Ceftazidime-Avibactam Treatment Regimen for Complicated Infections Caused by Gram-Negative Bacteria

Antimicrobial Spectrum and Resistance Considerations

Ceftazidime-avibactam is effective against Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, Klebsiella pneumoniae carbapenemase (KPC)-producing organisms, and OXA-48-producing Carbapenem-Resistant Enterobacterales (CRE) 1, 2
Ceftazidime-avibactam is not effective against Metallo-β-lactamase (MBL)-producing organisms, such as NDM, VIM, and IMP 1, 2

For patients with CRE infections producing serine carbapenemases (KPC, OXA-48), the standard dosing regimen of 2.5 grams every 8 hours has shown reduced mortality compared to other antimicrobial therapies 2
For patients with metallo-β-lactamase-producing CRE, combination of ceftazidime-avibactam with aztreonam is recommended, with significantly lower 30-day mortality (19.2% vs 44%) compared to other treatment options 3

Ceftazidime-avibactam may be associated with 182 fewer deaths per 1000 patients treated (RR 0.55, 95% CI 0.42-0.72) and 307 fewer treatment failures per 1000 patients (RR 0.49, 95% CI 0.34-0.70) for CRE infections 2, 5
Ceftazidime-avibactam has shown low-certainty evidence of non-inferiority to carbapenems for treatment of infections caused by resistant Enterobacterales in HAP/VAP 1

Resistance to ceftazidime-avibactam in KPC-producing organisms has been reported during treatment 1
Determining the carbapenemase type and/or ceftazidime-avibactam susceptibility before initiation of treatment is recommended whenever possible 2, 5
Combination therapy with aztreonam is recommended for metallo-β-lactamase producers 3
Ceftazidime-avibactam has been shown to be cost-effective for CRE bacteremia and pneumonia despite higher cost compared to other antibiotics 2