Chakraborty Deepika, Bhatia Mohit, Gupta Pratima, Nagaraj Geetha, Shamanna Varun, Srinitha P, Ashwini K V, Ravikumar K L
Microbiology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, Delhi, IND.
Microbiology, All India Institute of Medical Sciences, Rishikesh, IND.
Cureus. 2025 Mar 9;17(3):e80312. doi: 10.7759/cureus.80312. eCollection 2025 Mar.
Carbapenem-resistant (CRKP) is a major public health concern, particularly in immunocompromised and critically ill patients. Colistin and tigecycline are among the last-resort treatment options, while the primary driver of CRKP emergence is carbapenemase production, especially carbapenemase (KPC) and metallo-β-lactamase (MBL). A thorough understanding of its resistance mechanisms is essential for selecting the most effective antimicrobial therapy. This study aimed to evaluate the diagnostic accuracy of the modified Hodge test (MHT) and modified carbapenem inactivation method (mCIM) in detecting molecular resistance mechanisms in CRKP clinical isolates.
This exploratory study consisted of 65 CRKP isolates, which were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonik GmbH, Bremen, Germany). Antimicrobial susceptibility testing was performed using the BD Phoenix system. The test isolates were subjected to MHT and mCIM and later shipped to the Central Research Laboratory (CRL), Bengaluru, India, where they were subjected to polymerase chain reaction (PCR) and whole-genome sequencing (WGS).
PCR detected , , , and genes in 79.7%, 10.2%, 64.4%, and 1.7% CRKP isolates, respectively. The PCR results were concordant with WGS. The MHT demonstrated an overall sensitivity of 60.3%, specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 4.2% for detecting carbapenemase production. It showed the highest sensitivity and specificity for (100%) and (75%) genes, respectively, with the highest PPV for (91.4%) and NPV for (100%). However, agreement between MHT and PCR for carbapenemase detection was negligible (Kappa: 0.049, p=0.223). A minimal but statistically significant agreement was noted for detection (Kappa: 0.314, p=0.007), while no significant agreement was observed for , , or genes. The mCIM had an overall sensitivity of 3.63%, specificity of 100%, PPV of 100%, and NPV of 1.8%. It exhibited the highest sensitivity (4.3%) and specificity (100%) for , with the highest PPV for (100%), and NPV for (98.1%). No statistically significant agreement was found between mCIM and PCR for carbapenemase detection (Kappa: 0.001, p=0.850).
Comprehensive assessment of the diagnostic accuracy of MHT and mCIM using WGS across a broad spectrum of multi-drug-resistant (MDR) organisms should be conducted at multiple centers to produce reliable data that can guide better clinical management of the patients.
耐碳青霉烯类肺炎克雷伯菌（CRKP）是一个重大的公共卫生问题，在免疫功能低下和重症患者中尤为如此。黏菌素和替加环素是最后的治疗选择之一，而CRKP出现的主要驱动因素是碳青霉烯酶的产生，尤其是碳青霉烯酶（KPC）和金属β-内酰胺酶（MBL）。全面了解其耐药机制对于选择最有效的抗菌治疗至关重要。本研究旨在评估改良 Hodge 试验（MHT）和改良碳青霉烯灭活方法（mCIM）在检测CRKP临床分离株分子耐药机制方面的诊断准确性。
本探索性研究包括65株CRKP分离株，采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）（德国不来梅布鲁克道尔顿公司）进行鉴定。使用BD Phoenix系统进行药敏试验。将受试分离株进行MHT和mCIM检测，随后运往印度班加罗尔的中央研究实验室（CRL），在那里进行聚合酶链反应（PCR）和全基因组测序（WGS）。
PCR分别在79.7%、10.2%、64.4%和1.7%的CRKP分离株中检测到 、 、 和 基因。PCR结果与WGS结果一致。MHT检测碳青霉烯酶产生的总体敏感性为60.3%，特异性为100%，阳性预测值（PPV）为100%，阴性预测值（NPV）为4.2%。它对 基因（100%）和 基因（75%）显示出最高的敏感性和特异性，对 基因（91.4%）显示出最高的PPV，对 基因（100%）显示出最高的NPV。然而，MHT与PCR在碳青霉烯酶检测方面的一致性可忽略不计（Kappa值：0.049，p = 0.223）。在 检测方面发现了最小但具有统计学意义的一致性（Kappa值：0.314，p = 0.007），而在 、 或 基因方面未观察到显著一致性。mCIM的总体敏感性为3.63%，特异性为100%，PPV为100%，NPV为1.8%。它对 显示出最高的敏感性（4.3%）和特异性（100%），对 显示出最高的PPV（100%），对 显示出最高的NPV（98.1%）。在碳青霉烯酶检测方面，mCIM与PCR之间未发现统计学意义上的一致性（Kappa值：0.001，p = 0.850）。
应在多个中心对多种多药耐药（MDR）生物体使用WGS全面评估MHT和mCIM的诊断准确性，以产生可靠数据，指导对患者更好的临床管理。
