Comparison of Ampicillin‐Sulbactam and Ticarcillin‐Clavulanic Acid in Patients With Chronic Renal Failure: Effects of Differential Pharmacokinetics on Serum Bactericidal Activity

Abstract

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 β‐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‐β‐lactamase‐producing (Nβ‐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 β‐lactamase‐producing (β‐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 β‐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 β‐lactamase degradation.