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Meningitis caused by Capnocytophaga canimorsus in a COVID-19 patient: a rare complication of dog bites

ABSTRACT

Capnocytophaga canimorsus is a gram-negative rod that is part of the commensal microbiota of dogs’ and cats’ mouths. In this case, we report an 85-year-old man with COVID-19 who had his right arm bitten by a dog. His symptoms were impaired consciousness, agitation and aggressive behavior. Physical examination revealed neck stiffness and Brudzinski’s sign. The cerebrospinal fluid culture was compatible with Capnocytophaga canimorsus. He required intensive care and received a 14-day prescription of meropenem. After 40 days of hospitalization, the patient was fully recovered and was discharged. This case highlights the importance of physician and microbiologist be awareness of this disease, mainly in patients with neurological symptoms after a dog or cat bite.

Capnocytophaga canimorsus; Meningitis; Dog; SARS-CoV-2; COVID-19

INTRODUCTION

Capnocytophaga canimorsus is a fastidious, fermenter, capnophilic, facultative anaerobic, fusiform or filamentous gram-negative rod found in the commensal oral microbiota of dogs and cats11. Chesdachai S, Tai DB, Yetmar ZA, Misra A, Ough N, Abu Saleh OA. The characteristics of Capnocytophaga infection: 10 years of experience. Open Forum Infect Dis. 2021;8:ofab175.. It was first reported as a cause of meningitis and septicemia in the 1970s. Transmission to humans may occur after a bite and rarely after dog/cat licking of pre-existing wounds33. Hannon DM, Harkin E, Donnachie K, Sibartie S, Doyle M, Chan G. A case of Capnocytophaga canimorsus meningitis and bacteraemia. Ir J Med Sci. 2020;189:251-2.. Infections related to feline exposure are less frequent11. Chesdachai S, Tai DB, Yetmar ZA, Misra A, Ough N, Abu Saleh OA. The characteristics of Capnocytophaga infection: 10 years of experience. Open Forum Infect Dis. 2021;8:ofab175.,22. Butler T, Weaver RE, Ramani TK, Uyeda CT, Bobo RA, Ryu JS, et al. Unidentified gram-negative rod infection: a new disease of man. Ann Intern Med. 1977;86:1-5.,44. Renzi F, Hess E, Dol M, Koudad D, Carlier E, Ohlén M, et al. Capsular serovars of virulent Capnocytophaga canimorsus are shared by the closely related species C. canis and C. cynodegmi. Emerg Microbes Infect. 2018;7:124.. Most of the infections occur in men over the age of 50 with a history of dog bites and immunocompromise22. Butler T, Weaver RE, Ramani TK, Uyeda CT, Bobo RA, Ryu JS, et al. Unidentified gram-negative rod infection: a new disease of man. Ann Intern Med. 1977;86:1-5.,33. Hannon DM, Harkin E, Donnachie K, Sibartie S, Doyle M, Chan G. A case of Capnocytophaga canimorsus meningitis and bacteraemia. Ir J Med Sci. 2020;189:251-2.. Although the pathogen has been reported worldwide, to the authors’ knowledge, there have been no previously reported cases of meningitis caused by this microorganism in Brazil. Herein, we report a case of meningitis caused by Capnocytophaga canimorsus and perform a brief literature review.

Medical records were reviewed during the patient’s hospitalization in September 2020 at the Hospital Sao Jose de Doencas Infecciosas (HSJ), an infectious disease center. We reviewed the literature for similar cases. The patient consented to the publication of his case and images. This study was approved by the Research Ethics Committee of the HSJ (Protocol Nº 4.963.906).

CASE REPORT

An 85-year-old man who lived in a rural area and had no previous history of comorbidities sought the emergency room with a dog bite on his right arm from 15 days prior to his admission. He reported having a 2-day fever (38.2 °C temperature) and a 5-day history of aggressive behavior, mental confusion, psychomotor agitation and impaired consciousness. On the physical examination, a healing wound measuring 3 × 2 cm was noted in the posterior region of his right arm. No signs of cutaneous or soft tissue infection were observed. The neurological examination revealed nuchal rigidity and Brudzinski’s sign. Laboratory findings on admission showed leukocytosis (15,000/mm3) and a low platelet cell count (9,000/mm3). The patient also presented an elevated C-reactive protein (187.7 mg/L). Liver and renal function tests were unremarkable. His glycosylated hemoglobin level was normal. Anti-HIV 1/2 Western blot was negative. Blood cultures were negative. Despite the absence of respiratory symptoms, because of the admission protocol of our intensive care unit (ICU), the patient performed a RT-PCR for SARS-CoV-2, which was positive. The diagnosis of COVID-19 was made through the amplification of the betacoronavirus E gene and the specific SARS-CoV-2 RdRp gene by RT-PCR.

