Age-Specific Resurgence in Invasive Pneumococcal Disease Incidence in the COVID-19 Pandemic Era and Its Association With Respiratory Virus and Pneumococcal Carriage Dynamics: A Time-Series Analysis.

Using multiple national surveillance systems, we found an increase in the incidence of invasive pneumococcal disease during after the relaxation of non-pharmaceutical interventions against COVID-19, which strongly varied by age. Age groups with higher incidence of respiratory syncytial virus and influenza also experienced higher increase in invasive pneumococcal disease incidence, with no change in pneumococcal carriage.

Improved Molecular Diagnosis and Culture of the Emerging Heteropathotype Enterohemorrhagic Escherichia coli O80:H2 Using Its Non-Melibiose-Fermenting and Antibiotic-Resistance Properties.

Enterohemorrhagic Escherichia coli (EHEC) O80:H2, belonging to sequence type ST301, is among the main causes of hemolytic and uremic syndrome in Europe, a major concern in young children. Aside from the usual intimin and Shiga toxin virulence factors (VFs), this emerging serotype possesses a mosaic plasmid combining extra-intestinal VF- and antibiotic resistance-encoding genes. This hybrid pathotype can be involved in invasive infections, a rare occurrence in EHEC infections. Here, we aimed to optimize its detection, improve its clinical diagnosis, and identify its currently unknown reservoir. O80:H2 EHEC strains isolated in France between 2010 and 2018 were phenotypically and genetically analyzed and compared with non-O80 strains. The specificity and sensitivity of a PCR test and a culture medium designed, based on the molecular and phenotypic signatures of O80:H2 EHEC, were assessed on a collection of strains and stool samples. O80:H2 biotype analysis showed that none of the strains (n = 137) fermented melibiose versus 5% of non-O80 EHEC (n = 19/352). This loss of metabolic function is due to deletion of the entire melibiose operon associated with the insertion of a 70-pb sequence (70mel), a genetic scar shared by all ST301 strains. This metabolic hallmark was used to develop a real-time PCR test (100% sensitivity, 98.3% specificity) and a melibiose-based culture medium including antibiotics, characterized by 85% specificity and sensitivity for clinical specimens. These new tools may facilitate the diagnosis of this atypical clone, help the food industry to identify the reservoir and improve our epidemiological knowledge of this threatening and emerging clone.

Association between the COVID-19 pandemic and pertussis derived from multiple nationwide data sources, France, 2013 to 2020.

BackgroundInterventions to mitigate the COVID-19 pandemic may impact other respiratory diseases.AimsWe aimed to study the course of pertussis in France over an 8-year period including the beginning of the COVID-19 pandemic and its association with COVID-19 mitigation strategies, using multiple nationwide data sources and regression models.MethodsWe analysed the number of French pertussis cases between 2013 and 2020, using PCR test results from nationwide outpatient laboratories (Source 1) and a network of the paediatric wards from 41 hospitals (Source 2). We also used reports of a national primary care paediatric network (Source 3). We conducted a quasi-experimental interrupted time series analysis, relying on negative binomial regression models. The models accounted for seasonality, long-term cycles and secular trend, and included a binary variable for the first national lockdown (start 16 March 2020).ResultsWe identified 19,039 pertussis cases from these data sources. Pertussis cases decreased significantly following the implementation of mitigation measures, with adjusted incidence rate ratios of 0.10 (95% CI: 0.04-0.26) and 0.22 (95% CI: 0.07-0.66) for Source 1 and Source 2, respectively. The association was confirmed in Source 3 with a median of, respectively, one (IQR: 0-2) and 0 cases (IQR: 0-0) per month before and after lockdown (p = 0.0048).ConclusionsThe strong reduction in outpatient and hospitalised pertussis cases suggests an impact of COVID-19 mitigation measures on pertussis epidemiology. Pertussis vaccination recommendations should be followed carefully, and disease monitoring should be continued to detect any resurgence after relaxation of mitigation measures.

Invasive Disease Potential of Pneumococcal Serotypes in Children After PCV13 Implementation.

