Department of Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Department of Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland; National Institute for Health and Medical Research (INSERM) European Unit (IAME), University of Fribourg, Fribourg, Switzerland; Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland; Institute for Microbiology, University of Lausanne and University Hospital Centre, Lausanne, Switzerland.
J Glob Antimicrob Resist. 2022 Sep;30:445-450. doi: 10.1016/j.jgar.2022.05.011. Epub 2022 May 23.
Multidrug-resistant Acinetobacter baumannii (MDR-Ab), particularly strains producing oxacillinase (OXA)-type carbapenemases, have rapidly emerged in health care settings as a frequent cause of serious infections with limited treatment options. This study evaluated the in vitro activity of sulbactam (SUL) combined with durlobactam (DUR) against a collection of carbapenemase-producing A. baumannii, and investigated the mechanisms of resistance.
Susceptibility testing was performed on 100 isolates by either broth microdilution or by the Epsilometer test. Isolates were screened for the insertion sequence ISAba1 upstream of the intrinsic chromosomal blaADC by polymerase chain reaction (PCR). Whole genome sequencing was performed on 25 SUL-DUR resistant isolates, and analyses were performed using the Center for Genomic Epidemiology platform. Target gene sequences were compared to A. baumannii American Type Culture Collection (ATCC) 17978.
SUL-DUR exhibited excellent activity against A. baumannii isolates with susceptibility levels as follows: amikacin, 18%; colistin, 91%; cefepime, 5%; imipenem, 0%; minocycline, 46%; SUL, 3%; sulbactam-cefoperazone, 8%; SUL-DUR, 71% (based on a breakpoint at 4 mg/L). Twenty-five non-New Delhi metallo-ß-lactamase (NDM)-producing isolates had SUL-DUR MIC values >4 mg/L, amongst which 14 isolates showed substitutions in penicillin-binding protein (PBP)3, previously shown to be associated with SUL-DUR resistance. Substitutions that have not previously been described were detected in SUL-DUR targets, namely PBP1a, PBP1b, PBP2, and PBP3. By contrast, there was no evidence of the involvement of permeability or efflux.
SUL-DUR exhibited excellent in vitro antibacterial activity against carbapenemase-producing A. baumannii isolates. Amongst the 25 resistant isolates, we identified a number of mechanisms which may be contributing factors, in particular PBP substitutions and the production of specific beta-lactamases.
耐多药鲍曼不动杆菌（MDR-Ab），尤其是产生氧西林酶（OXA）型碳青霉烯酶的菌株，在医疗机构中迅速成为严重感染的常见原因，而治疗选择有限。本研究评估了舒巴坦（SUL）与多尼培南（DUR）联合应用对碳青霉烯酶产生的鲍曼不动杆菌的体外活性，并研究了耐药机制。
通过肉汤微量稀释法或 Epsilometer 试验对 100 株分离株进行药敏试验。通过聚合酶链反应（PCR）筛选插入序列 ISAba1 在固有染色体 blaADC 上游的鲍曼不动杆菌。对 25 株 SUL-DUR 耐药分离株进行全基因组测序，并在基因组流行病学中心平台上进行分析。将目标基因序列与鲍曼不动杆菌美国典型培养物保藏中心（ATCC）17978 进行比较。
SUL-DUR 对鲍曼不动杆菌分离株表现出极好的活性，其药敏水平如下：阿米卡星，18%；多粘菌素，91%；头孢吡肟，5%；亚胺培南，0%；米诺环素，46%；SUL，3%；舒巴坦-头孢哌酮，8%；SUL-DUR，71%（基于 4mg/L 的断点）。25 株非新德里金属β-内酰胺酶（NDM）产生分离株的 SUL-DUR MIC 值>4mg/L，其中 14 株分离株的青霉素结合蛋白（PBP）3 发生取代，先前的研究表明这与 SUL-DUR 耐药有关。在 SUL-DUR 靶点中检测到了以前未描述的取代，即 PBP1a、PBP1b、PBP2 和 PBP3。相比之下，没有证据表明涉及通透性或外排。
SUL-DUR 对碳青霉烯酶产生的鲍曼不动杆菌分离株具有极好的体外抗菌活性。在 25 株耐药分离株中，我们确定了一些可能的机制，特别是 PBP 取代和特定β-内酰胺酶的产生。
