Proinflammatory Microenvironment During Kingella kingae Infection Modulates Osteoclastogenesis.

Kingella kingae is an emerging pathogen that causes septic arthritis, osteomyelitis, and bacteremia in children from 6 to 48 months of age. The presence of bacteria within or near the bone is associated with an inflammatory process that results in osteolysis, but the underlying pathogenic mechanisms involved are largely unknown. To determine the link between K. kingae and bone loss, we have assessed whether infection per se or through the genesis of a pro-inflammatory microenvironment can promote osteoclastogenesis. For that purpose, we examined both the direct effect of K. kingae and the immune-mediated mechanism involved in K. kingae-infected macrophage-induced osteoclastogenesis. Our results indicate that osteoclastogenesis is stimulated by K. kingae infection directly and indirectly by fueling a potent pro-inflammatory response that drives macrophages to undergo functional osteoclasts via TNF-α and IL-1ß induction. Such osteoclastogenic capability of K. kingae is counteracted by their outer membrane vesicles (OMV) in a concentration-dependent manner. In conclusion, this model allowed elucidating the interplay between the K. kingae and their OMV to modulate osteoclastogenesis from exposed macrophages, thus contributing to the modulation in joint and bone damage.

The effects of periodontitis associated microbiota on the development of oral squamous cell carcinoma.

Epidemiological data have shown that periodontal bacterial infection, periodontitis, and oral squamous cell carcinoma have close relationship on the disease progress and risk. However, the specific role of periodontal microbes and their mechanism in the development of oral squamous cell carcinoma is not yet clear. In our previous work, metagenomic Illumina Mi-seq analysis was used to identify tstructure and abundance of periodontital microbiome. Accoding to the results, we used Porphyromonas.spp. and Fusobacterium.spp. as the periodontitis positive microbiota; Neisseria.spp and Corynebacterium.spp as periodontitis negative microbiota (their average relative abundance were >5%). These representative strains of the above genus were used to infect OSCC cells to explore their effect on tumor cell biology behavior, and detect the expression level of the gene in related to inflammation, migration, invasion and cell cycle. We find that periodontitis positive correlated microbiota had a promoting effect on the development of oral squamous cell carcinoma in vitro by regulating mRNA and protein expression of IL-6, IL-8, MMP-9 and Cyclin-D1. Periodontitis negative correlated microbiota had suppression effect on the development of oral squamous cell carcinoma in vitro analysis.

Agricultural Injury-Associated Chromobacterium violaceum Infection in a Bangladeshi Farmer.

Chromobacterium violaceum is an emerging environmental pathogen that causes life-threatening infection in humans and animals. In October 2017, a Bangladeshi farmer was hospitalized with high-grade fever due to an agricultural injury-related wound infection. Bacteriological and 16S rRNA gene investigation detected C. violaceum in the wound discharge. The patient recovered successfully after a combination treatment with meropenem and ciprofloxacin, followed by prolonged medication to avoid recurrence. We strongly propose to incorporate C. violaceum in the differential diagnosis of wound and skin infections occurring in tropical and subtropical regions, especially when the injury was exposed to soil or sluggish water.

Lack of Additional Diagnostic Yield of 16s rRNA Gene PCR for Prosthetic Joint Infections.

INTRODUCTION: Medical management of prosthetic joint infections (PJIs) relies on the identification of causative organisms through traditional culture-based approaches to guide therapy. However, diagnosis of many PJIs remains challenging, with many clinically apparent infections remaining culture-negative. Molecular diagnostics have the potential to increase diagnostic yield, particularly among culture-negative PJIs. METHODS: Bone, tissue, or synovial fluid from patients with clinically identified PJIs were collected for inclusion in this study. Samples were assessed with traditional cultures and classified as culture-positive or -negative after 48 h. Samples subsequently underwent a Staphylococcus aureus-/Kingella kingae-specific PCR followed by a 16s rRNA gene PCR. RESULTS: A total of 77 unique patients with clinically identified PJIs contributed a total of 89 samples for inclusion in the study. There were 54 culture-negative and 35 culture-positive samples evaluated. The sensitivity and specificity of S. aureus PCR in culture-positive samples was 57.1% (95% CI, 34.1%-78.1%) and 92.9% (95% CI, 66.1%-98.9%), respectively. Among culture-positive samples, 16s rRNA gene PCR correctly identified 3 of 21 (14.3%) samples with S. aureus and 2 of 5 (40%) samples with Streptococcus spp. All molecular tests were negative in those with clinically identified, culture-negative PJI. CONCLUSIONS: Our study suggests that these diagnostic tools have a limited role in PJI diagnosis.

