Antibacterial Spectrum of Ceftazidime-Avibactam
Ceftazidime-avibactam provides targeted coverage against multidrug-resistant Gram-negative bacteria by inhibiting Ambler class A (including ESBL and KPC), class C (AmpC), and some class D (OXA-48) β-lactamases, but critically lacks activity against metallo-β-lactamase producers, Acinetobacter species, and anaerobic bacteria. 1, 2
Gram-Negative Coverage
Enterobacteriaceae
- Extended-spectrum β-lactamase (ESBL)-producing organisms including Escherichia coli, Klebsiella pneumoniae, Enterobacter species, Citrobacter species, and Serratia species 2, 3
- Klebsiella pneumoniae carbapenemase (KPC) producers, specifically KPC-2 and KPC-3 variants 1, 4, 5
- OXA-48 carbapenemase-producing Enterobacteriaceae, though some OXA-48 producers may not be covered 1, 6, 7
- Other Enterobacteriaceae including Proteus mirabilis, Proteus vulgaris, Providencia species, Morganella morganii, Salmonella species, and Shigella species 8
Pseudomonas aeruginosa
- Multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa strains, including those with AmpC β-lactamases and certain strains lacking OprD porin 4, 9
- Activity comparable to ceftolozane-tazobactam and amikacin against P. aeruginosa 9
Other Gram-Negative Organisms
- Haemophilus influenzae and Haemophilus parainfluenzae 8
- Neisseria meningitidis and Neisseria gonorrhoeae 8
- Yersinia enterocolitica 8
Gram-Positive Coverage (Limited)
- Staphylococcus aureus (methicillin-susceptible only) and Staphylococcus epidermidis 8
- Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus agalactiae 8
- No MRSA coverage—requires addition of vancomycin or linezolid when MRSA is suspected 4
Critical Coverage Gaps
Metallo-β-Lactamase Producers
- No activity against NDM, VIM, or IMP metallo-β-lactamase-producing organisms 1, 6, 7
- For MBL-producing carbapenem-resistant Enterobacteriaceae, combination therapy with aztreonam plus ceftazidime-avibactam is recommended rather than monotherapy 6
Acinetobacter Species
- No activity against Acinetobacter species due to intrinsic resistance from OXA-type carbapenemases not inhibited by avibactam 2, 6, 3
Anaerobic Bacteria
- No activity against anaerobic bacteria, including Bacteroides species (though many Bacteroides isolates are resistant to ceftazidime alone) 2, 4, 6
- Metronidazole must be added when treating polymicrobial infections requiring anaerobic coverage, such as complicated intra-abdominal infections or aspiration pneumonia 2, 4, 3
Other Organisms Without Coverage
- Burkholderia species 6, 3
- Stenotrophomonas maltophilia 6
- Clostridium difficile (though other Clostridium species may have some susceptibility) 8
Resistance Development Concerns
- KPC-variant resistance can emerge during treatment in 3.7-8.1% of patients, particularly with mutations in blaKPC-2 and blaKPC-3 genes 6
- "See-saw effect" may occur where variant KPC-3 enzymes develop reduced ceftazidime-avibactam susceptibility while regaining meropenem susceptibility 6
- Renal replacement therapy is an independent predictor of resistance development (p=0.009) 4
- Prior ceftazidime-avibactam administration increases risk of resistance emergence 6
Clinical Application Considerations
- For aspiration pneumonia, ceftazidime-avibactam is inappropriate as monotherapy due to lack of anaerobic coverage; only consider in healthcare-associated cases with suspected resistant Gram-negatives, and always combine with metronidazole 2
- For complicated intra-abdominal infections, always combine with metronidazole for anaerobic coverage 4, 3, 5
- Susceptibility testing should always be obtained when possible, as resistance patterns vary significantly by geographic region and institutional epidemiology 6