Search

Background Various bacterial and viral assemblages composing Cystic Fibrosis (CF) lung microbiota contribute to long-term lung function decline over time. Yet, the impact of individual microorganisms on pulmonary functions remains uncertain in children with CF. Methods As part of the 'Mucoviscidosis, respiratory VIruses, intracellular Bacteria and fastidious organisms'' project, children with CF were longitudinally followed in a Swiss multicentric study. Respiratory samples included mainly throat swabs and sputa samples for bacterial culture and 16S rRNA metagenomics and nasopharyngeal swabs for respiratory virus detection by molecular assays. Percentage of predicted Forced Expiratory Volume in one second (FEV1%) and Lung Clearance Index (LCI) were recorded. Results Sixty-one children, of whom 20 (32.8%) presented with at least one pulmonary exacerbation, were included. Almost half of the 363 nasopharyngeal swabs tested by RT-PCR were positive for a respiratory virus, mainly rhinovirus (26.5%). From linear mixed-effects regression models, P. aeruginosa (-11.35, 95%CI [-17.90; -4.80], p = 0.001) was significantly associated with a decreased FEV1%, whereas rhinovirus was associated with a significantly higher FEV1% (+4.24 95%CI [1.67; 6.81], p = 0.001). Compared to conventional culture, 16S rRNA metagenomics showed a sensitivity and specificity of 80.0% and 85.4%, respectively for detection of typical CF pathogens. However, metagenomics detected a bacteria almost twice more often than culture. Conclusions As expected, P. aeruginosa impacted negatively on FEV1% while rhinovirus was surprisingly associated with better FEV1%. Culture-free assays identifies significantly more pathogens than standard culture, with disputable clinical correlation.

BACKGROUND: Saliva reverse transcriptase-Polymerase chain reaction (RT-PCR) is an attractive alternative for the detection of severe acute respiratory syndrome coronavirus 2 in adults with less known in children. METHODS: Children with coronavirus disease 2019 symptoms were prospectively enrolled in a 1-month comparative clinical trial of saliva and nasopharyngeal (NP) RT-PCR. Detection rates and sensitivities of saliva and NP RT-PCR were compared as well as discordant NP and saliva RT-PCR findings including viral loads (VLs). RESULTS: Of 405 patients enrolled, 397 patients had 2 tests performed. Mean age was 12.7 years (range, 1.2-17.9). Sensitivity of saliva was 85.2% (95% confidence interval: 78.2%-92.1%) when using NP as the standard; sensitivity of NP was 94.5% (89.8%-99.2%) when saliva was considered as the standard. For a NP RT-PCR VL threshold of ≥103 and ≥104 copies/mL, sensitivity of saliva increases to 88.7% and 95.2%, respectively. Sensitivity of saliva and NP swabs was, respectively, 89.5% and 95.3% in patient with symptoms less than 4 days (P = 0.249) and 70.0% and 95.0% in those with symptoms ≥4-7 days (P = 0.096). The 15 patients who had an isolated positive NP RT-PCR were younger (P = 0.034), had lower NP VL (median 5.6 × 103 vs. 3.9 × 107, P < 0.001), and could not drool saliva at the end of the sampling (P = 0.002). VLs were lower with saliva than with NP RT-PCR (median 8.7 cp/mL × 104; interquartile range 1.2 × 104-5.2 × 105; vs. median 4.0 × 107 cp/mL; interquartile range, 8.6 × 105-1 × 108; P < 0.001). CONCLUSIONS: While RT-PCR testing on saliva performed more poorly in younger children and likely after longer duration of symptoms, saliva remains an attractive alternative to NP swabs in children.

Children younger than 36 months with fever without a source (FWS) are at risk of serious bacterial infections (SBI). The risk of occult bacteremia (OB) has been greatly reduced in vaccinated children. The aim of this study is to describe the epidemiology of SBI in children with FWS in our setting and to evaluate the performance of our management algorithm.We designed a prospective cohort study. We included children aged 0-36 months presenting with FWS in our emergency unit. Demographic and clinical characteristics, investigations, and management procedures were recorded at the time of inclusion. Information on clinical evolution, final diagnosis, and immunization history were obtained after 10 days. Potential predictors of SBI were compared between patients with and without SBI.Between October 2015 and September 2017, 173 children were recruited, with a median age of 4.4 months (2.1-1). Of these children, 166 (96%) were up to date with their vaccinations. A total of 47 children (27%) had a final diagnosis of SBI, which were all urinary tract infections (UTI). Presence of chills (odds ratio [OR] 5.6, 95% confidence interval [CI] 1.3-24.3), fever for2 days (OR 29.1, 95% CI 3.5-243.5), and age9 months (OR: 45.3, 95% CI: 4.9-415.7) were statistically significant predictors of UTI in a multivariate logistic regression. The sensitivity and specificity of our management algorithm were 100% (95% CI: 92.4-100%) and 21.4% (14.6-29.6%), respectively.In the setting of high vaccination coverage, we only identified SBI related to UTIs. We could not identify any OB. Our management algorithm was able to identify all SBI, but specificity was low. Refined criteria for screening of UTI could slightly increase this.