Recurrent Acute Septic Arthritis Caused by Kingella kingae in a 16-Month-Old Boy.

We describe the first case of 2 consecutive acute septic arthritis infections of both knees caused by the same virulent strain of Kingella kingae belonging to the virulent sequence type complex 14, in a 16-month-old boy. Both infections occurred after viral upper respiratory tract infections.

Laribacter hongkongensis: clinical presentation, epidemiology and treatment. A review of the literature and report of the first case in Denmark.

BACKGROUND: Laribacter hongkongensis is an emerging pathogen related to gastroenteritis that can cause invasive and even fatal disease. The aim of this review is to describe the clinical presentation, epidemiology, treatment options and implications for the clinical microbiology laboratory. METHODS: We searched Pubmed using the term Laribacter hongkongensis with limitations human and language English, and identified 35 publications with eight reports on human cases. RESULTS: We describe our first case of prolonged, travel-related gastroenteritis where Laribacter hongkongensis was isolated as the sole pathogen. Our review suggests that L. hongkongensis causes non-bloody acute diarrhoea with potential for invasive disease, since three cases of bacteraemia and one case of dialysis related peritonitis have been described previously. L. hongkongensis has primarily been described in Asia, but reports from Europe, North America and Australia suggests a worldwide distribution. Broad culturing with subsequent identification by the MALDI-TOF is the current strategy for detection of L. hongkongensis. Phenotypic susceptibility testing is necessary to guide the treatment choice. Few resistance genes have been described in L. hongkongensis. CONCLUSION: L. hongkongensis should be considered a potential cause of acute and prolonged diarrhoea. Clinicians must be aware of the test methods in the local clinical microbiology laboratory, since L. hongkongensis is difficult to detect and easily overlooked.

An Outbreak of Kingella Kingae Infections Complicating a Severe Hand, Foot, And Mouth Disease Outbreak in Nice, France, 2016.

We report the investigation methods for the diagnosis of an epidemic and culture-negative Kingella kingae endocarditis complicating a severe outbreak of hand, foot and mouth disease in a childcare center. The diagnosis was confirmed by polymerase chain reaction testing performed from cardiac tissue. Our findings argue for the systematic investigation of K. kingae outbreaks by using molecular tools in such context.

Kingella Kingae Chest Mass Mimicking a Tumor in an 11-Month-Old Baby.

Kingella kingae has been recognized as a common etiology of pediatric osteoarticular infections, especially among children younger than 5 years of age. In recent years, there have been reported cases of unusual manifestations. We report a rare case of a chest mass mimicking a tumor in an 11-month-old baby.

Kingella kingae Expresses Four Structurally Distinct Polysaccharide Capsules That Differ in Their Correlation with Invasive Disease.

Kingella kingae is an encapsulated gram-negative organism that is a common cause of osteoarticular infections in young children. In earlier work, we identified a glycosyltransferase gene called csaA that is necessary for synthesis of the [3)-ß-GalpNAc-(1→5)-ß-Kdop-(2→] polysaccharide capsule (type a) in K. kingae strain 269-492. In the current study, we analyzed a large collection of invasive and carrier isolates from Israel and found that csaA was present in only 47% of the isolates. Further examination of this collection using primers based on the sequence that flanks csaA revealed three additional gene clusters (designated the csb, csc, and csd loci), all encoding predicted glycosyltransferases. The csb locus contains the csbA, csbB, and csbC genes and is associated with a capsule that is a polymer of [6)-α-GlcpNAc-(1→5)-ß-(8-OAc)Kdop-(2→] (type b). The csc locus contains the cscA, cscB, and cscC genes and is associated with a capsule that is a polymer of [3)-ß-Ribf-(1→2)-ß-Ribf-(1→2)-ß-Ribf-(1→4)-ß-Kdop-(2→] (type c). The csd locus contains the csdA, csdB, and csdC genes and is associated with a capsule that is a polymer of [P-(O→3)[ß-Galp-(1→4)]-ß-GlcpNAc-(1→3)-α-GlcpNAc-1-] (type d). Introduction of the csa, csb, csc, and csd loci into strain KK01Δcsa, a strain 269-492 derivative that lacks the native csaA gene, was sufficient to produce the type a capsule, type b capsule, type c capsule, and type d capsule, respectively, indicating that these loci are solely responsible for determining capsule type in K. kingae. Further analysis demonstrated that 96% of the invasive isolates express either the type a or type b capsule and that a disproportionate percentage of carrier isolates express the type c or type d capsule. These results establish that there are at least four structurally distinct K. kingae capsule types and suggest that capsule type plays an important role in promoting K. kingae invasive disease.

