Kennel Cough’ in a Patient Following Allogeneic Hematopoietic Stem Cell Transplant

LETTER TO THE EDITOR ‘Kennel Cough’ in a patient following allogeneic hematopoietic stem cell transplant

Bone Marrow Transplantation (2009) 44, 381–382; booster. After presenting to the veterinarian with the classic doi:10.1038/bmt.2009.22; published online 23 February 2009 honking cough and rhinorrhea, the dog was empirically treated with an antibiotic injection leading to a rapid improvement in her symptoms. A nasopharyngeal speci- Bordetella bronchiseptica is a Gram-negative coccobacillus men from the patient was sent for culture, with a specific that frequently causes infections in animals, including request to rule out B. bronchiseptica. The culture was atrophic rhinitis in swine, snuffles in rabbits and kennel positive for B. bronchiseptica, sensitive to the usual cough in dogs.1 The most common symptom of kennel antibiotics. He was treated with levofloxacin with an cough is a dry ‘honking’ cough. B. bronchiseptica belongs to improvement in his symptoms. On completion of the the same genus as the causative agent of whooping cough antibiotics, he had recurrent symptoms and his culture in humans, Bordetella pertussis, an organism that infects showed the persistence of B. bronchiseptica. He was treated only humans. Most infections with B. bronchiseptica occur with a second course of levofloxacin. His chest X-Ray did in immunocompromised individuals exposed to farm not show any evidence of pneumonia and his symp- or companion animals, although infections have been toms improved again. A third nasopharyngeal specimen, reported in immunocompetent patients.1–3 The organism is collected three weeks later, was also culture-positive for usually susceptible in vitro to the aminoglycosides, anti- B. bronchiseptica. He was then treated with a course of pseudomonal penicillins, quinolones, tetracycline, third- ciprofloxacin and doxycycline, on the basis of antimicrobial generation cephalosporins and trimethoprim–sulfamethox- susceptibility test results. While on this therapy, a repeat azole. Effective treatment is often difficult because of the specimen was culture-positive for B. bronchiseptica, now patient’s underlying disease and the ability of the organism with resistance to ciprofloxacin. As he continued to report a to invade and persist in epithelial cells. The two veterinary slight chronic cough, his treatment was changed to inhaled vaccines currently marketed are an avirulent live intranasal tobramycin, and after four weeks of treatment, his vaccine and a s.c. antigen extract vaccine. Although data nasopharyngeal specimens remained culture positive. He suggest that the intranasal route may be effective within 72 h, was observed off therapy and, because his symptoms had there is less data on the efficacy of the s.c. vaccine. resolved by this time, he did not receive further antibiotics. We present a case of B. bronchiseptica infection in a In total, he received 10 weeks of antibiotic therapy. patient with graft-versus-host disease (GVHD) after Despite the widespread prevalence and infection in the allogeneic hematopoietic SCT (allo-HSCT). A 29-year-old animal community, B. bronchiseptica infections in humans man with chemorefractory stage IIIB anaplastic large cell- are relatively rare, with the majority of cases involving lymphoma underwent a myeloablative conventional allo- patients who were immunocompromised. The prevalence of HSCT from a 10/10 matched unrelated donor after human infection has been increasing, possibly as a result of conditioning with TBI, thiotepa and CY. He received the AIDS epidemic4 and an increased number of organ tacrolimus, sirolimus and MTX for GVHD prophylaxis. transplants. Four earlier cases of human infection with His transplant course was notable for acute renal failure B. bronchiseptica have been reported in patients after and the nephrotic syndrome with a maximum creatinine allo-HSCT (Table 1). The first two cases may represent of 3.5 mg/dl, which resolved after the discontinuation of transmission from dogs to humans.5,6 The two more-recent sirolimus. Grade III gut GVHD was diagnosed by cases suggest nosocomial transmission as the two were sigmoidoscopy on day þ 90 and he was treated with described within three days of each other in the same steroids (max dose 2 mg/kg), in addition to the ongoing institution.7 These patients were frequently seen for follow- tacrolimus and mycophenolate mofetil (MMF). On up in the same clinic space, and pulsed-field gel electro- approximately day þ 170 he developed a flare of his gut phoresis analysis showed that the patients were infected GVHD while completing a slow taper of his prednisone with the same strain. necessitating an increase in steroid doses. On day þ 202, he Our case suggests transmission of B. bronchiseptica in a first reported a persistent productive cough. He also noted symptomatic puppy to a post transplant patient with dyspnea with exertion, but no fevers. Azithromycin was GVHD with continued colonization after multiple courses prescribed without relief in symptoms. Subsequently, he of antibiotics. This case, in addition to the four earlier reported that his four-month-old puppy had been diag- reported cases of B. bronchiseptica infections in allo-HSCT nosed with kennel cough approximately 2–3 weeks before recipients, has significant implications for the counseling we the start of his symptoms. The dog had received one dose provide our transplant patients. We need to continue to be of the s.c vaccine, BronchicinetCAe, without subsequent diligent and advise our patients to not only avoid sick Letter to the Editor 382 humans but also avoid animal contact, especially with sick animals and young animals who may have received live vaccines. Further, we need to carefully inquire about pet 7 exposures when our post transplant patients fall ill. Reference

