Adjuvant Efficacy of the ECMS-Oil on Immune Responses against Bordetella bronchiseptica in Mice through the TLR2/MyD88/NF-κB Pathway.

Bordetella infection can be efficiently prevented through vaccination. The current study investigated the effects of an extract of Cochinchina momordica seed (ECMS) combined with oil on the immune responses to the inactivated Bordetella vaccine in mice. Serum IgG and IgG1 level was significantly increased in ECMS-oil group compared to any other group (P < 0.05) 2 weeks after immunization, while groups ECMS200 µg/400 µg-oil had a markedly higher level of serum IgG2b and IgG3 than any other groups (P < 0.05). Moreover, lipopolysaccharide/ConA-stimulated proliferation of splenocytes was significantly enhanced in ECMS 400 µg-oil immunized mice in comparison with mice in any other group (P < 0.05). RT-PCR assay revealed that while ECMS800 µg-oil group had significantly higher levels of serum IL-4, IL-10, Toll-like receptor (TLR)2, and IL-1 beta than any other group (P < 0.05), the levels of serum IL-2, IL-4, and IL-10 were markedly increased in ECMS 400 µg-oil group as compared to any other groups (P < 0.05). Blood analysis showed that ECMS800 µg-oil and oil groups had a significantly higher number of immunocytes than any other groups (P < 0.05). There were significant differences in the number of IgG+, IgG2b+, and IgA+ cells in the lung between ECMS800 µg-oil group and any other groups (P < 0.05). Western blot analysis demonstrated that stimulation with ECMS 25 µg/mL or 50 ng/mL led to a significant increase in the expression of TLR2, MyD88, and NF-κB in Raw264.7 cells (P < 0.05). Compared with any other group, the expression of MyD88 was markedly increased in the cells stimulated with ECMS 50 ng/mL, as indicated by the RT-PCR analysis (P < 0.05). Overall, we observed that ECMS-oil efficiently enhanced the humoral or cellular immune responses against Bordetella and suggested that the mechanism of adjuvant activity of ECMS-oil might involve TLR2/MyD88/NF-κB signaling pathway.

Outbreak management of multidrug-resistant Bordetella bronchiseptica in 16 shelter-housed cats.

CASE SERIES SUMMARY: This case series describes an outbreak of multidrug-resistant (MDR) Bordetella bronchiseptica in 16 shelter-housed cats with infectious respiratory disease. Four cats presented with acute dyspnea on the same day, each with a history of previous upper respiratory disease that had resolved with treatment. Early diagnostic testing and culture and sensitivity allowed for targeted antimicrobial therapy and environmental interventions. A case definition based on exposure and clinical signs identified 12 additional presumptive cases, including the likely index case. Comprehensive outbreak management included diagnostic testing, risk assessment, vaccination, use of isolation and quarantine, increased surveillance and review of biosecurity practices. The outbreak resolved in 26 days. RELEVANCE AND NOVEL INFORMATION: Management of an MDR B bronchiseptica outbreak in shelter-housed cats has not been previously described. Along with standard population and environmental measures, early and appropriate use of necropsy, PCR and bacterial culture allowed rapid and appropriate use of effective, second-line antibiotics. Shelters are resource-challenged population centers. Veterinarians working in animal shelters can play an important role in helping to develop cost-efficient and effective antimicrobial stewardship practices for companion animal settings. Outbreak management expertise and funding for diagnostic testing, as well as application of the principles of antimicrobial stewardship, are essential components of shelter medicine practice.

Bordetella bronchiseptica infections in patients with HIV/AIDS: A case report and review of the literature.

