Meropenem

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Abstract
Meropenem is a carbapenem antibacterial agent with a broad spectrum of activity which encompasses Gram-negative, Gram-positive and anaerobic bacteria. Like other carbapenems, meropenem is stable against chromosomal and extended-spectrum β-lactamases. In patients with moderate to severe intra-abdominal infections, empirical mono therapy with meropenem achieved clinical response rates ranging from 91 to 100% in 7 randomised comparative trials. Efficacy rates were similar to those of imipenem/cilastatin (94 to 97%), clindamycin plus tobramycin (93%) and, overall, to cefotaxime plus metronidazole (75 to 100%), although there were differences between trials versus this combination regimen. According to limited data, meropenem also achieved clinical response rates of over 80% in patients with severe intra-abdominal infections. Meropenem is well tolerated, the most common adverse events being diarrhoea, rash, nausea/vomiting and inflammation at the injection site which are reported in 50 patients per study). In patients with intra-abdominal infections who failed therapy (4 to 16%), the most common persistent organisms following failure of meropenem therapy included Escherichia coli, other Enterobacteriaceae, enterococci, Streptococcus spp. and P. aeruginosa. Superinfections developed in similar numbers of patients receiving meropenem and comparator regimens. In the 2 cost analyses that compared delivery methods of meropenem, bolus administration was associated with delivery cost savings of approximately 30% in an Australian study and 45% in a UK study compared with an infusion of the drug. A recent overview of clinical trial data involving 9514 patients found that the overall incidence of adverse events, drug-related adverse events, adverse events leading to withdrawal and mortality were similar between meropenem, imipenem/cilastatin and combination regimens. Drug-related events most frequently associated with meropenem are diarrhoea (2.3%), rash (1.4%), nausea/vomiting (1.4%) and local inflammation at the injection site (1.1%). A concern with imipenem/cilastatin is that the incidence of gastrointestinal events is linked to the rate of administration and dosage of the drug, although these events can be managed by slowing the rate of infusion of the drug. Meropenem can, however, can be administered without regard to the rate of infusion or dose. A tolerability concern with β-lactam agents is their potential to cause CNS toxicity and seizures. With regard to the CNS, meropenem appears to be well tolerated, whereas imipenem/cilastatin is associated with a risk of seizures, particularly in those with predisposing factors such as renal dysfunction, underlying CNS pathology or advanced age. In an overview of 46 clinical trials, which excluded patients with meningitis and a history of CNS disorders, the incidence of meropenem-related seizures was 0.08% of treatment exposures compared with 0.28% with imipenem/cilastatin, 0.05% with cephalosporin-based regimens and 0% with clindamycin plus an aminoglycoside. Laboratory events most commonly associated with meropenem included thrombocytosis (1.6%) and increases in ALT (4.3%), AST (3.4%) and alkaline phosphatase (1.5%). Meropenem is indicated as monotherapy for the treatment of intra-abdominal infections. According to the manufacturer’s recommendations, meropenem should be administered at a dosage of 1.5 to 3 g/day in 3 divided doses depending on the type and severity of infection, the susceptibility of the pathogen(s) and the condition of the patient. This dosage range may, however, differ from that recommended on a national level. Meropenem can be administered as an intravenous bolus injection or infusion. Dosage adjustment is required in patients with renal impairment (CLCR ≤3 L/h) but not in the elderly (CLCR >3 L/h) or in patients with impaired hepatic function.

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