Journal List > Ann Lab Med > v.41(4) > 1146663

Chen, Wang, Lu, Cui, Ma, Lou, and Zhou: Human Pneumonia Caused by Bordetella hinzii: First Case in Asia and Literature Review
Dear Editor,
The genus Bordetella comprises 12 species, some of which cause human diseases. Bordetella hinzii widely exists in poultry and rodents and has occasionally been reported in humans wherein it has been confirmed as a causative agent of pulmonary and digestive infection, and bacteremia, almost invariably in patients with immunodeficiency [1,2]. Only 11 cases of human B. hinzii infection have been reported to date, and none has been found in Asia (Table 1). However, the clinical and epidemiologic characteristics of B. hinzii infection remain to be determined. Here, we describe the first Asian case of B. hinzii pneumonia to highlight the pathogenicity of this bacterium. As this case was identified during a routine surveillance organized by the Centers for Disease Control and Prevention, the need for ethical approval for the present study was exempted by the Institutional Review Board of Chengdu Fifth People’s Hospital, China; verbal consent was obtained from the patient for case presentation.
A 67-year-old woman was admitted to the Neurological Intensive Care Unit in Chengdu Fifth People’s Hospital on January 8, 2013 because of fatigue and loss of the abilities to stand, walk, and speak clearly. Computed tomography (CT) showed spontaneous intracerebral hemorrhage involving the ventricles of the brain. The patient had been suffering from type 2 diabetes in the past year but had no other remarkable medical history. After admission, she received symptomatic treatment, supplementary fluids, and antihypertensive treatment. She developed fever on the third day. Her vital signs included a temperature of 38°C; blood pressure, 148/70 mm Hg; pulse, 84 beats/min; and respiratory rate, 27 breaths/min. Routine blood examination showed a leukocyte count of 9.27×109/L; neutrophil percentage, 88.1%, lymphocyte percentage, 6.5%; platelet count, 91×109/L; and high sensitive C-reactive protein level, 28.9 mg/L. Chest CT examination showed scattered turbidity in both lungs. Therefore, a pulmonary infection was suspected and intravenous cefmetazole (1.5 g daily) was empirically selected and initiated. The patient’s condition improved, and she was discharged on January 15, 2013.
The blood culture result was negative. Direct gram staining and microscopic examination of the sputum revealed gram-negative rods in the neutrophils. After 18 hours incubation at 35°C, colorless colonies were detected on blood, chocolate, and MacConkey agar plates, which were all gram-negative rods. One isolate from each plate was selected for identification. Initial identification performed using the API 20NE strip (bioMérieux, Lyons, France) classified the isolate as Bordetella avium with a 96.6% confidence, which could not be used to distinguish species in the genus Bordetella. The selected isolate from the blood agar plate, designated strain A2799, was subject to further identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) (Bruker, Leipzig, Germany) and 16S rRNA gene sequencing. Both methods classified this strain as B. hinzii. Antibiotic susceptibility testing was performed using the Kirby-Bauer method. The strain was found to be susceptible to the most commonly used antibiotics, and our patient recovered well through therapy with cefmetazole, which is similar to cefoxitin and ceftazidime, to which the strain was found to be susceptible.
Furthermore, the whole-genome sequence of A2799 (GenBank accession no. SRP081450) was obtained. Phylogenetic trees were constructed using a distance matrix based on the presence or absence of genes (pan-genome tree) and single nucleotide polymorphisms in the core genome (core-genome tree) for A2799 and 27 other Bordetella strains (Fig. 1). In both trees, A2799 clustered with two B. hinzii strains and with B. pseudohinzii, further suggesting that A2799 is B. hinzii. The three “classical” Bordetella species, B. pertussis, B. parapertussis, and B. bronchiseptica, were closely associated in both the pan-genome and core-genome phylogenetic trees, indicating that these three species were derived from a recent common ancestor (Fig. 1).
Our patient had been suffering from cerebral hemorrhage but had no history of physical injury or trauma on admission. In patients with B. hinzii infections, the medical history often reveals a recent exposure to poultry. However, there was a history of avian exposure for this patient. Thus, the exact nature of the exposure in our patient remains unknown.
The identification of B. hinzii was inconclusive or inaccurate with a biochemical identification system, consistent with a previous case [1]. 16S rRNA gene sequencing and routine MALDI-TOF-MS are reliable for identifying B. hinzii [1]. Furthermore, whole-genome sequencing is increasingly being applied to identify clinical microorganisms. Therefore, it is likely that some species that could not previously be identified by traditional biochemical methods will increasingly be discovered. B. hinzii infection is rare but potentially fatal. However, antibiotic therapy often results in a favorable outcome.

