CARBAPENEMS


I. Pharmacology

  1. Belong to the beta-lactam family
    1. Cross-allergenicity with other beta-lactams as high as 50% in skin-test studies; contraindicated in pts with h/o anaphylaxis with a penicillin or cephalosporin
  1. Antimicrobial spectra
    1. Active against most pathogenic gm- and gm+ aerobies and anaerobes, including enterococcus and pseudomonas
    2. Not active against MRSA, enterococcus faecium, or stenotrophomonas maltophila
    3. Only bacteriostatic against enterococcus; many use in combination w/an aminoglycoside for gm- or enterococcal infections
    4. Imipenem is more active against gm+ aerobes and meropenem against gm- aerobes, but the clinical significance of this is unknown
      1. Studies comparing the two haven't shown any clinical differences except one study which suggested better clinical efficacy of meropenem in GYN infections (mentioned w/o citation in UW Pharm Letter)
  1. Excreted unchanged in urine through both glomerular filtration & tubular secretion
    1. Dose adjustement is necessary in renal failure
  1. Must adjust dosing in pts with renal insufficiency or if < 70kg
  2. Distribute through most tissues including CSF
  3. Adverse f/x
    1. Imipenem may cause nausea during infusion, esp. if rapid
    2. Seizures (incidence about 0.5%)
      1. Risk may be less with meropenem than imipenem (based on animal studies)
      2. Risk factors for carbapenem-induced sz include renal insufficiency, excessive dosage, h/o sz, presence of CNS lesions, and infections with Pseudomonas
      3. "Evidence of an absence of drug-associated neurotoxicity in meningitic patients exists to a greater extent for meropenem than imipenem" (UW Pharm Letter 1/99)
  1. Clinical use
    1. Most appropriate for use in nosocomial infections w/multiply resistant pathogens or as an alternative to multi-drug regimens for polymicrobial infections
    2. Rarely appropriate for community-acquired infections
    3. Should not be used for monotherapy of serious pseudomonal infections (combination with an Aminoglycoside is preferable)

II. Imepenem/cilastatin (Primaxin)

  1. Cilastatin inhibits dehydropeptidase, an enzyme in prox. renal tubule which otherwise de-activates imipenem
  2. Dose: 250mg Q6h or 500mg Q6-8h, or 1g Q6-8h depending on severity of infection and degree of microbial susceptibility

III. Meropenem (Merrem)

  1. Dose: 1g Q8h (2g Q8h has been used for meningitis), less if renal impairment is present
  2. Has the advantage of being capable of being administered in less volume than imipenem, for pts requiring fluid restriction

IV. Ertapenem (Invanz) 1g IV Q24h--Narrower antimicrobial spectrum c/w other carbapenems--little-to-no activity against Psuedomonas or Acinetobacter; less gram-positive activity than Imipenem; no activity against MRSA or atypicals

(Source: UW Pharm Letter 12/98 & 1/99; others)