Ceftazidime-Avibactam is NOT Optimal for Acinetobacter Infections
Ceftazidime-avibactam should not be used for Acinetobacter infections because avibactam does not improve the activity of ceftazidime against Acinetobacter species, and all tested Acinetobacter baumannii isolates remain resistant to this combination. 1, 2
Microbiological Evidence Against Use
The fundamental problem is mechanistic:
Avibactam does not enhance ceftazidime activity against Acinetobacter species because the resistance mechanisms in Acinetobacter (primarily OXA-type carbapenemases and efflux pumps) are not inhibited by avibactam 1, 2
In vitro testing of 40 multidrug-resistant A. baumannii clinical isolates demonstrated that all isolates except one (39/40) were resistant to ceftazidime-avibactam, with MIC values remaining in the resistant range 3
Avibactam inhibits Ambler class A, class C, and some class D β-lactamases, but the predominant carbapenemases in Acinetobacter (OXA-23, OXA-24, OXA-58) are class D enzymes that are not effectively inhibited 1, 4
Alternative Treatment Approaches for MDR Acinetobacter
Since ceftazidime-avibactam monotherapy fails, consider these evidence-based alternatives:
Combination Therapy Options
If ceftazidime-avibactam must be used (e.g., polymicrobial infection), it requires combination with other agents:
Ceftazidime-avibactam + colistin showed synergistic activity against 5/5 tested MDR A. baumannii strains at 1× MIC in time-kill assays 3
Ceftazidime-avibactam + tobramycin demonstrated synergistic activity against 4/5 strains 3
Ceftazidime-avibactam + tigecycline showed synergistic activity against 4/5 strains 3
At 4× MIC, all combinations showed additive effects with no antagonism observed 3
Preferred Agents for Carbapenem-Resistant Acinetobacter
The guidelines explicitly note that imipenem-relebactam is not active against carbapenem-resistant A. baumannii (CRAB) 5, highlighting that newer β-lactam/β-lactamase inhibitor combinations generally fail against this pathogen.
Critical Clinical Caveat
Do not empirically use ceftazidime-avibactam for suspected Acinetobacter infections. The 2022 ESCMID guidelines state that "insufficient evidence is available for imipenem-relebactam, cefiderocol and ceftazidime-avibactam" for carbapenem-resistant Pseudomonas aeruginosa 5, and this applies even more strongly to Acinetobacter where the drug has no intrinsic activity.
The real-world clinical experience study specifically excluded Acinetobacter from analysis, focusing on P. aeruginosa and ESBL-producing Enterobacterales, further confirming this agent has no established role in Acinetobacter treatment 6.