AMINOGLYCOSIDE ADMINISTRATION AS A SINGLE DAILY DOSE - AN IMPROVEMENTTO CURRENT PRACTICE OR A REPEAT OF PREVIOUS ERRORS

Despite the availability of newer and safer antibacterials, aminoglyco sides continue to play a major role in the management of infections in hospitalised patients. The concept of single daily dose (SDD) regimen s was introduced many years ago and is now receiving much attention as an alternative regimen for this class of drugs. To evaluate the ratio nale and clinical support for SDD schemes, we conducted a 'MEDLINE' se arch to locate relevant preclinical and clinical literature pertaining to this issue. The results of animal model and noncomparative clinica l data tended to be variable and inconclusive. We were able to identif y 28 prospective comparative clinical trials; however, only one was ra ndomised, double-blind and of sufficient sample size to detect differe nces in efficacy between treatment arms, should any exist. Despite the se flaws, our review suggests that SDD schemes appear to be no more ef ficacious and no less toxic, but may be less costly, than traditional multiple daily dose schemes. We also assessed the predicted dispositio n of tobramycin/gentamicin in 415 patients with known pharmacokinetic parameters. With doses of 7 mg/kg at intervals of between 24 and 60 ho urs (depending upon renal function), the maximum serum concentration a t steady-state (C-max(ss)) varied from 8.5 to 55.6 mg/L, while the C-m in(ss) was <2.0 mg/L in the majority of patients. Mid-interval serum a minoglycoside 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 shou ld be adopted as standard clinical practice. Empirical weight-based do sage schemes appear to yield widely variable serum aminoglycoside conc entrations which could be considered therapeutically inadequate or tox ic.