Posaconazole cerebrospinal concentrations in an HIV-infected patient with brain mucormycosis

Abstract

of daptomycin by Etest (AB Biodisk) was 0.125 mg/L. Informed consent was obtained from the patient’s next of kin and therapy with daptomycin was started at a daily dose of 8 mg/kg; the other antibiotics were stopped. The high dose of daptomycin was chosen because of the elevated volume of distribution (which is typical of septic patients, together with lower plasma albumin concentrations) and because polysulphone daptomycin clearance is higher than for other types of ultrafiltration. It was not possible to determine plasma concentrations of daptomycin, and we therefore decided to monitor plasma concentrations of creatinine phosphokinase (CPK), aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase to exclude myopathy, a wellrecognized adverse effect of daptomycin. Since CPK can be eliminated by CVVH, we also measured the ultrafiltrate concentrations of CPK. The plasma concentration of CPK always remained ≤200 IU/L (normal: 50–397 IU/L) and the ultrafiltered CPK concentration never exceeded 86 IU/L. The patient’s condition improved and therapy was discontinued after 14 days. Dosing of antibiotics for patients in intensive care can be challenging, particularly when they undergo renal replacement therapy. Ideally, plasma concentrations should be checked regularly, but this may be impractical in real time. Data from in vitro models of CRRT suggest that a substantial amount of daptomycin can be removed. Since we could not monitor antibiotic concentrations in order to avoid subtherapeutic exposure, we decided to use a higher daily dose (8 mg/kg) and no adverse effects were demonstrated. Despite the limitations of this report we suggest that higher doses can be given safely in CRRT, but patients should be closely monitored for evidence of myopathy. Further studies, with plasma monitoring, are required to refine dosage regimens for CRRT.