The use of eculizumab in Capnocytophaga canimorsus associated thrombotic microangiopathy: a case report.

BACKGROUND: The use of complement inhibition is well established for complement mediated thrombotic microangiopathy, but its role in secondary forms of thrombotic microangiopathy is debated. We here present a case of thrombotic microangiopathy triggered by Capnocytophaga canimorsus, illustrating the diagnostic difficulties in discriminating between different thrombotic microangiopathies, and the dilemmas regarding how to treat this disease entity. CASE PRESENTATION: A previously healthy 56-year-old woman presented with fever and confusion. She was diagnosed with sepsis from Capnocytophaga canimorsus and thrombotic microangiopathy. Marked activation of both T-cells, endothelium and complement were documented. She was successfully treated with antimicrobial therapy, the complement inhibitor eculizumab and splenectomy. After several weeks, a heterozygote variant in complement factor B was localized, potentially implying the diagnosis of a complement mediated TMA over an isolated infection related TMA. CONCLUSIONS: We discuss the possible interactions between complement activation and other findings in severe infection and argue that complement inhibition proved beneficial to this patient's rapid recovery.

Bilateral acute renal cortical necrosis after a dog bite: case report.

BACKGROUND: Capnocytophaga canimorsus is a Gram-negative capnophilic rod and part of dogs/cats' normal oral flora. It can be transmitted by bites, scratches, or even by contact of saliva with injured skin. Asplenic patients and patients with alcohol abuse are at particular risk for fulminant C. canimorsus sepsis. However, also immunocompetent patients can have a severe or even fatal infection. This is the first case of a severe C. canimorsus infection in an immunocompromised host complicated by acute renal cortical necrosis with a "reverse rim sign" in contrast-enhanced computed tomography on hospital admission. CASE PRESENTATION: We report the case of a 44-year functionally asplenic patient after an allogeneic stem cell transplantation, who presented with septic shock after a minor dog bite injury 4 days prior. Because of abdominal complaints, epigastric pain with local peritonism, and radiological gallbladder wall thickening, an abdominal focus was suspected after the initial work-up. The patient underwent emergent open cholecystectomy, but the clinical suspicion of abdominal infection was not confirmed. Septic shock was further complicated by cardiomyopathy and disseminated intravascular coagulation. As a causative pathogen, C. canimorsus could be isolated. The clinical course was complicated by permanent hemodialysis and extensive acral necrosis requiring amputation of several fingers and both thighs. CONCLUSION: We present a severe case of a C. canimorsus infection in a functionally asplenic patient after a minor dog bite. The clinical course was complicated by septic shock, disseminated intravascular coagulation, and the need for multiple amputations. In addition, the rare form of acute renal failure - bilateral acute renal cortical necrosis - was visible as "reverse rim sign" on computed tomography scan. This case is an example of the potential disastrous consequences when omitting pre-emptive antibiotic therapy in wounds inflicted by cats and dogs, particularly in asplenic patients.

An uncommon cause of sepsis following dog exposure.

ABSTRACT: Capnocytophaga canimorsus is a bacteria commonly found in the normal oral cavity of dogs that can cause bacteremia in immunocompromised patients following a dog bite. This case describes sepsis and disseminated intravascular coagulation associated with C. canimorsus in a patient with a history of alcohol abuse. Clinicians must be alert to the risk factors for this infection and provide appropriate prophylaxis following dog bites.

A rare case of purulent meningitis caused by Capnocytophaga canimorsus in the Czech Republic - case report and review of the literature.

BACKGROUND: Invasive infections caused by Capnocytophaga canimorsus are rare. Immunocompromised patients, who report being bitten by or having a close contact with an animal, represent a high-risk group for this infection. There are only few dozens of infections by this bacteria manifesting as purulent meningitis reported worldwide. The reported case is a first reported case of purulent meningitis caused by by Capnocytophaga canimorsus in Czech Republic with only a limited risk factor history. CASE PRESENTATION: The patient, a 74 years old man, was referred to the infectious diseases department of a teaching hospital with clear signs of developing purulent meningitis. His anamnestic data did not show any unusual findings. He was treated for compensated diabetes mellitus type II. The blood cultures were negative and the etiological agent did not grow from the cerebrospinal fluid (CSF) on common media. Eventually, it was identified by detecting pan-bacterial DNA and DNA sequencing. Subsequently, the pathogen was confirmed by anaerobic cultivation from CSF. Only after then the patient recalled being bitten by his German shepherd puppy during play. The patient was successfully treated intravenously by ceftriaxone. CONCLUSIONS: Purulent meningitis caused by Capnocytophaga spp. is a rare disease, but it needs to be considered in patients at risk with pre-existing conditions, who report close contact with or being bitten by an animal. It is important to test for this microbe in cases with negative microbiological results for the more common agents.

