Lee Helen S, Plechot Kamryn, Gohil Shruti, Le Jennifer
Department of Pharmacy, University of California Irvine Health, Orange, CA, USA.
Department of Medicine, Division of Infectious Diseases, University of California Irvine, School of Medicine, Irvine, CA, USA.
Infect Dis Ther. 2021 Jun;10(2):687-697. doi: 10.1007/s40121-021-00417-7. Epub 2021 Mar 26.
Clostridium difficile infection (CDI) is a leading cause of healthcare-associated infections, accounting for significant disease burden and mortality. The clinical spectrum of C. difficile ranges from asymptomatic colonization to toxic megacolon and fulminant colitis. CDI is characterized by new onset of ≥ 3 unformed stools in 24 h and is confirmed by laboratory test for the presence of toxigenic C. difficile. Currently, laboratory tests to diagnose CDI include toxigenic culture, glutamate dehydrogenase (GDH), nucleic acid amplification test (NAAT), and toxins A/B enzyme immunoassay (EIA). The sensitivities of these tests are variable with toxin EIA ranging from 53 to 60% and with NAAT at about 95%. Overall, the specificity is > 90% for these methods. However, the positive predictive value (PPV) depends on the disease prevalence with lower CDI rates associated with lower PPVs.Notably, the widespread use of the highly sensitive NAAT and its relatively lower clinical specificity have led to overdiagnosis of C. difficile by identifying carriers when NAAT is used as the sole diagnostic method. Overdiagnosis of C. difficile has resulted in unwarranted treatment, possibly attributing to resistance to metronidazole and vancomycin, increased risk for overgrowth of vancomycin-resistant enterococci strains in stool specimens, and increased hospitalization thereby impacting patient safety and healthcare costs.Strategies to optimize the clinical sensitivity and specificity of current laboratory tests are critical to differentiate the clinical CDI from colonization. To achieve high diagnostic yield, if preagreed institutional criteria for stool submission are not used, a multistep approach to CDI diagnosis is recommended, such as either GDH or NAAT followed by toxins A/B EIA in conjunction with laboratory stewardship by evaluating C. difficile test orders for appropriateness and providing feedback. Furthermore, antimicrobial stewardship, along with provider education on appropriate testing for C. difficile, is vital to differentiate CDI from colonization.
艰难梭菌感染（CDI）是医疗保健相关感染的主要原因，造成了重大的疾病负担和死亡率。艰难梭菌的临床谱范围从无症状定植到中毒性巨结肠和暴发性结肠炎。CDI的特征是24小时内出现≥3次不成形大便，并通过实验室检测产毒艰难梭菌来确诊。目前，诊断CDI的实验室检测包括产毒培养、谷氨酸脱氢酶（GDH）、核酸扩增试验（NAAT）以及毒素A/B酶免疫测定（EIA）。这些检测的敏感性各不相同，毒素EIA的敏感性为53%至60%，NAAT约为95%。总体而言，这些方法的特异性>90%。然而，阳性预测值（PPV）取决于疾病患病率，CDI发病率较低时PPV也较低。值得注意的是，高敏感性NAAT的广泛使用及其相对较低的临床特异性导致当将NAAT用作唯一诊断方法时，通过识别携带者而过度诊断艰难梭菌。艰难梭菌的过度诊断导致了不必要的治疗，这可能归因于对甲硝唑和万古霉素的耐药性、粪便标本中万古霉素耐药肠球菌菌株过度生长的风险增加以及住院时间延长，从而影响患者安全和医疗成本。优化当前实验室检测的临床敏感性和特异性的策略对于区分临床CDI和定植至关重要。为了获得高诊断率，如果未使用预先商定的粪便送检机构标准，建议采用多步骤的CDI诊断方法，例如先进行GDH或NAAT检测，然后进行毒素A/B EIA检测，并通过评估艰难梭菌检测医嘱的适宜性并提供反馈来进行实验室管理。此外，抗菌药物管理以及对医疗服务提供者进行关于艰难梭菌适当检测的教育，对于区分CDI和定植至关重要。
