2024 update of the AGIHO guideline on diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients with solid tumours and hematological malignancies

Michael Sandherr¹, Jannik Stemler^{2

3

4}, Enrico Schalk⁵, Tessa Hattenhauer⁶, Marcus Hentrich⁷, Bernd Hertenstein⁸, Christian Hohmann⁸, Sibylle C Mellinghoff^{2

3

4}, Rebekka Mispelbaum⁶, Christina Rieger⁹, Martin Schmidt-Hieber¹⁰, Rosanne Sprute³, Guenter Weiss¹¹, Oliver A Cornely^{2

3

4}, Larissa Henze^{12

13}, Cornelia Lass-Floerl¹⁴, Gernot Beutel¹⁵, Annika Y Classen^{3

16}, Noemi F Freise^{17

18}, Meinolf Karthaus¹⁹, Philipp Koehler², Robert Krause^{20

21}, Julia Neuhann³, Hans Martin Orth^{17

18}, Olaf Penack²², Markus Schaich²³, Karsten Spiekermann²⁴, Sebastian Voigt²⁵, Florian Weissinger²⁶, Elena Busch²⁷

Affiliations

¹ Specialist Clinic for Hematology and Oncology, Medical Care Center Penzberg, Germany.
² University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
³ University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany.
⁴ German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne Department, Cologne, Germany.
⁵ Department of Hematology, Oncology and Cell Therapy, Medical Faculty, Otto von Guericke University Magdeburg, Magdeburg, Germany.
⁶ Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, Bonn, Germany.
⁷ Department of Hematology and Oncology, Red Cross Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany.
⁸ Department of Medicine, Clinic I - Hematology, Oncology, Infectiology, Department of Intensive Care and Emergency Medicine, Klinikum Bremen-Mitte, Bremen, Germany.
⁹ Department of Hematology and Oncology Germering, Germering, Germany.
¹⁰ Clinic for Oncology, Hematology, Pneumology, Nephrology and Diabetology, Carl-Thiem Clinic, Cottbus, Germany.
¹¹ Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria.
¹² Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany.
¹³ Department of Internal Medicine II, Hematology, Oncology and Palliative Medicine, Asklepios Hospital Harz, Goslar, Germany.
¹⁴ Institut of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
¹⁵ Department of Internal Medicine, Hematology, Oncology and Stem Cell Transplantation, Medical University of Hannover, Hannover, Germany.
¹⁶ German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
¹⁷ Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
¹⁸ Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Germany.
¹⁹ Department Hematology, Oncology and Palliative Care, Klinikum Neuperlach and Harlaching, Munich, Germany.
²⁰ Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Austria.
²¹ BioTechMed, Graz, Austria.
²² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Tumorimmunology, Berlin, Germany.
²³ Department of Hematology, Oncology and Palliative Care, Rems-Murr-Klinikum Winnenden, Germany.
²⁴ Department of Medicine III, LMU University Hospital, LMU Munich, Germany.
²⁵ Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
²⁶ Evangelic Hospital Bethel, Bielefeld, Germany.
²⁷ Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.

PMID: 39973942
PMCID: PMC11836497
DOI: 10.1016/j.lanepe.2025.101214

Review

2024 update of the AGIHO guideline on diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients with solid tumours and hematological malignancies

Michael Sandherr et al. Lancet Reg Health Eur. 2025.

. 2025 Jan 31:51:101214.

doi: 10.1016/j.lanepe.2025.101214. eCollection 2025 Apr.

Authors

Affiliations

¹ Specialist Clinic for Hematology and Oncology, Medical Care Center Penzberg, Germany.
² University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
³ University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany.
⁴ German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne Department, Cologne, Germany.
⁵ Department of Hematology, Oncology and Cell Therapy, Medical Faculty, Otto von Guericke University Magdeburg, Magdeburg, Germany.
⁶ Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, Bonn, Germany.
⁷ Department of Hematology and Oncology, Red Cross Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany.
⁸ Department of Medicine, Clinic I - Hematology, Oncology, Infectiology, Department of Intensive Care and Emergency Medicine, Klinikum Bremen-Mitte, Bremen, Germany.
⁹ Department of Hematology and Oncology Germering, Germering, Germany.
¹⁰ Clinic for Oncology, Hematology, Pneumology, Nephrology and Diabetology, Carl-Thiem Clinic, Cottbus, Germany.
¹¹ Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria.
¹² Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany.
¹³ Department of Internal Medicine II, Hematology, Oncology and Palliative Medicine, Asklepios Hospital Harz, Goslar, Germany.
¹⁴ Institut of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
¹⁵ Department of Internal Medicine, Hematology, Oncology and Stem Cell Transplantation, Medical University of Hannover, Hannover, Germany.
¹⁶ German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
¹⁷ Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
¹⁸ Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Germany.
¹⁹ Department Hematology, Oncology and Palliative Care, Klinikum Neuperlach and Harlaching, Munich, Germany.
²⁰ Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Austria.
²¹ BioTechMed, Graz, Austria.
²² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Tumorimmunology, Berlin, Germany.
²³ Department of Hematology, Oncology and Palliative Care, Rems-Murr-Klinikum Winnenden, Germany.
²⁴ Department of Medicine III, LMU University Hospital, LMU Munich, Germany.
²⁵ Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
²⁶ Evangelic Hospital Bethel, Bielefeld, Germany.
²⁷ Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.

