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.

Review highlights the latest research in Kingella kingae and stresses that molecular tests are required for diagnosis.

AIM: The aim of this study was to provide an update on paediatric Kingella kingae infections. METHODS: We used the PubMed database to identify studies published in English, French and Spanish up to 15 November 2020. RESULTS: Kingella kingae colonised the oropharynx after the age of 6 months, and the mucosal surface was the portal of entry of the organism to the bloodstream and the source of child-to-child spread. Attending day care centres was associated with increased carriage rate and transmission and disease outbreaks were detected in day care facilities. Skeletal system infections were usually characterised by mild symptoms and moderately elevated inflammation markers, requiring a high clinical suspicion index. The organism was difficult to recover in cultures and molecular tests significantly improve its detection. Kingella kingae was generally susceptible to beta-lactam antibiotics, and skeletal diseases and bacteraemia responded to antimicrobial, leaving no long-term sequelae. However, patients with endocarditis frequently experienced life-threatening complications and the case fatality rate exceeded 10%. CONCLUSION: Kingella kingae was the prime aetiology of skeletal system infections in children aged 6-48 months. Paediatricians should be aware of the peculiar features of this infection and the need to use molecular tests for diagnosis.

Clinical presentations of Kingella kingae musculoskeletal infections in South Australian children.

AIM: This study aimed to alert clinicians to the spectrum of presentations of Kingella kingae musculoskeletal infections. METHODS: Between August 2010 and March 2018, 55 children presented with positive K. kingae polymerase chain reaction on joint fluid, bone or deep soft tissue collections involving the limbs and subsequently underwent retrospective medical record, radiological and laboratory review. Demographics and clinical information are presented. RESULTS: Median age at presentation was 15.9 months (range 4.3 months-10.7 years) and 64% were male. Septic arthritis was the most common diagnosis (95%), median duration of symptoms was 4 days, 65% had a preceding infection (e.g. upper respiratory or gastrointestinal) and 22% re-presented to emergency departments after prior discharge. The lower limb was involved in 84%, with the knee being most affected (55%). If the lower limb was involved, 82% of previously weight-bearing children had a limp or were unable to weight bear. On presentation, median temperature was 36.7°C and inflammatory markers were mildly elevated. No blood cultures grew K. kingae. Five synovial fluid cultures were positive for K. kingae. Plain radiography showed effusion, soft tissue swelling or a lesion in 53% of patients. All 41 ultrasounds showed effusion, soft tissue swelling or synovial thickening. One patient with delayed diagnosis later presented with avascular necrosis of the femoral head. CONCLUSION: Kingella kingae is difficult to diagnose due to non-specific symptoms, absence of fevers and often unremarkable blood tests. Despite generally having good long-term outcomes, our case of avascular necrosis suggests accurate diagnosis and treatment are important.

Temporal Association Between Rhinovirus Activity and Kingella kingae Osteoarticular Infections.

OBJECTIVE: To determine whether the seasonal distribution of Kingella kingae osteoarticular infections is similar to that of common respiratory viruses. STUDY DESIGN: Between October 2009 and September 2016, we extracted the results of K kingae-specific real-time polymerase chain reaction analyses performed for bone or joint specimens in patients from 2 pediatric tertiary care centers in Paris. We used data of respiratory virus detection from the Réseau National des Laboratoires network with coordination with the National Influenza Center of France. The Spearman rank correlation was used to assess a correlation between weekly distributions, with P < .05 denoting a significant correlation. RESULTS: During the 7-year study period, 322 children were diagnosed with K kingae osteoarticular infection, and 317 testing episodes were K kingae-negative. We observed high activity for both K kingae osteoarticular infection and human rhinovirus (HRV) during the fall (98 [30.4%] and 2401 [39.1%] cases, respectively) and low activity during summer (59 [18.3%] and 681 [11.1%] cases, respectively). Weekly distributions of K kingae osteoarticular infection and rhinovirus activity were significantly correlated (r = 0.30; P = .03). In contrast, no significant correlation was found between the weekly distribution of K kingae osteoarticular infection and other respiratory viruses (r = -0.17, P = .34 compared with respiratory syncytial virus; r = -0.13, P = .34 compared with influenza virus; and r = -0.22, P = .11 compared with metapneumovirus). CONCLUSION: A significant temporal association was observed between HRV circulation and K kingae osteoarticular infection, strengthening the hypothesis of a role of viral infections in the pathophysiology of K kingae invasive infection.

