{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:09:46Z","timestamp":1788404986126,"version":"build-2803163510"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Doxycycline has been recommended as a treatment option for non-severe community-acquired pneumonia (CAP) in adults. We sought to review the evidence for the efficacy of doxycycline in adult patients with mild-to-moderate CAP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of doxycycline versus comparator to assess the clinical efficacy. The primary outcome was the clinical cure rate. Random effects model meta-analyses were used to generate pooled odds ratio (OR) and evaluate heterogeneity (I2). Risk of bias (RoB) and quality of evidence (QoE) were evaluated using the Cochrane Risk of Bias 2.0 tool and GRADE methods, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 6 RCTs with 834 clinically evaluable patients. The trials were performed between 1984 and 2004. Comparators were 3 macrolides (roxithromycin, spiramycin, and erythromycin) and 3 fluoroquinolones (ofloxacin, fleroxacin, and levofloxacin). Four trials had an overall high RoB. The clinical cure rate was similar between the doxycycline and comparator groups (87.2% [381\/437] vs 82.6% [328\/397]; OR 1.29 [95% confidence interval {CI}: .73\u20132.28]; I2 = 30%; low QoE). Subgroup analysis of two studies with a low RoB showed significantly higher clinical cure rates in the doxycyline group (87.1% [196\/225] vs 77.8% [165\/212]; OR 1.92 [95% CI: 1.15\u20133.21]; P = .01; I2 = 0%). Adverse event rates were comparable between the doxycycline and comparator groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The efficacy of doxycycline was comparable to macrolides or fluoroquinolones in mild-to-moderate CAP and thus represents a viable treatment option. Considering the lack of recent trials, it warrants large-scale clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciac615","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T04:39:21Z","timestamp":1659069561000},"page":"683-691","source":"Crossref","is-referenced-by-count":28,"title":["Efficacy of Doxycycline for Mild-to-Moderate Community-Acquired Pneumonia in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.1093","volume":"76","author":[{"given":"Sang-Ho","family":"Choi","sequence":"first","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London , London , United Kingdom"},{"name":"Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Cesar","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London , London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy Arthur Chandos","family":"Snow","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London , London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed","family":"Saleem","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London , London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishkantha","family":"Arulkumaran","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London , London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervyn","family":"Singer","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London , London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/S0140-6736(18)32203-7","article-title":"Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980\u20132017: a systematic analysis for the global burden of disease study 2017","volume":"392","author":"Roth","year":"2018","journal-title":"Lancet"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1007\/s12325-020-01248-7","article-title":"Burden of community-acquired pneumonia and unmet clinical needs","volume":"37","author":"Ferreira-Coimbra","year":"2020","journal-title":"Adv Ther"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1136\/thx.2003.017756","article-title":"Risk factors of treatment failure in community-acquired pneumonia: implications for disease outcome","volume":"59","author":"Menendez","year":"2004","journal-title":"Thorax"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2334-14-61","article-title":"Clinical implications for patients treated inappropriately for community-acquired pneumonia in the emergency department","volume":"14","author":"Micek","year":"2014","journal-title":"BMC Infect Dis"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"iii1","DOI":"10.1136\/thx.2009.121434","article-title":"BTS Guidelines for the management of community acquired pneumonia in adults: update 2009","volume":"64","author":"Lim","year":"2009","journal-title":"Thorax"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1164\/rccm.201908-1581ST","article-title":"Diagnosis and treatment of adults with community-acquired pneumonia","volume":"200","author":"Metlay","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1164\/rccm.201402-0385CI","article-title":"Macrolide antibiotics and the risk of cardiac arrhythmias","volume":"189","author":"Albert","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"k678","DOI":"10.1136\/bmj.k678","article-title":"Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study","volume":"360","author":"Pasternak","year":"2018","journal-title":"BMJ"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1378\/chest.78.2.304","article-title":"Tissue levels of doxycycline in the human lung and pleura","volume":"78","author":"Thadepalli","year":"1980","journal-title":"Chest"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"905","DOI":"10.3390\/antibiotics9120905","article-title":"Use of oral tetracyclines in the