Imipenem

Imipenem is a broad-spectrum beta-lactam antibiotic belonging to the carbapenem class. It is used in the treatment of severe bacterial infections, particularly those resistant to other antibiotics. Due to its rapid inactivation by renal dehydropeptidase I, imipenem is always administered in combination with cilastatin, a dehydropeptidase inhibitor, which prevents its degradation in the kidneys, increasing its bioavailability and reducing the risk of nephrotoxicity.

Mechanism of Action:

Imipenem inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), essential enzymes for peptidoglycan synthesis. This binding disrupts the formation of the bacterial cell wall, leading to cell lysis and death. Its broad spectrum of activity stems from its ability to bind to a wide range of PBPs in various bacterial species.

Spectrum of Activity:

Imipenem possesses activity against a wide range of Gram-positive and Gram-negative bacteria, including:

• Aerobic and anaerobic Gram-positive bacteria (e.g., Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis)
• Aerobic and anaerobic Gram-negative bacteria (e.g., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis)

It is often reserved for infections caused by multidrug-resistant organisms.

Administration and Dosage:

Imipenem is administered intravenously. Dosage is determined based on the severity of the infection, the patient's renal function, and the susceptibility of the infecting organism.

Adverse Effects:

Common side effects of imipenem include nausea, vomiting, diarrhea, and injection site reactions. More serious adverse effects can include seizures (especially in patients with pre-existing central nervous system disorders), allergic reactions (including anaphylaxis), and Clostridioides difficile-associated diarrhea.

Drug Interactions:

Imipenem can interact with other medications. Particular caution is advised when co-administering with medications known to lower the seizure threshold, such as ganciclovir and valproic acid.

Resistance:

Bacterial resistance to imipenem can develop through various mechanisms, including the production of carbapenemases (enzymes that hydrolyze carbapenems), mutations in PBPs, and alterations in outer membrane permeability. The emergence of carbapenem-resistant organisms is a significant concern in healthcare settings.