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What is Imipenem/cilastatin and explain in detail?
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.Common side effects include nausea, diarrhea, and pain at the site of injection. Other side effects may include Clostridium difficile diarrhea and allergic reactions including anaphylaxis. It is unclear if use during pregnancy is safe for the baby. Imipenem is in the carbapenem family of medications and works by interfering with the bacterias cell wall. Cilastatin blocks the activity of dehydropeptidase I which prevents the breakdown of imipenem.Imipenem/cilastatin was first sold in 1987. It is on the World Health Organizations List of Essential Medicines.

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:
Upset stomach
Vomiting
Stomach painMajor side effects requiring medical attention:
Diarrhea
Rash
Fever
Facial swelling
Difficulty breathing
Unusual bleeding
SeizuresThis 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 ones 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.
It is important tell ones doctor or pharmacist ones medical history, especially of brain disorders (e.g., seizures, head injury, tumor), kidney disease, liver disease, and stomach/intestinal diseases (e.g., colitis).

Hepatotoxicity
In large clinical trials, imipenem was associated with transient and asymptomatic elevations in serum aminotransferase levels in about 6% of patients given the drug for five to 14 days. More serious hepatic injury from imipenem/cilastatin is rare, but jaundice and liver test abnormalities have been reported in 0.1% of patients in prospective trials of the agent. Several instances of cholestatic jaundice arising during or shortly after therapy have been reported with imipenem-cilastatin and other carbapenems. The latency to onset has been within one to three weeks, and the pattern of enzyme elevations is usually cholestatic. Immunoallergic features can occur, but autoantibodies are rare. The course is usually self-limiting, but at least one case of vanishing bile duct syndrome related to the carbapenems has been reported. Imipenem and other carbapenems have not been linked to cases of acute liver failure.

Mechanism of liver injury
The cause of the mild, transient serum enzyme elevations during imipenem-cilastatin therapy is not known. The cholestatic hepatitis attributed to imipenem-cilastatin and the carbapenems is probably immunoallergic and resembles the rare, clinically apparent liver injury that has been linked to penicillins and cephalosporins.

Outcome and management
The liver injury due to the carbapenems is usually mild and self-limited. Rarely, the carbapenems can cause a clinically apparent acute cholestatic hepatitis that is usually self-limiting and not requiring therapy or intervention. In patients with vanishing bile duct syndrome, corticosteroids are often used but have not been shown to be beneficial and are best avoided. Some patients may benefit from symptomatic therapy of the pruritus associated with cholestasis using antihistamines, ursodiol, or cholestyramine. Little information is available on possible cross-sensitivity to liver injury among the different betalactam antibiotics, but patients with clinically apparent liver injury due to imipenem should probably avoid the other carbapenems.

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 penicillin (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.

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.
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