Clinical complications in patients with primary and recurrent Clostridioides difficile infection: A real-world data analysis

Abstract

Objective: Clostridioides difficile infection and recurrent C. difficile infection result in substantial economic burden and healthcare resource use. Sepsis and bowel surgery are known to be serious complications of C. difficile infection. This study evaluated clinical complications in patients with C. difficile infection and recurrent C. difficile infection during a 12-month period following the primary C. difficile infection. Methods: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus™ database was conducted for patients aged 18–64 years with an index C. difficile infection episode requiring inpatient stay or an outpatient visit for C. difficile infection followed by a C. difficile infection treatment. Each C. difficile infection episode ended after a 14-day C. difficile infection-claim-free period was observed. Recurrent C. difficile infection was defined as a further C. difficile infection episode within an 8-week window following the claim-free period. Clinical complications were documented over 12 months of follow-up and stratified by the number of recurrent C. difficile infection episodes (0 rCDI, 1 rCDI, 2 rCDI, and 3+ rCDI). Results: In total, 46,571 patients with index C. difficile infection episode were included. During the 6-month pre-index, the mean (standard deviation) baseline Charlson comorbidity index score, by increasing the recurrent C. difficile infection group, was 1.2 (1.9), 1.5 (2.2), 1.8 (2.3), and 2.3 (2.5). During the 12-month follow-up, sepsis occurred in 16.5%, 27.3%, 33.1%, and 43.3% of patients, and subtotal colectomy or diverting loop ileostomy was performed in 4.6%, 7.3%, 8.9%, and 10.5% of patients, respectively, by increasing the recurrent C. difficile infection group. Conclusions: Reduction in recurrent C. difficile infection is an important step to reduce the burden of serious clinical complications, and new treatments are needed to reduce C. difficile infection recurrence.

Mortality, healthcare resource utilization, and cost among Medicare beneficiaries with Clostridioides difficile infection with and without sepsis

“… 18 A single-center study of patients with rCDI found a 22% BSI rate after CDI treatment with antibiotics. 20 In a claims study among a younger population (mean age 48 years) with CDI, sepsis occurred in 16.5%, 27.3%, 33.1%, and 43.3% of patients after 0, 1, 2, and 3+ rCDI episodes, respectively, during the 12-month follow-up, 19 supporting our finding of increased incidence among those with rCDI. The mean time to CDI recurrence in that study was approximately 30 days, similar to our study (range 31.6–35.0 days).…”

“… 17 Previous studies report that sepsis occurs in 16–43% of patients with CDI, with higher frequency after rCDI and for older patients. 18 – 21 This rate is much higher than the 6.0% incidence of sepsis for all hospitalized patients aged ⩾20 years in the United States. 22 …”

“…17 Previous studies report that sepsis occurs in 16-43% of patients with CDI, with higher frequency after rCDI and for older patients. [18][19][20][21] This rate is much higher than the 6.0% incidence of sepsis for all hospitalized patients aged ⩾20 years in the United States. 22 Clostridioides difficile rarely survives in the blood since it is an anaerobic bacterium; therefore, sepsis associated with CDI is typically caused by other bacteria and is hypothesized to result from C. difficile breaking down the mucosal barrier of the colon, resulting in bacterial translocation into the bloodstream.…”

What’s a Biofilm?—How the Choice of the Biofilm Model Impacts the Protein Inventory of Clostridioides difficile

“…If conditions are favorable, e.g., after antibiotic-induced dysbiosis when the reduced microbiome fails to convert primary bile acids into secondary bile acids, C. difficile spores are able to germinate to successively colonize the large intestine ( Theriot et al, 2014 ; Pike and Theriot, 2020 ). Even though antibiosis mostly stops the acute infection, C. difficile spores as well as some vegetative cells survive in the intestine and can subsequently cause a relapse as soon as antibiotic concentrations are sufficiently low ( Goulding et al, 2009 ; Chilton et al, 2018 ; Castro-Córdova et al, 2020 ; Feuerstadt et al, 2021 ; Normington et al, 2021 ). Initially, sporulation was assumed to be one of the major prerequisites for C. difficile’s persistence under clinical circumstances.…”

Gut microbiota and microbiota-based therapies for Clostridioides difficile infection

“…Patients with CDI often present with watery diarrhea and abdominal pain, but symptoms can also include fever, hypotension, or ileus in more severe cases (5); complications can include sepsis or colectomy/ileostomy (6)(7)(8)(9)(10)(11). Testing for CDI is recommended for patients who have unexplained, new onset diarrhea (at least 3 unformed stools over ≥24 h) using a nucleic acid amplification test alone or as part of an algorithm that includes glutamate dehydrogenase or stool toxin test (12).…”