- Email: [email protected]
Capnocytophaga canimorsus, a rare cause of bacterial meningitis
NEUROL-1718; No. of Pages 2 revue neurologique xxx (2016) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Letter to the editor
Capnocytophaga canimorsus, a rare cause of bacterial meningitis 1.
Case report
A 49-year-old man with no medical history was admitted to the emergency unit suffering from headaches, neck pain and a fever of 40 8C. The symptoms gradually worsened over 8 days. The patient had neck stiffness and photophobia. Neurological examination was normal, revealing no focal deficit. Laboratory analyses performed on admission revealed a biological inflammatory syndrome. As the cerebrospinal fluid (CSF) was turbid, analyses favored bacterial meningitis (Table 1). The computed tomography (CT) scan was normal. The patient had not been receiving antibiotic treatment before admission. However, after being transferred to the neurology unit, a detailed interview with the patient revealed that, 2 days before the onset of his fever (10 days before admission), he had been bitten by his pet dog, a tiny Maltese Bichon Frise. The wound was so small and superficial that the patient had not even bothered to disinfect it. On admission to hospital, the patient was perfectly conscious with coherent and fluent speech, and showed no particular neurological deficit. Ceftriaxone therapy was initiated at a dosage of 12 g/day. Brain MRI was normal with no meningeal enhancement (sequences: T1- and T2-weighted,
Table 1 – Blood and cerebrospinal fluid (CSF) results on admission and 3 weeks later. Admission 3 weeks later Blood Leukocyte count (n/mm3) Neutrophils (%) C-reactive protein (mg/L) Procalcitonin (ng/mL) Glucose (mmol/L) CSF CSF appearances Leukocyte count (n/mm3) Neutrophils (%) Glucose (blood lactose) (mmol/L) Protein level (g/L) Lactate concentration (mmol/L)
14 500 75.4 155 0.14 6.44
7700 50.9 3.5 0.11 5.1
Turbid 4100 60 2.27 2.34 6.14
Clear 174 8 2.60 0.55 2.00
fluid-attenuated inversion recovery [FLAIR] and diffusionweighted for differences in the apparent diffusion coefficient [dADC]). Three days after admission, one of the patient’s blood cultures revealed a Gram-negative filamentous bacillus. Capnocytophaga canimorsus was identified after 7 days of culture (chocolate agar plate incubated aerobically in 5% CO2). The organism was found to be susceptible to all antibiotics tested except gentamicin. These bacteria have never previously been found in CSF. The patient’s antibiotherapy was not modified after bacterial identification and was maintained for 4 weeks. Control biological analyses showed persistence of an inflammatory syndrome. However, the fever disappeared rapidly within 48 h of treatment initiation whereas the headaches persisted for a few days until he was finally sent home. Three weeks later, the patient’s neurological status was normal, despite control CSF analyses still being abnormal (Table 1). The 16S ribosomal RNA gene sequencing was negative on the control CSF.
2.
