{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T23:08:50Z","timestamp":1787267330607,"version":"build-2736575974"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Pharm Health Care Sci"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Atovaquone (Atov), a second-line drug, is used to treat patients with\n                      <jats:italic>Pneumocystis<\/jats:italic>\n                      pneumonia (PCP) who cannot tolerate sulfamethoxazole\/trimethoprim (SMX\/TMP). However, the efficacy and safety of Atov are based on clinical trials conducted in patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome, with limited data available on HIV-uninfected individuals with PCP (non-HIV PCP). In this study, we retrospectively evaluated the clinical outcomes of switching from SMX\/TMP to Atov in patients with non-HIV PCP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study included patients with non-HIV PCP who were admitted to Fukuoka University Hospital between 2016 and 2023 and initially received SMX\/TMP therapy. The primary endpoint was 30-day survival rate from the date of PCP diagnosis. Secondary endpoints included factors associated with mortality and the cumulative incidence of switching from SMX\/TMP to Atov.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 56 patients receiving SMX\/TMP therapy for PCP, 17 were switched to Atov due to SMX\/TMP-related side effects. The Kaplan\u2013Meier estimated 30-day survival was 76.9% in the \u201cremained on\u201d SMX\/TMP group and 82.4% in the \u201cswitched to\u201d Atov group (log-rank test,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.58). Univariable logistic regression analysis of 30-day mortality showed that switching to Atov was not associated with higher mortality compared with continued SMX\/TMP therapy (odds ratio 0.71, 95% confidence interval 0.17 to 3.05). The Kaplan\u2013Meier estimated cumulative incidence of switching from SMX\/TMP to Atov during the PCP treatment period was 33.8%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data suggest that switching from SMX\/TMP to Atov may not be associated with worse survival. Long-term administration of SMX\/TMP is often challenging due to its side effects, and in this study, more than 30% of patients were unable to tolerate its therapeutic dose. Our findings support the role of Atov as a viable second-line treatment for PCP in immunocompromised patients, such as those with non-HIV PCP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40780-025-00516-4","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:52:56Z","timestamp":1768315976000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical outcomes after switching from sulfamethoxazole-trimethoprim to atovaquone due to intolerance in patients with non-HIV Pneumocystis pneumonia: a single-center retrospective study"],"prefix":"10.1186","volume":"12","author":[{"given":"Yukino","family":"Shirakawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Higashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiomi","family":"Eguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Yamashina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadahiro","family":"Ikeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Kaneshige","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Uchiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Togawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Kamimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"516_CR1","doi-asserted-by":"publisher","first-page":"e0256452","DOI":"10.1371\/journal.pone.0256452","volume":"16","author":"T Tanaka","year":"2021","unstructured":"Tanaka T, Oshima K, Kawano K, Tashiro M, Tanaka A, Fujita A, et al. Nationwide surveillance of AIDS-defining illnesses among HIV patients in Japan from 1995 to 2017. PLoS ONE. 2021;16:e0256452. https:\/\/doi.org\/10.1371\/journal.pone.0256452.","journal-title":"PLoS ONE"},{"key":"516_CR2","doi-asserted-by":"publisher","first-page":"812698","DOI":"10.3389\/fmed.2022.812698","volume":"9","author":"J Duan","year":"2022","unstructured":"Duan J, Gao J, Liu Q, Sun M, Liu Y, Tan Y, et al. Characteristics and prognostic factors of non-HIV immunocompromised patients with Pneumocystis pneumonia diagnosed by metagenomics next-generation sequencing. Front Med (Lausanne). 