1. JAMA Internal Medicine May 2015 Volume 175, Number5 R1 조한샘 / Prof. 이창균

2. INTRODUCTION Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients Important goal must be the prevention of subsequent episodes Approximately 20% of patients will experience 1 or more recurrences Therapeutic options are limited To minimize modifiable risk factors such as Antibiotic exposure Proton pump inhibitor (PPI) use PPIs are still overprescribed

3. INTRODUCTION Although the association between PPI use and incident CDI is well established the evidence implicating PPIs with recurrence is limited to a few conflicting studies The objectives of our study were 3-fold To determine whether PPI use was associated with a risk of initial CDI recurrence. To assess what proportion of patients who developed CDI were taking a PPI for a non–evidence based indication To evaluate whether physicians discontinued unnecessary PPIs in the context of CDI

4. METHODS Description of the Cohort Retrospective cohort study Initial episode of health care–associated CDI between January 1, 2010, and January 30, 2013 and who survived for a minimum of 15 days Health care–associated CDI cases were those in which Symptoms occurred more than 3 days after admission Symptoms caused readmission in a patient who had been hospitalized within the previous 30 Symptoms and PCR for toxin B Exclusion Without 3 episodes of diarrhea Ileus, toxic megacolon, colitis results from computed tomography or colonoscopy, or autopsy-proven disease

5. METHODS Description of the Cohort Recurrence of CDI Recurrent symptoms Second positive C. difficile PCR (15 and 90 days after) There were 809 patients identified 55 were excluded because they died before day 15 Cohort of 754 patients whose cases were analyzed

6. METHODS Exposure Assessment Continuous PPI use Exposure defined as the receipt of a PPI at the time of the initial episode of C difficile Ongoing exposure for at least 75%of days in the hospital in those who remained hospitalized Discharge prescription for a PPI that was valid beyond 90 days after the initial episode Other Demographics The treatment of the initial episode of CDI The unit that the infection was attributed to (medical, surgical, critical care) The admitting hospital Length of stay. Age, sex, and date of death (if deceased) Patient comorbidities Vancomycin-resistant enterococci Methicillin-resistant Staphylococcus aureus

7. METHODS Antibiotic Reexposure 99%(752 of 754) of patients exposed to antibiotics before the initial episode of C difficile Antibiotic reexposure data Process of Evaluating Indications for PPIs Use Reviewed the indications for PPI use through a medical record Reviewed by a second physician Statistical Analysis Statistical software (STATA, version 13; StataCorp LP) Cox proportional hazards model To determine the cause specific hazards ratios for both initial recurrence and death as a competing risk Also performed competing risk regression to determine subdistribution hazard ratios for both end points

8. RESULTS Among 754 eligible patients 52 deaths without recurrence (6.9%) 193 documented recurrences (25.6%) 157 recurrences (81.3%) occurred between days 15 and 56. 509 survivors without documented recurrence within 90 days (67.5%)

9. RESULTS

11. The PPI users differed from nonusers in multiple ways experience a CDI recurrence (28.8% vs 20.6%, P =.007) or to die (10.3% vs 4.7%, P =.007) within 15 to 90 days of the initial episode. In the multivariable analysis, the following remained independently associated with the rate of recurrence age older than 75 years continuous PPI use length of stay vancomycin treatment of the initial episode

12. RESULTS

14. Among 458 of 754 patients (60.7%) who were taking a PPI at CDI diagnosis 90 of these 191 PPI users (47.1%) had an evidence-based indication for therapy M/C evidence based indication : Age older than 60 years with 2 other concurrent risk factors for peptic ulcer disease discontinued in only 3 of 458 patients(0.6%).

15. RESULTS

16. CONCLUSION Patients with continuous PPI use remained at elevated risk of CDI recurrence New drugs and fecal transplantation may represent future treatments of CDI Prevention of CDI recurrence should begin with the cessation of unnecessary PPIs We suggest that the cessation of unnecessary PPI use should be considered at the time of CDI diagnosis.