Carbapenems

Agents: imipenem/cilastatin, meropenem, ertapenem, doripenem

Carbapenems are among our most broad-spectrum antibacterial drugs, particularly imipenem, doripenem, and meropenem. They possess a beta-lactam ring and share the same mechanism of action of beta-lactams, but they are structurally unique and differ from both penicillins and cephalosporins.  Their broad spectrum makes them both appealing and unappealing for empiric therapy, depending on the infection being treated and the risk factors of the patient for a resistant organism. Imipenem, doripenem, and meropenem have similar spectra of activity; ertapenem has important deficiencies in its spectrum that must be learned.

Spectrum

Good: MSSA, streptococci, anaerobes, enteric GNRs,  Pseudomonas  (not ertapenem),  Acinetobacter  (not ertapenem), ESBL-producing GNRs

Moderate: enterococci (not ertapenem)

Poor : MRSA, penicillin-resistant streptococci

Adverse Effects

Similar to those of other beta-lactams, but with a higher propensity to induce seizures. This is particularly problematic with imipenem. Minimize the risk by calculating appropriate doses for patients with renal dysfunction and avoiding imipenem use in patients with meningitis, because it can cross the blood-brain barrier more readily.

Important Facts

• Imipenem is metabolized in the kidney to a nephrotoxic product. Cilastatin blocks the renal dehydropeptidase that catalyzes this reaction and prevents this metabolism from occurring. It is always co-administered with imipenem for this reason.

• Carbapenems are very broad-spectrum agents.  Imipenem, doripenem, and meropenem are particularly broad and should not be used empirically for most community-acquired infections. They are good choices for many types of nosocomial infections, particularly in patients who have received many other classes of antibiotics during their hospital stay.

• Although ertapenem has weaker activity than the other carbapenems for a few organisms, this activity is significant enough to change the utility of the drug. Ertapenem is a poor choice for many nosocomial infections, particularly nosocomial pneumonia in which both Pseudomonas and  Acinetobacter are important pathogens.  However, it is administered only once a day and thus more convenient than the other carbapenems, so it may be a better choice for home infusion therapy for susceptible infections.

• Carbapenems may elicit an allergic reaction in patients with a history of penicillin allergy. One study showed the incidence of such reactions to be as high as 50% with a proven penicillin allergy (keep in mind that many penicillin allergies are unproven), but more recent and better-performed studies have shown this num-ber to be much lower (close to 1%). Nevertheless, take the possibility of cross-reactivity seriously.  Keep in mind that even if the cross-reactivity is very low between these agents, patients with a history of allergy to any drug are more likely to react to another one.

What They’re Good For

All: mixed aerobic/anaerobic infections, infections caused by ESBL-producing organisms, intraabdominal infections Imipenem, doripenem, meropenem: nosocomial pneumonia, febrile neutropenia, other nosocomial infections

Don’t Forget!

Check your dosing in patients with renal dysfunction to minimize the risk of carbapenem-induced seizures.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.