Renal Insufficiency and Fosfomycin

Abstract

After the parenteral injection of 1 g sodium salt of fosfomycin the serum levels of the antibiotic are detected in a series of eight adult patients with different degrees of chronic renal insufficiencies four of them submitted to periodical dialysis. The results obtained reveal that the levels as well as the time of elimination of fosfomycin maintain an obvious relation to the degree of renal insufficiency in the patients.

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

“…25,30,31 This pattern is characteristic of a bicompartmental model. A cumulative effect is observed after multiple doses.…”

“…It should be noted that fosfomycin concentrations in cerebrospinal fluid are much greater during the acute phase of meningitis than in the absence of inflammation. 31,45 Moreover, fosfomycin concentrations in amniotic fluid, fetal blood, colostrum, and milk were 45%, 18%, 5%, and 4%, respectively, of blood concentrations. 30 Fosfomycin is almost completely eliminated by glomerular filtration, and 80%-95% of the dose is recovered unchanged in urine within 24 hours.…”

“…Because this target is very specific to the bacterial wall, fosfomycin is not metabolized in mammals. 30,31 In spite of its wide spectrum of antibacterial activity, pharmaceutical development of the molecule has been limited as a consequence of difficulties in determining its in vitro activity 15 and its clinical efficacy. 18,32 These issues have led to restricted therapeutic use of fosfomycin as a single agent.…”

“…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.…”

“…44,48,53 Fosfomycin trometamine is thought to dissociate into fosfomycin acid and trometamine at the absorption stage, 55 and then fosfomycin absorption is mediated via the intestinal phosphate transport system. 56 After a single dose of fosfomycin 3 g, the bioavailability ranges from 34% to 58%, 31,44,53,55,57 with a peak plasma concentration ranging from 12 to 32 mg/L and a delay of 2-4 hours. Because fosfomycin is not metabolized and the nonrenal clearance is negligible, 30 the main route of excretion is in the urine.…”