Bacterial Strain Type and Biomarkers Predict Mortality

Clostridium difficile genotype predicts mortality after C. difficile infection (CDI), and excess mortality correlates with genotype-specific changes in biomarkers.

The relationship between the specific bacterial strain types with changes in the host’s biomarkers strongly implicates inflammatory pathways as a factor in poor outcomes after CDI.

Scientists at the John Radcliffe Hospital (Oxford, UK) used multilocus sequence typing (MSLT) on strains isolated from C. difficile toxin enzyme immunoassay (EIA)-positive fecal samples from September 2006 to May 2011. The study involved 2,745 toxin-positive and 27,550 toxin-negative strains. The C. difficile toxin enzyme immunoassay used was from Meridian Bioscience (Cincinnati, OH, USA).

Overall, 14-day mortality was 13% in patients with EIA-positive samples versus 5% with EIA-negative samples. Strain polymerase chain reaction (PCR) ribotype 078/ST 11 was associated with the highest mortality at 25%, followed by PCR ribotype 27/ST 1 at 20%. Across a variety of blood or serum markers, the authors also found a significant variance in mean baseline neutrophil counts by genotype, and EIA-positivity versus EIA-negativity. Overall, biomarkers predicted 30% to 40% of strain-specific mortality differences.

Threshold levels of serum albumin equal to or less than 24.5 g/L, C- reactive protein (CRP) greater than 228 mg/L, white cell count (WBC) greater than 12 × 103 /µL, and increased respiratory rates were associated with an increased risk of all-cause mortality. A simple four variable prediction rule was devised based on these threshold levels and when tested on the initial data.

The authors concluded that MLST demonstrates that strain predicts mortality and severity biomarkers at both clade and individual sequence-type level. For patient monitoring, neutrophils/WBC ratios, CRP, and albumin are the key as C. difficile–associated biomarkers that are highly prognostic for short-term mortality. The study was published in the August 15, 2013, edition of the journal Clinical Infectious Diseases.

Related Links:

John Radcliffe Hospital

Meridian Bioscience