Infective Endocarditis by Capnocytophaga Species-A Narrative Review.

Bacteria belonging to the genus Capnocytophaga are thin, capnophilic, Gram-negative bacilli with tapered ends that include nine species that are isolated from the mouth of humans and animals and, from a phylogenetical perspective, they belong to the family Flavobacteriaceae. Two more species, namely C. endodontalis and C. stomatis have been recovered from a periapical abscess and human and animal infections, respectively. Capnocytophaga spp. can cause serious and potentially life-threatening infections in humans, such as bacteremia and meningitis, most commonly in the context of penetrating trauma as a result of contact with animals, especially after animal bites. Other invasive diseases such as osteomyelitis, septic arthritis, and infective endocarditis (IE) may also occur more rarely. The aim of this study was to review all previously described cases of IE by Capnocytophaga spp. and provide information about the epidemiology, microbiology, antimicrobial susceptibility, clinical characteristics, treatment, and outcomes of this infection. A narrative review based on a search in PubMed, the Cochrane Library, and Scopus was performed. Studies published until 11 September 2023 providing relevant data for IE caused by Capnocytophaga spp. in humans were included. A total of 31 studies containing data from 31 patients were included. A history of dog bites was present in 10 out of 26 patients (38.5%). A prosthetic valve was present in 3 patients (9.7%). The most commonly infected valve was the aortic valve, followed by the tricuspid valve. Fever, embolic phenomena, paravalvular abscess, and sepsis were the most common clinical presentations. Beta-lactams and aminoglycosides were the antimicrobials most commonly used. Surgery was performed in 20 patients (64.5%). Overall mortality reached 16.1%.

Factors affecting the quality and reproducibility of MALDI-TOF MS identification for human Capnocytophaga species.

Reproducibility and quality of MALDI-TOF MS spectra are critical in the identification process, however, information on the factors affecting the identification scores are scarce. Here, we studied the influence of various factors during the identification process of human oral Capnocytophaga species. The influence of two incubation times, plate-spotting reproducibility of two examiners, extraction technique, storage period of plates, and different laser repetition rates on the quality of MALDI-TOF MS identification of 34 human Capnocytophaga strains (including C. gingivalis, C. granulosa, C. haemolytica, C. leadbetteri, C. ochracea, C. sputigena, and Capnocytophaga genospecies AHN8471) was examined. The identification rate did not show a significant difference (P = 0.05) between the two incubation times, except that C. haemolytica needed a longer incubation time to be recognized at the genus level. The reproducibility of spotting between two examiners was ensured by following the manufacturer's instructions. At the species level, formic acid extraction improved the identification of species with limited representation in the database, such as C. haemolytica and C. granulosa. The storage of plates for one week decreased the identification scores. No significant difference (P = 0.39) was observed between the 60 Hz and 120 Hz laser repetition rates for identifying Capnocytophaga species to the genus or species level. In conclusion, the MALDI TOF MS offers a reliable Capnocytophaga identification after following the universal protocol, while the formic acid extraction is restricted to species with a limited number of strains in the database.

Bacterial peritonitis secondary to Capnocytophaga canimorsus

We present the case of a patient with liver cirrhosis and several previous episodes of ascitic decompensation, who was admitted for bacterial peritonitis secondary to Capnocytophaga canimorsus infection. The initial clinical presentation, diagnosis, treatment and resolution are described. This is the first case described of peritonitis caused by this agent in a patient with similar characteristics. (AU)

Thrombotic microangiopathy secondary to Capnocytophaga canimorsus bacteremia / Microangiopatía trombótica secundaria a bacteriemia por Capnocytophaga canimorsus

Capnocytophaga canimorsus is an Anaerobic Gram-Negative bacterium present in the oral microbiology of cats and dogs. It can produce infections in humans, being capable of causing severe complications with the development of septic shock. There are known cases where this bacterium developed medical complications like thrombotic microangiopathy and disseminated intravascular coagulation. We have the case of 79 years old male that developed thrombotic microangiopathy and splenic infarction linked to bacteraemia by Capnocytophaga canimorsus. Due to its severity, it was necessary to start renal replacement therapy and several sessions of plasmapheresis with good evolution. (AU)