Investigation of Kingella kingae Invasive Infection Outbreaks in Day Care Facilities: Assessment of a Rapid Genotyping Tool Targeting the DNA Uptake Sequence.

Outbreaks of Kingella kingae invasive infections have recently been reported in day care centers. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) revealed that although the invasive strains had widespread dissemination in the day care population, less virulent strains were also circulating in the facilities. However, these typing tools are costly, time-consuming, and labor-intensive and provide delayed results. A study was conducted to assess the performance of a rapid and cost-effective genotyping tool targeting the DNA uptake sequence (DUS) in the investigation of outbreaks of K. kingae disease. DUS typing (DUST) patterns of each strain from 7 different clusters were compared to distinguish genotypically linked strains from others. PFGE and, when available, MLST results were used as gold standards. DUST was assessed on 80 K. kingae isolates from Nir-Itzhak (n = 14), Tel-Nof (n = 14), Palmahim (n = 5), Umm-al-Fahm (n = 7), Eilat (n = 8), Nevatim (n = 15) in Israel and Paris, France (n = 17). A unique DUST pattern was involved in the Nir-Itzhak, Palmahim, Umm-al-Fahm, and Paris episodes. Two DUST patterns were found in Eilat, whereas at least 3 were identified in the Tel-Nof and Nevatim episodes. In total, 11 (13.8%) children carried a K. kingae isolate that differed from the outbreak strain. These results were concordant with those obtained with the traditional PFGE and MLST methods. DUST appears to be sensitive and specific in distinguishing the invasive outbreak strain from others in asymptomatic carriers and could be useful to limit unnecessary exposure of the entire day care population to selective antibiotic pressure.

A modified multilocus sequence typing protocol to genotype Kingella kingae from oropharyngeal swabs without bacterial isolation.

BACKGROUND: Outbreaks of Kingella kingae infection are an emerging public health concern among daycare attendees carrying epidemic clones in the oropharynx. However, genotyping of such epidemic clones from affected cases is limited by the low performance of current methods to detect K. kingae from blood samples and lack of specimens available from infected sites. We aimed at developing a modified multilocus sequence typing (MLST) method to genotype K. kingae strains from oropharyngeal samples without prior culture. We designed in silico MLST primers specific for K. kingae by aligning whole nucleotide sequences of abcZ, adk, aroE, cpn60, recA, and gdh/zwf genes from closely related species belonging to the Kingella and Neisseria genera. We tested our modified MLST protocol on all Kingella species and N. meningitidis, as well as 11 oropharyngeal samples from young children with sporadic (n = 10) or epidemic (n = 1) K. kingae infection. RESULTS: We detected K. kingae-specific amplicons in the 11 oropharyngeal samples, corresponding to sequence-type 6 (ST-6) in 6 children including the epidemic cases, ST-25 in 2 children, and 3 possible novel STs (ST-67, ST-68, and ST-69). No amplicon was obtained from other Kingella species and N. meningitidis. CONCLUSIONS: We herein developed a specific MLST protocol that enables genotyping of K. kingae by MLST directly from oropharyngeal samples. This discriminatory tool, with which we identified the first K. kingae outbreak caused by ST-6 in Europe, may be used in further epidemiological investigations.

Association between oropharyngeal carriage of Kingella kingae and osteoarticular infection in young children: a case-control study.