Infective endocarditis caused by Capnocytophaga canimorsus; a case report.

BACKGROUND: Capnocytophaga canimorsus is a gram-negative bacterium and an oral commensal in dogs and cats, but occasionally causes serious infections in humans. Septicemia is one of the most fulminant forms, but diagnosis of C. canimorsus infection is often difficult mainly because of its very slow growth. C. canimorsus infective endocarditis (IE) is rare and is poorly understood. Since quite a few strains produce ß-lactamase, antimicrobial susceptibility is pivotal information for adequate treatment. We herein report a case with C. canimorsus IE and the results of drug susceptibility test. CASE PRESENTATION: A 46-year-old man had a dog bite in his left hand 3 months previously. The patient was referred to our hospital for fever (body temperature > 38 °C), visual disturbance, and dyspnea. Echocardiography showed aortic valve regurgitation and vegetation on the leaflets. IE was diagnosed, and we initially administered cefazolin and gentamycin assuming frequently encountered microorganisms and the patient underwent aortic valve replacement. C. canimorsus was detected in the aortic valve lesion and blood cultures. It was also identified by 16S ribosome DNA sequencing. Ceftriaxone were started and continued because disk diffusion test revealed the isolate was negative for ß-lactamase and this case had cerebral symptoms. The patient successfully completed antibiotic treatment following surgery. CONCLUSIONS: We diagnosed C. canimorsus sepsis and IE by extended-period blood cultures and 16S ribosome DNA sequencing by polymerase chain reaction, and successfully identified its drug susceptibility.

Characterization of three strains of Capnocytophaga canis isolated from patients with sepsis.

Capnocytophaga canimorsus and Capnocytophaga cynodegmi, both commensal bacteria in the oral cavities of dogs and cats, are zoonotic pathogens. In particular, C. canimorsus causes sepsis and fatal septic shock. Recently, a novel Capnocytophaga species, C. canis, was isolated from the oral cavities of healthy dogs. It is reportedly oxidase-negative and therefore considered avirulent in humans. In the present study, three strains of C. canis were isolated from Japanese patients with sepsis. All three strains, HP20001, HP33001 and HP40001, were oxidase-positive. Nucleotide sequence identities of the 16S rRNA gene of the three strains to the C. canimorsus type strain ATCC35979, C. cynodegmi type strain ATCC49044 and C. canis type strain LMG29146 were 96.9-97.0%, 96.9-97.0% and 99.7-99.8%, respectively. Multi-locus sequence analysis based on seven house-keeping genes, dnaJ, fumC, glyA, gyrB, murG, trpB and tuf, revealed that the oxidase-positive C. canis strains isolated in Japan and oxidase-negative strains of C. canis from canine oral cavities in Switzerland were clustered in different genetic subgroups. These results indicate that the virulence of C. canis strains in humans is associated with oxidase activity.

Capnocytophaga canimorsus: An Emerging Pathogen in Immunocompetent Patients-Experience from an Emergency Department.

BACKGROUND: Capnocytophaga canimorsus is a bacterium of the normal oral flora of dogs and cats. Human infection is caused by animal bite but is rarely observed, mainly in immunocompromised patients. We present 2 cases of C. canimorsus infection that occurred in immunocompetent patients and caused multiorgan failure and in both cases severe neurologic involvement. CASE REPORT: In the first case, we present a 69-year-old immunocompetent woman with septic shock derived from skin and soft tissue infection after a dog's bite. She developed ischemic necrosis evolving to gangrene of both forefeet and hands, infective aortic endocarditis, and neurologic involvement caused by large hemispheric hypodense lesions compatible with ischemic septical lesions. In the second case, we present a 65-year-old immunocompetent man with meningitis after a dog's bite. Despite antibiotic therapy, he developed neurologic clinical deterioration, with right sensitive hemisyndrome associated with lack of strength and motor skills of the right hand. Radiologic findings were consistent with the diagnosis of cerebritis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinicians should always be aware of this pathogen, both in immunocompromised and immunocompetent patients, and consider prophylactic antibiotics after exposure.

