-
Views
-
Cite
Cite
Chonghua Li, David P. Nicolau, Philip D. Lister, Richard Quintiliani, Charles H. Nightingale, Pharmacodynamic study of β-lactams alone and in combination with β-lactamase inhibitors against Pseudomonas aeruginosa possessing an inducible β-lactamase, Journal of Antimicrobial Chemotherapy, Volume 53, Issue 2, February 2004, Pages 297–304, https://doi.org/10.1093/jac/dkh057
Close - Share Icon Share
Abstract
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.
