Relationship Between Bacterial Strain Type, Host Biomarkers, and Mortality in Clostridium difficile Infection

作者：Ann Sarah Walker, David W. Eyre, David H. Wyllie, Kate E. Dingle, David Griffiths, Brian S. F. Shine, Sarah J Oakley, Lily O’Connor, JOHN M. T. FINNEY, Alison J Vaughan, Derrick W. Crook, Mark H. Wilcox, Tim Peto · 发表于：Clinical Infectious Diseases · 年份：2013 · DOI：10.1093/cid/cit127 · 被引用次数：217 · 研究领域：Clostridium difficile and Clostridium perfringens research、Yersinia bacterium, plague, ectoparasites research、Nosocomial Infections in ICU

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 × 10(9) neutrophils/L for clades 5, 2 and 1, respectively, vs 7.0 × 10(9) neutrophils/L in EIA-negative controls (P < .0001) and 7.9 × 1...