van Duin David, Bonomo Robert A
Division of Infectious Diseases, University of North Carolina, Chapel Hill.
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.
Clin Infect Dis. 2016 Jul 15;63(2):234-41. doi: 10.1093/cid/ciw243. Epub 2016 Apr 20.
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.
头孢洛扎/他唑巴坦和头孢他啶/阿维巴坦是两种新型的β-内酰胺/β-内酰胺酶复合抗生素。这些抗生素的抗菌谱包括多重耐药（MDR）革兰氏阴性菌（GNB），包括铜绿假单胞菌。头孢他啶/阿维巴坦对产生肺炎克雷伯菌碳青霉烯酶的耐碳青霉烯肠杆菌科细菌也有活性。然而，阿维巴坦不能使金属β-内酰胺酶（如新型德里金属β-内酰胺酶）失活。头孢洛扎/他唑巴坦和头孢他啶/阿维巴坦都只有静脉制剂，肾功能正常的患者每日给药3次。临床试验表明，在治疗复杂性尿路感染和复杂性腹腔内感染（与甲硝唑合用时）时，这两种药物与对照药物相比无劣效性。肺炎研究的结果尚未报道。总之，头孢洛扎/他唑巴坦和头孢他啶/阿维巴坦是两种新型的第二代头孢菌素/β-内酰胺酶抑制剂组合。在进行适当的试验后，它们可能被证明对治疗多重耐药革兰氏阴性菌感染有用。抗菌药物管理对于保持这些药物的活性至关重要。
