Karlowsky James A, Lob Sibylle H, Raddatz Janet, DePestel Daryl D, Young Katherine, Motyl Mary R, Sahm Daniel F
Department of Scientific Affairs, IHMA, Schaumburg, Illinois, USA.
Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Clin Infect Dis. 2021 Jun 15;72(12):2112-2120. doi: 10.1093/cid/ciaa381.
Multidrug-resistant (MDR) bacteria are frequently defined using the criteria established by Magiorakos et al [Clin Microbiol Infect 2012;18:268-81]. Difficult-to-treat resistance (DTR) [Kadri et al, Clin Infect Dis 2018;67:1803-14] is a novel approach to defining resistance in gram-negative bacilli focusing on treatment-limiting resistance to first-line agents (all β-lactams and fluoroquinolones).
Clinical and Laboratory Standards Institute-defined broth microdilution minimum inhibitory concentrations (MICs) were determined for imipenem/relebactam, ceftolozane/tazobactam, and comparators against respiratory, intraabdominal, and urinary isolates of Enterobacterales (n = 10 516) and Pseudomonas aeruginosa (n = 2732) collected in 26 US hospitals in 2015-2017.
Among all Enterobacterales, 1.0% of isolates were DTR and 15.6% were MDR; 8.4% of P. aeruginosa isolates were DTR and 32.4% were MDR. MDR rates for Enterobacterales and DTR and MDR rates for P. aeruginosa were significantly higher (P < .05) in isolates collected in intensive care units (ICUs) than in non-ICUs and in respiratory tract isolates than in intraabdominal or urinary tract isolates. In addition, 82.4% of DTR and 92.1% of MDR Enterobacterales and 62.2% of DTR and 82.2% of MDR P. aeruginosa were imipenem/relebactam-susceptible, and 1.5% of DTR and 65.8% of MDR Enterobacterales and 67.5% of DTR and 84.0% of MDR P. aeruginosa were ceftolozane/tazobactam-susceptible.
MDR phenotypes defined using the Magiorakos criteria may overcall treatment-limiting resistance in gram-negative bacilli. In the US, DTR Enterobacterales were infrequent, while MDR Enterobacterales isolates and DTR and MDR P. aeruginosa were common. Imipenem/relebactam (Enterobacterales, P. aeruginosa) and ceftolozane/tazobactam (P. aeruginosa) retained in vitro activity against most DTR and MDR isolates.
多重耐药（MDR）细菌通常根据马焦拉科斯等人制定的标准进行定义[《临床微生物感染》2012年；18:268 - 281]。难治疗耐药（DTR）[卡德里等人，《临床感染病杂志》2018年；67:1803 - 1814]是一种定义革兰氏阴性杆菌耐药性的新方法，重点关注对一线药物（所有β - 内酰胺类和氟喹诺酮类）的治疗限制性耐药。
采用临床和实验室标准协会定义的肉汤微量稀释最低抑菌浓度（MIC），测定亚胺培南/瑞来巴坦、头孢洛扎/他唑巴坦及对照药物对2015 - 2017年在美国26家医院收集的肠杆菌科细菌（n = 10516）和铜绿假单胞菌（n = 2732）呼吸道、腹腔和尿液分离株的活性。
在所有肠杆菌科细菌中，1.0%的分离株为DTR，15.6%为MDR；8.4%的铜绿假单胞菌分离株为DTR，32.4%为MDR。重症监护病房（ICU）分离的肠杆菌科细菌的MDR率以及铜绿假单胞菌的DTR和MDR率显著高于非ICU（P < 0.05），呼吸道分离株的上述比率高于腹腔或尿液分离株。此外，82.4%的DTR和92.1%的MDR肠杆菌科细菌以及62.2%的DTR和82.2%的MDR铜绿假单胞菌对亚胺培南/瑞来巴坦敏感，1.5%的DTR和65.8%的MDR肠杆菌科细菌以及67.5%的DTR和84.0%的MDR铜绿假单胞菌对头孢洛扎/他唑巴坦敏感。
使用马焦拉科斯标准定义的MDR表型可能高估了革兰氏阴性杆菌中的治疗限制性耐药。在美国，DTR肠杆菌科细菌不常见，而MDR肠杆菌科细菌分离株以及DTR和MDR铜绿假单胞菌很常见。亚胺培南/瑞来巴坦（针对肠杆菌科细菌、铜绿假单胞菌）和头孢洛扎/他唑巴坦（针对铜绿假单胞菌）对大多数DTR和MDR分离株仍具有体外活性。
