Management of an outbreak of invasive Kingella kingae skeletal infections in a day care center.

BACKGROUND: Kingella kingae (Kk) is frequently responsible for invasive skeletal infections in children aged 3-36months. However, few outbreaks of invasive Kk infections in day care centers have been reported. The objective of the present study was to describe (a) the clinical and laboratory data recorded during an outbreak of invasive Kk skeletal infections, and (b) the management of the outbreak. METHOD: Four children from the same day care center were included in the study May and June 2019. We retrospectively analyzed the children's clinical presentation and their radiological and laboratory data. We also identified all the disease control measures taken in the day care center. RESULTS: We observed cases of septic arthritis of the wrist (case #1), shoulder arthritis (case #2), knee arthritis (case #3) ans cervical spondylodiscitis (case #4). All cases presented with an oropharyngeal infection and concomitant fever prior to diagnosis of the skeletal infection. All cases were misdiagnosed at the initial presentation. The mean (range) age at diagnosis was 10.75months (9-12). The three patients with arthritis received surgical treatment. All patients received intravenous and then oral antibiotics. In cases 1 and 2, Kk was detected using real-time PCR and a ST25-rtxA1 clone was identified. The outcome was good in all four cases. Four other children in the day care center presented with scabies during this period and were treated with systemic ivermectin. The Regional Health Agency was informed, and all the parents of children attending the day care center received an information letter. The day care center was cleaned extensively. CONCLUSION: Our results highlight the variety of features of invasive skeletal Kk infections in children and (given the high risk of transmission in day care centers) the importance of diagnosing cases as soon as possible.

In vitro characterization of biofilms formed by Kingella kingae.

The Gram-negative bacterium Kingella kingae is part of the normal oropharyngeal mucosal flora of children <4 years old. K. kingae can enter the submucosa and cause infections of the skeletal system in children, including septic arthritis and osteomyelitis. The organism is also associated with infective endocarditis in children and adults. Although biofilm formation has been coupled with pharyngeal colonization, osteoarticular infections, and infective endocarditis, no studies have investigated biofilm formation in K. kingae. In this study we measured biofilm formation by 79 K. kingae clinical isolates using a 96-well microtiter plate crystal violet binding assay. We found that 37 of 79 strains (47%) formed biofilms. All strains that formed biofilms produced corroding colonies on agar. Biofilm formation was inhibited by proteinase K and DNase I. DNase I also caused the detachment of pre-formed K. kingae biofilm colonies. A mutant strain carrying a deletion of the pilus gene cluster pilA1pilA2fimB did not produce corroding colonies on agar, autoaggregate in broth, or form biofilms. Biofilm forming strains have higher levels of pilA1 expression. The extracellular components of biofilms contained 490 µg cm-2 of protein, 0.68 µg cm-2 of DNA, and 0.4 µg cm-2 of total carbohydrates. We concluded that biofilm formation is common among K. kingae clinical isolates, and that biofilm formation is dependent on the production of proteinaceous pili and extracellular DNA. Biofilm development may have relevance to the colonization, transmission, and pathogenesis of this bacterium. Extracellular DNA production by K. kingae may facilitate horizontal gene transfer within the oral microbial community.

Identifying Reservoirs of Infections Caused by Kingella kingae: A Case-Control Study of Oropharyngeal Carriage of K. kingae Among Healthy Adults.

BACKGROUND: Kingella kingae is currently recognized as a significant pathogen of the pediatric population. Nevertheless, the possibility for adults to serve as a reservoir of healthy carriers has not been studied. METHOD: We conducted a monocentric transversal study on 228 healthy adults to define the carriage rate. Participants were recruited among the staff of a children's hospital, a population exposed to aerosolized droplets from children. A secondary analysis using a case-control method was conducted to assess risk factors for carriage. RESULTS: We demonstrated an oropharyngeal carriage rate of 2.2% in this population. However, there was a striking similarity in the carriage rate among children younger than 4 years of age and adults living with children of that age group (8.8%). Use of day-care facilities for their own children was also demonstrated as a risk factor for adult carriage. CONCLUSIONS: We were able to demonstrate the existence of adult carriage of K. kingae but our results point to transmission from children to adults. Our results do not allow us to conclude that professional exposure in a hospital setting is a risk factor for oropharyngeal carriage.