Discussion
C. canimorsus is a capnophilic, facultative-anaerobic, Gramnegative rod that grows slowly (up to 1 week) on blood (5% sheep’s blood in Columbia agar) or chocolate agar in 10% CO2. The media have to be incubated at 37 8C for at least 5 days. C. canimorsus is part of the commensal oral flora in dogs and cats, most of the time transmitted by bites, and less frequently by other types of contact with dogs and cats (such as scratches or licking) [1]. It was first isolated in 1976 by Bobo and Newton in a patient presenting with Gram-negative Bacillus meningitis [2]. Cases of human infection due to C. canimorsus are very uncommon, with an estimated incidence of 0.03 in one million population per year [3]. C. canimorsus bacteria usually cause localized ocular infections, arthritis, endocarditis and septicemia, with a reported mortality rate of 26% [1]. C. canimorsus meningitis is an exceptional cause of bacterial meningitis. In the most important prospective study of bacterial meningitis, van de Beek et al. [4] found no incidences of C. canimorsus meningitis in 696 cases while a recent review could find only 32 cases of such meningitis reported
Please cite this article in press as: Beltramone M. Capnocytophaga canimorsus, a rare cause of bacterial meningitis. Revue neurologique (2016), http://dx.doi.org/10.1016/j.neurol.2016.11.005
NEUROL-1718; No. of Pages 2
2
revue neurologique xxx (2016) xxx–xxx
worldwide between 1990 and 2014 [1]. However, these incidences are probably underestimates. Due to its very slow growth [5], which can take up to 15 days, C. canimorsus may not be detected by standard procedures, where CSF cultures are limited to 5 days. If not suspected by either bacteriologists or clinicians, these slow-growing bacteria may thus escape diagnosis. Most C. canimorsus meningitis has a subacute evolution, with a well-preserved clinical status in contrast to its biological results, which is characteristic of an acute bacterial infection and a low rate of mortality [5]. Our patient presented with minor symptoms (fever and headaches), despite the 7 days of evolution and turbid CSF. Most of the biological analyses were in favor of bacterial meningitis, such as CSF lactate, a reliable marker for identifying bacterial meningitis compared with any of the four other CSF markers usually considered (CSF glucose, CSF/ blood glycemia rate, CSF protein and number of leukocytes) [6]. Interestingly, procalcitonin (PCT) was normal in our patient, despite being one of the most sensitive biological markers for differentiating viral from bacterial acute meningitis [7]. PCT levels should therefore be considered early in cases of subacute meningitis. The dissociation between biological analyses and well-preserved neurological status could be explained by the fact that the C. canimorsus organism is able to avoid the immune system [8]. Thus, C. canimorsus infection is diagnostically challenging. In our present case, when the laboratory was informed of our suspicion of C. canimorsus infection, the prolonged CSF culture still appeared to be negative. However, new methods for identifying this bacterial strain have been developed. The 16S ribosomal RNA sequencing method is particularly invaluable for detecting bacterial meningitis even when antibiotics had been introduced prior to lumbar puncture, or in cases of fastidious or slow-growing bacterial meningitis [9]. Nevertheless, although the 16S rRNA polymerase chain reaction (PCR) technique is a precious diagnostic tool, a positive reaction may not necessarily ensure diagnosis. Indeed, in our patient, the result was negative, which might be explained by the 3-week delay between the onset of symptoms and 16S rRNA sequencing. Broad-spectrum antibiotherapy with third-generation cephalosporins is usually recommended before bacterial identification. Popiel and Vinh [10] have proposed recommendations for the management of Capnocytophaga meningitis: if no b-lactamase is detected, then high doses of penicillin may be considered whereas, if b-lactamase production is isolated, then third-generation cephalosporin or carbapenem should be introduced. In the absence of specific studies, the duration of treatment should probably range from 14 to 21 days, as is usually recommended for other types of bacterial meningitis.
Disclosure of interest The authors declare that they have no competing interest.
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
dog bites. Eur J Clin Microbiol Infect Dis 2015;34:1271–80. http://dx.doi.org/10.1007/s10096-015-2360-7. Bobo R, Newton E. A previously undescribed gram-negative bacillus causing septicemia and meningitis. Am J Clin Pathol 1976;65:564–9. van Samkar A, Brouwer MC, Schultsz C, van der Ende A, van de Beek D. Capnocytophaga canimorsus meningitis: three cases and a review of the literature. Zoonoses Public Health 2016;63:442–8. http://dx.doi.org/10.1111/zph.12248. van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004;351:1849–59. http://dx.doi.org/10.1056/NEJMoa040845. Le Moal G, Landron C, Grollier G, Robert R, Burucoa C. Meningitis due to Capnocytophaga canimorsus after receipt of a dog bite: case report and review of the literature. Clin Infect Dis 2003;36:e42–6. http://dx.doi.org/10.1086/345477. Huy NT, Thao NT, Diep DT, Kikuchi M, Zamora J, Hirayama K. Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis. Crit Care 2010;14:R240. http://dx.doi.org/ 10.1186/cc9395. Viallon A, Zeni F, Lambert C, Pozzetto B, Tardy B, Venet C, et al. High sensitivity and specificity of serum procalcitonin levels in adults with bacterial meningitis. Clin Infect Dis 1999;28:1313–6. http://dx.doi.org/10.1086/514793. Frieling JT, Mulder J, Hendriks T, Curfs JHA, Van Der Linden C, Sauerwein R. Differential induction of pro- and antiinflammatory cytokines in whole blood by bacteria: effects of antibiotic treatment. Antimicrob Agents Chemother 1997;41:1439–43. Beernink TMJ, Wever PC, Hermans MHA, Bartholomeus MGT. Capnocytophaga canimorsus meningitis diagnosed by 16S rRNA PCR. Pract Neurol 2016;16:136–8. http://dx.doi.org/ 10.1136/practneurol-2015-001166. Popiel K, Vinh D. Bobo-Newton syndrome: an unwanted gift from man’s best friend. Can J Infect Dis Med Microbiol 2013;24:209–14.
