Abstract
BackgroundHerpes 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.MethodsRespiratory 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 (> 105 HSV copies/mL) and low (103–105 HSV copies/mL) viral load.ResultsFifty-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 PaO2/FiO2 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).ConclusionsIn 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.
Highlights
Herpes simplex virus (HSV) replication can be detected in the respiratory secretions of a high proportion of ventilated intensive care unit (ICU) patients
Patient selection and Polymerase chain reaction (PCR) testing We retrospectively identified all adult ICU patients who were on ventilator support, received a diagnosis of ventilator-associated pneumonia (VAP) and PCR testing on clinical grounds, and had a viral load of > 103 herpes simples virus type 1 (HSV-1)/2 copies/mL by PCR in respiratory specimens within the period of January 1, 2013, through April 1, 2018
We suggest testing all patients with a diagnosis of VAP who do not respond to antibiotics for HSV replication in respiratory secretions
Summary
Herpes simplex virus (HSV) replication can be detected in the respiratory secretions of a high proportion of ventilated intensive care unit (ICU) patients. Several studies have shown that HSV-1 reactivation and active replication in the respiratory tract are common in mechanically ventilated intensive care unit (ICU) patients even without underlying immunosuppression, with reported rates of 5 to 64% [3]. A recent meta-analysis demonstrated a significant increase in mortality (odds ratio 1.8, 95% CI 1.2–2.6, p = 0.0001) for patients with HSV replication compared to patients without [8]. Whether this increase in mortality is caused by HSV reactivation or whether HSV reactivation is merely an indicator of a more severe underlying disease remains unclear
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