Imipenem/cilastatin, sold under the brand name Primaxin among others, is an antibiotic useful for the treatment of a number of bacterial infections. It is made from a combination of imipenem and cilastatin. Specifically it is used for pneumonia, sepsis, endocarditis, joint infections, intra-abdominal infections, and urinary tract infections. It is given by injection into a vein or muscle.[1]
Common side effects include nausea, diarrhea, and pain at the site of injection.[1] Other side effects may include Clostridioides difficile diarrhea and allergic reactions including anaphylaxis.[1] It is unclear if use during pregnancy is safe for the baby.[2] Imipenem is in the carbapenem family of medications and works by interfering with the bacteria's cell wall.[1] Cilastatin blocks the activity of dehydropeptidase I which prevents the breakdown of imipenem.[1]
Imipenem/cilastatin was first sold in 1987.[3] It is on the World Health Organization's List of Essential Medicines.[4]
Medical uses
Imipenem/cilastatin is used for lower respiratory tract infections, urinary tract infections, intra-abdominal infections, gynecologic infections, bacterial sepsis, bone and joint infections, skin and skin structure infections, endocarditis and polymicrobic infections.
It is a broad-spectrum beta-lactam containing equal quantities of imipenem and cilastatin.
Side effects
Common side effects for both forms are:
Major side effects requiring medical attention:
This medicine is passed through breast milk, so its use during pregnancy or breastfeeding should only be done when clearly needed. Primaxin is cleared from the body by the kidneys, so it is important to tell one's doctor about any other drugs being taken that are also cleared through the kidneys (such as other antibiotics), especially for older patients, as kidney function declines with age.
Patients who are allergic to penicillin, cephalosporins, and related drugs may react to imipenem.[5] It is important tell one's doctor or pharmacist one's medical history, especially of brain disorders (e.g., seizures, head injury, tumor), kidney disease, liver disease, and stomach/intestinal diseases (e.g., colitis).[6]
- Upset stomach
- Vomiting
- Stomach pain
Interactions
- valproic acid (Depakene, Stavzor)
- ganciclovir (Cytovene)
- probenecid (Benemid)
- penicillin antibiotics such as amoxicillin (Amoxil, Augmentin), ampicillin (Omnipen, Principen), dicloxacillin (Dycill, Dynapen), oxacillin (Bactocill), or phenoxymethylpenicillin (Beepen-VK, Ledercillin VK, Pen-V, Pen-Vee K, Pfizerpen, V-Cillin K, Veetids, and others); or
- cephalosporin antibiotics such as cefaclor (Ceclor), cefuroxime (Ceftin), cefadroxil (Duricef), cephalexin (Keflex), and others.[7]
Mechanism of action
Imipenem/cilastatin has the ability to kill a wide variety of bacteria. Imipenem is the active antibiotic agent and works by interfering with their ability to form cell walls, so the bacteria break up and die.
Imipenem is rapidly degraded by the renal enzyme dehydropeptidase if administered alone (making it less effective); the metabolites can cause kidney damage.[8] 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,
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
Availability and description
Primaxin IV is a combination of imipenem, cilastatin sodium, and sodium bicarbonate which is added as a buffer.[6] Primaxin IM lacks the sodium bicarbonate buffer.[9]
See also
External links
References
- Imipenem and Cilastatin The American Society of Health-System Pharmacists, retrieved 8 December 2016^
- Cilastatin / imipenem Use During Pregnancy www.drugs.com, retrieved 10 December 2016^
- Oxford Handbook of Infectious Diseases and Microbiology OUP Oxford, 2009