Conﬂict of interest

The authors declare no conﬂict of interest.

Acknowledgements sick dog Unknownpatient number 3 7 This work was supported by the National Institutes of Health (NIH) Grant T32 AI055409 (JDG). JD Goldberg1, M Kamboj2, R Ford1, TE Kiehn3, K Gilhuley3 and M-A Perales1 1Allogeneic Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering BAL, bloodSputumStool, Possible blood, lung tissue Yes 5 6 Cancer Center, New York, NY, USA; 2Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA and 3Microbiology Service, Department of Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, New York, NY, USA E-mail: [email protected]

LLL consolidation pulmonary inﬁltrates inﬁltrates References

1 Woolfrey BF, Moody JA. Human infections associated with Bordetella bronchiseptica. Clin Microbiol Rev 1991; 4: 243–255. 2 Mattoo S, Cherry JD. Molecular pathogenesis, epidemiology and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clin Microbiol Rev 2005; 18: 326–382. GVHD present Signs and symptoms Culture data Contact with 3 Gore T, Headley M, Laris R, Bergman JG, Sutton D, Horspool LJ et al. Intranasal kennel cough vaccine protecting dogs from experimental Bordetella bronchiseptica challenge within 72 h. Vet Rec 2005; 156: 482–483. 4 Dworkin MS, Sullivan PS, Buskin SE, Harrington RD, Olliffe

after allo-HSCT J, MacArthur RD. Bordetella bronchiceptica infection in human immunodeﬁciency virus-infected patients. Clin Infect Dis 1999;

regimen AblativeNon-ablative No AcuteAblative Acute+chronic Fever, hypoxia pulmonary Fever, ‘whoop-like’ cough, Cough, dyspnea28: 1095–1099. Sputum Yes Present case 5 Bauwens JE, Spach DH, Schacker TW, Mustafa MM, Bowden multiple myeloma.

¼ RA. Bordetella bronchiseptica pneumonia and bacteremia following bone marrow transplantation. J Clin Microbiol 1992; 30: 2474–2475. 6 Choy KW, Wulffraat NM, Wolfs TFW, Geelen SP, Kraaijeveld CA, Fleer A. Bordetella bronchiseptica respiratory infection in a

Bordetella bronchiseptica child after bone marrow transplantation. Pediatr Infect Dis J IgM syndrome lymphoma cell lymphoma 1999; 18: 481–483. 7 Huebner ES, Christman B, Dummer S, Tang Y-W, Goodman S. Hospital acquired Bordetella bronchiseptica following hematopoietic stem cell transplantation. J Clin Microbiol 2006; 44: Age Primary disease Conditioning bronchoalveolar lavage; MM 2581–2583. ¼ Human infection with Patient 1Patient 2Patient 3 20Patient 4Patient 7 5 AML 53 X-linked 50 hyper Hodgkin’s 29 IgA (k) Ablative MM Anaplastic large- Non-ablative No Acute Cough, ‘honking’ rhonchi, Cavitary lung nodule BAL No; contact with Table 1 Abbreviations: BAL

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