Avibactam (
NXL104,
AVE1330A) is a semi-synthetic, non-β-
lactam, β-lactamase inhibitor that is active against Ambler class A, class C, and some class D
serine β-lactamases. In this review, we summarize the in vitro data, pharmacology, mechanisms of action and resistance, and clinical trial data relating to the use of this agent combined with
ceftazidime for the treatment of
Gram-negative bacterial infections. The addition of
avibactam to
ceftazidime improves its in vitro activity against Enterobacteriaceae and Pseudomonas aeruginosa.
Avibactam does not improve the activity of
ceftazidime against Acinetobacter spp., Burkholderia spp., or most anaerobic Gram-negative rods. Pharmacodynamic data indicate that
ceftazidime-avibactam is bactericidal at concentrations achievable in human serum. Animal studies demonstrate that
ceftazidime-avibactam is effective in
ceftazidime-resistant Gram-negative
septicemia,
meningitis,
pyelonephritis, and
pneumonia. Limited clinical trials published to date have reported that
ceftazidime-avibactam is as effective as
therapy with a
carbapenem in complicated
urinary tract infection and complicated
intra-abdominal infection (combined with
metronidazole) including
infection caused by
cephalosporin-resistant Gram-negative isolates. Safety and tolerability of
ceftazidime-avibactam in clinical trials has been excellent, with few serious
drug-related adverse events reported. Given the abundant clinical experience with
ceftazidime and the significant improvement that
avibactam provides in its activity against contemporary β-lactamase-producing Gram-negative pathogens, it is likely this new combination agent will play a role in the empiric treatment of complicated
urinary tract infections (monotherapy) and complicated
intra-abdominal infections (in combination with
metronidazole) caused or suspected to be caused by antimicrobial-resistant pathogens (eg, extended spectrum
beta-lactamase-, AmpC-, or Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae and multidrug-resistant P. aeruginosa). Potential future uses also include
hospital-acquired pneumonia (in combination with antistaphylococcal and antipneumococcal agents) or treatment of skin and
soft tissue infections caused by antimicrobial-resistant Gram-negative pathogens (eg,
diabetic foot infections), but further clinical trials are required.