316 Table 1. Characteristics of Outbreaksa


No. Date 1


2 Organism Feb 12 Mar 13


Acinetobacter baumannii


Klebsiella pneumoniae


Cluster: No. of Related Isolates


3


A: 28 B: 2 C: 2


3 4


5 6 7 8


Jun 15 Jul 15


Aug 15 Dec 15 Apr 16 Jun 16


K. pneumoniae


Pseudomonas aeruginosa


A. baumannii P. putida


K. pneumoniae


Clostridium difficile


Total: 32 7 8


5 3 9


A: 2 B: 2 C: 2


9 Sep 16 C. difficile


Total: 6 4


Molecular Typing Method


PFGE PFGE


Duration of Transmission, Days


19


865 3


13


PFGE PFGE


PFGE PFGE


PFGE & WGS WGS


29 42


80 1


39 4


15 35


WGS 67


Transmission Route


Trauma ICU


ERCP ERCP ERCP


Bronchoscope Bronchoscope


Medical ICU


Bronchoscope Gastroscope Trauma Floor


Post Anesthesia Unit Pulmonology Floor


Medical ICU


Infections Potentially Prevented:


7-Day Intervention 1


20 0b 0b


5 5


3 0 5


0b 0b 0b


1 Total: 40


Note. PFGE, pulsed-field gel electrophoresis; WGS, whole-genome sequencing; ICU, intensive care unit; ERCP, endoscopic retrograde cholangiopancreatography. aThe correct transmission route was identified by the data mining program for all outbreaks. bOnly 2 isolates; cannot prevent any infections.


infected by the route. We arrive at the formula S by maximizing this expression in θ, which occurs at θ=b/r, and b, which occurs at either 0 or a. Because b=0 is a degenerate solution, it is disre- garded. The final score is the log of this maximum likelihood. The score above represents a nonnormalized log-likelihood.


Because it is not normalized, it is suitable for ranking routes but is not comparable across time as the number of case patient changes. Therefore, we estimated an extreme value statistic as the probability a route would score at least as highly as its observed score under the assumption that the case patients were uniformly randomly sampled (the null hypothesis). This P value is estimated numerically using importance sampling from the observed data. Researchers were initially blinded to the true routes of transmis-


sion in this analysis. However, it became clear during the develop- ment of the approach that this significantly reduced our ability to identify and correct data processing and modeling problems. For example, the charge codes for gastroscope procedures initially were not properly extracted and grouped from the EHR and therefore could not be identified in the analysis. On review, the correct charge codes for procedures using gastroscopes were grouped together as described above. The analysis was rerun, and the cor- rect exposure route was identified.


Results


The characteristics of the 9 outbreak investigations during the study period are shown in Table 1. For some investigations, molecular typing revealed several separate clusters. For example, for investigation no. 2, there were 2 clusters involving 2 isolates each. For 2 C. difficile outbreaks (nos. 8 and 9; 22%), epidemiologic investigation revealed that transmission occurred in the nursing


units where the patients resided. Furthermore, 3 investigations (33%) involved Klebsiella pneumoniae, 1 of which represented a polyclonal ERCP-related outbreak (no. 2),3 and 1 each involved bronchoscopy (no. 3) and gastroscopy (no. 7).12 In addition, 2 Acinetobacter baumanni investigations were determined to have been transmitted in intensive care units (nos. 1 and 5). One out- break each of Pseudomonas aeruginosa (no. 4) and P. putida (no. 6) were also considered to involve bronchoscopy as the source. All but 1 outbreak had ranges of 2–9 case patients with control


populations of ~4,000 to 56,000 patients (data not shown), depend- ing on the duration of the outbreak. The remaining outbreak (no. 2) had 28 case patients with 130,000 control patients. Overall, out- breaks had 185 average charge transactions per patient, 2 average room transactions per patient, and 263,777 total possible routes of transmission explored by the data mining program. The data mining program detected the correct routes of trans-


mission on the eighth patient of the ERCP outbreak and all other previous outbreaks on the second positive isolate of each out- break’s respective timeline. For example, for investigation no. 4, Pseudomonas aeruginosa transmission related to a bronchoscope, the bronchoscopy procedure was detected in 100% of cases from case 2 to case 6 (OR, 138; P=.02) on the second case (Fig. 1). Figure 2 shows investigation no. 3, Klebsiella pneumoniae trans- mission related to a bronchoscope. The bronchoscope is persist- ently ranked the highest plausible transmission route starting at the second patient (OR =140; P=.021). Table 1 displays the trans- mission routes that were both determined independently by infec- tion prevention and by the data mining program. Potential infections prevented are shown in Table 1 based upon


a 7- or 14-day intervention period given the delay in plausible intervention with real-time WGS and data mining analysis. In


Infections Potentially Prevented:


14-Day Intervention 1


20 0b 0b


3 4


2 0 3


0b 0b 0b


1 Total: 34


Alexander J. Sundermann et al


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