Risk Factors For Invasive Disease Research Articles

Shedding of nontyphoidal Salmonella by asymptomatic convalescing children under 5 years as a risk factor for invasive disease in Mukuru informal settlement in Nairobi, Kenya.

Asymptomatic fecal shedding of nontyphoidal Salmonella (NTS) is hypothesized to contribute to the human-to-human transmission of NTS especially in low-resource settings which could lead to invasive disease among high-risk populations, especially children. Our findings reiterate the hypothesis that human reservoirs could be important in the transmission of nontyphoidal Salmonella in sub-Saharan Africa. This underscores the importance of developing infection prevention measures which could include vaccine deployment and improving water, sanitation and hygiene infrastructure.

Limited Adaptation of Staphylococcus aureus during Transition from Colonization to Invasive Infection.

Staphylococcus aureus carriage is a risk factor for invasive infections. Unique genetic elements favoring the transition from colonizing to invasive phenotype have not yet been identified, and phenotypic adaptation traits are understudied. We therefore assessed phenotypic and genotypic profiles of 11 S. aureus isolate pairs sampled from colonized patients simultaneously suffering from invasive S. aureus infections. Ten out of 11 isolate pairs displayed the same spa and multilocus sequence type, suggesting colonization as an origin for the invasive infection. Systematic analysis of colonizing and invasive isolate pairs showed similar adherence, hemolysis, reproductive fitness properties, antibiotic tolerance, and virulence in a Galleria mellonella infection model, as well as minimal genetic differences. Our results provide insights into the similar phenotypes associated with limited adaptation between colonizing and invasive isolates. Disruption of the physical barriers of mucosa or skin was identified in the majority of patients, further emphasizing colonization as a major risk factor for invasive disease. IMPORTANCE S. aureus is a major pathogen of humans, causing a wide range of diseases. The difficulty to develop a vaccine and antibiotic treatment failure warrant the exploration of novel treatment strategies. Asymptomatic colonization of the human nasal passages is a major risk factor for invasive disease, and decolonization procedures have been effective in preventing invasive infections. However, the transition of S. aureus from a benign colonizer of the nasal passages to a major pathogen is not well understood, and both host and bacterial properties have been discussed as being relevant for this behavioral change. We conducted a thorough investigation of patient-derived strain pairs reflecting colonizing and invasive isolates in a given patient. Although we identified limited genetic adaptation in certain strains, as well as slight differences in adherence capacity among colonizing and invasive isolates, our work suggests that barrier breaches are a key event in the disease continuum of S. aureus.

Enhanced Vulnerability of Diabetic Mice to Hypervirulent Streptococcus agalactiae ST-17 Infection.

Streptococcus agalactiae (Group B Streptococcus, GBS) is the leading cause of neonatal sepsis and meningitis but has been recently isolated from non-pregnant adults with underlying medical conditions like diabetes. Despite diabetes being a key risk factor for invasive disease, the pathological consequences during GBS infection remain poorly characterized. Here, we demonstrate the pathogenicity of the GBS90356-ST17 and COH1-ST17 strains in streptozotocin-induced diabetic mice. We show that GBS can spread through the bloodstream and colonize several tissues, presenting a higher bacterial count in diabetic-infected mice when compared to non-diabetic-infected mice. Histological sections of the lungs showed inflammatory cell infiltration, collapsed septa, and red blood cell extravasation in the diabetic-infected group. A significant increase in collagen deposition and elastic fibers were also observed in the lungs. Moreover, the diabetic group presented red blood cells that adhered to the valve wall and disorganized cardiac muscle fibers. An increased expression of KC protein, IL-1β, genes encoding immune cell markers, and ROS (reactive oxygen species) production was observed in diabetic-infected mice, suggesting GBS promotes high levels of inflammation when compared to non-diabetic animals. Our data indicate that efforts to reverse the epidemic of diabetes could considerably reduce the incidence of invasive infection, morbidity and mortality due to GBS.