Capnocytophaga canimorsus es una bacteria anaerobia gramnegativa presente en la microbiología oral de gatos y perros. Puede producir infecciones en humanos, siendo capaz de provocar un diagnóstico severo con desarrollo de shock séptico. Existen casos descritos con complicaciones médicas como Microangiopatía Trombótica y Coagulación Intravascular Diseminada. Presentamos el caso de un varón de 79 años que desarrolló microangiopatía trombótica e infarto esplénico asociado a bacteriemia por Capnocytophaga canimorsus. Por su gravedad, fue necesario iniciar terapia de reemplazo renal y varias sesiones de plasmaféresis con buena evolución. (AU)

Characterization of CoCas9 nuclease from Capnocytophaga ochracea.

Cas9 nucleases are widely used for genome editing and engineering. Cas9 enzymes encoded by CRISPR-Cas defence systems of various prokaryotic organisms possess different properties such as target site preferences, size, and DNA cleavage efficiency. Here, we biochemically characterized CoCas9 from Capnocytophaga ochracea, a bacterium that inhabits the oral cavity of humans and contributes to plaque formation on teeth. CoCas9 recognizes a novel 5'-NRRWC-3' PAM and efficiently cleaves DNA in vitro. Functional characterization of CoCas9 opens ways for genetic engineering of C. ochracea using its endogenous CRISPR-Cas system. The novel PAM requirement makes CoCas9 potentially useful in genome editing applications.

Culture-negative Capnocytophaga canimorsus meningitis diagnosed by 16s ribosomal RNA polymerase chain reaction in an immunocompetent veterinarian and a review of the literature.

Capnocytophaga canimorsus is a fastidious, capnophilic and facultative anaerobic Gram-negative rod found commonly in the oral flora of dogs that may cause zoonotic infections such as cellulitis and eye infections. In immunocompromised patients, it may cause fulminant sepsis. Meningitis due to C. canimorsus is, however, a rare manifestation. This is the first reported case of C. canimorsus meningitis in Australia in an immunocompetent veterinarian diagnosed by 16s ribosomal RNA polymerase chain reaction.

A Novel 16S rRNA PCR-Restriction Fragment Length Polymorphism Assay to Accurately Distinguish Zoonotic Capnocytophaga canimorsus and C. cynodegmi.

The zoonotic bacteria Capnocytophaga canimorsus and C. cynodegmi, the predominant Capnocytophaga species in the canine oral biota, can cause human local wound infections or lethal sepsis, usually transmitted through dog bites. Molecular surveying of these Capnocytophaga species using conventional 16S rRNA-based PCR is not always accurate due to their high genetic homogeneity. In this study, we isolated Capnocytophaga spp. from the canine oral cavity and identified them using 16S rRNA and phylogenetic analysis. A novel 16S rRNA PCR-restriction fragment length polymorphism (RFLP) method was designed based on our isolates and validated using published C. canimorsus and C. cynodegmi 16S rRNA sequences. The results showed that 51% of dogs carried Capnocytophaga spp. Among these, C. cynodegmi (47/98, 48%) was the predominant isolated species along with one strain of C. canimorsus (1/98, 1%). Alignment analysis of 16S rRNA sequences revealed specific site nucleotide diversity in 23% (11/47) of the C. cynodegmi isolates, which were misidentified as C. canimorsus using previously reported species-specific PCR. Four RFLP types could be classified from all the isolated Capnocytophaga strains. The proposed method demonstrates superior resolution in distinguishing C. cynodegmi (with site-specific polymorphism) from C. canimorsus and especially in distinguishing C. canimorsus from other Capnocytophaga species. After in silico validation, this method was revealed to have an overall detection accuracy of 84%; notably, accuracy reached 100% in C. canimorsus strains isolated from human patients. Overall, the proposed method is a useful molecular tool for the epidemiological study of Capnocytophaga in small animals and for the rapid diagnosis of human C. canimorsus infections. IMPORTANCE With the increased number of small animal breeding populations, zoonotic infections associated with small animals need to be taken more seriously. Capnocytophaga canimorsus and C. cynodegmi are part of common biota in the mouths of small animals and can cause human infections through bites or scratches. In this study, C. cynodegmi with site-specific 16S rRNA sequence polymorphisms was erroneously identified as C. canimorsus during the investigation of canine Capnocytophaga by conventional PCR. Consequently, the prevalence of C. canimorsus is incorrectly overestimated in epidemiological studies in small animals. We designed a new 16S rRNA PCR-RFLP method to accurately distinguish zoonotic C. canimorsus from C. cynodegmi. After validation against published Capnocytophaga strains, this novel molecular method had high accuracy and could detect 100% of C. canimorsus-strain infections in humans. This novel method can be used for epidemiological studies and the diagnosis of human Capnocytophaga infection following exposure to small animals.

