Rare human skin infection with Corynebacterium ulcerans: transmission by a domestic cat
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- Corti, M.A.M., Bloemberg, G.V., Borelli, S. et al. Infection (2012) 40: 575. doi:10.1007/s15010-012-0254-5
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Corynebacterium ulcerans is mainly known for its ability to cause animal infections. Some strains of C. ulcerans produce diphtheria toxin, which can cause life-threatening cardiopathies and neuropathies in humans. Human cutaneous C. ulcerans infection is a very rare disease that mimics classical cutaneous diphtheria. We present a very rare case of a C. ulcerans skin infection caused by a non-diphtheria toxin-producing strain of C. ulcerans that resolved after 3 weeks of therapy with amoxicillin–clavulanate. A pet cat was the probable source of infection. The presence of C. ulcerans in the mouth of the cat was confirmed by 16S rRNA gene analysis and the API Coryne system. In cases of human infection with potentially toxigenic corynebacteria, it is important to determine the species and examine the isolate for diphtheria toxin production. If toxigenicity is present, diphtheria antitoxin should be administered immediately. Carriers and potential infectious sources of C. ulcerans include not only domestic livestock but also pet animals. For the primary prevention of disease caused by diphtheria toxin-producing corynebacteria, vaccination with diphtheria toxoid is recommended.
KeywordsCorynebacterium ulceransInfectionBacteriaZoonotic transmission
The course of the patient’s disease was favorable and, after 3 weeks of unchanged systemic antibiotic therapy and local antisepsis with aqueous chlorhexidine 0.1 % lotion, we noticed a remarkable improvement of the lesion on the hand, resulting in defect healing with a scar.
Subsequently, about 2 weeks after the end of clindamycin therapy, we took a swab from the mouth of the cat; Gram-positive rods identified as C. ulcerans or C. pseudotuberculosis were isolated on a 5 % sheep blood agar-based selective medium containing fosfomycin. Coryneform colonies were examined by 16S rRNA gene analysis and the API Coryne system. The sequence was submitted to GenBank under accession number HM136582. The 16S rRNA gene sequence showed 100 % homology with C. ulcerans. There was also a high homology (99.7 %) to C. pseudotuberculosis, requiring a further analysis for species assignment. Using the API Coryne system, the isolate was identified as C. ulcerans with a percentage identification value of 99.7 % and T-index value of 1. Both the analysis for the production of diphtheria toxin and PCR for Parapoxvirus, Orthopoxvirus, and Orf virus resulted negative.
There is no evidence of human-to-human transmission of C. ulcerans [1, 6], but rare cases of familial infection have been detected . In addition to domestic livestock, pet cats and dogs were recently suggested as possible carriers and transmission sources of this pathogen [11, 12]. Our case supports this conjecture. In the reported case, the domestic cat had suffered a cutaneous infection resembling the patient’s lesion. After antibiotic therapy, the cat was found to be carrying C. ulcerans in the mouth, suggesting that it may have been the source of the patient’s infection. As cultures were no longer available, molecular typing and comparison of the human and feline isolates was not possible. Nevertheless, the time course and the close contact suggest possible zoonotic transmission. Probably, the normal flora of the cat’s mouth will overcome C. ulcerans as a normal pathophysiologic process . Similarly to the prevention of pasteurellosis , hygienic precautions, such as the avoidance of contact of skin lesions with cat saliva and the use of appropriate antisepsis and disinfection procedures, are to be observed for a minimal transmission risk.
The microbiological diagnosis of C. ulcerans can be performed by culture from a swab of the infection site using the procedures fully described in the World Health Organization (WHO) “Manual for the laboratory diagnosis of diphtheria” . The microorganism can be distinguished from C. diphtheriae and C. pseudotuberculosis with a conventional biochemical kit test (e.g., API Coryne system) . After the identification of the correct species, an evaluation of diphtheria toxin production is recommended for all organisms that have the potential to produce this toxin. It is known that the ability to produce diphtheria toxin is carried in the structural gene, tox, mediated by infection of the bacterium by a corynebacteriophage . Rapid methods such as PCR have improved the identification of the diphtheria toxin gene . Not all PCR-positive strains of C. diphtheriae have a biologically active tox gene and express phenotypically the toxin . Nevertheless, tox gene-positive but non-toxigenic strains of C. ulcerans have, so far, not been documented . In our case, we used a real-time PCR for the detection of toxigenicity; however, a recent study has suggested that false-negative results may be obtained by this method . For this reason, an additional test to check for diphtheria toxin production (e.g., Elek test ) should be performed or the patient should be closely clinically observed for symptoms manifestation. In our case, we opted for the latter. If the patient presents any symptoms of toxemia, even without the confirmation of phenotypic active toxin production, diphtheria antitoxin should be administered as soon as possible. Serum sickness should be ruled out by scratch testing . The antibiotic management should be similar to the treatment for diphtheria . Although the organism is sensitive to most antibacterial agents in vitro, erythromycin is regarded as the antibiotic of choice . Since the clinical course of our patient under amoxicillin–clavulanate treatment was favorable, we did not change the therapy and the skin lesion healed completely. The value of diphtheria toxoid vaccination in preventing disease caused by toxigenic C. ulcerans has been the subject of debate [2, 21]. Previous vaccination with diphtheria toxoid did not modify the local disease process of our patient affected with non-toxigenic C. ulcerans. This could be explained by the fact that the local disease may be caused by other toxins such as the dermonecrotic toxin .
In conclusion, we present a very rare case of cutaneous infection with C. ulcerans, which has potential clinical complications similar to classic cutaneous diphtheria. All corynebacteria isolated from wounds (if growing as predominant organisms or in pure culture) should be identified to the species level. In case of toxigenic species such as C. diphtheriae, C. ulcerans, and C. pseudotuberculosis, they should be analyzed for diphtheria toxin production. If the isolate is found to produce toxin or the patient presents with related symptoms, the need for antitoxin administration should be evaluated immediately (in Switzerland, antitoxin is available from the Swiss Toxicological Information Centre, http://www.toxi.ch). Not only domestic livestock but also pets may be responsible for the transmission of this pathogen. Immunization with diphtheria toxoid will minimize the risk of diphtheria-like disease complications arising from infections due to toxigenic corynebacteria , but it seems not to be able to avoid non-toxigenic C. ulcerans local infections.
We thank the laboratory team of Triemli Hospital for their expert technical support.
Conflict of interest