JAC Advance Access published online on January 16, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh057
© 2004 by The British Society for Antimicrobial Chemotherapy
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Original article
1 School of Pharmacy, University
of Connecticut, Storrs, CT 06269; Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT 06102;
* Corresponding author. E-mail: dnicola{at}harthosp.org.
Received 8 July 2003
; revised 21 October 2003
; accepted 5 November 2003
Objectives: The antimicrobial efficacies
of 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 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, Pharmacodynamic study of
-lactams
alone and in combination with
-lactamase inhibitors against Pseudomonas
aeruginosa possessing
an inducible -lactamase
2 Center for Anti-Infective Research and Development,
and Division of Infectious
Diseases, Hartford Hospital, Hartford, CT 06102;
3 School of Medicine, Creighton University,
Omaha, NE 68178, USA
4 Center for Anti-Infective Research and Development,
and
-lactams alone and in combination
with -lactamase inhibitors were investigated
by applying a rabbit tissue cage model against a strain of Pseudomonas
aeruginosa with an inducible AmpC (iAmpC) -lactamase.-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.-lactamase inhibitor, tissue cage model, -lactamase induction
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