Postoperative Capnocytophaga Sputigena Presenting as Diffuse Recalcitrant Intra-abdominal Abscesses.

Capnocytophaga sputigena is rarely implicated as the cause of postsurgical intra-abdominal abscess because it is almost exclusively found in oral flora. Despite its rarity in intra-abdominal infection, there are examples of this atypical presentation, and an awareness of this organism as a potential etiology of surgical infection is relevant for both obstetric and general surgeons. We report a case of a young female who presented just over a week after an uncomplicated C-section with complaint of abdominal discomfort and fevers. Imaging revealed multiple intra-abdominal fluid collections and cultures revealed the presence of C. sputigena. Percutaneous drainage and intravenous antibiotics were unable to provide significant source control, so she underwent surgical exploration with a multi-specialty team of obstetric and acute care surgeons. Although postsurgical pelvic abscesses are rarely due to C. sputigena, this organism has been documented to serve as a source of intra-abdominal infection.

Antibiotic Resistance among Fusobacterium, Capnocytophaga, and Leptotrichia Species of the Oral Cavity.

PURPOSE: Antibiotics play an important role in treating periodontal diseases. Due to the effectiveness of antibiotic therapies, their usage in dentistry has significantly increased. The aim of this study focused on the in-vitro susceptibility of different gram-negative oral bacteria species - which are associated with periodontal diseases (Fusobacterium spp., Capnocytophaga spp. and Leptotrichia buccalis) and have different geographical origins (Asia and Europe) - against antimicrobials that are clinically relevant in dental therapy. MATERIALS AND METHODS: A total of 45 strains were tested (29 Fusobacterium spp., 13 Capnocytophaga spp. and 3 L. buccalis) that were either isolated from Chinese patients or were obtained from different strain collections. Their antimicrobial susceptibility to the antimicrobial agents benzylpenicillin, amoxicillin, amoxicillin-clavulanic acid, ciprofloxacin, moxifloxacin, clindamycin, doxycycline, tetracycline and metronidazole was tested using the E-Test. Strains with particular resistance to penicillin, clindamycin and metronidazole were further analysed for resistance genes. RESULTS: All tested bacterial isolates were sensitive to amoxicillin, amoxicillin-clavulanic acid, doxycycline and tetracycline, but showed variable sensitivity towards other antibiotics such as benzylpenicillin, ciprofloxacin, moxifloxacin, clindamycin and metronidazole. CONCLUSION: The results of the present study suggest that certain periodontal disease-related bacterial strains can be resistant towards antimicrobial agents commonly used in adjuvant periodontal therapy.

Capnocytophaga catalasegens sp. nov., isolated from feline oral cavities.

