Impact of acyclovir use on survival of patients with ventilator-associated pneumonia and high load herpes simplex virus replication
Lukas Schuierer, Michael Gebhard, Hans-Georg Ruf, Ulrich Jaschinski, Thomas M. Berghaus, Michael Wittmann, Georg Braun, Dirk H. Busch, Reinhard Hoffmann
Abstract
Abstract Background Herpes simplex virus (HSV) replication can be detected in the respiratory secretions of a high proportion of ventilated intensive care unit (ICU) patients. However, the clinical significance remains poorly defined. We investigated whether patients with ventilator-associated pneumonia not responding to antibiotics and in whom high levels of HSV could be detected in respiratory secretions benefit from acyclovir treatment. Methods Respiratory secretions (bronchoalveolar lavage fluid or tracheal aspirates) were tested for HSV replication by quantitative real-time PCR. ICU survival times, clinical parameters, and radiographic findings were retrospectively compared between untreated and acyclovir treated patients with high (> 10 5 HSV copies/mL) and low (10 3 –10 5 HSV copies/mL) viral load. Results Fifty-seven low and 69 high viral load patients were identified. Fewer patients with high viral load responded to antibiotic treatment (12% compared to 40% of low load patients, p = 0.001). Acyclovir improved median ICU survival (8 vs 22 days, p = 0.014) and was associated with a significantly reduced hazard ratio for ICU death (HR = 0.31, 95% CI 0.11–0.92, p = 0.035) in high load patients only. Moreover, circulatory and pulmonary oxygenation function of high load patients improved significantly over the course of acyclovir treatment: mean norepinephrine doses decreased from 0.05 to 0.02 μg/kg body weight/min between days 0 and 6 of treatment ( p = 0.049), and median PaO 2 /FiO 2 ratio increased from 187 to 241 between day 3 and day 7 of treatment ( p = 0.02). Chest radiographic findings also improved significantly ( p < 0.001). Conclusions In patients with ventilator-associated pneumonia, antibiotic treatment failure, and high levels of HSV replication, acyclovir treatment was associated with a significantly longer time to death in the ICU and improved circulatory and pulmonary function. This suggests a causative role for HSV in this highly selected group of patients.