Carbapenems Flashcards
What is the mechanism of action of carbapenems?
Carbapenems (e.g., imipenem, meropenem, ertapenem, doripenem) are beta-lactam antibiotics that bind to PBPs and inhibit peptidoglycan cross-linking, similar to other beta-lactams. They are very resistant to most beta-lactamases and are bactericidal.
Describe the spectrum of activity of carbapenems.
Carbapenems have a very broad spectrum: they cover most Gram-positive organisms (including MSSA, Streptococcus, and Enterococcus faecalis), most Gram-negative rods (including Pseudomonas aeruginosa for all except ertapenem), and anaerobes. Notable exceptions: they do not cover MRSA, VRE, and some atypicals. Ertapenem has no appreciable activity against Pseudomonas or Acinetobacter (while imipenem/mero/dori do).
What mechanisms of resistance can reduce carbapenem efficacy?
Bacteria may produce carbapenemases (e.g., KPC, NDM-1 enzymes) that hydrolyze carbapenems. In Gram-negatives like Pseudomonas, loss of specific porin channels (like OprD in Pseudomonas for imipenem) can confer resistance by preventing drug entry. Efflux pumps can also contribute. Altered PBPs are less common but can occur in some organisms.
Outline key pharmacokinetic features of carbapenems.
Carbapenems are IV only (no oral form). They distribute well into tissues and body fluids; meropenem reaches the CSF (used in meningitis). Imipenem is inactivated by renal dehydropeptidase I in the kidney, so it’s co-administered with cilastatin (a dehydropeptidase inhibitor) to prevent degradation and kidney toxicity. Other carbapenems (mero, dori, erta) don’t need cilastatin. All are renally excreted and require dose adjustment in renal impairment.
What major drug interactions do carbapenems have?
Carbapenems (especially imipenem) can lower seizure threshold; coadministration with drugs that also lower seizure threshold (like ganciclovir, cyclosporine, or bupropion) increases risk of seizures. Valproic acid levels drop significantly with carbapenems (due to increased clearance), leading to loss of seizure control. Probenecid can increase carbapenem levels by decreasing tubular secretion. No major CYP interactions.
What are common clinical uses for carbapenems?
Carbapenems are typically reserved for severe or polymicrobial infections, or when resistant organisms are suspected. They are used for hospital-acquired infections like complicated intra-abdominal infections, severe UTIs or pyelonephritis, aspiration pneumonia, sepsis with unknown source, and infections due to ESBL-producing Gram-negatives. Meropenem is used in bacterial meningitis (in penicillin-resistant pneumococcal meningitis). Ertapenem, being once daily, is used for outpatient IV therapy of things like diabetic foot infections (but remember its narrower spectrum).
When should carbapenems be avoided or used with caution?
Use with caution in patients with a history of seizures or CNS lesions, especially imipenem, due to seizure risk. Dose adjust in renal impairment to avoid CNS toxicity. In patients with severe beta-lactam allergy (anaphylaxis to penicillins), avoid carbapenems due to possible cross-reactivity (though incidence is low). Imipenem is generally avoided in meningitis due to seizures – meropenem is preferred for CNS infections.
List major adverse effects of carbapenems.
The most notable side effect is neurotoxicity: imipenem can cause seizures at high levels or if not dose-adjusted in renal dysfunction. All carbapenems can cause GI upset (nausea, diarrhea), rash, or infusion site reactions. There is some cross-allergy with other beta-lactams (rash, rarely anaphylaxis). Prolonged use may lead to superinfections like C. difficile colitis or yeast infections due to broad spectrum.
Is there a mnemonic for imipenem’s co-administration?
“The kill is lastin’ with cilastatin.” – Imipenem is always given with cilastatin to block its renal degradation, ensuring it remains effective (and not nephrotoxic).
