Evans Scott R, Hujer Andrea M, Jiang Hongyu, Hill Carol B, Hujer Kristine M, Mediavilla Jose R, Manca Claudia, Tran Thuy Tien T, Domitrovic T Nicholas, Higgins Paul G, Seifert Harald, Kreiswirth Barry N, Patel Robin, Jacobs Michael R, Chen Liang, Sampath Rangarajan, Hall Thomas, Marzan Christine, Fowler Vance G, Chambers Henry F, Bonomo Robert A
Center for Biostatistics in AIDS Research and the Department of Biostatistics, Harvard University, Boston, Massachusetts, USA
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
J Clin Microbiol. 2016 Dec 28;55(1):134-144. doi: 10.1128/JCM.01524-16. Print 2017 Jan.
The widespread dissemination of carbapenem-resistant Acinetobacter spp. has created significant therapeutic challenges. At present, rapid molecular diagnostics (RMDs) that can identify this phenotype are not commercially available. Two RMD platforms, PCR combined with electrospray ionization mass spectrometry (PCR/ESI-MS) and molecular beacons (MB), for detecting genes conferring resistance/susceptibility to carbapenems in Acinetobacter spp. were evaluated. An archived collection of 200 clinical Acinetobacter sp. isolates was tested. Predictive values for susceptibility and resistance were estimated as a function of susceptibility prevalence and were based on the absence or presence of beta-lactamase (bla) NDM, VIM, IMP, KPC, and OXA carbapenemase genes (e.g., bla, bla, and bla found in this study) against the reference standard of MIC determinations. According to the interpretation of MICs, 49% (n = 98) of the isolates were carbapenem resistant (as defined by either resistance or intermediate resistance to imipenem). The susceptibility sensitivities (95% confidence interval [CI]) for imipenem were 82% (74%, 89%) and 92% (85%, 97%) for PCR/ESI-MS and MB, respectively. Resistance sensitivities (95% CI) for imipenem were 95% (88%, 98%) and 88% (80%, 94%) for PCR/ESI-MS and MB, respectively. PRIMERS III establishes that RMDs can discriminate between carbapenem resistance and susceptibility in Acinetobacter spp. In the context of a known prevalence of resistance, SPVs and RPVs can inform clinicians regarding the best choice for empiric antimicrobial therapy against this multidrug-resistant pathogen.
耐碳青霉烯类不动杆菌属细菌的广泛传播带来了重大的治疗挑战。目前，能够识别这种表型的快速分子诊断方法（RMDs）尚无商业产品。对两种用于检测不动杆菌属细菌中碳青霉烯类耐药/敏感基因的RMD平台进行了评估，即聚合酶链反应（PCR）结合电喷雾电离质谱法（PCR/ESI-MS）和分子信标（MB）。对200株不动杆菌临床分离株的存档样本进行了检测。根据β-内酰胺酶（bla）NDM、VIM、IMP、KPC和OXA碳青霉烯酶基因（如本研究中发现的bla、bla和bla）的有无，针对最低抑菌浓度（MIC）测定的参考标准，估算了药敏和耐药的预测值。根据MICs的判读，49%（n = 98）的分离株对碳青霉烯类耐药（定义为对亚胺培南耐药或中介）。PCR/ESI-MS和MB对亚胺培南的药敏敏感性（95%置信区间[CI]）分别为82%（74%，89%）和92%（85%，97%）。PCR/ESI-MS和MB对亚胺培南的耐药敏感性（95%CI）分别为95%（88%，98%）和88%（80%，94%）。PRIMERS III证实，RMDs能够区分不动杆菌属细菌的碳青霉烯类耐药和敏感情况。在已知耐药率的情况下，特异度预测值（SPVs）和阳性预测值（RPVs）可为临床医生提供针对这种多重耐药病原体进行经验性抗菌治疗的最佳选择的参考信息。
