Pan-genome mediated therapeutic target mining in Kingella kingae and inhibition assessment using traditional Chinese medicinal compounds: an informatics approach.

Kingella kingae causes bacteremia, endocarditis, osteomyelitis, septic arthritis, meningitis, spondylodiscitis, and lower respiratory tract infections in pediatric patients. Usually it demonstrates disease after inflammation of mouth, lips or infections of the upper respiratory tract. To date, therapeutic targets in this bacterium remain unexplored. We have utilized a battery of bioinformatics tools to mine these targets in this study. Core genes were initially inferred from 55 genomes of K. kingae and 39 therapeutic targets were mined using an in-house pipeline. We selected aroG product (KDPG aldolase) involved in chorismate pathway, for inhibition analysis of this bacterium using lead-like metabolites from traditional Chinese medicinal plants. Pharmacophore generation was done using control ZINC36444158 (1,16-bis[(dihydroxyphosphinyl)oxy]hexadecane), followed by molecular docking of top hits from a library of 36,000 compounds. Top prioritized compounds were ZINC95914016, ZINC33833283 and ZINC95914219. ADME profiling and simulation of compound dosing (100 mg tablet) was done to infer compartmental pharmacokinetics in a population of 300 individuals in fasting state. PkCSM based toxicity analysis revealed the compounds ZINC95914016 and ZINC95914219 as safe and with almost similar bioavailability. However, ZINC95914016 takes less time to reach maximum concentration in the plasma and shows several optimal parameters compared to other leads. In light of obtained data, we recommend this compound for further testing and induction in experimental drug design pipeline.Communicated by Ramaswamy H. Sarma.

First documented outbreak of arthritis caused by Kingella kingae in a Spanish childcare center.

BACKGROUND: Recently, Kingella kingae (K. kingae) has been described as the most common agent of skeletal system infections in children 6 months-2 years of age. More exceptional is the clinical presentation in clusters of invasive K. kingae infections. We describe the investigation of the first outbreak of 3 cases of arthritis caused by K. kingae documented in Spain detected in a daycare center in Roses, Girona. PATIENTS AND METHODS: In December of 2015 surveillance throat swabs obtained from all attendees from the same class of the index daycare center were assessed to study the prevalence of K. kingae colonization. The sample was composed of 9 toddlers (range: 16-23 months of age). Investigation was performed by culture and K. kingae-specific RT-PCR. Combined amoxicillin-rifampicin prophylaxis was offered to all attendees who were colonized by K. kingae. Following antimicrobial prophylaxis, a new throat swab was taken to confirm bacterial eradication. RESULTS: K. kingae was detected by RT-PCR throat swabs in the 3 index cases and 5 of the 6 daycare attendees. Cultures were negative in all cases. After administration of prophylactic antibiotics, 3 toddlers were still positive for K. kingae-specific RT-PCR. CONCLUSIONS: Clusters of invasive K. kingae infections can occur in daycare facilities and closed communities. Increased awareness and use of sensitive detection methods are needed to identify and adequately investigate outbreaks of K. kingae disease. In our experience, the administration of prophylactic antibiotics could result in partial eradication of colonization. No further cases of disease were detected after prophylaxis.

Kingella kingae Spondylodiscitis: Treatment Failure With Flucloxacillin.

Kingella kingae infections generally respond well to most beta-lactam antibiotics. We investigated an antibiotic treatment failure in a 3-year-old with K. kingae L3-4 spondylodiscitis. Her disease progressed even after 19 days of high-dose intravenous flucloxacillin. The clinical isolate did not produce a beta-lactamase and despite phenotypic testing and whole-genome sequencing, the mechanism of flucloxacillin resistance remains unknown.

Primary Pyomyositis Caused by Kingella kingae in a 21-Month-old Infant: A Case Report.

