766 infection control & hospital epidemiology july 2018, vol. 39, no. 7
probiotics is in part due to relative safety and public accep- tance, which is supported by a substantial body of evidence suggesting efficacy.9–11 The interpretation of clinical trials is complicated by differences in probiotic agents and intended use, that is, primary versus secondary prevention. If proven effective, certain probiotic strains would be a relatively simple, safe, low-cost solution likely to be accepted by patients. We evaluated the impact of a hospital-wide policy to prescribe
a probiotic mixture to eligible adult antibiotic recipients. Wechose an agent (Bio-K+, Laval,Quebec,Canada) containing 3 Lactobacillus spp: L. acidophilus (CL1285), L. casei (LBC80R), and L. rhamnosus (CLR2). This agent hasbeenproveneffective and safe by meta-analysis11 of 3 randomized trials12–14 and in a single center before-and-after quality improvement initiative.15 We report our findings from this quality improvement intervention.
methods Setting and Population
We performed a before-and-after quality improvement inter- vention at a 694-bed teaching hospital near Chicago, Illinois. We compared 12-month baseline (October 1, 2012, through September 30, 2013) and intervention periods (November 1, 2013, through October 31, 2014). October 2013 served as a 1-month run-in period, during which probiotic distribution was implemented. We excluded all patients on neonatal, pediatric, and oncology units. To minimize the risk of adverse events, we excluded patients with leukopenia (white blood cell count <1,000 cells per mm3), pancreatitis, or transplant recipients regardless of unit location. The institutional review board deemed this study to be a quality improvement inter- vention, and full review was waived.
Intervention
Patients who were to receive their initial dose of antibiotics at the project hospital were prescribed probiotic capsules (Bio-K+, Laval, Quebec, Canada) containing 100 billion colony-forming units (CFUs) of probiotic, which had pre- viously been confirmed.16 The organisms were L. acidophilus (CL1285), L. casei (LBC80R), and L. rhamnosus (CLR2); alphanumeric designations represent a company-assigned trademark. The 3-strain probiotic mixture was to be initiated within 12 hours of the initial antibiotic dose; thus, patients receiving antibiotics before hospital admission were ineligible. Recipients of perioperative antibiotic prophylaxis were also excluded. Patients restricted from oral intake were not given probiotic capsules; however, those receiving enteral tube feedings were provided with a commercially available liquid slurry of the same probiotic preparation. The 3-strain pro- biotic mixture was administered during the antibiotic course and for 5 days after the final dose of antibiotic. Discharged patients were sent home with probiotic to complete their
entire course. Inpatient probiotic distribution required phar- macist review of antibiotic prescriptions including a manual review of an automated printout of clinically ineligible patients. We were unable to build probiotic distribution through the clinical decision support system.
Observational Hospital-Level Study
Our primary outcome was the incidence of hospital-onset CDI among all patients on eligible units. We used a clinical definition of CDI,17 requiring the presence of symptoms, determined by the hospital epidemiologist, and detection of C. difficile in stool. Clostridium difficile was detected by polymerase chain reaction (Xpert PCR assay, Cepheid, Sunnyvale, CA) during the entire project. We did not monitor patients after hospital discharge. We calculated the incidence rate ratio (IRR) and 95% confidence intervals (CIs) expressed per 10,000 patient days. We used segmented regression analysis to compare the incidence during baseline and inter- vention periods, reporting deviations in level (ie, test for immediate intervention effect) and slopes (ie, test for a delayed
intervention effect). Given the decline in incidence during the final 6 months of the intervention and based on previously identified postintervention delays in reducing CDI,18 we per- formed a post hoc analysis comparing the incidence between the initial and final 6 months of the intervention. We obtained the number of community-onset (CO) cases of C. difficile reported to the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) during the project period, which included emergency department patients and those cultured during their first 3 hospital days; rates were reported by quarter. We evaluated the trend in CO cases and included the number of CO cases in the segmented regression models. To evaluate C. difficile testing intensity, we evaluated the frequency at which patients were tested hospital- wide, and we compared the proportion of tests positive for C. difficile toxin between baseline and intervention periods. We routinely conducted in-person meetings at the project hospital, during which no changes in infection prevention programs and no new antibiotic stewardship initiatives were reported.
Case-Control Study
To conduct a patient-level analysis, we performed a matched case-control study, sampling patients hospitalized during the intervention. We selected CDI case patients who were eligible to receive probiotic (ie, receipt of a therapeutic course of antibiotics on an intervention unit, without clinical exclusions, and not receiving antibiotics on admission), and who devel- oped CDI ≥24 hours after antibiotic exposure. Control patients (ie, no CDI identified) were pair-matched to case patients by age (±10 years), temporal proximity of antibiotic initiation date (±10 days), and geographic proximity (hospital unit) when antibiotics were started. Control patients had to
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