Comparison of ampicillin-sulbactam and ticarcillin-clavulanic acid in patients with chronic renal failure: effects of differential pharmacokinetics on serum bactericidal activity
Hardin, T.C.; Butler, S.C.; Ross, S.; Wakeford, J.H.; Jorgensen, J.H.
PharmacoTherapy 14(2): 147-152
1994
ISSN/ISBN: 0277-0008 PMID: 8197032 Document Number: 423057
Study Objectives: To evaluate the pharmacodynamic antibacterial activity of ticarcillin-clavulanic acid (T-C) and ampicillin-sulbactam (A-S) combinations against reference bacterial strains in patients with end-stage renal disease maintained on long-term hemodialysis. Design. Randomized, crossover, controlled study. Setting. National Institutes of Health-funded general clinical research unit in a Veterans Administration Medical Center. Patients. Nine adult men with end-stage renal disease maintained on long-term hemodialysis. Two subjects did not complete the study due to problems of vascular access, and another withdrew for personal reasons. Interventions. On a nondialysis day, each subject was randomly administered either T-C 3.1 g or A-S 3 g as a slow intravenous infusion over 30 minutes. Serial blood samples were collected for measurement of antibiotic serum concentrations and determination of serum bactericidal titers. Following a washout period, the study was repeated with the alternative antibiotic combination. Measurements and Main Results. The mean observed apparent beta-half-life of clavulanic acid was substantially shorter than that for the other three drugs. The bactericidal activity of both A-S and T-C against non-beta-lactamase-producing (N-beta-LP) strains of S. aureus and E. coli was consistently high, as indicated by geometric mean SBTs of at least 1:5 at 24 hours. Against beta-lactamase-producing (beta-LP) S. aureus, the geometric mean SBTs for A-S were at least 1:25 throughout the study period, while the geometric mean SBTs for T-C decreased over 24 hours from 1:29 to 1:6. Against beta-LP E. coli, the bactericidal activities for both A-S and T-C were poor, with geometric mean peak SBTs of only 1:6 and 1:3, respectively. The geometric mean SBT for T-C against this E. coli strain had declined to 1:1 at 6 hrs. Conclusion. Increasing the dosing interval for T-C in patients with end-stage renal disease may lead to periods of insufficient clavulanic acid to protect ticarcillin from beta-lactamase degradation.