Assessment of adherence to the 2020 Surviving Sepsis Campaign guidelines for fluid resuscitation in children with suspected septic shock in paediatric emergency departments: a prospective multicentre study.

BACKGROUND: Paediatric sepsis is the leading cause of death in children under 5 years. No studies have evaluated the application of the Surviving Sepsis Campaign 2020 (SSC-2020) guidelines in paediatric emergency departments (PEDs). OBJECTIVE: To assess physician adherence to the SSC-2020 fluid resuscitation guidelines in children with suspected septic shock in PEDs. METHODS: This was a prospective multicentre observational study conducted in 21 French hospitals over 5 sequential weeks, between November 2021 and March 2022. Children with suspected septic shock and who received antimicrobial therapy within 72 hours were included. Primary outcome was SSC-2020 fluid resuscitation guidelines adherence (low 0-24%; moderate 25-74%; high 75-100%) according to: bolus volume of 10-20 mL/kg each, exclusive administration of balanced crystalloids at 1 and 24 hours of management, and initiation of fluid resuscitation within 1 hour of septic shock recognition. RESULTS: 63 children were included. 10 (16%) children had severe sepsis and 2 (3%) met the definition of septic shock. Compared with the SSC-2020 guidelines, 43 (68%) patients received boluses of 10-20 mL/kg; fluid resuscitation was initiated within 1 hour of septic shock recognition in 42 (76%) cases; balanced crystalloids were the only fluids administrated in 35 (56%) and 34 (55%) children at 1 and 24 hours of management, respectively. Main barriers reported by physicians were difficult intravenous access (43%), lack of team training (29%), workload constraints (28%), and absence or out-of-date protocols (24%). CONCLUSIONS: This study found high adherence for fluid resuscitation initiation but moderate adherence for bolus volume and fluid choice. TRIAL REGISTRATION NUMBER: NCT05066464.

Predictors of the Outcome at 2 Years in Neonates With Congenital Cytomegalovirus Infection.

BACKGROUND: Approximately 20% of neonates with congenital cytomegalovirus (cCMV) develop long-term sequelae. The ability to accurately predict long-term outcomes as early as the neonatal period would help to provide for appropriate parental counseling and treatment indications. With this study, we aimed to identify neonatal predictive markers of cCMV long-term outcomes. METHODS: As this study's subjects, we chose neonates diagnosed with cCMV in 13 hospitals throughout France recruited from 2013 to 2017 and evaluated for at least 2 years with thorough clinical, audiology, and imaging evaluations and psychomotor development tests. RESULTS: A total of 253 neonates were included, and 3 were later excluded because of the identification of a genetic disorder. A total of 227 were followed up for 2 years: 187/227 (82%) and 34/227 (15%) were infected after a maternal primary or nonprimary infection, respectively, 91/227 (40%) were symptomatic at birth, and 44/227 (19%) had cCMV sequelae. Maternal primary infection in the first trimester was the strongest prognosis factor (odds ratio = 38.34 [95% confidence interval, 5.02-293], P < .001). A predictive model of no risk of sequelae at 2 years of age according to normal hearing loss at birth, normal cerebral ultrasound, and normal platelet count had 98% specificity, 69% sensitivity, and 0.89 area under the curve (95% confidence interval, 0.83-0.96). CONCLUSIONS: In the studied population, children with normal hearing at birth, normal platelet count at birth, and a normal cranial ultrasound had no risk of neurologic sequelae and a low risk of delayed unilateral sensorineural hearing loss. The use of this model based on readily available neonatal markers should help clinicians establish a personalized care pathway for each cCMV neonate.

Anti-infective treatment of gastro-intestinal tract infections in children.

