Decreased phagocytosis and intracellular killing of bacteria in leukocytes of geriatric patients with Clostridioides difficile infections.

ABSTRACT

INTRODUCTION: Patients suffering from a Clostridioides (C.) difficile infection have a higher overall mortality than patients with similar co-morbidities. METHODS: Whole blood samples of 15 patients with C. difficile enteritis and 15 control patients matched for age and sex were used to analyse the capacity of blood phagocytes to internalize and kill encapsulated Escherichia (E.) coli. The median age of C. difficile patients and control patients was 81 and 82 years, respectively. Blood samples were co-incubated with E. coli for 15 or 30min. After 15min of co-incubation, extracellular bacteria were killed by gentamicin for 15-45 minutes. Then eukaryotic cells were lysed with distilled water, and the number of intracellular bacteria per ml whole blood was determined by quantitative plating on agar plates. Both groups were compared by Mann-Whitney U-test. RESULTS: After 15 or 30min of co-incubation, blood phagocytes from patients with C. difficile enteritis showed a reduced density of phagocytosed or adherent bacteria in comparison to blood phagocytes from control patients (15min p=0.046, 30min p=0.005). The density of intracellular bacteria decreased less rapidly over time in the blood from C. difficile patients [median Δlog CFU/ml x h (25th/ 75th percentile) -0.893 (-1.893/ -0.554) versus -1.483 (-2.509/ -1.028); p=0.02]. In line with these results, the percentage of intracellularly killed bacteria was decreased in phagocytes from C. difficile-infected patients compared to controls (median intracellular killing rate 64.3% for blood phagocytes from C. difficile patients versus 81.9% for blood phagocytes from control patients within 30 min of co-incubation, p = 0.048). CONCLUSION: Blood phagocytes from patients with C. difficile enteritis exhibited a reduced capacity to phagocytose and kill bacteria in comparison to blood phagocytes from age- and sex-matched control patients. Patients with C. difficile infection may have a higher disposition to develop infectious diseases than age- and sex-matched control patients.