Aminoglycoside administration as a single daily dose. An improvement to current practice or a repeat of previous errors?
Despite the availability of newer and safer antibacterials, aminoglycosides continue to play a major role in the management of infections in hospitalised patients. The concept of single daily dose (SDD) regimens was introduced many years ago and is now receiving much attention as an alternative regimen for this class of drugs. To evaluate the rationale and clinical support for SDD schemes, we conducted a 'MEDLINE' search to locate relevant preclinical and clinical literature pertaining to this issue. The results of animal model and noncomparative clinical data tended to be variable and inconclusive. We were able to identify 28 prospective comparative clinical trials; however, only one was randomised, double-blind and of sufficient sample size to detect differences in efficacy between treatment arms, should any exist. Despite these flaws, our review suggests that SDD schemes appear to be no more efficacious and no less toxic, but may be less costly, than traditional multiple daily dose schemes. We also assessed the predicted disposition of tobramycin/gentamicin in 415 patients with known pharmacokinetic parameters. With doses of 7 mg/kg at intervals of between 24 and 60 hours (depending upon renal function), the maximum serum concentration at steady-state (Cmaxss) varied from 8.5 to 55.6 mg/L, while the Cminss was < 2.0 mg/L in the majority of patients. Mid-interval serum aminoglycoside concentrations were < 0.5 mg/L in up to 23% of patients, suggesting possible underdosage in certain patients with this scheme. More conclusive clinical evidence is necessary before SDD schemes should be adopted as standard clinical practice. Empirical weight-based dosage schemes appear to yield widely variable serum aminoglycoside concentrations which could be considered therapeutically inadequate or toxic.
Marra
F
F
Department of Pharmacy, Vancouver Hospital and Health Sciences Centre, British Columbia, Canada.
Partovi
N
N
Jewesson
P
P
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D003428:Cross Infection / Q000188:drug therapy*; D004334:Drug Administration Schedule; D006801:Humans
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents