Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection.
Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection.
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DOI：
10.1093/cid/cit127
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发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
Infections in Oxfordshire Research Database
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文献类型：
--
作者：
Walker AS;Eyre DW;Wyllie DH;Dingle KE;Griffiths D;Shine B;Oakley S;O'Connor L;Finney J;Vaughan A;Crook DW;Wilcox MH;Peto TE;Infections in Oxfordshire Research Database
艰难梭菌基因型预测1893例酶免疫测定阳性/培养阳性成人的14天死亡率过高的死亡率与生物标志物的基因型特异性变化相关，强烈暗示炎症途径是不良结局的主要影响因素。聚合酶链反应核糖体型078/ST 11（进化枝5）与高死亡率相关;持续监测仍然是必要的。背景：尽管人们对生物标志物很感兴趣，但它们对临床结果的影响和细菌菌株的变异很少被综合数据库研究。 方法：从2006年9月至2011年5月，从英国牛津郡（约60万人）艰难梭菌毒素酶免疫测定（EIA）阳性粪便样本中分离的菌株进行多位点序列分型。 比较连续C.使用考克斯和针对人口统计学/临床因素调整的正态回归，对来自不同进化枝/序列类型（ST）和EIA阴性对照的艰难梭菌感染（CDIs）进行比较。结果：2222例成人中2745例EIA阳性样本（中位数78岁）的14天死亡率为13%，而20722例成人中27550例EIA阴性样本（中位数74岁）的14天死亡率为5%（绝对归因死亡率为7.7%; 95%CI为6.4%-9.0%）。 进化枝5的CDIs死亡率最高（25% [16/63];聚合酶链反应（PCR）核糖型078/ST 11），然后是进化枝2（20% [111/560]; 99%PCR核糖型027/ST 1）与进化枝1（12% [137/1168];校正P <0.0001）。在进化枝1内，ST 44（PCR核糖体型015）中14天死亡率仅为4%（84个中的3个）（相对于其它进化枝1，调整的P = 0.05）。平均基线中性粒细胞计数也因基因型而显著不同：分支5、2和1分别为12.4、11.6和9.5 × 109中性粒细胞/L，EIA阴性对照组为7.0 × 109中性粒细胞/L（P <0.0001），ST 44为7.9 × 109中性粒细胞/L（P = 0.08）。C.对死亡率和中性粒细胞/白色细胞计数（rho = 0.48）、C反应蛋白（rho = 0.43）、嗜酸性粒细胞计数（rho =-0.45）和血清白蛋白（rho =-0.47）的艰难梭菌型特异性影响。生物标志物预测了30%-40%的分支特异性死亡率差异。结论C. difficile基因型预测死亡率，并且过度死亡率与生物标志物的基因型特异性变化相关，强烈暗示炎症途径是CDI后不良结局的主要影响。PCR核糖体型078/ST 11（进化枝5）导致严重的CDI;因此持续的监测仍然是必要的。
Clostridium difficile genotype predicts 14-day mortality in 1893 enzyme immunoassay–positive/culture-positive adults. Excess mortality correlates with genotype-specific changes in biomarkers, strongly implicating inflammatory pathways as a major influence on poor outcome. Polymerase chain reaction ribotype 078/ST 11(clade 5) is associated with high mortality; ongoing surveillance remains essential. Background. Despite substantial interest in biomarkers, their impact on clinical outcomes and variation with bacterial strain has rarely been explored using integrated databases. Methods. From September 2006 to May 2011, strains isolated from Clostridium difficile toxin enzyme immunoassay (EIA)–positive fecal samples from Oxfordshire, United Kingdom (approximately 600 000 people) underwent multilocus sequence typing. Fourteen-day mortality and levels of 15 baseline biomarkers were compared between consecutive C. difficile infections (CDIs) from different clades/sequence types (STs) and EIA-negative controls using Cox and normal regression adjusted for demographic/clinical factors. Results. Fourteen-day mortality was 13% in 2222 adults with 2745 EIA-positive samples (median, 78 years) vs 5% in 20 722 adults with 27 550 EIA-negative samples (median, 74 years) (absolute attributable mortality, 7.7%; 95% CI, 6.4%–9.0%). Mortality was highest in clade 5 CDIs (25% [16 of 63]; polymerase chain reaction (PCR) ribotype 078/ST 11), then clade 2 (20% [111 of 560]; 99% PCR ribotype 027/ST 1) versus clade 1 (12% [137 of 1168]; adjusted P < .0001). Within clade 1, 14-day mortality was only 4% (3 of 84) in ST 44 (PCR ribotype 015) (adjusted P = .05 vs other clade 1). Mean baseline neutrophil counts also varied significantly by genotype: 12.4, 11.6, and 9.5 × 109 neutrophils/L for clades 5, 2 and 1, respectively, vs 7.0 × 109 neutrophils/L in EIA-negative controls (P < .0001) and 7.9 × 109 neutrophils/L in ST 44 (P = .08). There were strong associations between C. difficile-type-specific effects on mortality and neutrophil/white cell counts (rho = 0.48), C-reactive-protein (rho = 0.43), eosinophil counts (rho = −0.45), and serum albumin (rho = −0.47). Biomarkers predicted 30%–40% of clade-specific mortality differences. Conclusions. C. difficile genotype predicts mortality, and excess mortality correlates with genotype-specific changes in biomarkers, strongly implicating inflammatory pathways as a major influence on poor outcome after CDI. PCR ribotype 078/ST 11 (clade 5) leads to severe CDI; thus ongoing surveillance remains essential.
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