Predictors of Clostridioides difficile recurrence across a national cohort of veterans in outpatient, acute, and long-term care settings

Haley J Appaneal,Maya Beganovic,Sanja Avramovic,Aisling R Caffrey,Kerry L Laplante

doi:10.1093/ajhp/zxz032

Abstract

The greatest challenge in treating Clostridioides difficile infection (CDI) is disease recurrence, which occurs in about 20% of patients, usually within 30 days of treatment cessation. We sought to identify independent predictors of first recurrence among a national cohort of veterans with CDI. We conducted a case-control study among acute and long-term care Veterans Affairs (VA) inpatients and outpatients with a first CDI episode (positive stool sample for C. difficile toxin[s] and receipt of at least 2 days of CDI treatment) between 2010 and 2014. Cases experienced first recurrence within 30 days from the end of treatment. Controls were those without first recurrence matched 4:1 to cases on year, facility, and severity. Multivariable conditional logistic regression was used to identify predictors of first recurrence. We identified 32 predictors of first recurrence among 974 cases and 3,896 matched controls. Significant predictors included medication use prior to (probiotics, fluoroquinolones, laxatives, third- or fourth-generation cephalosporins), during (first- or second-generation cephalosporins, penicillin/amoxicillin/ampicillin, third- and fourth-generation cephalosporins), and after CDI treatment (probiotics, any antibiotic, proton pump inhibitors [PPIs], and immunosuppressants). Other predictors included current biliary tract disease, malaise/fatigue, cellulitis/abscess, solid organ cancer, medical history of HIV, multiple myeloma, abdominal pain, and ulcerative colitis. In a large national cohort of outpatient and acute and long-term care inpatients, treatment with certain antibiotics, PPIs, immunosuppressants, and underlying disease were among the most important risk factors for first CDI recurrence.

Highlights

Clostridium difficile is a gram-positive anaerobe that causes infectious diarrhea that can range in severity from mild to severe disease.[1]
Results highlight an important opportunity for antibiotic stewardship programs to target inappropriate antibiotic use and unnecessary pump inhibitors (PPIs) use, especially in patients with a history of Clostridium difficile infection (CDI)
A CDI episode was defined as a positive stool sample for C. difficile toxin(s) regardless of testing method during an inpatient admission or an outpatient encounter and receipt of at least two days of standard CDI treatment.[1, 19]

Summary

Introduction

Clostridium difficile is a gram-positive anaerobe that causes infectious diarrhea that can range in severity from mild to severe disease.[1] One of the greatest challenges in treating Clostridium difficile infection (CDI) effectively is the high recurrence rate. Reported CDI recurrence rates vary substantially from about 5% to as high as 50% due to differing prevalence in risk factors and definitions for recurrence between studies, recurrence typically occurs in about 20% of patients.[2,3,4,5] Following the first recurrence, the risk of an additional episode of CDI increases to between 45% and 65%.6. Recurrent CDI is challenging to treat and causes significant morbidity, mortality and reductions in quality of life.[7] Identifying those at highest risk for recurrence could allow for targeted initial CDI management and may improve patient outcomes.[2]

Methods

Results

Conclusion