BACKGROUND: Kingella kingae has been increasingly identified in patients with osteoarticular infections. Our main objective was to evaluate the association between carriage of K. kingae in the oropharynx of preschool children and osteoarticular infections. METHODS: We conducted this prospective case-control study in 2 tertiary care pediatric hospitals (Canada and Switzerland) between 2014 and 2016. Potential cases were children aged 6 to 48 months with a presumptive diagnosis of osteoarticular infection according to the treating emergency physician. Confirmed cases were those with diagnosis of osteomyelitis or septic arthritis proven by positive findings on technetium-labelled bone scan or magnetic resonance imaging or identification of a microorganism in joint aspirate or blood. For each case, we recruited 4 age-matched controls from among children presenting to the same emergency department for trauma. The independent variable was presence of oropharyngeal K. kingae DNA identified by a specific polymerase chain reaction assay. We determined the association between oropharyngeal carriage of K. kingae and definitive osteoarticular infection. RESULTS: The parents of 77 children admitted for suspected osteoarticular infection and 286 controls were invited to participate and provided informed consent. We identified K. kingae in the oropharynx of 46 (71%) of 65 confirmed cases and 17 (6%) of 286 controls; these results yielded an odds ratio of 38.3 (95% confidence interval 18.5-79.1). INTERPRETATION: Detection of oropharyngeal K. kingae was strongly associated with osteoarticular infection among children presenting with symptoms suggestive of such infection.

Low prevalence of Kingella kingae carriage in children aged 6-48 months in Sydney, Australia.

AIM: A prospective observational study was conducted to estimate the prevalence of oropharyngeal carriage of Kingella kingae in healthy Australian pre-school children. METHODS: Screening for carriage of K. kingae as well as Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus agalactiae, Staphylococcus aureus, Haemophilus influenzae, and K. kingae was undertaken using a single bacterial throat swab taken from well children aged 6 months to 4 years. Standard laboratory procedures were used for culture and identification of organisms. RESULTS: One hundred children were enrolled between October and December 2014 at the Children's Hospital at Westmead. Median age was 24.0 months (range 6.1-48.8 months); 52 children were male and 36 attended day-care facilities. Forty-one children had siblings aged less than 5 years and 67 children had siblings of any age. K. kingae oropharyngeal carriage was not detected in any of the children. Rates of carriage of other organisms were: 30% S. aureus, 21% H. influenzae, 2% S. pneumoniae and 2% S. pyogenes. Thirty-eight children were colonised with Kingella denitrificans. CONCLUSIONS: Our results suggest that prevalence of K. kingae carriage in pre-school children in Sydney is very low and support local and national guidelines that recommend flucloxacillin as empiric first-line therapy for children with osteoarticular infections. Studies conducted over the winter months and in other Australian centres could help answer outstanding questions regarding differences in carriage rates of K. kingae in children.

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.

Outbreaks of Invasive Kingella kingae Infections in Closed Communities.

OBJECTIVES: To describe the results of the epidemiologic investigation of outbreaks of invasive Kingella kingae infections among attendees at daycare facilities located in 4 closed communities in Israel. STUDY DESIGN: The preschool-aged population of communities with clusters of Kingella cases had oropharyngeal cultures performed. K kingae isolates from infected patients and healthy contacts were genotyped by pulsed field gel electrophoresis to determine the spread of outbreak strains. RESULTS: The affected closed communities (3 military bases and 1 "kibbutz" commune) were characterized by tight social and family networks and intensive mingling. The outbreaks affected 9 of 51 attendees (attack rate: 17.6%) age 8-19 months (median: 12 months), within a 21-day period. Cases included skeletal system infections (n = 8) and bacteremia (n = 1); K kingae isolates were confirmed by the use of blood culture vials and selective media. Clinical presentation was mild and acute-phase reactants were usually normal or only moderately elevated. Thirty out of 55 (54.5%) asymptomatic children carried the outbreak strains. Analysis of the 3 clusters in which the entire preschool-aged population was cultured revealed that 31 of 71 (43.7%) children younger than 24 months of age were colonized with K kingae organisms compared with 8 of 105 (7.6%) older children (P < .001). CONCLUSIONS: Clusters of invasive K kingae infections characterized by sudden onset, high attack rate, and wide dissemination of the outbreak strain can occur in daycare facilities and closed communities. Because the mild clinical presentation of invasive K kingae infections and the fastidious nature of the organism, a high index of suspicion and use of sensitive detection methods are recommended.

