1030. Chasing the Long Tail of Infectious Diseases: Detecting Capnocytophaga canimorsus and Pasteurella multocida Infections with A Plasma-based Microbial Cell-Free DNA Next Generation Sequencing Test

Background Capnocytophaga canimorsus (Cc) and Pasteurella multocida (Pm) are gram negative bacterial commensal pathogens typically from dogs or cats that can cause severe infection in humans when spread through licks, scratches or bites. The diagnosis of these infections can be limited by: (1) their fastidious nature and difficulty to culture; (2) the nonspecific manifestations of the infections; and (3) the unreliability of dog or cat exposure history. Open-ended microbial cell free DNA (mcfDNA) next-generation sequencing (NGS) offers a potential solution to overcome these limitations. Methods The Karius TestTM (KT) developed and validated in Karius’s CLIA certified/CAP accredited lab in Redwood City, CA detects mcfDNA in plasma. After mcfDNA is extracted and NGS performed, human reads are removed, and remaining sequences are aligned to a curated database of > 1500 organisms. McfDNA from organisms present above a statistical threshold are reported and quantified in molecules/µL (MPM). KT detections of Cc and Pm were reviewed from August 2017 - present; clinical information was obtained with test requisition or consultation upon result reporting. Results KT detected 5 cases of Cc (25,039 MPM +/- 41,062) and 8 cases of Pm (33,264 MPM +/- 69,301) (Table 1). All detections of Cc were in adults (60% male) and included 2 cases of culture-negative endocarditis (one with known liver disease) and one case of sepsis with diffuse rash. Pm detections occurred in 6 adults and 2 children (75% male) and included 2 cases of culture-negative endocarditis, and single cases each of endovascular graft infection, pneumonia, fever of unknown origin, and a cranial dog bite complicated by an abscess. Two patients had immunocompromising conditions including neuroblastoma and aplastic anemia. Conclusion Unbiased, plasma-based mcfDNA NGS provides a rapid, non-invasive test to diagnose diverse clinical infections by Cc and Pm. These cases highlight the potential of the KT to diagnose infections caused by fastidious/unculturable pathogens with non-specific clinical manifestations and broad differential diagnoses. Disclosures Nicholas R. Degner, MD, MPH, MS, Karius Inc. (Employee, Shareholder) Ricardo Galvan-Castillo, MD, Karius Inc. (Employee, Shareholder) Jose Alexander, MD, D(ABMM), FCCM, CIC, SM, MB(ASCP), BCMAS, Karius (Employee) Aparna Arun, MD, Karius (Employee) Ann Macintyre, DO, Karius, Inc. (Employee) Bradley Perkins, MD, Karius, Inc. (Employee) Asim A. Ahmed, MD, Karius, Inc. (Employee) Matthew Smollin, PharmD, Karius, Inc. (Employee)

Detection of Capnocytophaga canimorsus and Capnocytophaga cynodegmi in dogs with periodontal disease of Brazil

Capnocytophaga canimorsus e Capnocytophaga cynodegmi são bacilos Gram-negativos encontrados na microbiota oral de cães e gatos capazes de infectar humanos através de mordidas, lambidas ou contato próximo aos animais. As manifestações clínicas vão desde inflamação local da lesão a sepse, podendo ser seguida por óbito em humanos. O objetivo do trabalho foi detectar C. canimorsus e C. cynodegmi em amostras de curetagem subgengival de cães domiciliados atendidos em um Hospital Veterinário Público no Brasil, através da técnica de PCR. De 121 amostras testadas, a prevalência de C. canimorsus foi de 19% e de C. cynodegmi foi de 66,94%. Houve associação significativa entre a presença de C. cynodegmi e doença periodontal avançada. Conclui-se que os microrganismos estão circulantes na microbiota oral de cães domiciliados do Brasil, o que representa um risco à saúde pública devido ao seu potencial zoonótico. Visto a falta de estudos sobre esses microrganismos no país, se faz necessária a realização de pesquisas para compreender a patogenia, manifestações clínicas, diagnóstico e tratamento de infecções por C. canimorsus e C. cynodegmi no Brasil, visando a Saúde Única.

A Case of Capnocytophaga Canimorsus Meningitis in Immunocompetent Host: A Zoonotic Agent in the Lombardian Alpes in Italy

The author reports the case of C. canimorsus meningitis consecutive to Capnocytophaga canimorsus infection in a 51-year-old man. Human infection is rare but can lead to devastating outcomes. In patients in whom shortly after a dog or cat bite symptoms of meningitis occurred, C. canimorsus infection should be considered. The purpose of this report is to raise awareness of C. canimorsus among physicians when faced with a patient presenting with meningitis, who has been exposed to dogs or cats. Clinicians should adopt a higher clinical suspicion in the absence of classical risk factors. Although mortality is relatively low, survivors often have neurological sequelae. This case report highlights the importance of thorough history taking to assess risk of underlying C. canimorsus infection, even in immunocompetent hosts.

