What is the recommended Meropenem dosage for a patient?

Meropenem Dosing Recommendations

Standard Adult Dosing for Normal Renal Function

For most serious infections in adults with normal renal function, administer meropenem 1 gram IV every 8 hours as a 15-30 minute infusion. 1, 2

Infection-Specific Dosing

• Complicated intra-abdominal infections: 1 gram IV every 8 hours 1, 2
• Complicated skin and soft tissue infections: 500 mg IV every 8 hours (increase to 1 gram every 8 hours if Pseudomonas aeruginosa is suspected or confirmed) 1, 2
• Hospital-acquired or ventilator-associated pneumonia: 1-2 grams IV every 8 hours, depending on severity and risk of multidrug-resistant organisms 1, 3
• Meningitis: 2 grams IV every 8 hours 3
• Necrotizing soft tissue infections: 1 gram IV every 8 hours as part of combination therapy 3

---

Extended Infusion Strategy

For critically ill patients or when treating organisms with MIC ≥8 mg/L, administer meropenem as a 3-hour extended infusion rather than the standard 30-minute infusion. 3, 4

• Extended infusion optimizes the time that free drug concentrations remain above the MIC, which is the primary pharmacodynamic parameter for beta-lactam efficacy 3, 5
• This strategy is particularly important for carbapenem-resistant Enterobacteriaceae (CRE) infections 3
• For organisms with MIC 4-8 mg/L, consider extended infusion even in patients without renal impairment 4

---

Dosing in Renal Impairment

Reduce dosing frequency rather than individual dose size when adjusting for renal dysfunction—maintain the 1 gram dose whenever possible and extend the interval. 6, 4, 2

Creatinine Clearance-Based Adjustments

• CrCl >50 mL/min: Standard dosing (500 mg or 1 gram every 8 hours, depending on infection) 2
• CrCl 26-50 mL/min: Recommended dose every 12 hours 2
• CrCl 10-25 mL/min: Half the recommended dose every 12 hours 2
• CrCl <10 mL/min: Half the recommended dose every 24 hours 2

Critical Considerations for Renal Impairment

• Avoid reducing individual doses below 1 gram for serious infections, even in renal impairment—instead extend the dosing interval 6, 4
• This approach preserves peak concentrations needed for concentration-dependent bacterial killing 6, 4
• For organisms with MIC ≥8 mg/L, use extended 3-hour infusion even with renal impairment 6, 4
• Monitor for neurological toxicity if trough concentrations exceed 64 mg/L 6, 4

---

Dosing for Renal Replacement Therapy

Intermittent Hemodialysis (IHD)

Administer meropenem after dialysis sessions, not before, as approximately 50% of the drug is removed during hemodialysis. 6, 7

• Recommended dose: 500 mg to 1 gram IV after each dialysis session 6, 7
• Administering before dialysis leads to premature drug removal and subtherapeutic levels 6

Sustained Low-Efficiency Dialysis (SLED)

For patients on SLED, maintain the full 1 gram dose every 12 hours rather than reducing individual doses. 6, 4

• The 12-hour interval accounts for the prolonged elimination half-life in renal impairment 6
• Full doses preserve concentration-dependent bactericidal effects 6

Continuous Renal Replacement Therapy (CRRT)

For patients on CRRT, administer 1 gram IV every 8-12 hours, as CRRT removes 25-50% of meropenem. 6, 7, 8, 9

• CVVHDF removes 13-53% of meropenem 7, 8
• CVVHF removes 25-50% of meropenem 7
• Residual diuresis is a critical determinant of total drug clearance—patients with residual creatinine clearance >50 mL/min may require higher doses 6, 10
• Therapeutic drug monitoring is strongly recommended for all patients on CRRT to ensure adequate exposure 6, 9, 10

CRRT Dosing Algorithm Based on Residual Diuresis

• Oligoanuric patients (minimal residual diuresis): 500 mg every 8 hours as 30-minute bolus for susceptible organisms (MIC <2 mg/L) 10
• Patients with preserved diuresis: 500 mg every 8 hours as 3-hour extended infusion for susceptible organisms 10
• For organisms with MIC 2-4 mg/L: 500 mg every 6 hours (30-minute bolus for oligoanuric patients; 3-hour infusion for those with preserved diuresis) 10

---

Pediatric Dosing

Children ≥3 Months of Age

• Complicated skin/soft tissue infections: 10 mg/kg every 8 hours (maximum 500 mg per dose) 2
• Complicated intra-abdominal infections: 20 mg/kg every 8 hours (maximum 1 gram per dose) 2
• Meningitis: 40 mg/kg every 8 hours (maximum 2 grams per dose) 1, 2
• For Pseudomonas aeruginosa infections, use 20 mg/kg every 8 hours regardless of infection type 2

Infants <3 Months of Age

Dosing is based on gestational age (GA) and postnatal age (PNA): 2

• <32 weeks GA and PNA <2 weeks: 20 mg/kg every 12 hours 2
• <32 weeks GA and PNA ≥2 weeks: 20 mg/kg every 8 hours 2
• ≥32 weeks GA and PNA <2 weeks: 20 mg/kg every 8 hours 2
• ≥32 weeks GA and PNA ≥2 weeks: 30 mg/kg every 8 hours 2

---

Duration of Therapy

For most complicated intra-abdominal infections with adequate source control, treat for 5-7 days based on clinical response. 1, 3, 4

Infection-Specific Durations

• Complicated intra-abdominal infections: 5-7 days (may discontinue within 24 hours if no infection beyond gallbladder wall in cholecystitis with cholecystectomy) 1, 3
• Bloodstream infections/sepsis: 7-14 days depending on source control and clinical response 3
• Complicated urinary tract infections: 5-7 days 3
• Pneumonia: Minimum 7 days 3
• Meningococcal sepsis: 5 days if recovered 3
• Pneumococcal meningitis: 10-14 days 3
• Enterobacteriaceae meningitis: 21 days 3
• Vertebral osteomyelitis: 6 weeks 4
• Melioidosis (Burkholderia pseudomallei): 14 days intensive phase with meropenem, followed by 3-6 months eradication phase with trimethoprim-sulfamethoxazole 3

---

Critical Pitfalls to Avoid

• Never use meropenem monotherapy for polymicrobial infections like gangrenous bowel or necrotizing soft tissue infections—combination therapy with anti-MRSA agents is mandatory 4
• Do not delay antibiotic administration waiting for culture results—start empiric therapy immediately 4
• Meropenem has no activity against MRSA or VRE—add vancomycin or linezolid if these organisms are suspected 3
• Do not administer meropenem before hemodialysis sessions—this causes premature drug removal and treatment failure 6
• For carbapenem-resistant organisms, never use meropenem as monotherapy—combination therapy is required 3, 4
• Avoid reducing individual doses below 1 gram when treating serious infections in renal impairment—extend the interval instead 6, 4

---

Therapeutic Drug Monitoring

Consider therapeutic drug monitoring in critically ill patients, those on CRRT, and when treating resistant organisms with high MIC values. 6, 5, 9, 10

• Target: Maintain free drug concentrations above the pathogen's MIC for 40-100% of the dosing interval, depending on infection severity 5, 9
• Trough concentrations should remain below 64 mg/L to prevent neurological toxicity 6, 4
• TDM is particularly valuable in patients with augmented renal clearance, septic shock, or significant residual diuresis during CRRT 9, 10