Bordetella bronchiseptica in non-cystic fibrosis bronchiectasis.

Bordetella bronchiseptica is a rare pulmonary infection, often associated with zoonotic transmission. It has been described in immunocompromised patients and those with underlying pulmonary disease. However, there are no case series describing the spectrum of disease caused by Bordetella bronchiseptica in patients with non-cystic fibrosis bronchiectasis. Here, we report three cases of Bordetella bronchiseptica infection in patients with non-cystic fibrosis bronchiectasis and highlight the pathophysiology of the microbe. While the clinical presentation can be quite variable, it is important to note that Bordetella bronchiseptica can be a cause of pulmonary exacerbations and can be difficult to eradicate.

Introduction

Bordetellae are gram-negative, aerobic bacterial pathogens that can infect the respiratory tract of mammals [1]. Four species can infect humans: B. pertussis, B. parapertussis, B. holmesi, and B. bronchiseptica [1]. B. pertussis and B. parapertussis evolved from B. bronchiseptica, and while B. pertussis and B. parapertussis cause whooping cough in humans, B. bronchiseptica does not produce pertussis toxin [1,2]. However, B. bronchiseptica is capable of infecting animals and humans and is the cause of “kennel cough”, a form of tracheobronchitis in dogs [3]. Importantly, B. bronchiseptica is capable of zoonotic transmission [4].

The spectrum of disease caused by B. bronchiseptica is highly variable, ranging from asymptomatic or transient carriage, to persistent infections and even death [[4], [5], [6]]. Thus far, there have been case series describing B. bronchiseptica infections in patients with underlying lung disease such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis, and with systemic immunodeficiency or immunosuppression [[5], [6], [7], [8], [9]]. Occasionally, infection can involve healthy hosts who have come in contact with sick pets [5]. There are no case series on B. bronchiseptica infection in non-cystic fibrosis (non-CF) bronchiectasis. We present 3 cases. We observe that in patients with non-CF bronchiectasis, B. bronchiseptica may be associated with or without the symptoms of a pulmonary exacerbation. We describe the symptoms, the circumstances associated with isolation of the organism, and the treatment each patient received in this case series.

Case presentations

Case 1

The patient is a 53-year-old woman with primary ciliary dyskinesia who had previously grown Pseudomonas aeruginosa (P. aeruginosa) in 2 sputum cultures. She returned for an exacerbation with increased sputum production, worsening dyspnea, and weight loss. Sputum culture grew B. bronchiseptica. She responded well to a 14 day course of tetracycline. She had multiple other exacerbations and had 5 other sputum cultures isolating B. bronchiseptica exclusively over the next 2 years despite being on long courses of doxycycline. She reported animal contact with her pet dog but it was well and did not exhibit any symptoms of “kennel cough”.

Case 2

The patient is a 66-year-old man who was evaluated for persistent, productive cough. His cultures had grown B. bronchiseptica as well as Mycobacterium avium complex in the past. A follow-up sputum culture again grew B. bronchiseptica and methicillin sensitive Staphylococcus aureus, for which he was placed on levofloxacin. He demonstrated some improvement, but shortly thereafter had increased sputum production. He was again started on levofloxacin while awaiting another sputum culture, which isolated Aspergillus and Pantoea sp. Another sputum culture a few weeks later grew P. aeruginosa but the patient has since been lost to follow up. The patient also reported having several pet cats and dogs that were all in good health.

Case 3

The patient is a 70-year-old woman with a history of sarcoidosis and bronchiectasis who reported a productive cough. Routine sputum culture on her initial visit isolated B. bronchiseptica. The patient did not own a dog but she interacted with many dogs passing by her yard and her daughter also had two cats. As she was feeling relatively well during the time of the isolate, she was not started on antibiotics. However, she had an exacerbation 10 months later requiring hospitalization. Her sputum culture grew Haemophilus influenzae and was treated adequately with levofloxacin. She improved and was discharged to home.

Discussion

Although B. bronchiseptica is an uncommon cause of respiratory infections in humans, the clinical manifestations can be quite variable. Our descriptions of B. bronchiseptica infection in patients with non-CF bronchiectasis highlight this variability. The patient in case 1 had multiple cultures exclusively growing B. bronchiseptica, making this organism the likely culprit of the pulmonary exacerbations. The second case, however, grew B. bronchiseptica in association with other more usual respiratory pathogens making it difficult to ascertain a link to the pulmonary exacerbation. The third case points to asymptomatic carriage among patients with chronic lung disease.

Whether these distinct presentations reflect differences in the host immune response to the microbe versus the expression of different virulence factors by the microbe is unknown. There are several virulence factors that likely contribute to persistent infection. First, the microbe has adhesion proteins such as filamentous hemagglutinin (FHA) and fimbriae, allowing for attachment to mammalian airways [1]. These virulence factors are regulated by the Bordetella virulence gene, BvgAS [10]. Depending on the environment, BvgAS can adopt one of three phases: Bvg+ (virulent), Bvg- (nonvirulent) and Bvgi (intermediate). It has been shown that B. bronchiseptica can form biofilms in the Bvgi phase [10,11]. This could contribute to the persistence of infection, given the difficulty of antibiotics and innate immune cells in penetrating biofilms. Another mechanism by which B. bronchiseptica circumvents the immune response is via adaptations allowing for survival in acidified phagosomes in alveolar macrophages [12]. Finally, although there are no data on the exact mechanisms allowing for interspecies transmissibility, a screen of B. bronchiseptica mutants revealed that deletion of an extracellular polysaccharide (EPS) locus led to a substantial decrease in transmissibility between mice [13]. Furthermore, it was shown that the EPS mutant was less efficient at colonizing the respiratory tract of mice and demonstrated impaired bacterial shedding. These findings suggest that EPS is integral to the virulence of B. bronchiseptica.

Unfortunately, there are no specific guidelines for the treatment of B. bronchiseptica. The most effective antimicrobial agents appear to be the aminoglycosides, anti-pseudomonal penicillins, and tetracyclines [5,7]. Variable susceptibility is seen to trimethoprim/sulfamethoxazole and fluoroquinolones, though they can also be effective [3,5,7]. Antibiotic courses of 2–6 weeks may be needed and longer courses, up to 6 months, have been required for treatment of some immunocompromised patients [3,5,6]. Unlike B. pertussis, B. bronchiseptica infection does not respond to macrolides and resistance to beta-lactam antibiotics is common [1,5,7]. Chronic or recurrent infection may occur, even after the patient is not in contact with infected animals because of persistence of the bacterium, potentially in macrophages or epithelial cells [14,15]. In addition to antibiotic therapy, source control by identifying potentially infected pets and vaccination of pets to B. bronchiseptica is recommended to prevent zoonotic transmission [7].

Funding

This work was supported in part by National Institutes of Health T32 HL083808 (EK).