Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study.
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
Stefan Hagel: Institute for Infectious Diseases and Infection Control, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany. stefan.hagel@uni-jena.de. ORCID
Alessandra Oliva: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
Stefan Kluge: Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Valentina Galfo: Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.
Marco Falcone: Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.
Mathias W Pletz: Institute for Infectious Diseases and Infection Control, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.
Simone Lindau: Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt, Germany.
Nadja Käding: Department of Infectious Diseases and Microbiology, University of Luebeck, Luebeck, Germany.
Jan T Kielstein: Medical Clinic V Nephrology, Rheumatology, Blood Purification - Academic Teaching Hospital Braunschweig, Brunswick, Germany.
Michael Zoller: Department of Anaesthesiology, LMU University Hospital, LMU Munich, Munich, Germany.
Carlo Tascini: Department of Medicine (DMED), Infectious Diseases Clinic, University of Udine, Udine, Italy.
Sebastian Kintrup: Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany.
Dirk Schädler: Department for Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Claudia Spies: Department of Anaesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Berlin, Germany.
Francesco G De Rosa: Department of Medical Sciences, Infectious Diseases, University of Turin, Turin, Italy.
Alessandra Bandera: Infectious Diseases Unit, IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation, Milan, Italy.
Roberto Luzzati: Clinical Department of Medical, Surgical and Health Sciences, Trieste University, Trieste, Italy.
Sam Allen: Department of Microbiology, University Hospital Crosshouse, Kilmarnock, UK.
Loredana Sarmati: Department of Infectious Diseases, University Hospital Tor Vergata, Rome, Italy.
Antonio Cascio: Infectious and Tropical Diseases Unit, AOU Policlinico "P. Giaccone", University of Palermo, Palermo, Italy.
Nikolaos Kapravelos: Intensive Care Unit, G Papanikolaou General Hospital, Exohi, Thessaloniki, Greece.
Chinari P K Subudhi: Royal Bolton Hospital, Bolton, UK.
George Dimopoulos: Third Department of Critical Care Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Matthias G Vossen: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Abhijit M Bal: Department of Microbiology, Queen Elizabeth University Hospital, Glasgow, UK.
Mario Venditti: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
Claudio M Mastroianni: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
Thomas Borrmann: InfectoPharm Arzneimittel und Consilium GmbH, Heppenheim, Germany.
Christian Mayer: InfectoPharm Arzneimittel und Consilium GmbH, Heppenheim, Germany.
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.
