SINGLE DAILY DOSING
Single daily doses of aminoglycosides are at least as ef-fective as and no more toxic than multiple daily doses. Some studies suggest that single daily dosing may actu-ally be less nephrotoxic than more frequent dosing. Since aminoglycoside uptake across the brush border of proximal renal cortical tubular cells is saturable, giving a single large dose should result in less renal accumula-tion; this has now been shown in patients receiving a single bolus injection of gentamicin compared with those administered a continuous 24-hour intravenous infusion. One clinical trial recently demonstrated that ototoxicity was also reduced when single daily dosing was used.
The magnitude of the rapid-killing effect and the du-ration of the postantibiotic effect of the aminoglycosides are proportional to their peak concentration at the site of the infection; that is, the higher the peak concentra-tion, the more pronounced these effects. Giving amino-glycosides as a single daily dose results in a higher peak tissue concentration than if the total daily dose were di-vided and given more frequently. Single daily dosing with amikacin results in higher drug concentrations in the bronchial secretions of patients with pneumonia.
Clinical trials of single daily dosing of aminoglyco-sides have been done in adults, pregnant women, and children for a variety of indications, including serious infections, pelvic inflammatory disease, abdominal sep-sis, cystic fibrosis, and the empirical treatment of neu-tropenic patients with fever. While single daily dosing of aminoglycosides is justified in most patients, it may be inadequate when given to provide synergism with β-lactam antibiotics in enterococcal endocarditis.