We aimed to assess the invasive disease potential of non-PCV13 serotypes after the implementation of this vaccine. Most non-PCV13 serotypes had low invasive disease potential. Among serotypes with the highest invasive disease potential (12F, 24F, 38, 8, 33F, 22F, and 10A), all but 24F and 38 were included in PCV20.

Monitoring outpatient antibiotic utilization using reimbursement and retail sales data: a population-based comparison in France, 2012-17.

OBJECTIVES: To assess whether a retail sales database could be used to monitor antibiotic utilization in the outpatient setting at the national level. METHODS: We extracted 2012-17 outpatient antibiotic extrapolated retail sales (IQVIA's Xponent) and reimbursement data from the National Health Insurance (SNDS) in metropolitan France. We compared estimates of antibiotic use and consumption [number of antibiotic drug deliveries (DrID) and defined daily doses (DID) per 1000 inhabitants per day]. We relied on relative differences, Pearson's r statistics and time series using autoregressive integrated moving average (ARIMA) modelling to study: (i) differences in point estimates, (ii) correlation, and (iii) consistency in time trends between Xponent and SNDS. The analysis was conducted overall and in subgroups (age groups, therapeutic classes, major antimicrobial agents and regions). RESULTS: We analysed approximately 377 million antibiotic drug deliveries, comprising nearly 3.4 billion DDDs. Overall, Xponent slightly overestimated SNDS point estimates with yearly relative differences of +3.5% for DrID and +3.3% for DID. Peaks in relative differences were observed for July and August months. Relative differences were <5% in most subgroups, except for fosfomycin and three French regions. Overall and across most subgroups, the correlation between Xponent and SNDS monthly aggregated estimates was almost perfect (r ≥ 0.992 for all subgroups, except for one region). ARIMA modelling showed high consistency between Xponent's and SDNS's DrID time series, but detected timepoints where the series significantly diverged. CONCLUSIONS: IQVIA's Xponent and SNDS data were highly consistent. Xponent database seems suitable for monitoring outpatient antibiotic utilization in France.

Clavulanate combinations with mecillinam, cefixime or cefpodoxime against ESBL-producing Enterobacterales frequently associated with blaOXA-1 in a paediatric population with febrile urinary tract infections.

OBJECTIVES: Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of ß-lactamases and Enterobacterales' genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. MATERIALS AND METHODS: In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates' ST and their type of ß-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. RESULTS: All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant ß-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). CONCLUSIONS: Despite the frequent association of ESBL genes with inhibitor-resistant ß-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children.

Clinical Prediction of Iron Deficiency at Age 2 Years: A National Cross-sectional Study in France.

OBJECTIVE: To assess the diagnostic accuracy of existing clinical criteria and to develop prediction tools for iron deficiency in 2-year-old children. STUDY DESIGN: In a national cross-sectional study conducted in primary care pediatricians' practices throughout France, 2-year-old children were consecutively included (2016-2017). Multivariable logistic regression modeling and bootstrapping were used to develop several clinical models to predict iron deficiency (serum ferritin <12 µg/L). These models used the best criteria and combinations among the American Academy of Pediatrics' (AAP) criteria adapted to the European context (n = 10), then all potential predictors (n = 19). One model was then simplified into a simple prediction tool. RESULTS: Among 568 included infants, 38 had iron deficiency (6.7%). In univariable analyses, no significant association with iron deficiency was observed for 8 of the 10 adapted AAP criteria. Three criteria (both parents born outside the European Union, low weight at 1 year old, and weaning to cow's milk without supplemental iron) were retained in the AAP model, which area under the receiver operating characteristic curve, sensitivity, and specificity were 0.62 (95% CI, 0.58-0.67), 30% (95% CI, 22%-39%), and 95% (95% CI, 92%-97%), respectively. Four criteria were retained in a newly derived simple prediction tool (≥1 criterion among the 3 previous plus duration of iron-rich formula consumption <12 months), which area under the receiver operating characteristic curve, sensitivity, and specificity were 0.72 (95% CI, 0.65-0.79), 63% (95% CI, 47%-80%), and 81% (95% CI, 70%-91%), respectively. CONCLUSIONS: All prediction tools achieved acceptable diagnostic accuracy. The newly derived simple prediction tool offered potential ease of use. TRIAL REGISTRATION: ClinicalTrials.gov NCT02484274.

