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electronic newsletter. No other novel interventions specific to CDI were implemented. Our institution’s CDI testing throughout the study period was
unchanged. CDI testing was performed on liquid stools only (ie, the laboratory rejected formed stool samples) and the initial test was an immunoassay for the CDI antigen (glutamate dehydro- genase) and toxin A and B immunoassay (Quik Chek Complete, Techlab). Samples that were antigen positive but toxin negative underwent reflex nucleic acid amplification test (NAAT) testing, with an overall turnaround time of <24 hours. Toxigenic CDI was only defined as positive for both GDH and toxin or positive for both GDH and NAAT. For patients diagnosed with CDI, both the clinical pathway and treatment order set provided severity- based treatment recommendations. The BPA (Supplementary Fig. 3) was active for inpatients and
was generated upon chart entry only on patients with a positive Clostridoides difficile laboratory result without active orders for CDI treatment. Medications that suppressed theBPAincluded oral and intravenous metronidazole, oral vancomycin, or fidaxomicin. Accepting the BPA would direct the provider to the severity-based treatment order set. The BPA would remain active within the patient chart for 36 hours after the reporting of a positive result unless the alert was accepted or CDI treatment was ordered.
Outcomes
We assessed provider adherence to practice guidelines, with non- compliant therapy defined as wrong drug, dose, or route based on institutional guidelines (Supplementary Fig. 2), before and after implementation of this clinical decision support tool. The primary outcome was guideline-compliant initial CDI treatment. Secondary end points included resolution of diarrhea (<3 stools/day), length of stay, in-hospital mortality, 30-day recurrence, and readmission rate.
Statistical analysis
Descriptive statistics were reported for demographic data. Continuous variables were analyzed using a 2-tailed Student t test, or for nonnormally distributed data, the Mann-Whitney U test, and categorical variables were analyzed using the χ2 test with an α set at <0.05 for statistical significance. A power calculation indi- cated 130 total patients were required for 80% power to detect an increase in guideline-based prescribing from 40% to 70%.
Results
Atotal of 278 and409 laboratory-confirmed cases ofCDI occurred in 2013 and 2016,
respectively.Atotal of 145 charts were reviewed with 14 patients excluded based on the prespecified criteria (Figure 1), resulting in a total of 66 preimplementation controls and 65 postim- plementation cases. As subjects were not matched, there were some notable differences between the 2 groups (Supplementary Table 2). More subjects in the preimplementation group were immunocom- promised and more subjects in the postimplementation group had a history of
previousCDI.CDI severity was comparable between the 2 groups, with a slightly higher proportion of cases in the postimplementation group having mild-to-moderate infection. Accordingly, the postimplementation group had more cases of mild-to-moderate infection and, thus, a slightly higher proportion of cases initially treated with metronidazole monotherapy. Patients withCDI weremore likely to receive guideline-compliant
initialCDI therapy after implementation of the BPA and severity- based order set: 44 of 65 (67.7%) in the postimplementation
Holly L. Reed et al
Fig. 1. Study participants. Note. BPA, best practice alert.
group versus 26 of 66 (39.4%) in the preimplementation group (P = .014) (Table 1). The BPA was generated for 57 of the 65 postimplementation
cases who had no active orders for CDI treatment with alert accep- tance in 28 of 57 encounters (49%). When accepted, orders were subsequently signed from the CDI order set in 23 of 28 cases (82%), correlating with an overall positive response rate of 40%. As an institutional comparison, of all the 2016 nonquality metric BPAs, the positive response rate was 8.3%.
Discussion
Wehave demonstrated a significant improvement in the appropri- ateness of CDI therapy after implementation of the intervention. The increase in guideline-based prescribing was due to improve- ments in initial agent selection, route of administration, and antimicrobial dose (Supplementary Fig. 4). Prior to the implemen- tation of the BPA and linked order set, providers were more likely to order intravenous metronidazole, which has demon- strated inferior mortality outcomes compared to oral metronida- zole.8 Although we were not adequately powered to identify a statistically significant difference in CDI outcomes, it is reasonable to hypothesize based on other trials that improved guideline adherence will lead to fewer recurrences, improved lengths of stay, hospital costs, and readmission rates. A previous study using a BPA and linked CDI treatment order
set, activated by either an order for a C. difficile nucleic acid ampli- fication test (NAAT) or oral vancomycin, led to a significant increase in order-set utilization; however, the clinical decision sup- port tool did not increase guideline-based prescribing.9 This BPA was generated upon CDI test ordering; thus, many BPAs would have occurred in patients not needing therapy, resulting in alert fatigue. Also, patients prescribed CDI therapies other than oral vancomycin were not included and may have contributed to the lack of improvement in guideline-based prescribing. Finally, hav- ing the BPA linked to CDI test ordering may have increased the prescribing of CDI therapies for patients without a confirmed infection, leading to unnecessary antibiotic use and a risk for tox- icity or resistance. Numerous factors likely led to the improvement in initial
guideline-based prescribing in the postimplementation group. First, the BPA alerted providers to positive CDI results when no therapy orders were active, highlighting critical patient information that most clinicians would act on. The alert provided an immediate link to actionable severity-based treatment recommendations approved by the institution. Interestingly, only a portion of post- BPA cases had CDI treatment ordered through the BPA and order set, suggesting that education, either through the BPA and order set or the CDI clinical pathway, may have contributed to improved
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