High rate of oropharyngeal Kingella kingae carriage in New Zealand children.

AIM: This study aimed to describe the burden of disease and estimated rates of oropharyngeal carriage of Kingella kingae among New Zealand children. We compared polymerase chain reaction (PCR) and culture for the detection of this microorganism with a view to further development and implementation of K. kingae PCR in Christchurch Hospital. METHODS: Oropharyngeal swabs from children between 6 and 48 months of age were analysed by culture to estimate carriage rates of K. kingae. Samples of a subgroup of children between 12 and 24 months of age were also tested by PCR. In addition, a retrospective review was performed on all cases of invasive K. kingae disease and children with osteoarticular infections. RESULTS: Oropharyngeal cultures were positive for K. kingae in specimens from 4 out of 176 children (2.3%). PCR was significantly more sensitive and by PCR, the carriage rate rose to 22.9% (95% CI = 9.4-33.9%) (n = 48). From 2005 to 2015, 17 children between 6 and 48 months of age were identified with invasive infections due to K. kingae. Seventy-four children were found to have an osteoarticular infection. Most of these were culture-negative with a microbiological diagnosis made in only 15 cases (20.3%), only one due to K. kingae. CONCLUSIONS: We found a very high carriage rate of K. kingae in New Zealand children and poor performance of K. kingae culture. It is likely that many cases of invasive K. kingae infections remain undetected. We recommend the use of a K. kingae PCR in all children under 4 years of age with a possible osteoarticular infection.

Oropharyngeal Kingella kingae carriage in children: characteristics and correlation with osteoarticular infections.

BACKGROUND: The aim of this study was to investigate changes in oropharyngeal K. kingae carriage during the first 4 y of life, including seasonal variation and comparison of asymptomatic carriage with cases of invasive osteoarticular infections (OAI). METHODS: Oropharyngeal bacterial K. kingae carriage was screened in 744 healthy children aged 7-48 mo between January 2009 and December 2012. Oropharyngeal swabs were analyzed by rt-PCR targeting the DNA of K. kingae RTX toxin, epidemiological characteristics of asymptomatic carriers and OAI case patients were recorded. RESULTS: The carriage prevalence showed no significant difference between age groups or seasons. Compared with asymptomatic carriers, OAI cases were more likely to be aged from 7 to 12 mo (OR = 2.5; 95% CI (1.2-5.0)) and 13-24 mo (OR = 2.2; 95% CI (1.2-3.9)), and less likely over 36 mo (OR = 0.2; 95% CI (0.1-0.7)). Fewer OAI cases were identified in spring compared to asymptomatic carriers (OR = 0.3; 95% CI (0.1-0.7)), while more were detected in autumn (OR = 2.5; 95% CI (1.4-4.4)). CONCLUSION: Although oropharyngeal K. kingae colonization is a prerequisite for further invasive infection, this epidemiological study emphasizes that the carriage rate variations do not correlate with the variations of OAI incidence by gender, season, or age group.

Kingella kingae infections in children.

BACKGROUND: Improvements in culture techniques and molecular detection methods have led to findings indicating that, particularly in infants and young children, Kingella kingae is a significantly more important pathogen than previously thought. However, despite this, the pediatric community is still largely unaware of the existence of this organism. The aim of this review is therefore to summarise current knowledge of the epidemiology, transmission, clinical presentation, diagnosis and treatment of K. kingae infections in children. DISCUSSION: K. kingae is a common coloniser of the oropharynx, can be transmitted from child to child, and can cause outbreaks of infection. Invasive infections almost exclusively occur in children aged between six months and four years of age, and involve mainly joints and bone, less frequently the endocardium, and very rarely other localisations. With the exception of bacteremia and endocarditis, which can be followed by severe complications, the diseases due to K. kingae are usually accompanied by mild to moderate clinical signs and symptoms, and only slightly altered laboratory data. Moreover, they generally respond to widely used antibiotics, although resistant strains are reported. However, the mild symptoms and limited increase in the levels of acute phase reactants create problems because K. kingae disease may be confused with other clinical conditions that have a similar clinical picture. CONCLUSIONS: Although K. kingae was identified more than 50 years ago, it is poorly known by pediatricians and is not systematically sought in laboratories. Education is therefore necessary in order to reduce the risk of outbreaks, permit the early identification of K. kingae infections, and allow the prompt prescription of adequate therapeutic regimens capable of avoiding the risk of a negative evolution in those cases in which this elusive pathogen can cause significant clinical problems.