2022;9:812698. https:\/\/doi.org\/10.3389\/fmed.2022.812698.","journal-title":"Front Med (Lausanne)"},{"key":"516_CR3","doi-asserted-by":"publisher","first-page":"2323","DOI":"10.1016\/j.chest.2020.05.558","volume":"158","author":"A Ghembaza","year":"2020","unstructured":"Ghembaza A, Vautier M, Cacoub P, Pourcher V, Saadoun D. Risk factors and prevention of Pneumocystis jirovecii pneumonia in patients with autoimmune and inflammatory diseases. Chest. 2020;158:2323\u201332. https:\/\/doi.org\/10.1016\/j.chest.2020.05.558.","journal-title":"Chest"},{"key":"516_CR4","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1177\/1060028016650107","volume":"50","author":"LJ Avino","year":"2016","unstructured":"Avino LJ, Naylor SM, Roecker AM. Pneumocystis jirovecii pneumonia in the non-HIV-infected population. Ann Pharmacother. 2016;50:673\u20139. https:\/\/doi.org\/10.1177\/1060028016650107.","journal-title":"Ann Pharmacother"},{"key":"516_CR5","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s12890-022-02300-8","volume":"23","author":"L Huang","year":"2023","unstructured":"Huang L, Xu S, Huang Z, Chen Y, Xu N, Xie B. Risk factors associated with Pneumocystis jirovecii pneumonia in non-HIV immunocompromised patients and co-pathogens analysis by metagenomic next-generation sequencing. BMC Pulm Med. 2023;23:72. https:\/\/doi.org\/10.1186\/s12890-022-02300-8.","journal-title":"BMC Pulm Med"},{"key":"516_CR6","doi-asserted-by":"publisher","first-page":"59729","DOI":"10.18632\/oncotarget.19927","volume":"8","author":"Y Liu","year":"2017","unstructured":"Liu Y, Su L, Jiang SJ, Qu H. Risk factors for mortality from Pneumocystis carinii pneumonia (PCP) in non-HIV patients: a meta-analysis. Oncotarget. 2017;8:59729\u201339. https:\/\/doi.org\/10.18632\/oncotarget.19927.","journal-title":"Oncotarget"},{"key":"516_CR7","doi-asserted-by":"publisher","first-page":"e334","DOI":"10.1016\/S1473-3099(17)30303-1","volume":"17","author":"AH Limper","year":"2017","unstructured":"Limper AH, Adenis A, Le T, Harrison TS. Fungal infections in HIV\/AIDS. Lancet Infect Dis. 2017;17:e334\u201343. https:\/\/doi.org\/10.1016\/S1473-3099(17)30303-1.","journal-title":"Lancet Infect Dis"},{"key":"516_CR8","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1093\/infdis\/163.4.843","volume":"163","author":"WT Hughes","year":"1991","unstructured":"Hughes WT, Kennedy W, Shenep JL, Flynn PM, Hetherington SV, Fullen G, et al. Safety and pharmacokinetics of 566C80, a hydroxynaphthoquinone with anti-Pneumocystis carinii activity: a phase I study in human immunodeficiency virus (HIV)-infected men. J Infect Dis. 1991;163:843\u20138. https:\/\/doi.org\/10.1093\/infdis\/163.4.843.","journal-title":"J Infect Dis"},{"key":"516_CR9","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1056\/NEJM199111283252202","volume":"325","author":"J Falloon","year":"1991","unstructured":"Falloon J, Kovacs J, Hughes W, O\u2019Neill D, Polis M, Davey RT Jr, et al. A preliminary evaluation of 566C80 for the treatment of Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1991;325:1534\u20138. https:\/\/doi.org\/10.1056\/NEJM199111283252202.","journal-title":"N Engl J Med"},{"key":"516_CR10","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1056\/NEJM199305273282103","volume":"328","author":"W Hughes","year":"1993","unstructured":"Hughes W, Leoung G, Kramer F, Bozzette SA, Safrin S, Frame P, et al. Comparison of Atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl J Med. 1993;328:1521\u20137. https:\/\/doi.org\/10.1056\/NEJM199305273282103.","journal-title":"N Engl J Med"},{"key":"516_CR11","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1007\/s00296-021-04945-w","volume":"42","author":"S