Oct 4, 2014 - Corynebacterium pseudodiphtheriticum, a Gram-positive bacillus, is usually found as the normal commensal flora of the upper respiratory tract ...
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ISSN 0255-0857
Volume 32 Number 4 October 2014
Indian Journal of Medical Microbiology
Publication of Indian Association of Medical Microbiologists www.ijmm.org
October - December 2014
Case Reports
443
Diphtheria‑like illness in a fully immunised child caused by Corynebacterium pseudodiphtheriticum VA Indumathi, *R Shikha, DR Suryaprakash
Abstract Corynebacterium pseudodiphtheriticum is a common commensal flora of the upper respiratory tract in humans. Though the pathogenicity of C. pseudodiphtheriticum is not rare, its role as an opportunistic pathogen is mainly limited to the lower respiratory tract, particularly in patients with underlying systemic conditions or immune‑compromisation. We hereby present the first case of C. pseudodiphtheriticum causing diphtheria‑like illness affecting the upper respiratory tract of a 6‑year‑old fully immunised otherwise healthy child. In countries with very low incidence of diphtheria, C. pseudodiphtheriticum should be included in differential diagnosis for a child presenting with diphtheria‑like illness. Simple, rapid screening tests should be used to differentiate it from C. diphtheriae and hence, to prevent unnecessary concern in community. Key words: Corynebacterium pseudodiphtheriticum, diphtheria, membranous pharyngitis
Introduction Corynebacterium pseudodiphtheriticum, a Gram‑positive bacillus, is usually found as the normal commensal flora of the upper respiratory tract in humans. Though the pathogenicity of C. pseudodiphtheriticum is not rare, its role as an opportunistic pathogen is mainly limited to the lower respiratory tract, particularly in patients with underlying systemic conditions or immunosuppression.[1‑3] We hereby present a case of C. pseudodiphtheriticum causing diphtheria‑like illness affecting the upper respiratory tract of a fully immunised otherwise healthy child. Case Report A 6‑year‑old child presented with complaints of fever, sore throat, bilateral neck swelling and nasal obstruction since two days to the intensive care unit of MS Ramaiah Medical College. The child had history of proper immunisation against all common childhood diseases, and had no other significant past medical history or immuno‑compromisation. On general examination, child was toxic and febrile with tender submandibular and upper cervical lymphadenopathy. Examination of the upper respiratory tract revealed congestion of pharynx and presence of thick, white, leathery membrane and follicles over tonsils. X‑ray neck showed grade IV adenoids completely blocking posterior nasal space. A differential diagnosis of diphtheria and adenotonsillitis was made. The child was admitted in isolation ward and throat swab was sent for Albert’s stain and culture. *Corresponding author (email: ) Department of Microbiology (VIA, RS), Department of Ear, Nose, and Throat (DRS), Mathikere Sampangi Ramaiah Medical College, Bangalore, Karnataka, India Received: 02‑10‑2013 Accepted: 29-01-2014
Microbiological evaluation of throat swab revealed Kleb-Loeffler’s Bacilli (KLB) like organisms on Albert’s stain [Figure 1]. Growth on nutrient agar yielded predominantly small orange pigmented colonies, while non‑haemolytic colonies were observed on blood agar [Figure 2]. Gram’s stain of colonies revealed Gram‑positive bacilli. Biochemically the isolate was strongly positive for urease production, but was unable to produce acid from Hiss’s serum sugars including glucose, sucrose, maltose and starch. The isolate was identified as C. pseudodiphtheriticum on the basis of staining, culture and biochemical properties of the isolate. Elek’s gel precipitation test was negative. For confirmation, the isolate was sent on nutrient agar slope to microbiology department of Christian Medical College, Vellore and was confirmed as C. pseudodiphtheriticum by an automated system VITEK 2‑Compact (BioMeriux, Durham, NC, USA). Because of the toxic state of the patient, intravenous benzylpenicillin 1,000,000 IU/kg eight hourly and intravenous diphtheria antitoxin 90,000 IU over 2 h were started without waiting for laboratory report. However, ongoing management of the patient was justified on emergency basis by reporting KLB‑like organisms on Albert’s stain. Child improved gradually as fever subsided and lymphadenopathy reduced. Throat swab sent after 10 days of antibiotic treatment was negative for KLB‑like organisms. Fresh immunisation was started for the child. All close contacts were given a dose of diphtheria toxoid and erythromycin chemoprophylaxis until final microbiological report was available. Discussion Membranous pharyngitis can be associated with infection by many organisms such as C. diphtheriae, Streptococci, Epstein-Barr virus, Candida albicans, Borrelia vincenti, Herpes simplex virus,
