title: Ceftolozane/tazobactam and ceftazidime/avibactam: two novel β-lactam/β-lactamase inhibitor combination agents for the treatment of resistant Gram-negative bacterial infections.
abstract: The rise in resistant Gram-negative bacteria is a major concern and has led to difficulty in treating multidrug-resistant (MDR) infections. Two recently approved combination antibiotics, ceftolozane/tazobactam and ceftazidime/avibactam, may be effective in treating these resistant infections. Ceftolozane is a novel cephalosporin that has been developed in combination with tazobactam, a recognised β-lactamase inhibitor (BLI). Avibactam is a novel BLI combined with ceftazidime, a cephalosporin with an established history. Both of these β-lactam/BLI combination agents have been shown to retain in vitro activity against selected resistant Gram-negative pathogens, including Enterobacteriaceae and Pseudomonas aeruginosa; notably, ceftazidime/avibactam has demonstrated consistent activity against Klebsiella pneumoniae carbapenemase (KPC)-producing organisms. Both agents have been approved for the indications of complicated intra-abdominal infection (with metronidazole) and complicated urinary tract infection, and have ongoing phase 3 trials for the treatment of ventilator-associated and nosocomial pneumonia. This manuscript will review current data available regarding the spectrum of activity and clinical trials that led to the US Food and Drug Administration (FDA) approval of these agents. Both agents appear to be well tolerated and show promise in the treatment of MDR Gram-negative infections.
authors.affiliation: Northeastern University, Boston, MA, USA.
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Liscio
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Monica V
authors.initials: MV
authors.lastname: Mahoney
authors.affiliation: Northeastern University, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address: e.hirsch@neu.edu.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Hirsch
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D053961:Azabicyclo Compounds / Q000627:therapeutic use*; D002442:Ceftazidime / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000078142:Tazobactam
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D002511:Cephalosporins; D004338:Drug Combinations; D004791:Enzyme Inhibitors; C000595613:avibactam, ceftazidime drug combination; C000594038:ceftolozane, tazobactam drug combination; D010397:Penicillanic Acid; D002442:Ceftazidime; D000078142:Tazobactam
keywords: ESBL; KPC; Pseudomonas aeruginosa; cIAI; cUTI