M. Beltramone* Centre d’e´valuation et de traitement de la douleur, centre hospitalier universitaire la Timone, 264, rue Saint-Pierre, 13385 Marseille Cedex 5, France N. Moreau Service de neurologie, centre hospitalier Pays d’Aix, 13616 Aix-enProvence, France L. Martinez-Almoyna Poˆle de neurosciences cliniques, centre hospitalier universitaire Nord, chemin des Bourrely, 13015 Marseille, France *Corresponding author. E-mail address: [email protected] (M. Beltramone) Received 2 August 2016 Received in revised form 28 September 2016 Accepted 28 November 2016 Available online xxx
references http://dx.doi.org/10.1016/j.neurol.2016.11.005 0035-3787/# 2016 Elsevier Masson SAS. All rights reserved. [1] Butler T. Capnocytophaga canimorsus: an emerging cause of sepsis, meningitis, and post-splenectomy infection after
Please cite this article in press as: Beltramone M. Capnocytophaga canimorsus, a rare cause of bacterial meningitis. Revue neurologique (2016), http://dx.doi.org/10.1016/j.neurol.2016.11.005
Available online at
ScienceDirect www.sciencedirect.com
Letter to the editor
Capnocytophaga canimorsus, a rare cause of bacterial meningitis 1.
Case report
A 49-year-old man with no medical history was admitted to the emergency unit suffering from headaches, neck pain and a fever of 40 8C. The symptoms gradually worsened over 8 days. The patient had neck stiffness and photophobia. Neurological examination was normal, revealing no focal deficit. Laboratory analyses performed on admission revealed a biological inflammatory syndrome. As the cerebrospinal fluid (CSF) was turbid, analyses favored bacterial meningitis (Table 1). The computed tomography (CT) scan was normal. The patient had not been receiving antibiotic treatment before admission. However, after being transferred to the neurology unit, a detailed interview with the patient revealed that, 2 days before the onset of his fever (10 days before admission), he had been bitten by his pet dog, a tiny Maltese Bichon Frise. The wound was so small and superficial that the patient had not even bothered to disinfect it. On admission to hospital, the patient was perfectly conscious with coherent and fluent speech, and showed no particular neurological deficit. Ceftriaxone therapy was initiated at a dosage of 12 g/day. Brain MRI was normal with no meningeal enhancement (sequences: T1- and T2-weighted,
Table 1 – Blood and cerebrospinal fluid (CSF) results on admission and 3 weeks later. Admission 3 weeks later Blood Leukocyte count (n/mm3) Neutrophils (%) C-reactive protein (mg/L) Procalcitonin (ng/mL) Glucose (mmol/L) CSF CSF appearances Leukocyte count (n/mm3) Neutrophils (%) Glucose (blood lactose) (mmol/L) Protein level (g/L) Lactate concentration (mmol/L)
14 500 75.4 155 0.14 6.44
7700 50.9 3.5 0.11 5.1
Turbid 4100 60 2.27 2.34 6.14
Clear 174 8 2.60 0.55 2.00
fluid-attenuated inversion recovery [FLAIR] and diffusionweighted for differences in the apparent diffusion coefficient [dADC]). Three days after admission, one of the patient’s blood cultures revealed a Gram-negative filamentous bacillus. Capnocytophaga canimorsus was identified after 7 days of culture (chocolate agar plate incubated aerobically in 5% CO2). The organism was found to be susceptible to all antibiotics tested except gentamicin. These bacteria have never previously been found in CSF. The patient’s antibiotherapy was not modified after bacterial identification and was maintained for 4 weeks. Control biological analyses showed persistence of an inflammatory syndrome. However, the fever disappeared rapidly within 48 h of treatment initiation whereas the headaches persisted for a few days until he was finally sent home. Three weeks later, the patient’s neurological status was normal, despite control CSF analyses still being abnormal (Table 1). The 16S ribosomal RNA gene sequencing was negative on the control CSF.
