JAMA Internal Medicine May 2015 Volume 175, Number5
R1 조한샘 / Prof. 이창균
INTRODUCTION
•Clostridium difficile is the most common cause ofinfectious diarrhea in hospitalized patients
•Important goal must be the prevention of subsequentepisodes
•Approximately 20% of patients will experience 1 or morerecurrences
•Therapeutic options are limited
•To minimize modifiable risk factors such as
•Antibiotic exposure
•Proton pump inhibitor (PPI) use
•PPIs are still overprescribed
INTRODUCTION
•Although the association between PPI use and incidentCDI is well established the evidence implicating PPIs withrecurrence 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 initialCDI recurrence.
•To assess what proportion of patients who developed CDI weretaking a PPI for a non–evidence based indication
•To evaluate whether physicians discontinued unnecessary PPIs inthe context of CDI
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 hospitalizedwithin the previous 30
•Symptoms and PCR for toxin B
•Exclusion
•Without 3 episodes of diarrhea
•Ileus, toxic megacolon, colitis results from computed tomography orcolonoscopy, or autopsy-proven disease
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
METHODS
Exposure Assessment
•Continuous PPI use
•Exposure defined as the receipt of a PPI at the time of the initial episode of Cdifficile
•Ongoing exposure for at least 75%of days in the hospital in those who remainedhospitalized
•Discharge prescription for a PPI that was valid beyond 90 days after the initialepisode
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
METHODS
•Antibiotic Reexposure
•99%(752 of 754) of patients exposed to antibiotics before the initialepisode 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 recurrenceand death as a competing risk
•Also performed competing risk regression to determine subdistributionhazard ratios for both end points
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 90days (67.5%)
RESULTS
RESULTS
RESULTS
•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 remainedindependently associated with the rate of recurrence
•age older than 75 years
•continuous PPI use
•length of stay
•vancomycin treatment of the initial episode
RESULTS
RESULTS
RESULTS
•Among 458 of 754 patients (60.7%) who were taking aPPI at CDI diagnosis
•90 of these 191 PPI users (47.1%) had an evidence-basedindication for therapy
• M/C evidence based indication : Age older than 60 years with 2other concurrent risk factors for peptic ulcer disease
•discontinued in only 3 of 458 patients(0.6%).
RESULTS
CONCLUSION
•Patients with continuous PPI use remained at elevatedrisk of CDI recurrence
•New drugs and fecal transplantation may represent futuretreatments of CDI
•Prevention of CDI recurrence should begin with thecessation of unnecessary PPIs
•We suggest that the cessation of unnecessary PPI use should beconsidered at the time of CDI diagnosis.