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Carbapenems – Penicillin Derivative

Overview

Carbapenems are penicillin derivatives that have good activity against gram-positive and gram-negative aerobic and anaerobic bacteria. They are highly resistant to β-lactamase and have a very favorable spectrum of activity. A drawback of these agents is that they are available in IV form only. These agents are used in the treatment of severe community-acquired pneumonia when sepsis is a concern. The incidence of this adverse reaction is low (1%) and occurs predominantly in the elderly or in patients with predisposing CNS conditions. Carbapenem antibiotics include imipenem (Merck's Primaxin), meropenem (AstraZeneca's Merrem), and ertapenem (Merck's Invanz). This section reviews only imipenem/cilastatin because this class is generally used only in a small subset of community-acquired pneumonia patients.

Carbapenems - Penicillin Derivative

Mechanism Of Action

Carbapenems, like the penicillins, bind to PBPs in bacteria and prevent bacterial cell-wall formation. By interrupting cell-wall formation, carbapenems induce cell lysis and death.

Imipenem/Cilastatin

Merck's imipenem/cilastatin (Primaxin) is a prototypical carbapenem. Imipenem is coadministered with cilastatin (a peptidase inhibitor) to prevent its metabolism into nephrotoxic products by peptidase enzymes in the body. Coadministration allows extended imipenem dosage intervals and causes less toxicity. Imipenem/cilastatin is usually reserved for severe community-acquired pneumonia in the intensive care setting for patients who develop sepsis. In this setting, the agent is often administered with an aminoglycoside. This agent is expected to retain patent protection through 2009 in the United States.

Carbapenems - Penicillin Derivative

A randomized trial compared imipenem/cilastatin with the third-generation cephalosporin ceftazidime (both IV) in 60 hospitalized patients with moderate to severe community-acquired pneumonia. The response rate in both arms was 70%, recorded as improvement in sputum, purulence, cough, and dyspnea scores.

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