Treatment of Metallo-β-Lactamase-Producing Carbapenem-Resistant Organisms
Introduction to Recommended Treatment Regimens
- For infections caused by metallo-β-lactamase-producing carbapenem-resistant organisms, the combination of ceftazidime-avibactam with aztreonam is recommended due to significantly lower mortality rates compared to other treatment options 1, 2
Ceftazidime-Avibactam and Aztreonam Dosing
- Standard dosing for ceftazidime-avibactam is 2.5 g IV (2 g ceftazidime/0.5 g avibactam) every 8 hours administered as a 2-hour infusion 3, 4
- Prolonged infusion (3 hours) of ceftazidime-avibactam has been associated with improved 30-day survival 5, 6
- Standard aztreonam dosing is 2 g IV every 8 hours 7, 8
Combination Therapy and Efficacy
- The combination of ceftazidime-avibactam and aztreonam shows good in-vitro synergy against metallo-β-lactamase-producing CRE infections, as aztreonam is not hydrolyzed by metallo-β-lactamases 1, 9, 2
- This combination has demonstrated significantly lower 30-day mortality (19.2% vs 44%) and lower clinical failure rates compared to other antimicrobial therapies 1, 9, 10
Duration of Therapy
- For bloodstream infections, the recommended duration of therapy is 7-14 days 3, 11
- For complicated urinary tract infections, the recommended duration is 5-7 days 3, 11, 6
- For hospital-acquired or ventilator-associated pneumonia, treatment should last 10-14 days 3, 6
- Treatment should be continued for at least 48 hours after the patient becomes asymptomatic 6
Clinical Considerations
- Clinical improvement should be evident within 48-72 hours of initiating appropriate therapy 6
- The carbapenemase type produced by CRE strains should be ascertained before initiation of ceftazidime-avibactam treatment whenever possible 1, 9