26 Glenacre Crescent, Uddington, Glasgow G71 6EJ, UK
Sir,
Once-daily administration of gentamicin is probably more efficacious, and no more toxic, than multiple dosing,1 thus there is little indication for the traditional tds dosing, though it continues to be recommended by the British National Formulary. However, there are several notable disadvantages to the once-daily dosing regimen.
The recommended 7 mg/kg dose is considered too large and many centres, both in the USA and the UK tend to administer a smaller dose, e.g. 5 mg/kg.
Interpretation of levels is via the Hartford nomogram which is dependent on the full 7 mg/kg being given, levels being taken 614 h after the dose and the dose-to-sample interval being recorded on the request form. This is often not the case as the person who prescribes or administers the dose is often off duty 614 h later. Thus many centres do not measure levels at all or recommend a random level 1824 h following the dose, to detect cumulation. The former is unacceptable since there is a legal obligation to monitor gentamicin levels if given for more than 48 h and the legality as well as the utility of the latter is questionable.2
Additionally, there are too many contraindications to the once-daily regimen: in pregnant women and children, as well as patients with renal failure, neutropenia, endocarditis, cystic fibrosis, ascites and burns. In centres where once-daily administration is the default regimen, these contraindications can (and probably are) all too easily overlooked, especially by busy house officers.
Of further concern, are recent reports of side effects associated with once-daily dosing in certain patient groups: Bakri et al.3 reported a high rate of ototoxicity (5/28; 18%) in febrile neutropenic patients, while Koo et al.4 found a significant correlation between peak serum gentamicin concentration and nephrotoxicity in elderly patients.
The twice-daily regimen, on the other hand, is well tried and tested. The dose of 2 mg/kg bd (2.5 mg/kg bd for neutropenic patients) achieves adequate peak concentrations (510 mg/L at 1 h post-dose) in most cases. Given that gentamicin is often administered concomitantly with broad spectrum ß-lactam agents and has a pronounced post-antibiotic effect, the increased dose of 7 mg/kg may be regarded as overkill. Thus, the twice-daily gentamicin regimen has many fewer contraindications, is potentially associated with better compliance and easier interpretation than the once-daily regimen, while retaining most of the convenience of less frequent administration, probable increased efficacy and decreased toxicity over the thrice-daily regimen.
In conclusion, it is possible to adopt the twice-daily but not the once-daily regimen as the sole method of gentamicin administration, mainly because of the multiple exclusions above. Both regimens could co-exist in hospital antimicrobial policies, but further comparative work to explore feasibility and compliance as well as efficacy and toxicity is needed.
Notes
J Antimicrob Chemother 2001; 47: 121122
Tel: +44-1698-811250; Fax: +44-077997-14798; E-mail: mmorgan{at}bizonline.co.uk
References
1 . Prins, J. M., Kuijper, E. J., Tange, R. A. & Speelman, P. (1993). Once versus thrice daily gentamicin in patients with serious infection. Lancet 341, 3359.[ISI][Medline]
2 . MacGowan, A. P. & Reeves, D. S. (1994). Serum monitoring and practicalities of once-daily aminoglycoside dosing. Journal of Antimicrobial Chemotherapy 33, 34950.[ISI][Medline]
3 . El Bakri, F., Pallett, A., Smith, A. G. & Duncombe, A. S. (1998). Ototoxicity induced by once-daily gentamicin. Lancet 351, 14078.[ISI][Medline]
4 . Koo, J., Tight, R., Rajkumar, V. & Hawa, Z. (1996). Comparison of once daily versus pharmacokinetic dosing of aminoglycosides in elderly patients. American Journal of Medicine 101, 17783.[ISI][Medline]