Jinno","year":"2022","unstructured":"Jinno S, Akashi K, Onishi A, Nose Y, Yamashita M, Saegusa J. Comparative effectiveness of trimethoprim-sulfamethoxazole versus Atovaquone for the prophylaxis of Pneumocystis pneumonia in patients with connective tissue diseases receiving prolonged high-dose glucocorticoids. Rheumatol Int. 2022;42:1403\u20139. https:\/\/doi.org\/10.1007\/s00296-021-04945-w.","journal-title":"Rheumatol Int"},{"key":"516_CR12","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.jiac.2019.01.005","volume":"25","author":"T Kitazawa","year":"2019","unstructured":"Kitazawa T, Seo K, Yoshino Y, Asako K, Kikuchi H, Kono H, et al. Efficacies of atovaquone, pentamidine, and trimethoprim\/sulfamethoxazole for the prevention of Pneumocystis jirovecii pneumonia in patients with connective tissue diseases. J Infect Chemother. 2019;25:351\u20134. https:\/\/doi.org\/10.1016\/j.jiac.2019.01.005.","journal-title":"J Infect Chemother"},{"key":"516_CR13","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s15010-015-0851-1","volume":"44","author":"D Creemers-Schild","year":"2016","unstructured":"Creemers-Schild D, Kroon FP, Kuijper EJ, de Boer MG. Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim-sulfamethoxazole: lessons from an observational cohort study. Infection. 2016;44:291\u20139. https:\/\/doi.org\/10.1007\/s15010-015-0851-1.","journal-title":"Infection"},{"key":"516_CR14","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.3390\/pathogens11101169","volume":"11","author":"CH Jeon","year":"2022","unstructured":"Jeon CH, Kim SH, Kim S, Bae M, Lee SJ, Lim S. Pneumocystis jirovecii pneumonia in patients with solid malignancies: a retrospective study in two hospitals. Pathogens. 2022;11:1169. https:\/\/doi.org\/10.3390\/pathogens11101169.","journal-title":"Pathogens"},{"key":"516_CR15","doi-asserted-by":"publisher","first-page":"e0292507","DOI":"10.1371\/journal.pone.0292507","volume":"19","author":"K Miyake","year":"2024","unstructured":"Miyake K, Senoo S, Shiiba R, Itano J, Kimura G, Kawahara T, et al. Pneumocystis jirovecii pneumonia mortality risk associated with preceding long-term steroid use for the underlying disease: A multicenter, retrospective cohort study. PLoS ONE. 2024;19:e0292507. https:\/\/doi.org\/10.1371\/journal.pone.0292507.","journal-title":"PLoS ONE"},{"key":"516_CR16","doi-asserted-by":"publisher","first-page":"1380494","DOI":"10.3389\/fcimb.2024.1380494","volume":"14","author":"J Li","year":"2024","unstructured":"Li J, Mu X, Li H, Liu X. Clinical course and prognostic factors of Pneumocystis pneumonia with respiratory failure in non-HIV patients. Front Cell Infect Microbiol. 2024;14:1380494. https:\/\/doi.org\/10.3389\/fcimb.2024.1380494.","journal-title":"Front Cell Infect Microbiol"},{"key":"516_CR17","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1086\/342338","volume":"35","author":"JR Zahar","year":"2002","unstructured":"Zahar JR, Robin M, Azoulay E, Fieux F, Nitenberg G, Schlemmer B. Pneumocystis carinii pneumonia in critically ill patients with malignancy: a descriptive study. Clin Infect Dis. 2002;35:929\u201334. https:\/\/doi.org\/10.1086\/342338.","journal-title":"Clin Infect Dis"},{"key":"516_CR18","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1186\/s13054-018-2221-8","volume":"22","author":"JJ Schmidt","year":"2018","unstructured":"Schmidt JJ, Lueck C, Ziesing S, Stoll M, Haller H, Gottlieb J, et al. Clinical course, treatment and outcome of Pneumocystis pneumonia in immunocompromised adults: a retrospective analysis over 17 years. Crit Care. 2018;22:307. https:\/\/doi.org\/10.1186\/s13054-018-2221-8.","journal-title":"Crit Care"},{"key":"516_CR19","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.chest.2023.08.009","volume":"165","author":"T Nagai","year":"2024","unstructured":"Nagai T, Matsui H, Fujioka H, Homma Y, Otsuki A, Ito H, et al. Low-dose vs conventional-dose trimethoprim-sulfamethoxazole treatment for Pneumocystis pneumonia in patients not infected with HIV: A multicenter, retrospective observational cohort study. Chest. 