Toxigenic Corynebacterium ulcerans in Woman and Cat

Anja Berger, Ingrid Huber, Sophie-Susann Merbecks, Ingrid Ehrhard, Regina Konrad, Stefan Hörmansdorfer, Michael Hogardt,¹ and Andreas Sing¹

Author affiliations: National Consiliary Laboratory for Diphtheria, Oberschleißheim, Germany (A. Berger, R. Konrad, A. Sing); Bavarian Health and Food Safety Authority, Oberschleißheim (A. Berger, I. Huber, R. Konrad, S. Hörmansdorfer, M. Hogardt, A. Sing); and Public Health Laboratory of Saxony, Germany (S.-S. Merbecks, I. Ehrhard)
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To the Editor: Diphtheria and diphtheria-like illness are caused by Corynebacterium spp. that harbor the diphtheria toxin–encoding tox gene. Recently in many industrialized countries, cases of diphtheria-like infection caused by toxigenic C. ulcerans have outnumbered those caused by toxigenic C. diphtheriae (1,2). C. ulcerans infection was originally associated with consumption of raw milk and dairy products or contact with cattle, but C. ulcerans has increasingly been isolated from domestic animals such as pet dogs and cats (3–5). So far, isolation of an identical toxigenic C. ulcerans strain from an animal and its owner has been documented only for dogs (3,4) and a pig (6). We report the isolation of an identical toxigenic C. ulcerans strain from an asymptomtic pet cat and a person with pharyngeal diphtheria-like illness; therefore, it might be speculated that the woman has acquired her infection from the cat.
In November 2010, an 86-year-old woman with arterial hypertension and rheumatoid arthritis was admitted to an ear, nose, and throat clinic in Dresden, Germany, with a 3-day history of sore throat, hoarseness, and nasal respiratory obstruction. Fever was not reported. Because the patient had visible fibrinous rhinitis, a nasal and pharyngeal swab was obtained before treatment with amoxicillin was begun. The patient had no history of recent travel abroad or contact with livestock. Her complete vaccination status against diphtheria was unknown, but she had received a vaccination booster in 2006.
Toxigenic C. ulcerans grew from culture of the nasal swab specimen; it was identified by biochemical differentiation (API Coryne code 0111326; bioMèrieux, Nürtingen, Germany), rpoB sequencing (6), and MALDI-TOF analysis (MALDI Biotyper; Bruker Daltonics, Bremen, Germany) (7). Toxigenicity was verified by real-time PCR (8) and a modified Elek test (6).
Because the microbiological result suggested diphtheria-like illness, the patient was transferred to an infectious diseases department in an academic hospital, where she was isolated and treated with amoxicillin for 12 days. Because the patient's condition was stable and no severe complications occurred during her hospital stay, she was not given diphtheria antitoxin. Her predominant symptoms, such as sore throat and earache, improved after antimicrobial drug therapy, and she recovered quickly. Electrocardiogram performed before discharge from hospital showed no signs of myocarditis or other toxin-related effects, such as neurologic disorder.
Although person-to-person transmission of C. ulcerans has not yet convincingly been demonstrated, an outbreak investigation involving the patient's close contacts (6 family members, the physician, and 19 nurses and other health care workers) was conducted. Although all close contacts had completed the series of diphtheria toxoid vaccinations, they were all given postexposure prophylaxis with erythromycin.
Because of the zoonotic potential of human C. ulcerans infections, nasal and pharyngeal swab samples were collected from the patient's asymptomatic pet cat. Strains of tox-positive C. ulcerans (which we named KL251 and KL252) grew on culture; the API Coryne code was identical to that of the human isolate KL246. In contrast to the human isolate, which yielded a weakly positive Elek result, both isolates from the cat showed Elek-negative results.
Antimicrobial drug susceptibility testing of the 3 isolates was performed on Mueller-Hinton blood agar (supplemented with 5% sheep blood) by using the Etest system after overnight incubation at 37°C and in 5% CO₂. In the absence of standardized breakpoints for C. ulcerans, susceptibility was determined by using the Clinical Laboratory Standards Institute criteria for broth microbouillon dilution susceptibility testing for Corynebacterium spp. (9). All C. ulcerans strains were susceptible to amoxicillin, benzyl penicillin, ceftriaxone, erythromycin, and tetracycline (MICs 0.19–0.5 μg/mL) but less susceptible to clindamycin in vitro (MIC 2 μg/mL).
Sequencing of rpoB and tox showed 100% homology between the strains from the woman and the cat. Ribotyping revealing a U3-like ribotype (5), and multilocus sequence typing (10) confirmed the clonal identity of the strains.
The cat was given a combined preparation of benzyl penicillin and streptomycin. After completion of therapy, C. ulcerans no longer grew from nasal swab specimens from the woman or the cat.
Our findings of transmission of toxigenic C. ulcerans between a woman and her cat underline the zoonotic potential of this organism and highlight the need for more studies investigating the carrier status of companion animals such as cats and dogs. Although clindamycin is not a first-line drug for diphtheria therapy, the intermediate susceptibility of C. ulcerans against clindamycin underscores the necessity of standardized susceptibility testing for diphtheria cases because clindamycin-resistant toxigenic C. ulcerans strains in human infections have been recently reported (6). Toxigenic C. ulcerans strains are rare, but the numbers of human wound infections or diphtheria-like disease caused by C. ulcerans have increased in the past few years. However, detection of toxigenic C. ulcerans is often still incidental, often resulting in delayed specific therapy, including patient isolation or contact tracing.

Acknowledgments

We thank Wolfgang Schmidt, Karola Grünwald, Marzena Maggipinto, and Daniela Sebah for cultivation and microbiological and molecular characterization of the Corynebacteria.
The study was partially supported by the Bavarian State Ministry of the Environment and Public Health, by the European Commission's Directorate General for Health and Consumer Policy through the Diphtheria Surveillance Network, and by the German Federal Ministry of Health through the Robert Koch-Institute and its National Reference Laboratories Network.

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