Meropenem

Antibiotic Class:

Carbapenem

Antimicrobial Activity:

Aerobic gram-positive microorganisms:  S. aureus including penicillinase-producing strains, Group D streptococcus including Enterococcus spp., Streptococcus pneumoniae, S. pyogenes, S. viridans group

Aerobic gram-negative microorganisms:  Acinetobacter spp., Citrobacter spp., Enterobacter cloacae, E. coli, H. influenzae, K. pneumoniae, P. aeruginosa

Anaerobic gram-positive microorganisms:  Peptostreptococcus spp.

Anaerobic gram-negative microorganisms:  Bacteroides spp., Fusobacterium spp.

Mechanism of Action:

Cause rapid bacterial cell death by covalently binding to penicillin-binding proteins (PBPs) involved in the biosynthesis of mucopeptides in bacterial cell walls.  Bactericidal effects result through inhibition of cellular growth and division and the loss of cell wall integrity, eventually causing cell wall lysis.  The primary target is PBP 2.

Pharmacodynamics:

Carbapenems produce time-dependent killing.

Pharmacokinetics:

Cmax: 61.6mcg/ml; Half-life: 0.98 hours; Volume of distribution: 12.5L; Table 2

Adverse Effects:

Hematologic:  Bleeding, gastrointestinal hemorrhage, bone marrow aplasia (leucopenia, neutropenia, thrombocytopenia, anemia)

Cardiovascular System:  Phlebitis or thrombophlebitis

Central Nervous System:  Headache, insomnia, agitation, confusion, dizziness, nervousness, paresthesia, hallucinations; Seizures

Gastrointestinal:  Nausea, abdominal pain, vomiting, diarrhea, constipation

Renal:  Dysuria, kidney failure

Hepatic:  Abnormalities of liver function tests

Dermatologic:  Rash, pruritus

Dosage:

20 mL (500mg meropenem) injection vial for intravenous administration

30 mL (1g meropenem) injection vial for intravenous administration

100 mL (500mg meropenem) vial:  powder for reconsitution for intravenous administration

100 mL (1g meropenem) vial:  powder for reconsitution for intravenous administration

Intra-abdominal infections: 1 g IV every 8 hrs

Meningitis, bacterial: 2 g IV every 8 hrs

Disease state based dosing:

Renal failures: Table 4

Hepatic failures: Dosage adjustment is not required.

Dosing during Continuous Renal Replacement Therapy

CVVH (Continuous venovenous hemofiltration): 1g IV q12h

CVVHD (Continuous venovenous hemodialysis): 1g IV q12h

CVVHDF (Continuous venovenous hemodiafiltration) 1g IV q12h

Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.

Contraindications/Warnings/Precautions:

Precautions:  Anaphylactic reactions to beta-lactam antibiotics, renal impairment, patients with epilepsy, history of seizures or other neurological disorders, Liver dysfunction (possible hepatotoxic effects)

Drug Interactions:

Live Typhoid Vaccine (moderate severity):  A decreased immunological response to the vaccine

Pregnancy:

Category B: No evidence of risk in humans but studies inadequate.

Monitoring Requirements:

Therapeutic:Resolution of clinical signs of infection (fever, decreased white blood cell count), Culture and sensitivity, CBC w/differential, urinalysis, temperature

Toxicity: Hepatic and renal function tests during therapy

Brand names/Manufacturer:

         Merrem/Astra Zeneca in the following countries: United States, Italy, Australia, Canada, Mexico, New Zealand

         Merrem/Astra Zeneca in the following countries: United Kingdom, Ireland, Sweden, South Africa, Belgium, Switzerland, Spain, Germany, Netherlands, Denmark, Portugal, Hong Kong, Israel, Norway, Thailand, Singapore, Finland, Brazil, Malaysia, Greece, Chile, Hungary, and the Czech Republic

         Optinem/Astra Zenica in Austria

         Meropen/Sumitomo in Japan