Imipenem

The first carbapenem, imipenem-cilastatin (Primaxin), is a chemically stable analogue of thienamycin produced by Streptomyces cattleya. The antibacterial spectrum of imipenem is among the broadest of all of the p-lactam antibiotics. Imipenem is active against most gram-positive, gram-negative, and anaerobic bacteria. When compared with the in vitro activities of third-generation cephalosporins, imipenem is more potent against E. faecalis, B. fragilis, and P. aeruginosa. Imipenem's stability against p-lactamases is attributable to the trans position of the 6-hydroxyethyl side chain on the p-lactam ring. Organisms resistant to imipenem include E. faecium, Stenotrophomonas mal-tophilia, and MRSA.

Imipenem-cilastatin is only available for intramuscular or intravenous administration because oral bioavailability is poor. The enzyme, dehydropeptidase I, present in renal tubules, converts imipenem to an inactive metabolite. To decrease metabolic clearance, imipenem is combined with cilastatin, an inhibitor of dehydropeptidase I. Additional pharmacokinetic information appears in Table 45.2.

Imipenem-cilastatin is one of the drugs of first choice for the empirical therapy of many polymicrobial pulmonary, intraabdominal, and soft tissue infections. The notable adverse effect of imipenem-cilastatin is seizures affecting 1% of patients. Risk factors for seizures are old age, head trauma, previous seizure disorder, cerebrovascular accident, and renal failure. Among patients with a history of penicillin allergy, 10% are cross-sensitive to imipenem-cilastatin.

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