The kidneys and the urinary tract are a common source of infection in children of all ages, especially infants and young children. The main risk factors for sequelae after urinary tract infections (UTI) are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction. UTI should be considered in every child with fever without a source. The differentiation between upper and lower UTI is crucial for appropriate management. Method of urine collection should be based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. Treatment of UTI should be based on practical considerations regarding age and presentation with adjustment of the initial antimicrobial treatment according to antimicrobial sensitivity testing. All children, regardless of age, should have an ultrasound of the urinary tract performed after pyelonephritis. In general, antibiotic prophylaxis is not recommended.Conclusion: Based on recent data and in line with international guidelines, multidisciplinary Swiss consensus recommendations were developed by members of Swiss pediatric infectious diseases, nephrology, and urology societies giving the clinician clear recommendations in regard to diagnosis, type and duration of therapy, antimicrobial treatment options, indication for imaging, and antibiotic prophylaxis.What is Known:•Urinary tract infections (UTI) are a common and important clinical problem in childhood. Although children with pyelonephritis tend to present with fever, it can be difficult on clinical grounds to distinguish cystitis from pyelonephritis, particularly in young children less than 2 years of age.•Method of urine collection is based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture.What is New:•Vesicoureteric reflux (VUR) remains a risk factor for UTI butper seis neither necessary nor sufficient for the development of renal scars. Congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction play a more important role as causes of long-term sequelae. In general, antibiotic prophylaxis is not recommended.•A switch to oral antibiotics should be considered already in young infants. Indications for invasive imaging are more restrictive and reserved for patients with abnormal renal ultrasound, complicated UTI, and infections with pathogens other than E. coli.

Objectives Imipenem is a broad-spectrum antibacterial agent used in critically ill neonates after failure of first-line treatments. Few studies have described imipenem disposition in this population. The objectives of our study were: (i) to characterize imipenem population pharmacokinetics (PK) in a cohort of neonates; and (ii) to conduct model-based simulations to evaluate the performance of six different dosing regimens aiming at optimizing PK target attainment. Methods A total of 173 plasma samples from 82 neonates were collected over 15 years at the Lausanne University Hospital, Switzerland. The majority of study subjects were preterm neonates with a median gestational age (GA) of 27 weeks (range: 24–41), a postnatal age (PNA) of 21 days (2–153) and a body weight (BW) of 1.16 kg (0.5–4.1). PK data were analysed using non-linear mixed-effect modelling (NONMEM). Results A one-compartment model best characterized imipenem disposition. Population PK parameters estimates of CL and volume of distribution were 0.21 L/h and 0.73 L, with an interpatient variability (CV%) of 20.1% on CL in a representative neonate (GA 27 weeks, PNA 21 days, BW 1.16 kg, serum creatinine, SCr 46.6 μmol/L). GA and PNA exhibited the greatest impact on PK parameters, followed by SCr. These covariates explained 36% and 15% of interindividual variability in CL, respectively. Simulated regimens using a dose of 20–25 mg/kg every 6–12 h according to postnatal age led to the highest PTA (T>MIC over 100% of time). Conclusions Dosing adjustment according to BW, GA and PNA optimizes imipenem exposure in neonates.