Understanding the epidemiology of iNTS disease in Africa in preparation for future iNTS- vaccine studies in endemic countries: Seroepidemiology in Africa of iNTS (SAiNTS) Study Protocol [Version 9.0

Background: Non-typhoidal Salmonella (NTS) are a major cause of bloodstream infections amongst children in sub-Saharan Africa. A clear understanding of the seroepidemiology and correlates of protection for invasive NTS (iNTS) in relation to key risk factors (malaria, anaemia, malnutrition) in children in Africa is needed to inform strategies for disease control including vaccine implementation. Methodology: The SAiNTS study is a prospective community cohort study with paired serology samples from 2500 children 0-5 years at baseline and three months to measure age-stratified acquisition of lipopolysaccharide (LPS) O-antigen antibody (IgG) and serum bactericidal activity to the main serovars causing iNTS (Salmonella typhimurium and S. enteritidis). Children are selected from mapped and censused randomly selected households in Chikwawa, Malawi; an area with substantial malaria burden. The sampling framework is set within a malaria vaccination (RTS,S/ AS01) phase 4 cluster randomized trial (EPIMAL), allowing exploration of the impact of malaria vaccination on acquisition of immunity to NTS. Data on risk factors for invasive disease: malaria, anaemia and malnutrition as well as indicators of socioeconomic status and water and sanitation, will be collected using rapid diagnostic tests, anthropometry and electronic CRF’s. Stool sample analysis includes NTS culture and pan-Salmonella polymerase chain reaction to assess enteric exposure and biomarkers of environmental enteric dysfunction. Cases with iNTS disease will be followed up for comparison with community controls. Conclusions: The final cohort of 2500 children will allow investigation into the impact of risk factors for iNTS on the acquisition of immunity in children 0-5 years in an endemic setting, including comparisons to partner sero-epidemiology studies in three other sub-Saharan African sites. The data generated will be key to informing iNTS disease control measures including targeted risk factor interventions and vaccine implementation through investigation of correlates of protection and identifying windows of immune susceptibility in at-risk populations.

Multilocus Sequence Typing Reveals Extensive Genetic Diversity of the Emerging Fungal Pathogen Scedosporium aurantiacum

Scedosporium spp. are the second most prevalent filamentous fungi after Aspergillus spp. recovered from cystic fibrosis (CF) patients in various regions of the world. Although invasive infection is uncommon prior to lung transplantation, fungal colonization may be a risk factor for invasive disease with attendant high mortality post-transplantation. Abundant in the environment, Scedosporium aurantiacum has emerged as an important fungal pathogen in a range of clinical settings. To investigate the population genetic structure of S. aurantiacum, a MultiLocus Sequence Typing (MLST) scheme was developed, screening 24 genetic loci for polymorphisms on a tester strain set. The six most polymorphic loci were selected to form the S. aurantiacum MLST scheme: actin (ACT), calmodulin (CAL), elongation factor-1α (EF1α), RNA polymerase subunit II (RPB2), manganese superoxide dismutase (SOD2), and β-tubulin (TUB). Among 188 global clinical, veterinary, and environmental strains, 5 to 18 variable sites per locus were revealed, resulting in 8 to 23 alleles per locus. MLST analysis observed a markedly high genetic diversity, reflected by 159 unique sequence types. Network analysis revealed a separation between Australian and non-Australian strains. Phylogenetic analysis showed two major clusters, indicating correlation with geographic origin. Linkage disequilibrium analysis revealed evidence of recombination. There was no clustering according to the source of the strains: clinical, veterinary, or environmental. The high diversity, especially amongst the Australian strains, suggests that S. aurantiacum may have originated within the Australian continent and was subsequently dispersed to other regions, as shown by the close phylogenetic relationships between some of the Australian sequence types and those found in other parts of the world. The MLST data are accessible at http://mlst.mycologylab.org. This is a joined publication of the ISHAM/ECMM working groups on “Scedosporium/Pseudallescheria Infections” and “Fungal Respiratory Infections in Cystic Fibrosis”.

