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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 (&gt;\u200910<jats:sup>5<\/jats:sup>HSV copies\/mL) and low (10<jats:sup>3<\/jats:sup>\u201310<jats:sup>5<\/jats:sup>HSV copies\/mL) viral load.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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,<jats:italic>p<\/jats:italic>\u2009=\u20090.001). Acyclovir improved median ICU survival (8 vs 22\u2009days,<jats:italic>p<\/jats:italic>\u2009=\u20090.014) and was associated with a significantly reduced hazard ratio for ICU death (HR\u2009=\u20090.31, 95% CI 0.11\u20130.92,<jats:italic>p<\/jats:italic>\u2009=\u20090.035) 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\u2009\u03bcg\/kg body weight\/min between days 0 and 6 of treatment (<jats:italic>p<\/jats:italic>\u2009=\u20090.049), and median PaO<jats:sub>2<\/jats:sub>\/FiO<jats:sub>2<\/jats:sub>ratio increased from 187 to 241 between day 3 and day 7 of treatment (<jats:italic>p<\/jats:italic>\u2009=\u20090.02). Chest radiographic findings also improved significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13054-019-2701-5","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T16:02:59Z","timestamp":1578672179000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Impact of acyclovir use on survival of patients with ventilator-associated pneumonia and high load herpes simplex virus replication"],"prefix":"10.1186","volume":"24","author":[{"given":"Lukas","family":"Schuierer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gebhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Georg","family":"Ruf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Jaschinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Berghaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wittmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk H.","family":"Busch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1514-1183","authenticated-orcid":false,"given":"Reinhard","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,10]]},"reference":[{"key":"2701_CR1","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1093\/infdis\/jit458","volume":"209","author":"H Bradley","year":"2014","unstructured":"Bradley H, Markowitz LE, Gibson T, McQuillan GM. 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