2.
Discussion
C. canimorsus is a capnophilic, facultative-anaerobic, Gramnegative rod that grows slowly (up to 1 week) on blood (5% sheep’s blood in Columbia agar) or chocolate agar in 10% CO2. The media have to be incubated at 37 8C for at least 5 days. C. canimorsus is part of the commensal oral flora in dogs and cats, most of the time transmitted by bites, and less frequently by other types of contact with dogs and cats (such as scratches or licking) [1]. It was first isolated in 1976 by Bobo and Newton in a patient presenting with Gram-negative Bacillus meningitis [2]. Cases of human infection due to C. canimorsus are very uncommon, with an estimated incidence of 0.03 in one million population per year [3]. C. canimorsus bacteria usually cause localized ocular infections, arthritis, endocarditis and septicemia, with a reported mortality rate of 26% [1]. C. canimorsus meningitis is an exceptional cause of bacterial meningitis. In the most important prospective study of bacterial meningitis, van de Beek et al. [4] found no incidences of C. canimorsus meningitis in 696 cases while a recent review could find only 32 cases of such meningitis reported
Please cite this article in press as: Beltramone M. Capnocytophaga canimorsus, a rare cause of bacterial meningitis. Revue neurologique (2016), http://dx.doi.org/10.1016/j.neurol.2016.11.005
NEUROL-1718; No. of Pages 2
2
revue neurologique xxx (2016) xxx–xxx
worldwide between 1990 and 2014 [1]. However, these incidences are probably underestimates. Due to its very slow growth [5], which can take up to 15 days, C. canimorsus may not be detected by standard procedures, where CSF cultures are limited to 5 days. If not suspected by either bacteriologists or clinicians, these slow-growing bacteria may thus escape diagnosis. Most C. canimorsus meningitis has a subacute evolution, with a well-preserved clinical status in contrast to its biological results, which is characteristic of an acute bacterial infection and a low rate of mortality [5]. Our patient presented with minor symptoms (fever and headaches), despite the 7 days of evolution and turbid CSF. Most of the biological analyses were in favor of bacterial meningitis, such as CSF lactate, a reliable marker for identifying bacterial meningitis compared with any of the four other CSF markers usually considered (CSF glucose, CSF/ blood glycemia rate, CSF protein and number of leukocytes) [6]. Interestingly, procalcitonin (PCT) was normal in our patient, despite being one of the most sensitive biological markers for differentiating viral from bacterial acute meningitis [7]. PCT levels should therefore be considered early in cases of subacute meningitis. The dissociation between biological analyses and well-preserved neurological status could be explained by the fact that the C. canimorsus organism is able to avoid the immune system [8]. Thus, C. canimorsus infection is diagnostically challenging. In our present case, when the laboratory was informed of our suspicion of C. canimorsus infection, the prolonged CSF culture still appeared to be negative. However, new methods for identifying this bacterial strain have been developed. The 16S ribosomal RNA sequencing method is particularly invaluable for detecting bacterial meningitis even when antibiotics had been introduced prior to lumbar puncture, or in cases of fastidious or slow-growing bacterial meningitis [9]. Nevertheless, although the 16S rRNA polymerase chain reaction (PCR) technique is a precious diagnostic tool, a positive reaction may not necessarily ensure diagnosis. Indeed, in our patient, the result was negative, which might be explained by the 3-week delay between the onset of symptoms and 16S rRNA sequencing. Broad-spectrum antibiotherapy with third-generation cephalosporins is usually recommended before bacterial identification. Popiel and Vinh [10] have proposed recommendations for the management of Capnocytophaga meningitis: if no b-lactamase is detected, then high doses of penicillin may be considered whereas, if b-lactamase production is isolated, then third-generation cephalosporin or carbapenem should be introduced. In the absence of specific studies, the duration of treatment should probably range from 14 to 21 days, as is usually recommended for other types of bacterial meningitis.