Three bacterial strains, KC07075, KC07079 and KC07084T, were isolated from the oral cavity of cats in 2007 in Japan. These strains were Gram-negative rods, exhibited gliding motility, grew in air with 5 % CO2, and showed oxidase activity, but not catalase activity. The 16S rRNA gene sequences of the three strains were 100 % identical. The 16S rRNA gene sequence of strain KC07084T showed 92.1 and 91.9% identity to the type strains of Capnocytophaga canis and Capnocytophaga felis, respectively, and showed 89.3-91.6% identity to other Capnocytophaga species. The major cellular fatty acids of strain KC07084T were iso-C15 : 0 (58.4 %) and summed feature 11 (13.1 %). The G+C content of DNA from strain KC07084T was 33.7 mol%, and the genome size was 2.92 Mbp. Strains KC07075, KC07079 and KC07084T showed digital DNA-DNA hybridization values (dDDH) values of 99.9 % and average nucleotide identity (ANI) values of 99.98 % with each other, strain KC07084T had dDDH values of 18.7-28.2 % and ANI values of 67.12-72.30 % to the type strains of other Capnocytophaga species. All known species of the genus Capnocytophaga inhabiting the oral cavity of dogs and cats have catalase activity, but the three strains, including type strain KC07084T, lacked catalase activity. These results of the phylogenetic analysis of the 16S rRNA gene sequence, biochemical characteristics, and dDDH and ANI values suggest that strain KC07084T represents a novel species. We propose the name Capnocytophaga catalasegens sp. nov., with KC07084T as the type strain (=JCM 32682T=DSM 107252T).

[Five cases of C. canimorsus during a short period of time at Östersund Hospital, Sweden]. / Fem fall av C canimorsus på kort tid vid Östersunds sjukhus.

We report a sudden increase in the number of cases of C. canimorsus bacteremia during 3 months in 2022 at Östersund Hospital, Sweden. Prior to these cases, the most recent one in the region occurred in 2015. Among the five cases, one suffered from meningitis and one was diagnosed as endocarditis. Dog contact was present in all cases, although dog bites could only be verified in two. Improved diagnostics could not be an explanation to the surge, since the analysis method for blood culture had been the same since 2015. No corresponding increase was noted nationally, according to the Public Health Agency of Sweden. The isolates have been included in the ongoing global study with the aim to explore Capnocytophaga in humans and animals using comparative genomics and genome wide association studies. The study is supported by several ESCMID (European Society of Clinical Microbiology and Infectious Diseases) study groups.

Hemoadsorption as part of a multimodal therapy concept to treat Capnocytophaga sepsis with thrombocytopenia and multiple organ failure.

BACKGROUND: Capnocytophaga, a bacteria native to the oral flora of canines, in rare cases can lead to severe infections resulting in septic shock, respiratory tract infection, and multiple organ failure. In case of trauma following animal bites with rapidly progressing clinical courses, also adjunctive therapeutic measures such as extracorporeal blood purification therapies might be beneficial. CASE PRESENTATION: We report on a 68-year-old male who was hospitalized with fever, oliguria and repeated vomiting after suffering a minor bite by his dog. On admission, he was diagnosed with sepsis. In addition, his coagulation status was markedly deranged resulting in the administration of mass transfusions to stabilize his coagulative status. Following detection of Capnocytophaga canimorsus, anti-infective therapy was initiated. In the context of a progressive respiratory deterioration and an increasing vigilance disorder, he had to be intubated. Due to development of renal failure, dialysis was started in conjunction with CytoSorb hemoadsorption therapy to control the hyperinflammatory condition. All of the applied therapeutic measures led to a rapid clinical stabilization, a control of the hyperinflammatory situation, and an improvement in his neurological status. The therapy was well tolerated with no complications encountered. CONCLUSIONS: This case supports the clinical recognition of severe Capnocytophaga infection that can lead to critical conditions even in immunocompetent patients. Combined broad spectrum antibiotic therapy, mass transfusions, CRRT, and CytoSorb hemoadsorption therapy resulted in a control of the critical situation. However, further research is needed to fully elucidate the role of hemoadsorption in this rare but life-threatening setting.

