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 3weeks 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 recommende

Bloemberg, G.

Borelli, S.

Corti, M.

Eich, G.

Hoelzle, L.

Kutzner, H.

Lautenschlager, S.

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CASE REPORTRare human skin infection with Corynebacterium ulcerans:transmission by a domestic catM. A. M. Corti • G. V. Bloemberg •S. Borelli • H. Kutzner • G. Eich • L. Hoelzle •S. LautenschlagerReceived: 5 December 2011 / Accepted: 1 March 2012 / Published online: 9 March 2012 Springer-Verlag 2012Abstract Corynebacterium ulcerans is mainly known forits ability to cause animal infections. Some strains ofC. ulcerans produce diphtheria toxin, which can cause life-threatening cardiopathies and neuropathies in humans.Human cutaneous C. ulcerans infection is a very rare dis-ease that mimics classical cutaneous diphtheria. We presenta very rare case of a C. ulcerans skin infection caused by anon-diphtheria toxin-producing strain of C. ulcerans thatresolved after 3 weeks of therapy with amoxicillin–cla-vulanate. A pet cat was the probable source of infection.The presence of C. ulcerans in the mouth of the cat wasconfirmed by 16S rRNA gene analysis and the API Corynesystem. In cases of human infection with potentially toxi-genic corynebacteria, it is important to determine the spe-cies and examine the isolate for diphtheria toxin production.If toxigenicity is present, diphtheria antitoxin should beadministered immediately. Carriers and potential infectioussources of C. ulcerans include not only domestic livestockbut also pet animals. For the primary prevention of diseasecaused by diphtheria toxin-producing corynebacteria, vac-cination with diphtheria toxoid is recommended.Keywords Corynebacterium ulcerans  Infection Bacteria  Zoonotic transmissionIntroductionCorynebacterium ulcerans is primarily known as an animalpathogen and is a commensal in horses and cattle [1]. Inveterinary medicine, it is a recognized cause of mastitis incows and has been isolated from raw cow’s milk. Zoonotichuman infections have been reported, usually among ruralpopulations with direct contact to domestic livestock [1].The global epidemiology of human infections caused byC. ulcerans is not well understood [2]. Many strains ofC. ulcerans produce the diphtheria toxin [3] and causeexudative pharyngitis in humans indistinguishable fromdiphtheria [4], with local pseudomembrane production andpotential systemic cardiac or neurologic manifestations aslife-threatening complications. Independently of diphtheriatoxin production, some strains produce a dermonecrotictoxin [5]. Skin infections caused by C. ulcerans have veryrarely been reported so far (Table 1). As in this reportedcase, the clinical manifestation is undistinguishable fromclassical cutaneous diphtheria [1, 6].Case reportA 29-year-old otherwise healthy male developed a cuta-neous ulcer on the right hand measuring about 1 cm inM. A. M. Corti  S. Borelli  S. Lautenschlager (&)Outpatient Clinic of Dermatology, Triemli Hospital,Herman Greulich Strasse 70, 8004 Zurich, Switzerlande-mail: stephan.lautenschlager@triemli.stzh.chG. V. BloembergInstitute of Medical Microbiology,University of Zurich, Zurich, SwitzerlandH. KutznerDermatohistopathologische Gemeinschaftspraxis,Friedrichshafen, GermanyG. EichDepartment of Internal Medicine, Triemli Hospital,Zurich, SwitzerlandL. HoelzleInstitute of Veterinary Bacteriology,University of Zurich, Zurich, Switzerland123Infection (2012) 40:575–578DOI 10.1007/s15010-012-0254-5diameter with undermined elevated edges, covered with agray–brown membrane (Fig. 1). In addition, on the back ofhis hand and over the fourth and fifth fingers, there was aclearly outlined area of erythema (Fig. 1). No signs oflymphangitis or lymphadenopathy were detected and thepatient did not report any other symptoms. The laboratoryfindings, including the inflammatory markers (C-reactiveprotein [CRP] 1.5 mg/l and leukocytes 9.40 9 109/l) andthe antistreptolysin titer, were normal. We took a swabfrom the lesion and started oral therapy with amoxicillin–clavulanate (625 mg, three times a day). Culture of theswab on 5 % sheep blood agar produced a growth of nor-mal skin flora and, as major pathogens, Enterococcusspecies and dry waxy colonies of Gram-positive rods weresubsequently identified