Gastroenteritis is most often viral in origin and Rotavirus and Norovirus most frequently implicated in young children. Stool-based multiplex Polymerase Chain Reaction (PCR) can detect bacteria, viruses or parasites that may or may not be responsible for gastroenteritis (colonization). While the etiological profile of these digestive infections has greatly benefited from PCR, in the absence of underlying pathologies the presence of potential pathogens does not justify anti-infectious treatment. Indeed, very few bacterial causes require antibiotic treatment, apart from shigellosis, severe forms of salmonellosis and a few Campylobacter sp. infections. The development of antibiotic resistance in Salmonella sp., Shigella sp. and Campylobacter sp. is a cause for concern worldwide, limiting therapeutic options. The antibiotics proposed in this guide are in line with the joint recommendations of the European Society of Pediatric Infectious Diseases and the European Society of Pediatric Gastroenterology and Nutrition. Azithromycin is preferentially used to treat infections with Shigella sp. or Campylobacter sp. Ceftriaxone and ciprofloxacin are recommended for salmonellosis requiring antibiotic therapy. Empirical treatments without bacterial identification are not indicated except in cases of severe sepsis or in subjects at risk (e.g., sickle-cell disease). Metronidazole should be prescribed only for acute intestinal amebiasis after microbiological confirmation.

Antimicrobial treatment of skin and soft tissue infections.

Bacterial skin infections are common in children, and frequently do not require systemic antibiotic therapy, particularly for superficial forms. In these cases, washing (with soap and water) and careful rinsing of the lesion are the key points of treatment. A semiotic analysis must precede any therapeutic decision to assess the appropriateness of antibiotic therapy, need for drainage (which may be spontaneous or surgical) and possible existence of symptoms related to toxin production, which are frequent signs of severity. The bacterial species most frequently implicated in children are Staphylococcus aureus and Streptococcus pyogenes. Given the low incidence of methicillin-resistant S. aureus in France (<10%), the first-line antibiotic treatment is amoxicillin-clavulanate, to which an anti-toxin treatment such as clindamycin may be added for patients with overt toxin signs.

A French study of cocaine intoxication/exposure in children (2010-2020).

BACKGROUND AND OBJECTIVE: In the European Union, the record of cocaine-related seizures indicates an expanding supply. The purity has also been increasing. The health impact of these trends remains poorly documented, in particular, the changes and clinical manifestations of intoxication in young children. We attempted to evaluate the trend in French pediatric admissions for cocaine intoxication/exposure over an 11-year period (2010-2020). METHODS: A retrospective, national, multicenter, study of a pediatric cohort. All children less than 15 years of age admitted to a tertiary-level pediatric emergency unit for proven cocaine intoxication (compatible symptoms and positive toxicological screening) during the reference period were included. RESULTS: Seventy-four children were included. Forty-six percent were less than 6 years old. Annual admissions increased by a factor of 8 over 11 years (+700%) and 57% of all cases were admitted in the last two years. The main clinical signs were neurologic (59%) followed by cardiovascular symptoms (34%). Twelve patients were transferred to the pediatric intensive care unit. Factors significantly associated with the risk of being transferred to the pediatric intensive care unit were initial admission to the pediatric resuscitation area (P < 0.001), respiratory impairment (P < 0.01), mydriasis (P < 0.01), cardiovascular symptoms (P = 0.014), age of less than 2 years (P = 0.014). Blood and/or urine toxicological screening isolated eighteen other substances besides cocaine in 46 children (66%). CONCLUSION: Children are collateral victims of the changing trends in cocaine availability, use and purity. Admissions of intoxicated children to pediatric emergency departments are more frequent and there is an increase in severe presentations. Therefore, this is a growing public health concern.

Clinical Value of Serial Quantitative Analysis of Cytomegalovirus DNA in Blood and Saliva Over the First 24 Months of Life in Congenital Infection: The French Cymepedia Cohort.