RATIONALE: Bordetella bronchiseptica is a common cause of upper respiratory tract infections in domesticated dogs and cats and a rare zoonotic pathogen in immunocompromised humans. With increasing numbers of people acquiring pets and spending time with them in confined spaces due to COVID-19 lockdowns, it is important to be aware of adverse health consequences brought about by this interaction. We present a case of B bronchiseptica pneumonia in a patient with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and review key characteristics of an additional 30 cases of B bronchiseptica infections in 29 patients with HIV/AIDS that were identified by literature review. PATIENT CONCERNS: A 61-year-old male with HIV/AIDS who was not on antiretroviral therapy and had advanced immunosuppression with a CD4+ T-lymphocyte count of 3 cells/µL sought medical attention for multiple somatic issues including subjective fevers, shortness of breath, and intermittent chest pain. DIAGNOSIS: Computed tomography of the chest identified bilateral nodular opacities in the lower lobes with scattered areas of ground glass opacities. B bronchiseptica was identified in sputum culture by mass spectrometry followed by supplementary biochemical testing. INTERVENTIONS: Empiric broad-spectrum antibiotics were initiated and changed to levofloxacin after susceptibility testing was completed. OUTCOMES: The patient was discharged after symptomatic improvement with levofloxacin. LESSONS: Pneumonia with interstitial infiltrates in the setting of advanced CD4 lymphocyte depletion is the most common clinical syndrome caused by B bronchiseptica in patients with HIV/AIDS, and may be accompanied by sepsis. Advanced immune suppression, as well as chronic medical conditions, for example, alcoholism, diabetes, and renal failure that compromise host defenses are also commonly found in cases of B bronchiseptica infection in patients who do not have HIV infection. Reported animal contact among patients was not universal. Isolates were susceptible to aminoglycosides, carbapenems, fluoroquinolones, but typically resistant to most cephalosporins.

Gamithromycin in swine: Pharmacokinetics and clinical evaluation against swine respiratory disease.

The pharmacokinetics of gamithromycin were evaluated in 26 male castrated and female crossbred swine administered gamithromycin 15% w/v (Zactran®, Boehringer Ingelheim) intravenously at 6 mg/kg bodyweight or intramuscularly at 3, 6 or 12 mg/kg bodyweight. Blood samples were collected up to Day 10 to establish the plasma profile of gamithromycin, bioavailability and dose proportionality. When administered by intramuscular injection at 6 mg/kg BWT, pharmacokinetic parameters were as follows: area under the curve until last quantifiable plasma concentration, 5.13 ± 0.957 µg*hours/ml; maximum plasma concentration, 960 ± 153 ng/ml at 5 to 15 min; terminal half-life of 94.1 ± 20.4 hr. Absolute bioavailability was 92.2%. Increase in systemic exposure was proportional to the gamithromycin dose level over the range 3-12 mg/kg BWT. No gender-related statistically significant difference in exposure was observed. For clinical evaluation of Zactran® against swine respiratory disease, 305 pigs from six commercial farms in three countries in Europe with signs associated with Actinobacillus pleuropneumoniae and/or Haemophilus parasuis and/or Pasteurella multocida and/or Bordetella bronchiseptica were used. At each site, animals were treated once in a 1:1 ratio with a single intramuscular dose of Zactran® (6 mg gamithromycin/kg bodyweight) or Zuprevo® (4% w/v tildipirosin at 4 mg/kg bodyweight; MSD Animal Health) at the recommended dose respectively. Animals were observed and scored daily for 10 consecutive days for signs of swine respiratory disease (depression, respiration and rectal temperature), and animals presenting signs of clinical swine respiratory disease (Depression Score 3 and/or Respiratory Score 3 associated with Rectal Temperature > 40.0°C) were removed from the study and considered as treatment failure. Animals which remained in the study were individually assessed for 'treatment success' or 'treatment failure' (Depression Score ≥ 1 and Rectal Temperature > 40.0°C or Respiratory Score ≥ 1 and Rectal Temperature > 40.0°C). Using a non-inferiority hypothesis test (non-inferiority margin = 0.10), the proportion of treatment successes in the Zactran® group (97%) was equivalent to or better than that in the Zuprevo® group (93%).

Bordetella bronchiseptica: a rare cause of meningitis.

BACKGROUND: Bordetella bronchiseptica is a gram-negative, obligate aerobic coccobacillus known to cause disease in domesticated animals and pets. In humans, B. bronchiseptica commonly leads to respiratory infections like pneumonia or bronchitis, and animal contact usually precedes the onset of symptoms. CASE PRESENTATION: We report a case of post-traumatic B. bronchiseptica meningitis without recent surgery in the setting of immunosuppression with a monoclonal antibody. Our case concerns a 77-year-old male with ulcerative colitis on infliximab who sustained a mechanical fall and developed a traumatic cerebrospinal fluid leak complicated by meningitis. He received meropenem then ceftazidime during his hospital course, and temporary neurosurgical drain placement was required. His clinical condition improved, and he was discharged at his baseline neurological status. CONCLUSIONS: B. bronchiseptica is an unusual cause of meningitis that may warrant consideration in immunocompromised hosts with known or suspected animal exposures. To better characterize this rare cause of meningitis, we performed a systematic literature review and summarized all previously reported cases.

