Corynebacterium diphtheriae is a noncapsulated, club-shaped facultative anaerobic Gram-positive bacilli. Opportunistic or cutaneous co-infection caused by this microorganism, especially non-toxigenic strains, has become important in travellers1. The skin lesions are generally ulcerative with a torpid and nonspecific evolution, which usually appear after a bite or minor trauma2. These infections have a low incidence3, which is why this microorganism is often not considered as the first etiological diagnosis, so in many of the cases can be unnoticed. A study of two cases of infection by C. diphtheriae and Streptococcus pyogenes was performed. The microorganisms were isolated from swabs of wound exudates and were identified by mass spectrometry (MALDI-TOF MS, Bruker©) and were confirmed with the amplification and sequencing of the 16S rRNA gene. Diphtheria toxin was performed by PCR4.
Case 1A 28-year-old man with a recent travel history to Philippines attended for an incised wound on the back of the left foot of 15 days of evolution, with signs of cellulitis. The case was oriented as cellulitis and started intravenous treatment with ceftriaxone 1g for 5 days and linezolid 600mg for 3 days, after that the treatment were change to oral azithromycin for one week. In culture, S. pyogenes and C.diphtheriae were isolated. Antibiotic susceptibility testing (AST) was performed and both microorganisms were susceptible to penicillin and erythromycin. Diphtheria toxin was negative. The patients evolving favourably and subsequently decided to administer a booster of diphtheria vaccine.
Case 2A 32-year-old man, with a recent travel history to Southeast Asia for 2 months. Attended for a traumatic wound in the heel and erythematous and crusted lesions of 2-3cm in the right leg. Physical examination reveals a peripheral pustule with inflammation of an inguinal node without signs of cellulitis in the peripheral skin. The case was oriented as skin infection by biting of overinfected arthropods. Serology was requested for Dengue, Chikungunya and culture. S. pyogenes and C.diphtheriae were isolated. AST was performed and both microorganisms were susceptible to penicillin and erythromycin. Serologies for Dengue and Chikungunya were negative. Treatment with oral erythromycin 500mg every six hour for 14 days was started, contact study was carried out and reinforcement of the diphtheria vaccine was administered. Diphtheria toxin was negative; the patient was evaluated for 2 weeks, showing resolution of both traumatic wound and satellite lesions.
Cutaneous infection by C. diphtheriae is uncommon, tends to be of torpid evolution and produce nonspecific lesions, so clinical suspicion is low. In recent years this infection has been linked mainly with travellers to endemic areas including Southeast Asia, some countries such as Cambodia, India, Indonesia, Malaysia, New Guinea, Philippines, Thailand, Brazil and others5,6. A study in Vancouver reports 37 cases of cutaneous diphtheria for non-toxigenic strains 8 which demonstrates the high distribution of these strains. In Europe, the data was based mainly on patients with a recent travel history7, except in some Eastern European countries, which are considered an endemics areas2.
Other risk factors for the infection included population with low socioeconomic resources, alcohol abuse, drugs, HIV infection, hepatitis, cirrhosis8,3, Identification of Gram positive bacilli colonies may be considered in some cases as non-pathogenic microbiota by the genus of Corynebacterium, and presence of C.diphtheriae may be misidentified. In these cases we can apply the MALDI-TOF MS, it's an easy technique and effective cost2.
Co-infection is a common clinical presentation. S. pyogenes, Staphylococcus aureus, methicillin-resistant S. aureus, Arcanobacterium haemolyticum and species of coagulase-negative staphylococci 8 are the more frequently association. In 2016 a third case of cutaneous diphtheria was also reported where colonies of A. haemolyticum were also isolated in a 50-year-old patient with a recent travel history to Guinea Bissau and mimicking pyoderma gangrenosum9.
Benzylpenicillin and macrolides were considered first line treatment in cases of diphtheria, but in 2015 the first case of C. diphtheriae resistant to penicillin was published in a cutaneous infection by a non-toxigenic strain in the United Kingdom 10 However, benzylpenicilin continue to be the first option for treatment in case of diphtheria. In our cases the both strains and both S.pyogenes were susceptible to penicillin and erythromycin. In Spain in 2015, the first case of diphtheria was reported since 1986, in a 6-year-old unvaccinated child, who progressed unfavourably and died after one month of medical treatment. However, in relation to cutaneous diphtheria, no previous reports have been found.
The number of travellers continues to increase in Spain and Europe, which can increase the incidence of these mixed infections. The recent travel history should be recognized as an epidemiological data to highlight not only the clinical diagnosis but also the microbiological one.
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