[Fulminant sepsis after Capnocytophaga canimorsus infection]. / Fulminante Sepsis nach Capnocytophaga-canimorsus-Infektion.

Capnocytophaga canimorsus is a Gram-negative bacterium present in the oral cavities of cats and dogs. It is known for its capability to cause life-threatening sepsis following a dog bite, especially in immunocompromised patients. We report the case of a 67-year-old man who suffered from septic shock and multiorgan failure presumably following contamination of a pre-existing minor skin lesion by canine saliva. The purpose of this report is to raise awareness of Capnocytophaga canimorsus among physicians when faced with a patient presenting with fulminant septic shock and Gram-negative bacteremia, who has been exposed to dogs.

Capnocytophaga canimorsus Sepsis Following a Minor Dog Bite to the Finger: Case Report.

Capnocytophaga canimorsus is a gram-negative bacillus present in the oral cavities of 22% to 74% of healthy dogs. Capnocytophaga canimorsus has unique virulence factors that enable it to evade the human immune system and cause life-threatening sepsis following a dog bite. We report a previously well 68-year-old woman who presented with septic shock and multiorgan failure following a seemingly minor dog bite to the finger. The patient required intensive care treatment, intravenous antibiotic therapy, and multiple surgical procedures including amputation of the affected finger. The septicemia and coagulopathy that ensued resulted in gangrene and amputation of additional fingers and toes. The purpose of this report is to raise awareness of this organism among hand surgeons when faced with a patient presenting in septic shock and minimal signs at the site of a dog bite.

Multidrug-resistant oral Capnocytophaga gingivalis responsible for an acute exacerbation of chronic obstructive pulmonary disease: Case report and literature review.

INTRODUCTION: Capnocytophaga genus was recently known to highly contribute to the beta-lactam (BL) and macrolide-lincosamide-streptogramin (MLS) resistance gene reservoir in the oral microbiota (BL: blaCSP-1 and blaCfxA; MLS: erm(F) and erm(C)). But fluoroquinolone (FQ) resistance remains uncommon in literature, without available data on resistance mechanisms. CASE REPORT: For the first time, a case of acute exacerbation of chronic obstructive pulmonary disease (COPD) was described in a 78-year-old immunocompetent patient due to a multidrug-resistant Capnocytophaga gingivalis isolate with significant microbiological finding. C.gingivalis acquired resistance to third generation cephalosporins (blaCfxA3 gene), MLS (erm(F) gene), and fluoroquinolones. Genetics of the resistance, unknown as regards fluoroquinolone, was investigated and a substitution in QRDR of GyrA was described (Gly80Asn substitution) for the first time in the Capnocytophaga genus. LITERATURE REVIEW: A comprehensive literature review of Capnocytophaga spp. extra-oral infection was conducted. Including the present report, on 43 cases, 7 isolates were BL-resistant (17%), 4 isolates were MLS-resistant (9.5%) and 4 isolates were FQ-resistant (9.5%). The studied clinical isolate of C.gingivalis was the only one to combine resistance to the three groups of antibiotics BL, MLS and FQ. Four cases of Capnocytophaga lung infection were reported, including three infections involving C. gingivalis (two FQ resistant) and one involving C. sputigena. CONCLUSION: This multidrug-resistant C. gingivalis isolate illustrated the role of oral flora as a reservoir of antibiotic resistance and its contribution to the limitation of effective antibiotics in severe respiratory infections.

The lipopolysaccharide from Capnocytophaga canimorsus reveals an unexpected role of the core-oligosaccharide in MD-2 binding.

Capnocytophaga canimorsus is a usual member of dog's mouths flora that causes rare but dramatic human infections after dog bites. We determined the structure of C. canimorsus lipid A. The main features are that it is penta-acylated and composed of a "hybrid backbone" lacking the 4' phosphate and having a 1 phosphoethanolamine (P-Etn) at 2-amino-2-deoxy-d-glucose (GlcN). C. canimorsus LPS was 100 fold less endotoxic than Escherichia coli LPS. Surprisingly, C. canimorsus lipid A was 20,000 fold less endotoxic than the C. canimorsus lipid A-core. This represents the first example in which the core-oligosaccharide dramatically increases endotoxicity of a low endotoxic lipid A. The binding to human myeloid differentiation factor 2 (MD-2) was dramatically increased upon presence of the LPS core on the lipid A, explaining the difference in endotoxicity. Interaction of MD-2, cluster of differentiation antigen 14 (CD14) or LPS-binding protein (LBP) with the negative charge in the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) of the core might be needed to form the MD-2 - lipid A complex in case the 4' phosphate is not present.