Cranial computed tomography was normal. Based on the suspicion of meningitis, a cerebrospinal fluid (CSF) analysis was performed. This revealed glucose levels of 9 mg/dL, a protein concentration of 171.3 mg/dL, a white blood cell count of 727 cells/mm3 with 89% polymorphonucleocytes and a CSF Gram stain with gram-negative bacilli (Figure 1A). During hospitalization, CSF culture samples revealed translucent, spotty and flat colonies on a chocolate agar plate after 48 h of incubation at 35 °C with 5% CO2 (Figures 1B and BC), with no growth on MacConkey agar or without CO2. At first, Vitek®2 GN ID card (Biomérieux, Marcy-l’Étoile, France) found three potentially identifiable microorganisms with low discrimination: Sphingomonas paucimobilis (34%), Chryseobacterium indologenes (33%), and Brevundimonas diminuta/Brevundimonas vesiculares (33%). Due to the low discrimination, a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF – VITEK MS®) (Biomérieux, Marcy- l’Étoile, France) was performed and C. canimorsus was identified with a 99.9% confidence value. The patient had no clinical improvement during the first 5 days of ceftriaxone treatment. Thus, he received meropenem with a prompt clinical response. He was admitted to an ICU due to loss of consciousness, although he did not require orotracheal intubation and was discharged from the ICU after 5 days. The patient was discharged after a 14-day regimen of meropenem with full clinical resolution of his symptoms. He presented no sequelae at the six-month follow-up.

Figure 1
A) Gram stain of C. canimorsus culture showing fusiform gram-negative rod. The same microscopic appearance that have been found on the CSF Gram stain; B-C) CSF culture with translucent, stained, and flat colonies on a chocolate agar plate after 48h of incubation at 35 °C with 5% CO2.

DISCUSSION

Many species of microorganisms with varying degrees of human pathogenicity have been identified in the oral flora of canids and felines. C. canimorsus is not a unique organism that causes infection in humans through dog bites. Capnocytophaga cynodeginia and Capnocytophaga canis are also part of the gingival flora of dogs and cats, although they usually present themselves as mild and localized cutaneous and soft tissue infections44. Renzi F, Hess E, Dol M, Koudad D, Carlier E, Ohlén M, et al. Capsular serovars of virulent Capnocytophaga canimorsus are shared by the closely related species C. canis and C. cynodegmi. Emerg Microbes Infect. 2018;7:124.. Infection due to C. canimorsus may present itself as a fever, skin wounds with infection, fatigue, gastrointestinal symptoms, and purpura44. Renzi F, Hess E, Dol M, Koudad D, Carlier E, Ohlén M, et al. Capsular serovars of virulent Capnocytophaga canimorsus are shared by the closely related species C. canis and C. cynodegmi. Emerg Microbes Infect. 2018;7:124.,55. Butler T. Capnocytophaga canimorsus: an emerging cause of sepsis, meningitis, and post-splenectomy infection after dog bites. Eur J Clin Microbiol Infect Dis. 2015;34:1271-80.. This case did not show any skin rash or purpura but was considered a severe disease based on sepsis criteria and central nervous system involvement upon presentation. The prognosis of meningitis caused by this microorganism is usually better than acute sepsis22. Butler T, Weaver RE, Ramani TK, Uyeda CT, Bobo RA, Ryu JS, et al. Unidentified gram-negative rod infection: a new disease of man. Ann Intern Med. 1977;86:1-5.,55. Butler T. Capnocytophaga canimorsus: an emerging cause of sepsis, meningitis, and post-splenectomy infection after dog bites. Eur J Clin Microbiol Infect Dis. 2015;34:1271-80.. It is hypothesized that the incubation period after dog bites is longer for meningitis, giving more time for an immune response to develop33. Hannon DM, Harkin E, Donnachie K, Sibartie S, Doyle M, Chan G. A case of Capnocytophaga canimorsus meningitis and bacteraemia. Ir J Med Sci. 2020;189:251-2.,55. Butler T. Capnocytophaga canimorsus: an emerging cause of sepsis, meningitis, and post-splenectomy infection after dog bites. Eur J Clin Microbiol Infect Dis. 2015;34:1271-80.. Few cases of Capnocytophaga canimorsus-meningitis in immunocompetent patients have been described (Table 1).

Table 1
Description of reported cases of meningitis caused by Capnococytophaga canimorsus in immunocompetent hosts from 1994 to 2021.

