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Meropenem: Mechanism of Action, Adverse Effects and Dosage

Meropenem is a broad-spectrum beta-lactam antibiotic from the carbapenem group and is effective against a broad spectrum of both gram-positive and gram-negative bacteria.

Mechanism of Action:

Meropenem inhibits the peptidoglycan synthesis of the bacterial wall: it binds to so-called penicillin-binding proteins (peptidoglycan synthetases) and inhibits the polymerization of the peptidoglycan and covalent cross-linking of the bacterial wall. Meropenem is very stable against beta-lactamases, including ESBL.

Antibiotic Spectrum of Meropenem:

A broad spectrum of activity against both gram-positive and gram-negative bacteria, including Pseudomonas, enterococci, and anaerobes. Compared to imipenem, it has a broader antibiotic spectrumin against gram-negative bacteria, but is somewhat weaker in against gram-positive bacteria (such as enterococci).

Urological Indications for Meropenem:

Reserve antibiotic for severe complicated urinary tract infections (pyelonephritis, catheter-associated infections, prostatitis, epididymitis) and urosepsis, after the failure of other broad-spectrum antibiotics or for treatment of multi-resistant bacteria.

Pharmacokinetics of Meropenem:

• Only intravenous administration is possible.
• Half-life 1 hour, minimal hepatic metabolism, unchanged renal excretion in 70%.

Adverse Effects of Meropenem

Meropenem is better tolerated than imipenem.

• Frequent diarrhea, vomiting, and nausea. Rare pseudomembranous colitis.
• Allergic reactions occur in 1–3%, with a low risk of cross-allergy to penicillin or cephalosporins.
• CNS: Tremor, myoclonus, epilepsy, confusion, dizziness. Meronem causes fewer neurotoxic side effects than imipenem.
• Positive direct Coombs test, very rare hemolytic anemia or leukopenia.
• Drop in blood pressure with rapid intravenous administration.
• Hepatotoxicity is possible.

Drug Interactions:

Meropenem lowers the valproic acid level. An increase in INR is possible when given together with warfarin.

Contraindications:

Allergy to carbapenems, history of seizures, or CNS disorders. Use with caution in cases of allergy to penicillin or cephalosporins or during pregnancy.

Dosage of Meropenem

• 500–1000 mg meronem 1-1-1 (every 8 hours) for adults, depending on the severity of the infection.
• Children receive 10–20 mg/kg body weight every 8 hours.
• A dose reduction is necessary in cases of renal insufficiency: the maximum dose of meronem is 1000 mg every 12 hours for a GFR of 50–25 ml/min, 500 mg every 12 hours for a GFR of 25–10 ml/min, and 500 mg every 24 hours for a GFR below 10 ml/min.

References

H. R. Brodt, A. Hörauf, M. Kresken, W. Solbach, and T. Welte, Infektionstherapie: Antibiotika, Virostatika, Antimykotika, Antiparasitäre Wirkstoffe. Thieme, 2023.

  Deutsche Version: Pharmakologie und Nebenwirkungen von Meropenem

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