JAC Advance Access originally published online on January 16, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Antimicrobial Chemotherapy (2004) 53, 297-304
© 2004 The British Society for Antimicrobial Chemotherapy
Pharmacodynamic study of ß-lactams alone and in combination with ß-lactamase inhibitors against Pseudomonas aeruginosa possessing an inducible ß-lactamase
1 School of Pharmacy, University of Connecticut, Storrs, CT 06269; 2 Center for Anti-Infective Research and Development, and 3 Division of Infectious Diseases, Hartford Hospital, Hartford, CT 06102; 4 School of Medicine, Creighton University, Omaha, NE 68178, USA
Received 8 July 2003; returned 15 September 2003; revised 21 October 2003; accepted 5 November 2003
Objectives: The antimicrobial efficacies of ß-lactams alone and in combination with ß-lactamase inhibitors were investigated by applying a rabbit tissue cage model against a strain of Pseudomonas aeruginosa with an inducible AmpC (iAmpC) ß-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 ß-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: piperacillin, tazobactam, ticarcillin, clavulanate, ß-lactamase inhibitor, tissue cage model, ß-lactamase induction
* Correspondence address. Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA. Tel: +1-860-545-3941; Fax: +1-860-545-3992; E-mail: dnicola{at}harthosp.org
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. A. Stubbs, M. Balcewich, B. L. Mark, and D. J. Vocadlo Small Molecule Inhibitors of a Glycoside Hydrolase Attenuate Inducible AmpC-mediated beta-Lactam Resistance J. Biol. Chem., July 20, 2007; 282(29): 21382 - 21391. [Abstract] [Full Text] [PDF]
|
|