768 infection control & hospital epidemiology july 2018, vol. 39, no. 7
capsules alone (66%); a substantial minority (34%) received at least 1 dose as slurry. The mean age was 67 (±14 SD) years and the mean length of stay was 17 (±14 SD) days. On average, case patients had a worse severity of illness than control patients: 3.7 versus 3.3 (P=.004). The most common sources of admission were home (62%), nursing home (24%), or inter- facility acute-care transfer (11%). Case patients were no less likely to have received probiotic
than control patients: 18 of 68 (26%) versus 17 of 68 (25%). The mean number of days of probiotic receipt was similar for case patients and control patients: 4.4 days versus 3.9 days, respectively. In multivariable models, we found no protective effect from probiotics by either conditional logistic regression or proportional hazards models. By conditional logistic regression, factors associated with CDI were tube feeding (adjusted odds ratio [aOR], 4.6; 95% CI, 1.3–17; P=.02), chronic kidney disease (aOR, 4.2; 95% CI, 1.1–17; P=.04), high severity of illness (aOR, 2.6; 95% CI, 1.1–6.2, P=.03), and peptic ulcer disease (OR,5;95%CI,2.4–250; P=.007). Probiotic receipt did not reduce CDI risk (aOR, 0.95; 95% CI, 0.8–1.2; P=.65). Because missed doses were common, we looked for patterns
associated with missing a probiotic dose. Missing a dose was not associated with presence of a feeding tube, sex, comor- bidity, or day of the week. Because of variability in staffing, we expected that a specific day of the week might be associated with missing doses, but we detected no differences in probiotic receipt across days of the week.
discussion
In this large before-and-after evaluation of a probiotic agent to prevent CDI among hospital patients receiving antibiotic therapy, we found a possible delayed benefit from the inter- vention. Meta-analyses summarizing individual randomized controlled trials provide evidence that certain probiotic agents
on the detection of C. difficile with isolation of patients, the decline in CDI rate was not immediate but occurred over time.18 We speculate that the delayed probiotic effect could be due to several independent or synergistic factors. First, our intervention hospital had a relatively high baseline rate of CDI, which might have contributed to high-density environmental contamination. The effectiveness of a probiotic may be related to the environmental burden of C. difficile spores; for example, probiotic might be more effective during relatively low-inoculum exposures. Thus, a reduction in environmental burden (eg, surface contamination) would be needed before probiotic effect is realized. Such an explanation is supported by the known prolonged environmental survival of C. difficile spores.22 Second, probiotics might reduce the excretion of viable organisms, and because the intensity of environmental contamination contributes to patient acquisition,23 a gradual reduction in contamination would lead to reduced patient acquisition over time. Third, the possible ‘herd effect’ likely to result from saturating high-risk patients with probiotics was not achieved during our intervention given the substantial proportion of case patients ineligible for probiotic receipt (41%). Fourth, given the before-and-after design, enhance- ments or deteriorations in infection control practices may have been unrecognized by the project team. However, there were no changes in environmental cleaning policies, antimicrobial stewardship activities, or modifications to other infection control policies during the study period. Specifically, the laboratory assay (PCR) results for C. difficile toxin detection remained constant throughout the baseline and intervention periods. Because we were unable to electronically extract patient-
can significantly reduce the risk of CDI.9–11 Despite consistent findings across probiotic formulations (ie, low between-study heterogeneity), one challenge facing clinicians and institutions is to select the optimal probiotic agent. Here, 2 major decision points are (1) whether to choose bacterial probiotic (usually inclusive of a Lactobacillus spp.) or yeast probiotic (eg, Saccharomyces boulardii) and (2) whether the agent should have >1 organism. Such choices are driven by evidence of efficacy, safety, and cost. Because evidence from 3 randomized controlled trials and a single-center before-and-after study showed similar reductions in CDI, we chose a multispecies formulation comprising L. acidophilus (CL1285), L. casei (LBC80R), and L. rhamnosus (CLR2).12–15 Although our implementation did not reduce overall CDI incidence during the entire 12-month intervention period, we found a reduction in CDI during the final 6 months of the intervention. The delayed reduction in CDI rate is consistent with the
following prior studies. In a before-and-after intervention similar to ours, the CDI rate declined several months after introduction of probiotic.15 In a separate intervention focused
level antibiotic and probiotic receipt data, we evaluated the association between probiotic receipt and CDI through a matched case-control study. To control for known major confounders, we matched case-control pairs on age, patient- care unit, and date of onset for antibiotic administration. We found that cases had higher severity-of-illness scores than controls; however, after adjusting for severity of illness, we found no protective effect from the probiotic. Despite this negative finding,we expect that therewere critical unmeasured factors that increased risk of CDI among case patients. Ideally, we would have had comprehensive assessments of each patient’s severity of illness on initiation of antibiotics. Also, prehospitalization antibiotic exposure data would have been a useful surrogate for disruption of a patient’s microbiome, but it was not available.24 It is possible that the probiotic mixture had a beneficial
effect unmeasured in the case-control study, such as mod- ulating C. difficile in antibiotic recipients who were colonized but not symptomatic. Such a possibility is suggested by Freedberg et al25 in their proposed ‘herd effect’ of antibiotics, wherein antibiotics taken by individual patients puts other patients at risk for CDI.25 In the study by Freedberg et al, receipt of antibiotics by prior hospital room occupants was associated with increased risk for CDI in subsequent occupants
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