as C. ulcerans by the API Corynesystem (bioMe´rieux, Gene`ve, Switzerland) and by a posi-tive fermentation test for glycogen and trehalose. Real-timepolymerase chain reaction (PCR) analysis for the presenceof the diphtheria toxin gene [7] using chromosomal DNAextracted from the C. ulcerans isolate was negative, indi-cating the lack of diphtheria toxin production. The patienthad been vaccinated with diphtheria toxoid 10 years earlierduring military service. The general condition of thepatient remained good for the duration of the treatmentand, as he showed no signs of cardiopathy or neuropathy,diphtheria antitoxin titration or administration was thoughtnot to be necessary.The course of the patient’s disease was favorable and,after 3 weeks of unchanged systemic antibiotic therapy andlocal antisepsis with aqueous chlorhexidine 0.1 % lotion,we noticed a remarkable improvement of the lesion on thehand, resulting in defect healing with a scar.On further inquiry, the patient remembered an episodeof sore throat and fever 3 weeks before the appearance ofthe cutaneous lesion. Swabs taken from the throat of thepatient 2 weeks after the end of antibiotic therapy producedonly the growth of normal flora. The patient denied anycontacts with horses or cows but the pet cat of the patienthad lesions similar to the patient in its mouth and on a paw1 week earlier. The cat’s veterinarian clinically suspected aneoplasm or a bullous skin disease and, therefore, per-formed two skin biopsies that revealed a suppurative skininfection with edema of the dermis and an infiltration ofneutrophils (Fig. 2). Broad-range bacterial 16S rRNA genePCR [8] using an extract of the paraffin-embedded tissuedid not detect bacterial DNA. However, this could be dueto reduced sensitivity of the PCR in formalin-fixed, par-affin-embedded tissue [9]. The cat received systemictherapy with clindamycin (5.5 mg/kg body weight every12 h orally for 32 days), which resulted in completeregression of all lesions.Subsequently, about 2 weeks after the end of clinda-mycin therapy, we took a swab from the mouth of thecat; Gram-positive rods identified as C. ulcerans orC. pseudotuberculosis were isolated on a 5 % sheep bloodagar-based selective medium containing fosfomycin.Coryneform colonies were examined by 16S rRNA geneanalysis and the API Coryne system. The sequence wassubmitted to GenBank under accession numberTable 1 Reported cases of Corynebacterium ulcerans skin infectionsReference Year Number ofpatientsCountry ToxigenicstrainWagner et al. [6] 2001 1 Germany UncertainDeWinter et al. [22] 2005 3 Canada YesWerchniak et al. [23] 2007 1 USA YesFig. 1 Ulcer of 1 cm in diameter with undermined edges, coveredwith a gray–brown membrane. Erythema on the back of the right handand over the fourth and fifth fingers (lower inset photograph)Fig. 2 Biopsy specimen of the cat’s lips revealing a suppurativemucosal infection with edema of the dermis and an infiltration ofneutrophils. HE 910 and 940576 M. A. M. Corti et al.123HM136582. The 16S rRNA gene sequence showed 100 %homology with C. ulcerans. There was also a highhomology (99.7 %) to C. pseudotuberculosis, requiring afurther analysis for species assignment. Using the APICoryne system, the isolate was identified as C. ulceranswith a percentage identification value of 99.7 % andT-index value of 1. Both the analysis for the production ofdiphtheria toxin and PCR for Parapoxvirus, Orthopoxvirus,and Orf virus resulted negative.DiscussionThere is no evidence of human-to-human transmission of C.ulcerans [1, 6], but rare cases of familial infection have beendetected [10]. In addition to domestic livestock, pet cats anddogs were recently suggested as possible carriers andtransmission sources of this pathogen [11, 12]. Our casesupports this conjecture. In the reported case, the domesticcat had suffered a cutaneous infection resembling thepatient’s lesion. After antibiotic therapy, the cat was found tobe carrying C. ulcerans in the mouth, suggesting that it mayhave been the source of the patient’s infection. As cultureswere no longer available, molecular typing and comparisonof the human and feline isolates was not possible. Never-theless, the time course and the close contact suggest pos-sible zoonotic transmission. Probably, the normal flora of thecat’s mouth will overcome C. ulcerans as a normal