Intestinal helminth co-infection is an unrecognised risk factor for increased pneumococcal carriage density and invasive disease

Infection with Streptococcus pneumoniae is the leading cause of death in children and burden of disease is greatest where helminth infections are also common. We investigated the impact of intestinal helminth co-infection on pneumococcal carriage; a risk factor for invasive disease. We used a mouse co-infection model and clinical data to assess the impact of co-infection on carriage density. Co-infection in mice was associated with increased pneumococcal carriage density and dissemination into lungs. Helminth-infected children also exhibited increased carriage density as compared to uninfected children. Anthelmintic treatment may be a cost-effective method of reducing pneumococcal disease burden in lower-income countries.

IBT-V02: A Multicomponent Toxoid Vaccine Protects Against Primary and Secondary Skin Infections Caused by Staphylococcus aureus.

Staphylococcus aureus causes a wide range of diseases from skin infections to life threatening invasive diseases such as bacteremia, endocarditis, pneumonia, surgical site infections, and osteomyelitis. Skin infections such as furuncles, carbuncles, folliculitis, erysipelas, and cellulitis constitute a large majority of infections caused by S. aureus (SA). These infections cause significant morbidity, healthcare costs, and represent a breeding ground for antimicrobial resistance. Furthermore, skin infection with SA is a major risk factor for invasive disease. Here we describe the pre-clinical efficacy of a multicomponent toxoid vaccine (IBT-V02) for prevention of S. aureus acute skin infections and recurrence. IBT-V02 targets six SA toxins including the pore-forming toxins alpha hemolysin (Hla), Panton-Valentine leukocidin (PVL), leukocidin AB (LukAB), and the superantigens toxic shock syndrome toxin-1 and staphylococcal enterotoxins A and B. Immunization of mice and rabbits with IBT-V02 generated antibodies with strong neutralizing activity against toxins included in the vaccine, as well as cross-neutralizing activity against multiple related toxins, and protected against skin infections by several clinically relevant SA strains of USA100, USA300, and USA1000 clones. Efficacy of the vaccine was also shown in non-naïve mice pre-exposed to S. aureus. Furthermore, vaccination with IBT-V02 not only protected mice from a primary infection but also demonstrated lasting efficacy against a secondary infection, while prior challenge with the bacteria alone was unable to protect against recurrence. Serum transfer studies in a primary infection model showed that antibodies are primarily responsible for the protective response.

Neonatal Exposure to Staphylococcus aureus in the Neonatal Intensive Care Unit: Identifying Reservoirs Among Colonized Healthcare Workers and Parents

Background:Staphylococcus aureus (S. aureus) is the second most common cause of healthcare-acquired infections in neonates. S. aureus colonization is a known risk factor for invasive disease. Aside from healthcare workers (HCWs), recent data suggest that parents are important reservoirs of S. aureus in the neonatal intensive care unit (NICU). S. aureus typically colonizes the nares, but it can also colonize other anatomic locations such as the throat. Objective: Our objectives were to identify and compare S. aureus colonization among HCWs and parents and to identify and compare different sites of S. aureus colonization. Methods: Between April 2015 and July 2016, we performed 4 point-prevalence surveys and collected nares and throat swabs from HCWs (nurses, respiratory therapists, nurse practitioners, and physicians) at a quaternary-care NICU. During an overlapping period, we screened parents of neonates in the NICU for S. aureus colonization using nares, throat, groin, and perianal cultures as a part of an ongoing randomized control trial. Cultures from both studies were collected using standardized methods. ESwabs were used to collect samples, which were inoculated into broth for enrichment and subsequently cultured onto chromogenic agar to differentiate between MSSA and MRSA. Results: The prevalence of methicillin susceptible S. aureus (MSSA) colonization was 46% (105/226) in HCWs and 28% (239/842) in parents. The prevalence of methicillin resistant S. aureus (MRSA) colonization was 2.2% (5/226) in HCWs and 2.2% (19/842) in parents. Of those who were colonized with S. aureus, 35% (79/226) of HCWs and 46.5% (160/344) of parents had nares and throat colonization while 11.5% (26/226) of HCWs and 12.2% (42/344) of parents had only throat colonization but not nares colonization. Of those who were MRSA colonized, 1.3% (3/226) of HCWs and 1.8% (15/842) of parents had a positive nares and throat culture as compared to 0.9% (2/226) of HCWs and 0.2% (2/842) of parents had only positive throat cultures. Additionally, 68% (175/257) were colonized with S. aureus at any swabbed site including nares, throat, groin, or perinanal areas. However, only 30% (77/257) of parents had only nares colonization as compared to 58.8% (151/257) had throat and nares colonization, 38.1% (98/257) had nares and groin colonization, and 37.4% (96/257) had nares and perianal colonization. Conclusions: HCWs had greater prevalence of S. aureus colonization compared to parents. As expected, the nares was the most common site of MSSA and MRSA, but a large proportion of S. aureus colonized HCWs and parents had only throat colonization. Given the prevalence of S. aureus in non-nares sites of HCWs and parents in the NICU, further studies should examine the role of non-nares carriers in the transmission of S. aureus in this population.Funding: NoneDisclosures: Aaron Milstone reports consultancy with Becton Dickinson.

