Real-World Data on the Effectiveness and Use of Intravenous Fosfomycin for the Treatment of Difficult-to-Treat Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria—A Subgroup Analysis from the FORTRESS Study

INTRODUCTION: This subgroup analysis of the FORTRESS study aimed to evaluate clinical and microbiological outcomes, treatment patterns, and safety of intravenous fosfomycin (FOS)-containing regimens for the treatment of infections due to carbapenem-resistant (CR) Gram-negative bacteria in a real-world setting. METHODS: Interim data from patients treated with FOS for infections due to CR pathogens were analyzed from the ongoing prospective, multicenter, multinational, observational FORTRESS study. Key outcomes included patient demographics, clinical and infection characteristics at baseline, treatment patterns, and indications of FOS use, as well as clinical, microbiological, and safety outcomes. Exploratory Firth univariate and multivariate logistic regression were performed to identify factors associated with successful clinical response. RESULTS: The subgroup included 161 patients (median age 60 years, 30.4% female, median APACHE II score 15), of whom 59.6% required intensive care, and 41.6% had sepsis at baseline. The most common indications for FOS therapy were hospital-acquired/ventilator-associated pneumonia (28.0%), bacteremia/sepsis (26.1%), and complicated urinary tract infections (24.8%). Infections were predominantly caused by Klebsiella pneumoniae (62.7%), Pseudomonas aeruginosa (28.6%), and Acinetobacter baumannii (17.4%). Carbapenem resistance was mainly mediated by Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM). In the majority of patients, FOS was part of a combination regimen (91.3%), with ceftazidime-avibactam being the most frequently used partner antibiotic. Overall, clinical success was achieved in 79.4% of patients, while the successful clinical response and microbiological cure rates were 87.5% and 81.3% at the end of FOS treatment, respectively. All-cause in-hospital mortality was 9.9%. Electrolyte imbalances were the most commonly reported adverse drug reactions, but they were mostly not treatment-limiting. CONCLUSIONS: The real-world data of this subgroup analysis suggest that FOS-containing regimens were associated with generally favorable clinical and microbiological outcomes and acceptable tolerability in patients with severe infections due to CR Gram-negative bacteria.

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Journal
Infectious Diseases and Therapy
Published
2026-08-14
DOI
https://doi.org/10.1007/s40121-026-01413-5
Primary Topic
Antibiotic Resistance in Bacteria
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article
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article

Real-World Data on the Effectiveness and Use of Intravenous Fosfomycin for the Treatment of Difficult-to-Treat Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria—A Subgroup Analysis from the FORTRESS Study

Giovanna Russelli, Evangelos J. Giamarellos‐Bourboulis, Giusy Tiseo, Michael Zöller et al.
Infectious Diseases and Therapy
Antibiotic Resistance in Bacteria
article

Real-World Data on the Effectiveness and Use of Intravenous Fosfomycin for the Treatment of Difficult-to-Treat Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria—A Subgroup Analysis from the FORTRESS Study

Giovanna Russelli, Evangelos J. Giamarellos‐Bourboulis, Giusy Tiseo, Michael Zöller, Despina Hatzilia, Francesco Alessandri, Loredana Sarmati, Valentina Galfo, Christian Mayer, Alessandra Oliva, Stelios F. Assimakopoulos, Laura Campogiani, Alessandra Mularoni, Marco Falcone, Christina Iasonidou, Francesca Ferretti, Antonio Cascio, Dominik Jarczak, Stavrina Avgeropoulou, Stefan Hagel, Stefan Kluge, Annalisa Saracino, Jan T. Kielstein, Abhijit M. Bal, George Dimopoulos, Klaus‐Friedrich Bodmann, Thomas Borrmann, Claudio M. Mastroianni, Eleni Mouloudi, Valerio Del Bono, Mathias W. Pletz, Pavlos Myrianthefs, Kai Zacharowski, Markos Marangos, Ivan Gentile, Alessandro Capone, Giancarlo Ceccarelli, Matthias G. Vossen, Alessandra Bandera, Daniele R. Giacobbe, Matteo Bassetti, Carlo Tascini, the FORTRESS study group
article en

Abstract

INTRODUCTION: This subgroup analysis of the FORTRESS study aimed to evaluate clinical and microbiological outcomes, treatment patterns, and safety of intravenous fosfomycin (FOS)-containing regimens for the treatment of infections due to carbapenem-resistant (CR) Gram-negative bacteria in a real-world setting. METHODS: Interim data from patients treated with FOS for infections due to CR pathogens were analyzed from the ongoing prospective, multicenter, multinational, observational FORTRESS study. Key outcomes included patient demographics, clinical and infection characteristics at baseline, treatment patterns, and indications of FOS use, as well as clinical, microbiological, and safety outcomes. Exploratory Firth univariate and multivariate logistic regression were performed to identify factors associated with successful clinical response. RESULTS: The subgroup included 161 patients (median age 60 years, 30.4% female, median APACHE II score 15), of whom 59.6% required intensive care, and 41.6% had sepsis at baseline. The most common indications for FOS therapy were hospital-acquired/ventilator-associated pneumonia (28.0%), bacteremia/sepsis (26.1%), and complicated urinary tract infections (24.8%). Infections were predominantly caused by Klebsiella pneumoniae (62.7%), Pseudomonas aeruginosa (28.6%), and Acinetobacter baumannii (17.4%). Carbapenem resistance was mainly mediated by Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM). In the majority of patients, FOS was part of a combination regimen (91.3%), with ceftazidime-avibactam being the most frequently used partner antibiotic. Overall, clinical success was achieved in 79.4% of patients, while the successful clinical response and microbiological cure rates were 87.5% and 81.3% at the end of FOS treatment, respectively. All-cause in-hospital mortality was 9.9%. Electrolyte imbalances were the most commonly reported adverse drug reactions, but they were mostly not treatment-limiting. CONCLUSIONS: The real-world data of this subgroup analysis suggest that FOS-containing regimens were associated with generally favorable clinical and microbiological outcomes and acceptable tolerability in patients with severe infections due to CR Gram-negative bacteria.

Infectious Diseases and Therapy
University of Pisa (IT), Goethe University Frankfurt (DE), University of Rome Tor Vergata (IT), University of Udine (IT), Universität Hamburg (DE), University of Patras (GR), National and Kapodistrian University of Athens (GR), Policlinico Umberto I (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), LMU Klinikum (DE), Ospedale Maggiore (IT), Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IT), Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari (IT), University Medical Center Hamburg-Eppendorf (DE), Klinikum Weiden (DE), Klinikum Braunschweig (DE), University Hospital Frankfurt (DE), Jena University Hospital (DE), Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo (IT), Ospedale Policlinico San Martino (IT), Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" di Palermo (IT), InfectoPharm (Germany) (DE), KAT General Hospital of Attica (GR), G. Papanikolaou General Hospital (GR), Queen Elizabeth University Hospital (GB), Lewisham and Greenwich NHS Trust (GB), Azienda Ospedaliera Universitaria Pisana (IT), Hellenic Institute for the Study of Sepsis (GR), Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IT), University of Bari Aldo Moro (IT), University of Naples Federico II (IT), Medical University of Vienna (AT), Friedrich Schiller University Jena (DE), Ludwig-Maximilians-Universität München (DE), University of Genoa (IT), Sapienza University of Rome (IT), University of Palermo (IT)
Pfizer, AstraZeneca, Sanofi, Moderna, Shionogi, Swedish Orphan Biovitrum
Good health and well-being
Openalex Percentile: Top 17%
Antibiotic Resistance in Bacteria
DOIOpen Access PDFOpenAlex
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