Outbreaks of Kingella kingae infections in daycare facilities.

During the past decade, transmission of the bacterium Kingella kingae has caused clusters of serious infections, including osteomyelitis, septic arthritis, bacteremia, endocarditis, and meningitis, among children in daycare centers in the United States, France, and Israel. These events have been characterized by high attack rates of disease and prevalence of the invasive strain among asymptomatic classmates of the respective index patients, suggesting that the causative organisms benefitted from enhanced colonization fitness, high transmissibility, and high virulence. After prophylactic antibacterial drugs were administered to close contacts of infected children, no further cases of disease were detected in the facilities, although test results showed that some children still carried the bacterium. Increased awareness of this public health problem and use of improved culture methods and sensitive nucleic acid amplification assays for detecting infected children and respiratory carriers are needed to identify and adequately investigate outbreaks of K. kingae disease.

Major intercontinentally distributed sequence types of Kingella kingae and development of a rapid molecular typing tool.

Although Kingella kingae is the most common etiology of osteoarticular infections in young children, is a frequent cause of bacteremia in those younger than 4 years, and has been involved in clusters of invasive infections among daycare center attendees, the population structure of the species has not been systematically studied. Using multilocus sequence typing, we investigated the genetic diversity of the largest intercontinental collection of K. kingae strains to date. To facilitate typing of bacterial isolates, we developed a novel genotyping tool that targets the DNA uptake sequence (DUS). Among 324 strains isolated from asymptomatic carriers and patients from Israel, Europe, North America, and Australia with various invasive forms of the disease from 1960 to 2013, we identified 64 sequence types (STs) and 12 ST complexes (STcs). Five predominant STcs, comprising 72.2% of all strains, were distributed intercontinentally. ST-6 was the most frequent, showing a worldwide distribution, and appeared genotypically isolated by exhibiting few neighboring STs, suggesting an optimal fitness. ST-14 and ST-23 appeared to be the oldest groups of bacteria, while ST-25 probably emerged more recently from the highly evolutive ST-23. Using the DUS typing method, randomly chosen isolates were correctly classified to one of the major STcs. The comprehensive description of K. kingae evolution would help to detect new emerging clones and decipher virulence and fitness mechanisms. The rapid and reproducible DUS typing method may serve in the initial investigation of K. kingae outbreaks.

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.

Beta-lactamase production by Kingella kingae in Israel is clonal and common in carriage organisms but rare among invasive strains.

The purpose of this study was to investigate the prevalence of ß-lactamase and the genomic clonality of a large collection of Kingella kingae isolates from Israeli patients with a variety of invasive infections and asymptomatic pharyngeal carriers. ß-lactamase production was studied by the nitrocefin method and the minimum inhibitory concentrations (MICs) of penicillin and amoxicillin-clavulanate were determined by the epsilon (Etest) method. The genotypic clonality of isolates was investigated by pulsed-field electrophoresis (PFGE). ß-lactamase was found in 2 of 190 (1.1 %) invasive isolates and in 66 of 429 (15.4 %) randomly chosen carriage organisms (p < 0.001). Overall, 73 distinct PFGE clones were identified (33 among invasive organisms and 56 among carriage isolates). ß-lactamase production was found to be limited to four distinct PFGE clones, which were common among carriage strains but rare among invasive strains, and all organisms in the collection belonging to these four clones expressed ß-lactamase. The penicillin MIC of ß-lactamase-producing isolates ranged between 0.094 and 2 mcg/mL (MIC50: 0.25 mcg/mL; MIC90: 1.5 mcg/mL) and that of amoxicillin-clavulanate between 0.064 and 0.47 mcg/mL (MIC50: 0.125 mcg/mL; MIC90: 0.125 mcg/mL). The penicillin MIC of ß-lactamase non-producing isolates ranged between <0.002 and 0.064 mcg/mL (MIC50: 0.023 mcg/mL; MIC90: 0.047 mcg/mL). Although ß-lactamase production is prevalent among K. kingae organisms carried by healthy carriers, the low invasive potential of most colonizing clones results in infrequent detection of the enzyme in isolates from patients with clinical infections. The exceptional presence of ß-lactamase among invasive organisms correlates with the favorable response of K. kingae infections to the administration of ß-lactamase-susceptible antibiotics.