Neurodevelopmental Outcomes after Premedication with Atropine/Propofol vs Atropine/Atracurium/Sufentanil for Neonatal Intubation: 2-Year Follow-Up of a Randomized Clinical Trial.

This study followed 173 newborn infants in the PREmedication Trial for Tracheal Intubation of the NEOnate multicenter, double-blind, randomized controlled trial of atropine-propofol vs atropine-atracurium-sufentanil for premedication before nonemergency intubation. At 2 years of corrected age, there was no significant difference between the groups in death or risk of neurodevelopmental delay assessed with the Ages and Stages Questionnaire. Trial registration Clinicaltrials.gov: NCT01490580.

A large-scale outbreak of hand, foot and mouth disease, France, as at 28 September 2021.

We report a large-scale outbreak of hand, foot and mouth disease (HFMD) in France. As at 28 September 2021, 3,403 cases have been reported (47% higher than in 2018-19). We prospectively analysed 210 clinical samples; 190 (90.5%) were enterovirus-positive. Most children presented with atypical HFMD. Coxsackievirus (CV)A6 (49.5%; 94/190) was predominant; no enterovirus A71 was detected. Dermatological and neurological complications of HFMD justify prospective syndromic and virological surveillance for early detection of HFMD outbreaks and identification of associated types.

Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.

Changes in Invasive Pneumococcal Disease Spectrum After 13-Valent Pneumococcal Conjugate Vaccine Implementation.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) implementation has led to a sharp decrease in invasive pneumococcal disease (IPD) due to the reduction in PCV serotypes. We aimed to describe the changes in the spectrum of IPD and its clinical presentations after 13-valent PCV (PCV13) implementation. METHODS: This prospective, hospital-based, active surveillance involved 130 pediatric wards and microbiology departments throughout France. We analyzed IPD cases from 2011 to 2016 for which a pneumococcal isolate was sent to the National Reference Center for Pneumococci for serotyping. Clinical data recorded were medical history, vaccination status, type of IPD, clinical features, and short-term evolution. RESULTS: Among 1082 IPD cases, we observed a 35.3% decrease (95% confidence interval, 29.2%-41.8%]) and the median age shifted from 38.3 months to 23.7 months (P = .007). The change in IPD type was mostly due to a reduction in bacteremic pneumonia frequency (from 42.1% to 19.1%; P < .001). Among the emerging non-PCV13 types (NVTs), those known to have the highest disease potential (8, 12F, 24F, and 33F) were isolated more frequently in patients without underlying conditions and were able to induce all IPD clinical presentations including bacteremic pneumonia. Conversely, serotypes with lower disease potential (15A, 15BC, 16F, and 23B) were rarely isolated from bacteremic pneumonia cases and were particularly involved in IPD in patients with underlying conditions (35.8%). CONCLUSIONS: Besides the decrease in IPD after 7-valent, then 13-valent PCV implementation, the spectrum of the remaining IPD cases showed significant changes, with substantial discrepancies across NVTs implicated in terms of clinical features and underlying conditions.

Community antibiotic prescribing for children in France from 2015 to 2017: a cross-sectional national study.

OBJECTIVES: To assess recent community antibiotic prescribing for French children and identify areas of potential improvement. METHODS: We analysed 221 768 paediatric (<15 years) visits in a national sample of 680 French GPs and 70 community paediatricians (IQVIA's EPPM database), from March 2015 to February 2017, excluding well-child visits. We calculated antibiotic prescription rates per 100 visits, separately for GPs and paediatricians. For respiratory tract infections (RTIs), we described broad-spectrum antibiotic use and duration of treatment. We used Poisson regression to identify factors associated with antibiotic prescribing. RESULTS: GPs prescribed more antibiotics than paediatricians [prescription rate 26.1 (95% CI 25.9-26.3) versus 21.6 (95% CI 21.0-22.2) per 100 visits, respectively; P < 0.0001]. RTIs accounted for more than 80% of antibiotic prescriptions, with presumed viral RTIs being responsible for 40.8% and 23.6% of all antibiotic prescriptions by GPs and paediatricians, respectively. For RTIs, antibiotic prescription rates per 100 visits were: otitis, 68.1 and 79.8; pharyngitis, 67.3 and 53.3; sinusitis, 67.9 and 77.3; pneumonia, 80.0 and 99.2; bronchitis, 65.2 and 47.3; common cold, 21.7 and 11.6; bronchiolitis 31.6 and 20.1; and other presumed viral RTIs, 24.1 and 11.0, for GPs and paediatricians, respectively. For RTIs, GPs prescribed more broad-spectrum antibiotics [49.8% (95% CI 49.3-50.3) versus 35.6% (95% CI 34.1-37.1), P < 0.0001] and antibiotic courses of similar duration (P = 0.21). After adjustment for diagnosis, antibiotic prescription rates were not associated with season and patient age, but were significantly higher among GPs aged ≥50 years. CONCLUSIONS: Future antibiotic stewardship campaigns should target presumed viral RTIs, broad-spectrum antibiotic use and GPs aged ≥50 years.