treatment of adult patients with community-acquired bacterial pneumonia: a literature review on the often-overlooked antibiotic class","volume":"9","author":"Bidell","year":"2020","journal-title":"Antibiotics (Basel"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"Rob 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: an emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/jrsm.1260","article-title":"Introduction, comparison, and validation of meta-essentials: a free and simple tool for meta-analysis","volume":"8","author":"Suurmond","year":"2017","journal-title":"Res Synth Methods"},{"key":"2023021818292061700_"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12874-017-0315-7","article-title":"Trial sequential analysis in systematic reviews with meta-analysis","volume":"17","author":"Wetterslev","year":"2017","journal-title":"BMC Med Res Methodol"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2165\/00003495-198700341-00015","article-title":"An open randomised comparison of ofloxacin and doxycycline in lower respiratory tract infections","volume":"34","author":"Harazim","year":"1987","journal-title":"Drugs"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/jac\/22.Supplement_B.155","article-title":"Comparison of spiramycin and doxycycline in the treatment of lower respiratory infections in general practice","volume":"22","author":"Biermann","year":"1988","journal-title":"J Antimicrob Chemother"},{"key":"2023021818292061700_","first-page":"548","article-title":"Multicentric study of efficiency and tolerance of roxithromycin compared to doxycycline in broncho-pulmonary infections. (In French)","volume":"36","author":"Charpin","year":"1988","journal-title":"Path Biol"},{"key":"2023021818292061700_","first-page":"1014","article-title":"Twice daily dosing of erythromycin acistrate in the treatment of acute bronchitis and pneumonia","volume":"43","author":"Wiesner","year":"1993","journal-title":"Arzneimittel-Forschung"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/jac\/39.4.499","article-title":"Atypical pneumonia in the Nordic countries: aetiology and clinical results of a trial comparing fleroxacin and doxycycline","volume":"39","author":"Norrby","year":"1997","journal-title":"J Antimicrob Chemother"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1365-2710.2009.01073.x","article-title":"Doxycycline vs Levofloxacin in the treatment of community-acquired pneumonia","volume":"35","author":"Mokabberi","year":"2010","journal-title":"J Clin Pharm Ther"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"e02008","DOI":"10.1128\/AAC.02008-16","article-title":"In vitro activities of lefamulin and other antimicrobial agents against macrolide-susceptible and macrolide-resistant Mycoplasma pneumoniae from the United States, Europe, and China","volume":"61","author":"Waites","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1093\/cid\/ciz395","article-title":"Microbiology and preclinical review of omadacycline","volume":"69","author":"Karlowsky","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ijid.2018.10.004","article-title":"Antimicrobial activity of ceftaroline and comparator agents tested against organisms isolated from patients with community-acquired bacterial pneumonia in Europe, Asia, and Latin America","volume":"77","author":"Sader","year":"2018","journal-title":"Int J Infect Dis"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.diagmicrobio.2013.01.023","article-title":"Contemporary tetracycline susceptibility testing: doxycycline MIC methods and interpretive criteria (CLSI and EUCAST) performance when testing gram-positive pathogens","volume":"76","author":"Jones","year":"2013","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"vii5","DOI":"10.1093\/jac\/dky156","article-title":"Antimicrobial susceptibility testing of invasive isolates of Streptococcus pneumoniae from Canadian patients: the SAVE study, 2011\u201315","volume":"73","author":"Karlowsky","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.diagmicrobio.2017.10.010","article-title":"Activity of omadacycline tested against Streptococcus pneumoniae from a global surveillance program (2014)","volume":"90","author":"Pfaller","year":"2018","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1001\/archinte.159.3.266","article-title":"Doxycycline is a cost-effective therapy for hospitalized patients with community-acquired pneumonia","volume":"159","author":"Ailani","year":"1999","journal-title":"Arch Intern Med"},{"key":"2023021818292061700_","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1086\/341983","article-title":"Doxycycline for treatment of community-acquired pneumonia","volume":"35","author":"Johnson","year":"2002","journal-title":"Clin Infect Dis"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciac615\/45506248\/ciac615.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/76\/4\/683\/49255855\/ciac615.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/76\/4\/683\/49255855\/ciac615.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T03:15:18Z","timestamp":1700882118000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/76\/4\/683\/6651448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,29]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,7,29]]},"published-print":{"date-parts":[[2023,2,18]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciac615","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,2,15]]},"published":{"date-parts":[[2022,7,29]]}}}