OBJECTIVE: To evaluate cytomegalovirus (CMV) viral load dynamics in blood and saliva during the first 2 years of life in symptomatic and asymptomatic infected infants and to identify whether these kinetics could have practical clinical implications. STUDY DESIGN: The Cymepedia cohort prospectively included 256 congenitally infected neonates followed for 2 years. Whole blood and saliva were collected at inclusion and months 4 and 12, and saliva at months 18 and 24. Real-time CMV polymerase chain reaction (PCR) was performed, results expressed as log10 IU/mL in blood and in copies per milliliter in saliva. RESULTS: Viral load in saliva progressively decreased from 7.5 log10 at birth to 3.3 log10 at month 24. CMV PCR in saliva was positive in 100% and 96% of infants at 6 and 12 months, respectively. In the first month of life, neonatal saliva viral load of less than 5 log10 was related to a late CMV transplacental passage. Detection in blood was positive in 92% of neonates (147/159) in the first month of life. No viral load threshold values in blood or saliva could be associated with a high risk of sequelae. Neonatal blood viral load of less than 3 log10 IU/mL had a 100% negative predictive value for long-term sequelae. CONCLUSIONS: Viral loads in blood and saliva by CMV PCR testing in congenital infection fall over the first 24 months. In this study of infants affected mainly after primary maternal infection during pregnancy, all salivary samples were positive in the first 6 months of life and sequelae were not seen in infants with neonatal blood viral load of less than 3 log10 IU/mL.

Developing and Validating an Individual-Level Deprivation Index for Children's Health in France.

BACKGROUND: Deprivation generates many health inequalities. This has to be taken in account to enhance appropriate access to care. This study aimed to develop and validate a pediatric individual-level index measuring deprivation, usable in clinical practice and in public health. METHODS: The French Individual Child Deprivation Index (FrenChILD-Index) was designed in four phases: item generation then reduction using the literature review and expert opinions, and index derivation then validation using a cross-sectional study in two emergency departments. During these last two phases, concordance with a blinded evaluation by an expert enabled us to determine thresholds for two levels of moderate and severe deprivation. RESULTS: The generation and reduction phases retained 13 items. These were administered to 986 children for the derivation and validation phases. In the validation phase, the final 12 items of the FrenChILD-Index showed for moderate deprivation (requiring single specific care for deprived children) a sensitivity of 96.0% [92.6; 98.7] and specificity of 68.3% [65.2; 71.4]. For severe deprivation (requiring a multidisciplinary level of care), the sensitivity was 96.3% [92.7; 100] and specificity was 91.1% [89.2; 92.9]. CONCLUSIONS: The FrenChILD-Index is the first pediatric individual-level index of deprivation validated in Europe. It enables clinical practice to address the social determinants of health and meet public health goals.

Shift in Clinical Profile of Hospitalized Pneumonia in Children in the Non-pharmaceutical Interventions Period During the COVID-19 Pandemic: A Prospective Multicenter Study.

Non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 were implemented in March 2020. These measures were followed by a major impact on viral and non-viral diseases. We aimed to assess the impact of NPI implementation in France on hospitalized community-acquired pneumonia (hCAP) frequency and the clinical and biological characteristics of the remaining cases in children. We performed a quasi-experimental interrupted time-series analysis. Between June 2014 and December 2020, eight pediatric emergency departments throughout France reported prospectively all cases of hCAP in children from age 1 month to 15 years. We estimated the impact on the monthly number of hCAP using segmented linear regression with autoregressive error model. We included 2,972 hCAP cases; 115 occurred during the NPI implementation period. We observed a sharp decrease in the monthly number of hCAP after NPI implementation [-63.0% (95 confidence interval, -86.8 to -39.2%); p < 0.001]. Children with hCAP were significantly older during than before the NPI period (median age, 3.9 vs. 2.3 years; p < 0.0001), and we observed a higher proportion of low inflammatory marker status (43.5 vs. 33.1%; p = 0.02). Furthermore, we observed a trend with a decrease in the proportion of cases with pleural effusion (5.3% during the NPI period vs. 10.9% before the NPI; p = 0.06). NPI implementation during the COVID-19 (coronavirus disease 2019) pandemic led not only to a strong decrease in the number of hCAP cases but also a modification in the clinical profile of children affected, which may reflect a change in pathogens involved.

