Meropenem Prolonged Infusion for MDR Proteus mirabilis
For multidrug-resistant Proteus mirabilis infections, meropenem with prolonged (extended) infusion over 3 hours is strongly recommended, using 1-2 grams IV every 8 hours depending on infection severity and MIC values. 1, 2
Rationale for Prolonged Infusion
Prolonged infusion of β-lactams for pathogens with high minimum inhibitory concentration (MIC) is specifically recommended by current guidelines (Strong recommendation, low quality of evidence). 1 This approach optimizes the pharmacodynamic target of maintaining drug concentrations above the MIC for at least 70% of the dosing interval, which is critical for time-dependent antibiotics like meropenem. 2
- Extended infusion over 3 hours is particularly indicated when meropenem MIC is ≥8 mg/L. 2, 3
- For critically ill patients with healthcare-associated infections, prolonged or continuous infusions should be considered to optimize pharmacodynamic targets. 2, 3
- Meta-analysis data demonstrates that prolonged infusion of meropenem is associated with higher clinical success rates (OR 2.10,95% CI 1.31-3.38) and lower mortality (RR 0.66,95% CI 0.50-0.88) compared to intermittent bolus administration. 4
Specific Dosing Recommendations
Standard dosing:
- 1 gram IV every 8 hours by extended infusion (3 hours) for most MDR infections including bloodstream infections, complicated intra-abdominal infections, and complicated urinary tract infections. 2, 3
- 2 grams IV every 8 hours by extended infusion (3 hours) for severe infections, pneumonia, or when MIC values are elevated (≥8-16 mg/L). 2
No loading dose is required for meropenem, which distinguishes it from other antibiotics like colistin or tigecycline that do require loading doses. 2
Clinical Considerations for MDR Proteus mirabilis
- Proteus mirabilis is listed as an FDA-approved indication for meropenem in complicated skin and skin structure infections. 5
- However, tigecycline lacks in vitro activity against P. mirabilis, making meropenem a superior choice for this pathogen. 1
- Infectious disease consultation is highly recommended in the management of infections caused by multidrug-resistant organisms (Strong recommendation, low quality of evidence). 1
- Antimicrobial susceptibility testing should guide final antibiotic selection and allow for potential de-escalation. 1
Treatment Duration
Duration should be tailored to infection site:
- 5-7 days for complicated intra-abdominal infections and complicated urinary tract infections, individualized based on source control adequacy and clinical response. 2, 3
- 7-14 days for bloodstream infections or sepsis, depending on source control and clinical response. 2
- At least 7 days for pneumonia. 2
Important Caveats
Recent high-quality RCT data (MERCY trial, 2023) showed no significant difference between continuous and intermittent meropenem administration for the composite outcome of mortality and emergence of pandrug-resistant bacteria (47% vs 49%, P=0.60). 6 However, this trial used intermittent dosing every 8 hours, not traditional bolus administration, and the continuous infusion still achieved equivalent (not inferior) outcomes. The meta-analysis of earlier studies favoring prolonged infusion remains valid for comparing extended infusion versus rapid bolus. 4
Prolonged infusion is most beneficial when:
- MIC values are between 2-8 mg/L (significant improvement in target attainment). 7
- For MIC >4 mg/L or when targeting 100% fT>MIC, increasing the dose may be more effective than simply prolonging infusion time. 7
- Patients have normal to moderately impaired renal function (CrCl >60 mL/min); those with severe renal impairment may achieve adequate levels even with standard infusion. 7
Combination therapy considerations: