Characterizing Risk Factors for Clostridioides difficile Infection among Hospitalized Patients with Community-Acquired Pneumonia

Abstract

Objective: Hospitalized patients with community-acquired pneumonia (CAP) are at risk of developing Clostridioides difficile infection (CDI). We developed and tested clinical decision-rules for identifying CDI risk in this patient population. Methods: The study was a single-center retrospective, case-control analysis of hospitalized adult patients empirically treated for CAP between January 1, 2014 and March 3, 2018. Differences between cases (CDI diagnosed within 180 days following admission) and controls (no test result indicating CDI during the study period) with respect to pre-hospitalization variables were modeled to generate propensity scores. Post-admission variables were used to predict case status on each post-admission day where: a) ≥1 additional case was identified, and b) each model strata contained ≥15 subjects. Models were developed and tested using Optimal Discriminant Analysis and Classification Tree Analysis. Results: Forty-four cases and 181 controls were included. The median time to diagnosis was 50 days post-admission. After weighting, three models were identified (20-, 117-, and 165-days post-admission). The day 20 model yielded the greatest [weighted (w)] accuracy (wROC area=0.826) and the highest chance-corrected accuracy (wESS=65.3). Having a positive culture (odds 1:4, p=0.001), receipt of ceftriaxone + azithromycin for a defined infection (odds 3:5, p=0.006), and continuation of empiric broad-spectrum antibiotics with activity against P. aeruginosa when no pathogen was identified (odds 1:8, p=0.013) were associated with CDI on day 20. Conclusion: Three models were identified that accurately predicted CDI in hospitalized patients treated for CAP. Antibiotic use increased the risk of CDI in all models, underscoring the importance of antibiotic stewardship.

Potential Cost Savings Associated with Targeted Substitution of Current Guideline-Concordant Inpatient Agents with Omadacycline for the Treatment of Adult Hospitalized Patients with Community-Acquired Bacterial Pneumonia at High Risk for Clostridioides difficile Infections: Results of Healthcare-Decision Analytic Model from the United States Hospital Perspective

“…There are (1) well-documented concerns with HCA-CDIs [8,10,11], (2) clinical and economic consequences associated with HCA-CDIs [9][10][11][29][30][31][35][36][37][38], and (3) a need for better proactive primary HCA-CDI prevention strategies [14,15,20]. As such, the intent of this study was to assess the economic impact of prioritizing the use of omadacycline (an agent approved for the treatment of adult patients CABP that has a documented lower propensity to cause CDI [21][22][23][24]), over other guideline-concordant inpatient therapies (fluoroquinolones and ceftriaxone) [19], in hospitalized CABP patients at high risk for CDI [3].…”

“…As such, the intent of this study was to assess the economic impact of prioritizing the use of omadacycline (an agent approved for the treatment of adult patients CABP that has a documented lower propensity to cause CDI [21][22][23][24]), over other guideline-concordant inpatient therapies (fluoroquinolones and ceftriaxone) [19], in hospitalized CABP patients at high risk for CDI [3]. It is well documented that the use of guideline-concordant antibiotics such as fluoroquinolones and the advanced generation cephalosporins are associated with increased CDI risks [1][2][3][4][5][6][7]16,19] (especially in CABP patients at an increased risk of developing CDI [18,20,25]), and CDI rates can be reduced by limiting their use [26][27][28]. For this study, patients with a DRS ≥ 6 were considered high risk [3].…”

“…In the model, the use of guidelineconcordant CABP inpatient treatments (i.e., fluoroquinolones and ceftriaxone) was replaced with omadacycline. The underlying model assumptions were: (1) CDI rates in hospitals can be reduced by limiting the use of broad-spectrum antibiotics such as fluoroquinolones and ceftriaxone [20,[26][27][28], (2) omadacycline has a lower propensity to induce CDI relative to current guideline-concordant inpatient CABP treatments [1][2][3][4][5][6][7][21][22][23], and (3) omadacycline has the potential to minimize CDI events [21,25]. For the study population, it is estimated that 1 million adult patients in the United States of America are hospitalized with suspected or documented CABP annually [17] and 10% of CABP admissions occur in patients with a DRS ≥ 6 [3,21] (Table 1).…”

“…Despite their increased propensity to cause CDIs, especially in patients at an increased risk of developing CDI, third-generation cephalosporins and fluoroquinolones continue to be the preferred first-line agents for hospitalized patients with suspected or documented CABP [1][2][3][4][5][6][7]16,19]. In a recent real-world evidence study, hospitalized CABP patients who received ceftriaxone plus azithromycin, one of the mostly used guidelineconcordant CABP treatment regimens, were at substantially higher odds of developing HCA-CDI relative to other treatments [20].…”