anaerobic Gram-positive and Gram-negative organisms, including Staphylococcus aureus, Streptococcus pyogenes, S. agalactiae, S. viridans- group streptococci, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis and Peptostreptococcus species. Imipenem/cilastatin was approved for use in the United States in 1985. Imipenem/cilastatin is indicated for the treatment of severe or complicated skin, tissue, joint, respiratory tract, intra-abdominal, urinary tract and urogenital infections, but not meningitis (as it does not pass through the blood brain barrier), endocarditis, and sepsis due to susceptible organisms. Its use is generally restricted to severe infections largely in hospitalized patients. The recommended dosage is 250 mg to 1 gram given intravenously every 6 to 8 hours or in intramuscular doses of no more than 1.5 gm daily, usually for five to 14 days. It is commercially available as Primaxin as 250-mg or 500-mg infusion bottles for IV use or 500-mg or 750-mg vials of lyophilized powder for IM injection. The most common side effects of imipenem are diarrhea, nausea, vomiting, skin rash, pruritus, and injection-site reactions. Pharmacology Mechanism of action Imipenem inhibits bacterial cell-wall synthesis by binding to penicillin-binding proteins; cilastatin prevents renal metabolism of imipenem. Bioavailability Intramuscular injection: imipenem: 60–75% cilastatin: 95–100% Distribution The drug is distributed rapidly and widely to most tissues and fluids, including sputum, pleural fluid, peritoneal fluid, interstitial fluid, bile, aqueous humor, reproductive organs, and bone; highest concentrations occur in pleural fluid, interstitial fluid, peritoneal fluid, and reproductive organs; low concentrations occur in CSF; it crosses the placenta, and enters breast milk Protein binding imipenem: 13–21% cilastatin, 40% Metabolism Imipenem is metabolized in the kidney by dehydropeptidase 1; activity is blocked by cilastatin. Elimination Half-life (both drugs): 60 min; prolonged with renal impairment. Excretion (both drugs): Urine (~70% as unchanged drug) Availability and description Primaxin IV is a combination of imipenem, cilastatin sodium, and sodium bicarbonate which is added as a buffer. Primaxin IM lacks the sodium bicarbonate buffer. See also Imipenem/cilastatin/relebactam References External links Carbapenem antibiotics Combination antibiotics Peripherally selective drugs Merck & Co. brands World Health Organization essential medicines Wikipedia medicine articles ready to translate