What are the recommended meropenem dosing regimens for adults and children, including adjustments for impaired renal function, continuous renal replacement therapy, infusion duration, treatment duration, and suitable alternative agents?

Meropenem Dosing Guidelines

Standard Adult Dosing by Indication

For most severe infections in adults with normal renal function, administer meropenem 1 gram IV every 8 hours as a 30-minute infusion, with extended 3-hour infusions reserved for resistant organisms (MIC ≥8 mg/L) or critically ill patients. 1, 2

Infection-Specific Regimens

Community-Acquired Infections (Non-Critical)

• Complicated intra-abdominal infections: 1 gram IV every 8 hours 3, 2
• Complicated skin/soft tissue infections: 1 gram IV every 8 hours 2
• Complicated urinary tract infections: 1 gram IV every 8 hours 2

Severe/Healthcare-Associated Infections

• Hospital-acquired pneumonia/ventilator-associated pneumonia: 1 gram IV every 8 hours (consider 2 grams for high-risk MDR) 2
• Carbapenem-resistant Enterobacterales (CRE) infections: 1 gram IV every 8 hours by 3-hour extended infusion as part of combination therapy 1, 2
• Necrotizing skin/soft tissue infections: 1-2 grams IV every 8 hours (mandatory combination with vancomycin or linezolid for MRSA coverage) 2

Central Nervous System Infections

• Bacterial meningitis (Enterobacterales, ESBL organisms): 2 grams IV every 8 hours 3, 2
• Pneumococcal meningitis (highly resistant strains): 2 grams IV every 8 hours 3

Critical Illness with Preserved Renal Function

• ICU patients: Consider 2 grams IV every 8 hours with extended infusion to compensate for increased clearance and altered pharmacokinetics 1

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Pediatric Dosing

Administer meropenem 60 mg/kg/day divided every 8 hours (maximum 6 grams/day) for complicated intra-abdominal infections in children. 3

• Standard pediatric dose: 20 mg/kg IV every 8 hours 3
• Meningitis: 40 mg/kg IV every 8 hours (maximum 2 grams per dose) 3
• Neonates with necrotizing enterocolitis: Meropenem as part of broad-spectrum regimen with ampicillin and metronidazole 3

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Renal Impairment Adjustments

For patients with renal impairment, maintain the full 1-gram dose but extend the dosing interval rather than reducing individual doses, as this preserves peak concentrations needed for concentration-dependent killing. 4

Dosing by Creatinine Clearance

CrCl 26-50 mL/min

• 1 gram IV every 12 hours 4

CrCl 10-25 mL/min

• 500 mg IV every 12 hours 4

CrCl <10 mL/min

• 500 mg IV every 24 hours 4

Intermittent Hemodialysis (IHD)

• Administer meropenem doses after dialysis sessions to prevent premature drug removal, as approximately 50% is eliminated during each session. 4, 5
• Dosing: 500 mg IV after each dialysis session 4

Sustained Low-Efficiency Dialysis (SLED)

• Maintain the full 1-gram dose every 12 hours to preserve concentration-dependent bactericidal activity. 4

Continuous Renal Replacement Therapy (CRRT)

• Administer 1 gram IV every 8-12 hours, as CRRT removes 25-50% of meropenem (CVVHF) or 13-53% (CVVHDF). 4, 5, 6
• Therapeutic drug monitoring is strongly recommended for all CRRT patients to ensure adequate exposure 1, 4
• Residual diuresis significantly impacts clearance; patients with residual CrCl >50 mL/min require higher doses 4

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Extended Infusion Strategy

Administer meropenem as a 3-hour extended infusion when treating organisms with MIC ≥8 mg/L or carbapenem-resistant Enterobacterales to maximize time above MIC. 1, 2

Indications for Extended Infusion

• Carbapenem-resistant infections 1, 2
• Critically ill patients with healthcare-associated infections 1
• Organisms with elevated MIC (≥8 mg/L) 1, 2
• ICU patients with altered pharmacokinetics 1

Pharmacodynamic Rationale

• Meropenem exhibits time-dependent killing; efficacy requires free drug concentrations above MIC for 40-70% of the dosing interval 7
• Extended infusion increases the percentage of time above MIC (%T>MIC), particularly critical for resistant organisms 7
• Target trough concentration: maintain free drug levels 4-6 times above MIC for optimal outcomes in critically ill patients 2

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Continuous Infusion Considerations

Continuous infusion may be used in ICU patients but requires preparation of fresh infusion bags every 6 hours due to meropenem's limited stability at room temperature. 1

• Stability constraint: 6-12 hours at room temperature 1, 2
• Consider for deep infection foci, major pharmacokinetic changes, or high MIC risk 2
• Therapeutic drug monitoring mandatory to maintain plasma concentrations above pathogen MIC 1

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Treatment Duration by Infection Type

Community-Acquired Pneumonia

• Mild-to-moderate: 5-7 days (when afebrile ≥48 hours and clinically stable) 2
• Severe: 7 days fixed course 2

Intra-Abdominal Infections

• With adequate source control: 5-7 days 3, 1, 2
• Cholecystectomy for acute cholecystitis: Discontinue within 24 hours unless infection extends beyond gallbladder wall 3
• Deep-seated abscesses or inadequate source control: Extend beyond 7 days 1, 2

