From the FDA Drug Label
Imipenem and Cilastatin for Injection (I.V.) is a combination of imipenem and cilastatin. Imipenem is a penem antibacterial drug [see Microbiology ( 12.4)] . Cilastatin is a renal dehydropeptidase inhibitor that limits the renal metabolism of imipenem.
Imipenem, when administered alone, is metabolized in the kidneys by dehydropeptidase I, resulting in relatively low levels in urine. Cilastatin, an inhibitor of this enzyme, effectively prevents renal metabolism of imipenem so that when imipenem and cilastatin sodium are given concomitantly, adequate antibacterial levels of imipenem are achieved in the urine
The mechanism of action of imipenem and cilastatin is as follows:
- Imipenem is a penem antibacterial drug that works by inhibiting bacterial cell wall synthesis.
- Cilastatin is a renal dehydropeptidase inhibitor that prevents the renal metabolism of imipenem, allowing adequate antibacterial levels of imipenem to be achieved in the urine. The combination of imipenem and cilastatin allows for effective antibacterial activity against a wide range of bacteria 1.
From the Research
Imipenem-cilastatin is a combination antibiotic medication that works through two distinct mechanisms, with imipenem killing bacteria by binding to penicillin-binding proteins and cilastatin inhibiting the enzyme dehydropeptidase-1 in the kidneys to prevent imipenem breakdown. The mechanism of action of imipenem involves binding to penicillin-binding proteins in bacterial cell walls, disrupting cell wall synthesis and causing bacterial cell death, as noted in studies such as 2. It has a broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria. Cilastatin, on the other hand, is not an antibiotic but serves as a protective agent for imipenem, inhibiting the enzyme dehydropeptidase-1 in the kidneys, which would otherwise rapidly break down imipenem, reducing its effectiveness and potentially causing kidney toxicity, as explained in 3. Some key points about imipenem-cilastatin include:
- Imipenem has the widest spectrum of antimicrobial activity of currently available beta-lactam agents, as mentioned in 4
- Cilastatin increases the urinary recovery of active imipenem to about 70% of the dose when a combination of imipenem and cilastatin in a 1:1 ratio is used, as noted in 3
- The combination is particularly valuable for treating serious infections including intra-abdominal infections, pneumonia, sepsis, and complicated urinary tract infections, especially when caused by multidrug-resistant organisms, as discussed in 5 and 6
- The standard adult dosage typically ranges from 500 mg to 1 gram administered intravenously every 6-8 hours, adjusted based on infection severity and renal function. Recent studies, such as 6, have led to the development of new combinations, including imipenem/cilastatin sodium/relebactam, which has been approved for the treatment of complicated urinary tract infection and complicated intra-abdominal infection due to drug-resistant bacterial pathogens.