Imipenem is a broad-spectrum betalactam antibiotic used for severe bacterial infections caused by susceptible organisms. Because imipenem is rapidly inactivated by renal dehydropeptidase I, it is given in combination with cilastatin, a DHP-I inhibitor which increases half-life and tissue penetration of imipenem. Imipenem/cilastatin, like other carbapenems, binds to bacterial penicillin-binding proteins and interferes with bacterial cell wall integrity and synthesis. It has activity against many aerobic and 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
"Cilastatin mixture with Imipenem". Drug Information Portal. U.S. National Library of Medicine.