PMID: 39973942
PMCID: PMC11836497
DOI: 10.1016/j.lanepe.2025.101214

Abstract

Febrile Neutropenia is an emergency in the treatment of cancer patients. It requires prompt and evidence-based clinical and antimicrobial management. The implementation of standard operating procedures (SOP) across hospitals and outpatient cancer departments can improve the outcome of FN patients by reducing FN-related morbidity and mortality and by the continuation of cancer treatment. This guideline describes an evidence-based approach to risk stratification, epidemiology, diagnosis, and treatment. It is provided by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and is an update of the 2017 version. Emerging aspects in epidemiology, diagnostic procedures, risk stratification, first-line antimicrobial treatment, empiric antifungal treatment and the duration of antimicrobial treatment are discussed and rated on evidence-based strength of recommendation and quality of evidence as described by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). By this, the aim of this guideline is to provide evidence-based recommendations on the management of febrile neutropenia in cancer patients for the practicing clinician.

Keywords: AGIHO; Algorithm; Antimicrobial treatment; Cancer; Evidence-based guideline; Febrile Neutropenia; Leukemia.

PubMed Disclaimer

Conflict of interest statement

MS: honoraria from Novartis, Roche, BMS, Janssen, Astra Zeneca, Lilly. Board member of Bavarian Cancer Society. EB: travel support by DGIIN. MH: received lecture fees from Amgen, Beigene, Eusa Pharma, Gilead, Janssen, Jazz Pharma, and served on advisory boards of Amgen, Beigene, BMS, Eusa Pharma, Janssen, Merck, and Sanofi. PK: reports grants or contracts from German Federal Ministry of Research and Education (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine (NUM) and the State of North Rhine-Westphalia; Consulting fees Ambu GmbH, Gilead Sciences, Mundipharma Research Limited, Noxxon N.V. and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., Datamed GmbH, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, HELIOS Kliniken GmbH, Jazz Pharmaceuticals Germany GmbH, Lahn-Dill-Kliniken GmbH, medupdate GmbH, MedMedia GmbH, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC, streamedup! GmbH, University Hospital and LMU Munich and VITIS GmbH; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Research Limited and Pfizer Pharma; A pending patent currently reviewed at the German Patent and Trade Mark Office (DE 10 2021113007.7); Other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. TH, RM: Travel support: Janssen, Takeda, Advisory board: Janssen. TH: honoraria for publication in HIV Medicine, literature research support by GILEAD. CR: served as a speaker and received Honoria from: AbbVie, AstraZeneca, Basilea, BioNTech, Bristol Myers Squibb, Glaxo Smith Kline, Janssen Cilag GmbH, Pfizer Pharma International, Moderna, Merck Sharp & Dohme, Roche Pharma AG, Sanofi Pasteur AG. OP: has received honoraria or travel support from Alexion, Gilead, Jazz, MSD, Neovii, Novartis, Pfizer and Therakos. He has received research support from Incyte and Priothera. He is member of advisory boards to Alexion, Equillium Bio, Jazz, Gilead, Novartis, MSD, Omeros, Orca Bio, Priothera, Sanofi, Shionogi and SOBI. RK: None for this manuscript. CLF: has received institutional grants from Gilead Sciences and Astellas Pharma, personal consulting fees from Gilead Sciences and Merck Sharp and Dohme, and payments or honoraria for lectures/presentations from Gilead Sciences, Merck Sharp and Dohme, Pfizer, BioMerieux, F2G, Immy, Shionogi. MS: none. HMO: received honoraria for lectures from Merck Serono GmbH. RS: honoraria for lectures from Akademie für Infektionsmedizin e.V., Hikma and Pfizer and travel support from Pfizer. AYC reports grants or contracts from German Federal Ministry of Research and Education (BMBF)/DLR, German Center