Tansarli Giannoula S, Falagas Matthew E, Fang Ferric C
Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA.
Department of Medicine, Alfa Institute of Biomedical Science, Athens, Greece.
J Clin Microbiol. 2025 Jan 31;63(1):e0097724. doi: 10.1128/jcm.00977-24. Epub 2024 Dec 12.
The laboratory diagnosis of infection (CDI) is controversial. Nucleic acid amplification tests (NAAT) and toxin enzyme immunoassays (EIA) are most widely used, often in combination. However, the interpretation of a positive NAAT and negative toxin immunoassay (NAAT+/EIA-) is uncertain. PubMed and EMBASE were searched for studies reporting clinical outcomes in NAAT+/EIA- versus NAAT+/EIA+ patients. Forty-six studies comprising 33,959 patients were included in this meta-analysis. All-cause mortality (RR 0.96, 95% CI 0.80-1.15), attributable mortality (RR 0.61, 95% CI 0.20-1.91), fulminant CDI (RR 0.83, 95% CI 0.57-1.20), radiographic evidence of CDI (RR 0.87, 95% CI 0.65-1.16), total CDI complications (RR 0.95, 95% CI 0.59-1.53), colectomies (RR 0.78, 95% CI 0.34-1.79), and ICU admission (RR 1.04, 95% CI 0.84-1.30) did not significantly differ between NAAT+/EIA- and NAAT+/EIA+ patients. However, rates of recurrent (RR 0.62, 95% CI 0.50-0.77) or severe (RR 0.74, 95% CI 0.63-0.88) CDI were significantly lower in NAAT+/EIA- patients than in NAAT+/EIA+ patients. The pooled prevalence of NAAT+/EIA- patients who were treated with antibiotics for CDI was 73.4% (pooled proportion 0.72, 95% CI 0.52-0.88). NAAT+/EIA- patients have lower rates of recurrence and are at reduced risk for severe CDI compared with NAAT+/EIA+ patients but have a risk of CDI-related complications and mortality comparable to that of NAAT+/EIA+ patients. Toxin results cannot rule in or rule out CDI, and the decision whether to treat symptomatic NAAT+/EIA- patients for CDI should be based on clinical presentation and not on the toxin result.IMPORTANCE infection (CDI) is a common cause of healthcare-associated infections and the leading cause of antibiotic-associated diarrhea. However, the laboratory diagnosis of CDI, primarily done by nucleic acid amplification test (NAAT) and enzyme immunoassay (EIA), is controversial, especially in patients who test positive by NAAT but negative by EIA. In this systematic review, we compared the clinical outcomes of NAAT+/EIA- versus NAAT+/EIA+ patients and found that the two groups have similar risk of mortality and CDI-related complications. However, NAAT+/EIA- patients had significantly lower rates of recurrence and severe CDI than NAAT+/EIA+ patients, and most NAAT+/EIA- patients received CDI therapy. Toxin testing can help to predict the likelihood of CDI recurrence or severe infection, but the toxin result should not be a determining factor in the administration of CDI therapy. The decision on whether to treat NAAT+/EIA- patients should be based on clinical assessment.
艰难梭菌感染（CDI）的实验室诊断存在争议。核酸扩增检测（NAAT）和毒素酶免疫测定（EIA）应用最为广泛，且常常联合使用。然而，NAAT检测结果为阳性而毒素免疫测定结果为阴性（NAAT+/EIA-）的情况该如何解读尚不确定。检索了PubMed和EMBASE数据库，查找报告NAAT+/EIA-患者与NAAT+/EIA+患者临床结局的研究。本荟萃分析纳入了46项研究，共33959例患者。全因死亡率（风险比0.96，95%置信区间0.80 - 1.15）、归因死亡率（风险比0.61，95%置信区间0.20 - 1.91）、暴发性CDI（风险比0.83，95%置信区间0.57 - 1.20）、CDI的影像学证据（风险比0.87，95%置信区间0.65 - 1.16）、CDI总并发症（风险比0.95，95%置信区间0.59 - 1.53）、结肠切除术（风险比0.78，95%置信区间0.34 - 1.79）以及入住重症监护病房（ICU）（风险比1.04，95%置信区间0.84 - 1.30）在NAAT+/EIA-患者与NAAT+/EIA+患者之间并无显著差异。然而，NAAT+/EIA-患者的复发性（风险比0.6)2，95%置信区间0.50 - 0.77）或严重CDI（风险比0.74，95%置信区间0.63 - 0.88）发生率显著低于NAAT+/EIA+患者。接受抗生素治疗CDI的NAAT+/EIA-患者的合并患病率为73.4%（合并比例0.72，95%置信区间0.52 - 0.88）。与NAAT+/EIA+患者相比，NAAT+/EIA-患者的复发率较低，发生严重CDI的风险也较低，但发生CDI相关并发症和死亡的风险与NAAT+/EIA+患者相当。毒素检测结果既不能确诊也不能排除CDI，对于有症状的NAAT+/EIA-患者是否进行CDI治疗的决策应基于临床表现，而非毒素检测结果。重要性艰难梭菌感染（CDI）是医疗相关感染的常见原因，也是抗生素相关性腹泻的主要原因。然而，CDI的实验室诊断主要通过核酸扩增检测（NAAT）和酶免疫测定（EIA）进行，存在争议，尤其是在NAAT检测为阳性但EIA检测为阴性的患者中。在本系统评价中，我们比较了NAAT+/EIA-患者与NAAT+/EIA+患者的临床结局，发现两组的死亡率和CDI相关并发症风险相似。然而，NAAT+/EIA-患者的复发率和严重CDI发生率显著低于NAAT+/EIA+患者，且大多数NAAT+/EIA-患者接受了CDI治疗。毒素检测有助于预测CDI复发或严重感染的可能性，但毒素检测结果不应成为CDI治疗给药的决定因素。对于是否治疗NAAT+/EIA-患者的决策应基于临床评估。