Diagnostic Accuracy of Routinely Available Biomarkers to Predict Bacteremia in Children With Community-Acquired Pneumonia: A Secondary Analysis of the GPIP/ACTIV Pneumonia Study in France, 2009-2018.

Objective(s): Blood cultures (BC), when performed in children seen in the emergency department with community-acquired pneumonia (CAP), are most of the time sterile. We described the diagnostic accuracy of white blood cells (WBC), absolute neutrophils count (ANC), C-reactive protein (CRP), and procalcitonin (PCT) to predict blood culture (BC) result in childhood CAP. Study Design: Secondary analysis of a prospective study carried out in eight pediatric emergency departments (France, 2009-2018), including children (≤15 years) with CAP. Analyses involved univariate comparisons and ROC curves. Results: We included 13,752 children with CAP. BC was positive in 137 (3.6%) of the 3,829 children (mean age 3.7 years) in whom it was performed, mostly with Streptococcus pneumoniae (n = 107). In children with bacteremia, ANC, CRP and PCT levels were higher (median 12,256 vs. 9,251/mm3, 223 vs. 72 mg/L and 8.6 vs. 1.0 ng/mL, respectively; p ≤ 0.002), but WBC levels were not. The area under the ROC curve of PCT (0.73 [95%CI 0.64-0.82]) was significantly higher (p ≤ 0.01) than that of WBC (0.51 [0.43-0.60]) and of ANC (0.55 [0.46-0.64]), but not than that of CRP (0.66 [0.56-0.76]; p = 0.21). CRP and PCT thresholds that provided a sensitivity of at least 90% were 30 mg/L and 0.25 ng/mL, respectively, for a specificity of 25.4 and 23.4%, respectively. CRP and PCT thresholds that provided a specificity of at least 90% were 300 mg/L and 20 ng/mL, respectively, for a sensitivity of 31.3 and 28.9%, respectively. Conclusions: PCT and CRP are the best routinely available predictive biomarkers of bacteremia in childhood CAP.

Clinical course and cost assessment of infants with a first episode of acute bronchiolitis presenting to the emergency department: Data from the GUERANDE clinical trial.

INTRODUCTION: Bronchiolitis is the leading cause of hospitalization for infants but its economic burden is not well documented. Our objective was to describe the clinical evolution and to assess the 1-month cost of a first episode of acute bronchiolitis presenting to the emergency department (ED). METHODS: Our study was an epidemiologic analysis and a cost study of the cohort drawn from the clinical trial GUERANDE, conducted in 24 French pediatric EDs. Infants of 6 weeks to 12 months of age presenting at pediatric EDs with a first episode of bronchiolitis were eligible. The costs considered were collected from a societal viewpoint, according to the recommendations of the French National Health Authority. RESULTS: A total of 777 infants were included with a median age of 4 months. A total of 57% were hospitalized during the month following the first consultation in the ED, including 28 (3.6%) in an intensive care unit. The mean length of stay was 4.2 days (SD = 3.7). The average time to relief of all symptoms was 13 days (SD = 7). Average total cost per patient was €1919 (95% confidence interval: 1756-2138) from a societal perspective, mostly due to hospitalization cost. The estimated annual cost of bronchiolitis in infants was evaluated to be between €160 and €273 million in France. DISCUSSION: Bronchiolitis represent a high cost for the health care system and broadly for society, with hospitalizations costs being the main cost driver. Thus significant investments should be made to develop innovative therapies, to reduce the number of hospitalizations and length of stay.

Unintentional cannabis poisoning in toddlers: A one year study in Marseille.

