Abstract and Introduction

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.

Introduction

Streptococcus pyogenes, also known as group A Streptococcus (GAS), is a ubiquitous pathogen that produces an array of human disease, including focal infections (e.g., pharyngitis, pyoderma) with or without localized suppurative complications; invasive soft tissue infections (e.g., myositis, necrotizing fasciitis); and systemic, often fatal, infections (e.g., bacteremia, toxic shock syndrome). In addition, 2 postinfectious complications (glomerulonephritis and rheumatic heart disease) attributable to GAS have been well described^[1–3]. Although GAS remains susceptible to penicillin, treatment with alternative or combination therapies, such as macrolides, clindamycin, and other second-line antimicrobial medications, is common because of patient β-lactam allergies, dosing convenience, infection severity, and patient acuity^[4]. In contrast to its predictable β-lactam susceptibility, GAS resistance to other classes of antimicrobial drugs has been increasingly reported^[5–7]. In the face of ongoing dissemination of the MLS_B (macrolide, lincosamide, and streptogramin B) resistance phenotypes among GAS isolates, the Centers for Disease Control and Prevention (CDC) has labeled macrolide-resistant GAS an emerging threat of concern^[8].

As 1 component of its Active Bacterial Core surveillance (ABCs) system, the CDC Emerging Infections Program, part of the National Center for Emerging and Zoonotic Infectious Diseases, Division of Preparedness and Emerging Infections, provides ongoing population-based assessments of GAS infections from 10 sites in the United States. Annual reports produced by the program estimate the incidence of invasive GAS (iGAS) infections within the United States doubled from 2009 to 2019; total numbers of infections increased from ≈11,000 cases (3.6 cases/100,000 population) to >25,000 cases (7.6 cases/100,000 population)^[9,10]. Concomitant with this change, substantial increases in the proportion of iGAS isolates resistant to erythromycin and clindamycin have been reported; overall resistance rates climbed from <10% in 2010 to near 25% by 2017^[11]. Populations at risk for such macrolide-resistant iGAS infections have been predominantly persons 18–64 years of age; incidence is high among persons with a history of intravenous drug use (IVDU) and persons experiencing homelessness^[11,12].

West Virginia, USA, has seen a noticeable increase in annual rates of iGAS erythromycin resistance; at West Virginia University Medicine System (WVUMed) hospitals in Morgantown, rates increased from 37% in 2019 to 54% in 2020 and 87% in 2021. The state also has an extremely high per capita rate of drug overdose^[13]. On the basis of all those considerations, we conducted a study to review clinicoepidemiology of iGAS infections within the region and to characterize specific phenotypic and genotypic antimicrobial resistance traits of corresponding available isolates.