Escherichia coli O80 hybrid pathotype strains producing Shiga toxin and ESBL: molecular characterization and potential therapeutic options.

OBJECTIVES: Enterohaemorrhagic Escherichia coli (EHEC) infections may be complicated by haemolytic uraemic syndrome (HUS). The emerging worldwide EHEC serogroup O80 has acquired a mosaic plasmid combining extraintestinal virulence and antibiotic resistance. This hybrid pathotype is associated with invasive infections that require antibiotic therapy, classically not recommended in EHEC infections, increasing the risk of HUS. We characterized two ESBL-producing O80 EHEC strains, which is an unusual resistance mechanism among EHECs, and determined the safest therapy to be used for invasive infections. METHODS: WGS of two strains isolated from the stools of an asymptomatic carrier and a patient with HUS was performed using Illumina and Nanopore technologies. Generated reads were combined to assemble genomes. We determined the safest therapy by comparing Shiga toxin (Stx) production by the two strains in the presence of several antibiotics. RESULTS: The strains were genetically close to the O80 EHEC clone, belonging to ST301 and harbouring stx2d, eae-ξ, ehxA and genes characteristic of the extraintestinal virulence plasmid pS88. Long-read sequencing identified the acquisition of an additional plasmid harbouring CTX-M-type genes (blaCTX-M-14 and blaCTX-M-1). Azithromycin decreased Stx production at subinhibitory concentrations, ciprofloxacin increased it and imipenem had no major effect. The combination of azithromycin and imipenem overall reduced Stx production. CONCLUSIONS: Acquisition of an additional plasmid harbouring ESBL genes is a step towards increasing the risk of O80 EHEC dissemination and represents a serious public health concern. The combination of azithromycin and imipenem reduced Stx production and suggests that this combination could be tested in clinical trials.

Diversity and trends in population structure of ESBL-producing Enterobacteriaceae in febrile urinary tract infections in children in France from 2014 to 2017.

BACKGROUND: The population structure of extraintestinal pathogenic Escherichia coli evolves over time, notably due to the emergence of antibiotic-resistant clones such as ESBL-producing Enterobacteriaceae (ESBL-E). OBJECTIVES: To analyse by WGS the genetic diversity of a large number of ESBL-E isolated from urinary tract infections in children from paediatric centres across France between 2014 and 2017 and collected by the National Observatory of febrile urinary tract infection (FUTI) caused by ESBL-E. METHODS: A total of 40 905 Enterobacteriaceae-positive urine cultures were identified. ESBL-E were found in 1983 samples (4.85%). WGS was performed on 251 ESBL-E causing FUTI. STs, core genome MLST (cgMLST), serotype, fimH allele, ESBL genes and presence of papGII key virulence factor were determined. RESULTS: E. coli and Klebsiella pneumoniae were found in 86.9% (218/251) and 11.2% (28/251) of cases, respectively. Several STs predominate among E. coli such as ST131, ST38, ST69, ST73, ST95, ST405, ST12 and ST1193, while no ST emerged in K. pneumoniae. E. coli ST131, ST38 and ST1193 increased during the study period, with a heterogeneity in papGII prevalence (64.5%, 35% and 20% respectively). Most isolates harboured the CTX-M type (97%) with a predominance of blaCTX-M-15. blaCTX-M-27, an emerging variant in E. coli, is found in various STs. cgMLST enabled discrimination of clusters within the main STs. CONCLUSIONS: The predominance of ST131, and the emergence of other STs such as ST38 and ST1193 combined with ESBL genes deserves close epidemiological surveillance considering their high threat in infectious disease. cgMLST could be a discriminant complementary tool for the analyses.

