Related Experiment Video
Updated: Jun 14, 2026
Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Detection of Central Nervous System Pathogens
Published on: April 17, 2026
Real-World Data on the Use of Intravenous Fosfomycin for the Treatment of Central Nervous System Infections: a
Dominik Jarczak1, Stefan Kluge2, Martin Kieninger3
1Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. d.jarczak@uke.de.
Introduction:
Central nervous system (CNS) infections are associated with high morbidity and mortality, and their management is challenged by antimicrobial resistance and limited cerebrospinal fluid (CSF) penetration of many antibiotics. Intravenous fosfomycin (FOS) offers broad-spectrum activity, favourable pharmacokinetics and reliable CSF penetration, making it a potential partner in combination therapy for severe CNS infections. This interim subgroup analysis of the prospective FORTRESS study evaluated real-world treatment patterns, effectiveness and safety of FOS in patients with CNS infections.
Methods:
FORTRESS is an ongoing multicentre, non-interventional, international study enrolling patients receiving FOS for severe infections. We analysed patients with documented CNS infections among 1019 enrolled up to June 2025. Effectiveness endpoints at end of treatment (EOT) included clinical success (composite endpoint defined as successful clinical response plus concomitant microbiological cure), successful clinical response (defined as complete or partial resolution of signs and symptoms), microbiological cure, clinical failure and in-hospital mortality. Safety outcomes included adverse drug reactions (ADRs; including serious ADRs) and laboratory parameters.
Results:
A total of 64 patients with CNS infections were included, of which most were critically ill at baseline, with high rates of ICU admission (90.6%), sepsis (42.2%) and mechanical ventilation (35.9%). Included patients were treated for ventriculitis (53.1%), brain abscess/empyema (26.6%), bacterial meningitis (26.6%) and shunt infections (18.8%), mainly caused by Staphylococcus spp. (48.8%). FOS was administered exclusively in combination regimens, generally as second- or third-line therapy, at high daily doses (median 22.1 g/day). At EOT, clinical success was achieved in 82.8% of patients, a successful clinical response in 92.2% and microbiological cure in 85.9%. All-cause in-hospital mortality was 12.5%. Outcomes were especially favourable in bacterial meningitis (94.1% clinical success) and Gram-positive infections (96.6% clinical success). FOS was generally well tolerated. Electrolyte imbalances were the most common ADRs but were mainly mild and did not require treatment modification.
Conclusions:
These interim real-world data suggest that FOS, used in combination with other antimicrobial agents, is an effective and well-tolerated treatment option for severely ill patients with CNS infections.
Trial Registration:
ClinicalTrials.gov identifier, NCT02979951.
Insights
Intravenous fosfomycin (FOS) combination therapy shows promising results for severe central nervous system (CNS) infections. Real-world data indicate high clinical success rates and good tolerability in critically ill patients.
Area of Science:
- Infectious Diseases
- Pharmacology
- Critical Care Medicine
Background:
- Central nervous system (CNS) infections present significant challenges due to antimicrobial resistance and poor antibiotic penetration.
- Intravenous fosfomycin (FOS) demonstrates broad-spectrum activity, favorable pharmacokinetics, and reliable cerebrospinal fluid (CSF) penetration.
- FOS is a potential adjunctive therapy for severe CNS infections.
Purpose of the Study:
- To evaluate real-world treatment patterns, effectiveness, and safety of FOS in patients with CNS infections.
- To analyze outcomes in critically ill patients receiving FOS as part of combination therapy.
- To assess FOS efficacy in specific CNS infection subtypes and against Gram-positive pathogens.
Main Methods:
- Interim subgroup analysis of the prospective, international, non-interventional FORTRESS study.
- Inclusion of 64 patients with documented CNS infections treated with FOS up to June 2025.
- Evaluation of clinical success, clinical response, microbiological cure, and in-hospital mortality at end of treatment (EOT).
Main Results:
- FOS was used in combination regimens, often as second- or third-line therapy, at high daily doses (median 22.1 g/day).
- High rates of clinical success (82.8%), successful clinical response (92.2%), and microbiological cure (85.9%) were observed at EOT.
- Outcomes were particularly favorable for bacterial meningitis (94.1% clinical success) and Gram-positive infections (96.6% clinical success).
- All-cause in-hospital mortality was 12.5%; FOS was generally well-tolerated with manageable electrolyte imbalances.
Conclusions:
- Interim real-world data suggest FOS combination therapy is effective for severe CNS infections.
- FOS demonstrates good tolerability in critically ill patients requiring intensive care.
- FOS represents a valuable option in managing complex CNS infections, especially those caused by Gram-positive bacteria.
Related Concept Videos
01:29Drug Delivery: Parenteral Route
There are three primary parenteral routes: intravenous (IV), intramuscular (IM), and subcutaneous (SC). The IV route introduces the drug directly into the bloodstream, ensuring immediate action. The IM route...
01:27Cryptococcal Meningitis
01:22Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence
01:28Acute Pyelonephritis II: Diagnostic Studies and Management
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:30Urinary Tract Infection III: Diagnostic Studies and Interprofessional Care