Management of Meningitis with CRE Cultures
Initial Assessment and Antibiotic Selection
- The Infectious Diseases Society of America recommends ceftazidime-avibactam 2.5g IV every 8 hours infused over 3 hours for CRE bloodstream infections when the isolate is susceptible in vitro 1, 2
- Meropenem-vaborbactam 4g IV every 8 hours or imipenem-cilastatin-relebactam 1.25g IV every 6 hours are alternatives for susceptible CRE 1, 2
- Polymyxin B-based combination therapy is recommended for severe CRE infections when newer agents are unavailable or the organism is resistant 3, 1
- For polymyxin dosing in normal renal function: loading dose of 300mg colistin methanesulfonate (CMS) (9 million units) infused over 0.5-1 hour, followed by maintenance dose of 300-360mg CMS (9-10.9 million units) divided in two doses 2
Critical Management Principles
- Combination antimicrobial therapy should be based on susceptibility testing results 3, 1
- The selection of combination agents must account for synergistic effects confirmed by antimicrobial synergy testing when possible 4, 5
- Therapeutic drug monitoring (TDM) is strongly suggested for polymyxins, aminoglycosides, and carbapenems in CRE meningitis 4, 5, 6
Agents to Avoid
- Do not use tigecycline for CRE meningitis—it has poor CSF penetration and is not recommended for bloodstream infections or CNS infections 2
- Tigecycline monotherapy is associated with higher mortality compared to combination therapy for CRE bloodstream infections 2