Patterns of Kingella kingae Disease Outbreaks.

BACKGROUND: Kingella kingae outbreaks occur sporadically in childcare centers but remain poorly understood and difficult to identify. METHODS: To provide the basis of a better knowledge of K. kingae outbreaks patterns that may help to guide identification and management strategies, we collected epidemiological, clinical and laboratory data from all reported K. kingae outbreaks, and those from 2 new Israel outbreaks in 2014. RESULTS: Nine outbreaks were identified in the USA, Israel and France from 2003 to 2014. Twenty-seven children with a median age of 14 ± 4.1 months were affected, male:female ratio of 1.4:1. Outbreaks demonstrated seasonal patterns from the 10th to the 45th weeks, a mean duration of 13.1 ± 8.4 days, a mean attack rate of 17.3 ± 5.1% and a case-fatality rate of 3.7% (1/27). Seventy-four percentage of children had fever (20/27), and the mean values of white blood cell count and C-reactive protein level were 14.6 ± 4.5 × 10/L and 23.8 ± 24.1 mg/L, respectively. Osteoarticular infections accounted for 88.9% of cases (24/27), bacteremia 7.4% (2/27), endocarditis 3.7% (1/27) and meningitis 3.7% (1/27). Specific real-time polymerase chain reaction demonstrated higher performance than culture methods in the diagnosis of case patients and investigations of oropharyngeal K. kingae carriage among close contacts, and multilocus sequence typing methods revealed that ST-6 and ST-25 invasive strains were responsible for multiple country-dependent outbreaks. Coviral infections were identified in the majority of K. kingae outbreaks, notably those causing oral ulcers. CONCLUSIONS: K. kingae outbreaks displayed severe K. kingae diseases that were poorly confirmed with culture methods. We argue for the use of genomic technologies to investigate further K. kingae outbreaks.

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.

Iatrogenic meningitis caused by Neisseria sicca/subflava after intrathecal contrast injection, Australia.

We report a case of invasive Neisseria sicca/subflava meningitis after a spinal injection procedure during which a face mask was not worn by the proceduralist. The report highlights the importance of awareness of, and adherence to, guidelines for protective face mask use during procedures that require sterile conditions.

Genotyping, local prevalence and international dissemination of ß-lactamase-producing Kingella kingae strains.

ß-lactamase production has been sporadically reported in the emerging Kingella kingae pathogen but the phenomenon has not been studied in-depth. We investigated the prevalence of ß-lactamase production among K. kingae isolates from different geographical origins and genetically characterized ß-lactamase-producing strains. Seven hundred and seventy-eight isolates from Iceland, the USA, France, Israel, Spain and Canada were screened for ß-lactamase production and, if positive, were characterized by PFGE and MLST genotyping, as well as rtxA, por, blaTEM and 16S rRNA sequencing. ß-lactamase was identified in invasive strains from Iceland (n=4/14, 28.6%), the USA (n=3/15, 20.0%) and Israel (n=2/190, 1.1%) and in carriage strains in the USA (n=5/17, 29.4%) and Israel (n=66/429, 15.4%). No French, Spanish or Canadian isolates were ß-lactamase producers. Among ß-lactamase producers, a perfect congruency between the different typing methods was observed. Surprisingly, all US and Icelandic ß-lactamase-producing isolates were almost indistinguishable, belonged to the major international invasive PFGE clone K/MLST ST-6, but differed from the four genetically unrelated Israeli ß-lactamase-producing clones. Representative strains of different genotypes produced the TEM-1 enzyme. K. kingae ß-lactamase producers exhibit a clear clonal distribution and have dissimilar invasive potential. The presence of the enzyme in isolates belonging to the major worldwide invasive clone K/ST-6 highlights the possible spread of ß-lactam resistance, and emphasizes the importance of routine testing of all K. kingae clinical isolates for ß-lactamase production.

A prospective study of intrafamilial oropharyngeal transmission of Kingella kingae.

