Emergence of Erythromycin-Resistant Invasive Group A Streptococcus, West Virginia, USA, 2020-2021

Abstract

Clindamycin and β-lactam antibiotics have been mainstays for treating invasive group A Streptococcus (iGAS) infection, yet such regimens might be limited for strains displaying MLS_B phenotypes. We investigated 76 iGAS isolates from 66 patients in West Virginia, USA, during 2020-2021. We performed emm typing using Centers for Disease Control and Prevention guidelines and assessed resistance both genotypically and phenotypically. Median patient age was 42 (range 23-86) years. We found 76% of isolates were simultaneously resistant to erythromycin and clindamycin, including all emm92 and emm11 isolates. Macrolide resistance was conferred by the plasmid-borne ermT gene in all emm92 isolates and by chromosomally encoded ermA, ermB, and a single mefA in other emm types. Macrolide-resistant iGAS isolates were typically resistant to tetracycline and aminoglycosides. Vulnerability to infection was associated with socioeconomic status. Our results show a predominance of macrolide-resistant isolates and a shift in emm type distribution compared with historical reports.

Keywords: Streptococcus pyogenes; United States; West Virginia; antimicrobial resistance; bacteria; clindamycin; constitutive; drug resistance; emm92; erythromycin; inducible; invasive group A Streptococcus; streptococci.

Figure 1

Geographic distribution of patients with invasive group A Streptococcus infection in West Virginia, USA, 2020–2021. A total of 56 iGAS isolates were collected from patients in 20 counties. Residence status for 9 patients was undocumented, and 9 patients were listed as homeless; in those cases, we used the county of residence for the billing address. Nine isolates were from neighboring counties in Pennsylvania and Maryland. The predominant emm type in the 3 West Virginia counties containing the most isolates was emm92 (10 isolates in Harrison County, 6 in Marion County, and 8 in Monongalia County) (Appendix Table 3).

Figure 2

Assessment of emm type, infection source, and IVDU history of patients with invasive group A Streptococcus infection in this study, West Virginia, USA, 2020–2021. Anatomic source of infection and the status of patient IVDU history is shown corresponding to emm type. Size of the colored sections indicates the relative number of isolates per emm type. IVDU, intravenous drug use; SSTI, skin and soft tissue infection.

Figure 3

emm type distribution and MLS_B resistance among invasive group A Streptococcus isolates, West Virginia, USA, 2020–2021. A) Temporal analysis of isolate emm type by 3-month periods. Specimens harboring isolates were collected during January 2020–June 2021, represented by consecutive quarters numbered 1–6. Graph indicates trend of emm92 isolates predominating each quarter over the study period. B, C) MLS_B susceptibility and resistance profiles. The number of isolates resistant to erythromycin (B) and clindamycin (C) by emm type was determined on the basis of antimicrobial susceptibility testing. Isolates were deemed nonsusceptible to clindamycin if they had either an inducible or constitutive resistance phenotype and deemed susceptible in the absence of growth as determined by D-test.

Figure 4

Detection of the methyl transferase genes ermA, ermB, and ermT in invasive group A Streptococcus (iGAS) isolates, West Virginia, USA, 2020–2021. A) Distribution of the pRW35-like plasmid among iGAS isolates. Presence of pRW35-like plasmid DNA was detected only in iGAS emm92-type isolates (representative samples are shown). B) PCR detection of the ermT-gene. The ermT-specific amplicon of 452 bp was detected in emm92 isolates using plasmid DNA as a template. C, D) Detection of the ermA and ermB genes. Chromosomal DNA was used as a template to detect the 612-bp-ermA (C) and 663-bp-ermB (D) amplicons present in several different emm types. A 347-bp-mefA amplicon was detected in a single emm22 isolate (data not shown).