Sir, Dr Parienti reminds us, in his comments 1 on the DAUFIN trial, 2 that simpler is not always better, even if the adherence rate was better with once-daily regimens than with twice-daily regimens according to a recent meta-analysis 3 (but the effect was only modest and more pronounced at the time of treatment initiation). Treatment interruptions are a risk factor for non-nucleotide reverse transcriptase inhibitor (NNRTI) resistance development, but no difference has been shown when nevirapine was adminis- tered once or twice a day. 4 More early virological failures with resistance to efavirenz have been observed with didanosine/lamivudine/efavirenz once a day compared with zidovudine/lamivudine þ efavirenz twice a day, 5 but the adherence rate was not different between treatment arms; therefore, the resistance mutations are probably more associated with the NRTI background choice. Despite a non-optimal adherence rate with the once-daily regimen in the DAUFIN trial, the high virological failure rate remains unexplained, and the same virological failures have been observed in a study by Lapadula et al., 6 which evaluated the tenofovir, emtricitabine and nevirapine combination, but with a twice-a-day nevirapine administration. Finally, if we agree that simpler is not always better, on the other hand, it is not worse. According to clinical trials, as well as real life, most of the patients on antiretroviral treatment remain in virological success while more and more combinations are administered once daily. Transparency declarations C. A. has received consulting fees from Gilead and GlaxoSmithKline and lecture fees from Bristol-Myers Squibb, GlaxoSmithKline and Merck. All other authors: none to declare. References 1. Parienti JJ. Comment on: High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients. J Antimicrob Chemother 2009; 63: 1080. 2. Rey D, Hoen B, Chavanet P et al. High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients. J Antimicrob Chemother 2009; 63: 380–8. 3. Parienti JJ, Bangsberg DR, Verdon R et al. Better adherence with once-daily antiretroviral regimens: a meta-analysis. Clin Infect Dis 2009; 48: 484–8. 4. Parienti JJ, Massari V, Descamps D et al. Predictors of virologic failure and resistance in HIV-infected patients treated with nevirapine- or efavirenz-based antiretroviral therapy. Clin Infect Dis 2004; 38: 1311–6. 5. Berenguer J, Gonzalez J, Ribera E et al. Didanosine, lamivudine, and efavirenz versus zidovudine, lamivudine, and efavirenz for the initial treatment of HIV type 1 infection: final analysis (48 weeks) of a prospective, randomized, noninferiority clinical trial, GESIDA 3903. Clin Infect Dis 2008; 47: 1083–92. 6. Lapadula G, Costarelli S, Quiros-Roldan E et al. Risk of early viro- logical failure of once-daily tenofovir– emtricitabine plus twice-daily nevirapine in antiretroviral therapy-naive HIV-infected patients. Clin Infect Dis 2008; 46: 1127–9. Journal of Antimicrobial Chemotherapy doi:10.1093/jac/dkp053 Advance Access publication 27 February 2009 Comment on: Aminoglycoside drugs in clinical practice: an evidence-based approach Emma Edmond Keuleyan 1 * and Krastju Georgiev Kirilov 2 1 Department of Clinical Microbiology, Medical Institute— Ministry of the Interior, Sofia, Bulgaria; 2 Department of Cardiology, Medical Institute—Ministry of the Interior, Sofia, Bulgaria Keywords: sepsis, infective endocarditis, antibiotic combinations, guidelines *Corresponding author. Tel: þ359-2-9821451; Fax: þ359-2- 9542875; E-mail: emma_keuleyan@yahoo.com Sir, We read with great interest the recently published review ‘Aminoglycoside drugs in clinical practice: an evidence-based approach’. 1 We welcome the authors’ intention to present an evidence-based approach to aminoglycoside use, which they do in the form of a systematic review of the literature, followed by a meta-analysis. We would like to raise several points: (i) The authors have stated that ‘Resistant bacteria have renewed our interest in the aminoglycoside drugs’. While this is partly true, we would argue that interest has never diminished as these drugs are widely used, regarded as being effective as monotherapy and in combination, and are being increasingly seen as a treatment and surgical prophylactic alternative to many b-lactam antibiotics, which, rightly or wrongly, are per- ceived as more potent initiators of Clostridium difficile colitis. (ii) The authors state that there is interest in aminoglycoside use for Gram-negative infections that are resistant to ‘more efficacious and less toxic drugs’. We would question which drugs are more efficacious and of course if the organisms are resistant to these agents, efficacy would be unlikely. (iii) Later, the reader’s attention is drawn to Acinetobacter bau- mannii, Pseudomonas aeruginosa and Klebsiella spp. (because they are resistant to the above-mentioned drugs), with the statement that ‘The alternatives are usually amino- glycosides, colistin and ( potentially) tigecycline’, with a suggestion for comparative clinical trials. As far as we know, Acinetobacter spp. are inherently resistant to aminoglycosides. 2 (iv) Regarding infective endocarditis, the authors recommend that ‘Practitioners would be well advised to use published guidelines, but within their limits, to take into account the fact that combination treatment is not supported by evi- dence’. The authors point out that trials with small numbers of patients were in favour of monotherapy (without amino- glycosides), but they ‘did not reach statistical significance’. Lack of evidence is not an argument against a practice. Such recommendations made by the working groups of scientific Letters to the Editor 1081