To evaluate the intrafamilial oropharyngeal transmission of Kingella kingae, we conducted a prospective study among pairs of siblings. We found that 55% of children who suffered from osteoarticular infections due to K. kingae, and 40% of asymptomatic carriers of K. kingae had siblings with positive oropharyngeal carriage.

A randomized controlled trial for reducing risks for sexually transmitted infections through enhanced patient-based partner notification.

OBJECTIVES: We sought to assess the effectiveness of approaches targeting improved sexually transmitted infection (STI) sexual partner notification through patient referral. METHODS: From January 2002 through December 2004, 600 patients with Neisseria gonorrhoeae or Chlamydia trachomatis were recruited from STI clinics and randomly assigned to either a standard-of-care group or a group that was counseled at the time of diagnosis and given additional follow-up contact. Participants completed an interview at baseline, 1 month, and 6 months and were checked at 6 months for gonorrhea or chlamydial infection via nucleic acid amplification testing of urine. RESULTS: Program participants were more likely to report sexual partner notification at 1 month (86% control, 92% intervention; adjusted odds ratio [AOR] = 1.8; 95% confidence interval [CI] = 1.02, 3.0) and were more likely to report no unprotected sexual intercourse at 6 months (38% control, 48% intervention; AOR = 1.5; 95% CI = 1.1, 2.1). Gonorrhea or chlamydial infection was detected in 6% of intervention and 11% of control participants at follow-up (AOR = 2.2; 95% CI = 1.1, 4.1), with greatest benefits seen among men (for gender interaction, P = .03). CONCLUSIONS: This patient-based sexual partner notification program can help reduce risks for subsequent STIs among urban, minority patients presenting for care at STI clinics.

Outbreak of osteomyelitis/septic arthritis caused by Kingella kingae among child care center attendees.

OBJECTIVE: Kingella kingae often colonizes the oropharyngeal and respiratory tracts of children but infrequently causes invasive disease. In mid-October 2003, 2 confirmed and 1 probable case of K kingae osteomyelitis/septic arthritis occurred among children in the same 16- to 24-month-old toddler classroom of a child care center. The objective of this study was to investigate the epidemiology of K kingae colonization and invasive disease among child care attendees. METHODS: Staff at the center were interviewed, and a site visit was performed. Oropharyngeal cultures were obtained from the staff and children aged 0 to 5 years to assess the prevalence of Kingella colonization. Bacterial isolates were subtyped by pulsed-field gel electrophoresis (PFGE), and DNA sequencing of the 16S rRNA gene was performed. A telephone survey inquiring about potential risk factors and the general health of each child was also conducted. All children and staff in the affected toddler classroom were given rifampin prophylaxis and recultured 10 to 14 days later. For epidemiologic and microbiologic comparison, oropharyngeal cultures were obtained from a cohort of children at a control child care center with similar demographics and were analyzed using the same laboratory methods. The main outcome measures were prevalence and risk factors for colonization and invasive disease and comparison of bacterial isolates by molecular subtyping and DNA sequencing. RESULTS: The 2 confirmed case patients required hospitalization, surgical debridement, and intravenous antibiotic therapy. The probable case patient was initially misdiagnosed; MRI 16 days later revealed evidence of ankle osteomyelitis. The site visit revealed no obvious outbreak source. Of 122 children in the center, 115 (94%) were cultured. Fifteen (13%) were colonized with K kingae, with the highest prevalence in the affected toddler classroom (9 [45%] of 20 children; all case patients tested negative but had received antibiotics). Six colonized children were distributed among the older classrooms; 2 were siblings of colonized toddlers. No staff (n = 28) or children aged <16 months were colonized. Isolates from the 2 confirmed case patients and from the colonized children had an indistinguishable PFGE pattern. No risk factors for invasive disease or colonization were identified from the telephone survey. Of the 9 colonized toddlers who took rifampin, 3 (33%) remained positive on reculture; an additional toddler, initially negative, was positive on reculture. The children of the control child care center demonstrated a similar degree and distribution of K kingae colonization; of 118 potential subjects, 45 (38%) underwent oropharyngeal culture, and 7 (16%) were colonized with K kingae. The highest prevalence again occurred in the toddler classrooms. All 7 isolates from the control facility had an indistinguishable PFGE pattern; this pattern differed from the PFGE pattern observed from the outbreak center isolates. 16S rRNA gene sequencing demonstrated that the outbreak K kingae strain exhibited >98% homology to the ATCC-type strain, although several sequence deviations were present. Sequencing of the control center strain demonstrated more homology to the outbreak center strain than to the ATCC-type strain. CONCLUSIONS: This is the first reported outbreak of invasive K kingae disease. The high prevalence in the affected toddler class and the matching PFGE pattern are consistent with child-to-child transmission within the child care center. Rifampin was modestly effective in eliminating carriage. DNA sequence analysis suggests that there may be considerable variability within the species K kingae and that different K kingae strains may demonstrate varying degrees of pathogenicity.

