Antimicrobials · Carbapenems
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Meropenem is a carbapenem antibiotic that acts by binding to penicillin-binding proteins (PBPs) to inhibit bacterial cell wall synthesis.
Meropenem provides broad-spectrum coverage including Gram-positive, Gram-negative, and anaerobic organisms.
Meropenem is the drug of choice for empiric treatment of hospital-acquired pneumonia and febrile neutropenia.
Meropenem is not active against methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecium, or Stenotrophomonas maltophilia.
Meropenem has a lower seizure threshold risk compared to imipenem-cilastatin, making it the preferred carbapenem in patients with CNS pathology.
Meropenem is primarily renally excreted, requiring dose adjustment in patients with renal impairment.
Meropenem is the preferred agent for treating extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae infections.
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A 68-year-old male is admitted to the ICU for septic shock secondary to a suspected intra-abdominal infection. He has a history of epilepsy currently managed with levetiracetam. Physical exam reveals diffuse abdominal tenderness and rebound guarding. His creatinine clearance is 45 mL/min. The team decides to initiate broad-spectrum empiric antibiotic therapy.
Which of the following carbapenems is the most appropriate choice for this patient given his neurological history?
Meropenem
Meropenem is preferred over imipenem in patients with a history of seizures because it has a significantly lower risk of inducing CNS toxicity and lowering the seizure threshold.
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Classification
Carbapenem class of beta-lactams.
Indications
Hospital-acquired pneumonia, intra-abdominal infections, and meningitis.
Mechanism of Action
Binds penicillin-binding proteins (PBPs) to inhibit bacterial cell wall synthesis.
Side Effects
Diarrhea, nausea, seizures.
Contraindications / Monitoring
Anaphylaxis to beta-lactams. Monitor renal function.
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Mechanism of Action
Meropenem exerts bactericidal activity by binding to penicillin-binding proteins (PBPs), specifically PBP2 and PBP3. This action inhibits the final transpeptidation step of peptidoglycan synthesis in the bacterial cell wall. It is highly resistant to hydrolysis by most beta-lactamases, including extended-spectrum beta-lactamases (ESBL).
Unique Properties
Unlike imipenem, meropenem does not require co-administration with cilastatin because it is stable against renal dehydropeptidase-I. It exhibits superior penetration into the cerebrospinal fluid (CSF), making it a preferred agent for bacterial meningitis.
Indications
Indicated for empiric treatment of hospital-acquired pneumonia and complicated intra-abdominal infections. It is a gold-standard choice for infections caused by ESBL-producing organisms. Also used for febrile neutropenia and meningitis.
Pharmacokinetics
Excreted primarily via renal filtration; dosage adjustments are mandatory in patients with creatinine clearance <50 mL/min. It has a short half-life, typically requiring dosing every 8 hours. It does not undergo significant hepatic metabolism.
Side Effects & Adverse Events
Common side effects include diarrhea, nausea, and rash. The most significant risk is seizures, particularly in patients with pre-existing CNS disorders or renal impairment. Anaphylaxis is a rare but life-threatening hypersensitivity reaction.
Contraindications
Hypersensitivity to any component of the drug or other beta-lactams due to the risk of cross-reactivity. Use with extreme caution in patients with a history of seizures or epilepsy, as the drug lowers the seizure threshold.
Monitoring
Monitor renal function (BUN/Creatinine) to guide dose adjustments. Observe for signs of superinfection, such as Clostridioides difficile-associated diarrhea. In prolonged therapy, monitor complete blood count for potential thrombocytopenia.
Clinical Pearls
Always consider meropenem for ESBL infections when the patient is clinically unstable. Remember the carbapenem class is the drug of choice for ESBL but lacks activity against MRSA and Enterococcus faecium.