France is the country with the highest prevalence of cannabis use in Europe, despite the fact that cannabis has not been legalized. This prevalence is still increasing along with THC content in cannabis products. In the meantime, unintentional cannabis poisoning by ingestion in toddlers is constantly rising. The aim of this study was to document children's cannabis poisoning biologically and clinically. Plasma and urine samples were extracted by solid phase extraction and analyzed by liquid chromatography coupled to tandem mass spectrometry. Children under 4 years old admitted in pediatric emergency departments for cannabis intoxication between February 1st 2019 and January 31st 2020 were included in this study. Twenty-six children were included (14 female and 12 male), the mean age was 17 months (10-41 months). THC, 11-OH-THC and THC-COOH plasma concentrations ranged from 2.9 to 93 ng/mL, 2.6-65 ng/mL and 29-914 ng/mL, respectively. The most frequent symptoms were drowsiness and hypotonia. Six critical cases were observed: 5 coma and 1 respiratory depression. All children having THC plasma concentrations over 60 ng/mL were in coma. Cannabis poisoning in toddlers become more frequent, 9 cases/year were reported in Marseille in 2007 and 26 cases/year in this study. There is a rising in severe clinical cases, particularly coma. These observations could be explained by an increase in THC content in cannabis products, and a trivialization of cannabis consumption. The unintentional ingestion of cannabis by children is a serious public health concern, and cannabis legalization could worsen this problem.

Circulation of enterovirus A71 during 2019-2020, Marseille, France.

Enteroviruses A71 (EVs-A71) are known to cause serious neurological infections, especially in the pediatric population. We report here eight cases of EV-A71 infection diagnosed in Marseille over the past 2 years (seven cases in 2019 and one case in 2020). Only children under 5 years of age were affected, including one case of acute flaccid paralysis. Viral RNA was detected by RT-PCR in peripheral samples for all cases (feces and upper respiratory samples). Phylogenetic analyses based on VP1 and 2C3C coding regions revealed that all these cases of EV-A71 infection were caused by viruses belonging to the subgenogroup C1 that currently circulates in Europe and that these viruses are genetically closed to other EVs-A71 recently detected in European countries. These data therefore reinforce the usefulness of the enterovirus surveillance network and the need for systematic screening for EV-A71 in case of an enteroviral infection. This study therefore suggests that the systematic screening for EV-A71 in case of enteroviral infection could provide additional data for enterovirus surveillance networks.

Impact of Viral Seasonal Outbreaks on Crowding and Health Care Quality in Pediatric Emergency Departments.

ABSTRACT: In pediatric emergency departments (PEDs), seasonal viral outbreaks are believed to be associated with an increase of workload, but no quantification of this impact has been published. A retrospective cross-sectional study aimed to measure this impact on crowding and health care quality in PED. The study was performed in 1 PED for 3 years. Visits related to bronchiolitis, influenza, and gastroenteritis were defined using discharge diagnoses. The daily epidemic load (DEL) was the proportion of visits related to one of these diagnoses. The daily mean of 8 crowding indicators (selected in a published Delphi study) was used. A total of 93,976 children were admitted (bronchiolitis, 2253; influenza, 1277; gastroenteritis, 7678). The mean DEL was 10.4% (maximum, 33.6%). The correlation between the DEL and each indicator was significant. The correlation was stronger for bronchiolitis (Pearson R from 0.171 for number of hospitalization to 0.358 for length of stay). Between the first and fourth quartiles of the DEL, a significant increase, between 50% (patients left without being seen) and 8% (patient physician ratio), of all the indicators was observed. In conclusion, seasonal viral outbreaks have a strong impact on crowding and quality of care. The evolution of "patients left without being seen" between the first and fourth quartiles of DEL could be used as an indicator reflecting the capacity of adaptation of an emergency department to outbreaks.

Real-Time Measurement of Crowding in Pediatric Emergency Department: Derivation and Validation Using Consensual Perception of Crowding (SOTU-PED).

