A Brief Review of Carbapenems

Carbapenems are often considered to have the broadest spectrum of activity among all antibiotic classes.

Carbapenems are often considered to have the broadest spectrum of activity among all antibiotic classes.

Closely related to penicillins, carbapenems are bactericidal beta-lactam antibiotics that bind to penicillin-binding proteins (PBPs). By binding and inactivating these proteins, carbapenems inhibit the synthesis of the bacterial cell wall, which leads to cell death.1,2

Each carbapenem has its own affinity to specific subtypes of PBPs. Some bacteria demonstrate intrinsic resistance to the carbapenems. 1,2

For example, methicillin-resistant Staphylococcus aureus (MRSA) has resistance via PBP2a, while Enterococcus faecium has resistance via PBP5. Resistance can also occur through the loss of porin activity (eg, OprD), which is common to Pseudomonas aeruginosa.1,2

Gram-Positive Coverage1,2

Generally, carbapenems work against various Gram-positive bacteria. They exhibit low minimum inhibitory concentrations on organisms like methicillin-susceptible S. aureus, S. pyogenes, and S. pneumoniae. They have poor coverage of MRSA and enterococcal infections because of their aforementioned intrinsic resistance.

Gram-Negative Coverage1,2

Carbapenems also have good activity against most Gram-negative bacteria, including Enterobacter, E. coli, Morganella morganii, and Klebsiella. For the very resistant P. aeruginosa, doripenem and meropenem are highly potent because they require multiple drug resistance pathways. Imipenem is slightly less potent for P. aeruginosa, and ertapenem should not be used for P. aeruginosa because of poor activity.

Anaerobic Coverage1,2

All carbapenems have fairly good coverage against anaerobes. Although they can be used for intra-abdominal infections, they are not always first-line therapy for this indication.

Atypical Coverage1,2

Carbapenems do not cover atypical bacteria because these bacteria lack a cell wall that carbapenems attack.

Clinical Pearls1,2

  • Imipenem has the highest risk for seizure across the carbapenems.
  • Imipenem is broken down in the kidneys to a toxic metabolite by the DHP-1 enzyme. Cilastatin is used to sustain the body’s levels of imipenem and prevent nephrotoxicity.
  • Meropenem is the only carbapenem approved for meningitis, for which it can be used as alternative therapy.
  • Monitoring the renal function is vital because carbapenems should be dose adjusted.
  • A 2014 study looked at cross-reaction between carbapenems and penicillins by use of immunoglobulin E skin testing. Imipenem and meropenem were tested against the penicillins (mainly amoxicillin) and cross-reactivity was found to be 1%, which is significantly lower than what previous reports found.3

Common Doses For Non-Complicated Cases1,2

Doripenem (Doribax): 500 mg IV every 8 hours

Ertapenem (Invanz): 1 g IV every 24 hours

Imipenem/cilastatin (Primaxin): 250 mg to 500 mg IV every 6 to 8 hours

Meropenem (Merrem): 1 g IV every 8 hours

References

1. Zhanel GG, Wiebe R, Dilay L, et al. Comparative Review of the Carbapenems. Drugs. 2007;67(7): 1027-1052.

2. Comparison of Carbapenem Antibiotics. Pharmacist’s Letter / Prescriber’s Letter. 2007;(23): 1-4.

3. Gaeta F, Valluzzi RL, Alonzi C, et al. Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins. J Allergy Clin Immunol. 2014;135(4): 972-976.