The Carrier Status of Streptococcus pneumoniae in a Multi-National Medical Student Population.

Nasopharyngeal carriage of Streptococcus pneumoniae (S. pneumoniae) is a well-established risk factor for invasive disease. An unnecessarily high incidence of morbidity attributed to S. pneumoniae is vaccine-preventable. The objectives of this study were to determine the prevalence of S. pneumoniae carriage and to analyze the different vaccination schemes in a multinational population of final-year medical students. An observational cross-sectional study including final-year medical students attending their Infectious Diseases rotation. One nasal and pharyngeal swab were collected from each participant who underwent a minimum eight-hour period of fasting and without rinsing or brushing teeth. Written informed consent was obtained from all participants. A univariate statistical analysis was carried out with statistical significance set at p <0.05. Fifty students agreed to participate in this study (age range: 23-35, average: 24.86 ± 2.12 years). Six (12%) students had the pneumococcal vaccine: four (16%) from the foreign group and two (8%) from the Romanian group (OR: 2.19, 95% CI: 0.36-13.21, p=0.39). The carrier status for S. pneumoniae was 0%. A total of 12 (24%) specimens yielded microbial presence: S. aureus (n=8), S. pyogenes (n=1), Group C Streptococcus (n=1), Group G Streptococcus (n=1) and K. pneumoniae (n=1). All 13 (26%) specimens of alpha-hemolysis were identified from foreign students (OR: 55.08, 95% CI: 3.02-1003.75, p=0.0068), but had no clinical relevance, S. pneumoniae being ruled out. The carrier status among vaccinated participants was 0%. The rate of microorganism isolation was twice that in Romanian students compared to foreign students.

Longitudinal Population Dynamics of Staphylococcus aureus in the Nasopharynx During the First Year of Life.

Background: Staphylococcus aureus colonization is a risk factor for invasive disease. Few studies have used strain genotype data to study S. aureus acquisition and carriage patterns. We investigated S. aureus nasopharyngeal carriage in infants in an intensively sampled South African birth cohort.Methods: Nasopharyngeal swabs were collected at birth and fortnightly from 137 infants through their first year of life. S. aureus was characterized by spa-typing. The incidence of S. aureus acquisition, and median carriage duration for each genotype was determined. S. aureus carriage patterns were defined by combining the carrier index (proportion of samples testing positive for S. aureus) with genotype diversity measures. Persistent or prolonged carriage were defined by a carrier index ≥0.8 or ≥0.5, respectively. Risk factors for time to acquisition of S. aureus were determined.Results: Eighty eight percent (121/137) of infants acquired S. aureus at least once. The incidence of acquisition at the species and genotype level was 1.83 and 2.8 episodes per child-year, respectively. No children had persistent carriage (defined as carrier index of >0.8). At the species level 6% had prolonged carriage, while only 2% had prolonged carriage with the same genotype. Carrier index correlated with the absolute number of spa-CCs carried by each infant (r = 0.5; 95% CI 0.35–0.62). Time to first acquisition of S. aureus was shorter in children from households with ≥5 individuals (HR 1.06, 95% CI 1.07–1.43), with S. aureus carrier mothers (HR; 1.5, 95% CI 1.2–2.47), or with a positive tuberculin skin test during the first year of life (HR; 1.81, 95% CI 0.97–3.3).Conclusion: Using measures of genotype diversity, we showed that S. aureus NP carriage is highly dynamic in infants. Prolonged carriage with a single strain occurred rarely; persistent carriage was not observed. A correlation was observed between carrier index and genotype diversity.

