Article
Intrathecal penetration of fosfomycin in patients with ventriculitis – a prospective observational study
Intrathekale Penetration von Fosfomycin bei Patienten mit Ventrikulitis – eine prospektive Beobachtungsstudie
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Published: | May 25, 2022 |
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Objective: For treatment of ventriculitis, vancomycin and meropenem are frequently used as empiric treatment but cerebrospinal fluid (CSF) penetration is highly variable and may result in subtherapeutic concentrations. Fosfomycin (FOF) has been suggested for combination antibiotic therapy enhancing gram-positive and gram-negative coverage, but data are sparse, so far. Therefore, we studied CSF penetration of FOF in ventriculitis.
Methods: With ethics approval, patients receiving a continuous infusion of FOF for ventriculitis at a starting dose of 24g/d were included, and patient data, including serum and CSF concentrations for FOF were prospectively collected twice weekly from CSF drains. Antibiotic CSF penetration ratio was calculated for each patient. The dose was subsequently adapted according to TDM values, targeting CSF concentrations above the antibiotic resistance breakpoint.
Results: Seventeen patients with 43 CSF/serum pairs were included. Infections were caused by coagulase-negative Staphylococci (n=10), Enterobacterales (n=6), and S. aureus (n=1). Mean FOF serum concentration was 257 ± 157 mg/L and the CSF concentration 127 ± 93 mg/L. Considering only the first measurements in each patient before a possible dose adaption, mean serum and CSF concentrations were 268 ± 157 mg/L and 158 ± 120 mg/L. Mean CSF penetration was 50 ± 22% with a coefficient of determination (R2) of 0.65. We found 98% of CSF levels above the antibiotic resistance breakpoint of 32 mg/L. No adverse toxicity was observed.
Conclusion: Penetration of FOF into the CSF is high, reliably leading to concentrations above the resistance breakpoint. Continuous administration of FOF appears to be a reasonable approach for antibiotic combination therapy in patients suffering from ventriculitis.