Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy-associated ventriculitis

Abstract

The present pharmacokinetic study indicates that 8 g of fosfomycin three times per day should provide sufficient antimicrobial concentrations in the CSF for the overall treatment period. Thus, the co-administration of fosfomycin could be useful for the treatment of ventriculitis caused by susceptible pathogens.

Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections

“…In this respect, some studies have found that fosfomycin demonstrates concentration-dependent killing activity against strains of Escherichia coli and Proteus mirabilis in vitro as well as strains of S. pneumoniae in vivo [38,39]. However, other studies have noted timedependent bactericidal activity of fosfomycin against S. aureus strains in vitro [32,40].…”

“…In patients with ventriculostomy-associated ventriculitis who received 8 g of i.v. fosfomycin three times daily, the CSF-to-serum fosfomycin AUC ratio has been found to be 27% at steady state [32]. Fosfomycin has also been shown to achieve clinically relevant drug concentrations in the brain parenchyma [29].…”

Fosfomycin and Its Application in the Treatment of Multidrug-Resistant Enterobacteriaceae Infections

“…A cumulative effect is observed after multiple doses. 31,43 The main pharmacokinetic parameters are presented in Table 1. Serum protein binding is estimated at below 3%, which allows a large tissue availability.…”

“…Impairment of hepatic function has little impact on the plasma elimination half-life of fosfomycin. 44 In spite of 40 years of evolution of methods to determine fosfomycin concentrations, there has been almost no progress in lowering the limit of sensitivity of the assays, which is approximately 1 mg/L by gas chromatography 43,49,50 or by capillary gas chromatography, 51,52 while by microbiological methods, it is reported to be 0.7-1.5 mg/L when mentioned. 47,48,53,54 …”

“…After two hours of exposure to different concentrations of the antibiotic, these authors observed a postantibiotic effect in the range of 3.2-4.7 hours. According to Pfausler et al 43 optimal killing is time-dependent, but requires fosfomycin concentrations at least eight times the minimum inhibitory concentration (MIC) in the medium. In a study in which Gram-negative infected catheters were treated with fosfomycin or other antibiotics alone or in combination, no regimen was able to eliminate the organisms.…”