{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:47:32Z","timestamp":1789620452861,"version":"build-2803163510"},"reference-count":23,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008678","name":"Leipzig University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008678","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: In recent years, there has been a significant increase in cases of tularemia, a rare zoonotic disease caused by Francisella tularensis, in Europe. Methods: To investigate the epidemiological, clinical, and therapeutic characteristics of tularemia patients in Germany, we performed a retrospective evaluation of tularemia cases treated between 2010 and 2025 at selected treatment centers of the Permanent Working Group of Competence and Treatment Centers for High Consequence Infectious Diseases (STAKOB) at the Robert Koch Institute. Results: A total of 65 patients (median age: 48.5 years; 66.2% male) were identified. Most common manifestation was ulceroglandular (70.7%), followed by oropharyngeal (13.8%), pulmonary (10.8%), oculoglandular (7.7%), typhoidal (4.6%), and meningitic (4.6%). Serological confirmation of the diagnosis was achieved in all patients (90.8% ELISA, 46.2% Western blot). PCR-based direct pathogen detection was successful in 26.2%. Bloodstream infection was detected in 4.6%. Median incubation period was 7 days (IQR: 4\u201310), with fever being the most common symptom in 96.9% and lymphadenopathy in 46.2%. Median time to recovery was 56 days (IQR: 37\u201380) in patients diagnosed and treated early (\u22643 weeks after symptom onset), compared to 84 days (IQR: 66\u2013182) in patients with late diagnosis (&gt;3 weeks after symptom onset; p = 0.015). Empirical therapy with beta-lactam antibiotics was initiated in 49.2% of cases. Following suspicion of tularemia, 96.9% received recommended treatment with fluoroquinolones, tetracyclines, or aminoglycosides. Conclusions: Delayed diagnosis and inappropriate initial therapy can significantly prolong disease courses and increase morbidity. Early treatment with effective antibiotics, considering the intrinsic beta-lactam resistance of Francisella tularensis, leads to faster recovery.<\/jats:p>","DOI":"10.3390\/antibiotics14111169","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T09:44:53Z","timestamp":1763631893000},"page":"1169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical Characteristics and Treatment Strategies in a Cohort of Patients with Tularemia: A Retrospective Multicenter Analysis of 65 Cases in Germany"],"prefix":"10.3390","volume":"14","author":[{"given":"Benjamin","family":"Arnold","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Tropical Medicine, Hospital St. Georg gGmbH, 04129 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Trawinski","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Leipzig University Medical Center, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Kellner","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Tropical Medicine, Hospital St. Georg gGmbH, 04129 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3053-6730","authenticated-orcid":false,"given":"Hans-Martin","family":"Orth","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6083-4946","authenticated-orcid":false,"given":"Daniela","family":"Tominski","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Auguste Viktoria Klinikum, 12157 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Mikolajewska","sequence":"additional","affiliation":[{"name":"Center for Biological Threats and Special Pathogens, Strategy and Incident Response, Clinical Management and Infection Control, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4504-2371","authenticated-orcid":false,"given":"Katja","family":"Rothfuss","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology, Robert Bosch Hospital, 70376 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gesa","family":"Grupe","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Respiratory and Critical Care Medicine, Charit\u00e9-Universit\u00e4tsmedizin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Ruf","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Immunology, Palliative Medicine, Infectious Diseases and Tropical Medicine, Klinikum M\u00fcnchen-Schwabing, 80804 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6377-7499","authenticated-orcid":false,"given":"Friedrich","family":"Reichert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Olgahospital, Klinikum Stuttgart, 70174 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Jacob","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for <i>Francisella tularensis<\/i>, Center for Biological Threats and Special Pathogens, Highly Pathogenic Microorganisms (ZBS 2), Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Heuner","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for <i>Francisella tularensis<\/i>, Center for Biological Threats and Special Pathogens, Highly Pathogenic Microorganisms (ZBS 2), Robert Koch Institute, 13353 Berlin, Germany"},{"name":"Cellular Interactions of Bacterial Pathogens, Center for Biological Threats and Special Pathogens, Highly Pathogenic Microorganisms (ZBS 2), Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Marx","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy, Hospital St. Georg gGmbH, 04129 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-5785","authenticated-orcid":false,"given":"Christoph","family":"L\u00fcbbert","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Tropical Medicine, Hospital St. Georg gGmbH, 04129 Leipzig, Germany"},{"name":"Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Leipzig University Medical Center, 04103 Leipzig, Germany"},{"name":"Interdisciplinary Center for Infectious Diseases, Leipzig University Medical Center, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","unstructured":"Robert Koch Institute (RKI) (2025, July 24). Infektionsepidemiologisches Jahrbuch Meldepflichtiger Krankheiten f\u00fcr 2022. Available online: https:\/\/edoc.rki.de\/handle\/176904\/11825."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1183\/09031936.03.00088903","article-title":"Tularaemia","volume":"21","author":"Berglund","year":"2003","journal-title":"Eur. Respir. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1017\/S0950268814002398","article-title":"The status of tularemia in Europe in a one-health context: A review","volume":"143","author":"Hestvik","year":"2015","journal-title":"Epidemiol. Infect."},{"key":"ref_4","first-page":"114","article-title":"Tularaemia: A perusal of three hundred thirty-nine cases","volume":"115","author":"Dienst","year":"1963","journal-title":"J. La. State Med. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S1473-3099(15)00355-2","article-title":"Tularaemia: Clinical aspects in Europe","volume":"16","author":"Maurin","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1128\/AAC.05305-11","article-title":"The class A \u03b2-lactamase FTU-1 is native to Francisella tularensis","volume":"56","author":"Antunes","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/jac\/dkx460","article-title":"Antibiotic susceptibility of Francisella tularensis subsp. holarctica strains isolated from tularaemia patients in France between 2006 and 2016","volume":"73","author":"Caspar","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_8","unstructured":"Robert Koch Institute (RKI) (2025, July 24). Robert Koch-Institut: SurvStat@RKI 2.0. Available online: https:\/\/survstat.rki.de."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1900603","DOI":"10.2807\/1560-7917.ES.2019.24.42.1900603","article-title":"Large outbreak of tularaemia, central Sweden, July to September 2019","volume":"24","author":"Dryselius","year":"2019","journal-title":"Euro Surveill."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Appelt, S., Faber, M., K\u00f6ppen, K., Jacob, D., Grunow, R., and Heuner, K. (2020). Francisella tularensis Subspecies holarctica and Tularaemia in Germany. Microorganisms, 8.","DOI":"10.3390\/microorganisms8091448"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.15585\/mmwr.mm735152a1","article-title":"Tularaemia-United States, 2011\u20132022","volume":"73","author":"Rich","year":"2025","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"678","DOI":"10.3201\/eid3104.240414","article-title":"Epidemiology of Tularemia among Humans and Animals, Baden-Wuerttemberg, Germany, 2012\u20132022","volume":"31","author":"Nothdurfter","year":"2025","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","first-page":"1405","article-title":"Prolonged course of tick-borne ulceroglandular tularaemia in a 20-year-old patient in Germany\u2014Case report and review of the literature","volume":"134","author":"Taege","year":"2009","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e70094","DOI":"10.1002\/vms3.70094","article-title":"An Emerging Role for Ticks as Vectors of Tularaemia in Sweden","volume":"11","author":"Grandi","year":"2025","journal-title":"Vet. Med. Sci."},{"key":"ref_15","first-page":"102492","article-title":"Clinical characteristics of and diagnostic approaches to human Francisella tularensis infection: A retrospective, monocentric case study from Germany","volume":"1","author":"Schneitler","year":"2025","journal-title":"Ticks Tick-Borne Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"O1042","DOI":"10.1111\/1469-0691.12741","article-title":"Evaluation of tularaemia courses: A multicentre study from Turkey","volume":"20","author":"Erdem","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.3201\/eid2112.150634","article-title":"Water as Source of Francisella tularensis Infection in Humans, Turkey","volume":"21","author":"Kilic","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1093\/cid\/ciad689","article-title":"Tularaemia Clinical Manifestations, Antimicrobial Treatment, and Outcomes: An Analysis of US Surveillance Data, 2006\u20132021","volume":"78","author":"Wu","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1093\/cid\/ciae098","article-title":"Targeting Tularaemia: Clinical, Laboratory, and Treatment Outcomes from an 11-year Retrospective Observational Cohort in Northern Sweden","volume":"78","author":"Plymoth","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1093\/cid\/ciad736","article-title":"Systematic Review: Clinical Features, Antimicrobial Treatment, and Outcomes of Human Tularaemia, 1993\u20132023","volume":"78","author":"Nelson","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1086\/322601","article-title":"Tularaemia epidemic in northwestern Spain: Clinical description and therapeutic response","volume":"33","author":"Herreros","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s00112-022-01671-w","article-title":"Ulcer and lymphadenitis after tick bite","volume":"173","author":"Pfeil","year":"2025","journal-title":"Monatsschrift Kinderheilkd."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr7402a1","article-title":"Tularemia Antimicrobial Treatment and Prophylaxis: CDC Recommendations for Naturally Acquired Infections and Bioterrorism Response, United States, 2025","volume":"74","author":"Nelson","year":"2025","journal-title":"MMWR Recomm. Rep."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/11\/1169\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T05:17:50Z","timestamp":1763788670000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/11\/1169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":23,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["antibiotics14111169"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14111169","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]}}}