Association of Laribacter hongkongensis in community-acquired gastroenteritis with travel and eating fish: a multicentre case-control study.

BACKGROUND: Laribacter hongkongensis has been recovered from several patients with gastroenteritis. However, the causative role of this organism in human gastroenteritis is still unproven, and sources of the bacterium are unknown. We undertook a multicentre case-control study to investigate the association of L hongkongensis with gastroenteritis. METHODS: Faecal samples from patients with community-acquired gastroenteritis and controls were cultured for L hongkongensis. Targeted food surveillance was done to identify potential sources of this bacterium. All isolates of this organism from patients and food items were characterised by pulsed-field gel electrophoresis and ribotyping. FINDINGS: During a 4-month period, L hongkongensis was recovered from 17 of 3788 patients with community-acquired gastroenteritis, but was absent in 1894 controls (p=0.001). Those who were culture-positive for this bacterium had a recent history of travel (ten [59%] patients vs two [6%] of 34 matched controls, p<0.0001), of fish consumption (16 [94%] vs 19 [56%], p=0.009), and of eating minced freshwater fish meat (five [29%] vs one [3%], p=0.012). We recovered 25 L hongkongensis isolates from intestinal samples of freshwater fish and two from minced freshwater fish meat. Bacteria with the same pulsed-field gel electrophoretic pattern and ribotype were recovered from one patient and a sample of minced freshwater fish meat, which was from the same retail market recently visited by the patient. We did not see this particular combination of electrophoretic pattern and ribotype in any other isolates. INTERPRETATION: L hongkongensis is associated with community-acquired gastroenteritis and traveller's diarrhoea. However, its causative role has not been shown. Freshwater fish is one source of this bacterium.

Person-to-person transmission of Kingella kingae among day care center attendees.

Fifty Kingella kingae organisms, isolated from tonsillar cultures of day care center attendees during an 11-month period, and 60 isolates derived from epidemiologically unrelated individuals, including 19 isolates from respiratory carriers and 41 isolates from patients with invasive infections, were typed by immunoblotting, pulsed-field gel electrophoresis, and ribotyping. One strain, defined by unique immunoblotting, pulsed-field gel electrophoresis, and ribotyping patterns, represented 14 day care isolates (28%) and was frequently isolated during the first half of the follow-up period; a second strain represented 23 (46%) isolates and prevailed during the last 5 months. Children frequently carried the same strain continuously or intermittently for weeks or months, when it was replaced by a new strain. Epidemiologically unrelated organisms showed greater variability, and no strain represented >5% of isolates. The present results support person-to-person transmission of K. kingae among young children in the day care setting.

[Dog bite infections associated with CDC group EF-4a. Report of 2 cases]. / Infecciones por mordedura de perro asociadas a CDC grupo EF-4a. Comunicación de 2 casos.

