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Imipenem: Mechanism of Action, Side Effects and Dosage

Imipenem 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:

Imipenem inhibits the synthesis of the bacterial wall's peptidoglycan by binding to so-called penicillin-binding proteins (peptidoglycan synthetases), thereby preventing the polymerization of peptidoglycan and the covalent cross-linking of the bacterial wall. Imipenem is very stable against beta-lactamases, including ESBL.

Antibiotic Spectrum of Imipenem:

A broad spectrum of activity against both gram-positive and gram-negative bacteria, including Pseudomonas, enterococci, and anaerobes.

Urological Indications for Imipenem:

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 Imipenem:

• Only intravenous administration is possible.
• Imipenem is administered in a fixed 1:1 combination with the dihydropeptidase cilastatin, which slows down the metabolism of imipenem and reduces nephrotoxicity.
• Half-life 1–2 hours, unchanged renal excretion in 70%.

Side Effects of 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 and nephrotoxicity are possible.

Drug Interactions:

Imipenem 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 Imipenem/Cilastatin

• Imipenem/cilastatin 500 mg/500 mg 1-1-1-1 (every 6 hours) or 1000 mg/1000 mg 1-1-1 (every 8 hours) for adults, depending on the severity of the infection.
• Children receive 15–25 mg/15–25 mg per kg body weight every 6 hours.
• A dose reduction is necessary in cases of renal insufficiency: imipenem/cilastatin 500 mg/500 mg every 8 hours for a GFR of 60–30 ml/min, and 500 mg/500 mg every 12 hours for a GFR of 30–15 ml/min.

References

Simon und Stille 1997 SIMON, C. ; STILLE, W.: Antibiotika-Therapie in Klinik und Praxis.
9. Auflage.
Stuttgart New York : Schattauer, 1997

  Deutsche Version: Pharmakologie und Nebenwirkungen von Imipenem

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