Pharmacokinetics of meropenem in patients with renal failure and patients receiving renal replacement therapy

Meropenem is a well established carbapenem antibacterial with a wide spectr um of activity against Gram-positive and Gram-negative bacteria, including beta -lactamase producers and Pseudomonas aeruginosa. Because of its clinic al and bacteriological efficacy, meropenem is an important antimicrobial dr ug in the treatment of serious infections in adults and in children. Meropenem is predominately excreted unchanged in the urine, and thus dosage adjustments are necessary in patients with renal insufficiency and those u ndergoing intermittent haemodialysis (IHD) or various forms of continuous r enal replacement therapy (CRRT), such as continuous venovenous haemodialysi s, continuous venovenous haemodiafiltration (CVVHDF), continuous venovenous haemofiltration (CVVHF) or continuous ambulatory peritoneal dialysis (CAPD ). The half-life of meropenem (approximately 1 hour in healthy volunteers) is prolonged up to 13.7 hours in anuric patients with end-stage renal disease, In patients receiving renal replacement therapy, half-life is influenced b y drug-specific factors as well by membrane and treatment modalities (IHD, CRRT or CAPD). Plasma meropenem concentrations reach a peak of between 53 a nd 62 mg/L after the administration of meropenem 1g intravenously to health y volunteers, up to 53 mg/L after meropenem 0.5g in haemodialysis patients, and between 18 and 45 mg/L after meropenem Ig during CRRT in critically il l patients. Approximately 50% of meropenem is eliminated by IHD, 25 to 50% by CVVHF and 13 to 53% by CVVHDF Such differences are not negligible and demonstrate th e great influence of the treatment modality on the elimination of the drug during renal replacement therapy. Thus, physicians run the risk of un derdo sing with this antimicrobial drug because of the quite different recommenda tions in the literature. Because of the excellent tolerability profile of m eropenem, such underadministration should be avoided.