From the FDA Drug Label
Therapeutic concentrations of ceftazidime are achieved in the following body tissues and fluids... Cerebrospinal fluid 2 g q8hr IV 5 120 min 9.8 (inflamed meninges) Cerebrospinal fluid 2 g q8hr IV 6 180 min 9.4
Ceftazidime-avibactam does have meningeal penetration, as evidenced by the presence of therapeutic concentrations in the cerebrospinal fluid, particularly in cases of inflamed meninges 1. Key points:
- The concentration of ceftazidime in cerebrospinal fluid is 9.8 mcg/mL at 120 minutes after administration in patients with inflamed meninges.
- The concentration of ceftazidime in cerebrospinal fluid is 9.4 mcg/mL at 180 minutes after administration. Note: Avibactam is a beta-lactamase inhibitor that, when combined with ceftazidime, enhances its antimicrobial activity against certain beta-lactamase-producing organisms. However, the provided drug label information primarily focuses on ceftazidime.
From the Research
Ceftazidime-avibactam has limited meningeal penetration, making it suboptimal for treating central nervous system infections. The most recent and highest quality study on this topic is not available in the provided evidence, but based on the available data, it is known that ceftazidime, a component of ceftazidime-avibactam, achieves cerebrospinal fluid (CSF) concentrations that are lower than those in serum, indicating limited penetration into the CSF 2. This limited penetration is a concern for treating central nervous system infections, such as meningitis, where high CSF concentrations of antibiotics are necessary for effective treatment.
Meningeal Penetration of Ceftazidime
- The study by 2 found that ceftazidime concentrations in CSF ranged from 2 to 30 micrograms/ml, which is lower than the concentrations achieved in serum.
- Another study by 3 reported a mean ceftazidime CSF concentration of 7.4 micrograms/ml, which is still lower than the concentrations achieved in serum.
- The study by 4 found a mean ceftazidime CSF concentration of 6.7 micrograms/ml, which is also lower than the concentrations achieved in serum.
Implications for Treatment
- Alternative antimicrobials with better CSF penetration should be considered as first-line options for central nervous system infections.
- If ceftazidime-avibactam must be used for CNS infections due to highly resistant organisms, higher doses may be needed, and it should ideally be used in combination with other agents that have better meningeal penetration.
- Intrathecal or intraventricular administration has been attempted in some case reports but is not standard practice and lacks robust clinical evidence.
- When treating patients with both systemic and CNS infections caused by resistant gram-negative bacteria, a different antibiotic regimen for the CNS component is typically necessary.
Conclusion Not Provided as per Guidelines
Instead, the key points are summarized above, highlighting the limited meningeal penetration of ceftazidime-avibactam and the implications for treatment of central nervous system infections.