Genotyping of invasive Kingella kingae isolates reveals predominant clones and association with specific clinical syndromes.

BACKGROUND: Despite the increasing recognition of Kingella kingae as an important pathogen of early childhood, the relative frequency and invasiveness of different strains of the organism has not been investigated. A study was conducted to determine the association of K. kingae genotypes with specific clinical syndromes and the temporal and geographic distribution of invasive clones. METHODS: A collection of 181 invasive K. kingae strains, isolated between 1991 and 2012 from Israeli patients with bacteremia, skeletal system infections, or endocarditis, were typed by pulsed-field gel electrophoresis (PFGE). In addition, the correspondence between PFGE, multilocus sequence types (MLSTs), and rtxA gene sequencing results was also examined for organisms belonging to the predominant PFGE clones isolated from asymptomatic carriers and patients with invasive infections. RESULTS: A total of 32 different K. kingae clones were identified by PFGE, of which 5 (B, H, K, N, and P) caused 72.9% of all invasive infections, and were recovered during the 21-year period from different regions of the country. Clone K was significantly associated with bacteremia, clone N with skeletal system infections, and clone P with bacterial endocarditis. Strains belonging to the same PFGE clone, either carried asymptomatically or causing different invasive infections, shared MLST complexes and exhibited identical or closely related rtxA alleles. CONCLUSIONS: Although K. kingae exhibits noteworthy genetic heterogeneity, a limited number of distinct clones cause the majority of invasive infections in Israel, exhibiting genetic stability, long-term persistence, and wide geographic dispersal. K. kingae strains also show significant association with specific clinical syndromes.

Carriage of Neisseria lactamica in 1- to 29-year-old people in Burkina Faso: epidemiology and molecular characterization.

Neisseria lactamica is a true commensal bacterium occupying the same ecological niche as the pathogenic Neisseria meningitidis, which is responsible for outbreaks and large epidemics, especially in sub-Saharan Africa. To better understand the epidemiology of N. lactamica in Africa and its relationship to N. meningitidis, we studied N. lactamica carriage in 1- to 29-year-old people living in three districts of Burkina Faso from 2009 to 2011. N. lactamica was detected in 18.2% of 45,847 oropharyngeal samples. Carriage prevalence was highest among the 2-year-olds (40.1%) and decreased with age. Overall prevalence was higher for males (19.1%) than females (17.5%) (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04 to 1.18), while among the 18- to 29-year-olds, carriage prevalence was significantly higher in women (9.1%) than in men (3.9%) (OR, 2.49; 95% CI, 1.94 to 3.19). Carriage prevalence of N. lactamica was remarkably homogeneous in the three districts of Burkina Faso and stable over time, in comparison with carriage of N. meningitidis (P. A. Kristiansen et al., Clin. Vaccine Immunol. 18:435-443, 2011). There was no significant seasonal variation of N. lactamica carriage and no significant change in carriage prevalence after introduction of the serogroup A meningococcal conjugate vaccine, MenAfriVac. Multilocus sequence typing was performed on a selection of 142 isolates. The genetic diversity was high, as we identified 62 different genotypes, of which 56 were new. The epidemiology of N. lactamica carriage and the molecular characteristics of carried isolates were similar to those reported from industrialized countries, in contrast to the particularities of N. meningitidis carriage and disease epidemiology in Burkina Faso.