This patient arrived with a clinical syndrome of meningitis. The symptoms, however, were unspecific and could be compatible with infection due to several agents. Thus, the differential diagnosis is important. The pathogens that usually cause meningitis in the elderly are Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis and Listeria monocytogenes. Patients who undergo neurosurgery are more likely to present S. aureus or Pseudomonas aeruginosa. Rare causes of meningoencephalitis related to dog bites are Pasteurella multocida and rabies66. Choi C. Bacterial meningitis in aging adults. Clin Infect Dis. 2001;33:1380-5..

Brazil uses a national health information system on diseases of compulsory notification (SINAN) to record all patients seeking medical care in public health facilities following direct contact with an animal suspected of rabid77. Duarte NF, Almeida CP, Negreiros JA, Duarte BH, Santos LJ, Garcia MH, et al. Importância dos canídeos silvestre na epidemiologia da raiva no Estado do Ceará, Nordeste, Brasil, 2003-2013. In: Anais da 27ª Reunião Internacional de Raiva nas Américas; 2016 Out 23-28; Belém, Brasil. Ananindeua: IEC; 2016.. In Ceara State, Northeastern Brazil, where the dog bite occurred, SINAN recorded 219,504 attacks on humans by potentially rabid mammals, with dogs being the main aggressors88. Laguardia J, Domingues CM, Carvalho C, Lauerman CR, Macário E, Glatt R. Sistema de informação de agravos de notificação em saúde (Sinan): desafios no desenvolvimento de um sistema de informação em saúde. Epidemiol Serv Saude. 2004;13:135-47.. There is no data available in the country regarding other bite-related complications. Due to the absence of additional data from these reported bites, we do not know the complete extent of non-rabies complications in Brazil. To date, no other similar cases of C. canimosus-meningitis have been reported in Brazil. The diagnosis of C. canimorsus infection is challenging. To reach the diagnosis, high clinical suspicion associated with assertive microbiological methods is necessary. Microbiological diagnosis may be delayed as the blood culture results usually take up to 14 days. In our case, MALDI-TOF-MS was performed to reach the diagnosis since the Vitek®2 GN card (Biomerieux, Marcy- l’Étoile, France) was unable to differentiate the poorly discriminated microorganisms, since it did not contain the biochemicals needed for identifying Capnocytophaga species. Furthermore, the three suggested bacteria had no metabolic correspondence with the isolated bacteria, as they were non-fermenting and aerobic. MALDI-TOF-MS is a new and powerful technique for detecting a large array of proteins rather than just small molecules. In many studies, this technique outperformed conventional methods. MALDI-TOF-MS is a rapid diagnostic method that is less affected by culture media, cultivation conditions or incubation time99. Dingle TC, Butler-Wu SM. Maldi-tof mass spectrometry for microorganism identification. Clin Lab Med. 2013;33:589-609..

Chesdachai et al.11. Chesdachai S, Tai DB, Yetmar ZA, Misra A, Ough N, Abu Saleh OA. The characteristics of Capnocytophaga infection: 10 years of experience. Open Forum Infect Dis. 2021;8:ofab175. found that meningitis associated with Capnocytophaga bacteremia primarily occurs in immunocompromised patients. Capnocytophaga infection may cause a life-threatening condition. The main risk factors are immunosuppressive medications, hematologic malignancies, diabetes, hematopoietic stem cell transplantation, renal disease, alcohol use disorder, solid organ transplantation and splenectomy1010. Jolivet-Gougeon A, Buffet A, Dupuy C, Sixou JL, Bonnaure-Mallet M, David S, et al. In vitro susceptibilities of Capnocytophaga isolates to beta-lactam antibiotics and beta-lactamase inhibitors. Antimicrob Agents Chemother. 2000;44:3186-8.,1111. Mendes FR, Bruniera FR, Schmidt J, Cury AP, Rizeck C, Higashino H, et al. Capnocytophaga sputigena bloodstream infection in hematopoietic stem cell transplantations: two cases report and review of the literature. Rev Inst Med Trop Sao Paulo. 2020;62:e48.

12. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59:147-59.

13. Blanche P, Sicard D, Meyniard O, Ratovohery D, Brun T, Paul G. Capnocytophaga canimorsus lymphocytic meningitis in an immunocompetent man who was bitten by a dog. Clin Infect Dis. 1994;18:654-5.

14. Beltramone M, Moreau N, Martinez-Almoyna L. Capnocytophaga canimorsus, a rare cause of bacterial meningitis. Rev Neurol (Paris). 2017;173:74-5.

15. Delman M, Chalikonda D, Haroian N, Djurkovic S. Capnocytophaga canimorsus meningitis in an immunocompetent woman: a case report and review of the literature. Infect Dis Clin Pract. 2017;25:57-61.