Disclosure of interest The authors declare that they have no competing interest.
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
dog bites. Eur J Clin Microbiol Infect Dis 2015;34:1271–80. http://dx.doi.org/10.1007/s10096-015-2360-7. Bobo R, Newton E. A previously undescribed gram-negative bacillus causing septicemia and meningitis. Am J Clin Pathol 1976;65:564–9. van Samkar A, Brouwer MC, Schultsz C, van der Ende A, van de Beek D. Capnocytophaga canimorsus meningitis: three cases and a review of the literature. Zoonoses Public Health 2016;63:442–8. http://dx.doi.org/10.1111/zph.12248. van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004;351:1849–59. http://dx.doi.org/10.1056/NEJMoa040845. Le Moal G, Landron C, Grollier G, Robert R, Burucoa C. Meningitis due to Capnocytophaga canimorsus after receipt of a dog bite: case report and review of the literature. Clin Infect Dis 2003;36:e42–6. http://dx.doi.org/10.1086/345477. Huy NT, Thao NT, Diep DT, Kikuchi M, Zamora J, Hirayama K. Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis. Crit Care 2010;14:R240. http://dx.doi.org/ 10.1186/cc9395. Viallon A, Zeni F, Lambert C, Pozzetto B, Tardy B, Venet C, et al. High sensitivity and specificity of serum procalcitonin levels in adults with bacterial meningitis. Clin Infect Dis 1999;28:1313–6. http://dx.doi.org/10.1086/514793. Frieling JT, Mulder J, Hendriks T, Curfs JHA, Van Der Linden C, Sauerwein R. Differential induction of pro- and antiinflammatory cytokines in whole blood by bacteria: effects of antibiotic treatment. Antimicrob Agents Chemother 1997;41:1439–43. Beernink TMJ, Wever PC, Hermans MHA, Bartholomeus MGT. Capnocytophaga canimorsus meningitis diagnosed by 16S rRNA PCR. Pract Neurol 2016;16:136–8. http://dx.doi.org/ 10.1136/practneurol-2015-001166. Popiel K, Vinh D. Bobo-Newton syndrome: an unwanted gift from man’s best friend. Can J Infect Dis Med Microbiol 2013;24:209–14.
M. Beltramone* Centre d’e´valuation et de traitement de la douleur, centre hospitalier universitaire la Timone, 264, rue Saint-Pierre, 13385 Marseille Cedex 5, France N. Moreau Service de neurologie, centre hospitalier Pays d’Aix, 13616 Aix-enProvence, France L. Martinez-Almoyna Poˆle de neurosciences cliniques, centre hospitalier universitaire Nord, chemin des Bourrely, 13015 Marseille, France *Corresponding author. E-mail address: [email protected] (M. Beltramone) Received 2 August 2016 Received in revised form 28 September 2016 Accepted 28 November 2016 Available online xxx
references http://dx.doi.org/10.1016/j.neurol.2016.11.005 0035-3787/# 2016 Elsevier Masson SAS. All rights reserved. [1] Butler T. Capnocytophaga canimorsus: an emerging cause of sepsis, meningitis, and post-splenectomy infection after
Please cite this article in press as: Beltramone M. Capnocytophaga canimorsus, a rare cause of bacterial meningitis. Revue neurologique (2016), http://dx.doi.org/10.1016/j.neurol.2016.11.005