The authors report a rare case of an unusual primary pyomyositis of the biceps cruralis assigned to Kingella kingae in a 21-month-old girl. The reported case demonstrated that primary pyomyositis may be encountered during invasive infection due to K. kingae even if this manifestation remains rare. This bacterial etiology must, therefore, be evoked when a primary pyomyositis is observed, and this is in particular in children under 4 years of age.

Primary Septic Arthritis Among Children 6 to 48 Months of Age: Implications for PCR Acquisition and Empiric Antimicrobial Selection.

INTRODUCTION: Primary septic arthritis requires unique evaluation and treatment considerations for children in the 6- to 48-month age range because of the spectrum of identified pathogens and high rate of negative cultures. The purpose of this study is to evaluate primary septic arthritis in this age group in order to differentiate children with infection caused by Kingella kingae from those with other confirmed pathogens and those with no identified pathogen. METHODS: Preschool children who underwent multidisciplinary evaluation and treatment for septic arthritis between 2009 and 2019 were retrospectively studied. Three cohorts were established for comparison of clinical and laboratory features of primary septic arthritis: (1) confirmed K. kingae, (2) confirmed other pathogen, and (3) presumed (without identified pathogen). RESULTS: Among 139 children with septic arthritis, 40 (29%) were confirmed K. kingae, 29 (21%) other pathogen, and 70 (50%) presumed. Children with Kingella and those with presumed septic arthritis had significantly lower initial C-reactive protein (4.8 and 4.5 vs. 9.3 mg/dL) and fewer febrile hospital days (0.2 and 0.4 vs. 1.3 d) than children with other confirmed pathogens. Children with other pathogens had higher rates of bacteremia (38% vs. 0%) and positive joint fluid cultures (86% vs. 15%) than that of children with Kingella. The rate of polymerase chain reaction (PCR) acquisition was 38 of 40 (95.0%) Kingella cases, 18 of 29 (62.1%) other pathogen cases, and 33 of 70 (47.1%) presumed cases. CONCLUSIONS: K. kingae was the most commonly identified pathogen among 6-month to 4-year-old children. The Kingella and other identified pathogens in this study serve to guide empiric antimicrobial recommendations for this age range. Because of similarities between children with septic arthritis because of K. kingae and those with no identified pathogen, it is likely that an unrecognized burden of Kingella resides in culture negative cases, particularly if no PCR is sent. Systematic evaluation, including PCR acquisition, and a high index of suspicion for K. kingae are recommended to thoroughly evaluate septic arthritis in preschool children. LEVEL OF EVIDENCE: Level III-Retrospective cohort comparison.

Neisseria sicca: A Rare Cause of Bacterial Conjunctivitis.

BACKGROUND Neisseria-associated conjunctivitis is a rare cause of bacterial conjunctivitis in adults, with Neisseria gonorrhoeae as the primarily identified infectious strain. Here, we present a rare case of bacterial conjunctivitis due to Neisseria sicca in a 34-year-old immunocompetent man with no prior medical or ocular history. CASE REPORT A 34-year-old man with no significant past medical or ocular history presented with a 3-day history of left periorbital edema, ocular pain, and copious purulent discharge. Bacterial conjunctivitis was suspected due to the rapidity of onset and purulence. Peripheral corneal thinning was identified. Preliminary culture results showed gram-negative diplococci, and the patient was treated for gonococcal infection. Final cultures identified Neisseria sicca, a rarely pathogenic strain of Neisseria species. CONCLUSIONS This is the second reported case of Neisseria sicca-associated conjunctivitis, and the first reported case to have corneal involvement. Neisseria sicca, while typically non-pathogenic, may manifest as conjunctivitis in immunocompetent hosts with a low-risk sexual history.

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.

Case Report: A Polymicrobial Vision-Threatening Eye Infection Associated with Polysubstance Abuse.

We report a patient with risk factors for both microbial keratitis and endophthalmitis, which were initially challenging to distinguish. Cultures of corneal scrapings yielded several organisms, including an uncultivable Gram-negative rod, eventually identified as Kingella negevensis. Kingella negevensis is so named because most strains have been isolated in the Negev, a desert region of southern Israel. The epidemiology of K. negevensis remains incompletely understood. We found no other reports in the literature of this organism causing microbial keratitis.