ABSTRACT: Our study aimed to develop and validate a real-time crowding composite scale for pediatric emergency department (PED). The study took place in one teaching PED for 2 months. The outcome was the perception of crowding evaluated by triage nurses and pediatricians on a 10-level Likert scale. Triage nurses evaluated crowding at each moment of a child's admission and pediatrician at each moment of a child's discharge. The outcome was the hourly mean of all evaluations of crowding (hourly crowding perception). For analysis, originally, we only selected hours during which more than 2 nurses and more than 2 pediatricians evaluated crowding and, moreover, during which evaluations were the most consensual. As predictors, we used hourly means of 10 objective crowding indicators previously selected as consensual in a published French national Delphi study and collected automatically in our software system. The model (SOTU-PED) was developed over a 1-month data set using a backward multivariable linear regression model. Then, we applied the SOTU-PED model on a 1-month validation data set. During the study period, 7341 children were admitted in the PED. The outcome was available for 1352/1392 hours, among which 639 were included in the analysis as "consensual hours." Five indicators were included in the final model, the SOTU-PED (R2 = 0.718). On the validation data set, the correlation between the outcome (perception of crowding) and the SOTU-PED was 0.824. To predict crowded hours (hourly crowding perception >5), the area under the curve was 0.957 (0.933-0.980). The positive and negative likelihood ratios were 8.16 (3.82-17.43) and 0.153 (0.111-0.223), respectively. Using a simple model, it is possible to estimate in real time how crowded a PED is.

Morbidity and Mortality Patterns in Children Admitted to Hospital in Thai Binh, Vietnam: A Five-year Descriptive Study with a Focus on Infectious Diseases.

The objective of this study was to describe the overall pattern of morbidity and mortality of children seen at the Thai Binh Paediatric Hospital in Vietnam, with a focus on infectious diseases. A retrospective review of hospitalisation records was conducted from 1 January 2015 to 31 December 2019. Data were obtained from a total of 113,999 records. The median age of patients was 18 months, with 84.0% of patients aged <5 years. Infectious diseases accounted for 61.0% of all cases. The most prevalent diseases were lower respiratory tract infections (32.8%), followed by gastrointestinal infections (13.3%) and confirmed influenza (5.4%). Most infections were not microbiologically documented. A total of 81.4% patients received at least one antibiotic. Most patients (97.0%) were hospitalised for less than 15 days. Regarding outcomes, 87.8% patients were discharged home with a favourable outcome. Twelve percent were transferred to the Vietnam National Children's Hospital because their condition had worsened and 0.1% died. In total, infectious diseases accounted for 40.4% of deaths, followed by neonatal disorders (34.6%). Our data serves a basis for the identification of needs for diagnostic tools and for future evaluation of the effect of the targeted implementation of such facilities. Point-of-care tests, including real-time polymerase chain reaction assays to identify common pathogens should be implemented for more accurate diagnosis and more appropriate antibiotic use.

Factors Associated With Severe SARS-CoV-2 Infection.

BACKGROUND: Initial reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children suggested that very young age and comorbidities may increase risk of severe evolution, but these findings remained to be confirmed. We aimed to analyze the clinical spectrum of hospitalized pediatric SARS-CoV-2 infection and predictors of severe disease evolution. METHODS: We conducted a French national prospective surveillance of children hospitalized with SARS-CoV-2 infection. We included all children with confirmed SARS-CoV-2 infection in 60 hospitals during February 15 to June 1, 2020. The main outcome was the proportion of children with severe disease, defined by hemodynamic or ventilatory (invasive or not) support requirement. RESULTS: We included 397 hospitalized children with SARS-CoV-2 infection. We identified several clinical patterns, ranging from paucisymptomatic children, admitted for surveillance, to lower respiratory tract infection or multisystem inflammatory syndrome in children. Children <90 days old accounted for 37% of cases (145 of 397), but only 4 (3%) had severe disease. Excluding children with multisystem inflammatory syndrome in children (n = 29) and hospitalized for a diagnosis not related to SARS-CoV-2 (n = 62), 23 of 306 (11%) children had severe disease, including 6 deaths. Factors independently associated with severity were age ≥10 years (odds ratio [OR] = 3.4, 95% confidence interval: 1.1-10.3), hypoxemia (OR = 8.9 [2.6-29.7]), C-reactive protein level ≥80 mg/L (OR = 6.6 [1.4-27.5]). CONCLUSIONS: In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children <90 days old were at the lowest risk of severe disease evolution. This may help physicians to better identify risk of severe disease progression in children.

