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IntroductionBordetella bronchiseptica, a small

gram-negative coccobacillus, is pre-dominantly a pathogen causing infec-tion in cats, dogs, horses, guinea pigs,rabbits, and pigs (1,2). Human infectionis rare, occurring primarily in immuno-

compromised patients and occasionallyin healthy hosts after contact with sickpets or farm animals. Clinical presenta-tion is diverse, ranging from respiratoryto central nervous system infections.There have been a few reported cases ofnosocomial infection with this organismin severely immune-deficient individuals.We report a case of B. bronchisepticanosocomial infection in an immuno-compromised patient with no knownexposure to animals.

Case ReportA 75-year-old female was diagnosed

with mantle cell lymphoma 11 years ago,at which time she underwent chemo-therapy and autologous stem cell trans-plantation with complete remission.In 2007, the lymphoma recurred. Shereceived three courses of bortezomiband rituximab, followed by high-dosecyclophosphamide, and was admittedto University Hospital for peripheralblood stem cell transplantation.

Mailing Address: Donald Blair, M.D., 750East Adams St., Syracuse, NY 13210. Tel.:315-464-5533. E-mail: BlairD@upstate.edu

Case Report

Bordetella bronchiseptica: an Emerging Nosocomial Pathogen inImmunocompromised PatientsAbhishek Bose, M.D.,1 Waleed Javaid, M.D.,1 Elias Ashame, M.D.,1 Deanna Kiska, Ph.D.,2 Scott Riddell, Ph.D.,2 and DonaldBlair, M.D.,1 1Department of Medicine, 2Department of Pathology, State University of New York, Upstate Medical University,Syracuse, New York

118 0196-4399/00 (see frontmatter) © 2008 Elsevier Clinical Microbiology Newsletter 30:15,2008

On admission, the patient was alert,oriented, and in no distress. Her temp-erature was 36.4°C; heart rate, 74 beats/min; blood pressure, 115/68; respiratoryrate, 16 breaths/min; and oxygen satur-ation, 100% on room air. Other thanconjunctival pallor, her physical exami-nation was unremarkable. The whiteblood cell count was 2.8 × 109 cells/L;hemoglobin, 92 g/L; hematocrit, 26.3%;and platelet count, 246 × 109 cells/L.Electrolytes, liver function tests, coag-ulation profile, and renal functionwere within normal limits. Chest X rayshowed no evidence of cardiopulmo-nary disease.

The patient was treated with carmus-tine, followed by peripheral blood stemcell transplantation. She developed asystemic reaction during the stem celltransfusion, becoming hypoxic andhypotensive. Pneumonia and pulmonaryedema necessitated intubation; severalattempts at weaning were unsuccessful.Tracheostomy and percutaneous endo-scopic gastrostomy tubes were placed.Fever persisted despite treatment withbroad-spectrum antibiotics.

Computed tomography (CT) scan ofthe chest showed a new cavitary lesionin the left lower lobe. A sputum culturegrew an oxidase-negative, lactose-non-fermenting, gram-negative rod. Empirictherapy with amphotericin B was begun.Examination of a CT-guided needle bio-psy specimen revealed fibrosis, with noevidence of fungi. She remained ventila-tor dependent and febrile, with worsen-ing right upper lobe infiltrates (Fig. 1).Open-lung biopsy showed acute andorganizing pneumonia (Fig. 2). Culturesfor mycobacteria and fungi and a directfluorescence antibody stain for pneumo-cystis were negative.

Routine bacterial culture of the lungbiopsy specimen revealed moderategrowth of a gram-negative rod on sheepblood and chocolate agars after 24 h.The isolate was oxidase and catalasepositive and demonstrated lactose-nonfermenting colonies on subcultureto MacConkey agar.

The organism isolated from thesputum and lung biopsy specimenswas identified as B. bronchiseptica bythe Vitek GNI (bioMérieux, Durham,NC). DNA sequence analysis of a 528-bp fragment of 16S rRNA gene (posi-tions 7 to 535 of Escherichia coli 16SrRNA gene) was performed to confirm

the identification (3). A GenBankBLAST search of 425 bp of attainablesequence revealed 100% identity withB. bronchiseptica (BX640449), Borde-

tella parapertussis (BX640434), andBordetella pertussis (BX640420).These species and Bordetella holmesiiare closely related, forming a single

Figure 1.Appearance of acute and organizing pneumonia with neutrophilic infiltrates andcollagen formation.

Figure 2. CT chest scan showing right upper lobe airspace disease (arrow).

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cluster in phylogenetic analyses (4). Thesequence analysis results, the phenotypiccharacteristics of growth on MacConkeyagar, and the positive oxidase and ureasereactions confirmed the isolate’s identityas B. bronchiseptica.