BackgroundSaliva RT-PCR is an attractive alternative for the detection of SARS-CoV-2 in adults with much less known in children.MethodsChildren and adolescents with symptoms suggestive of COVID-19 were prospectively enrolled in a comparative clinical trial of saliva and nasopharyngeal (NP) RT-PCR between November and December 2020. Detection rates and sensitivities of saliva and NP RT-PCR were compared. Participants with discordant NP and saliva RT-PCR results including viral load (VL) were also analyzed.ResultOut of 405 patients enrolled, 397 patients had two tests performed. Mean age was 12.7 years (range 1.2-17.9). Detection rates were 22.9% (95%CI 18.8-27.1%) by saliva RT-PCR, 25.4% (21.2-29.7%) by NP RT-PCR, and 26.7% (22.4-31.1%) by any test. The sensitivity of saliva was 85.2% (78.2-92.1%) when using NP as the gold standard; in contrast, when saliva was considered the gold standard, the sensitivity of NP was 94.5% (89.8-99.2%).For a NP RT-PCR VL threshold of ≥103 and ≥104 copies/ml, sensitivity of saliva increases to 88.7% and 95.2% respectively. Sensitivity of saliva and NP swabs was respectively 89.5% and 95.3% in patient with symptoms less than 4 days (p=0.249) and 70.0% and 95.0% in those with symptoms ≥ 4 to 7 days (p=0.096). The 15 patients who had an isolated positive NP RT-PCR were significantly younger (p=0.034), had a lower NP VL (median 5.6×103 vs 3.9×107, p4; IQR 1.2×104-5.2×105; vs median 4.0×107cp/ml; IQR 8.6×105-1.x108; pConclusionSaliva PCR shows diagnostic performances close to NP RT-PCR for SARS-CoV2 detection in most symptomatic outpatient children and adolescents.

The article “Swiss consensus recommendations on urinary tract infections in children”

Summary Objectives To review the impact of the timeliness of antibiotic therapy on the outcome of patients with sepsis or septic shock. Methods We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science, Open-SIGLE databases, ClinicalTrials.gov and the metaRegister of Controlled Trials on July 27, 2020 for relevant studies on the timing of antibiotic therapy in adult patients with sepsis or septic shock. The primary outcome measure was all-cause crude or adjusted mortality at reported time points. Results We included 35 sepsis studies involving 154,330 patients. Nineteen studies (54%) provided information on the appropriateness of antibiotic therapy in 20,062 patients of whom 16,652 patients (83%) received appropriate antibiotics. Twenty-four studies (68.6%) reported an association between time-to-antibiotics and mortality. Time thresholds associated with patient's outcome varied considerably between studies consisting of a wide range of time cutoffs (1 h, 125 min, 3 h or 6 h) in 14 studies, hourly delays (derived from the analyses of time intervals ranging from to 1 to 24 h) in 8 studies or time-to-antibiotic in 2 studies. Analyses of subsets of studies that focused on patients with septic shock (11 studies, 12,756 patients) or with sepsis (6 studies, 24,281 patients) yielded similar results. Conclusions While two-thirds of sepsis studies reported an association between early administration of antibiotic therapy and patient outcome, the time-to-antibitiocs metrics varied significantly across studies and no robust time thresholds emerged.

Some uncertainties remain regarding SARS-CoV-2 diagnostic procedures and seroprevalence studies in children. RT-PCR assays conducted on nasopharyngeal (NP) swabs remain the gold standard for SARS-CoV-2 diagnostic in children as in adults. Saliva samples might replace soon NP swabs as similar sensitivities have been reported from both samples in adults, but not yet in children. Rapid antigen testing is currently performed on NP swabs collected from children within 4 days of their symptom onset. Serology testing is an essential diagnostic tool in seroprevalence studies, which might guide in the future public health decisions.Certaines questions demeurent sur le diagnostic de SARS-CoV-2 et sur la séroprévalence chez l’enfant. Les outils moléculaires de type RT-PCR effectués sur des prélèvements nasopharyngés (NP) restent le gold standard du diagnostic de SARS-CoV-2 chez l’enfant comme chez l’adulte. Les frottis NP pourraient peut-être être prochainement remplacés par des frottis salivaires pour lesquels une sensibilité similaire aux frottis NP a été démontrée chez l’adulte, mais pas encore chez l’enfant. Les tests antigéniques effectués sur des frottis NP sont actuellement déployés chez les enfants consultant dans les 4 jours suivant le début de leurs symptômes. Les tests sérologiques sont un outil incontournable aux études de séroprévalence et permettront d’orienter des décisions de santé publique.