Clinical response to 2 protocols of aerosolized gentamicin in 46 dogs with Bordetella bronchiseptica infection (2012-2018).

BACKGROUND: Bordetella bronchiseptica (Bb) infection commonly causes respiratory disease in dogs. Gentamicin delivered by aerosol maximizes local drug delivery without systemic absorption but clinical response to protocols remains undetermined. OBJECTIVES: To compare the clinical response to 2 protocols of aerosolized delivery of gentamicin in bordetellosis. ANIMALS: Forty-six dogs with Bb infection confirmed by culture or quantitative polymerase chain reaction on bronchoalveolar lavage. METHODS: Retrospective study. Administration of aerosolized gentamicin for ≥10 minutes q12h for ≥3 weeks using 4 mg/kg diluted with saline (group 1) or undiluted 5% solution (group 2). Clinical response firstly assessed after 3-4 weeks and treatment pursued by 3-weeks increments if cure not reached. Cure defined as absence of cough persisting at least a week after treatment interruption. RESULTS: Demographic data were similar between both groups. Clinical cure at 3-4 weeks was more frequently observed with the use of undiluted solution (19/33 vs 3/13 dogs, P = .03) in association with a shorter median duration of treatment (4 vs 6 weeks, P = .01). Dogs from group 2 having less than 1000 cells/µL in lavage were also more likely to be cured at 3-4 weeks than dogs with more than 1000 cells/µL [9/9 vs 10/19, P = .006] and median duration of treatment in that subgroup of animals was reduced (3 vs 5 weeks, P = .02). CONCLUSION AND CLINICAL IMPORTANCE: Aerosolized delivery of gentamicin seems effective for inducing clinical cure in Bb infection. Clinical response appears better using undiluted 5% solution, particularly in the subgroup of dogs having less than 1000 cells/µL in lavage.

Viral and bacterial coinfection of the respiratory tract in a 10-month-old child.

A 10-month-old child, immunised appropriately for age, presented with a history of cough, vomiting, diarrhoea, increased work of breathing and eye redness for 1 week. She was treated for suspected bronchiolitis with supportive oxygen and hypertonic saline nebulisation. In view of continuing fever spikes and persistent oxygen requirement, she was evaluated further. Her inflammatory markers were raised, blood film showed neutrophils left shift with toxic granulations and chest X-ray was suggestive of the right upper lobe segmental atelectasis suggestive of a bacterial infection. Her nasopharyngeal aspirate for multiplex tandem PCR was positive for adenovirus, respiratory syncytial virus and Bordetella species. She was treated with oral clarithromycin for 5 days which improved her symptoms. She was discharged with further follow-up. Coinfection with bacteria or atypical bacteria in children with acute respiratory tract infection is common and this coinfection can induce serious illness.

Isolation of Bordetella trematum from the respiratory tract of a patient with lung cancer: a case report.

We report the case of isolation of Bordetella trematum from the respiratory tract of a patient with lung carcinoma. This gram-negative, opportunistic rod was firstly described in 1996. To date, only several strains of Bordetella trematum have been isolated and reported, mostly from skin and soft tissue infections. The patient was admitted to the ICU of the Pulmonary Department in incipient septic shock with respiratory failure. Intravenous fluid resuscitation and non-invasive ventilation were administered immediately. A broad spectrum antibiotic piperacillin/tazobactam was administered empirically after sampling of material for microbiological examination. The bronchoscopy showed a large cavern of decayed tumour invading into mediastinum. Both sample cultures showed significant quantities of gram-negative non-fermenting bacteria. The isolate was identified using MALDI-TOF MS as Bordetella trematum and the identification was confirmed using 16S ribosomal RNA sequencing. In the last few years, routine bacterial identification using MALDI-TOF MS has enabled correct discrimination of this species. Nevertheless, isolation of Bordetella trematum in clinical samples is still very uncommon, and it is appropriate to confirm the species identification via 16S ribosomal RNA sequencing. To our knowledge, this is the first case of B. trematum isolated from the human respiratory tract since its first description. The clinical significance of Bordetella trematum in the rapid deterioration of the patient's status remains unclear.

Effects of famciclovir in cats with spontaneous acute upper respiratory tract disease.

