Limitations of Ceftazidime-Avibactam Coverage

Organism-Specific Coverage Gaps

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, affecting treatment of infections caused by these organisms 1, 2, 3
The Infectious Diseases Society of America recommends combination therapy with aztreonam plus ceftazidime-avibactam for infections caused by MBL-producing carbapenem-resistant Enterobacteriaceae (CRE) rather than ceftazidime-avibactam monotherapy 4
Ceftazidime-avibactam does not improve activity against Stenotrophomonas maltophilia, a non-fermenter bacterium 5

Some OXA-48 producers are not covered by ceftazidime-avibactam, which has activity against certain class D (OXA-48) carbapenemases but is inactive against other class D enzymes, as reported by the European Society of Clinical Microbiology and Infectious Diseases 2, 3
KPC-variant resistance, including mutations in blaKPC-2 and blaKPC-3 genes, can lead to ceftazidime-avibactam resistance in 3.7%-8.1% of treated patients, according to the Clinical Microbiology and Infection journal 2, 3, 6
The "see-saw effect" may occur, where variant KPC-3 enzymes show reduced ceftazidime-avibactam susceptibility while becoming susceptible to meropenem again, as noted by the Journal of Microbiology, Immunology and Infection 5

Prior administration of ceftazidime-avibactam increases the risk of resistance emergence, and may result in replacement of MBLs as the predominant carbapenemase in carbapenemase-producing K. pneumoniae isolates, as warned by the Journal of Microbiology, Immunology and Infection 5
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, as stated by the Journal of Microbiology, Immunology and Infection 5
Susceptibility testing should always be obtained when possible, as resistance patterns can vary significantly by geographic region and institutional epidemiology, as recommended by the Journal of Microbiology, Immunology and Infection and the Clinical Microbiology and Infection journal 1, 2