Successful treatment of Bordetella bronchiseptica pneumonia by minocycline in anti-neutrophil cytoplasmic antibodies-associated vasculitis patient

Successful treatment of Bordetella bronchiseptica pneumonia by minocycline in anti-neutrophil cytoplasmic antibodies-associated vasculitis patient

J Infect Chemother xxx (2016) 1e3 Contents lists available at ScienceDirect Journal of Infection and Chemotherapy journal homepage: http://www.elsev...

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J Infect Chemother xxx (2016) 1e3

Contents lists available at ScienceDirect

Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic

Case report

Successful treatment of Bordetella bronchiseptica pneumonia by minocycline in anti-neutrophil cytoplasmic antibodies-associated vasculitis patient Yuji Ito a, *, Keiichi Uemura b a b

Department of General Internal Medicine, Chutoen General Medical Center, Shizuoka, Japan Department of Microbiology, Chutoen General Medical Center, Shizuoka, Japan

a r t i c l e i n f o

a b s t r a c t

Article history: Received 27 January 2016 Received in revised form 13 June 2016 Accepted 16 June 2016 Available online xxx

Bordetella bronchiseptica is a bacterial pathogen usually isolated from animals and rarely causes human infections. There are, however, some reports that B. bronchiseptica causes human respiratory infections in immunocompromised patients or those with underlying respiratory diseases, although there is a lack of treatment guidelines. An 80-year-old woman was admitted to our hospital to treat anti-neutrophil cytoplasmic antibodies-associated vasculitis. On the 16th day after admission, she complained of a productive cough with right pleuritic pain and had low-grade fever. After chest CT scans, we diagnosed pneumonia. Gram stain of her sputum revealed moderate levels of gram-negative coccobacilli, which was later identified as B. bronchiseptica by mass spectrometry. According to the result of minimum inhibitory concentration, we successfully treated the pneumonia with minocycline. This case suggests that B. bronchiseptica pneumonia can be treated by minocycline if the minimum inhibitory concentration is less than 0.25 mg/mL. © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Keywords: Bordetella bronchiseptica Pneumonia Minocycline Immunocompromised host

1. Introduction

2. Case report

Since Ferry NS published the first case of Bordetella bronchiseptica of a respiratory tract infection in a dog in 1911 [1], it has been demonstrated to occur in various mammals. Unlike Bordetella pertussis, B. bronchiseptica had been rarely believed to cause human infections; however, some recent reports have shown B. bronchiseptica respiratory infections, particularly in immunocompromised patients or in those with underlying respiratory diseases [2]. Because B. bronchiseptica primarily causes animal infection, the Clinical and Laboratory Standards Institute (CLSI) provides information of antimicrobial susceptibility testing for this pathogen in animals [3] but not in humans [4]. Here, we report a case of a B. bronchiseptica pneumonia successfully treated by minocycline.

An 80-year-old woman was admitted to our hospital due to an induction therapy for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. She had a 1-month history of lowgrade fever and biopsy-proven leukocytoclastic vasculitis (without granulomas) of the lower extremities. Her medical history was unremarkable. She did not smoke and drink at all. She had a dog in her house. Blood test results revealed C-reactive protein at 69.4 mg/L and MPO-ANCA > 300 U/mL. Urinary analysis revealed glomerulonephritis. Chest imaging revealed bronchiectasis and some interstitial pneumonia. We diagnosed ANCA-associated vasculitis. We started 14-day induction therapy consisting of intravenous methylprednisolone at 60 mg per day. After the induction therapy, corticosteroids were switched to oral prednisolone at 40 mg per day and oral azathioprine at 50 mg per day added. Sixteen days following the start of therapy, she began to complain of a productive cough with right pleuritic pain and of a low-grade fever. Her blood pressure was 137/72 mmHg, with pulse rate at 86 beats/min. Oxygen saturation was 95% while breathing ambient air. Physical examination identified tenderness in the 5th intercostal space,

* Corresponding author. 1-1 Shoubugaike, Kakegawa, Shizuoka, Japan. Tel.: þ81 537 21 5555; fax: þ81 537 28 8971. E-mail address: [email protected] (Y. Ito).

http://dx.doi.org/10.1016/j.jiac.2016.06.008 1341-321X/© 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Ito Y, Uemura K, Successful treatment of Bordetella bronchiseptica pneumonia by minocycline in antineutrophil cytoplasmic antibodies-associated vasculitis patient, J Infect Chemother (2016), http://dx.doi.org/10.1016/j.jiac.2016.06.008

