Pharmacology: Pharmacodynamics: Effects on the Nervous System: Animal studies have indicated that meropenem induces fewer seizures than imipenem-cilastatin and clinical data from the manufacturer have substantiated this. Comparison of data from 4872 patients with a variety of infections (including meningitis) treated with meropenem with that from 4752 patients who received other antibacterials, principally cephalosporin-based regimens or imipenem-cilastatin, showed that meropenem was not associated with any greater risk of seizures than the other antibacterials and was likely to have less neurotoxic potential than imipenem-cilastatin, making it a suitable drug to use in the treatment of meningitis.
Pharmacokinetics: Following intravenous injection of meropenem 0.5 and 1 g over 5 minutes, peak plasma concentrations of about 50 and 112 micrograms/mL respectively are attained. The same doses infused over 30 minutes produce peak plasma concentrations of 23 and 49 micrograms/mL, respectively.
Meropenem has a plasma elimination half-life of about 1 hour; this may be prolonged in patients with renal impairment and is also slightly prolonged in children. Meropenem is widely distributed into body tissues and fluids including the CSF and bile. It is approximately 2% bound to plasma proteins. It is more stable to renal dehydropeptidase I than imipenem and is mainly excreted in the urine by tubular secretion and glomerular filtration. About 70% of a dose is recovered unchanged in the urine over a 12-hour period and urinary concentrations above 10 micrograms/mL are maintained for up to 5 hours after a 500-mg dose. Meropenem is reported to have one metabolite (ICI-213689), which is inactive and is excreted in the urine. Meropenem is removed by haemodialysis.
Microbiology: Antimicrobial Actions: Meropenem is slightly more active than imipenem against Enterobacteriaceae and slightly less active against Gram-positive organisms. Like Imipenem, it is bactericidal and acts similarly to the penicillins by inhibiting synthesis of the bacterial cell wall. It has a very broad spectrum of activity in vitro, including activity against Gram-positive and Gram-negative aerobic and anaerobic organisms, and is stable to hydrolysis by beta-lactamases produced by most bacterial species. Cilastatin, the enzyme inhibitor given in association with imipenem, appears to have no antibacterial activity.
Most Gram-positive cocci are sensitive including most streptococci, and both penicillinase- and non-penicillinase-producing staphylococci, although its activity against methicillin-resistant Staphylococcus aureus is variable. Imipenem has good to moderate activity against Enterococcus faecalis, but most E. faecium are resistant. Nocardia, Rhodococcus, and Listeria spp. are also sensitive.
Among Gram-negative bacteria, imipenem is active against many of the Enterobacteriaceae including Citrobacter and Enterobacter spp., Escherichia coli, Klebsiella, Proteus, Providencia, Salmonella, Serratia, Shigella, and Yersinia spp. Its activity against Pseudomonas aeruginosa is similar to that of ceftazidime. Imipenem is also active against Acinetobacter spp. and Campylobacter jejuni, and also against Haemophilus influenzae and Neisseria spp., including beta-lactamase-producing strains.