Doripenem

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An overview of the antibiotic doripenem


Doripenem
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Doripenem is a carbapenem antibiotic used in the treatment of severe bacterial infections. It is a member of the beta-lactam class of antibiotics, which work by inhibiting cell wall synthesis in bacteria, leading to cell death. Doripenem is particularly effective against a broad range of Gram-negative bacteria, including Pseudomonas aeruginosa.

Mechanism of Action

Doripenem exerts its antibacterial effects by binding to penicillin-binding proteins (PBPs) located inside the bacterial cell wall. This binding inhibits the final transpeptidation step of peptidoglycan synthesis, which is essential for bacterial cell wall integrity. The disruption of cell wall synthesis ultimately leads to bacterial cell lysis and death.

Clinical Uses

Doripenem is primarily used to treat complicated intra-abdominal infections and urinary tract infections, including pyelonephritis. It is also used in the treatment of nosocomial pneumonia, including ventilator-associated pneumonia. Due to its broad-spectrum activity, doripenem is often reserved for severe infections caused by multi-drug resistant organisms.

Pharmacokinetics

Doripenem is administered intravenously and has a half-life of approximately one hour. It is primarily excreted unchanged in the urine, making it suitable for treating urinary tract infections. The drug's pharmacokinetic profile allows for effective penetration into various body tissues, including the lungs and abdominal cavity.

Side Effects

Common side effects of doripenem include nausea, diarrhea, headache, and rash. Serious side effects may include allergic reactions, seizures, and Clostridium difficile infection. As with other beta-lactam antibiotics, caution is advised in patients with a history of penicillin allergy.

Resistance

Bacterial resistance to doripenem can occur through various mechanisms, including the production of beta-lactamase enzymes that degrade the antibiotic, alterations in PBPs, and changes in porin channels that reduce drug uptake. The emergence of carbapenem-resistant Enterobacteriaceae (CRE) is a significant concern in clinical settings.

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Contributors: Prab R. Tumpati, MD