Ceftazidime-Avibactam CNS Penetration
Ceftazidime-avibactam demonstrates good central nervous system penetration with CSF/serum concentration ratios of 35-59% for ceftazidime and 51-57% for avibactam, making it an effective option for treating CNS infections caused by susceptible multidrug-resistant gram-negative bacteria. 1
CNS Penetration Characteristics
- Ceftazidime-avibactam shows significantly better CNS penetration than many other antibiotics used for CNS infections, with recent studies demonstrating CSF/serum concentration ratios (AUCCSF/AUCserum) of 0.35-0.59 for ceftazidime and 0.51-0.57 for avibactam 1
- This penetration is considerably higher than traditional agents like vancomycin (1-5% penetration) and comparable to linezolid (66% penetration) 2
- In patients with external ventriculostomies, ceftazidime alone has shown median AUCCSF/AUCserum ratios of 0.054, which is lower than what is observed with the addition of avibactam 3
- The avibactam component consistently achieves CSF concentrations ≥1 μg/mL throughout the dosing interval, which is critical for effective β-lactamase inhibition 4
Clinical Implications for CNS Infections
- Ceftazidime-avibactam can achieve CSF concentrations ranging from 15.0-29.0 μg/mL for the ceftazidime component and 0.92-4.20 μg/mL for the avibactam component 4
- These concentrations exceed the MICs for most susceptible pathogens, including KPC-producing Enterobacterales and difficult-to-treat resistant Pseudomonas aeruginosa 4
- For CNS infections caused by carbapenem-resistant organisms, ceftazidime-avibactam has demonstrated both clinical and microbiological cure in case series 5
- Standard dosing of ceftazidime-avibactam (2.5g IV every 8 hours) appears to achieve sufficient CSF concentrations for treating susceptible pathogens 4
Comparison with Other Antibiotics for CNS Infections
- Meropenem has traditionally been the drug of choice for nosocomial meningitis and ventriculitis, particularly for gram-negative infections 6
- Colistin has poor CNS penetration even with inflamed meninges, often requiring intrathecal or intraventricular administration in addition to systemic therapy 6
- For OXA-48-like producing carbapenem-resistant Enterobacterales infections, ceftazidime-avibactam is recommended as first-line treatment, including for CNS infections 6
Therapeutic Considerations
- Therapeutic drug monitoring (TDM) is recommended when treating CNS infections with ceftazidime-avibactam, with sampling of both blood and CSF when possible 7
- Target CSF concentrations should be above the MIC of the isolated bacteria throughout the dosing interval 7
- Extended infusions may help maintain therapeutic concentrations in the CSF for longer periods 8
- For CNS infections caused by multidrug-resistant pathogens, combination therapy may be considered, though ceftazidime-avibactam monotherapy has shown efficacy in some cases 5
Treatment Duration and Monitoring
- For nosocomial meningitis/ventriculitis, a 21-day course of antimicrobial therapy is generally recommended 6
- Monitoring of CSF sterilization through repeated cultures can help tailor the duration of therapy 6
- Surgical drainage of focal abscesses and removal of any foreign body should be performed whenever possible to improve treatment outcomes 2
Ceftazidime-avibactam represents an important therapeutic option for CNS infections caused by resistant gram-negative pathogens, with pharmacokinetic data supporting its ability to achieve therapeutic concentrations in the CSF.