Carbapenems
GENERAL PRINCIPLES
Imipenem-cilastatin (500 mg-1 g IV/IM q6-8h), meropenem (1-2 g IV q8h or 500 mg IV q6h), and ertapenem (1 g IV q24h) are the currently available carbapenems in the United States.
Carbapenems exert their bactericidal effect by interfering with cell wall synthesis, similar to PCNs and cephalosporins, and are active against many gram-positive and most gram-negative bacteria, including anaerobes. They are among the antibiotics of choice for infections caused by organisms producing AmpC or ESBLs. Imipenem-cilastatin is the most active carbapenem against ampicillin-susceptible E. faecalis and can also be used for treating Nocardia and some atypical mycobacterial infections.TREATMENT
• Carbapenems are important agents for treatment of many antibiotic-resistant bacterial infections at most body sites. These agents are commonly used for severe polymicrobial infections, including Fournier gangrene, intra-abdominal catastrophes, and sepsis in immunocompromised hosts.
• Notable bacteria that are resistant to carbapenems include ampicillin-resistant enterococci, MRSA, Stenotrophomonas, and KPC- and MBL-producing gram-negative organisms. In addition, ertapenem does not provide reliable coverage against P. aeruginosa, Acinetobacter, or enterococci; therefore, imipenem or meropenem would be preferred for empiric treatment of nosocomial infections when these pathogens are suspected. Meropenem is the preferred carbapenem for treatment of CNS infections.
• Meropenem-Vaborbactam (4 g IV q8h) contains meropenem plus the novel boron-based β-lactamase inhibitor vaborbactam. This agent is FDA-approved for treatment of cUTIs. Meropenem-vaborbactam has unique activity against KPC-producing Enterobacterales, but not against MBL-producing strains. Notably, vaborbactam does not appreciably enhance the activity of meropenem against Pseudomonas or Acinetobacter species.
Because of the meropenem component, this agent is reliably active against MSSA and anaerobes. Of note, the standard recommended dose of meropenem-vaborbactam contains 2 g of meropenem, a dose previously reserved for CNS infections.• Imipe nem-cilastatin-re Iebactam (1.25 g IV q6h) combines the activity of imipenem-cilastatin with relebactam, a novel β-lactamase inhibitor similar to avibactam. Notably, each 1.25 g contains 500 mg of imipenem, 500 mg of cilastatin, and 250 mg of relebactam. This agent is FDA-approved for cUTIs, including pyelonephritis, complicated intra-abdominal infections, and HABP/VABP. Compared to imipenem-cilastatin alone, imipenem-cilastatin-relebactam does offer additional activity against Pseudomonas and KPC-producing CRE.
SPECIAL CONSIDERATIONS
• Adverse events: Carbapenems can precipitate seizure activity, especially in older patients, individuals with renal insufficiency, and patients with preexisting seizure disorders or other CNS pathology, and should be avoided in these patients unless there is no alternative therapy. Like cephalosporins, carbapenems have been rarely associated with anaphylaxis, interstitial nephritis, elevated LFTs, anemia, and leukopenia.
• Patients who are allergic to PCNs/cephalosporins may have a cross-hypersensitivity reaction to carbapenems, and these agents should be avoided in patients with severe PCN allergy without prior skin testing, desensitization, or both. Prolonged therapy (>2 wk) is typically monitored with a weekly serum creatinine, LFTs, and CBC.
• Carbapenems also possess a unique drug interaction with valproic acid and derivatives, resulting in reduced concentrations of these anti-epileptic medications. This, together with the aforementioned CNS toxicity, can precipitate seizures in individuals with epilepsy on valproic acid derivatives. Concomitant use should be considered a contraindication.