Clinical and Biologic Characteristics of Kingella kingae -Induced Septic Arthritis of the Knee in Young Children.

BACKGROUND AND OBJECTIVES: Septic arthritis of the knee is presumed to be the most frequent form of Kingella kingae -induced osteoarticular infection. This study aimed to report on the clinical course, biological parameters, and results of microbiological investigations among children with K. kingae -induced septic arthritis of the knee. It also assessed the modified Kocher-Caird criteria's ability to predict K. kingae -induced septic arthritis of the knee. METHODS: The medical charts of 51 children below 4 years old with confirmed or highly probable K. kingae -induced arthritis of the knee were reviewed. Data were gathered on the five variables in the commonly-used Kocher-Caird prediction algorithm (body temperature, refusal to bear weight, leukocytosis, erythrocyte sedimentation rate, and C-reactive protein level). RESULTS: Patients with K. kingae -induced arthritis of the knee usually presented with a mildly abnormal clinical picture and normal or near-normal serum levels of acute-phase reactants. Data on all five variables were available for all the children: 7 children had zero predictors; 8, 20, 12, and 4 children had 1, 2, 3, and 4 predictors, respectively; no children had 5 predictors. This gave an average of 1.96 predictive factors and a subsequent probability of ≤ 62.4% of infectious arthritis in this pediatric cohort. CONCLUSIONS: Because the clinical features of K. kingae -induced arthritis of the knee overlap with many other conditions affecting this joint, the Kocher-Caird prediction algorithm is not sensitive enough to effectively detect K. kingae -induced septic arthritis of the knee. Excluding K. kingae -induced arthritis of the knee requires performing nucleic acid amplification assays on oropharyngeal swabs and joint fluid from those young children presenting with effusion of the knee, even in the absence of fever, leukocytosis, or a high Kocher-Caird score.

The Kingella kingae PilC1 MIDAS Motif Is Essential for Type IV Pilus Adhesive Activity and Twitching Motility.

Kingella kingae is an emerging pathogen that has recently been identified as a leading cause of osteoarticular infections in young children. Colonization with K. kingae is common, with approximately 10% of young children carrying this organism in the oropharynx at any given time. Adherence to epithelial cells represents the first step in K. kingae colonization of the oropharynx, a prerequisite for invasive disease. Type IV pili and the pilus-associated PilC1 and PilC2 proteins have been shown to mediate K. kingae adherence to epithelial cells, but the molecular mechanism of this adhesion has remained unknown. Metal ion-dependent adhesion site (MIDAS) motifs are commonly found in integrins, where they function to promote an adhesive interaction with a ligand. In this study, we identified a potential MIDAS motif in K. kingae PilC1 which we hypothesized was directly involved in mediating type IV pilus adhesive interactions. We found that the K. kingae PilC1 MIDAS motif was required for bacterial adherence to epithelial cell monolayers and extracellular matrix proteins and for twitching motility. Our results demonstrate that K. kingae has co-opted a eukaryotic adhesive motif for promoting adherence to host structures and facilitating colonization.

Surface Anchoring of the Kingella kingae Galactan Is Dependent on the Lipopolysaccharide O-Antigen.

Kingella kingae is a leading cause of bone and joint infections and other invasive diseases in young children. A key K. kingae virulence determinant is a secreted exopolysaccharide that mediates resistance to serum complement and neutrophils and is required for full pathogenicity. The K. kingae exopolysaccharide is a galactofuranose homopolymer called galactan and is encoded by the pamABC genes in the pamABCDE locus. In this study, we sought to define the mechanism by which galactan is tethered on the bacterial surface, a prerequisite for mediating evasion of host immune mechanisms. We found that the pamD and pamE genes encode glycosyltransferases and are required for synthesis of an atypical lipopolysaccharide (LPS) O-antigen. The LPS O-antigen in turn is required for anchoring of galactan, a novel mechanism for association of an exopolysaccharide with the bacterial surface. IMPORTANCE Kingella kingae is an emerging pediatric pathogen and produces invasive disease by colonizing the oropharynx, invading the bloodstream, and disseminating to distant sites. This organism produces a uniquely multifunctional exopolysaccharide called galactan that is critical for virulence and promotes intravascular survival by mediating resistance to serum and neutrophils. In this study, we established that at least some galactan is anchored to the bacterial surface via a novel structural interaction with an atypical lipopolysaccharide O-antigen. Additionally, we demonstrated that the atypical O-antigen is synthesized by the products of the pamD and pamE genes, located downstream of the gene cluster responsible for galactan biosynthesis. This work addresses how the K. kingae exopolysaccharide can mediate innate immune resistance and advances understanding of bacterial exopolysaccharides and lipopolysaccharides.

First report of Kingella kingae infection in a paediatric population in Accra, Ghana.