Complete genome sequence of the dog commensal and human pathogen Capnocytophaga canimorsus strain 5.

Capnocytophaga canimorsus is a commensal Gram-negative bacterium, originally isolated from a dog's mouth, that causes septicemia in humans. C. canimorsus has the unusual ability to feed on host cells, including phagocytes. This capacity depends on surface-exposed glycan-foraging systems. Here we present the first complete genome sequence of a C. canimorsus strain (Cc5).

Cluedo - Source identification in a case of septicemia fatality caused by Capnocytophaga canimorsus.

The Gram negative pathogen Capnocytophaga canimorsus is a frequent commensal in the oral cavity of cats and dogs. Although the bacterium is generally considered harmless, infections in humans can occur displaying a broad spectrum of clinical syndromes. This makes a clinical diagnosis difficult. The patient in the present case was 67 years old and presented to the emergency room (ER) with pain in the upper right abdomen and clinical signs of a feverish infection. The only noticeable record in the patient´s medical history was a splenectomy in childhood. The anamnesis revealed that the patient was the owner of two dogs. After a suspected diagnosis of sepsis the patient was transferred to the intensive care unit (ICU), where his medical condition deteriorated rapidly. Despite intensive care measures as well as the fast initialization of a broad-spectrum antibiotic therapy, the patient died 37 h after his presentation in the ER. The search for the causative pathogen turned out to be challenging. Eventually, molecular biological methods assisted in solving the puzzle. It could be demonstrated that the pathogen, found in the patient´s blood, was also present in one of his dogs' oral cavity.

"My Dog Deafened Me!": Case Report of Capnocytophaga canimorsus Infection and Literature Review.

Capnocytophaga canimorsus infection is an emerging zoonotic disease that could cause meningitis and subsequent sensorineural hearing loss (SNHL), especially in the immunocompromised population. It is a gram-negative rod that belongs to the normal oral flora of dogs and cats and may be transmitted to humans by biting or licking. Our case report and literature review showed that this postmeningitic SNHL has distinct features from common bacterial meningitis-related SNHL. We therefore discuss the diagnostic, therapeutic, and preventive aspects of this uncommon cause of SNHL. Because it is now the second-most common dog-bite transmitted pathogen, otolaryngologists are more likely to encounter this zoonotic disease and should be aware of its characteristics. Laryngoscope, 129:41-43, 2019.

Capsular serovars of virulent Capnocytophaga canimorsus are shared by the closely related species C. canis and C. cynodegmi.

Capnocytophaga canimorsus is a dog oral commensal bacterium that causes rare but life-threatening generalized infections in humans who have been in contact with its animal hosts. Two other dog commensals, Capnocytophaga canis and Capnocytophaga cynodegmi, cause rare, mild local infections. To date, nine capsular serovars have been described in C. canimorsus. Here, we serotyped 112 strains of Capnocytophaga spp. isolated from human infections. The C. canimorsus strains (86 of 96, 89.6%) belonged to serovars A, B, or C with relative frequencies of approximately 30% for each serovar. The high prevalence of the A, B, and C serovars in strains isolated from humans, compared to the previously described low prevalence of these serovars among dog isolates (7.6%), confirms that these three serovars are more virulent to humans than other serovars and suggests that the low incidence of disease may be linked to the low prevalence of the A, B, and C serovars in dogs. We serotyped six strains of C. canis and ten strains of C. cynodegmi and, surprisingly, found one C. canis and three C. cynodegmi strains to be of capsular serovar B. This observation prompted us to test 34 dog-isolated C. canis and 16 dog-isolated C. cynodegmi strains. We found four C. canis strains belonging to serovar A and one belonging to serovar F. In contrast, no dog-isolated C. cynodegmi strain could be typed with the available antisera. This work demonstrates that virulence-associated capsular polysaccharides (A, B, and C) are not specific to the C. canimorsus species.

Antimicrobial treatment of Capnocytophaga infections.

