Is it appropriate to give meropenem 1 g intravenously once daily?

Meropenem 1 gram IV Once Daily Dosing

No, meropenem 1 gram IV once daily is not appropriate—meropenem must be dosed every 8 hours (or every 12 hours in renal impairment) because its efficacy depends on maintaining plasma concentrations above the minimum inhibitory concentration for at least 40-70% of the dosing interval, which cannot be achieved with once-daily administration. 1

Standard Dosing Requirements

FDA-Approved Dosing Regimens

• Standard adult dose: 500 mg IV every 8 hours for complicated skin and skin structure infections, or 1 gram IV every 8 hours for complicated intra-abdominal infections 1
• Administration method: Infuse over 15-30 minutes, or administer as IV bolus over 3-5 minutes for 1-gram doses 1
• Pharmacokinetic rationale: Meropenem has an elimination half-life of approximately 1 hour, with up to 70% recovered unchanged in urine 2

Why Every-8-Hour Dosing Is Mandatory

• Time-dependent killing: Beta-lactam antibiotics like meropenem require plasma concentrations to remain above the pathogen's MIC for 40-70% of the dosing interval to achieve bactericidal activity 3
• Rapid elimination: With a half-life of only 1 hour and predominantly renal clearance, once-daily dosing would result in sub-therapeutic concentrations for the majority of the 24-hour period 2
• Clinical failure risk: Inadequate meropenem levels lead to therapeutic failure and promote antimicrobial resistance 4

Guideline-Recommended Dosing by Clinical Scenario

Complicated Intra-Abdominal Infections

• Non-critically ill patients: 1 gram IV every 8 hours for 5-7 days 3, 5
• Critically ill patients: 1 gram IV every 8 hours via extended infusion (over 3 hours) when treating healthcare-associated infections 3, 5

Necrotizing Skin and Soft Tissue Infections

• Standard regimen: 1 gram IV every 8 hours as part of mandatory combination therapy with MRSA coverage (vancomycin or linezolid) 3
• High-dose option: 2 grams IV every 8 hours for suspected necrotizing fasciitis or systemic toxicity 3

Hospital-Acquired Pneumonia

• Low MDR risk: 1 gram IV every 8 hours 3
• High MDR risk or P. aeruginosa coverage: 2 grams IV every 8 hours via extended infusion 3

Central Nervous System Infections

• Meningitis: 2 grams IV every 8 hours for Enterobacteriaceae or suspected ESBL organisms 3

Renal Dose Adjustments (The Only Time Dosing Interval Changes)

Creatinine Clearance-Based Modifications

• CrCl >50 mL/min: Standard dose every 8 hours 1
• CrCl 26-50 mL/min: Recommended dose every 12 hours 1
• CrCl 10-25 mL/min: Half the recommended dose every 12 hours 1
• CrCl <10 mL/min: Half the recommended dose every 24 hours 1

Critical caveat: Even in severe renal impairment (CrCl <10 mL/min), the maximum interval is every 24 hours—not because once-daily dosing is optimal, but because this represents the longest safe interval in patients who cannot clear the drug 1

Optimization Strategies for Resistant Organisms

Extended Infusion Indications

• Carbapenem-resistant Enterobacteriaceae (CRE): 1 gram IV every 8 hours via 3-hour extended infusion 3, 5
• Organisms with MIC ≥8 mg/L: Extended infusion over 3 hours to maximize time above MIC 3, 5
• Critically ill patients: Prolonged infusion preferred to achieve pharmacodynamic targets 3

High-Dose Regimens

• KPC-producing K. pneumoniae with MIC ≥16 mg/L: 2 grams IV every 8 hours via 3-hour extended infusion 3
• Severe pneumonia: 2 grams IV every 8 hours for at least 7 days 3

Common Pitfalls to Avoid

Dosing Errors

• Never use once-daily dosing for meropenem in patients with normal or mildly impaired renal function—this guarantees sub-therapeutic levels for most of the dosing interval 1, 4
• Do not confuse with ertapenem: Ertapenem (a different carbapenem) can be dosed once daily, but meropenem cannot due to its shorter half-life 3
• Avoid under-dosing in CRRT: Patients on continuous renal replacement therapy require higher doses than predicted by creatinine clearance alone due to significant extracorporeal drug removal (48% cleared by filter) 6

Spectrum Gaps

• Meropenem does NOT cover MRSA or VRE—add vancomycin or linezolid when empiric MRSA coverage is needed 3, 5
• No loading dose required for meropenem, unlike colistin or tigecycline 3

Stability Concerns

• Extended 3-hour infusions are safe and recommended, but true 24-hour continuous infusions may have stability issues 5

Aminoglycoside Comparison (Once-Daily Dosing Context)

The confusion about once-daily dosing may stem from aminoglycosides, which ARE appropriately dosed once daily:

• Tobramycin and amikacin: Once-daily dosing achieves higher airway concentrations than multiple daily dosing in cystic fibrosis patients 7
• Mechanism difference: Aminoglycosides exhibit concentration-dependent killing with a prolonged post-antibiotic effect, whereas meropenem exhibits time-dependent killing without significant post-antibiotic effect 7

Bottom line: The pharmacodynamic principles that justify once-daily aminoglycoside dosing do not apply to meropenem 7, 2