Association between National Treatment Guidelines for Upper Respiratory Tract Infections and Outpatient Pediatric Antibiotic Use in France: An Interrupted Time-Series Analysis.

OBJECTIVE: To test whether updated clinical practice guidelines for managing upper respiratory tract infections released in France in November 2011 were associated with changes in national outpatient pediatric antibiotic use. STUDY DESIGN: We performed an interrupted time-series analysis using national antibiotic dispensation data in French children from January 2009 to December 2017 (IQVIA Suivi de la Dispensation Médicale database). We described the overall evolution of antibiotic prescription rates and modeled the changes in the proportion of amoxicillin and the proportion of broad-spectrum antibiotics following the guidelines in 2 age groups (0-5 and 6-14 years old). RESULTS: We analyzed 123 million pediatric antibiotic prescriptions. The most commonly prescribed individual antibiotic agent was amoxicillin (37.7%). Over the study period, the annual antibiotic prescription rate decreased by 33.1% (from 1387 to 928 per 1000 pediatric inhabitants per year), consistently across age groups and major antibiotic agents except for amoxicillin (+14.4%). After the release of the guidelines, we observed a gradual increase in the proportion of amoxicillin (relative change 5 years postintervention of +64.3% [95% CI 51.6-80.1] and +28.4% [21.1-36.2] for children 0-5 and 6-14 years, respectively) concomitantly with a gradual decrease in the proportion of broad-spectrum antibiotics (relative change 5 years postintervention of -26.1% [-29.3, -23.7] and -19.8% [-22.1, -16.0] for children 0-5 and 6-14 years old, respectively). CONCLUSIONS: The 2011 guidelines for upper respiratory tract infections preceded changes in outpatient pediatric antibiotic use at the national level, with a replacement of broad-spectrum antibiotics by amoxicillin.

Epidemiology of Community-Onset Severe Bacterial Infections in Children and Its Evolution: A Population-Based Study in France.

OBJECTIVES: To describe the epidemiology of community-onset severe bacterial infections in children and its recent evolution. DESIGN: Prospective, observational, population-based study from 2009 to 2014. SETTING: An administrative area accounting for 13% of the French pediatric population. PATIENTS: All children 1 month to 16 years old who died before admission or were admitted to a PICU for a community-onset severe bacterial infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The incidence and mortality rate of community-onset severe bacterial infections were compared with data from a reference population-based study conducted between 2000 and 2006, that is, before national recommendations for antimeningococcal C and antipneumococcal generalized vaccinations. Among the 261 children included (median age 25 mo), 28 (10.7%) died. The main diagnoses were meningitis (n = 85; 32%) and purpura fulminans (n = 59; 22%). The most common isolated bacteria were Neisseria meningitidis (n = 75; 29%), including 47 (63%) cases of serogroup B and 15 (20%) serogroup C, Streptococcus pneumoniae (n = 49, 19%), and Staphylococcus aureus (n = 15; 6%). The incidence of community-onset severe bacterial infections was three per 100,000 person-years (95% CI, 2.6-3.3) and had decreased by 53% from the reference period. Mortality rate was 0.3 per 100,000 person-years (95% CI, 0.2-0.4) and had decreased by 73% from the reference period. The incidence of community-onset severe bacterial infections caused by N. meningitidis and S. pneumoniae was 0.8 and 0.5 per 100,000 person-years and had decreased by 70% and 67% from the reference period. The incidence of community-onset severe bacterial infections-related to Staphylococcus aureus was 0.16 per 100,000 person-years and had increased by 220% from the reference period. CONCLUSIONS: The incidence and mortality rate of community-onset severe bacterial infections, except for S. aureus infection, have decreased in France. N. meningitidis and S. pneumoniae continue to account for many infections, which indicates the need for better vaccination coverage and spectrum.

