Invasive Multidrug-Resistant emm93.0 Streptococcus pyogenes Strain Harboring a Novel Genomic Island, Israel, 2017-2019

Abstract

Invasive group A Streptococcus (iGAS) infections have increased in Israel since 2016 as successful lineages have emerged. We report the emergence and outbreak of a multidrug-resistant S. pyogenes emm93.0, sequence type 10, among iGAS infections in Israel since 2017. This type has been observed very rarely in other countries. During this period, emm93.0 was the cause of 116 infections in Israel and became the leading type during 2018. Most of the infections were from bacteremia (75%), and most patients were male (76%). We observed infections across Israel, mainly in adults. Of note, we observed multidrug resistance for clindamycin, tetracycline, and trimethoprim/sulfamethoxazole. Whole-genome sequencing confirmed clonality among geographically disseminated isolates. The local emm93.0 sequence type 10 clone contained a novel genomic island harboring the resistance genes lsa(E), lnu(B), and ant (6)-Ia aph(3')-III. Further phenotypic and genomic studies are required to determine the prevalence of this resistance element in other iGAS types.

Figure 1

Incidence of emm types and clusters among 2,947 iGAS cases in Israel during 2014–2019 and potential vaccine coverage. A) Ten most common emm types, by incidence per 100,000 population for each year. Each color bar section represents 1 of the top 10 emm types; gray bar sections represent all other emm types. Dashed line represents the percentage of top 10 emm types from total cases each year. B) Ten most common emm clusters, by incidence per 100,000 population for each year. All emm types were assigned to emm clusters. Each color bar section represents a top 10 emm cluster; gray bar sections represent other emm clusters. Dashed line represents the percentage of potential coverage of 26-valent vaccine for each year; dotted line represents the percentage of potential coverage of 30-valent vaccine for each year. iGAS, invasive group A Streptococcus.

Figure 2

Ratio of male to female case-patients with invasive group A Streptococcus (N = 2,263) for selected emm types in Israel, 2016–2019. Asterisks (*) indicate significant results (p<0.05). Double asterisks (**) indicate significant results with Fisher exact test statistic value <0.00001.

Figure 3

Age distribution among total invasive group A Streptococcus case-patients (N = 2,258) and emm93.0 case-patients (N = 116,of which 113 were of known age) Israel, 2016–2019.

Figure 4

Epidemiologic curve of invasive group A Streptococcus emm93.0 type cases, Israel, April 2016–December 2019. Bar color indicates specimen source and whether the strains in the sample were analyzed by WGS. Other category includes sterile body fluid or vaginal swab specimen. WGS, whole-genome sequencing.

Figure 5

Demographic dispersal of invasive group A Streptococcus (iGAS) emm93.0 type cases by year, Israel. Colors indicate specimen source; other indicate sterile bodily fluids. Dot size is proportional to the number of cases. A) 2016, 1 case of emm93.0 B) 2017, 24/25 emm93.0 cases. C) 2018, 54/59 emm93.0 cases. D) 2019, 27/31 emm93.0 type of 31 iGAS cases.

Figure 6

Minimum spanning tree of invasive group A Streptococcus emm93.0 type from Israel, 2016–2019, and global strains (Spain and Kenya). Tree is based on whole-genome multilocus sequence typing comparison of selected emm93.0 strains and global strains with logarithmic scaling. Node color represents the country origin of the sample. Nodes are labeled by sample number key for those from this outbreak; those from Spain and Kenya are labeled by Sequence Read Archive accession number (Appendix 1 Table 2). Numbers on branches indicate the number of allelic differences between those 2 strains.

Figure 7

Schematic comparison of the integration site of the prophage carrying antimicrobial resistance genes for 2 invasive group A Streptococcus emm93.0 type strains from Israel and 1 from Spain. Arrows indicate gene arrangement in the presumed insertion site of the prophage, the rlmD gene (purple). The prophage contains gene sequences of antibiotic resistance related genes (ant(6)Ia, aph(3')IIIa, lsaE and lnuB), phage related genes and other non-Streptococcus genes. The gray regions indicate 80%–100% sequence identity.