Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study

Abstract Introduction Intravenous fosfomycin (FOS) is a broad-spectrum antibiotic primarily used in combination therapy to treat severe infections caused by both Gram-positive (GP) and Gram-negative (GN) pathogens, including multi-drug resistant (MDR) bacteria. The aim of this study, the largest to...

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Main Authors: Klaus-Friedrich Bodmann, Stefan Hagel, Alessandra Oliva, Stefan Kluge, Alessandra Mularoni, Valentina Galfo, Marco Falcone, Mathias W. Pletz, Simone Lindau, Nadja Käding, Jan T. Kielstein, Michael Zoller, Carlo Tascini, Sebastian Kintrup, Dirk Schädler, Claudia Spies, Francesco G. De Rosa, Szilvia Radnoti, Alessandra Bandera, Roberto Luzzati, Sam Allen, Loredana Sarmati, Antonio Cascio, Nikolaos Kapravelos, Chinari P. K. Subudhi, George Dimopoulos, Matthias G. Vossen, Abhijit M. Bal, Mario Venditti, Claudio M. Mastroianni, Thomas Borrmann, Christian Mayer
Format: Article
Language:English
Published: Adis, Springer Healthcare 2025-03-01
Series:Infectious Diseases and Therapy
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Online Access:https://doi.org/10.1007/s40121-025-01125-2
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author Klaus-Friedrich Bodmann
Stefan Hagel
Alessandra Oliva
Stefan Kluge
Alessandra Mularoni
Valentina Galfo
Marco Falcone
Mathias W. Pletz
Simone Lindau
Nadja Käding
Jan T. Kielstein
Michael Zoller
Carlo Tascini
Sebastian Kintrup
Dirk Schädler
Claudia Spies
Francesco G. De Rosa
Szilvia Radnoti
Alessandra Bandera
Roberto Luzzati
Sam Allen
Loredana Sarmati
Antonio Cascio
Nikolaos Kapravelos
Chinari P. K. Subudhi
George Dimopoulos
Matthias G. Vossen
Abhijit M. Bal
Mario Venditti
Claudio M. Mastroianni
Thomas Borrmann
Christian Mayer
author_facet Klaus-Friedrich Bodmann
Stefan Hagel
Alessandra Oliva
Stefan Kluge
Alessandra Mularoni
Valentina Galfo
Marco Falcone
Mathias W. Pletz
Simone Lindau
Nadja Käding
Jan T. Kielstein
Michael Zoller
Carlo Tascini
Sebastian Kintrup
Dirk Schädler
Claudia Spies
Francesco G. De Rosa
Szilvia Radnoti
Alessandra Bandera
Roberto Luzzati
Sam Allen
Loredana Sarmati
Antonio Cascio
Nikolaos Kapravelos
Chinari P. K. Subudhi
George Dimopoulos
Matthias G. Vossen
Abhijit M. Bal
Mario Venditti
Claudio M. Mastroianni
Thomas Borrmann
Christian Mayer
author_sort Klaus-Friedrich Bodmann
collection DOAJ
description Abstract Introduction Intravenous fosfomycin (FOS) is a broad-spectrum antibiotic primarily used in combination therapy to treat severe infections caused by both Gram-positive (GP) and Gram-negative (GN) pathogens, including multi-drug resistant (MDR) bacteria. The aim of this study, the largest to date, was to evaluate the effectiveness, safety, usage patterns, and patient characteristics of FOS in a real-world setting. Methods Interim analysis of an ongoing, prospective, non-interventional, multicentre study in five European countries, involving centres in Germany, Italy, the United Kingdom, Greece, and Austria. Results A total of 716 patients were enrolled between January 2017 and November 2023 (mean age: 62.8 years, APACHE II: 18.3, SOFA: 6.7). Main indications for FOS were bacteraemia/sepsis (23.6%), complicated urinary tract infections (18.0%), and bone and joint infections (17.4%). Other indications included hospital-acquired/ventilator-associated pneumonia (11.0%), complicated skin and soft tissue infections (9.1%), bacterial meningitis/central nervous system (CNS) infections (7.8%), and infective endocarditis (6.4%). Most common pathogens identified were Staphylococcus aureus (31.4%, including methicillin-resistant S. aureus), Klebsiella spp. (including K. pneumoniae) (17.2%), Escherichia coli (14.2%), coagulase-negative staphylococci (12.9%), other Enterobacterales (10.9%), and Pseudomonas aeruginosa (8.4%). In 34.6% of patients, an MDR pathogen was involved. Carbapenem resistance (CR) was high in Klebsiella spp. infections (59/123, 48.0%). In most patients, FOS was used in combination therapy (90.2%). The median dose was 15 g/day. Overall, clinical success and clinical response were favourable with 75.3% and 83.4% at the end of FOS treatment. Clinical success rates in infections caused by MDR or CR pathogens were 78.0% and 81.8%, respectively. Microbiological cure was achieved in 82.4% of all patients. Electrolyte imbalances were the most frequently observed adverse drug reactions, while gastrointestinal disorders were rare. Conclusion The results from this study suggest that FOS is a safe and effective option as combination partner in the treatment of patients with severe infections caused by both GP and GN pathogens, including deep-seated infections and/or involvement of MDR bacteria. Trial Registration ClinicalTrials.gov identifier, NCT02979951.
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spelling doaj-art-7e52d1039b6e4772b7ebb90a67ea7c632025-08-20T02:12:02ZengAdis, Springer HealthcareInfectious Diseases and Therapy2193-82292193-63822025-03-0114476579110.1007/s40121-025-01125-2Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS StudyKlaus-Friedrich Bodmann0Stefan Hagel1Alessandra Oliva2Stefan Kluge3Alessandra Mularoni4Valentina Galfo5Marco Falcone6Mathias W. Pletz7Simone Lindau8Nadja Käding9Jan T. Kielstein10Michael Zoller11Carlo Tascini12Sebastian Kintrup13Dirk Schädler14Claudia Spies15Francesco G. De Rosa16Szilvia Radnoti17Alessandra Bandera18Roberto Luzzati19Sam Allen20Loredana Sarmati21Antonio Cascio22Nikolaos Kapravelos23Chinari P. K. Subudhi24George Dimopoulos25Matthias G. Vossen26Abhijit M. Bal27Mario Venditti28Claudio M. Mastroianni29Thomas Borrmann30Christian Mayer31Kliniken Nordoberpfalz AGInstitute for Infectious Diseases and Infection Control, Jena University Hospital, Friedrich-Schiller-UniversityDepartment of Public Health and Infectious Diseases, Sapienza University of RomeDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfIRCCS-ISMETTDepartment of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, University of PisaDepartment of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, University of PisaInstitute for Infectious Diseases and Infection Control, Jena University Hospital, Friedrich-Schiller-UniversityDepartment of Anaesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Frankfurt, Goethe-University FrankfurtDepartment of Infectious Diseases and Microbiology, University of LuebeckMedical Clinic V Nephrology, Rheumatology, Blood Purification - Academic Teaching Hospital BraunschweigDepartment of Anaesthesiology, LMU University Hospital, LMU MunichDepartment of Medicine (DMED), Infectious Diseases Clinic, University of UdineDepartment of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital MuensterDepartment for Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-HolsteinDepartment of Anaesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité – Universitätsmedizin BerlinDepartment of Medical Sciences, Infectious Diseases, University of TurinKliniken Nordoberpfalz AGInfectious Diseases Unit, IRCCS Ca’ Granda Ospedale Maggiore Policlinico FoundationClinical Department of Medical, Surgical and Health Sciences, Trieste UniversityDepartment of Microbiology, University Hospital CrosshouseDepartment of Infectious Diseases, University Hospital Tor VergataInfectious and Tropical Diseases Unit, AOU Policlinico “P. Giaccone”, University of PalermoIntensive Care Unit, G Papanikolaou General HospitalRoyal Bolton HospitalThird Department of Critical Care Medicine, Medical School, National and Kapodistrian University of AthensDivision of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of ViennaDepartment of Microbiology, Queen Elizabeth University HospitalDepartment of Public Health and Infectious Diseases, Sapienza University of RomeDepartment of Public Health and Infectious Diseases, Sapienza University of RomeInfectoPharm Arzneimittel und Consilium GmbHInfectoPharm Arzneimittel