Infection Control & Hospital Epidemiology
Table 1. (Continued ) Patient
32 33
43
Organism CR-KP
CR-KP
Isolate Source Respiratory
Respiratory
Epidemiologic Classification Unrelated MDRO
No B1 exposure
Note. MDR-PA, multidrug-resistant Pseudomonas aeruginosa; CR-KP, carbapenem-resistant Klebsiella pneumoniae. aIsolate unavailable for molecular analysis. bPossible outbreak: patients whose death occurred within 10 days of bronchoscope B1 exposure such that subsequent recovery and epidemiologic classification of isolates from clinical
cultures could not be assessed. cPseudo-outbreak: patients with isolates obtained from culture during exposure to bronchoscope B1 who had no subsequent recovery of outbreak-related isolates. dOutbreak: patients with isolates recovered from a clinical culture ≥1 day after bronchoscope B1 exposure.
Clinical Outcome Alive
B1 borescopy and culture
Borescopy revealed that the lumen of B1 was physically defective and contained proteinaceous debris. Culture of bronchoscope B1 in December 2014 identified 3 CR-KP and 1 MDR-PA isolates.
Bacterial genotyping
PFGE demonstrated that the 3 CR-KP B1 scope isolates and the subset of CR-KP isolates were genetically related (data not shown). Of the 33 case patients, 16 patients did not have MDR- PA or CR-KP isolates available for WGS (Fig. 1). Phylogenetic analysis of the 24 isolates available for genomic comparison from 17 case patients revealed clustering of patient- and bronchoscope- derived isolates that was concordant with the epidemiology. Overall, 7 CR-KP patient isolates were highly related to the B1 isolate CR-KP112 with ≤4 SNP differences identified (Fig. 2A). Of these patients, 6 had exposure to bronchoscope B1 prior to becoming CR-KP culture positive. One patient (patient 15) was exposed to B1 after CR-KP culture positivity, supporting patient 15 as a possible index patient. The B1 isolates CR-KP113 and CR-KP114 were nearly identical to CR-KP112, with ≤3 SNP differences. Isolate CR-KP106 collected from patient 33 who lacked B1 exposure showed 510 SNP differences from B1 isolate CR-KP112 (Fig. 2A). Isolate CR-KP103, collected 12 days after B1 exposure from patient 32, had 30,206 SNP differences from B1 isolate CR-KP112, suggesting that B1 was not the source of this patient’s CR-KP infection. Moreover, 12 MDR-PA patient isolates clustered with B1
isolate MDR-PA114 on the phylogenetic tree with ≤6 SNP dif- ferences (Fig. 2B). One isolate from patient 26 (MDR-PA012), collected 56 days after B1 exposure, had >29,000 SNP differences from isolate MDR-PA014, indicating that B1 was an unlikely source of this patient’s MDR-PA–positive culture. In addition, 7 patients with B1 exposure had clinical cultures
positive for both CR-KP and MDR-PA (Fig. 1, patients 18, 19, 21, 24, 26, 28, and 29). Of 5 patients with both MDR-PA and CR-KP isolates available for WGS, 4 were genetically related to isolates recovered from bronchoscope B1 (Fig. 2A and B, patients 18, 21, 24, and 28). Together, these genomic data sug- gest transmission to patients of CR-KP and MDR-PA from bronchoscope B1. We identified 6 case patients without B1 exposure during
the cluster’s peak period, including 1 patient whose isolate (CR-KP111) was genetically related to the outbreak (13 SNP differences) (Figs. 1 and 2A). No epidemiologic link to the MICU cluster was identified, suggesting an undetected horizontal transmission route.
Clinical histories and epidemiologic designation
Of the 23 patients with B1 exposure, only 1 patient (patient 32) was considered unrelated to the outbreak because the clinical CR-KP isolate was genetically distinct from the CR-KP isolate recovered from the B1 bronchoscope (Table 1; Fig. 2). Three patients (patients 1, 5, and 15) were considered possible index patients. Of the remaining 19 patients with exposure to the B1 bronchoscope, 4 patients with MDR-PA or CR-KP recovered from follow-up respiratory cultures were classified as “outbreak” cases. However, 5 patients died within 10 days with no other clinical specimens classified as “possible outbreak.” Furthermore, 9 patients whose follow-up respiratory cultures were MDRO negative and 1 patient without follow-up respiratory cultures were characterized as “pseudo-outbreak” cases. Isolates from 8 B1-exposed patients were unavailable for WGS. In all, 10 B1-exposed patients died: by definition, all 5 patients classified as “possible outbreak” died; 3 of 4 patients classified as “outbreak” died; and 2 patients classified as “pseudo-outbreak” died. Our investigation did not include an analysis of attributable mortality.
Discussion
We have described the contamination of a single bronchoscope with 2 different MDR pathogens and an outbreak and pseudo- outbreak that involved at least 19 patients. We presume that horizontal transmission from a contaminated bronchoscope to patients undergoing bronchoscopy was the source of infection among outbreak and possible outbreak cases, and we hypothesize that the pseudo-outbreak occurred due to contamination of patient specimens as they were being withdrawn from the bronchoscope, a phenomenon that has been previously descri- bed.16 However, we cannot exclude transient colonization. Although pseudo-outbreaks are not considered true infections, they can nonetheless lead to adverse patient outcomes due to receipt of unnecessary antimicrobial therapy or other treatments. Our investigation revealed 2 putative CR-KP index patients
(patients 5 and 15). The temporal proximity of patient 15’s infection with subsequent B1-related CR-KP infections suggests that this patient was the likely index case. However, the 21 SNP differences between CR-KP isolates obtained from patient 5 (CR-KP102) and B1 (CR-KP112) do not rule out the possibility that patient 5 was the index case (Fig. 2A). After detecting microbial contamination of B1, UPMC-P
instituted bedside precleaning of bronchoscopes with an enzy- matic solution with a goal of reducing the likelihood of luminal biofilm formation. More recently, bronchoscope storage was reconfigured so the flexible portion of each device would hang
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