Objectives: The contribution of intracellular and fastidious bacteria in Cystic fibrosis (CF) pulmonary exacerbations, and progressive lung function decline remains unknown. This project aimed to explore their impact on bacterial microbiota diversity over time in CF children. Methods: Sixty-one children enrolled in the MUCOVIB multicentre prospective cohort provided 746 samples, mostly nasopharyngeal swabs, throat swabs and sputa which were analysed using culture, specific real-time qPCRs and 16S rRNA amplicon metagenomics. Results: Chlamydia pneumoniae (n = 3) and Mycoplasma pneumoniae (n = 1) were prospectively documented in 6.6% of CF children. Microbiota alpha-diversity in children with a documented C. pneumoniae was highly variable, similarly to children infected with Staphylococcus aureus or Pseudomonas aeruginosa. The transition from routine follow-up visits to pulmonary exacerbation (n = 17) yielded variable changes in diversity indexes with some extreme loss of diversity. Conclusions: The high rate of C. pneumoniae detection supports the need for regular screenings in CF patients. A minor impact of C. pneumoniae on the microbial community structure was documented. Although detected in a single patient, M. pneumoniae should also be considered as a possible aetiology of lung infection in CF subjects., This study documented Chlamydia pneumoniae in 4.9% of children with cystic fibrosis, stressing the need for routine screening, and investigated its impact on airway microbiota by 16S amplicon-based metagenomics.

Children infected with SARS-CoV-2 are underrepresented during the current COVID-19 outbreak. Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children. From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic. In particular, children present significantly less fever, cough and pneumonia compared to adults. However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1. No vertical transmission of SARS-CoV-2 has been described so far.Les enfants sont sous-représentés durant la pandémie COVID-19 actuelle. Contrairement aux autres virus respiratoires, dans la majorité des clusters familiaux, ce sont les parents qui infectent les enfants. Les évidences cliniques chinoises et italiennes suggèrent que les enfants présentent souvent un tableau clinique peu sévère et qu’ils sont fréquemment asymptomatiques. Notamment, les enfants présentent moins de fièvre, de toux et de pneumonies comparés aux adultes. Toutefois, plus de cas de pneumonies ont été reportés chez des enfants infectés par SARS-CoV-2 que chez ceux qui le sont par H1N1. Aucun cas de transmission verticale de SARS-CoV-2 n’a été démontré récemment.

A previously healthy 9-year-old boy presented with a history of fatigue for 3 weeks, pain in both calves for 2 days, and a mild cough, without fever. His medical history was negative and vaccinations were up to date. Examination by his pediatrician only showed decreased deep tendon reflexes (DTR) in both lower limbs. Blood count (white blood cells [WBC] 5.4 G/L, hemoglobin [Hb] 138 g/L, thrombocytes [Tc] 251 G/L), thyroid-stimulating hormone (1.76 mU/L), creatine kinase (CK) level (104 U/L), and erythrocyte sedimentation rate (3 mm/h) were all normal. Epstein-Barr virus monotest was negative and blood serology suggested a past infection.

Multidrug resistance (MDR) has emerged in hospitals due to the use of several agents administered in combination or sequentially to the same individual. We reported earlier MDR inCandida lusitaniaeduring therapy with amphotericin B (AmB), azoles and candins. We used here comparative genomic approaches between the initial susceptible isolate and 4 other isolates with different MDR profiles. From a total of 18 non-synonymous SNPs (NSS) in genome comparisons with the initial isolate, six could be associated with MDR. One of the SNPs occurred in a putative transcriptional activator (MRR1) resulting in a V668G substitution in isolates resistant to azoles and 5-fluorocytosine (5-FC). We demonstrated by gene editing thatMMR1acted by upregulation ofMFS7(a multidrug transporter) in the presence of the V668G substitution.MFS7itself mediated not only azole resistance but also 5-FC resistance, which represents a novel resistance mechanism for this drug class. Three other distinct NSS occurred inFKS1(a glucan synthase that is targeted by candins) in three candin-resistant isolates. Lastly, two other NSS inERG3andERG4(ergosterol biosynthesis) resulting in non-sense mutations were revealed in AmB-resistant isolates, one of which accumulated the 2ERGNSS. AmB-resistant isolates lacked ergosterol and exhibited sterol profiles consistent withERG3andERG4defects. In conclusion, this genome analysis combined with genetics and metabolomics helped to decipher the resistance profiles identified in this clinical case. MDR isolates accumulated 6 different mutations conferring resistance to all antifungal agents used in medicine. This case study illustrates the capacity ofC. lusitaniaeto rapidly adapt under drug pressure within the host.ImportanceAntifungal resistance is an inevitable phenomenon when fungal pathogens get exposed to antifungal drugs. These drugs can be grouped in 4 distinct classes (azoles, candins, polyenes, pyrimidine analogs) and are used in different clinical settings. Failures in therapy implicates the sequential or combined use of these different drug classes, which can result in some cases in the development of multidrug resistance (MDR). MDR is particularly challenging in the clinic since it drastically reduces possible treatment alternatives. In this study, we report the rapid development of MDR inCandida lusitaniaein a patient, which became resistant to all known antifungal agents used up to now in medicine. To understand how MDR developed inC. lusitaniae, whole genome sequencing followed by comparative genome analysis was undertaken in sequential MDR isolates. This helped to detect all specific mutations linked to drug resistance and explained the different MDR patterns exhibited by the clinical isolates.

