Meroject

Approved Indications:

• Complicated intra-abdominal infections (cIAI) in adults and children.
• Complicated skin and skin structure infections (cSSSI).
• Bacterial meningitis, including in neonates and children.
• Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).
• Septicemia (gram-negative, gram-positive, and polymicrobial).
• Complicated urinary tract infections (cUTI) including pyelonephritis.

Clinically Accepted Off-Label Uses:

• Empiric therapy for febrile neutropenia.
• Infections caused by extended-spectrum beta-lactamase (ESBL) producing organisms.
• Nosocomial infections due to multi-drug resistant (MDR) Gram-negative organisms.
• Pulmonary exacerbations in cystic fibrosis patients (IV or inhaled).

Route: Intravenous (IV) only

Adults:

• Mild to moderate infections: 500 mg IV every 8 hours.
• Severe infections (e.g., meningitis, HAP): 1 g to 2 g IV every 8 hours.
• Infuse over 15–30 minutes (standard) or extended over 3 hours (preferred for resistant organisms).

Pediatric Dosage:

• >3 months to 12 years: 10–40 mg/kg IV every 8 hours (max 2 g/dose).
• Neonates (<3 months): 20 mg/kg IV every 8–12 hours based on gestational and postnatal age.

Special Populations:

• Renal impairment (CrCl <50 mL/min):
• CrCl 26–50: 1 g q12h
• CrCl 10–25: 1 g q24h
• CrCl <10: 500 mg q24h
• Hemodialysis: Dose post-dialysis
• Hepatic impairment: No dose adjustment needed.
• Elderly: No adjustment unless renal function is impaired.

Meropenem is a broad-spectrum carbapenem antibiotic that inhibits bacterial cell wall synthesis. It binds to multiple penicillin-binding proteins (PBPs), primarily PBP-2 and PBP-3, interfering with peptidoglycan cross-linking. This leads to bacterial cell wall instability, lysis, and death. It is stable against most beta-lactamases, including ESBLs, and exhibits potent activity against gram-negative bacilli, gram-positive cocci, and anaerobes.

• Absorption: Not orally absorbed; given only intravenously.
• Distribution: Widely distributed; excellent penetration into CSF, pleural fluid, and peritoneal fluid.
• Volume of distribution (Vd): ~0.25 L/kg
• Protein binding: ~2%
• Metabolism: Limited hepatic metabolism
• Half-life: ~1 hour in adults; longer in neonates or renal impairment
• Elimination: Renal (70% as unchanged drug); requires dose adjustment in renal impairment

Pregnancy:

• FDA Pregnancy Category B
• Animal studies have not shown fetal harm. Use during pregnancy only if clearly needed.

Lactation:

• Excreted in small amounts in breast milk.
• Generally considered compatible with breastfeeding.
• Monitor infant for diarrhea or candidiasis if used for prolonged periods.

• Primary Class: Antibacterial
• Subclass: Carbapenem β-lactam antibiotic

• Known hypersensitivity to meropenem or any component of the formulation.
• History of severe allergic reactions to carbapenems or other β-lactam antibiotics.
• Do not administer intrathecally.

• Hypersensitivity Reactions: Risk of serious anaphylactic reactions; use with caution in patients allergic to penicillins or cephalosporins.
• Seizure Risk: Especially in patients with CNS disorders or renal impairment.
• Clostridioides difficile-associated diarrhea: Possible with prolonged use.
• Superinfections: Risk of fungal or bacterial overgrowth with extended therapy.
• Monitor Renal Function: Essential during long-term use or in high-risk patients.
• Prolonged Therapy: Requires liver and hematologic monitoring.

Common Adverse Effects:

• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain.
• Central Nervous System: Headache.
• Dermatologic: Rash, pruritus.
• Local: Pain or inflammation at injection site.

Serious/Rare Adverse Effects:

• Hypersensitivity reactions: Anaphylaxis, Stevens-Johnson syndrome.
• Seizures: Especially with renal dysfunction or high doses.
• Hematologic: Neutropenia, thrombocytopenia, eosinophilia.
• Liver: Elevated AST, ALT, or bilirubin.
• Infections: Risk of secondary fungal infections or C. difficile.

• Valproic Acid: May significantly reduce serum levels, increasing seizure risk. Avoid concomitant use.
• Probenecid: Inhibits renal tubular secretion, increasing plasma concentrations of meropenem.
• Other β-lactams or nephrotoxic drugs: Increased risk of renal toxicity if used together with aminoglycosides or vancomycin.

CYP450:
Meropenem is not metabolized by cytochrome P450 enzymes and does not inhibit or induce them.

• WHO AWaRe Classification: Meropenem is listed in the Reserve category to be used as a last-resort antibiotic.
• IDSA 2023 Recommendations: Support meropenem use for severe infections due to ESBL-producing organisms.
• Updated CLSI & EUCAST breakpoints: Allow for more refined susceptibility interpretation for resistant Gram-negative pathogens.
• Cystic Fibrosis Guidelines: Meropenem is part of first-line IV therapy for resistant pulmonary infections.

• Unreconstituted Powder:
• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Reconstituted Solution:
• Use immediately or store at 2°C to 8°C (refrigerated) for up to 24 hours.
• Do not freeze.
• Visually inspect for particulate matter or discoloration before use.
• Handling:
• Use aseptic technique during preparation.
• Discard unused portions.
• Avoid mixing with other drugs in the same IV line unless compatibility confirmed.