Comparison of ampicillin-sulbactam and ticarcillin-clavulanic acid in patients with chronic renal failure: effects of differential pharmacokinetics on serum bactericidal activity.
OBJECTIVE
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.


METHODS
Randomized, crossover, controlled study.


METHODS
National Institutes of Health-funded general clinical research unit in a Veterans Administration Medical Center.


METHODS
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.


METHODS
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.


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.


CONCLUSIONS
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.
Hardin
T C
TC
Department of Pharmacology, University of Texas Health Science Center at San Antonio.
Butler
S C
SC
Ross
S
S
Wakeford
J H
JH
Jorgensen
J H
JH
D000328:Adult; D000368:Aged; D000667:Ampicillin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D002969:Clavulanic Acids / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D004359:Drug Therapy, Combination / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D015610:Serum Bactericidal Test; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013407:Sulbactam / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D013982:Ticarcillin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors
D002969:Clavulanic Acids; D065093:beta-Lactamase Inhibitors; C035444:sultamicillin; D000667:Ampicillin; C043215:ticarcillin-clavulanic acid; D013982:Ticarcillin; D013407:Sulbactam