Little information on the efficacy and pharmacokinetics of letermovir among immunocompromised children is currently available. We describe here the use of letermovir in a 2-year-old immunocompromised child with ganciclovir-resistant cytomegalovirus disease who required extracorporeal membrane oxygenation. Detailed information on therapeutic-drug-monitoring measures and dosage adjustments for letermovir is provided.

BackgroundPopulation-based studies assessing the impact of pneumococcal conjugate vaccines (PCV) on burden of pneumococcal sepsis in children are lacking. We aimed to assess this burden following introduction of PCV-13 in a nationwide cohort study.MethodsThe Swiss Pediatric Sepsis Study (September 2011 to December 2015) prospectively recruited children ResultsChildren with pneumococcal sepsis (n = 117) accounted for a crude incidence of 2.0 per 100 000 children (95% confidence interval [CI] 1.7–2.4) and 25% of community-acquired sepsis episodes. Case fatality rate was 8%. Forty-two (36%) patients required PICU admission. Children with meningitis (29; 25%) were more often infected by serotypes not included in PCV (69% vs 31%; P < .001). Sixteen (26%) of 62 children up to date with PCV immunization presented with vaccine failure, including 11 infected with serotype 3. In multivariable analyses, children with meningitis (odds ratio [OR] 6.8; 95% CI 2.4–19.3; P < .001) or infected with serotype 3 (OR 2.8; 95% CI 1.1–7.3; P = .04) were more often admitted to PICU. Children infected with serotype 3 had longer LOS (β coefficient 0.2, 95% CI .1–1.1; P = .01).ConclusionsThe incidence of pneumococcal sepsis in children shortly after introduction of PCV-13 remained substantial. Meningitis mostly due to non-vaccine serotypes and disease caused by serotype 3 represented significant predictors of severity.

Respiratory syncytial virus (RSV)–associated deaths in Canadian children during 2003–2013 were predominantly associated with chronic medical conditions and immunocompromised states among infants. One in 5 deaths occurred among patients with no known risk factors for severe RSV., Background Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in children. Mortality rates in previously healthy children hospitalized with RSV are

While genetic polymorphisms play a paramount role in tuberculosis (TB), less is known about their contribution to the severity of diseases caused by other intracellular bacteria and fastidious microorganisms. We searched electronic databases for observational studies reporting on host factors and genetic predisposition to infections caused by intracellular fastidious bacteria published up to 30 May 2014. The contribution of genetic polymorphisms was documented for TB. This includes genetic defects in the mononuclear phagocyte/T helper cell type 1 (Th1) pathway contributing to disseminated TB disease in children and genome-wide linkage analysis (GWAS) in reactivated pulmonary TB in adults. Similarly, experimental studies supported the role of host genetic factors in the clinical presentation of illnesses resulting from other fastidious intracellular bacteria. These include IL-6 -174G/C or low mannose-binding (MBL) polymorphisms, which are incriminated in chronic pulmonary conditions triggered by C. pneumoniae, type 2-like cytokine secretion polymorphisms, which are correlated with various clinical patterns of M. pneumoniae infections, and genetic variation in the NOD2 gene, which is an indicator of tubal pathology resulting from Chamydia trachomatis infections. Monocyte/macrophage migration and T lymphocyte recruitment defects are corroborated to ineffective granuloma formation observed among patients with chronic Q fever. Similar genetic polymorphisms have also been suggested for infections caused by T. whipplei although not confirmed yet. In conclusion, this review supports the paramount role of genetic factors in clinical presentations and severity of infections caused by intracellular fastidious bacteria. Genetic predisposition should be further explored through such as exome sequencing.