Notes

AUTHOR CONTRIBUTIONS

Zhou H designed the study. Chen D, wang H, Lu X performed the data collection and sampling and carried out the experiments. Cui Y, Ma X, Lou J, Zhou H carried out the sequencing and data analysis. Chen D, Lou J and Zhou H wrote the manuscript. All authors read and approved the final version of the manuscript.

CONFLICTS OF INTEREST

No potential conflicts of interest relevant to this article were reported.

RESEARCH FUNDING

This work was supported by grants from the Priority Project on Infectious Disease Control and Prevention (grant numbers 2017ZX10303405-002 and 2018ZX10201002-005) from the Ministry of Science and Technology of the People’s Republic of China.

REFERENCES

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Fig. 1
Phylogenetic trees based on whole-genome sequencing and analysis. (A) Phylogenetic tree based on the gene content (pan-genome tree). (B) Phylogenetic tree based on 810 core-genome single nucleotide polymorphisms (core-genome tree).
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Table 1
Previous cases of human infection caused by Bordetella hinzii
Year Country Clinical diagnosis Gender Age Epidemiology Immunosuppression status Method of strain identification Antibiotics treated Outcome Reference
1957 France NR NR NR NR NR Identification of new species through PAGE of whole-cell proteins, Fatty acid methyl ester analysis, DNA-DNA and DNA-rRNA hybridization NR NR [2]
1992 Switzerland Pulmonary symptoms Male 51 NR None API 20 NFT (NE) system, alkali production from malonate and PAGE of whole-cell proteins Amoxicillin-clavulanic acid, ciprofloxacin Recovered [3]
1994 United States Bacteremia Male 42 NR Immunosuppressed (AIDS) API NFT, whole-cell fatty acid analysis and DNA-DNA hybridization Vancomycin; ceftriaxone; ceftriaxone, rifampin Recovered [4]
1999 United States Cholestasis and bacteremia Male 69 Had attended a cookout at a farm 2 weeks before admission None Traditional biochemical testing and 16S rRNA gene sequence analysis Ampicillin-sulbactam, cefotetan; ampicillin, gentamicin, metronidazole; ticarcillin-sulbactam, ciprofloxacin Died [5]
2000 Spain Respiratory tract infection NR NR No avian exposure Immunosuppressed (AIDS) Traditional biochemical testing and 16S rRNA gene sequence analysis NR NR [6]
2001 Germany Chronic cholangitis Male 29 NR Immunosuppressed (liver transplant recipient) Traditional biochemical testing and 16S rRNA gene sequence analysis Piperacillin-tazobactam, gentamicin; amphotericin B, flucytosine, vancomycin, and meropenem Died [7]
2007 United Kingdom Flu-like symptoms Male 79 NR Immunosuppressed (myelodysplastic syndrome) Genotypic methods and gene sequence analysis (ompA, 16S rRNA gene) Amoxicillin, clavulanic acid; vancomycin, ceftazidime Recovered [8]
2008 United States Fevers, full-body rash, fatigue; respiratory distress Female 36 NR Immunosuppressed (Epstein–Barr virus viremia and lymphoma) Cellular fatty acid analysis and 16S rRNA gene sequence analysis Amoxicillin-clavulanic acid, oxacillin, vancomycin, trimethoprim–sulfamethoxazole, doxycycline, linezolid, meropenem, itraconazole. Died [9]
2013 Spain Respiratory symptoms Female 85 NR NR MALDI-TOF–MS; 16S rRNA gene sequence analysis Amoxicillin-clavulanate Unclear [10]
2013 France Pulmonary infection Male 43 Avian exposure Immunosuppressed (leukemia, diabetes, vascular hypertension, and non-symptomatic chronic bronchiectasis before the allograft) MALDI-TOF-MS; 16S rRNA gene sequence analysis Ciprofloxacin; trimethoprim/sulfamethoxazole; piperacillin/tazobactam, ciprofloxacin; vancomycin Recovered [1]
2014 France Chronic obstructive pulmonary disease Male 74 No recent exposure to pets and poultry Immunosuppressed (vascular hypertension, dyslipidemia, prostate cancer, ischemic heart disease) MALDI-TOF-MS; 16S rRNA gene sequence analysis Piperacillin/tazobactam, vancomycin Recovered [1]
2013 China Pneumonia Female 67 No avian exposure Cerebral hemorrhage MALDI-TOF-MS; 16S rRNA gene sequence analysis Cefmetazole Recovered This study

Abbreviations: NR, not reported; PAGE, polyacrylamide gel electrophoresis; AIDS, acquired immune deficiency syndrome; MALDI-TOF–MS, matrix-assisted laser desorption/ionization-time of flight mass spectrometry; rRNA, ribosomal RNA.

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