Meropenem exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. According to the Lippincott Textbook of Pharmacology, meropenem binds to penicillin-binding proteins (PBPs) on the bacterial cell wall, disrupting peptidoglycan cross-linking. This weakens the cell wall, leading to osmotic instability and cell lysis.

The Lange Basic & Clinical Pharmacology highlights meropenem’s resistance to most beta-lactamases, including extended-spectrum beta-lactamases (ESBLs) and AmpC enzymes. Its broad spectrum includes activity against Pseudomonas aeruginosa, Enterobacteriaceae, Streptococcus pneumoniae, and anaerobes like Bacteroides fragilis.

Meropenem is indicated for:

1. Severe Bacterial Infections:
   • Intra-Abdominal Infections: Peritonitis, abscesses.
   • Respiratory Tract Infections: Pneumonia (hospital-acquired and ventilator-associated).
   • Urinary Tract Infections (UTIs): Complicated pyelonephritis.
   • Skin and Soft Tissue Infections: Cellulitis, necrotizing fasciitis.
   • Bone and Joint Infections: Osteomyelitis, septic arthritis.
2. Central Nervous System (CNS) Infections: Meningitis (especially in neonates and children).
3. Febrile Neutropenia: In immunocompromised patients.
4. Septicemia: Bloodstream infections.

The BNF emphasizes its role as a first-line agent for empiric therapy in life-threatening infections and its use in infections caused by multidrug-resistant organisms.

Dosing varies by infection severity, patient age, and renal function:

Adults and Children (>3 months):

• Moderate Infections: 500 mg IV every 8 hours.
• Severe Infections (e.g., meningitis, septicemia): 1 g IV every 8 hours.
• Febrile Neutropenia: 1 g IV every 8 hours.

Neonates and Infants (<3 months):

• Meningitis: 20–40 mg/kg IV every 8–12 hours.
• Other Infections: 20 mg/kg IV every 8–12 hours.

Renal Impairment:

• Creatinine Clearance (CrCl) 26–50 mL/min: 500 mg–1 g every 12 hours.
• CrCl 10–25 mL/min: 250–500 mg every 12 hours.
• CrCl <10 mL/min: 250–500 mg every 24 hours.

Administration Tips:

• IV Infusion: Dilute in 50–100 mL of compatible fluid (e.g., 0.9% saline) and infuse over 15–30 minutes.
• Avoid Bolus Injection: To reduce the risk of seizures.

Meropenem is generally well-tolerated, but potential side effects include:

• Common:
  • Gastrointestinal disturbances (diarrhea, nausea, vomiting).
  • Injection site reactions (pain, inflammation).
  • Headache.
• Serious (Rare):
  • Hypersensitivity reactions (anaphylaxis, Stevens-Johnson syndrome).
  • Clostridioides difficile-associated diarrhea (CDAD).
  • Seizures (especially with high doses or renal impairment).
  • Hematologic effects (thrombocytopenia, leukopenia).

1. Contraindications: Hypersensitivity to carbapenems or severe beta-lactam allergy.
2. Renal Impairment: Dose adjustment is critical to avoid toxicity.
3. Seizure Risk: Use with caution in patients with CNS disorders or renal dysfunction.
4. Pregnancy and Lactation: Use only if benefits outweigh risks (limited safety data).
5. Pediatric Use: Safe for neonates and children, but dosing must be weight-based.

Key interactions per the BNF and Lange Basic & Clinical Pharmacology:

• Valproic Acid: Meropenem reduces valproic acid levels, increasing seizure risk.
• Probenecid: Reduces renal excretion, increasing meropenem levels (avoid concurrent use).
• Other Nephrotoxic Drugs (e.g., aminoglycosides): Increased risk of kidney damage.
• Oral Anticoagulants (e.g., warfarin): Enhanced anticoagulant effect (monitor INR).

• Generic: Meropenem trihydrate.
• Brand Names: Merrem®, Meronem®.