Ceftazidime/Avibactam and Ceftolozane/Tazobactam: Second-generation β-Lactam/β-Lactamase Inhibitor Combinations.
Ceftolozane/tazobactam and ceftazidime/avibactam are 2 novel β-lactam/β-lactamase combination antibiotics. The antimicrobial spectrum of activity of these antibiotics includes multidrug-resistant (MDR) gram-negative bacteria (GNB), including Pseudomonas aeruginosa. Ceftazidime/avibactam is also active against carbapenem-resistant Enterobacteriaceae that produce Klebsiella pneumoniae carbapenemases. However, avibactam does not inactivate metallo-β-lactamases such as New Delhi metallo-β-lactamases. Both ceftolozane/tazobactam and ceftazidime/avibactam are only available as intravenous formulations and are dosed 3 times daily in patients with normal renal function. Clinical trials showed noninferiority to comparators of both agents when used in the treatment of complicated urinary tract infections and complicated intra-abdominal infections (when used with metronidazole). Results from pneumonia studies have not yet been reported. In summary, ceftolozane/tazobactam and ceftazidime/avibactam are 2 new second-generation cephalosporin/β-lactamase inhibitor combinations. After appropriate trials are conducted, they may prove useful in the treatment of MDR GNB infections. Antimicrobial stewardship will be essential to preserve the activity of these agents.
Division of Infectious Diseases, University of North Carolina, Chapel Hill.
David
D
van Duin
Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center Division of Infectious Diseases and HIV Medicine, Department of Medicine Department of Molecular Biology and Microbiology Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Robert A
RA
Bonomo
D053961:Azabicyclo Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002442:Ceftazidime / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002511:Cephalosporins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D006801:Humans; D065093:beta-Lactamase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics
D053961:Azabicyclo Compounds; D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; C519491:ceftolozane; C543519:avibactam; D002442:Ceftazidime
Enterobacteriaceae; Pseudomonas; ceftazidime/avibactam; ceftolozane/tazobactam; multidrug resistance