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Y. Ito, K. Uemura / J Infect Chemother xxx (2016) 1e3

where we also found coarse crackles on auscultation. Her white blood cell count was 25,000/mm3; hemoglobin level, 9.4 g/dL; and platelet count, 295,000/mm3. Urea nitrogen was 20.2 mg/dL; creatinine, 0.77 mg/dL; C-reactive protein, 0.78 mg/dL; total protein, 5.9 g/dL; and albumin, 2.7 g/dL. Liver function tests and electrolytes in the blood were normal. Chest X-ray (Fig. 1A) and CT scans (Fig. 1B) of the chest revealed new consolidation in the subpleural space. Gram stain of her sputum contained polymorphonuclear leukocytes and revealed moderate levels of gramnegative coccobacilli without the presence of other bacterium. Acid-fast stain of the sputum was negative. After a 3-day course of ceftriaxone was intravenously administered, the result of the sputum culture, however, revealed B. bronchiseptica with beta-lactamase, which was confirmed by mass spectrometry [MALDI ToF-MS (Bruker Daltonik, Japan)] with a score of 2.338 (Fig. 2). Considering the high minimum inhibitory concentration (MIC) for cefotaxime, we switched from intravenous ceftriaxone to a 14-day course of oral minocycline at 100 mg BID in

accordance with the results of MIC of B. bronchiseptica (Table 1). The fever rapidly decreased, and the consolidation seen on chest X-ray disappeared 2 weeks later. We did not observe any relapse of B. bronchiseptica pneumonia since the completion of this course of antibiotic treatment.

Table 1 Minimum inhibitory concentrations of B. bronchiseptica in the present case. Antibiotics

MIC

Penicillin G Ampicillin/sulbactam Cefazolin Cefotaxime Azithromycin Minocycline Levofloxacin Co-trimoxazole

>4 mg/mL 16 mg/mL >4 mg/mL >32 mg/mL 2 mg/mL 0.25 mg/mL 1 mg/mL 40 mg/mL

Fig. 1. Chest X-ray (Panel A) shows new consolidation (arrow). Computed tomography of the chest (Panel B) shows new consolidation (arrow).

Fig. 2. The result of mass spectrometry from this patient (lower part) is consistent with the reference mass spectrometry of B. bronchiseptica in the MALDI Biotyper library (upper part).

Please cite this article in press as: Ito Y, Uemura K, Successful treatment of Bordetella bronchiseptica pneumonia by minocycline in antineutrophil cytoplasmic antibodies-associated vasculitis patient, J Infect Chemother (2016), http://dx.doi.org/10.1016/j.jiac.2016.06.008

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3. Discussion When an infection occurs, it requires several important factors for pathogenesis: presence of pathogenic microorganisms and overcoming the immunity of the host and proliferation. The former is a matter of affinity to some tissues. B. bronchiseptica is a Gram-negative coccobacillus and one of the seven species of Bordetella. It usually colonizes the respiratory tract of several animals, including dogs, pigs, cats, rabbits, mice, rats, guinea pigs, sheep, horses, and bears, and causes respiratory tract infection in the animals (i.e., “canine cough”) [5]. After an incubation period that ranges from 1 to 8 days, clinical signs occur and last for 1e2 weeks. Infections with B. bronchiseptica in animals vary from asymptomatic cases to severe bronchopneumonia. Infected dogs may shed the pathogen for 2e3 months after clinical recovery. Although B. pertussis and Bordetella parapertussis are exclusively human pathogens, B. bronchiseptica infection in humans that are not considered to be natural hosts is rare; however, it has been documented in both healthy and immunocompromised hosts. Wermli D et al. [2] reported that 3 out of 8 human patients infected with B. bronchiseptica were exposed to animals, particularly cats; 3 patients were immunocompromised; and 4 patients had chronic respiratory illness. In our case, it is possible that B. bronchiseptica was transmitted to the patient's respiratory tract from her dog. In order to confirm the hypothesis above, we collected the samples from the mouth of her dog and transported them to the microbiological laboratory for culture analysis. The result of the culture test did not prove that B. bronchiseptica was in her dog's mouth. This may be because B. bronchiseptica had been eliminated, after transmission, from her dog's respiratory tract before our sampling. The development of human infections of B. bronchiseptica, particularly HIV or malignancy, requires an immunocompromised host [6]. This was the case with our patient. A majority of the infections are respiratory tract infections, some are peritonitis [7], and some are meningitis [8]. Although there is no established study about the prognosis of B. bronchiseptica infection, Wermli D et al. [2] reported a case series demonstrating that the mortality rate was 12.5%. The detection of microorganisms sometimes depends on the conventional knowledge and skills of the laboratory staff. It takes a long time to become an experienced technician. Even with such technicians, it takes time to conventionally detect microorganisms. Technical progression of laboratory systems in recent years has allowed for more accurate detection of pathogens in a shorter time [9]. Based on technologies such as mass spectrometry, we have identified several rare pathogens that cause human infections more than previously expected [10]. Although, in this case, both mass spectrometry and the conventional method of biochemical characteristics indicating B. bronchiseptica were conducted, mass spectrometry helped us to confirm the pathogen responsible for the infection 2 days earlier as compared to the conventional method of biochemical characteristics. Newer technologies improve the time to effective and optimal antibiotic therapy and may also reduce mortality [11,12]. We treated B. bronchiseptica pneumonia in this case by minocycline according to the MIC. Brogan et al. [13] reported an average sputum minocycline concentration of 0.83 ± 1.0 mg/mL in a series of patients receiving minocycline at 200 mg per day. It is possible that this sputum concentration of minocycline sufficiently overcame the MIC of minocycline in this patient. In our case, the minocycline dose to treat pneumonia was selected after the result of susceptibility testing, which concluded in successful treatment. There are some reports describing the susceptibility testing of B. bronchiseptica [14,15]. These show that this bacterium is susceptible to piperacillin, tetracyclines, aminoglycosides,

