Corynebacterium ulcerans in an Immunocompromised Patient with Diphtheria and Her Dog

Abstract

Corynebacterium ulcerans causes zoonotic infections, such as diphtheria and extrapharyngeal infections. We report here the first case of a diphtheria-like illness caused by C. ulcerans in France and transmitted likely by a dog to an immunocompromised woman. CASE REPORTA 47-year-old woman was admitted in the emergency room at the Bicêtre University Hospital (Le Kremlin-Bicêtre, France) for severe dyspnea in October 2003. She was immunocompromised due to treatment by prednisone at 6 mg/daily, tacrolimus at 12 mg/daily, and mycophenolate nofetil at 1 g/daily since she had undergone a kidney graft 1 year previously. Ten days prior to her admission to Bicêtre Hospital, the patient had been treated to no avail for sinusitis by oral amoxicillin-clavulanic acid (2 g/daily).Physical examination revealed severe stridor. She had fever at 38°C and mild tachycardia. The endoscopic examination identified a pseudomembranous exudate covering the nasopharynx and laryngeal vestibulum, ulceration, and subglottic constriction. A blood test found an increase of C-reactive protein (100 g/ml) and a white blood cell count of 3,500/l. This severe dyspnea indicated intubation, and the patient was subsequently hospitalized in the intensive care unit.Throat swab showed coryneform and gram-positive rods. After 24 h of incubation on sheep blood agar at 37°C in 5% CO 2 , shiny and whitish colonies grew that produced a slight hemolysis. Microscopic examination of these colonies revealed gram-positive, coryneform rods arranged in palisades. They were catalase positive, showed a positive reaction for urease, were negative for pyrazinamidase, and fermented glucose, ribose, maltose, and glycogen. These characteristics corresponded to those of Corynebacterium ulcerans. Biochemical identification was confirmed by partial sequencing of the 16S rRNA gene that showed 99% identity of the sequence of that strain with that of a C. ulcerans reference strain (11).Since C. ulcerans may acquire lysogenic ␤-corynephages coding for a diphtheria-like toxin (DT), PCR test (using primers DT1 and DT2 for detection of tox gene of C. diphtheriae (6) was performed that showed the presence of the DT-like gene in C. ulcerans. Disk diffusion susceptibility testing was performed on Mueller-Hinton blood agar (supplemented with 5% [vol/vol] sheep blood) after overnight incubation at 35°C and 5% CO 2 . In the absence of standardized breakpoints for Corynebacterium, antibiotic susceptibility was determined by using the NCCLS criteria for Streptococcus spp. other than Streptococcus pneumoniae (10).

Prevalence of Corynebacterium ulcerans in dogs in Osaka, Japan

“…Although C. ulcerans can cause mouth ulcers (Lartigue et al, 2005) and bronchopneumonia (Sykes et al, 2010), all C. ulcerans-positive dogs were asymptomatic, regardless of the toxigenicity of the isolate. Our studies suggest that although weakly virulent, C. ulcerans is readily transmitted among dogs.…”

“…Human infections are caused by ingestion of untreated milk (Bostock et al, 1984) or by close contact with a variety of animals (De Zoysa et al, 2005;Hatanaka et al, 2011;Noguchi et al, 2009;Schuhegger et al, 2009;Tiwari et al, 2008;Yoshimura et al, 2010). Dogs are of pronounced importance because they are sometimes linked to serious human cases (Hogg et al, 2009;Lartigue et al, 2005).…”

Characterization of Corynebacterium species in macaques

“…It has been reported as a cause of pharyngitis, granulomatous pneumonia, and less commonly diphtheria, in humans (Funke et al, 1997). The traditional association of C. ulcerans infection of humans is zoonotic transmission from cattle or the consumption of raw milk from infected cattle (Lartigue et al, 2005). It is now the most common cause of diphtheria in the UK (Wagner et al, 2010).…”

“…It is now the most common cause of diphtheria in the UK (Wagner et al, 2010). Recent literature also suggests that C. ulcerans isolated from domestic pigs (Schuhegger et al, 2009), domestic cats (De Zoysa et al, 2005) and dogs (Lartigue et al, 2005;Katsukawa et al, 2009) may be a reservoir for human infection. We have previously described C. ulcerans from a case of mastitis in a bonnet macaque and as a frequent contaminant of cephalic implants from macaques used in cognitive neuroscience (Fox & Frost, 1974;Bergin et al, 2000).…”

Antibodies to tetanus, diphtheria and pertussis among healthy adults vaccinated according to the French vaccination recommendations

“…The last reported cases of diphtheria were observed in non-vaccinated adults or children; since 1989, one case of Corynebacterium diptheriae was observed in a non-vaccinated French child who died in Nepal in 1997, one case of toxigenic Corynebacterium ulcerans in 2003 in an immunocompromised patient contaminated by her dog 5 and several imported cases of Corynebacterium diphtheriae infection (www.invs.sante.fr/ surveillance/diphterie/default.htm; accessed 1 st December 2008). 6 However, although vaccination coverage is very high for children and adolescents, it decreases with age, to a greater degree than for tetanus or polio; only 32% of adults aged more than 70 years have been vaccinated against diphtheria in the last 10 years.…”