Fatal septic shock due to Capnocytophaga canimorsus bacteremia masquerading as COVID-19 pneumonia - a case report

Background Capnocytophaga canimorsus (C. canimorsus) infections are rare and usually present with unspecific symptoms, which can eventually end in fatal septic shock and multiorgan failure. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related coronavirus disease 2019 (COVID-19), on the other hand, is predominantly characterized by acute respiratory failure, although other organ complications can occur. Both infectious diseases have in common that hyperinflammation with a cytokine storm can occur. While microbial detection of C. canimorsus in blood cultures can take over 48 h, diagnosis of SARS-CoV-2 is facilitated by a widely available rapid antigen diagnostic test (Ag-RDT) the results of which are available within half an hour. These Ag-RDT results are commonly verified by a nucleic acid amplification test (NAAT), whose results are only available after a further 24 h. Case presentation A 68-year-old male patient with the diagnosis of COVID-19 pneumonia was referred to our Intensive Care Unit (ICU) from another hospital after testing positive on an Ag-RDT. While the initial therapy was focused on COVID-19, the patient developed a fulminant septic shock within a few hours after admission to the ICU, unresponsive to maximum treatment. SARS-CoV-2 NAATs were negative, but bacteremia of C. canimorsus was diagnosed post-mortem. Further anamnestic information suggest that a small skin injury caused by a dog leash or the subsequent contact of this injury with the patient’s dog could be the possible point of entry for these bacteria. Conclusion During the acute phase of hyperinflammation and cytokine storm, laboratory results can resemble both, sepsis of bacterial origin or SARS-CoV-2. This means that even in the light of a global SARS-CoV-2 pandemic, where this diagnosis provides the most salient train of thoughts, differential diagnoses must be considered. Ag-RDT can contribute to early detection of a SARS-CoV-2 infection, but false-positive results may cause fixation errors with severe consequences for patient outcome.

Capnocytophaga canimorsus and infective endocarditis—making a dog’s dinner of the aortic valve: a case report

Background Capnocytophaga canimorsus, a bacterium found in the oral cavities of healthy cats and dogs, is rarely reported as a cause of infective endocarditis. In this report we describe such a case in a young, male dog owner who presented acutely unwell in heart failure. Case summary A 47-year-old male presented with a subacute onset of fever, night sweats, weight loss, dyspnoea, and peripheral oedema. On clinical examination typical features of infective endocarditis, heart failure, and aortic regurgitation were found. The patient had no conventional risk factors for infective endocarditis but was a dog owner. Transthoracic echocardiography revealed vegetations on the right coronary and non-coronary cusps of the aortic valve causing severe eccentric aortic regurgitation and left ventricular dilatation. Initial blood cultures taken prior to the initiation of antimicrobial therapy showed no growth. The patient underwent aortic valve and root replacement and a 16S ribosomal RNA polymerase chain reaction (16S rRNA PCR) of the resected aortic valve tissue, using the additional primer set 785F/1175R targeting the V5–7 region of 16S rRNA, identified C. canimorsus. The patient was treated post-operatively with a 6-week course of meropenem and made a good recovery. Discussion Suspicion of C. canimorsus causing infective endocarditis should be considered in culture-negative infective endocarditis in individuals who have close contact with dogs or cats. Those who are immunocompetent can be susceptible to this infection and so this diagnosis should not be disregarded in healthy individuals. A 16S rRNA PCR can help identify this bacterium and should be used early in cases of culture-negative infective endocarditis.

Capnocytophaga canimorsus meningitis and bacteraemia without a dog bite in an immunocompetent individual

We describe the case of an immunocompetent 75-year-old man with Capnocytophaga canimorsus bacteraemia and meningitis. C. canimorsus is commonly found in the oral flora of dogs with human infection typically occurring following a bite. Unusually, while our patient was a dog owner, there was no history of bite nor scratch mark. Admission blood cultures flagged positive for Gram-negative bacilli, but prolonged molecular analysis was required before C. canimorsus was isolated in blood and cerebrospinal fluid. There is a high mortality rate in invasive infection, and in our patient’s case, antibiotic therapy was commenced prior to laboratory confirmation with our patient making a complete recovery. This case highlights the importance of including C. canimorsus in the differential diagnosis of unwell patients who keep dogs, even without a bite. This case occurred amid heightened awareness of COVID-19, which may represent predisposition for zoonoses during social isolation and increased human–pet contact.

Capnocytophaga canimorsus Bloodstream Infection Associated with an Urticarial Exanthem

Background. Capnocytophaga canimorsus is a fastidious, slow-growing, Gram-negative rod that is a commensal bacterium in normal gingival flora of canine and feline species. Infection with the organism may cause disease ranging from flu-like symptoms to disseminated intravascular coagulation (DIC), fulminant sepsis, meningitis, and endocarditis with an overall fatality rate of 6–26%. Risk factors for infection from C. canimorsus include immunosuppression, alcoholism, and asplenia. Case Presentation. We describe an unusual case with a relatively indolent clinical course and an urticarial exanthem in an otherwise young immunocompetent patient with a history of type 1 diabetes. The patient presented to the Emergency Department (ED) with a <1-day history of rhinorrhea, fever, and dyspnea. He met sepsis criteria on initial presentation, but left against medical advice and returned to the ED the following day, with new arthralgias and a diffuse rash, multiple erythematous, tender macules scattered across his trunk and extremities, and tonsillar erythema. He had not taken the doses of the prescribed amoxicillin. Blood cultures two days later signaled positive for growth with the Gram stain showing a Gram-negative rod. Three 7-8 cm tender targetoid lesions with central clearing were identified on the patient’s back. The patient reported two nonengorged ticks crawling on his body a week prior and sustaining a dog bite to his ear three weeks before presentation. Ultimately, the organism was identified as C. canimorsus through MALDI-TOF mass spectrometry and additional biochemical testing. He was given appropriate antibiotics and improved clinically thereafter. Despite the patient’s bacteremia, he never progressed to fulminant sepsis and followed a mild clinical course with several unusual characteristics. C. canimorsus is an uncommon cause of illness in humans, but is an important pathogen to consider when evaluating a patient with a dog bite, known risk factors, and an urticarial exanthem as empiric treatment may prevent severe outcomes.