OBJECTIVES: The aim of this study was to assess the effects of famciclovir administration in cats with spontaneously acquired acute upper respiratory tract disease. METHODS: Twenty-four kittens with clinical signs of acute upper respiratory tract disease were randomly allocated to receive doxycycline (5 mg/kg PO q12h) alone (group D; n = 12) or with famciclovir (90 mg/kg PO q12h; group DF; n = 12) for up to 3 weeks. Clinical disease severity was scored at study entry and daily thereafter. Oculo-oropharyngeal swabs collected at study entry and exit were assessed using quantitative PCR for nucleic acids of feline herpesvirus type 1 (FHV-1), feline calicivirus (FCV), Chlamydia felis, Bordetella bronchiseptica and Mycoplasma felis. RESULTS: The median (range) age of cats was 1.5 (1-6) months in group D vs 1.6 (1-5) months in group DF (P = 0.54). Pathogens detected in oculo-oropharyngeal swabs at study entry included FCV (n = 13/24; 54%), M felis (n = 8/24; 33%), FHV-1 (n = 7/24; 29%), C felis (n = 7/24; 29%) and B bronchiseptica (n = 3/24; 12%). Median (range) duration of clinical signs was 11.5 (3-21) days in group DF and 11 (3-21) days in group D (P = 0.75). Median (range) total disease score at the end of the study did not differ between groups (group D 1 [1-1] vs group DF 1 [1-3]; P = 0.08). CONCLUSIONS AND RELEVANCE: This study revealed no significant difference in response to therapy between cats treated with doxycycline alone or with famciclovir; cats improved rapidly in both groups. However, identification of FHV-1 DNA was relatively uncommon in this study and clinical trials focused on FHV-1-infected cats are warranted to better evaluate famciclovir efficacy.

Bordetella bronchiseptica experimental model development in pigs and efficacy evaluation of a single intramuscular injection of gamithromycin (Zactran® for Swine) against Bordetella bronchiseptica-associated respiratory disease in experimentally infected piglets.

In the Bordetella bronchiseptica infection model development study, twenty-eight piglets were inoculated with B. bronchiseptica strain of either canine (109  CFU/ml) or swine (108 and 109  CFU/ml) origin; swine origin strain at 109  CFU/ml was chosen for the efficacy assessment study due to higher incidence and severity of gross and histopathological lesions compared with other strains. To assess efficacy of gamithromycin against B. bronchiseptica, forty piglets were experimentally inoculated on Day 0 and clinical signs were scored as per severity. Animals were then treated either with gamithromycin or saline on Day 3. The Global Clinical Scores in gamithromycin-treated group were consistently lower than the saline-treated control group from Day 4 onwards and were 0 and 40 in the gamithromycin-treated and saline-treated control groups, respectively, on Day 6. Severity and frequency of gross and histopathological observations were significantly lower in gamithromycin-treated animals compared with saline-treated controls. The efficacy of Zactran® for Swine at the label dose for the treatment of B. bronchiseptica-associated respiratory disease was demonstrated based on the faster reduction in clinical signs as early as 1 day post-gamithromycin treatment and based on the significant difference in the severity of macroscopic and microscopic lung lesions 10 days post-gamithromycin treatment.

Diagnóstico diferencial de Bordetella bronchiseptica por RT-PCR en un niño con tos paroxística sin antecedentes patológicos previos / Differential diagnosis by RT-PCR of Bordetella bronchiseptica in a child without previous pathologic antecedents suffering whooping cough

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A case of cervical subcutaneous abscess due to Bordetella hinzii.

We present a case of subcutaneous infection caused by Bordetella hinzii in a healthy male. The isolate was successfully identified by gyrB gene sequencing. B. hinzii cannot be distinctively identified using 16S rRNA gene sequencing or by biochemical methods. The number of cases infected with B. hinzii might be underestimated owing to the difficulty in accurate identification, which can be achieved by gyrB gene sequencing to gain knowledge about the species.

Bordetella trematum infection: case report and review of previous cases.