und Consilium GmbHAbstract Introduction Intravenous fosfomycin (FOS) is a broad-spectrum antibiotic primarily used in combination therapy to treat severe infections caused by both Gram-positive (GP) and Gram-negative (GN) pathogens, including multi-drug resistant (MDR) bacteria. The aim of this study, the largest to date, was to evaluate the effectiveness, safety, usage patterns, and patient characteristics of FOS in a real-world setting. Methods Interim analysis of an ongoing, prospective, non-interventional, multicentre study in five European countries, involving centres in Germany, Italy, the United Kingdom, Greece, and Austria. Results A total of 716 patients were enrolled between January 2017 and November 2023 (mean age: 62.8 years, APACHE II: 18.3, SOFA: 6.7). Main indications for FOS were bacteraemia/sepsis (23.6%), complicated urinary tract infections (18.0%), and bone and joint infections (17.4%). Other indications included hospital-acquired/ventilator-associated pneumonia (11.0%), complicated skin and soft tissue infections (9.1%), bacterial meningitis/central nervous system (CNS) infections (7.8%), and infective endocarditis (6.4%). Most common pathogens identified were Staphylococcus aureus (31.4%, including methicillin-resistant S. aureus), Klebsiella spp. (including K. pneumoniae) (17.2%), Escherichia coli (14.2%), coagulase-negative staphylococci (12.9%), other Enterobacterales (10.9%), and Pseudomonas aeruginosa (8.4%). In 34.6% of patients, an MDR pathogen was involved. Carbapenem resistance (CR) was high in Klebsiella spp. infections (59/123, 48.0%). In most patients, FOS was used in combination therapy (90.2%). The median dose was 15 g/day. Overall, clinical success and clinical response were favourable with 75.3% and 83.4% at the end of FOS treatment. Clinical success rates in infections caused by MDR or CR pathogens were 78.0% and 81.8%, respectively. Microbiological cure was achieved in 82.4% of all patients. Electrolyte imbalances were the most frequently observed adverse drug reactions, while gastrointestinal disorders were rare. Conclusion The results from this study suggest that FOS is a safe and effective option as combination partner in the treatment of patients with severe infections caused by both GP and GN pathogens, including deep-seated infections and/or involvement of MDR bacteria. Trial Registration ClinicalTrials.gov identifier, NCT02979951.https://doi.org/10.1007/s40121-025-01125-2FosfomycinStaphylococcus aureusCarbapenem-resistant EnterobacteralesBacteraemiaInfective endocarditisMDR
spellingShingle Klaus-Friedrich Bodmann
Stefan Hagel
Alessandra Oliva
Stefan Kluge
Alessandra Mularoni
Valentina Galfo
Marco Falcone
Mathias W. Pletz
Simone Lindau
Nadja Käding
Jan T. Kielstein
Michael Zoller
Carlo Tascini
Sebastian Kintrup
Dirk Schädler
Claudia Spies
Francesco G. De Rosa
Szilvia Radnoti
Alessandra Bandera
Roberto Luzzati
Sam Allen
Loredana Sarmati
Antonio Cascio
Nikolaos Kapravelos
Chinari P. K. Subudhi
George Dimopoulos
Matthias G. Vossen
Abhijit M. Bal
Mario Venditti
Claudio M. Mastroianni
Thomas Borrmann
Christian Mayer
Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study
Infectious Diseases and Therapy
Fosfomycin
Staphylococcus aureus
Carbapenem-resistant Enterobacterales
Bacteraemia
Infective endocarditis
MDR
title Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study
title_full Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study
title_fullStr Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study
title_full_unstemmed Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study
title_short Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study
title_sort real world use effectiveness and safety of intravenous fosfomycin the fortress study
topic Fosfomycin
Staphylococcus aureus
Carbapenem-resistant Enterobacterales
Bacteraemia
Infective endocarditis
MDR
url https://doi.org/10.1007/s40121-025-01125-2
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