Neisseria elongata endocarditis of a native aortic valve.

Neisseria elongata is a part of the common bacterial flora of the oropharynx but has caused sepsis, osteomyelitis and infective endocarditis on rare occasions. We report the case of a 56-year-old Caucasian woman who was admitted to hospital with a 5-week history of fever, malaise and fatigue. Two blood cultures grew Gram-negative rods which were confirmed to be N. elongata subspecies nitroreducens via bacterial DNA sequence analysis. An echocardiogram showed a large mobile vegetation on the right and non-coronary cusps of the aortic valve. The patient underwent aortic valve replacement and antibiotic therapy for 6 weeks. We suggest that clinicians should consider extended antibiotic treatment and early surgical evaluation based on the nature and aggressiveness of N. elongata.

[Kingella kingae septicemia in a patient with coxsackievirus infection]. / Septicémie à Kingella kingae chez une patiente présentant une infection à virus Coxsackie.

Kingella kingae is a gram-negative cocci present in the oral flora ; this organism is difficult to isolate by conventional culture techniques ; it can be detected after longer incubation period (more than 6 days) in blood culture. It is responsible of various infectious diseases, especially in children below 3 years-old where it is a cause of arthritis and osteomyeli tis. It is included in HACEK organisms responsible of 2 to 3 % of all cases of native endocarditis. The case report is the case of a young women with Kingella kingae septicemia in a context of oral lesions from Coxsackie virus infection ; treatment by ciprofloxacine permit a complete resolution of symptoms. Differential diagnosis is made about conditions with oral lesions. This article is an occasion to review literature about this unusual organism and clinical presentation. Improvements in laboratory method will in the future increase incidence and prevalence of infections caused by Kingella kingae.

Le Kingella kingae est un cocci Gram-négatif présent dans la flore buccale ; c'est un organisme qui est difficile à isoler par les techniques de culture conventionnelles ; ainsi, il peut être mis en évidence après des périodes d'incubation plus longues (plus de 6 jours) dans les hémocultures. Il est responsable de diverses pathologies infectieuses, notamment chez l'enfant où il peut occasionner une arthrite ou une ostéomyélite, essentiellement en-dessous de l'âge de 3 ans. Il fait partie des organismes HACEK responsables de 2 à 3 % des endocardites infectieuses. Le cas rapporté dans cet article est celui d'une jeune femme présentant une septicémie à Kingella kingae dans un contexte de lésions buccales dues à une infection par virus Coxsackie ; un traitement antibiotique par ciprofloxacine a permis une résolution complète des symptômes. Cet article est l'occasion d'une revue de la littérature concernant cette présentation clinique et ce germe inhabituels.

Meningitis and Bacteremia Due to Neisseria cinerea following a Percutaneous Rhizotomy of the Trigeminal Ganglion.

Neisseria cinerea is a human commensal. The first known case of meningitis and bacteremia due to Neisseria cinerea following percutaneous glycerol instillation of the trigeminal ganglion is reported. Conventional phenotypic methods and complete 16S RNA gene sequencing accurately identified the pathogen. Difficulties in differentiation from pathogenic neisseriae are discussed.

Kingella kingae: carriage, transmission, and disease.