Because no CLSI methods are avail-able for B. bronchiseptica susceptibilitytesting, a non-standardized Kirby-Baueragar disk diffusion test was attemptedby using plain Mueller-Hinton agar andEnterobacteriaceae breakpoints. Theorganism demonstrated susceptibilityto trimethoprim/sulfamethoxazole,ciprofloxacin, piperacillin/tazobactam,imipenem, and tetracycline. Despitetreatment with piperacillin/tazobactam,the patient deteriorated, developedmulti-organ dysfunction, and expired.Discussion

Ferry (5) first described B. bronchi-septica as a cause of canine infection.A common respiratory tract pathogen inwild and domestic animals, it is knownto cause “kennel cough,” or infectioustracheobronchitis, in dogs (1); otitismedia and tracheal bronchitis in rabbits;and atrophic rhinitis in swine (2). Theorganism was first cultured from humansin the early 1970s (6). It is one of eightspecies in the genus Bordetella, mostof which are strict aerobes with optimalgrowth at 35 to 37°C. B. pertussis isthe most fastidious species, requiringenriched, selective media for isolation.B. bronchiseptica and the other speciesgrow on routine media, such as sheepblood and MacConkey agars. Identif-ication of most species can be accom-plished with a minimal battery ofphenotypic tests, including oxidase,nitrate reduction, urease, motility, andgrowth on blood and MacConkey agars(7). Sequencing of 16S rRNA gene hasbeen used for definitive identificationof some Bordetella species. In our case,partial sequencing of 16S rRNA genewas not definitive but served to rule outother oxidase-positive, gram-negativerods, particularly Oligella ureolyticaand Ralstonia paucula, which may bemisidentified as B. bronchiseptica whencommercial identification systems areused (7). A combination of phenotypic

and genotypic results was necessary toconfirm the identification of the isolate.

While there are no established treat-ment guidelines, the most effectiveantimicrobial agents against B. bronchi-septica appear to be the aminoglycosides,anti-pseudomonal penicillins, tetracy-clines, and chloramphenicol. Variablesusceptibility is seen to trimethoprim-sulfomethoxazole, flouroquinolones,and rifampin. Isolates are usually resis-tant to macrolides, clindamycin, andampicillin (2). There is no consensusregarding duration of treatment. Severalauthors (8,9) reported complete eradica-tion within 2 weeks of therapy, whereasimmunocompromised patients mightrequire a longer duration of treatment(10).

To date, there have been about 60reported cases of culture-confirmed B.bronchiseptica infection in humans, witha wide variety of presentations, includingmeningitis, endocarditis, pneumonia,whooping cough, nosocomial tracheo-bronchitis, and sinusitis. The majorityof infected patients had some form ofunderlying immunosupression, such asdiabetes, AIDS, lymphoma, or leuke-mia. (2,11). B. bronchiseptica infectionin bone marrow transplant patients hasbeen reported rarely (12-14). In ourpatient, who was severely immunocom-promised following non-myeloablativestem cell transplantation, the B.bronchiseptica infection presented as ahospital-acquired pneumonia, which wasstrongly suggestive of nosocomialtransmission.

Among the published cases of B.bronchiseptica infection following bonemarrow transplantation, only half haddocumented recent or close exposure toanimals (12-14). Thus, the commonlyaccepted epidemiological risk factor ofanimal contact does not explain its occur-rence in these hospitalized, immunosup-pressed individuals. Immunosuppressionper se may be an independent risk factorfor nosocomial transmission. Additionalnosocomial infections with this unusualpathogen may be anticipated.References1. Wright, N.G. et al. 1973. Bordetella

bronchiseptica: a re-assessment of itsrole in canine respiratory disease. Vet.Rec. 93:486-487.

2. Woolfrey, B.F. and J.A. Moody. 1991.Human infections associated with Bor-detella bronchiseptica. Clin. Microbiol.Rev. 4:243-255.

3. Brosuis, J.M. et al, 1978. Completenucleotide sequence of a 16S ribosomalRNA gene from Escherichia coli. Proc.Natl. Acad. Sci. USA 75:4801-4805.

4. Kattar, M.M. et al. 2000. Application of16S rRNA gene sequencing to identifyBordetella hinzii as the causative agentof fatal septicemia. J. Clin. Microbiol.38:789-794.

5. Ferry, N.S. 1910. A preliminary reportof the bacterial findings in caninedistemper. Am. Vet. Rev. 37:499-504.

6. Snell, J.J.S. 1973. The distribution andidentification of non-fermenting bac-teria, p. 145. Public Health Lab. Serv.Monogr. Ser. no. 4.

7. Loeffelholz, M.J. and G.N. Sanden.2007. Bordetella, p. 803-814. In M.A.Pfaller et al. (ed.), Manual of clinicalmicrobiology, 9th ed. ASM Press,Washington, DC.

8. Woodard, D.R., L.A. Cone, and K.Fostvedt. 1995. Bordetella bronchi-septica infection in patients withAIDS. Clin. Infect. Dis. 20:193-194.

9. Papasian, C.J. et al. 1987. Bordetellabronchiseptica bronchitis. J. Clin.Microbiol. 25:575-577.

10. Gomez, L.M. et al. 1998. Bacterialpneumonia due to Bordetella bronchi-septica in a patient with acute leukemia.Clin. Infect. Dis. 26:1002-1003.

11. Dworkin, M.S. et al. 1999. Bordetellabronchiseptica infection in humanimmunodeficiency virus-infectedpatients. Clin. Infect. Dis. 28:1095-1099.

12. Bauwens, J.E. et al. 1992. Bordetellabronchiseptica pneumonia and bacter-emia following bone marrow transplan-tation. J. Clin. Microbiol. 30:2474-2475.

13. Choy, K.W. et al. 1999. Bordetella bron-chiseptica respiratory infection in achild after bone marrow transplantation.Pediatr. Infect. Dis. J. 18:481-483.

14. Huebner, E.S. et al. 2006. Hospital-acquired Bordetella bronchisepticainfection following hematopoietic stemcell transplantation. J. Clin. Microbiol.44:2581-2583.