Journal Article

Pharmacodynamic study of β-lactams alone and in combination with β-lactamase inhibitors against <i>Pseudomonas aeruginosa</i> possessing an inducible β-lactamase

Chonghua Li, David P. Nicolau, Philip D. Lister, Richard Quintiliani and Charles H. Nightingale

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 53, issue 2, pages 297-304
Published in print February 2004 | ISSN: 0305-7453
Published online February 2004 | e-ISSN: 1460-2091 | DOI:
Pharmacodynamic study of β-lactams alone and in combination with  β-lactamase inhibitors against Pseudomonas aeruginosa possessing  an inducible β-lactamase

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Objectives: The antimicrobial efficacies of β-lactams alone and in combination with β-lactamase inhibitors were investigated by applying a rabbit tissue cage model against a strain of Pseudomonas aeruginosa with an inducible AmpC (iAmpC) β-lactamase.

Methods: Two sterilized golf Wiffle balls were surgically implanted in the rabbit dorsal cervical area. After 4 weeks, Wiffle balls had filled with tissue cage fluid (TCF), in which 2 mL of 106 cfu/mL of the test isolate were inoculated. To achieve the same T > MIC as in humans, 400 mg/kg of the β-lactams alone and in combination was administered twice a day via subcutaneous injection. The dosing regimens were as follows: piperacillin alone, 4 g piperacillin/0.5 g tazobactam; ticarcillin alone, 3 g ticarcillin/0.1 g clavulanate; and 3 g ticarcillin/ 0.3 g clavulanate.

Results: The changes in bacterial counts (log cfu/mL) after the 3 day treatments were as follows: 1.03 ± 0.97 (control), –1.31 ± 0.61 (piperacillin), –2.81 ± 0.53 (4 g piperacillin/0.5 g tazobactam), –1.61 ± 0.68 (ticarcillin), –3.42 ± 0.75 (3 g ticarcillin/0.1 g clavulanate) and –1.65 ± 1.47 log cfu/mL (3 g ticarcillin/0.3 g clavulanate). AmpC induction by high-dose clavulanate was observed in rabbit TCF, and was confirmed by the in vitro induction study.

Conclusions: The study indicated that tazobactam significantly enhanced the antibacterial activity of piperacillin against iAmpC P. aeruginosa; clavulanate had synergy with the antibacterial activity of ticarcillin at low concentration, but had no effect on ticarcillin at high concentration due to AmpC induction by clavulanate.

Keywords: Keywords: piperacillin, tazobactam, ticarcillin, clavulanate, β-lactamase inhibitor, tissue cage model, β-lactamase induction

Journal Article.  5189 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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