BACKGROUND: Group EF-4 bacteria make up part of the normal flora of the oral cavity of dogs and cats. Few reports have been published on the incidence of human infections by this group of bacteria and these are associated with animal bite or scratch. Two cases of infections by CDC group EF-4 by dog bite were diagnosed in 1996 by the Bacteriology Laboratory of the authors' hospital. These cases are herein described and the biochemical analysis and profile of sensitivity of this little known group of bacteria evaluated. METHODS: Two clinical cases of infection by CDC group EF-4a by dog bite are described. Identification of the bacteria was performed by conventional biochemical tests and quantitative antibiotic sensitivity to 12 antibiotics was carried out by the seried broth macrodilution method. RESULTS: The two strains isolated corresponded to biovar "a" of group EF-4 being sensitive to: ampicillin, ceftriaxone, aminoglycosides, chloramphenicol, rifamipicin, TMS and ciprofloxacin, intermediate sensitivity to erythromycin and were resistant to cefalotine, oxacillin and vancomycin. With respect to penicillin, one of the strains was sensitive and the other presented intermediate sensitivity. Neither of the strains produced beta lactamase. CONCLUSIONS: Although Pasteurella sp. is usually considered in dog bite wounds, the possible presence of group EF-4 should be taken into account since the sensitivity of both microorganisms against penicillin and cefalotin, which are effective against Pasteurella but less active against group EF-4 bacteria differ.

Respiratory carriage of Kingella kingae among healthy children.

The role of Kingella kingae as an invasive pathogen of young children is being increasingly recognized, but the niche of the organism in the respiratory tract and its prevalence in the normal flora of children remain unknown. To investigate these two aspects throat and nasopharyngeal cultures were obtained every 2 weeks from two cohorts of children, ages 6 to 42 months on enrollment, attending a day-care center in southern Israel. To determine the age-related prevalence of K. kingae, throat cultures were obtained from children ages 6 months to 14 years hospitalized for elective surgery who had not received antibiotics during the previous 30 days and from healthy infants younger than 6 months attending a well-baby-care clinic for routine vaccinations. During an 11-month follow-up 109 of 624 (27.5%) throat cultures but none of the nasopharyngeal cultures obtained from 48 day-care center attendees grew K. kingae. The monthly prevalence of K. kingae ranged from 6.1 to 34.6% with December and April peaks. Overall 35 of 48 (72.9%) children had at least one positive culture for the organism. Among the 27 children who had > or = 2 positive cultures, continuous and intermittent patterns of carriage were observed. None of the colonized children experienced an invasive K. kingae infection. The prevalence of pharyngeal carriage among surgical patients was 8.0%, and the organism was not isolated from any of the infants younger than 6 months attending the well-baby-care clinic.

Branhamella catarrhalis in children and adults. A study of prevalence, time of colonisation, and association with upper and lower respiratory tract infections.

The colonisation rate of Branhamella catarrhalis in patients from 0 to 45 years of age was examined. Of 561 women admitted to hospital in labour, 6 (1%) carried B. catarrhalis in their throats but none carried the organism in their vaginas. None of 534 newborn babies became colonised at birth or during their 5 days' stay in hospital. Neither were 102 neonates < 1 month of age in hospital colonised. The maximum colonisation rate during childhood was observed in children 1-48 months of age with 143 of 266 (54%) children colonised. Among children 4-15 years of age, four of 57 (7%) children with healthy respiratory tracts were colonised. Significantly more children with upper or lower respiratory tract infections (RTI) were colonised (68%) than were children without such infections (36%), (P < 0.001). After recovery from RTI, the isolation rate in the RTI group fell to that of the non-RTI group. A seasonal variation in prevalence was not observed. Of all the strains of B. catarrhalis isolated, 84% produced beta-lactamase.

A prospective study of isolation of Moraxella catarrhalis in a hospital during the winter months.

Sputum samples submitted to the microbiology laboratory from general medical and respiratory wards were monitored for Moraxella catarrhalis on a prospective basis. All isolates were typed by restriction endonuclease typing. Nosocomial spread was found both by the clustering of cases and typing of isolates. Sampling of the environment of some cases was performed. Seven out of 37 samples revealed environmental contamination. Sampling for persistence of the organism in the environment was positive on one occasion out of 13. Evaluation of acquisition of M. catarrhalis in relation to length of stay showed that the average length of stay of a case with M. catarrhalis was considerably longer than average patient stay without M. catarrhalis. Four patients had two isolates available for typing. The type of M. catarrhalis was different on the second occasion to that on the first. Nosocomial spread of M. catarrhalis in the setting of general medical and respiratory wards was found to occur in the winter months.