By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
SYNOPSIS: Evidence indicates increasingly frequent recovery of non-toxigenic Corynebacterium diphtheriae in wound cultures, along with further recognition of endocarditis caused by this organism.
SOURCE: Karmarkar EN, Fitzpatrick T, Himmelfarb ST, et al. Cluster of non-toxigenic Corynebacterium diphtheriae infective endocarditis and rising background C. diphtheriae cases — Seattle, Washington 2020-2023. Clin Infect Dis 2024; Feb 1:ciae094. doi: 10.1093/cid/ciae. [Online ahead of print].
Karmarkar and colleagues report five cases of endocarditis due to non-toxigenic Corynebacterium diphtheriae seen in a hospital system in Seattle between Sept. 1, 2020, and April 1, 2023. All five patients were male. Only two patients had cardiac risk factors — one with cardiac failure and one with a prosthetic heart valve. Four patients had “likely” recent skin injuries — one each with a traumatic injury and a chronic wound, while two patients had recently injected drugs.
Initial therapy of patients with endocarditis included vancomycin and a beta-lactam in each case with bloodstream clearance in one to three days in 4/5; one patient died at 48 hours without clearance. Three patients experienced cerebral emboli with infarction and three patients had splenic or renal infarcts. Two patients underwent cardiac surgery, including the only survivor. Death occurred at 48 hours, 96 hours, six days, and 30 days.
These five patients with endocarditis were among 44 individuals with any infection yielding C. diphtheriae during the same interval, with an increasing number in the last year of study. Of the total, 75% were male and had a median age of 44 years (range, 23-73 years), 86% had a mental health diagnosis, and 77% were experiencing homelessness. All but three patients (7%) had a skin wound or breakdown and 35 patients (80%) had had wound infections in the previous year. In the previous three months, 29/39 patients (79%) had smoked/inhaled drugs and 16/39 patients (41%) had injected them.
All five individuals with endocarditis had monomicrobial bacteremia, while this was true of only 1/39 non-endocarditis patients. Most wounds were polymicrobial, with Staphylococcus aureus and/or Streptococcus pyogenes recovered together with C. diphtheriae. All 44 C. diphtheriae isolates were susceptible to vancomycin, trimethoprim-sulfamethoxazole, tetracycline, linezolid, levofloxacin, and erythromycin, while 3% were resistant to clindamycin and all were non-susceptible (95% intermediate) to ceftriaxone. Of the 39 patients without endocarditis, four (10%) died.
COMMENTARY
Infective endocarditis caused by C. diphtheriae (a non-toxigenic strain) was first described in the Johns Hopkins Hospital Bulletin in 1893. This remains a rare infection, but cases are being reported with increasing frequency and, unlike toxigenic C. diphtheriae, it is not preventable with a vaccine.
In addition to the cases reviewed here, Lovelock and colleagues also recently reported five cases of endocarditis (although one is only “possible”) due to non-toxigenic C. diphtheriae occurring in South Africa.1 Although four of the cases occurred in close geographic proximity and all infections involved the same organism strain, no epidemiological links could be detected. Only one patient had a history of substance abuse and poor living conditions. Only one individual, who had a prosthetic valve, had a cardiac risk factor, and this was the only patient who survived.
The frequent finding of mixed infections, at least in wound infections, reported by Karmarkar et al has increased alertness in their clinical laboratories. As they stated, they now “identify any ‘diphtheroids’ to the species level in wound cultures if the organism is predominant, in pure culture, or present in cultures with S. aureus and Group A Streptococcus, rather than considering them to be contaminants.” Their laboratory uses MALDI-ToF for organism identification.
As stated by the Seattle group, there is no high-
quality evidence regarding the optimal antibiotic therapy of endocarditis due to non-toxigenic C. diphtheriae. They noted that, while resistance was rare to non-existent, except regarding ceftriaxone, there are reports of increasing resistance to fluoroquinolones, daptomycin, gentamicin, and some beta-lactams.
REFERENCE
- Lovelock T, du Plessis M, van der Westhuizen C, et al. Non-toxigenic Corynebacterium diphtheriae endocarditis: A cluster of five cases. S Afr J Infect Dis 2024;39:539.