Kingella kingae is a common etiology of pediatric bacteremia and the leading agent of osteomyelitis and septic arthritis in children aged 6 to 36 months. This Gram-negative bacterium is carried asymptomatically in the oropharynx and disseminates by close interpersonal contact. The colonized epithelium is the source of bloodstream invasion and dissemination to distant sites, and certain clones show significant association with bacteremia, osteoarthritis, or endocarditis. Kingella kingae produces an RTX (repeat-in-toxin) toxin with broad-spectrum cytotoxicity that probably facilitates mucosal colonization and persistence of the organism in the bloodstream and deep body tissues. With the exception of patients with endocardial involvement, children with K. kingae diseases often show only mild symptoms and signs, necessitating clinical acumen. The isolation of K. kingae on routine solid media is suboptimal, and detection of the bacterium is significantly improved by inoculating exudates into blood culture bottles and the use of PCR-based assays. The organism is generally susceptible to antibiotics that are administered to young patients with joint and bone infections. ß-Lactamase production is clonal, and the local prevalence of ß-lactamase-producing strains is variable. If adequately and promptly treated, invasive K. kingae infections with no endocardial involvement usually run a benign clinical course.

Kingella kingae sequence type-complex 14 arthritis in a 16-month-old child in Greece.

We describe the first case of Kingella kingae arthritis in a 16-month-old girl in Greece, which has been diagnosed by novel molecular techniques. A joint aspiration of her knee was performed before the initiation of antibiotics, as well as on the 5th and 14th day of empiric antimicrobial therapy. The synovial fluid white blood cell count decreased from 65,000 to 1500 cells/mm, but the percentage of neutrophils remained 90% in all 3 specimens. Molecular analysis of the synovial fluid specimens by real-time polymerase chain reaction and multilocus sequence typing enabled us to reveal the presence of K. kingae belonging to the international sequence type-complex 14, which persisted up to the fifth day of antibiotic therapy.

Purpura fulminans managed with multi-limb amputation: substituted judgment and surrogate decision-making in the surgical management of necrotizing soft tissue infections.

BACKGROUND: Purpura fulminans (PF) is a rare but lethal complication of severe infection. Aggressive surgical debridement of irreversibly devitalized tissue improves survival frequently at the cost of disfigurement. The ethical dilemma of surrogate decision-making for these often incapacitated patients presents a unique challenge for acute care surgeons managing necrotizing soft tissue infections (NSTI). METHODS: Case presentation and scholarly discussion of substituted judgment. RESULTS: A previously healthy 72-y-old fisherman developed PF as a consequence of Neisseria meningiditis severe sepsis requiring bilateral partial finger amputations and bilateral below-knee amputations of the affected gangrenous extremities. Skin biopsy confirmed the clinical impression of disseminated intra-vascular coagulation (DIC). During his 55-d hospitalization, medical decisions were made by a surrogate because the patient's mental status failed to recover to his pre-morbid baseline. A literature review revealed a paucity of data on the accuracy of a health care agent's ability to represent a patient's preferences accurately in elective as well as emergency surgery. CONCLUSIONS: Patients with NSTI and the surgeons who care for them are often confronted with the need to make prompt decisions of radical debridement or amputation. These patients are frequently incapable of making these decisions because of the severity of systemic illness. In such cases, physicians must help patient surrogates or health care agents (when identified) navigate a complex process of acute interventions balancing known or inferred patient's wishes. We urge surgeons to become familiar with the concept of substituted judgment and the challenges of surrogate decision-making.

RTX toxin plays a key role in Kingella kingae virulence in an infant rat model.

Kingella kingae is a human oral bacterium that can cause diseases of the skeletal system in children and infective endocarditis in children and adults. K. kingae produces a toxin of the RTX group, RtxA. To investigate the role of RtxA in disease pathogenesis in vivo, K. kingae strain PYKK081 and its isogenic RtxA-deficient strain KKNB100 were tested for their virulence and pathological consequences upon intraperitoneal injections in 7-day-postnatal (PN 7) rats. At the doses above 8.0 × 10(6) cells/animal, PYKK081 was able to cause a fatal illness, resulting in rapid weight loss, bacteremia, and abdominal necrotic lesion formation. Significant histopathology was observed in thymus, spleen, and bone marrow. Strain KKNB100 was less toxic to animals. Neither weight loss, bacteremia, nor histopathological changes were evident. Animals injected with KKNB100 exhibited a significantly elevated circulating white blood cell (WBC) count, whereas animals injected with PYKK081 had a WBC count that resembled that of the uninfected control. This observation parallels the subtleties associated with clinical presentation of K. kingae disease in humans and suggests that the toxin contributes to WBC depletion. Thus, our results demonstrate that RtxA is a key K. kingae virulence factor. Furthermore, our findings suggest that the PN 7 rat can serve as a useful model for understanding disease caused by K. kingae and for elucidating diagnostic parameters in human patients.