BACKGROUND: Bordetella trematum is an infrequent Gram-negative coccobacillus, with a reservoir, pathogenesis, a life cycle and a virulence level which has been poorly elucidated and understood. Related information is scarce due to the low frequency of isolates, so it is important to add data to the literature about this microorganism. CASE PRESENTATION: We report a case of a 74-year-old female, who was referred to the hospital, presenting with ulcer and necrosis in both legs. Therapy with piperacillin-tazobactam was started and peripheral artery revascularization was performed. During the surgery, a tissue fragment was collected, where Bordetella trematum, Stenotrophomonas maltophilia, and Enterococcus faecalis were isolated. After surgery, the intubated patient was transferred to the intensive care unit (ICU), using vasoactive drugs through a central venous catheter. Piperacillin-tazobactam was replaced by meropenem, with vancomycin prescribed for 14 days. Four days later, levofloxacin was added for 24 days, aiming at the isolation of S. maltophilia from the ulcer tissue. The necrotic ulcers evolved without further complications, and the patient's clinical condition improved, leading to temporary withdrawal of vasoactive drugs and extubation. Ultimately, however, the patient's general condition worsened, and she died 58 days after hospital admission. CONCLUSIONS: Despite being a rare finding, B. trematum is typically associated with the clinical manifestation of disorders that predispose to ulcer development, which can be infected by microorganisms. The combination of antibiotic therapy and surgical debridement plays a key role in preventing systemic infections. Monitoring the appearance of new cases of B. trematum is essential, since it can be an emerging microorganism. Isolating and defining the clinical relevance of unusual bacteria yields a more accurate perspective in the development of new diagnostic tools and allows for assessment of proper antimicrobial therapy.

Bordetella pertussis in a four-time kidney transplant recipient: A call for immunization programs at transplant centers.

Pertussis, or whooping cough, is a highly contagious respiratory illness caused most frequently by Bordetella pertussis. Clinical presentation ranges in severity, but life-threatening illness disproportionately affects children and immunocompromised individuals. Acellular vaccines for pertussis have been available for decades, and they are recommended throughout the lifespan. A patient who had received a kidney transplant presented with respiratory distress and dry cough as manifestations of co-infection with B pertussis and Bordetella parapertussis/bronchiseptica. The goal of this case report was to highlight the importance of immunization programs at transplant centers, which are in the unique position to care for patients both with end-stage organ disease and in the post-transplant setting.

Chronic cough and cystic lung disease caused by Bordetella bronchiseptica in a patient with AIDS.

A 24-year-old man with a history of HIV and large B cell lymphoma (currently in remission) presented with fever, dry cough and dizziness. His CD4+ count was undetectable, and the HIV viral load was 109 295 cop/mL. Physical examination revealed fever, hypotension and tachycardia with coarse breath sounds in the middle and lower chest zones bilaterally. Chest imaging showed diffuse abnormal micronodular and patchy infiltrates, without focal consolidation. A cavitary lesion was noted measuring 5×2 cm in axial dimensions within the left lower lobe and multiple small cystic lesions in the background. Bronchoalveolar lavage fluid culture grew Bordetella bronchiseptica The patient was empirically treated with vancomycin and piperacillin-tazobactam for multifocal pneumonia with concerns for sepsis and was started on combined antiretroviral therapy (cART) with abacavir/dolutegravir/lamivudine. Symptoms improved after day 3 of therapy, and the patient was discharged home on 2 weeks of moxifloxacin, in addition to the cART and appropriate chemoprophylaxis.

Spondylodiscitis caused by Bordetella holmesii, a misrecognized pathogen emerging in invasive infections.

We report a case of spondylodiscitis caused by Bordetella holmesii, an emergent pathogen. This small Gram-negative rod was first known as a cause of invasive infections on asplenic patients. This case describes a spondylodiscitis due to this bacterium in an immunocompetent patient. This article underlines the interest of prolonged incubation for specimens in case of spondylodiscitis and shows us the contributions of mass spectrometry for easy and rapid identification of such bacterium.

Misdiagnosis of Bordetella bronchiseptica Respiratory Infection as Bordetella pertussis by Multiplex Molecular Assay.

Multiplex polymerase chain reaction (PCR) tests are useful for the rapid detection of pathogens, though diagnostic challenges may arise. We report 2 immunocompromised patients with Bordetella bronchiseptica respiratory infection misdiagnosed as Bordetella pertussis using PCR, including discussion of transmission, diagnostic testing, clinical implications, and infection control considerations.

Bordetella bronchiseptica bloodstream infection in a renal transplant patient.

Bordetella bronchiseptica is a gram-negative coccobacillus that infects animals, but rarely affects humans. B. bronchiseptica has been reported to cause disease in immunocompromised hosts. We present a case of a 61-year-old man with a renal transplant who developed B. bronchiseptica bacteremia likely as a result of close contact between dogs and his skin cancer biopsy sites. The patient was successfully treated with 2 weeks of oral levofloxacin. This case alerts physicians to B. bronchiseptica as a cause of bacteremia in solid organ transplant patients with exposure to animals.