16. Bertin N, Brosolo G, Pistola F, Pelizzo F, Marini C, Pertoldi F, et al. Capnocytophaga canimorsus: an emerging pathogen in immunocompetent patients-experience from an emergency department. J Emerg Med. 2018;54:871-5.

17. Malik F, Orchard W, Jacob G. Rare case of Capnocytophaga canimorsus meningitis in a man without risk factors. BMJ Case Rep. 2021;14:e241686.

18. Asif AA, Roy M, Tellier BR, Ahmad S. Capnocytophaga canimorsus meningitis diagnosed using next-generation sequencing of microbial cell-free DNA. IDCases. 2021;24:e01126.
-1919. O’Riordan F, Ronayne A, Jackson A. Capnocytophaga canimorsus meningitis and bacteraemia without a dog bite in an immunocompetent individual. BMJ Case Rep. 2021;14:e242432.. Although the patient did not have these aforementioned risk factors, his age may have played a significant role in the severity of the infection. Data from literature suggest that the stimulation of the immune system throughout our lives may induce immune changes, probably due to unbalanced inflammatory profiles, which can lead to a weaker immune system. The extent of this immunodepression can vary according to the individual2020. Rymkiewicz PD, Heng YX, Vasudev A, Larbi A. The immune system in the aging human. Immunol Res. 2012;53:235-50..

We cannot confirm the role of SARS-CoV-2 infection in the patient’s immunity. He did not present with any respiratory symptoms, and steroid administration was not necessary in his case. A positive test for SARS-CoV-2 in this patient was an incidental finding since it is less likely that these two infections are related. During the pandemic, COVID-19 infections were much more common than C. canimorsus infections. Therefore, it is possible to diagnose a wide variety of patients with asymptomatic COVID-19 infections, even in those with rare conditions. The case occurred during the second COVID-19 wave in Brazil, when most cases were caused by the Gamma (P.1) variant. At the time of diagnosis, reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 in CSF was not available at our center.

Treatment is usually based on the susceptibility tests of blood or CSF cultures. In general, β-lactam antibiotics, third-generation cephalosporins, doxycycline, clindamycin and chloramphenicol or carbapenems are effective against C. canimorsus. Some guidelines suggest that the preferred intravenous agents should include clindamycin, doxycycline, cefuroxime and meropenem1212. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59:147-59.. The patient was treated with meropenem for 14 days and had a good clinical response. Although he was treated for a prolonged period, mainly due to the severity of the case, more studies are necessary to better understand the duration of antibiotic therapy. Infection prophylaxis after a dog/cat bite with amoxicillin/clavulanic acid is possible. Doxycycline or clindamycin can be considered in case of penicillin allergy11. Chesdachai S, Tai DB, Yetmar ZA, Misra A, Ough N, Abu Saleh OA. The characteristics of Capnocytophaga infection: 10 years of experience. Open Forum Infect Dis. 2021;8:ofab175.,1010. Jolivet-Gougeon A, Buffet A, Dupuy C, Sixou JL, Bonnaure-Mallet M, David S, et al. In vitro susceptibilities of Capnocytophaga isolates to beta-lactam antibiotics and beta-lactamase inhibitors. Antimicrob Agents Chemother. 2000;44:3186-8.,1212. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59:147-59..

CONCLUSION

Herein, we present a rare case of meningitis caused by C. canimorsus in a patient coinfected with SARS-CoV-2. This report is special because it describes a rare case of a SARS-CoV-2 infected immunocompetent patient with a severe neurological disease due to C. canimorsus, and the diagnosis was possible only due to the high discrimination achieved by MALDI-TOF. This case highlights the importance of awareness about this disease and maintaining a high index of suspicion when a patient presents neurological symptoms compatible with meningitis and a history of dog or cat bite and/or licking. Molecular methods are usually necessary for the prompt diagnosis and may not be available in every center, worldwide.

ACKNOWLEDGMENTS

The authors would like to acknowledge all the residents and staff of the Hospital Sao Jose de Doencas Infecciosas in Fortaleza, Brazil, for their valuable support. We would also like to acknowledge the Central Laboratory of Public Health of Ceara State (LACEN-CE) and DASA Laboratory for the availability of MALDI-TOF-MS.