Q Fever and Kingella kingae Endocarditis in a Toddler: A Rare Coinfection Case.

A toddler after tetralogy of Fallot graft repair in infancy was diagnosed with endocarditis. Blood cultures were positive for Kingella kingae and serology was positive Coxiella burnetii. He was treated medically and surgically. A postoperative specimen polymerase chain reaction confirmed a coinfection. A comprehensive patient history was imperative for identification of an unlikely infection at this age.

Short-course antibiotic treatment of bone and joint infections in children: a retrospective study at Montpellier University Hospital from 2009 to 2013.

BACKGROUND: Acute haematogenous bone and joint infections (AHBJI) represent a diagnostic and therapeutic emergency in children, with significant potential sequelae in the case of delayed treatment. Although historically the recommendations for treatment have been based on surgery and prolonged antibiotic therapy, recent studies have demonstrated that short-course antibiotic therapy is also effective. OBJECTIVES: We evaluated a short-term antibiotic protocol for both osteomyelitis and septic arthritis in a 6 year retrospective study at the University Hospital of Montpellier. METHODS: This protocol was based on an initial intravenous treatment with a re-evaluation after 48 h and an early switch to oral therapy in the case of a favourable clinical course for a minimum total duration of 15 days. Antibiotics were selected based on local microbiological epidemiology and systematically adapted to bacteriological results. RESULTS: One hundred and seventy-six cases of AHBJI were included, comprising 56 patients with osteomyelitis, 95 with septic arthritis and 25 who had both of these. The aetiological agent was identified in 42% of the cases, with the main pathogens being Staphylococcus aureus (39%) and Kingella kingae (27%). The mean intravenous treatment duration was 4 days, while the total treatment duration was 15 days. There were no treatment failures, mild sequelae occurred in 1% of the cases and the secondary surgical revision rate was 7%. CONCLUSIONS: The results of this study are comparable to those reported for evaluations of prolonged antibiotic therapy protocols, thus indicating that a common short-term antimicrobial therapy for the management of both osteomyelitis and septic arthritis (minimum of 15 days) is a viable option for treating AHBJI in children. Further prospective studies to confirm these findings are hence warranted.

[Kingella kingae bone and joint infections]. / Arthrites à Kingella kingae chez l'enfant : à propos de six cas.

We report six cases of children with probable or confirmed Kingella kingae bone and joint infections (BJI) and discuss the role of this pathogen in the pediatric population. The advent of Polymerase Chain Reaction (PCR) led to the recognition of the importance of Kingella kingae in several human diseases, particularly in BJI affecting children aged 6 to 48 months. Kingella kingae infections in children have most often a good prognosis provided that the diagnosis is discussed, appropriate diagnostic methods are performed and effective antibiotics are prescribed.

Nous rapportons 6 cas probables ou confirmés d'infections ostéoarticulaires (IOA) à Kingella kingae et proposons une revue de l'implication de ce pathogène en pédiatrie. L'avènement de la PCR (Polymerase Chain Reaction) a mis en lumière son rôle dans diverses maladies humaines, en particulier les IOA chez les enfants âgés de 6 à 48 mois. Le pronostic des infections à Kingella kingae chez l'enfant est le plus souvent bon, pour autant que le diagnostic soit évoqué, que les méthodes diagnostiques adéquates soient utilisées et qu'une antibiothérapie appropriée soit instaurée.

Kingella kingae Septic Arthritis in an Older-Than-Expected Child.