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Indian Journal of Medical Microbiology
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Figure 2: (a) Nutrient agar plate showing small orange pigmented colonies. (b) Blood agar plate showing non-haemolytic colonies
Figure 1: Albert’s stain showing green coloured bacilli with bluish-black granules
Arachanobacterium hemolyticum. However, the presence of thick adherent pseudomembrane, tender lymphadenopathy and cervical swelling with low grade fever in a child presenting with sore throat provoke a high index of suspicion of diphtheria. In such cases, antitoxin treatment should be started with presumptive diagnosis of diphtheria on clinical grounds and without waiting for laboratory confirmation of causative microorganism and its toxigenicity.[4] In our case also, with provisional diagnosis of diphtheria, the antitoxin and antibiotic treatment was started without waiting for laboratory report. However, isolation of C. pseudodiphtheriticum from this patient was a surprising etiological factor, which led us to search the literature to review the pathogenicity of this organism. C. pseudodiphtheriticum, previously known as C. hofmannii, has been reported uncommonly, but not rarely, as an opportunistic pathogen of human beings. The most commonly reported site of pathogenicity for this organism is lower respiratory tract. However, majority of the cases with C. pseudodiphtheriticum infection either were immunocompromised or had any underlying systemic conditions.[1‑3] In a case series reported by Manzella et al., out of 17 adult patients with respiratory tract infection from whose sputum C. pseudodiphtheriticum was isolated, there were 12 cases of bronchitis and 5 of pneumonia with all patients having an underlying systemic condition.[2] Morinaga et al., reported two cases of respiratory tract infection by C. peudodiphthericum as an exacerbation of chronic obstructive pulmonary disease and pneumonia - both in the presence of underlying respiratory disease.[5] Diphtheria‑like illness of upper respiratory tract caused by C. pseudodiphtheriticum is rarely reported in literature. Literature search on “Pubmed” database yielded only three cases of exudative pharyngitis caused
by C. pseudodiphtheriticum. Out of these three cases, two cases have been reported in adult patients. The first case was a 54‑year‑old male with necrotising tracheitis, while the second case was from a 32‑year‑old male Uzbek national.[1,6] Another case report of exudative pharyngitis caused by C. pseudodiphtheriticum in a 4‑year‑old girl was reported by Izurieta et al.[3] The presentation of illness in both cases - case reported by Izurieta et al., and our case - was almost similar except the previously reported case had not been immunised for any of the common childhood diseases. This makes our case a rare report in term of ability of C. pseudodiphtheriticum to cause diphtheria‑like illness in a fully immunised, otherwise healthy child. The strain of C. pseudodiphtheriticum isolated in our case was non‑toxigenic, a finding similar to that reported by Izurieta et al. This finding suggests involvement of virulence factors and pathogenic mechanism other than toxin mediated mechanism. Hence clinical as well as microbiological improvement in our case was the result of action of antibiotic on pathogenic C. pseudodiphtheriticum and not the effect of diphtheria antitoxin, though the later was started on the basis of Albert’s stain report. Till now, little is known about the virulence factors and pathogenesis of C. pseudodiphtheriticum. In an experimental study, Souza et al., found that C. pseudodiphtheriticum can invade and survive within HEp‑2 cells.[7] They explained some mechanisms, which may be relevant for in vivo infections, allowing C. pseudodiphtheriticum to breach the epithelial cell barrier and enter deeper tissues. They also suggested epithelial cell attachment as an essential step for dissemination of some strains throughout the respiratory tract and to other sites in human body. Accordingly the pathogenicity of C. pseudodiphtheriticum is not limited to respiratory tract infection only. The second most common site of infection is endocardium.[8,9] Other rarely reported infections caused by this organism include keratitis and conjunctivitis, septic arthritis, suppurative lymphadenitis, cutaneous infection and genitourinary infection.[7] Being an emerging pathogen for humans, routine screening for C. pseudodiphtheriticum should be employed
