis model

Evaluation of aztreonam, cefoperazone, latamoxef and ceftazidime in the hamster colitis model. Weinberg, Diane S.; Fernandes, Prabhavathi B.; Kao, Chi Chien; Clark, Junius M.; Bonner, Daniel P.; Sykes, Richard B. (Squibb Inst. Med. Res., Princeton, NJ 08540, USA). J. Antimicrob. Chemother., 18(6), 729-45 (English) 1986. CODEN: JACHDX. ISSN: 0305-7453. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Aztreonam [78110-38-0], ceftazidime [72558-82-8], cefoperazone [62893-19-0] and latamoxef (moxalactam) [64952-97-2] were evaluated in a hamster model for antibiotic-assocd. colitis. Aztreonam, a novel monocyclic b-lactam antibiotic specifically directed against aerobic gram-neg. bacteria with limited activity against Gram-pos. and anaerobic bacteria, did not cause hemorrhagic cecitis and death in hamsters when administered i.p. or orally. Quant. cecal cultures showed no changes in the anaerobic cecal microflora of hamsters treated i.p. with aztreonam and only a temporary decrease in anaerobic Gram-neg. bacilli in hamsters treated orally. Clostridium difficile And its cytotoxin were not present in these animals. Parenteral administration of ceftazidime also did not affect the anaerobic cecal microflora or cause cecitis. However, when given orally, ceftazidime suppressed the anaerobic cecal microflora and a lethal C. difficile-induced cecitis developed. Latamoxef or cefoperazone given parenterally resulted in cecitis and death in 5 days with marked changes in the anaerobic cecal microflora and C. difficile present in the cecal contents of these animals. The lethal hemorrhagic cecitis obsd. in this study was indistinguishable from that seen in the clindamycin-induced colitis model in the hamster. The possible correlation of these findings to gastrointestinal disturbances as a complication of antibiotic therapy in humans is discussed.