Introduction: Kingella kingae is recognized as a frequent source of childhood bacteremia and the commonest agent of skeletal system infections in children 6 months - 4 years old. Several factors, including difficulty in detecting this fastidious organism in routine laboratory assays, result in underdiagnosis of the infections. Species-specific nucleic acid amplification assays, however, significantly improve the detection of K. kingae in blood samples. The aim of this study was to detect K. kingae infection in young children in Accra, Ghana. Methods: a cross-sectional based study was carried out in three hospitals in Accra. Children with febrile illness and directed by a clinician for blood culture were recruited. Blood samples collected were analysed by culture and polymerase chain reaction (PCR), using universal prokaryotic and K. kingae rtxA primers. Results: blood samples from 232 children (mean age 20.10 ± 12.57 months) were analysed. Bacteremia (72.4%) was the highest clinical diagnosis particularly in the 12-24 months age group. Only 7 (3.1%) samples showed bacterial growth and were negative for Kingella. PCR with universal prokaryotic primers succeeded in 223 (96.1%) out of 232 samples. PCR with K. kingae rtxA toxin primers was positive for 12 (5.4%) samples, all diagnosed as bacteremia, out of the 223 samples. Eleven (91.7%) out of the 12 K. kingae PCR positives were culture-negative. Conclusion: Kingella kingae was detected only by PCR specific for the K. kingae rtxA toxin. Kingella kingae may be a potential cause of bacteremia and hence febrile illness in young children living in Accra, Ghana.

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.

Neisseria lactamica Controlled Human Infection Model.

Neisseria lactamica is a nonpathogenic commensal of the human upper respiratory tract that has been associated with protection against N. meningitidis colonization and disease. We have previously utilized the N. lactamica controlled human infection model to investigate the protective effect of N. lactamica colonization on N. meningitidis colonization, the nature of cross-reactive immune responses mounted toward N. meningitidis following N. lactamica colonization, and the microevolution of N. lactamica over a 5-month colonization period. More recently, we have assessed the possibility of utilizing genetically modified strains of N. lactamica to enable use of the commensal as a vehicle for prolonged exposure of the nasopharynx of humans to antigens of interest, expressed in carried organisms. A controlled infection with N. lactamica expressing the meningococcal antigen NadA has been executed and the results demonstrate that this strategy is effective at generating immune responses to the target antigen. Throughout this chapter, we outline in a step-by-step manner the methodologies utilized when performing controlled human infection with N. lactamica including procedures relating to: (1) the dilution of N. lactamica stock vials to derive intranasal inocula, (2) the delivery of intranasal inocula to human volunteers, (3) the determination of N. lactamica colonization status following intranasal inoculation using oropharyngeal swabbing and nasal wash sampling, (4) the microbiological procedures utilized to identify N. lactamica colonization among study volunteers, and (5) the identification of N. lactamica colonies as strain Y92-1009 using polymerase chain reaction.

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.

Microbiology of septic arthritis in young Auckland children.

BACKGROUND: Kingella kingae is an important cause of septic arthritis in young children, with modern laboratory methods leading to increased detection. Prevalence of this pathogen in New Zealand, where there are high rates of childhood infections due to Staphylococcus aureus and Streptococcus pyogenes, is not known. METHODS: We conducted a retrospective review of children <5 years with septic arthritis (without osteomyelitis) at a tertiary children's hospital in Auckland, over 10 years (2005-2014). Data were collected on demographics, microbiology, clinical presentation, investigations and management. RESULTS: Of the 68 cases of septic arthritis, 57 (83.8%) occurred in children aged <24 months. Among those <3 months, Streptococcus agalactiae (Group B streptococcus) was predominant (45.5% of 11 cases), followed by S. aureus (36.4%). The most common pathogen in those 3 to <12 months was Streptococcus pneumoniae (38.5% of 13 cases). In children aged 12 to <24 months, K. kingae was most common (30.3% of 33 cases). Of the 12 cases of K. kingae, 91.7% were identified from synovial fluid culture. All K. kingae isolates were susceptible to amoxicillin. CONCLUSIONS: K. kingae is the leading pathogen in septic arthritis in New Zealand children aged 12 to <24 months. Routine inoculation of synovial fluid into blood culture bottles at time of sample collection, in addition to use of polymerase chain reaction methods, should be encouraged to improve detection rates. For infants and preschool children presenting with single joint septic arthritis, empiric antibiotics should include cover for S. aureus and K. kingae.

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.

Native joint infections in Iceland 2003-2017: an increase in postarthroscopic infections.

OBJECTIVES: Nationwide study on the epidemiology, clinical characteristics and outcomes among patients with native joint infection (NJI) in Iceland, 2003-2017. METHODS: All positive synovial fluid culture results in Iceland were identified and medical records reviewed. RESULTS: A total of 299 NJI (40 children and 259 adults) were diagnosed in Iceland in 2003-2017, with a stable incidence of 6.3 cases/100 000/year, but marked gender difference among adults (33% women vs 67% men, p<0.001). The knee joint was most commonly affected, and Staphylococcus aureus was the most common isolate in both adults and children, followed by various streptococcal species in adults and Kingella kingae in children. NJI was iatrogenic in 34% of adults (88/259) but comprised 45% among 18-65 years and a stable incidence. Incidence of infections following arthroscopic procedures in adults increased significantly compared with the previous decade (9/100 000/year in 1990-2002 vs 25/100 000/year in 2003-2017, p<0.01) with no significant increase seen in risk per procedure. The proportion of postarthroscopic NJI was 0.17% overall but 0.24% for knee arthroscopy. Patients with postarthroscopic infection were more likely to undergo subsequent arthroplasty when compared with other patients with NJI (p=0.008). CONCLUSIONS: The incidence of NJI in Iceland has remained stable. The proportion of iatrogenic infections is high, especially among young adults, with an increase seen in postarthroscopic infections when compared with the previous decade. Although rare, NJI following arthroscopy can be a devastating complication, with significant morbidity and these results, therefore, emphasise the need for firm indications when arthroscopic treatment is considered.

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.