Extracellular concentrations of fosfomycin in lung tissue of septic patients

Abstract

We conclude that fosfomycin achieves antimicrobially effective concentrations in infected lung tissue.

Fosfomycin

“…Intravenous fosfomycin seems also to exhibit good penetration into infected lung tissue; the ratio of the AUC 0 -ϱ for lung to the AUC 0 -ϱ for plasma was 0.63 in a study evaluating the ability of a single 4-g intravenous dose of fosfomycin to penetrate lung tissue of septic patients. In that study, fosfomycin's mean C max and AUC 0 -ϱ were higher in healthy than in infected lungs (131.6 Ϯ 110.6 mg/liter versus 107.5 Ϯ 60.2 mg/liter and 367.6 Ϯ 111.9 mg · h/liter versus 315.1 Ϯ 151.2 mg · h/liter, respectively) (191). Finally, fosfomycin achieves adequate concentrations in pleural fluid (due to both infectious and noninfectious etiology) for at least 12 h following the end of infusion.…”

Pharmacodynamic and pharmacokinetic considerations in the treatment of critically Ill patients infected with carbapenem-resistant Enterobacteriaceae

“…The breakpoint set by EUCAST for fosfomycin against Enterobacteriaceae is 32 mg/mL, 70 which is a concentration achievable in many body tissues including the lungs and interstitial spaces. [70][71][72][73] There is wide variation in the dosing regimens described in the limited reports of intravenous fosfomycin for CRE infections, ranging up to 24 g of drug daily divided 3 or 4 times a day. 74,75 Optimal pharmacodynamic targets for fosfomycin are unclear; historically it has been considered a time-dependent agent, but some recent pharmacodynamic studies with fosfomycin against E. coli have shown the fAUC/MIC ratio to be most predictive of efficacy.…”

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

“…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 …”

“…Elimination is prolonged, with mean concentrations above 128 mg/L for more than 24 hours. 52,53 The concentration achieved in urine is the main criterion for the break points chosen by the Clinical and Laboratory Standards Institute. 58 When fosfomycin is taken with food, the peak urinary concentration is lower and appears later.…”