[Rare complication of a dog bite: Capnocytophaga species bacteremia followed by an hemolytic uremic syndrome]. / Cas clinique. Complication méconnue des morsures canines : syndrome hémolytique et urémique suite à une bactériémie à Capnocytophaga Canimorsus.

Dog bites are a frequent reason for medical consultation. These can be responsible for severe infectious complications. Bacteria of the genus Capnocytophaga species are Gram-negative bacilli commonly found in the oral cavity of certain animals such as dogs and cats. Following a dog bite or wound contamination with animal spit, these bacteria can cause local (cellulitis), systemic and invasive manifestations (bacteremia, endocarditis, meningitis) or lead to rare and dreadful complications such as thrombotic microangiopathies. The identification of Capnocytophaga is slow due to their specific characteristics and their culture conditions. The treatment of Capnocytophaga species infections is based on antibiotic therapy with amoxicillin - clavulanic acid as the first choice. Although different types of Capnocytophaga have been described, C. Canimorsus appears to be associated with a higher rate of atypical complications. Here is the description of an immunocompetent patient who presented with C. Canimorsus bacteremia complicated by hemolytic uremic syndrome following a dog bite.

Les morsures de chien représentent un motif fréquent de consultation. Celles-ci peuvent entraîner des complications infectieuses graves. Les bactéries du genre Capnocytophaga species sont des bacilles Gram négatif fréquemment retrouvés dans la cavité buccale de certains animaux comme les chiens et les chats. à la suite d'une morsure canine ou d'une contamination de plaie par de la salive animale, ces bactéries peuvent provoquer des manifestations locales (cellulite), systémiques et invasives (bactériémie, endocardite, méningite) ou entraîner des complications rares et redoutables comme les microangiopathies thrombotiques. L'identification des Capnocytophaga est lente de par leurs caractéristiques propres et leurs conditions de mise en culture. Le traitement des infections à Capnocytophaga species repose sur une antibiothérapie par amoxicilline-acide clavulanique en première intention. Bien que différents types de Capnocytophaga aient été décrits, C. Canimorsus semble associé à un taux plus élevé de complications atypiques. Nous décrivons ici le cas d'une patiente immunocompétente ayant présenté une bactériémie à C. Canimorsus compliquée d'un syndrome hémolytique et urémique dans les suites d'une morsure de chien.

Lethal Waterhouse-Friderichsen syndrome caused by Capnocytophaga canimorsus in an asplenic patient.

BACKGROUND: Capnocytophaga canimorsus, a Gram-negative rod, belongs to the Flavobacteriaceae family and colonizes the oropharynx of dogs and cats. Infections with C. canimorsus are rare and can induce a systemic infection with a severe course of the disease. So far, only five case reports of C. canimorsus infections associated with Waterhouse-Friderichsen Syndrome (WFS) have been reported with only two of the patients having a history of splenectomy. CASE PRESENTATION: Here, we report a fatal case of WFS due to C. canimorsus bacteremia and mycetal superinfection in a 61-year-old female asplenic patient. Despite extensive therapy including mechanical ventilation, antibiotic coverage with meropenem, systemic corticosteroids medication, vasopressor therapy, continuous renal replacement therapy, therapeutic plasma exchange, multiple transfusions of blood products and implantation of a veno-arterial extracorporeal membrane oxygenation the patient died 10 days after a dog bite. The autopsy showed bilateral hemorrhagic necrosis of the adrenal cortex and septic embolism to heart, kidneys, and liver. Diagnosis of C. canimorsus was prolonged due to the fastidious growth of the bacteria. CONCLUSIONS: The occurrence of a severe sepsis after dog bite should always urge the attending physician to consider C. canimorsus as the disease-causing pathogen. A therapeutic regimen covering C. canimorsus such as aminopenicillins or carbapenems should be chosen. However, despite maximum therapy, the prognosis of C. canimorsus-induced septic shock remains very poor. Asplenic or otherwise immunocompromised patients are at higher risk for a severe course of disease and should avoid exposure to dogs and cats and consider antibiotic prophylaxis after animal bite.