Nguyen Lynn, Garcia Joshua, Gruenberg Katherine, MacDougall Conan
Department of Clinical Pharmacy, University of California San Francisco School of Pharmacy, 533 Parnassus Ave, U-585, Box 0622, San Francisco, CA, 94143-0622, USA.
Department of Pharmacy Practice, Marshall B. Ketchum University College of Pharmacy, Fullerton, CA, USA.
Curr Infect Dis Rep. 2018 Jun 6;20(8):23. doi: 10.1007/s11908-018-0629-6.
As the sixth most common nosocomial pathogen in the USA, Pseudomonas aeruginosa poses a significant threat to patients within the healthcare system. Its intrinsic and acquired resistance mechanisms also significantly limit the choices for antimicrobial therapy, prompting an increase in the research and development of antibacterial agents with enhanced activity against multidrug-resistant (MDR) P. aeruginosa. While many approved and pipeline antibiotics have activity against wild-type P. aeruginosa, only four new antibiotics have promising activity against MDR P. aeruginosa: ceftazidime-avibactam (Avycaz®), ceftolozane-tazobactam (Zerbaxa®), cefiderocol, and imipenem-cilastatin/relebactam. The goal of this paper is to review the epidemiology and mechanisms of resistance in P. aeruginosa as well as explore the newly approved and pipeline agents that overcome these mechanisms of resistance.
Ceftazidime-avibactam and ceftolozane-tazobactam are currently FDA-approved and available for use, while cefiderocol and imipenem-cilastatin/relebactam are in development. Current evidence suggests ceftazidime-avibactam and ceftolozane-tazobactam both may have a role in treatment of MDR P. aeruginosa infections. Ceftolozane-tazobactam appears to be modestly more potent against P. aeruginosa, but emergence of resistance has been noted in various reported cases. Trials are ongoing for cefiderocol and imipenem-cilastatin/relebactam and early results appear promising. The aforementioned agents fill important gaps in the antibiotic armamentarium, particularly for patients with MDR P. aeruginosa infections who otherwise have extremely limited and often toxic antibiotic options. However, resistance to all of these agents will likely emerge, and additional antibiotic development is warranted to provide sufficient options to successfully manage MDR P. aeruginosa infections.
作为美国第六大常见的医院病原体，铜绿假单胞菌对医疗系统中的患者构成重大威胁。其内在和获得性耐药机制也显著限制了抗菌治疗的选择，促使针对多重耐药（MDR）铜绿假单胞菌活性增强的抗菌药物的研发增加。虽然许多已批准和正在研发的抗生素对野生型铜绿假单胞菌有活性，但只有四种新抗生素对MDR铜绿假单胞菌有有前景的活性：头孢他啶-阿维巴坦（Avycaz®）、头孢洛扎-他唑巴坦（Zerbaxa®）、头孢地尔和亚胺培南-西司他丁/瑞来巴坦。本文的目的是综述铜绿假单胞菌的流行病学和耐药机制，并探索新批准和正在研发的克服这些耐药机制的药物。
头孢他啶-阿维巴坦和头孢洛扎-他唑巴坦目前已获美国食品药品监督管理局（FDA）批准并可使用，而头孢地尔和亚胺培南-西司他丁/瑞来巴坦正在研发中。目前的证据表明，头孢他啶-阿维巴坦和头孢洛扎-他唑巴坦在治疗MDR铜绿假单胞菌感染中都可能发挥作用。头孢洛扎-他唑巴坦对铜绿假单胞菌的活性似乎略强，但在各种报道的病例中已注意到耐药性的出现。头孢地尔和亚胺培南-西司他丁/瑞来巴坦的试验正在进行，早期结果似乎很有前景。上述药物填补了抗生素库中的重要空白，特别是对于患有MDR铜绿假单胞菌感染的患者，否则他们的抗生素选择极其有限且往往有毒性。然而，对所有这些药物的耐药性可能会出现，因此有必要进一步研发抗生素，以提供足够的选择来成功治疗MDR铜绿假单胞菌感染。