Epidemiology of non‐typhoid Salmonella infection in the Australian Capital Territory over a 10‐year period

To describe the epidemiology of non-typhoid Salmonella (NTS) infection in the Australian Capital Territory (ACT), including factors associated with hospitalisation. This was a retrospective descriptive and observational study of culture-confirmed NTS infections using data collected from ACT public health, public pathology and hospital services in the period 2003-2012. Outcome measures include incidence and NTS serotype for total reported and hospitalised cases and focus of infection, complications and antibiotic susceptibility for hospitalised cases. In total, 1469 cases of NTS infection were reported, with the crude annual incidence increasing from 24.4 to 61.3 cases per 100 000 population; 14% were hospitalised, representing an incidence of 5.9 hospitalisations per 100 000 population, without significant change over time. Hospitalisation incidence peaked at the extremes of age. Comorbid disease and age ≥ 80 years were associated with complications during hospitalisation. Salmonella serotype Typhimurium was the most common serotype, accounting for 64% of NTS. Independent risk factors for invasive disease included non-S. Typhimurium serotype (aRR 5.46, 95%CI 1.69-17.65 P = 0.005), ischaemic heart disease (aRR 4.18, 95%CI 1.20-14.60 P = 0.025) and haematological malignancy (aRR 6.93, 95%CI 2.54-18.94 P < 0.001). Among hospitalised patients, resistance to ampicillin, ceftriaxone, trimethoprim-sulfamethoxazole and quinolones was 9.9%, 0%, 4.4% and 2.5% respectively. NTS notifications in the ACT have increased over time, with outbreaks of food-borne disease contributing to this increase. Crude age-specific incidence is highest in the very young, while rates of hospitalisation are highest in the elderly. Comorbid disease and infection with a non-S. Typhimurium serotype were associated with complicated NTS disease course. Antimicrobial resistance in NTS is low and has not increased over time.

Non‐typhoidal Salmonella infections in children: Review of literature and recommendations for management

Non-typhoidal Salmonellae are a major cause of infectious diarrhoea worldwide and can cause invasive diseases, including bacteraemia, meningitis and osteomyelitis. Young or immunocompromised children and those with underlying conditions such as sickle cell disease are particularly vulnerable to invasive disease. There has been an increase in the rate of resistant non-typhoidal Salmonella, which is associated with invasive disease and hospitalisation. The intracellular nature of non-typhoidal Salmonella protects against extracellular antibiotics and can facilitate disease relapse, particularly meningitis. Effective antimicrobial agents with good intracellular penetration include azithromycin, fluoroquinolones and third-generation cephalosporins. Antibiotic treatment of non-typhoidal Salmonella gastroenteritis is only indicated if there are risk factors for invasive disease as it can prolong excretion and does not shorten the duration of gastrointestinal symptoms. Optimal choice and length of therapy for gastroenteritis and invasive disease in children is not clear. Here, we provide a review of the literature and treatment recommendations.

Delayed Treatment of a Dog Bite Resulting in Devastating Capnocytophaga Sepsis in an Alcoholic Patient With Functional Asplenia

Capnocytophaga canimorsus is a slow-growing gram-negative rod found in the normal oral flora of 20% to 25% of dogs. It is usually transmitted to humans by dog bite or exposure, causing symptoms ranging from local wound irritation to sepsis, meningitis, and death. Asplenia, alcohol abuse, and steroid use are risk factors for invasive disease, but this infection also occurs in the normal host.