Meningitis (Pathogen-Specific)

• Meningococcal: 5 days (if clinically recovered) 2
• Pneumococcal: 10 days (stable patients) to 14 days (slower response) 2
• Haemophilus influenzae: 10 days 2
• Enterobacterales: 21 days 2
• Listeria monocytogenes: 21 days 2

Melioidosis (Burkholderia pseudomallei)

• Intensive phase: Minimum 14 days; extend to 4-8 weeks for critically ill patients, extensive pulmonary disease, deep-seated collections, organ abscesses, osteomyelitis, septic arthritis, or neurologic involvement 2
• Mandatory eradication phase: 3-6 months oral trimethoprim-sulfamethoxazole to prevent relapse 2

Necrotizing Skin/Soft Tissue Infections

• 7-10 days IV therapy with adequate surgical debridement 2
• Extend to 10-14 days for inadequate source control, persistent systemic toxicity, or extensive tissue involvement 2

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Therapeutic Drug Monitoring (TDM)

Perform TDM in ICU patients with clinical signs of potential toxicity, those receiving CRRT, or patients with expected pharmacokinetic variability. 1, 4

Target Concentrations

• Maintain free trough concentrations above pathogen MIC 1
• Optimal target: Free trough 4-6 times above MIC for critically ill patients 2
• Toxicity threshold: Trough concentration >64 mg/L associated with neurological adverse effects 1, 4

Monitoring Indications

• Renal replacement therapy (all modalities) 1, 4
• ICU patients with altered pharmacokinetics 1
• Clinical signs of toxicity (behavioral changes, delirium, hallucinations, agitation, seizures) 4
• Treatment failure or suboptimal response 1

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Step-Down to Oral Therapy

Transition to oral antibiotics only after resolution of systemic toxicity, afebrile >48 hours, and demonstration of clinical stability. 2

Clinical Stability Criteria

• Temperature ≤37.8°C 2
• Heart rate ≤100 bpm 2
• Respiratory rate ≤24 breaths/min 2
• Systolic blood pressure ≥90 mmHg 2
• Oxygen saturation ≥90% 2
• Able to maintain oral intake 2
• Normal mental status 2

Oral Step-Down Options

• Amoxicillin-clavulanate 875/125 mg twice daily for susceptible organisms 2
• Levofloxacin 750 mg daily plus metronidazole 500 mg three times daily for penicillin-allergic patients 2
• Ciprofloxacin 500-750 mg twice daily for susceptible Gram-negative pathogens 2

Melioidosis Exception

• Mandatory oral trimethoprim-sulfamethoxazole for 3-6 months after intensive phase to prevent relapse 2

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Alternative Agents

When Meropenem Cannot Be Used

For β-lactam allergies (non-severe):

• Aztreonam plus metronidazole for Gram-negative and anaerobic coverage 3
• Fluoroquinolone (ciprofloxacin or levofloxacin) plus metronidazole 3, 2

For severe β-lactam allergies:

• Aminoglycoside-based regimen (gentamicin or tobramycin) plus metronidazole 3
• Aztreonam plus metronidazole plus vancomycin (for Gram-positive coverage) 3

Carbapenem-sparing alternatives for severe infections:

• Piperacillin-tazobactam 3.375-4.5 grams IV every 6 hours 2
• Cefepime 2 grams IV every 8 hours (for susceptible organisms) 3

For meningitis when meropenem unavailable:

• Ceftriaxone 2 grams IV every 12 hours or cefotaxime 2 grams IV every 4-6 hours 3
• Add vancomycin for pneumococcal meningitis with penicillin/cephalosporin resistance 3

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Critical Pitfalls to Avoid

Underdosing in ICU Patients

• ICU patients with preserved renal function have increased clearance and volume of distribution; standard doses may be inadequate 1
• Consider 2 grams every 8 hours or extended infusion for critically ill patients 1

Premature Drug Removal in Dialysis

• Never administer meropenem before hemodialysis sessions; always dose after dialysis to prevent subtherapeutic levels 4

Monotherapy for Necrotizing Infections

• Meropenem lacks MRSA activity; mandatory combination with vancomycin or linezolid for necrotizing skin/soft tissue infections 2

Delayed Surgical Intervention

• Antibiotics are adjunctive; urgent surgical debridement within 1 hour is mandatory for necrotizing fasciitis or gas gangrene 2
• Warning signs: pain disproportionate to findings, skin anesthesia, "wooden-hard" tissue, rapid expansion, gas on imaging, crepitus, systemic toxicity 2

Inadequate Duration for CNS Infections

• Do not stop meropenem before 21 days for Enterobacterales or Listeria meningitis; premature discontinuation risks treatment failure 2

Stability Issues with Continuous Infusion

• Meropenem degrades at room temperature; prepare fresh infusion bags every 6 hours 1, 2

Neurological Toxicity

• Monitor for behavioral changes, delirium, hallucinations, agitation, and seizures, especially in older adults, patients with seizure history, or those with trough concentrations >64 mg/L 4
• Meropenem has lower pro-convulsive activity than imipenem but still carries risk in renal dysfunction 4

Inappropriate De-Escalation

• For extensively resistant organisms (e.g., carbapenem-susceptible but otherwise MDR), meropenem represents appropriate definitive therapy; do not de-escalate when no narrower-spectrum alternatives exist 2