2024;165:58\u201367. https:\/\/doi.org\/10.1016\/j.chest.2023.08.009.","journal-title":"Chest"},{"key":"516_CR20","doi-asserted-by":"publisher","first-page":"e1252","DOI":"10.1093\/cid\/ciac386","volume":"76","author":"H Hammarstr\u00f6m","year":"2023","unstructured":"Hammarstr\u00f6m H, Krifors A, Athlin S, Friman V, Golestani K, H\u00e4llgren A, et al. Treatment with reduced-dose trimethoprim-sulfamethoxazole is effective in mild to moderate Pneumocystis jirovecii pneumonia in patients with hematologic malignancies. Clin Infect Dis. 2023;76:e1252\u201360. https:\/\/doi.org\/10.1093\/cid\/ciac386.","journal-title":"Clin Infect Dis"},{"key":"516_CR21","doi-asserted-by":"publisher","first-page":"e001508","DOI":"10.1136\/rmdopen-2020-001508","volume":"7","author":"Y Ishikawa","year":"2021","unstructured":"Ishikawa Y, Nakano K, Tokutsu K, Miyata H, Fujino Y, Matsuda S, et al. Estimation of treatment and prognostic factors of Pneumocystis pneumonia in patients with connective tissue diseases. RMD Open. 2021;7:e001508. https:\/\/doi.org\/10.1136\/rmdopen-2020-001508.","journal-title":"RMD Open"},{"key":"516_CR22","doi-asserted-by":"publisher","first-page":"435","DOI":"10.11150\/kansenshogakuzasshi.87.435","volume":"87","author":"M Yotsumoto","year":"2013","unstructured":"Yotsumoto M, Shinozawa K, Yamamoto Y, Sekine Y, Fukutake K. Status of use and side effects of Atovaquone for the treatment and prevention of Pneumocystis pneumonia in HIV infected patients in Japan\u2014from 1997 to 2012\u2014the clinical study group for AIDS Drugs, supported by health and labor science grants from the ministry of health, labor and Welfare, Japan. Kansenshogaku Zasshi. 2013;87:435\u201340. https:\/\/doi.org\/10.11150\/kansenshogakuzasshi.87.435.","journal-title":"Kansenshogaku Zasshi"},{"key":"516_CR23","first-page":"161","volume-title":"The JAID\/JSC guide to clinical management of infectious diseases 2023","author":"The Japanese Association for Infectious Diseases, the Japanese Society of Chemotherapy","year":"2023","unstructured":"The Japanese Association for Infectious Diseases, the Japanese Society of Chemotherapy. The JAID\/JSC guide to clinical management of infectious diseases 2023. Tokyo: Kyorinsha Co., Ltd.; 2023. pp. 161\u20132."},{"key":"516_CR24","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1001\/archinte.1995.00430110015002","volume":"155","author":"KA Sepkowitz","year":"1995","unstructured":"Sepkowitz KA, Brown AE, Armstrong D. Pneumocystis carinii pneumonia without acquired immunodeficiency syndrome: more patients, same risk. Arch Intern Med. 1995;155:1125\u20138.","journal-title":"Arch Intern Med"},{"key":"516_CR25","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1001\/jama.2023.9844","volume":"330","author":"S Zhou","year":"2023","unstructured":"Zhou S, Aitken SL. Prophylaxis against Pneumocystis jirovecii pneumonia in adults. JAMA. 2023;330:182\u20133. https:\/\/doi.org\/10.1001\/jama.2023.9844.","journal-title":"JAMA"}],"container-title":["Journal of Pharmaceutical Health Care and Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40780-025-00516-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40780-025-00516-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40780-025-00516-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T03:05:16Z","timestamp":1768359916000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40780-025-00516-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["516"],"URL":"https:\/\/doi.org\/10.1186\/s40780-025-00516-4","relation":{},"ISSN":["2055-0294"],"issn-type":[{"value":"2055-0294","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]},"assertion":[{"value":"23 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Ethics Committee of Fukuoka University (approval number: H25-02-005). Informed consent was not required due to the retrospective nature of this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5"}}