Background Human rhinovirus/enterovirus (HRV/ENT) infections are commonly identified in children with acute respiratory infections (ARIs), but data on their clinical severity remain limited. Objectives We compared the clinical severity of HRV/ENT to respiratory syncytial virus (RSV), influenza A/B (FLU), and other common respiratory viruses in children. Patients/Methods Retrospective study of children with ARIs and confirmed single positive viral infections on mid-turbinate swabs by molecular assays. Outcome measures included hospital admission and, for inpatients, a composite endpoint consisting of intensive care admission, hospitalization >5 days, oxygen requirements or death. Results A total of 116 HRV/ENT, 102 RSV, 99 FLU, and 64 other common respiratory viruses were identified. Children with single HRV/ENT infections presented with significantly higher rates of underlying immunosuppressive conditions compared to those with RSV (37·9% versus 13·6%; P < 0·001), FLU (37·9% versus 22%; P = 0·018) or any other single viral infection (37·9% versus 22·5%; P = 0·024). In multivariable analysis adjusted for underlying conditions and age, children with HRV/ENT infections had increased odds of hospitalization compared to children with RSV infections (OR 2·6; 95% CI 1·4, 4·8; P < 0·003) or FLU infections (OR 3·0; 95% CI 1·6, 5·8

Background Several enterovirus (EV) genotypes can result in aseptic meningitis, but their routes of access to the central nervous system remain to be elucidated and may differ between the pediatric and adult populations. Objective To assess the pattern of viral shedding in pediatric and adult subjects with acute EV meningitis and to generate EV surveillance data for Switzerland. Study design All pediatric and adult subjects admitted to the University Hospitals of Geneva with a diagnosis of EV meningitis between 2013 and 2015 were enrolled. A quantitative EV real-time reverse transcriptase (rRT)-PCR was performed on the cerebrospinal fluid (CSF), blood, stool, urine and respiratory specimens to assess viral shedding and provide a comparative analysis of pediatric and adult populations. EV genotyping was systematically performed. Results EV positivity rates differed significantly between pediatric and adult subjects; 62.5% of pediatric cases (no adult case) were EV-positive in stool and blood for subjects for whom these samples were all collected. Similarly, the EV viral load in blood was significantly higher in pediatric subjects. Blood C-reactive protein levels were lower and the number of leucocytes/mm3 in the CSF were higher in non-viremic than in viremic pediatric subjects, respectively. A greater diversity of EV genotypes was observed in pediatric cases, with a predominance of echovirus 30 in children ≥3 years old and adults. Conclusion In contrast to adults, EV-disseminated infections are predominant in pediatric subjects and show different patterns of EV viral shedding. This observation may be useful for clinicians and contribute to modify current practices of patient care.

Outbreaks of Streptococcus pyogenes hypervirulent clones are constant public health threats. In western Switzerland, an increase of severe cases of S. pyogenes invasive infections was observed between December 2015 and March 2016. Our aim was (i) to investigate these cases by the use of Whole Genome Sequencing (WGS) and (ii) to determine the specific virulome and resistome of each isolate in order to undertake adequate public health measures. Eleven Streptococcus pyogenes strains isolated from 11 patients with severe invasive infections between December 13, 2015 and March 12, 2016 were included in our study. Practically, emm-typing, MLST and WGS were used to investigate the relatedness between the isolates. The presence of virulence and antibiotic resistance genes as well as mutations in transcriptional regulators of virulence and in genes encoding for antibiotic targets were assessed. Three and two groups of isolates shared the same emm-type and ST type, respectively. Single Nucleotide Polymorphism (SNP) analysis revealed 14 to 32 SNPs between the strains of the same emm-type group, ruling out the possibility of a clonal outbreak. Mutations found in covS and rocA could partially explain an increased virulence. As these reassuring results were obtained in less than 10 days, no specific hospital hygiene and no dedicated public health measures had to be undertaken. WGS is a powerful technique to discriminate between closely related strains, excluding an outbreak in less than 10 days. Moreover, WGS provided extensive data on the virulome and resistome of all these strains. Electronic supplementary material The online version of this article (doi:10.1007/s10096-017-2905-z) contains supplementary material, which is available to authorized users.

Cardiobacterium hominis is a well-known commensal bacterium of the oral cavity and an agent of infective endocarditis in humans. Here, we provide a draft genome sequence of a pathogenic strain isolated from blood cultures of a patient with infectious endocarditis.

Influenza vaccination programmes are assumed to have a herd effect and protect contacts of vaccinated persons from influenza virus infection. We searched MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Global Health and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to March 2014 for studies assessing the protective effect of influenza vaccination vs no vaccination on influenza virus infections in contacts. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. Of 43,082 screened articles, nine randomised controlled trials (RCTs) and four observational studies were eligible. Among the RCTs, no statistically significant herd effect on the occurrence of influenza in contacts could be found (OR: 0.62; 95% CI: 0.34–1.12). The one RCT conducted in a community setting, however, showed a significant effect (OR: 0.39; 95% CI: 0.26–0.57), as did the observational studies (OR: 0.57; 95% CI: 0.43–0.77). We found only a few studies that quantified the herd effect of vaccination, all studies except one were conducted in children, and the overall evidence was graded as low. The evidence is too limited to conclude in what setting(s) a herd effect may or may not be achieved.

