856 infection control & hospital epidemiology july 2018, vol. 39, no. 7


figure 2. Temporal evolution of the S. pyogenes outbreak. Duplicate isolates are not reflected in the table. There may be >1 strain on some dates. Isolates from staff members are not reflected in this figure. NOTE. WGS, whole-genome sequencing.


Cluster C3 contained 3 isolates from the community, 3


isolates from ward E, and 1 isolate fromward D. These patients had xerosis but not recurrent skin infections, which differ- entiated them from the outbreak in ward A. Of these 7 sam- ples, 6 were emm type 120.0, and all were ST168. These isolates had pairwise SNP differences of 26–58. No epidemiological link could be established between wards D and E or their community isolates. The outbreak control team therefore considered cluster C3 not to have arisen from recent person- to-person transmissions and likely to represent sporadic cases of infection with common community S. pyogenes strains.


Practicalities of WGS and Its Influence on Infection Prevention and Control Measures


The outbreak control team decided on the timing of WGS depending on the number and characteristics of affected patients, the number of involved staff members, and the geographical distribution of the affected wards. The results of WGS-guided specific infection control interventions at differ- ent points in time over the investigation period are described in Table 1. The outbreak peaked between September and October and resolved by November 2016 (Figure 3). The average cost of WGS over the outbreak period was US


$220 per isolate, with a minimum turnaround time of 8 days. In contrast, the cost of emm typing by Sanger sequencing, once established at the Department of Laboratory Medicine in Tan Tock Seng Hospital was US$146 per isolate, with a turnaround time of 3 days.


discussion


Whole-genome sequencing generated typing data in a clini- cally relevant period for the management of this outbreak.


Additionally, it provided greater resolution compared to emm typing in identifying a cluster with ongoing transmissions. In this study, skin carriage acted as the main reservoir for


S. pyogenes in cluster C1, with none of the patients having throat colonization. All cluster C1 isolates were of emm type 4, which accounts for 14% of emm types circulating in Asia19 and belongs to the emm E pattern group. The emm pattern genotype is used as a marker for tissue site tropism of S. pyogenes strains. Patterns A to C are associated with throat infections; pattern D is considered skin specific. Pattern E strains are considered general; they are associated with either throat or skin infection.19–21 A dermatologist was appointed to the institution, and individual patient skin care plans were implemented (Supplemental Material section 4). This intervention led to an improvement in the patients’ skin conditions, with no further S. pyogenes infections in the index ward. Serious consideration was given to the use of institution-


wide antibiotic treatment for S. pyogenes with the discovery of multiward involvement of S. pyogenes infections. This inter- vention has previously been described to control outbreaks of S. pyogenes in long-term care facilities.6,11,22 Given the num- bers of patients and staff members in the institution (at least 3,000), the cost, logistics, complexity, and possible adverse effects of this intervention would have been significant. The greater discriminatory power ofWGS allowed detection of the recent transmission events in cluster C1 and the nonclonal sporadic nature of infections of clusters C2 and C3. This information allowed outbreak control interventions to be ward- and patient-based rather than institution-wide (Table 1). It also avoided unnecessary ward closures and restrictions on patient movement that would have disrupted the normal functioning of the facility for both inpatients and outpatients.


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