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We read with great interest the recent paper by Schuierer et al., who conclude that acyclovir treatment was associated with a significantly longer time to death in the intensive care unit (ICU), reduced hazard ratio for ICU death, and improved circulatory and pulmonary oxygenation function in patients with ventilatorassociated pneumonia (VAP) not responding to antibiotic treatment and with high herpes simplex virus (HSV) load. They suggest testing all patients with a diagnosis of antibiotic refractory VAP for HSV replication in respiratory secretions and considering acyclovir treatment if more than 10 copies/mL are detected [1]. We would like to make some comments. First, this area remains controversial as several prospective studies have failed to show an increase in mortality associated with HSV infection [2] and the only prospective therapeutic study is limited by small sample size and prophylactic (rather than treatment) dosing [3]. Also, as clinicians, we need to take into account the side effects of the drugs we prescribe and indeed acyclovir is not a benign drug. Nephrotoxicity is the most important side effect of acyclovir, with an overall incidence of AKI of 13%, half of which are KDIGO grade 2/3 [4]. AKI has been found to occur more frequently in patients with pre-existing chronic kidney disease (CKD), diabetes, and in patients treated with higher daily doses of acyclovir [4]. Despite its importance, the acyclovir dose that patients received was not reported in this study [1]. Furthermore, for a study of a drug with known renal toxicity, there is a striking paucity of information regarding renal parameters. There is an upward trend in the incidence of dialysis in those receiving acyclovir, though the difference was not statistically significant, perhaps due to the small number of patients [1]. It should also be noted that acyclovir may be more toxic if given in conjunction with some antibiotics, such as was the case in this study [1]. In a recent study looking at acyclovir-associated AKI, multivariate analysis indicated that the presence of diabetes, concomitant non-steroidal anti-inflammatory drugs (NSAIDs), and vancomycin use were independent risk factors for acyclovir-associated AKI, and higher mortality was observed in AKI patients [5]. Nephrotoxicity associated with IV acyclovir is common and necessitates renal function monitoring. Randomised control trials with more comprehensive data on dose and renal parameters are needed before recommendations regarding acyclovir treatment in the setting of VAP can be made.

Acyclovir for ventilator-associated pneumonia refractory to antibiotics and with high viral herpes simplex load: we are not sure