Capnocytophaga spp. are normal inhabitants of the oropharyngeal flora. They are also involved in periodontal diseases or animal bites, complicated by septicaemia with dissemination to a great variety of sites, both in immunocompetent and immunocompromised hosts. This review will focus on their pathogenesis, spectrum of clinical infections and susceptibility to disinfectants and antibiotics. The spread of beta-lactamase-producing strains limits the use of beta-lactams as first-line treatments, underlying the necessity to test the in vitro susceptibility of clinical strains. Many antimicrobial treatments have been used, despite an absence of randomised studies and guidelines regarding the duration of treatment according to infected sites. Imipenem/cilastatin, clindamycin or beta-lactamase inhibitor combinations are always effective and their use can be recommended in all infections.

Dental and periodontal health, and microbiological and salivary conditions in patients with or without diabetes undergoing haemodialysis.

OBJECTIVE: The aim of this cross-sectional study was to evaluate the dental and periodontal health, as well as the microbiological and salivary conditions, of patients with and without diabetes mellitus (DM) who are receiving haemodialysis. METHODS: One-hundred and fifty-nine haemodialysis patients were included and divided into groups according to the pre-existing diabetes status: DM or no DM. The oral examination included dental findings and assessment of the periodontal situation. The periodontal condition was classified as healthy/mild, moderate or severe periodontitis. Subgingival biofilm samples were analysed using the polymerase chain reaction. The salivary diagnostics included measurement of unstimulated and stimulated salivary flow, pH and buffer capacity. Statistical analyses used Fisher's test, the t-test and the Mann-Whitney U-test (α = 5%). RESULTS: The dental findings showed no significant difference between patients with and without DM (P = 0.44). The prevalence of periodontitis was high (96% in patients with DM and 97% in patients who did not have DM) and there was no significant difference between the groups (P = 0.71). There was a higher prevalence of Porphyromonas gingivalis, Parvimonas micros, Eubacterium nucleatum and Capnocytophaga spp. in patients without DM (P < 0.05). The salivary pH was significantly higher in patients without DM (P < 0.01). CONCLUSION: While differences in the prevalence of periodontal pathogenic bacteria and in the salivary pH were detected between the groups, the dental and periodontal status was comparable between patients with and without DM. Accordingly, DM appears to have no decisive influence on the oral health in patients treated with haemodialysis who have well-controlled diabetes.

[Meningitis due to Capnocytophaga canimorsus without dog bite]. / Méningite à Capnocytophaga canimorsus sans notion de morsure de chien.

INTRODUCTION: Capnocytophaga canimorsus is a fusiform and filamentous gram-negative rod, part of the normal oral flora of dogs and cause rare human febrile acute meningitis, usually severe but curable. OBSERVATION: A sixty years old man presented a severe acute meningitis with fever and confusion. CSF show 4,000 cells/mm3 with 83% neutrophilis, increased protein level (5,02 g/L), very low glucose and positive Gram stain result. The patient fully and quickly recovered with antibiotherapy for 22 days. Bacteriological diagnosis was made by genomic study from CSF culture. The patient has a close contact with his dog without being recently bitten. DISCUSSION: Diagnosis, suggested by bites or contact with dog or cat, gram-negative bacilli with gram stain of CSF specimen, is possible by prolonged culture of CSF or blood sample, with if necessary genomic study. Antibioprophylaxis is strongly recommended in cases of deep bite wounds and for immunocompromised patients.

Evidence for a LOS and a capsular polysaccharide in Capnocytophaga canimorsus.

Capnocytophaga canimorsus is a dog's and cat's oral commensal which can cause fatal human infections upon bites or scratches. Infections mainly start with flu-like symptoms but can rapidly evolve in fatal septicaemia with a mortality as high as 40%. Here we present the discovery of a polysaccharide capsule (CPS) at the surface of C. canimorsus 5 (Cc5), a strain isolated from a fulminant septicaemia. We provide genetic and chemical data showing that this capsule is related to the lipooligosaccharide (LOS) and probably composed of the same polysaccharide units. A CPS was also found in nine out of nine other strains of C. canimorsus. In addition, the genomes of three of these strains, sequenced previously, contain genes similar to those encoding CPS biosynthesis in Cc5. Thus, the presence of a CPS is likely to be a common property of C. canimorsus. The CPS and not the LOS confers protection against the bactericidal effect of human serum and phagocytosis by macrophages. An antiserum raised against the capsule increased the killing of C. canimorsus by human serum thus showing that anti-capsule antibodies have a protective role. These findings provide a new major element in the understanding of the pathogenesis of C. canimorsus.