UCLA Clinical Microbiology Laboratory, Department of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
Front Cell Infect Microbiol. 2021 Mar 15;11:561880. doi: 10.3389/fcimb.2021.561880. eCollection 2021.
Carbapenem-resistant (CRKP) frequently causes hospital-acquired infections and is associated with high morbidity and mortality. CRKP can have multiple resistance mechanisms and only a few can be routinely detected by commercial molecular or phenotypic assays making surveillance for CRKP particularly challenging. In this report, we identified and characterized an unusual non-carbapenemase-producing CRKP carrying a rare plasmid-borne inducible AmpC gene, . The isolate was recovered from blood culture of a 67-year-old female presenting with sepsis post bladder surgery and ureteral stent removal. The primary isolate displayed an indeterminate susceptibility pattern for ceftriaxone by broth microdilution, but was susceptible by disk diffusion with one colony growing within the zone of inhibition. The ceftriaxone resistant colony was sub-cultured and had a minimum inhibitory concentration (MIC) of 2 ug/ml for imipenem (intermediate) and a zone size of 18 mm for ertapenem (resistant), but remained susceptible to cefepime and meropenem. Further phenotypic characterization of this sub-cultured isolate showed carbapenemase activity. Whole genome sequencing (WGS) revealed the presence of two subpopulations of a (MLST sequence type 11) from the primary blood culture isolate: one pan-susceptible to beta-lactams tested and the other resistant to the 3 generation cephalosporins and ertapenem. WGS analysis identified the resistant harboring IncFIB(K) and IncR plasmids and the presence of plasmid-borne beta-lactam resistance genes and , an inducible AmpC gene. Additional resistance genes against quinolones (), aminoglycoside (), sulfonamide (), and tetracycline ((A)) were also identified. DHA-1 positive have been previously identified outside the US, particularly in Asia and Europe, but limited cases have been reported in the United States and may be underrecognized. Our study highlights the importance of using both extended phenotypic testing and WGS to identify emerging resistance mechanisms in clinical Enterobacterales isolates with unusual antimicrobial resistance patterns.
耐碳青霉烯肠杆菌科细菌（CRKP）常引起医院获得性感染，与高发病率和死亡率相关。CRKP 可能具有多种耐药机制，并且仅少数机制可通过商业分子或表型检测常规检测，因此对 CRKP 的监测尤其具有挑战性。在本报告中，我们鉴定并表征了一种罕见的不产碳青霉烯酶的 CRKP，其携带一种罕见的可诱导 AmpC 基因。该分离株从一名 67 岁女性的血培养中分离出来，该女性在膀胱手术后和输尿管支架取出后出现败血症。初步分离株在肉汤微量稀释法中对头孢曲松表现出不确定的敏感性模式，但在纸片扩散法中，一个菌落生长在抑菌圈内时对头孢曲松敏感。头孢曲松耐药的菌落经过传代培养后，对亚胺培南的最小抑菌浓度（MIC）为 2 ug/ml（中介），对厄他培南的抑菌圈大小为 18mm（耐药），但对头孢吡肟和美罗培南仍敏感。对该传代培养分离株的进一步表型特征分析显示其具有碳青霉烯酶活性。全基因组测序（WGS）显示，来自原发性血培养分离株的 （MLST 序列类型 11）存在两种亚群：一种对测试的β-内酰胺类药物均敏感，另一种对第三代头孢菌素和厄他培南耐药。WGS 分析鉴定出该耐药株携带 IncFIB(K)和 IncR 质粒，以及携带质粒的β-内酰胺类耐药基因和，一个可诱导的 AmpC 基因。还鉴定了针对喹诺酮类（）、氨基糖苷类（）、磺胺类（）和四环素类（）的其他耐药基因（）。DHA-1 阳性的 已在除美国以外的地方被发现，特别是在亚洲和欧洲，但在美国报告的病例有限，可能被低估了。我们的研究强调了在具有不寻常抗菌药物耐药模式的临床肠杆菌科分离株中，使用扩展表型检测和 WGS 来识别新出现的耐药机制的重要性。
