Pharmacokinetic aspects of cerebrospinal fluid penetration of fosfomycin

Abstract

Even today antibiotic therapy of postoperative or posttraumatic meningitis remains a problem. In patients in a neurosurgical intensive care unit, nosocomial microorganisms with high resistance are mainly found. There are no antibiotics available which have simultaneously a good efficacy on the higher resistant nosocomial microorganisms and a good penetration through the blood-brain or blood-cerebrospinal fluid barrier. We analysed the cerebrospinal fluid (CSF) penetration of fosfomycin carrying out the investigations in patients in whom a CSF drainage was required for a neurosurgical indication. The blood-brain barrier was considered to be largely intact (total CSF protein and cell counts with in the normal range). Five or 10 g fosfomycin were administered to adults in 30 min infusions. After administration of 5 g, the CSF concentration formed a plateau between 8.6 and 9.9 micrograms/ml 3 to 6 h after the infusion. Increasing the dose infused (10 g) markedly shortened the latency period between reaching a sufficient concentration of fosfomycin in the CSF. With repeated doses of fosfomycin (3 X 5 g/day) the concentration in the CSF did not fall below the therapeutic level. Even in the presence of an intact blood-brain barrier, fosfomycin in our investigation showed a satisfactory penetration into the CSF. This is attributable to the favourable physicochemical state of fosfomycin (relative molecular mass 182).