Carbapenems

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 enzymes 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, complicated acute exacerbations of chronic bronchitis when sepsis is of concern. The incidence of adverse reactions is low (about 1%) and occurs predominantly among the elderly or patients with predisposing central nervous system conditions. Carbapenem antibiotics include imipenem (Merck's Primaxin), meropenem (AstraZeneca's Merrem), and ertapenem (Merck's Invanz). This section reviews only imipenem/cilastatin, as this class is generally used in only a small subset of patients with acute exacerbations of chronic bronchitis.

Because carbapenems are broad-spectrum agents, they are usually reserved for complicated infections or for patients who are severely ill. Using these drugs carefully, in consultation with an infectious disease specialist when possible, helps preserve their effectiveness and reduces the risk that bacteria will develop resistance.

Mechanism of Action

Like the penicillins, carbapenems bind to penicillin-binding proteins in bacteria and prevent bacterial cell wall formation. By interrupting cell wall formation, carbapenems induce cell lysis and death.

This mechanism places carbapenems in the broader β-lactam antibiotic family, which all target bacterial cell wall synthesis but may differ in spectrum of activity and resistance to β-lactamase enzymes.

Imipenem/cilastatin

Imipenem/cilastatin (Merck's Primaxin) is a prototypical carbapenem. Imipenem is coadministered with cilastatin (a peptidase inhibitor) to prevent its metabolism into nephrotoxic metabolic end products by peptidase enzymes in the body. Coadministration allows extended imipenem dosing intervals and results in less toxicity. Imipenem/cilastatin is usually reserved for severe acute exacerbations of chronic bronchitis in the intensive care setting for patients developing sepsis. In this setting, the agent is often administered with an aminoglycoside. This agent will retain its patent protection through 2009 in the United States, but lost its patent protection in Europe and Japan in 2005.

Acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious events that can lead to respiratory failure, longer hospital stays, and a higher risk of complications. For this reason, treatment decisions often involve careful assessment of the patient's overall condition, risk factors, and likely causative organisms.

Clinical trial evidence

An open-label trial compared imipenem/cilastatin with meropenem (both IV) in 173 hospitalized patients with severe acute exacerbations of chronic obstructive pulmonary disease. The clinical response at the end of treatment was favorable in both groups, with a cure or improvement achieved in 97.6% of the meropenem patients and in 96.3% of the imipenem/cilastatin patients. Nausea or vomiting was reported more frequently in patients treated with imipenem/cilastatin, whereas an increase in aminotransferases (indicative of liver damage) was reported in the meropenem group.

Overall, the trial suggests that both imipenem/cilastatin and meropenem are highly effective options for treating severe exacerbations in this population, with slightly different adverse effect profiles. Choice of agent may depend on individual patient factors, local resistance patterns, and clinician experience, and should always be guided by a healthcare professional familiar with the patient's overall clinical picture.