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fluoroquinolones, and co-trimoxazole. However, the results from these studies were mostly based on in vitro susceptibility testing, despite there being a lack of CLSI interpretation guidelines in human infections [4]. CLSI guideline in animal infections [3] recommends the use of ampicillin, tulathromycin, and florfenicol. Among those agents, only ampicillin is used for human infections that may be resistant to B. bronchiseptica infection in humans [15]. There are currently no guidelines for the duration of treatment either. Berkowitz et al. [6] recommended a course of antibiotic therapy for 2e4 weeks; however, that may depend on the clinical courses and patient's backgrounds. Because many therapeutic agents, including immunosuppressants, are in development, we expect an increased number of infectious diseases with bacteria that rarely cause human infection. In addition to the accurate identification of pathogens, it is important to accumulate similar therapeutic experiences and to develop treatment guidelines for rare pathogens. Conflict of interest None. Acknowledgments The authors would like to thank Enago (www.enago.jp) for the English language review. References [1] Ferry NS. Etiology of canine distemper. J Infect Dis 1911;8:399e420. [2] Wernli D, Emonet S, Schrenzel J, Harbarth S. Evaluation of eight cases of confirmed Bordetella bronchiseptica infection and colonization over a 15-year period. Clin Mircobiol Infect 2011;17:201e3. [3] Clinical and Laboratory Standards Institute. VET01eS2 Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals; second informational supplement. 2013. [4] Clinical and Laboratory Standards Institute. M100eS25 Performance standards for antimicrobial susceptibility testing; twenty-fifth informational supplement. 2015. [5] Bhardwaj M, Singh BR, Vadhana P. Bordetella bronchiseptica infection and Kennel cough in dogs. Adv Anim Vet Sci 2013;1:1e4. [6] Berkowitz DM, Bechara RI, Wolfenden LL. An unusual cause of cough and dyspnea in an immunocompromised patient. Chest 2007;131:1599e602. [7] Dlamini NR, Bhamjee A, Levick P, Unlacke E, Ismail H, Smith A. Spontaneous bacterial peritonitis and pneumonia caused by Bordetella bronchiseptica. J Infect Dev Ctries 2012;6:588e91. [8] Belen O, Campos JM, Cogen PH, Jantausch BA. Postsurgical meningitis caused by Bordetella bronchiseptica. Pediatr Infect Dis J 2003;22:380e1. [9] Seng P, Drancourt M, Gouriet F, La Scola B, Fournier PE, Rolain JM, et al. Ongoing revolution in bacteriology: routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Clin Infect Dis 2009;49:543e51. [10] Seng P, Abat C, Rolain JM, Colson P, Lagier JC, Gouriet F, et al. Identification of rare pathogenic bacteria in a clinical microbiology laboratory: impact of matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 2013;51:2182e94. [11] Suzuki H, Hitomi S, Yaguchi Y, Tamai K, Ueda A, Kamata K, et al. Prospective intervention study with a microarray-based, multiplexed, automated molecular diagnosis instrument (Verigene system) for the rapid diagnosis of bloodstream infections, and its impact on the clinical outcomes. J Infect Chemother 2015;21:849e56. [12] Huang AM, Newton D, Kunapuli A, Gandhi TN, Washer LL, Isip J, et al. Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia. Clin Infect Dis 2013;57:1237e45. [13] Brogan TD, Neale L, Ryley HC, Davies BH, Charles J. The secretion of minocycline in sputum during therapy of bronchopulmonary infection in chronic chest diseases. J Antimicrob Chemother 1977;3:247e51. [14] Woolfrey BF, Moody JA. Human infections associated with Bordetella bronchiseptica. Clin Microbiol Rev 1991;4:243e55. [15] Garcia-de-la-Fuente C, Guzman L, Cano ME, Aguero J, Sanjuan C, Rodriguez C, et al. Microbiological and clinical aspects of respiratory infections associated with Bordetella bronchiseptica. Diagn Microbiol Infect Dis 2015;82:20e5.

Please cite this article in press as: Ito Y, Uemura K, Successful treatment of Bordetella bronchiseptica pneumonia by minocycline in antineutrophil cytoplasmic antibodies-associated vasculitis patient, J Infect Chemother (2016), http://dx.doi.org/10.1016/j.jiac.2016.06.008