Buyukyanbolu Ecem, Argotsinger Jill, Beck Eric T, Chamberland Robin R, Clark Andrew E, Daniels Anne R, Liesman Rachael, Fisher Mark, Gialanella Philip, Hand Jonathan, Harrington Amanda T, Humphries Romney M, Huse Holly, Hamilton-Seth Robert, Hankins Julia D, Kufel Wesley D, Riddell Scott W, Marino Jamie, Westblade Lars F, Mochon A Brian, Narayanan Navaneeth, Kirn Thomas J, Pierce Virginia M, Potula Raghava, Tekle Tsigereda, Simner Patricia J, Tibbetts Robert J, Vu Christine, Abbo Lilian M, Martinez Octavio, Dumm Rebekah E, Nicolau David P, Asempa Tomefa E
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
Advocate Lutheran General Hospital, Park Ridge, Illinois, USA.
Antimicrob Agents Chemother. 2025 Aug 6;69(8):e0037925. doi: 10.1128/aac.00379-25. Epub 2025 Jul 17.
Infections caused by carbapenem-resistant complex (ABC) are associated with high mortality rates and limited treatment options. This study aims to evaluate the activity of clinically utilized antimicrobials against a contemporary collection of ABC isolates with a predominant carbapenem-resistant phenotype. Geographically dispersed US medical centers ( = 22) provided non-duplicate respiratory and bloodstream ABC isolates for surveillance testing. Antimicrobial susceptibility testing was conducted by broth microdilution and interpreted according to Clinical & Laboratory Standards Institute (CLSI) and Food and Drug Administration (FDA) breakpoints. ABC isolates ( = 523) from respiratory tract (74.4%) and blood (25.6%) sources were recovered from patients (2023-2024). Forty percent were obtained from intensive care unit patients. Carbapenem non-susceptibility was observed in 76.9% of isolates and was more common among respiratory tract cultures. The addition of durlobactam to sulbactam decreased the MIC by three-doubling dilutions from 32 to 4 µg/mL, increasing the susceptibility rate to 96.9% from 33.8%. Genome sequencing of sulbactam-durlobactam non-susceptible isolates (16/523; = 3.1%) revealed MBL and non-enzymatic resistance mechanisms. Cefiderocol inhibited 93.5% and 76.1% of isolates at CLSI and FDA susceptible breakpoints, respectively. Minocycline susceptibility was <50%, while tigecycline and eravacycline MIC were 1/2 and 0.5/1 µg/mL, respectively. Sulbactam-durlobactam displayed high activity against sulbactam (95.4%), carbapenem (96.3%), and cefiderocol (95.2%) non-susceptible isolates. Susceptibility rates of clinically utilized antimicrobials against a US collection of ABC isolates ranged from 23% to 97%, with meropenem displaying the lowest rate and sulbactam-durlobactam demonstrating the highest overall rate. Sulbactam-durlobactam activity was preserved against sulbactam, carbapenem, and cefiderocol non-susceptible isolates among respiratory tract and bloodstream isolates.
耐碳青霉烯类复合菌（ABC）引起的感染与高死亡率和有限的治疗选择相关。本研究旨在评估临床使用的抗菌药物对当代一组以耐碳青霉烯类为主表型的ABC分离株的活性。美国各地分散的22家医疗中心提供了非重复的呼吸道和血流ABC分离株用于监测检测。采用肉汤微量稀释法进行药敏试验，并根据临床和实验室标准协会（CLSI）及美国食品药品监督管理局（FDA）的断点进行判读。从2023年至2024年的患者中分离出523株ABC分离株，其中呼吸道来源的占74.4%，血液来源的占25.6%。40%的分离株来自重症监护病房患者。76.9%的分离株对碳青霉烯类不敏感，在呼吸道培养物中更为常见。舒巴坦与度洛巴坦联合使用使最低抑菌浓度（MIC）从32 μg/mL降低了三个稀释倍数至4 μg/mL，敏感率从33.8%提高到96.9%。对舒巴坦-度洛巴坦不敏感的分离株（16/523；占3.1%）进行全基因组测序，发现了金属β-内酰胺酶（MBL）和非酶促耐药机制。头孢地尔在CLSI和FDA的敏感断点分别抑制了93.5%和76.1%的分离株。米诺环素的敏感率<50%，而替加环素和依拉环素的MIC分别为1/2和0.5/1 μg/mL。舒巴坦-度洛巴坦对舒巴坦（95.4%）、碳青霉烯类（96.3%）和头孢地尔（95.2%）不敏感的分离株显示出高活性。临床使用的抗菌药物对美国一组ABC分离株的敏感率在23%至97%之间，美罗培南的敏感率最低，舒巴坦-度洛巴坦的总体敏感率最高。舒巴坦-度洛巴坦对呼吸道和血流分离株中对舒巴坦、碳青霉烯类和头孢地尔不敏感的分离株仍保持活性。
