Organisms Not Covered by Ceftazidime-Avibactam
Ceftazidime-avibactam does not cover organisms producing metallo-β-lactamases (MBLs) such as NDM, VIM, or IMP, and has limited to no activity against Acinetobacter species, Burkholderia species, and most anaerobic bacteria. 1
Key Coverage Gaps by Organism Type
Gram-Negative Organisms with Specific Resistance Mechanisms
- Metallo-β-lactamase (MBL) producers: Avibactam does not inhibit Ambler class B metallo-β-lactamases including NDM, VIM, and IMP enzymes 1
- For infections caused by MBL-producing carbapenem-resistant Enterobacteriaceae (CRE), combination therapy with aztreonam plus ceftazidime-avibactam is recommended rather than ceftazidime-avibactam monotherapy 2
Non-Fermenters with Poor Coverage
- Acinetobacter species: Ceftazidime-avibactam does not improve activity against Acinetobacter spp., including carbapenem-resistant Acinetobacter baumannii (CRAB) 3, 4
- Burkholderia species: No meaningful activity against Burkholderia spp. 4
- Stenotrophomonas maltophilia: Not covered by ceftazidime-avibactam 1
Carbapenem-Resistant Organisms with Specific β-lactamases
- Some OXA-48 producers: While ceftazidime-avibactam has activity against certain class D (OXA-48) carbapenemases, it is inactive against other class D enzymes 1
- Carbapenem-resistant Pseudomonas aeruginosa: Demonstrated low susceptibility (75.8%) to ceftazidime-avibactam 5
- Carbapenem-resistant Escherichia coli: Only 33.3% susceptibility rate 5
Anaerobic Bacteria
- Most anaerobic Gram-negative rods: Ceftazidime-avibactam does not improve activity against most anaerobic bacteria 3, 4
- Limited exceptions with some activity: Bacteroides fragilis, Clostridium perfringens, Prevotella spp., and Porphyromonas spp. may have some susceptibility 3
- For complicated intra-abdominal infections, metronidazole must be added to ceftazidime-avibactam to provide anaerobic coverage 1, 4
Clinical Implications and Resistance Concerns
Emerging Resistance Patterns
- KPC-variant resistance: Mutations in blaKPC-2 and blaKPC-3 genes can lead to ceftazidime-avibactam resistance, occurring in 3.7%-8.1% of treated patients 1
- "See-saw effect": Variant KPC-3 enzymes may show reduced ceftazidime-avibactam susceptibility while paradoxically becoming susceptible to meropenem again 1
- Novel β-lactamases: VEB-25 enzyme has been described in ceftazidime-avibactam-resistant strains independent of prior drug exposure 1
Risk Factors for Resistance Development
- Prior administration of ceftazidime-avibactam increases risk of resistance emergence 1
- May result in replacement of MBLs as the predominant carbapenemase in carbapenemase-producing K. pneumoniae isolates 1
Important Caveats
When treating KPC-3 producers with ceftazidime-avibactam, combination therapy with a carbapenem or colistin may be considered to prevent resistance emergence, though evidence for routine combination therapy remains insufficient 1. Always obtain susceptibility testing when possible, as resistance patterns can vary significantly by geographic region and institutional epidemiology 1.