Non-toxigenic Corynebacterium diphtheriae infective endocarditis with embolic events: a case report

Abstract

Background Corynebacterium diphtheriae (C. diphtheriae) infections, usually related to upper airways involvement, could be highly invasive. Especially in developing countries, non-toxigenic C. diphtheriae strains are now emerging as cause of invasive disease like endocarditis. The present case stands out for reinforcing the high virulence of this pathogen, demonstrated by the multiple systemic embolism and severe valve deterioration. It also emphasizes the importance of a coordinated interdisciplinary work to address all these challenges related to infectious endocarditis. Case presentation A 21-year-old male cocaine drug abuser presented to the emergency department with a 1-week history of fever, asthenia and dyspnea. His physical examination revealed a mitral systolic murmur, signs of acute arterial occlusion of the left lower limb, severe arterial hypotension and acute respiratory failure, with need of vasoactive drugs, orotracheal intubation/mechanical ventilation, empiric antimicrobial therapy and emergent endovascular treatment. The clinical suspicion of acute infective endocarditis was confirmed by transesophageal echocardiography, demonstrating a large vegetation on the mitral valve associated with severe valvular regurgitation. Abdominal ultrasound was normal with no hepatic, renal, or spleen abscess. Serial blood cultures and thrombus culture, obtained in the vascular procedure, identified non-toxigenic C. diphtheriae, with antibiotic therapy adjustment to monotherapy with ampicillin. Since the patient had a severe septic shock with sustained fever, despite antimicrobial therapy, urgent cardiac surgical intervention was planned. Anatomical findings were compatible with an aggressive endocarditis, requiring mitral valve replacement for a biological prosthesis. During the postoperative period, despite an initial clinical recovery and successfully weaning from mechanical ventilation, the patient presented with a recrudescent daily fever. Computed tomography of the abdomen revealed a hypoattenuating and extensive splenic lesion suggestive of abscess. After sonographically guided bridging percutaneous catheter drainage, surgical splenectomy was performed. Despite left limb revascularization, a forefoot amputation was required due to gangrene. The patient had a good clinical recovery, fulfilling 4-weeks of antimicrobial treatment. Conclusion Despite the effectiveness of toxoid-based vaccines, recent global outbreaks of invasive C. diphtheriae infectious related to non-toxigenic strains have been described. These infectious could be highly invasive as demonstrated in this case. Interdisciplinary work with an institutional “endocarditis team” is essential to achieve favorable clinical outcomes in such defiant scenarios.

Cardiac arrest associated with non-toxigenic corynebacterium diphtheria strain: A case report

“…Similar cases of bacteremia and significant clinical sequelae resulting from non-toxigenic diphtheria are rare ( 28 ). In developed countries, such cases are even rarer and typically present in patients with an immunocompromised condition, such as those with a history of IV drug use ( 29 , 30 ). Our patient had no known pre-existing conditions (immunological or otherwise), was established with preventative, outpatient care, and had no incidental diagnosis despite prior hospitalization and work up by specialists.…”

“…Cardiogenic toxicity due systemic infection with C. diphtheria is uncommon in developed countries ( 31 ). Such cases resulting from non-toxin producing strains are rare, even outside of the U.S. ( 30 ). These factors taken together make the case unusual.…”

Corynebacterium rouxii, a recently described member of the C. diphtheriae group isolated from three dogs with ulcerative skin lesions

“…It remains to be determined whether the negative tox gene is – like in C. belfantii – a constant feature in this species, which might directly influence its role as a human diphtheria pathogen. On the other hand, even severe human infections with non-toxigenic strains must not be underestimated with respect to the pathogenic potential (de Santis et al 2020 ; Massmann et al 2020 ). With four more animal isolates from three dogs from this study and one fox (Sing et al 2016 ) and possibly also from two cat isolates from the USA (Hall et al 2010 ) it is tempting to speculate and remains to be determined whether C. rouxii is also a zoonotic pathogen.…”

A multiomic approach to defining the essential genome of the globally important pathogen Corynebacterium diphtheriae

“…Whilst the toxin is considered the major virulence factor in C. diphtheriae, in recent years several other virulence factors have been identified that act independently of the toxin [6][7][8][9][10][11][12][13][14]. Indeed, an increasing number of systemic infections caused by non-toxigenic C. diphtheriae strains, such as endocarditis, septic arthritis and osteomyelitis, have been reported across the globe [8,[15][16][17][18][19]. Furthermore, a growing number of Corynebacterium species have been reported to cause opportunistic infection [20][21][22][23][24], or disease in animals [25], with at least 67 species being of clinical or veterinary importance [26].…”