An increase in non-toxigenic Corynebacterium diphtheriae cases in Philadelphia, PA, USA

Non-toxigenic Corynebacterium diphtheriae is increasingly recognized as a clinically important pathogen, particularly in association with chronic, non-healing cutaneous ulcers and, in some cases, invasive disease such as septic arthritis, osteomyelitis, bacteremia, and endocarditis. Prior reports suggest that individuals with substance use disorder and unstable housing are at heightened risk, but data characterizing the spectrum of disease in the United States remain limited. At our inner-city hospital system in Philadelphia, which serves a population with high rates of substance use and homelessness, we observed an increase in non-toxigenic C. diphtheriae isolates beginning in 2021. We conducted a retrospective chart review of all patients (35 unique patients, 38 discreet admissions) with cultures yielding non-toxigenic C. diphtheriae from 2021 through 2024, collecting demographic, clinical, and microbiological data. Most isolates out of the 38 discreet admissions (68.4%) were from skin and soft tissue sources, while 23.7% were from blood cultures. The majority (86.8%) of isolates from the 38 admissions were biovar mitis, with biovar gravis identified in 13.2%. Most patients had a history of substance use disorder (81.6%) and unstable housing (60.5%). These findings suggest that non-toxigenic C. diphtheriae may not be a benign colonizer in this population and should be considered a potential pathogen, particularly in patients with wounds and social risk factors. Further research is needed to clarify its clinical significance and to guide treatment decisions, including antimicrobial selection.