Association between SARS-CoV-2 infection and Kawasaki-like multisystem inflammatory syndrome: a retrospective matched case-control study, Paris, France, April to May 2020.

We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Kawasaki disease (KD)-like multisystem inflammatory syndrome in a retrospective case-control study in France. RT-PCR and serological tests revealed SARS-CoV-2 infection in 17/23 cases vs 11/102 controls (matched odds ratio: 26.4; 95% confidence interval: 6.0-116.9), indicating strong association between SARS-CoV-2 infection and KD-like illness. Clinicians should keep a high level of suspicion for KD-like illness during the COVID-19 pandemic.

Independent Host Factors and Bacterial Genetic Determinants of the Emergence and Dominance of Escherichia coli Sequence Type 131 CTX-M-27 in a Community Pediatric Cohort Study.

The recent emergence and diffusion in the community of Escherichia coli isolates belonging to the multidrug-resistant and CTX-M-27-producing sequence type 131 (ST131) C1-M27 cluster makes this cluster potentially as epidemic as the worldwide E. coli ST131 subclade C2 composed of multidrug-resistant isolates producing CTX-M-15. Thirty-five extended-spectrum beta-lactamase (ESBL)-producing ST131 isolates were identified in a cohort of 1,885 French children over a 5-year period. They were sequenced to characterize the ST131 E. coli isolates producing CTX-M-27 recently emerging in France. ST131 isolates producing CTX-M-27 (n = 17), and particularly those belonging to the C1-M27 cluster (n = 14), carried many resistance-encoding genes and predominantly an F1:A2:B20 plasmid type. In multivariate analysis, having been hospitalized since birth (odds ratio [OR], 10.9; 95% confidence interval [CI], 2.4 to 48.8; P = 0.002) and being cared for in a day care center (OR, 9.4; 95% CI, 1.5 to 59.0; P = 0.017) were independent risk factors for ST131 CTX-M-27 fecal carriage compared with ESBL-producing non-ST131 isolates. No independent risk factor was found when comparing CTX-M-15 (n = 11)- and CTX-M-1/14 (n = 7)-producing ST131 isolates with ESBL-producing non-ST131 isolates or with non-ESBL-producing isolates. Several factors may contribute to the increase in fecal carriage of CTX-M-27-producing E. coli isolates, namely, resistance to multiple antibiotics, capacity of the CTX-M-27 enzyme to hydrolyze both cefotaxime and ceftazidime, carriage of a peculiar F-type plasmid, and/or capacity to colonize children who have been hospitalized since birth or who attend day care centers.

Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) implementations led to major changes in serotype distribution and antibiotic resistance in carriage, accompanied by changes in antibiotic consumption. OBJECTIVES: To assess the dynamic patterns of antimicrobial non-susceptibility across non-PCV13 serotypes following PCV implementations. METHODS: We conducted a quasi-experimental interrupted time series analysis based on a 17 year French nationwide prospective cohort. From 2001 to 2018, 121 paediatricians obtained nasopharyngeal swabs from children with acute otitis media who were aged 6 months to 2 years. The main outcome was the rate of penicillin-non-susceptible pneumococci (PNSP), analysed by segmented regression. RESULTS: We enrolled 10 204 children. After PCV13 implementation, the PNSP rate decreased (-0.5% per month; 95% CI -0.9 to -0.1), then, after 2014, the rate slightly increased (+0.7% per month; 95% CI +0.2 to +1.2). Global antibiotic use within the previous 3 months decreased over the study period (-22.2%; 95% CI -33.0 to -11.3), but aminopenicillin use remained high. Among the main non-PCV13 serotypes, four dynamic patterns of penicillin susceptibility evolution were observed, including unexpected patterns of serotypes emerging while remaining or even becoming penicillin susceptible. In contrast to PNSP strains, for these latter patterns, the rate of co-colonization with Haemophilus influenzae increased concomitant with their emergence. CONCLUSIONS: In a context of continuing high antibiotic selective pressure, a progressive increase in PNSP rate was observed after 2014. However, we highlighted an unexpected variability in dynamic patterns of penicillin susceptibility among emerging non-PCV13 serotypes. Antibiotic resistance may not be the only adaptive mechanism to antimicrobial selective pressure, and co-colonization with H. influenzae may be involved.