Transmission of Staphylococcus aureus between mothers and infants in an African setting

Staphylococcus aureus colonization is a risk factor for invasive disease. There is a need to understand S. aureus colonization in infancy as the burden of S. aureus infections in infants is high. We aimed to investigate the transmission of S. aureus between mothers and their newborns during the first year after delivery in an African setting. In a longitudinal cohort study, colonization of Gabonese mother–infant pairs was assessed at delivery and after 1, 9 and 12 months. Swabs were taken from mothers (nares, mammillae) and infants (nares and throat). Isolates were characterized and risk factors for colonization were assessed using a standardized questionnaire. We recruited 311 mothers and 318 infants including seven sets of twins. Maternal and infant colonization rates declined synchronously following a peak after 1 month at 40% (mothers) and 42% (infants). Maternal colonization was a risk factor for S. aureus carriage in infants. Based on spa typing, direct mother-to-infant transmission was evident in 5.6%. Of all methicillin-resistant isolates (<n = 9), 44.4% were related to the USA300 clone; 56.7% (<n = 261) of all S. aureus carried Panton–Valentine leukocidin encoding genes. Direct mother-to-infant transmission was rare and cannot explain the increase of carriage in infants within the first month. A transmission from external sources is likely and challenges the S. aureus infection control in newborns and infants in an African setting. The detection of USA300-related MRSA fuels the concern about the spread of this clone in Central Africa.

Carbohydrate Availability Regulates Virulence Gene Expression in Streptococcus suis

Streptococcus suis is a major bacterial pathogen of young pigs causing worldwide economic problems for the pig industry. S. suis is also an emerging pathogen of humans. Colonization of porcine oropharynx by S. suis is considered to be a high risk factor for invasive disease. In the oropharyngeal cavity, where glucose is rapidly absorbed but dietary α-glucans persist, there is a profound effect of carbohydrate availability on the expression of virulence genes. Nineteen predicted or confirmed S. suis virulence genes that promote adhesion to and invasion of epithelial cells were expressed at higher levels when S. suis was supplied with the α-glucan starch/pullulan compared to glucose as the single carbon source. Additionally the production of suilysin, a toxin that damages epithelial cells, was increased more than ten-fold when glucose levels were low and S. suis was growing on pullulan. Based on biochemical, bioinformatics and in vitro and in vivo gene expression studies, we developed a biological model that postulates the effect of carbon catabolite repression on expression of virulence genes in the mucosa, organs and blood. This research increases our understanding of S. suis virulence mechanisms and has important implications for the design of future control strategies including the development of anti-infective strategies by modulating animal feed composition.

Effect of 2 referral intervals on diagnostic discordance between cytology and histology at a colposcopy clinic

ObjectiveTo determine the effect of the time interval between cervical cytology screening and histology at treatment on grade of cervical disease. MethodsIn a retrospective cross-sectional study at a colposcopy clinic in Soweto, Johannesburg, South Africa, data were compared from women with cytologic abnormalities referred for colposcopy between April 2003 and June 2010 to determine whether early (≤180days) or late (>180days) referral had an impact on dysplasia grade. ResultsIn the early and late referral groups, there were 213 (13.43%) and 201 (14.63%) women, respectively, with upgrading of cervical dysplasia (P=0.35), and 1373 (86.57%) and 1173 (85.37%) women, respectively, with downgrading or no change (P=0.35). Risk factors for upgrading were HIV infection (odds ratio [OR], 1.63; P<0.001) and condom use (OR, 1.30; P=0.02). Four cases (0.68%) of invasion among women with low-grade squamous intraepithelial lesion (LSIL) and 50 cases (2.11%) among women with high-grade SIL (HSIL) were not detected by cytology. Risk factors for invasive disease on histology were age (OR, 1.09 per year; P<0.001), parity (OR, 1.32 per pregnancy; P<0.001), and HSIL on cytology (OR, 3.17; P=0.03). ConclusionThere was no difference in the up- or downgrading of cervical dysplasia between the 2 referral groups.