patho-physiologic process [13]. Similarly to the prevention ofpasteurellosis [14], hygienic precautions, such as theavoidance of contact of skin lesions with cat saliva and theuse of appropriate antisepsis and disinfection procedures, areto be observed for a minimal transmission risk.The microbiological diagnosis of C. ulcerans can beperformed by culture from a swab of the infection siteusing the procedures fully described in the World HealthOrganization (WHO) ‘‘Manual for the laboratory diagnosisof diphtheria’’ [15]. The microorganism can be distin-guished from C. diphtheriae and C. pseudotuberculosiswith a conventional biochemical kit test (e.g., API Corynesystem) [16]. After the identification of the correct species,an evaluation of diphtheria toxin production is recom-mended for all organisms that have the potential to producethis toxin. It is known that the ability to produce diphtheriatoxin is carried in the structural gene, tox, mediated byinfection of the bacterium by a corynebacteriophage [17].Rapid methods such as PCR have improved the identifi-cation of the diphtheria toxin gene [15]. Not all PCR-positive strains of C. diphtheriae have a biologically activetox gene and express phenotypically the toxin [18]. Nev-ertheless, tox gene-positive but non-toxigenic strains ofC. ulcerans have, so far, not been documented [6]. In ourcase, we used a real-time PCR for the detection oftoxigenicity; however, a recent study has suggested thatfalse-negative results may be obtained by this method [19].For this reason, an additional test to check for diphtheriatoxin production (e.g., Elek test [15]) should be performedor the patient should be closely clinically observed forsymptoms manifestation. In our case, we opted for thelatter. If the patient presents any symptoms of toxemia,even without the confirmation of phenotypic active toxinproduction, diphtheria antitoxin should be administered assoon as possible. Serum sickness should be ruled out byscratch testing [20]. The antibiotic management should besimilar to the treatment for diphtheria [10]. Although theorganism is sensitive to most antibacterial agents in vitro,erythromycin is regarded as the antibiotic of choice [1].Since the clinical course of our patient under amoxicillin–clavulanate treatment was favorable, we did not change thetherapy and the skin lesion healed completely. The value ofdiphtheria toxoid vaccination in preventing disease causedby toxigenic C. ulcerans has been the subject of debate [2,21]. Previous vaccination with diphtheria toxoid did notmodify the local disease process of our patient affectedwith non-toxigenic C. ulcerans. This could be explained bythe fact that the local disease may be caused by other toxinssuch as the dermonecrotic toxin [1].In conclusion, we present a very rare case of cutaneousinfection with C. ulcerans, which has potential clinicalcomplications similar to classic cutaneous diphtheria. Allcorynebacteria isolated from wounds (if growing as pre-dominant organisms or in pure culture) should be identifiedto the species level. In case of toxigenic species such asC. diphtheriae, C. ulcerans, and C. pseudotuberculosis,they should be analyzed for diphtheria toxin production. Ifthe isolate is found to produce toxin or the patient presentswith related symptoms, the need for antitoxin administra-tion should be evaluated immediately (in Switzerland,antitoxin is available from the Swiss Toxicological Infor-mation Centre, http://www.toxi.ch). Not only domesticlivestock but also pets may be responsible for the trans-mission of this pathogen. Immunization with diphtheriatoxoid will minimize the risk of diphtheria-like diseasecomplications arising from infections due to toxigeniccorynebacteria [10], but it seems not to be able to avoidnon-toxigenic C. ulcerans local infections.Acknowledgment We thank the laboratory team of Triemli Hos-pital for their expert technical support.Conflict of interest None.References1. Meyer DK, Reboli AC. Other coryneform bacteria and rhodo-coccus. 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Rare human skin infection with Corynebacterium ulcerans: transmission by a domestic cat

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Rare human skin infection with Corynebacterium ulcerans: transmission by a domestic cat

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