Kingella kingae typically causes musculoskeletal infection in young children between the ages of 6 months and 4 years who may be in close contact with other similarly aged children who are colonized with the organism in their oropharynx. Kingella infections have rarely been described in older individuals with chronic medical conditions or immune compromise. This is a case report of a healthy, older child who developed an invasive infection due to Kingella kingae. Clinical and laboratory details are provided of an otherwise healthy 11-year-old female who developed an acute onset of septic arthritis of her shoulder. The organism was identified by culture and 16S polymerase chain reaction. Her clinical course necessitated an antibiotic change after the organism was correctly identified. The affected child had close contact with a 2-year-old sibling who recently had a viral upper respiratory infection. This case illustrates the potential for Kingella kingae to rarely cause invasive infection in older, healthy children. Supplemental laboratory techniques may be helpful to identify this organism. Although it is reasonable to limit the antibiotic spectrum for older children, clinicians should be aware of this possibility, particularly if there is a history of close contact with young children.

Espondilodiscitis por Kingella kingae: A propósito de un caso de presentación atípica / Atypical presentation of Spondylodiscitis by Kingella Kingae: a case report

La espondilodiscitis infecciosa es una infección poco frecuente en niños, con mayor incidencia en menores de 6 años. Se presenta el caso de una paciente de 8 años, que se internó por dolor lumbar de 2 meses de evolución, afebril. La radiografía, tomografía e imagen por resonancia magnética nuclear fueron compatibles con espondilodiscitis a nivel de L4-L5. Luego de 10 días de antibioticoterapia empírica con clindamicina, con regular respuesta, se realizó punción ósea y se aisló Kingella kingae. Existe un aumento en la incidencia de infecciones osteoarticulares por Kingella kingae en lactantes y niños pequeños. La reemergencia en los últimos años se justifica por la optimización en las técnicas de cultivo, el uso de sistemas automatizados y de técnicas moleculares de diagnóstico. Kingella kingae es un patógeno que ha adquirido importancia en los últimos años en las infecciones osteoarticulares.

Infectious Spondylodiscitis is a rare infection in children. It is more frequent in patients under 6 years of age. We report the case of an 8-year-old patient with lumbar pain for 2 months, without fever. Xrays, computed tomography and magnetic resonance imaging all three showed spondylodiscitis L4-L5. After a 10-day antibiotic treatment with clindamycin with regular response, a bone puncture was performed isolating Kingella kingae (Kk). Ostearticular infections caused by Kk have increased among infants and children. Due to improvement in culture techniques, the usage of automatic systems and assessment molecular techniques, these infections re-emerged in the past few years. Kk is a pathogen that has lately become significant in osteoarticular infections.

[Atypical presentation of Spondylodiscitis by Kingella Kingae: a case report]. / Espondilodiscitis por Kingella kingae: A propósito de un caso de presentación atípica.

Infectious Spondylodiscitis is a rare infection in children. It is more frequent in patients under 6 years of age. We report the case of an 8-year-old patient with lumbar pain for 2 months, without fever. Xrays, computed tomography and magnetic resonance imaging all three showed spondylodiscitis L4-L5. After a 10-day antibiotic treatment with clindamycin with regular response, a bone puncture was performed isolating Kingella kingae (Kk). Ostearticular infections caused by Kk have increased among infants and children. Due to improvement in culture techniques, the usage of automatic systems and assessment molecular techniques, these infections re-emerged in the past few years. Kk is a pathogen that has lately become significant in osteoarticular infections.

La espondilodiscitis infecciosa es una infección poco frecuente en niños, con mayor incidencia en menores de 6 años. Se presenta el caso de una paciente de 8 años, que se internó por dolor lumbar de 2 meses de evolución, afebril. La radiografía, tomografía e imagen por resonancia magnética nuclear fueron compatibles con espondilodiscitis a nivel de L4-L5. Luego de 10 días de antibioticoterapia empírica con clindamicina, con regular respuesta, se realizó punción ósea y se aisló Kingella kingae. Existe un aumento en la incidencia de infecciones osteoarticulares por Kingella kingae en lactantes y niños pequeños. La reemergencia en los últimos años se justifica por la optimización en las técnicas de cultivo, el uso de sistemas automatizados y de técnicas moleculares de diagnóstico. Kingella kingae es un patógeno que ha adquirido importancia en los últimos años en las infecciones osteoarticulares.