To the Editors: A previously healthy, 17-year-old male (patient A) presented with rapidly progressing left foot erythema, swelling and tenderness. Following admission, his exam rapidly worsened with the development of bullae and ecchymosis, and he was emergently taken to surgery for concerns of a necrotizing soft tissue infection. Intraoperative findings were consistent with severe, necrotizing inflammation. Tissue cultures were positive for group A Streptococcus (GAS). He was diagnosed with a necrotizing soft tissue infection and required 3 additional debridements with eventual skin flap placement. He was hospitalized for 29 days and received 4 weeks of antibiotics (predominantly cefazolin or cephalexin). Antibiotic chemoprophylaxis was discussed with the family during the first week of admission, but was declined. Sixteen days into patient A’s hospitalization, his 4-year-old brother (patient B) developed fever, nausea, vomiting and a nodular rash. He was admitted, and blood cultures were positive for GAS. Workup was notable for a urine culture that was positive for GAS with 11–100, 000 colony forming unit/mL, thought to be secondary to high-grade bacteremia rather than the primary source of infection. Imaging studies (echocardiogram, computed tomography scan of abdomen/pelvis and computed tomography of sinuses) did not reveal any clear nidus of infection. He received 6 days of intravenous ampicillin and 1 dose of intramuscular penicillin for primary bacteremia with rapid clinical improvement. On the seventh day of patient B’s admission, the father of both patients developed a febrile illness with a nodular rash like patient B. No diagnostic tests were performed, but he rapidly improved 24 hours after initiation of an unknown oral antibiotic. Following confirmation of the second invasive GAS (iGAS) infection, the rest of the family (mother and 2 younger sisters) received 5 days of antibiotic chemoprophylaxis with amoxicillin. GAS isolates from both patients were sent for whole-genome sequencing. The 2 isolates were much more like each other than any other publicly available sequences on GenBank (Fig. 1A and B). Additionally, there were 0 observed single-nucleotide polymorphisms between the 2 isolates (Fig. 1C), and the most closely related isolates were at least 63 single-nucleotide polymorphisms away. FIGURE 1.: Colorado Department of Public Health and Environment performed paired-end Illumina whole genome sequencing on the patient A and B isolates and generated assemblies using TheiaProkIlluminaPEPHB (https: //github. com/theiagen/publicₕealthbioinformatics/tree/main). A: Mash-distance-based neighbor-joining tree of patient A/B isolate sequences (nodes circled blue) and all other (n = 346) publicly available Streptococcus pyogenes ST46 isolate sequences on GenBank as of July 2025, created using Mashtree v1. 4. 6 (https: //github. com/lskatz/mashtree). The left panel represents the entire tree. The right panel is zoomed in on the region containing patient A/B isolates. Yellow nodes represent known isolates from Colorado (n = 11). B: Core genome, recombination-masked, maximum likelihood phylogenetic tree inferred using SnippyStreamlinePHB v3. 1. 0 (https: //github. com/theiagen/publicₕealthbioinformatics/tree/main) of patient A/B genome sequences (green box) and the 21 most closely related publicly available ST46 genome sequences aligned to reference genome GCA₀41429915. 1. Leaves are labeled with the BioSample ID, collection date, and location. C: Core genome pairwise SNP distance matrix of patient A/B isolate sequences (green) of the same set of isolates in (B). These cases highlight the increased risk of GAS transmission and subsequent infection of household contacts of patients diagnosed with iGAS infections. Current literature suggests the risk of secondary iGAS in household contacts is 300- to 2000-fold higher than the background rate. 1 National United States iGAS guidelines were last revised in 2002 and based on 2 observational studies with limited cases. 2 While the guidelines provide recommendations regarding some high-risk populations (ie, >65 years old, injection drug use), there is no mention of other potentially high-risk groups such as infant–mother dyads or households with 2 or more confirmed infections, which differs from guidelines around the world. Furthermore, studies evaluating efficacy and safety of antibiotic chemoprophylaxis consist almost entirely of outbreak reports and case series, 3 although a recent nationwide study from the Netherlands showed a reduction in secondary iGAS cases following an expanded antibiotic prophylaxis policy. 4 Given the significant morbidity and mortality and rising incidence of iGAS infections, 5 further studies evaluating the risk of transmission and review of current guidelines is needed.
Showalter et al. (Mon,) studied this question.