Risk Factors for Severe Pneumonia According to WHO 2005 Criteria Definition Among Children <5 Years of Age in Thai Binh, Vietnam: A Case-Control Study.

Vietnam is one of the 15 countries where the prevalence of child pneumonia is highest. It is a major cause of admission in pediatric hospitals. However, little is known on the burden of severe pneumonia and their risk factors in children <5 years of age in Vietnam. A case-control study was conducted among children aged 2-59 months presenting with pneumonia at the Pediatric Provincial Hospital of Thai Binh. Cases were children with severe pneumonia while controls included those with non-severe pneumonia as defined by the World Health Organization (WHO) classification of 2005. Eighty-three cases and 83 controls were included. Sex ratio was 2.19. Children with severe pneumonia were significantly less likely to receive antibiotics preadmission compared to children with non-severe pneumonia [odds ratio (OR) = 0.16, 95% confidence interval (CI) = 0.06-0.42]. The main risk factors of severe pneumonia were a lack of immunization (OR = 4.77, 95% CI = 1.80-12.65), an exposure to cigarette smoke (OR = 3.87, 95% CI = 1.62-9.23), and having a mother with a low level of education. Children with severe pneumonia were 25 times more likely to present with associated measles with p < 0.0001 and five times more likely to present with diarrhea than children with non-severe pneumonia (p < 0.0001). Improving immunization coverage, educating parents about the risks of passive smoking and the recognition of respiratory distress signs, and facilitating early antibiotic access for infants with acute pulmonary disease should reduce the burden of such illnesses. To implement a national, multicenter study about pneumonia in children, more precise inclusion criteria should be chosen, including radiological and/or biological assessment.

Long-term Association of 13-Valent Pneumococcal Conjugate Vaccine Implementation With Rates of Community-Acquired Pneumonia in Children.

Importance: In several countries, 5 years after 13-valent pneumococcal conjugate vaccine (PCV13) implementation, serotype replacement has been reported for invasive pneumococcal disease, which raises concerns about the long-term outcome of PCV13 implementation. The long-term effect of vaccination on community-acquired pneumonia (CAP) remains unknown. Objective: To assess the long-term outcome of PCV13 implementation on CAP in children. Design, Setting, and Participants: This quasi-experimental, population-based, interrupted time-series analysis was based on a prospective multicenter study conducted from June 2009 to May 2017 in 8 French pediatric emergency departments. All patients 15 years and younger with chest radiography-confirmed CAP were included. Exposures: Community-acquired pneumonia. Main Outcomes and Measures: The number of CAP cases per 1000 pediatric emergency department visits over time, analyzed using a segmented regression model, adjusted for influenza-like illness syndromes. Results: We enrolled 12 587 children with CAP, including 673 cases of CAP with pleural effusion (5.3%), 4273 cases of CAP requiring hospitalization (33.9%), 2379 cases of CAP with high inflammatory biomarkers (18.9%), and 221 cases of proven pneumococcal CAP (1.8%). The implementation of PCV13 in 2010 was followed by a sharp decrease in the frequency of CAP (-0.8% per month [95% CI, -1.0% to -0.5% per month]), from 6.3 to 3.5 cases of CAP per 1000 pediatric emergency department visits until May 2014, then a slight increase since June 2014 (0.9% per month [95% CI, 0.4%-1.4% per month]), until 3.8 cases of CAP per 1000 pediatric emergency department visits in May 2017. There were marked immediate decreases in cases of CAP with pleural effusion (-48% [95% CI, -84% to -12%]), CAP requiring hospitalization (-30% [95% CI, -56% to -5%]), and CAP with high inflammatory biomarkers (-30% [95% CI, -54% to -6%]), without any rebound thereafter. Conclusions and Relevance: The changes associated with PCV13 use 7 years after implementation remain substantial, especially for CAP with pleural effusion, CAP requiring hospitalization, and CAP with high inflammatory biomarkers. Emerging non-PCV13 serotypes may be less likely involved in severe CAP than invasive pneumococcal disease.