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Case Reports
for clinical samples of patients with diphtheria‑like presentation. Special measures are needed to control dissemination of diphtheria. The delay in ruling out the diagnosis of diphtheria, as in our case, results in the unnecessary tracing of the patient’s close contacts and use of chemoprophylaxis to community contacts as well as hospital staff. Simple and rapid screening tests used for identification of various members of the Corynebacterium species in such patients may be invaluable in preventing unnecessary concern in the community. Simple screening tests, which can quickly differentiate C. pseudodiphtheriticum from C. diphtheriae, include inability to ferment glucose, maltose and sucrose, positive urease, negative cysteinase and positive pyrazinamidase tests.[3] Antibiotic sensitivity of C. pseudodiphtheriticum has been evaluated in many studies. Based on the tests for determination of minimum inhibitory concentrations (MICs) of antibiotics, Manzella et al., and Ahmed et al., noted uniform susceptibility of all isolates to the beta‑lactam antibiotics.[2,10] Morris et al., also recommended use of penicillin alone or in combination with an aminoglycoside for bacteriologic cure.[8] To conclude, we would like to emphasise that C. pseudodiphtheriticum should not be ignored as a coloniser, keeping this case report and related discussion in the background. To the best of our knowledge, this is the first case of diphtheria‑like illness caused by C. pseudodiphtheriticum in a fully immunised, otherwise healthy child. In countries where incidence of diphtheria is now very low, like in India, C. pseudodiphtheriticum should be included in differential diagnosis for a child presenting with membranous pharyngitis or diphtheria‑like illness and simple, rapid screening tests should be used to differentiate it from C. diphtheriae. In addition, as the non‑toxigenicity of C. pseudodiphtheriticum does not rule out its pathogenic ability especially in children, further studies are needed to know its virulence factors, pathogenic mechanisms and its mode of transmission.
Unique case and review. Rev Infect Dis 1991;13:73‑6. 2. Manzella JP, Kellog JA, Parsey KS. Corynebacterium pseudodiphtheriticum: A respiratory tract pathogen in adults. Clin Infect Dis 1995;20:37‑40. 3. Izurieta HS, Strebel PM, Youngblood T, Hollis DG, Popviv T. Exudative pharyngitis possibly due to Corynebacterium pseudodiphtheriticum, a new challenge in the differential diagnosis of diphtheria. Emerg Infect Dis 1997;3:65‑8. 4. Ellner PD. Exudative pharyngitis possibly due to Corynebacterium pseudodiphtheriticum. Emerg Infect Dis 1997;3:242‑3. 5. Morinaga Y, Yanagihara K, Yamada K, Nakamura S, Izumikawa K, Seki M, et al. Two cases of Corynebacterium pseudodiphtheriticum respiratory tract infection. Kansenshogaku Zasshi 2010;84:65‑8. 6. Santos MR, Gandhi S, Vogler M, Hanna BA, Holzman RS. Suspected diphtheria in an Uzbek national: Isolation of Corynebacterium pseudodiphtheriticum resulted in a false‑positive presumptive diagnosis. Clin Infect Dis 1996;22:735. 7. Souza MC, Santos LS, Gomes DL, Sabbadini PS, Santos CS, Camello TC, et al. Aggregative adherent strains of Corynebacterium pseudodiphtheriticum enter and survive within Hep‑2 epithelial cells. Mem Inst Oswaldo Cruz 2012;107:486‑93. 8. Morris A, Guild I. Endocarditis due to Corynebacterium pseudodiphtheriticum: Five case reports, review, and antibiotic susceptibilities of nine strains. Rev Infect Dis 1991;13:887‑92. 9. Wilson ME, Shapiro DS. Native valve endocarditis due to Corynebacterium pseudodiphtheriticum. Clin Infect Dis 1992;15:1059‑60. 10. Ahmed K, Kawakami K, Watanabe K, Mitsushima H, Nagatake T, Matsumoto K. Corynebacterium pseudodiphtheriticum: A respiratory tract pathogen. Clin Infect Dis 1995;20:41‑6. Access this article online Quick Response Code:
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Acknowledgement The authors acknowledge Department of Microbiology, Christian Medical College, Vellore, India for their help in confirmation of C. pseudodiphtheriticum isolate by Vitek 2‑Compact (BioMeriux, Durham, NC, USA).
References 1. Colt HG, Morris JF, Marston BJ, Sewell DL. Necrotizing tracheitis caused by Corynebacterium pseudodiphtheriticum:
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DOI: 10.4103/0255-0857.142250
How to cite this article: Indumathi VA, Shikha R, Suryaprakash DR. Diphtheria-like illness in a fully immunised child caused! by Corynebacterium pseudodiphtheriticum. Indian J Med Microbiol 2014;32:443-5. Source of Support: Nil, Conflict of Interest: None declared.
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