Molecular diagnostic tests have greatly increased our knowledge regarding the contribution of respiratory viruses in respiratory illnesses in children, mainly lower respiratory tract infections. Respiratory syncytial virus, rhinovirus (RV) and human metapneumovirus (hMPV) are predominant viral agents identified in children. Notwithstanding the importance of respiratory viruses in children, treatment and prophylactic options remain limited. These include palivizumab, a monoclonal antibody prophylactically administred to high risk children against RSV, vaccines and antivirals such as oseltamivir targeting influenza viruses.

Background The role of respiratory viruses in cystic fibrosis (CF) exacerbations is incompletely understood. Methods Cross-sectional study of CF children with a pulmonary exacerbation. Mid-turbinate swabs were tested by a direct immunofluorescent antibody assay and a multiplex PCR panel (ResPlex II v2.0, Qiagen). Resplex II was also applied to sputum or throat swab samples. Pulmonary function tests and quality of life and severity scores were recorded. Sputum cell counts, bacterial density and cytokines were measured. Results 26/43 (60.5%) subjects tested positive for at least one respiratory virus by any diagnostic method applied to any sample type. Virus-positive patients were younger ( p =0.047), more likely to be male ( p =0.029), and had higher CF clinical severity ( p =0.041) and lower quality of life (physical) scores ( p =0.023) but similar IL-8, neutrophil percentage and elastase levels. Conclusions Compared to non-viral exacerbations, viral-related exacerbations were associated with worse severity and quality of life scores but similar pulmonary inflammation.

Background Inconsistent intra-individual microbiota between upper and lower respiratory niches has been reported among infants with Cystic Fibrosis (CF). We aimed to investigate the concordance between the bacterial community composition of 20 oropharyngeal (OP) samples and 20 corresponding sputa, collected from children with CF above one year of age. Methods As part of the”‘cystic fibrosis, respiratory viruses, intracellular bacteria and fastidious organisms’’ (MUCOVIB) project, all children under 18 years of age with diagnosed CF were recruited into a swiss multicentric study. Respiratory samples included OP swabs collected from all children in addition to sputa collected from those able to expectorate. Sequencing and data analysis of amplicons of the V3–V4 variable region of the 16S rRNA-encoding gene were performed. Paired-read were assembled with PANDAseq and clustered into operational taxonomic units (OTUs) using vsearch and assigned to taxonomical ranks using Qiime and the EzBioCloud database. Non-metric multidimensional scaling, ANOVA and PERMANOVA were used to analyze the bacterial diversity in upper and lower respiratory niches. Results Fifty-eight children, of whom 29 (50%) provided 51 sputa samples. From these 29, 10 patients (40 samples) provided concomitant OP and sputa samples collected during the same visit. Equivalent species diversity (alpha-diversity; Shannon index) was documented from both upper and lower samples (P = 0.26). In most cases, hierarchical clustering based on OTU presence/absence clustered upper and lower samples from the same patient and during the same visit, thus suggesting a signature microbiota in most patients. A similar variance of bacterial microbiota was observed in upper and lower respiratory niches (P = 0.9422), with some differences in species composition. Conclusion Our preliminary findings conducted on a small subset of patients, suggested a good intra-individual concordance of the microbiota in upper and lower respiratory niches, thus suggesting that OP swabs could be used as proxy to measure bacterial biodiversity among children with CF unable to expectorate. Disclosures All authors: No reported disclosures.