for Infection Research (DZIV e.V.) and honoraria for lectures from Akademie für Infektionsmedizin e.V. JS: has received research grants by the German Federal Ministry of Education and Research (BMBF), Noscendo and Basilea Pharmaceuticals; has received speaker honoraria by AbbVie, Hikma, Pfizer and Gilead; has been a consultant to Gilead, Produkt & Markt GmbH, Alvea Vax and Micron Research, all outside the submitted work. LH: none. MSH (COI in the last 3 years): Employment or Leadership Position: Carl Thiem Clinic, Cottbus, Germany (head)Advisory Role or Expert Testimony: AbbVie, Amgen GmbH, Bristol Myers Squibb GmbH & Co. KG, Gilead Sciences, Glaxo Smith Kline GmbH & Co. KG, Incyte, MICE, NewConceptOncology, Pfizer Deutschland, Sanofi-Aventis Deutschland GmbH, Shionogi GmbH, Stemline Therapeutics (no personal fees) Stock Ownership: no Patent, Copyright, Licensing: no Honoraria: no Financing of Scientific Research: no. Other Financial Relationships: financial support of educational meetings at the Carl-Thiem-Klinikum Cottbus by Celgene GmbH, Janssen-Cilag GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, Roche Pharma AG, Takeda Pharma Vertrieb GmbH & Co. KG, Vifor Pharma Deutschland GmbH (no personal fees) Immaterial Conflicts of Interest: no. JN: none. FW none. OAC: grants or contracts from BMBF, Cidara, DZIF, EU-DG RTD, F2G, Gilead, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Abbvie, AiCuris, Basilea, Biocon, Boston Strategic Partners, Cidara, Seqirus, Gilead, GSK, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Mundipharma, Noxxon, Octapharma, Pardes, Partner Therapeutics, Pfizer, PSI, Scynexis, Seres, Shionogi, The Prime Meridian Group; Speaker and lecture honoraria from Abbott, Abbvie, Akademie für Infektionsmedizin, Al-Jazeera Pharmaceuticals/Hikma, amedes, AstraZeneca, Deutscher Ärzteverlag, Gilead, GSK, Grupo Biotoscana/United Medical/Knight, Medscape/WebMD, MedUpdate, MSD, Moderna, Mundipharma, Noscendo, Paul-Martini-Stiftung, Pfizer, Sandoz, Seqirus, Shionogi, streamedup!, Touch Independent, Vitis; Payment for expert testimony Cidara; Participation on a DRC or DSMB for Cidara, IQVIA, Janssen, MedPace, PSI, Pulmocide. BH: none. SM: Grant by DZIF, Honoraria by Octapharma, Pfizer, consulting Octapharma, AGIHO lead of vaccination recommendation. MSH: honoraria by Shionogi, NCO. GW: honoraria by Abbvie, AstraZeneca, GSK, Lilly, MSD, Pfizer, Sandoz, Takeda, Vifor. GB: honoraria by NewConceptOncology, Shionogi, Jazz Pharmaceuticals. Travel support by German Society for Internal Intensive Care Medicine and Emergency Medicine. Board member iCHOP. AC: grants by DZIF eV, BMBF/DLR. Honoraria by Akademie für Infektionsmedizin. Travel grant by ESCMID, FEMS, Akademie für Infektionsmedizin. KS: honoraria by Gilead.

Figures

**Fig. 1**
First-line treatment of FN—high risk. MDR multi-drug resistant; MRSA multiresistant *Staphylococcus aureus*; VRE Vancomycin-resistant *Enterococci*; ESBL-E Extended-Spectrum-Betalactamase *Echerichia coli*, CRE Carbapenem resistant *Enterobacteriacae*; (a), (b).^,

**Fig. 2**
First-line treatment of FN—high risk, with clinical symptoms (a, b, c²⁶). CVC central venous catheter.

**Fig. 3**
First-line treatment in FN—standard-risk. FUO fever of unknown origin; MASCC Multinational Association for Supportive Care in Cancer score; CNS central nervous system.

**Fig. 4**
Second-line antibiotic treatment in patients with FN. CT computed tomography.

See this image and copyright information in PMC

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2024 update of the AGIHO guideline on diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients with solid tumours and hematological malignancies

Affiliations

2024 update of the AGIHO guideline on diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients with solid tumours and hematological malignancies

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

Full Text Sources

Miscellaneous