Spectrum of Beta-Lactamase Inhibition: Tazobactam vs Avibactam
Avibactam provides substantially broader beta-lactamase inhibition than tazobactam, most critically covering Klebsiella pneumoniae carbapenemases (KPC) and OXA-48 carbapenemases, while tazobactam is limited to inhibiting only Ambler class A enzymes (Richmond-Sykes class III penicillinases and cephalosporinases). 1, 2
Key Mechanistic Differences
Tazobactam Spectrum
- Tazobactam inhibits only Ambler Molecular class A enzymes, including Richmond-Sykes class III (Bush class 2b & 2b') penicillinases and cephalosporinases 2
- Tazobactam varies in its ability to inhibit class II and IV (2a & 4) penicillinases and does not reliably inhibit these enzymes 2
- Tazobactam does NOT inhibit AmpC beta-lactamases (chromosomally-mediated), which limits its utility against organisms harboring these enzymes 3
- Tazobactam does NOT inhibit extended-spectrum beta-lactamases (ESBLs) reliably, though piperacillin-tazobactam retains activity against some ESBL-producing Enterobacteriaceae 3
- Tazobactam has NO activity against carbapenemases of any type 2, 3
Avibactam Spectrum
- Avibactam inhibits Ambler class A enzymes including TEM, SHV, CTX-M (ESBLs), and critically, Klebsiella pneumoniae carbapenemases (KPC-2 and KPC-3) 1, 4
- Avibactam inhibits AmpC beta-lactamases, providing activity against organisms with chromosomally-mediated resistance 1, 5
- Avibactam inhibits certain OXA-48 carbapenemases, expanding coverage to this carbapenemase family 1, 4
- Avibactam does NOT inhibit metallo-beta-lactamases (MBLs) such as NDM-1, which is a critical limitation 1, 4, 6
- Avibactam does NOT inhibit OXA-type carbapenemases in Acinetobacter species (such as OXA-40 and OXA-69), resulting in intrinsic resistance 1, 7
Clinical Implications by Pathogen
ESBL-Producing Enterobacteriaceae
- Ceftazidime-avibactam demonstrates superior activity against ESBL producers with MIC50 of 0.125 μg/ml compared to ceftolozane-tazobactam's MIC50 of 0.38 μg/ml 6
- All ESBL isolates in comparative studies were susceptible to ceftazidime-avibactam, whereas one isolate was resistant to ceftolozane-tazobactam 6
- The European Society of Clinical Microbiology and Infectious Diseases recommends ceftazidime-avibactam as first-line treatment for ESBL-producing Enterobacterales 8
Carbapenem-Resistant Enterobacteriaceae (CRE)
- Ceftazidime-avibactam shows dramatically superior activity against CRE: 45% of CRE isolates were susceptible to ceftazidime-avibactam versus only 10% to ceftolozane-tazobactam 6
- The majority of OXA-48-producing isolates are susceptible to ceftazidime-avibactam, while very few NDM-1 isolates show susceptibility 6
- Piperacillin-tazobactam has NO activity against carbapenem-resistant organisms and should never be used for CRE 2, 3
Pseudomonas aeruginosa
- Both agents show comparable activity against P. aeruginosa: 94% susceptibility to ceftazidime-avibactam (MIC50 1.5 μg/ml) versus 97% to ceftolozane-tazobactam (MIC50 0.75 μg/ml) 6
- Ceftolozane-tazobactam demonstrates slightly lower MICs against P. aeruginosa in head-to-head comparisons 6
- Avibactam restores ceftazidime activity against P. aeruginosa with AmpC beta-lactamases and certain strains lacking OprD porin 1
Acinetobacter baumannii
- Neither avibactam nor tazobactam provides reliable activity against A. baumannii with OXA-type carbapenemases 7
- Combination with avibactam does not reduce beta-lactam MICs against A. baumannii harboring OXA-40 or OXA-69 carbapenemases 7
Critical Anaerobic Coverage Gap
- Both ceftazidime-avibactam and ceftolozane-tazobactam lack anaerobic activity, requiring metronidazole addition for intra-abdominal infections 5, 9, 10
- Piperacillin-tazobactam provides intrinsic anaerobic coverage including Bacteroides fragilis group, making it suitable for polymicrobial infections without additional agents 2, 3
- For aspiration pneumonia, ceftazidime-avibactam is NOT appropriate due to lack of anaerobic activity; piperacillin-tazobactam or ampicillin-sulbactam are preferred 4
Carbapenem-Sparing Strategy Context
- Ceftazidime-avibactam should be reserved for documented KPC or OXA-48 producers to preserve its activity and reduce carbapenem use 5, 8
- Piperacillin-tazobactam remains appropriate for less severe infections when ESBL is suspected and MIC ≤4 mg/L, though post-MERINO trial controversy exists 5
- Rapid molecular testing should guide selection between these agents to avoid unnecessary broad-spectrum coverage 5, 8