Background Recent population-based studies assessing the impact of pneumococcal conjugate vaccines (PCV) on the burden of pneumococcal sepsis in children are lacking. We aimed to define the burden of pneumococcal sepsis in children and assess predictors for severe outcomes following the introduction of PCV-13 in 2011 in a nationwide cohort study. Methods The Swiss Paediatric Sepsis Study prospectively recruited children Results From all 1,181 sepsis episodes recorded during the 4.3-year period, children with pneumococcal sepsis (n = 117) accounted for 10% of all sepsis episodes, and 25% of community-acquired sepsis episodes. Forty-two (36%) patients required PICU admission resulting in a mortality of 8%. Children presenting with meningitis (29; 25%) were more frequently admitted to PICU (69% vs. 25%; P < 0.001) and more likely infected by serotypes not included in vaccines (69% vs. 31%; P < 0.001) than those without meningitis. Pneumococcal serotypes 3, 19A, and 7F accounted for 49 (44%) pneumococcal sepsis episodes. From 62 children completely immunised with PCV, of whom 32 were infected with vaccine serotypes, 16 (50%) presented with vaccine failure, of whom 11 were infected with serotype 3. In multivariable analyses, children with meningitis (OR 6.8; 95% C.I 2.4–19.3; P < 0.001) and those infected with serotype 3 (OR 2.8; 95% C.I 1.1- 7.3; P = 0.04) were more likely admitted to PICU, and those infected with serotype 3 had a longer hospital stay (β-coefficient 0.2, 95% CI 0.1–1.1; P = 0.01). Conclusion The burden of pneumococcal sepsis in swiss children shortly after the introduction of PCV-13 remains important. Meningitis and serotype 3 were significant predictors of severity. Disclosures All authors: No reported disclosures.

Background Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. Methods We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. Results Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) −0.20 days, 95% CI −0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p

BACKGROUND Respiratory syncytial virus (RSV) is associated with significant morbidity and mortality in immunocompromised children. Data on the risk factors for acquisition and outcomes from RSV infections in this population are limited. METHODS This cohort study (2006 to 2011) included RSV-positive immunocompromised pediatric inpatients. Nasopharyngeal swabs were tested for RSV by direct immunofluorescence. Purposeful multiple regression was used to assess risk factors associated with community-acquired RSV (CA-RSV) infections and their outcomes compared with nosocomial (N-RSV) infections. Means and medians were compared using Student's t test and a nonparametric test, respectively. Proportions were compared using χ(2) or Fisher's exact test, as appropriate. RESULTS There were 117 RSV-positive patients of whom 42 (35.9%) presented with (N-RSV) infection. Overall, more than a third presented with lower respiratory tract infections, which resulted in a 28% admission rate to the intensive care unit and a mortality rate of 5%; the latter solely among patients with community-acquired infection. Subjects with CA-RSV presented with more advanced clinical evidence of lower tract disease with respiratory distress (eg, intercostal recession; odds ratio 2.5; 95% confidence interval: 1.1-5.6; P = 0.03) compared with those with N-RSV. Subjects with CA-RSV infections were less likely to have a prolonged hospital admission (odds ratio 0.7; 95% confidence interval: 0.5-0.8; P < 0.0001) relative to those with N-RSV infections. CONCLUSIONS RSV-related infections in immunocompromised children may result in poor outcomes, including mortality. Differences in mortality rates among those with CA-RSV compared with N-RSV warrant further study, with enhanced opportunities for prevention and early detection of infection.

Chlamydia pneumoniae: possible association with asthma in children

Molecular assays have resulted in increased detection of viral respiratory infections, including virus coinfection, from children with acute respiratory infections. Yet the clinical severity of virus coinfection compared to single virus infection remains uncertain. We performed a retrospective study of children presenting with acute respiratory infections comparing clinical severity of single respiratory virus infection to virus coinfection, detected on midturbinate swabs by molecular assays. Patient characteristics and measures of clinical severity were abstracted from health records. A total of 472 virus-infected children were included, 391 with a single virus infection and 81 with virus coinfection. Virus status did not affect admission to hospital (odds ratio (OR) = 0.8; 95 % confidence interval (CI) 0.5–1.4; p 0.491) or clinical disease severity among inpatients (OR = 0.8; 95% CI 0.5–1.5; p 0.515) after adjusting for age and underlying comorbidities. However, children infected with rhinovirus/enterovirus (HRV/ENT) alone were more likely to be admitted to the hospital compared to those coinfected with HRV/ENT and at least another virus, although this was not significant in multivariable analyses (OR 0.47; 95% CI 0.22–1.0; p 0.051). In multivariable analyses, children coinfected with respiratory syncytial virus (RSV) and other viruses were significantly more likely to present with radiologically confirmed pneumonia compared to those with an isolated RSV infection (OR 3.16, 95% CI 1.07–9.34, p 0.037). Equivalent clinical severity was observed between children with single virus infection and virus coinfection, although children coinfected with RSV and other viruses presented more frequently with pneumonia than those with single RSV infection. Increased disease severity observed among children with single HRV/ENT infection requires further investigation.