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. 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 (> 105 HSV copies/mL) and low (103–105 HSV copies/mL) viral load. 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 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). 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.

中文翻译：

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使用阿昔洛韦对呼吸机相关性肺炎和高负荷单纯疱疹病毒复制患者生存的影响

在大部分通风的重症监护病房 (ICU) 患者的呼吸道分泌物中可以检测到单纯疱疹病毒 (HSV) 复制。然而，临床意义仍然不明确。我们调查了呼吸机相关性肺炎患者对抗生素无反应以及呼吸道分泌物中可检测到高水平 HSV 的患者是否受益于阿昔洛韦治疗。通过定量实时 PCR 检测呼吸道分泌物（支气管肺泡灌洗液或气管抽吸物）的 HSV 复制。回顾性比较了未经治疗和阿昔洛韦治疗的高（> 105 HSV 拷贝/mL）和低（103-105 HSV 拷贝/mL）病毒载量患者的ICU 存活时间、临床参数和影像学结果。确定了 57 名低病毒载量患者和 69 名高病毒载量患者。对抗生素治疗有反应的高病毒载量患者较少（12% 与低病毒载量患者的 40% 相比，p = 0.001）。仅在高负荷患者中，阿昔洛韦改善了 ICU 中位生存期（8 天与 22 天，p = 0.014），并且与 ICU 死亡风险比显着降低（HR = 0.31，95% CI 0.11–0.92，p = 0.035）相关。此外，在阿昔洛韦治疗过程中，高负荷患者的循环和肺氧合功能显着改善：在治疗的第 0 天和第 6 天之间，去甲肾上腺素的平均剂量从 0.05 至 0.02 μg/kg 体重/分钟（p = 0.049），中位数降低PaO2/FiO2 比率在治疗的第 3 天和第 7 天之间从 187 增加到 241（p = 0.02）。胸部放射学检查结果也显着改善（p < 0.001）。对于呼吸机相关性肺炎、抗生素治疗失败的患者，和高水平的 HSV 复制，阿昔洛韦治疗与 ICU 中明显更长的死亡时间以及改善循环和肺功能有关。这表明 HSV 在这组高度选择的患者中具有致病作用。