Implementation of a pharmacy-driven program to improve nasal mupirocin use

Staphylococcus aureus is a leading cause of serious hospital-acquired infections and is associated with significant morbidity and mortality. Colonization with S. aureus within the anterior nares is a risk factor for invasive disease.1 Previous work at our institution revealed that active surveillance for S. aureus and de-colonization with nasal mupirocin and a chlorhexidine bath were associated with a decreased incidence of S. aureus colonization and hospital-acquired infections.2 However, the study results indicated that the overall adherence to the use of mupirocin was suboptimal, with only 46% of patients with S. aureus colonization receiving nasal mupirocin. Despite several attempts to educate our health care providers about the importance of decolonization with nasal mupirocin, adherence remained low. We sought to improve treatment adherence by implementing a pharmacy-driven nasal mupirocin ordering program as part of our hospital’s S. aureus screening and eradication protocol. Cleveland Clinic is a tertiary care, academic medical center with over 1300 beds, including 225 intensive care unit (ICU) beds. The inpatient pharmacy department includes over 82 full-time pharmacists and 125 full-time technicians and provides services 24 hours a day. A main central pharmacy provides services for the majority of hospitalized patients and supports four satellite pharmacies.

Cas groupés intrafamiliaux d’infection invasive communautaire à Streptococcus pyogenes (ou streptocoque du groupe A)

Streptococcus pyogenes or group A streptococcus (GAS) is responsible for serious invasive infections with a risk of secondary infection in patients with more contact than in the general population. Regardless of clustering, few intrafamilial invasive infections have been reported despite a recent increase in the incidence of invasive GAS disease. We report the cases of two brothers, one a boy of 8.5 years with toxic shock syndrome with no bacteria identified and the second, 1 week later, his 14.5-year-old brother in hospital for sepsis due to GAS. The occurrence of a confirmed case of invasive GAS and a probable case within such a short period met the definition of clustered cases. Both brothers showed no risk factors for invasive disease and no gateway including skin was found. Antibiotic therapy was initiated in the family as recommended by the French Higher Council of Public Hygiene.

Candida infection and colonization among non-trauma emergency surgery patients

Background: Candida is a significant pathogen among critically ill patients. However, candidiasis among non-trauma emergency surgery (NTES) patients has not been previously investigated. Herein we describe the incidence of both colonization and infection from Candida and risk factors for invasive disease in this population. Methods: For this retrospective single center study we included all NTES patients with ICU stay ≥4 days from May 1st, 2002 to April 30th, 2007. Patients were divided into 3 non-overlapping groups: 1) patients with Candida-infection, 2) patients with Candida colonization and 3) patients with negative Candida cultures. Groups were compared by univariate and multivariate analyses to identify significant risk factors for invasive candidiasis. Results: Of all 289 eligible patients, 63 (21.7%) fulfilled the criteria for Candida infection and 110 (38%) were included in the Candida colonization group. Interestingly, from the 63 patients with invasive candidiasis, 25 (39.7%) were infected by a non-albicans species. Upon multivariate analyses, ventilator-associated pneumonia (VAP) (Odds Ratio [OR]: 2.34; 95%, Confidence Interval [CI]: 1.213 - 4.533, p= 0.0112), bacteremia (OR: 4.778; 95%CI: 1.519 - 15.029, p= 0.0075) and surgical complications (OR: 3.903; 95%CI: 1.335 - 11.412, p= 0.0129) were independent risk factors for the development of Candida infection. Candida infection and colonization were both found to correlate with approximately $40,000 - 100,000 mean additional costs). Interestingly, candidemia was associated with 63% all-cause mortality. For all other forms of candidiasis, mortality was not significantly different among groups. Conclusion: We found thatCandidainfection is alarmingly high among NTES patients with prolonged intensive care unit (ICU) stay. Surgical complications and bacterial infections (VAP and bacteraemia) were significantly correlated with the development of candidiasis. Candidiasis reached a rate of 21.7/100 discharges, which is significantly higher than most established high-risk populations for candidiasis. Future studies should review the need for antifungal prophylaxis on this population.

Outbreak of Osteomyelitis/Septic Arthritis Caused byKingella kingaeAmong Child Care Center Attendees

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. 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. 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. 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.