Ž . Netherlands Journal of Medicine 52 1998 1–9 Current practice: Invited article Once-daily aminoglycosides: practical guidelines Jan M. Prins ) , Peter Speelman Academic Medical Centre, Department of Internal Medicine, DiÕision of Infectious Diseases, Tropical Medicine and AIDS, Room F4-221, Meibergdreef 9, Amsterdam 1105 AZ, Netherlands Received 3 April 1997; revised 26 August 1997; accepted 28 August 1997 Abstract There is ample evidence that once-daily dosing of aminoglycosides is preferable to the conventional regimens during the treatment of serious infections. Experimental and clinical studies also provide evidence that this regimen can be safely used in children, neutropenic patients and endocarditis. The use of once-daily tobramycin in cystic fibrosis merits further study, as the pharmacokinetics of the aminoglycosides are altered in these patients. The dose-adjustment strategy in patients with renal failure is still controversial, but reducing the daily dose whilst maintaining the q24-h interval has been demonstrated to be safe. Although the value of serum level monitoring in ensuring efficacy and avoiding toxicity has been overestimated in the past, especially in patients with renal failure, an undesirable accumulation of the aminoglycosides can occur. The best way to detect accumulation remains to be defined. q 1998 Elsevier Science B.V. Keywords: Aminoglycoside; Dosing schedule; Pharmacokinetics; Nephrotoxicity; Ototoxicity 1. Introduction Over the past decades, aminoglycosides have re- mained a mainstay of therapy for severe Gram-nega- tive infections, with approximately 1–2.5 defined Ž . daily dosages DDD per 100 bed days in the West- wx ern European hospitals 1 . The major drawback of this class of antibiotics is their potential for nephro- and ototoxicity. Especially the incidence of ototoxic- ity is often underestimated. For instance, 17.9% of ears screened for ototoxicity after aminoglycoside treatment showed hearing loss, as assessed by con- ) Corresponding author. Tel.: q31 20 5664380; fax: q31 20 6972286; e-mail: j.m.prins@amc.uva.nl ventional audiometry, whilst this percentage in- creased to 47% when frequencies up to 20 kHz were wx also tested 2 . Neuromuscular blockade has been reported, but this is sufficiently rare that clinical concern has focused on nephro- and ototoxicity. An additional problem is the important interpatient vari- ation in pharmacokinetics. Nomograms, which use body weight and estimated creatinine clearance, of- ten result in elevated trough levels or subtherapeutic wx peak levels 3 . During the past decade, new insights have been gained into the pharmacodynamics, and the patho- genesis of nephrotoxicity of aminoglycosides. As a result, controversy has arisen with respect to the preferred dosage regimen. These antibiotics were usually given thrice daily, but many in vitro and animal studies suggested that a once-daily regimen 0300-2977r98r$19.00 q 1998 Elsevier Science B.V. All rights reserved. Ž . PII S0300-2977 97 00071-5