REFERENCES

  • 1
    Chesdachai S, Tai DB, Yetmar ZA, Misra A, Ough N, Abu Saleh OA. The characteristics of Capnocytophaga infection: 10 years of experience. Open Forum Infect Dis. 2021;8:ofab175.
  • 2
    Butler T, Weaver RE, Ramani TK, Uyeda CT, Bobo RA, Ryu JS, et al. Unidentified gram-negative rod infection: a new disease of man. Ann Intern Med. 1977;86:1-5.
  • 3
    Hannon DM, Harkin E, Donnachie K, Sibartie S, Doyle M, Chan G. A case of Capnocytophaga canimorsus meningitis and bacteraemia. Ir J Med Sci. 2020;189:251-2.
  • 4
    Renzi F, Hess E, Dol M, Koudad D, Carlier E, Ohlén M, et al. Capsular serovars of virulent Capnocytophaga canimorsus are shared by the closely related species C. canis and C. cynodegmi. Emerg Microbes Infect. 2018;7:124.
  • 5
    Butler T. Capnocytophaga canimorsus: an emerging cause of sepsis, meningitis, and post-splenectomy infection after dog bites. Eur J Clin Microbiol Infect Dis. 2015;34:1271-80.
  • 6
    Choi C. Bacterial meningitis in aging adults. Clin Infect Dis. 2001;33:1380-5.
  • 7
    Duarte NF, Almeida CP, Negreiros JA, Duarte BH, Santos LJ, Garcia MH, et al. Importância dos canídeos silvestre na epidemiologia da raiva no Estado do Ceará, Nordeste, Brasil, 2003-2013. In: Anais da 27ª Reunião Internacional de Raiva nas Américas; 2016 Out 23-28; Belém, Brasil. Ananindeua: IEC; 2016.
  • 8
    Laguardia J, Domingues CM, Carvalho C, Lauerman CR, Macário E, Glatt R. Sistema de informação de agravos de notificação em saúde (Sinan): desafios no desenvolvimento de um sistema de informação em saúde. Epidemiol Serv Saude. 2004;13:135-47.
  • 9
    Dingle TC, Butler-Wu SM. Maldi-tof mass spectrometry for microorganism identification. Clin Lab Med. 2013;33:589-609.
  • 10
    Jolivet-Gougeon A, Buffet A, Dupuy C, Sixou JL, Bonnaure-Mallet M, David S, et al. In vitro susceptibilities of Capnocytophaga isolates to beta-lactam antibiotics and beta-lactamase inhibitors. Antimicrob Agents Chemother. 2000;44:3186-8.
  • 11
    Mendes FR, Bruniera FR, Schmidt J, Cury AP, Rizeck C, Higashino H, et al. Capnocytophaga sputigena bloodstream infection in hematopoietic stem cell transplantations: two cases report and review of the literature. Rev Inst Med Trop Sao Paulo. 2020;62:e48.
  • 12
    Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59:147-59.
  • 13
    Blanche P, Sicard D, Meyniard O, Ratovohery D, Brun T, Paul G. Capnocytophaga canimorsus lymphocytic meningitis in an immunocompetent man who was bitten by a dog. Clin Infect Dis. 1994;18:654-5.
  • 14
    Beltramone M, Moreau N, Martinez-Almoyna L. Capnocytophaga canimorsus, a rare cause of bacterial meningitis. Rev Neurol (Paris). 2017;173:74-5.
  • 15
    Delman M, Chalikonda D, Haroian N, Djurkovic S. Capnocytophaga canimorsus meningitis in an immunocompetent woman: a case report and review of the literature. Infect Dis Clin Pract. 2017;25:57-61.
  • 16
    Bertin N, Brosolo G, Pistola F, Pelizzo F, Marini C, Pertoldi F, et al. Capnocytophaga canimorsus: an emerging pathogen in immunocompetent patients-experience from an emergency department. J Emerg Med. 2018;54:871-5.
  • 17
    Malik F, Orchard W, Jacob G. Rare case of Capnocytophaga canimorsus meningitis in a man without risk factors. BMJ Case Rep. 2021;14:e241686.
  • 18
    Asif AA, Roy M, Tellier BR, Ahmad S. Capnocytophaga canimorsus meningitis diagnosed using next-generation sequencing of microbial cell-free DNA. IDCases. 2021;24:e01126.
  • 19
    O’Riordan F, Ronayne A, Jackson A. Capnocytophaga canimorsus meningitis and bacteraemia without a dog bite in an immunocompetent individual. BMJ Case Rep. 2021;14:e242432.
  • 20
    Rymkiewicz PD, Heng YX, Vasudev A, Larbi A. The immune system in the aging human. Immunol Res. 2012;53:235-50.
  • FUNDING: No funding was received for reporting this case.

Publication Dates

  • Publication in this collection
    06 May 2022
  • Date of issue
    2022

History

  • Received
    14 Feb 2022
  • Accepted
    5 Apr 2022
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