Ceftazidime-Avibactam for Neurosurgical Meningitis

Spectrum of Activity and Mechanism

The Infectious Diseases Society of America recommends ceftazidime-avibactam as it restores antibacterial activity against Ambler class A, class C, and some class D enzymes, but does not inhibit class B metallo-β-lactamases, which is critical for treating neurosurgical meningitis caused by specific organisms 1, 2

If a patient has a KPC, ESBL, AmpC, or OXA-48 producing organism, the guideline recommends using ceftazidime-avibactam monotherapy 2.5g IV q8h, based on evidence from the Journal of Microbiology, Immunology and Infection 1, 2
For metallo-β-lactamase producers, such as NDM, VIM, or IMP, the guideline suggests adding aztreonam to ceftazidime-avibactam, as the combination demonstrates improved 30-day mortality compared to other regimens for MBL-producing CRE bloodstream infections 5, 3, 4
If the carbapenemase type is unknown and the patient is critically ill, the guideline recommends starting ceftazidime-avibactam plus aztreonam empirically until susceptibilities return, based on guidance from Praxis Medical Insights 6

The guideline warns against using ceftazidime-avibactam alone for NDM-producing organisms, as it will fail due to lack of MBL inhibition, and recommends always adding aztreonam in this scenario 1, 3, 4, 5, 6

The guideline notes that ceftazidime-avibactam has a similar safety profile to comparator groups in CRE bloodstream infection studies, with no differences in frequency or profile of adverse effects, including hepatic, renal, and coagulation parameters 1, 2

The guideline states that ceftazidime-avibactam demonstrates significantly higher microbiological eradication and clinical cure rates compared to other antimicrobial regimens, with lower 30-day mortality in several studies, based on evidence from the Journal of Microbiology, Immunology and Infection 1, 2, 7