François Angoulvant

Early Impact of 13-Valent Pneumococcal Conjugate Vaccine on Community-Acquired Pneumonia in Children

BACKGROUND Pneumococcal serotypes 1, 3, 5, 7F, and 19A were the most implicated in community-acquired pneumonia (CAP) after implementation of 7-valent pneumococcal conjugate vaccine (PCV7). In France, the switch from PCV7 to 13-valent pneumococcal conjugate vaccine (PCV13) occurred in June 2010. An active surveillance network was set up to analyze the impact of PCV13 on CAP. METHODS An observational prospective study performed in 8 pediatric emergency departments from June 2009 to May 2012 included all children between 1 month and 15 years of age with chest radiography-confirmed pneumonia. Three 1-year periods were defined: pre-PCV13, transitional, and post-PCV13. RESULTS During the 3-year study period, among the 953 274 pediatric emergency visits, 5645 children with CAP were included. CAP with pleural effusion and documented pneumococcal CAP were diagnosed in 365 and 136 patients, respectively. Despite an increase (4.5%) in number of pediatric emergency visits, cases of CAP decreased by 16% (2060 to 1725) between pre- and post-PCV13 periods. The decrease reached 32% in infants in the same periods (757 to 516; P < .001). Between pre- and post-PCV13 periods, the proportion of CAP patients with a C-reactive protein level >120 mg/dL decreased from 41.3% to 29.7% (P < .001), the number of pleural effusion cases decreased by 53% (167 to 79; P < .001) and the number of pneumococcal CAP cases decreased by 63% (64 to 24; P = .002). The number of additional PCV13 serotypes identified decreased by 74% (27 to 7). CONCLUSIONS Our data suggest a strong impact of PCV13 on CAP, pleural effusion, and documented pneumococcal pneumonia, particularly cases due to PCV13 serotypes.

Fitness cost of antibiotic susceptibility during bacterial infection

The quest to stem antibiotic resistance might be exacerbated by enhanced fitness and virulence displayed by the drug-resistant microbes. Fit foes Myriad publications from Consumer Reports to Mother Jones have warned us about the pending peril that is antibiotic resistance. Scary survival statistics and gloomy graphs that depict decreases in new antimicrobial drugs over time make clear the damper resistance puts on our ability to keep infectious diseases under control. Now, Roux et al. add another unwelcome wrinkle to the scenario—in addition to limiting our repertoire of curative drugs, antibiotic resistance also appears to enhance microbial fitness and virulence. Most studies have investigated the selective advantage sported by drug-resistant strains during antibiotic treatment. But outside of the therapeutic arena, the phenotypic changes that confer drug resistance are thought—without experimental validation—to be accompanied by the dampening of in vivo fitness, virulence, and transmission. In the new work, the authors used a saturated transposon library of Pseudomonas aeruginosa to pinpoint genes that contributed to in vivo fitness during lung infections in animal models and found that genes that conferred both intrinsic and acquired antibiotic resistance also imparted an in vivo fitness advantage to Pseudomonas during infection. The authors confirmed their findings in two additional pathogenic bacteria—Acinetobacter baumannii and Vibrio cholerae—in mouse and rabbit infection models. Together, these findings warn that the fight against antibiotic resistance might be harder than we thought, given the enhanced fitness and virulence of our drug-resistant adversaries. Advances in high-throughput DNA sequencing allow for a comprehensive analysis of bacterial genes that contribute to virulence in a specific infectious setting. Such information can yield new insights that affect decisions on how to best manage major public health issues such as the threat posed by increasing antimicrobial drug resistance. Much of the focus has been on the consequences of the selective advantage conferred on drug-resistant strains during antibiotic therapy. It is thought that the genetic and phenotypic changes that confer resistance also result in concomitant reductions in in vivo fitness, virulence, and transmission. However, experimental validation of this accepted paradigm is modest. Using a saturated transposon library of Pseudomonas aeruginosa, we identified genes across many functional categories and operons that contributed to maximal in vivo fitness during lung infections in animal models. Genes that bestowed both intrinsic and acquired antibiotic resistance provided a positive in vivo fitness advantage to P. aeruginosa during infection. We confirmed these findings in the pathogenic bacteria Acinetobacter baumannii and Vibrio cholerae using murine and rabbit infection models, respectively. Our results show that efforts to confront the worldwide increase in antibiotic resistance might be exacerbated by fitness advantages that enhance virulence in drug-resistant microbes.

Molecular Diagnosis of Saksenaea vasiformis Cutaneous Infection after Scorpion Sting in an Immunocompetent Adolescent

ABSTRACT We report the first case of cutaneous mucormycosis after a scorpion sting in Tunisia. Histopathology showed broad aseptate hyphae suggestive of a Zygomycete. Saksenaea vasiformis was identified by PCR amplification and sequencing of the fungal DNA on a cutaneous biopsy. Successful treatment was obtained by surgery and liposomal amphotericin B.

Inter-Observer Variability in Chest Radiograph Reading for Diagnosing Acute Lung Injury in Children

Acute lung injury (ALI), including its most serious form called acute respiratory distress syndrome (ARDS), is a devastating disease that can occur at any age. ALI/ARDS accounts for only 5–8% of admissions to pediatric intensive care units (PICUs) but is fatal in 30–60% of cases. International multicenter prospective studies are needed to better understand pediatric ALI/ARDS. However, a reproducible definition of ALI/ARDS is crucial to ensure that study populations are homogeneous. We designed a retrospective review to test the inter‐observer variability of chest radiograph interpretation for presence of the American‐European Consensus Conference (AECC) radiographic criterion for ALI/ARDS. The medical files of 24 children ventilated for ALI/ARDS in our PICU between January 1993 and December 2002 were reviewed. Five pediatric radiologists and five pediatric intensivists interpreted one frontal chest radiograph (FCR) per patient taken on the day of ALI/ARDS diagnosis. Each reader indicated whether the radiograph showed the AECC radiographic criterion for ALI/ARDS. Data analysis involved comparing each reader to all the others based on the raw agreement and Kappa coefficient (κ). Features in the 24 patients were consistent with earlier studies. Global inter‐observer agreement beyond chance was fair (κ = 0.29 ± 0.02) among the five radiologists (κ = 0.26 ± 0.05) and among the five intensivists (κ = 0.29 ± 0.05). Thus, considerable inter‐observer variability occurred in assessing the radiographic criterion for ALI/ARDS, as previously shown in adults. Given the low incidence of ALI/ARDS in children, this variability may have a large impact in studies of pediatric ALI/ARDS. Pediatr Pulmonol. 2008; 43:987–991.

Clinical Features and Outcome of Pediatric Neisseria meningitidis Serogroup W135 Infection: A Report of 5 Cases

We describe 5 pediatric cases of Neisseria meningitidis serogroup W135 infection. Infectious and/or reactive extrameningeal involvement was frequent. One patient had a persistent postmeningococcal inflammatory syndrome. Four of 5 isolates belonged to the clonal complex 37. The important risk of extrameningeal complications must be borne in mind when treating children with N. meningitidis W135 infection.

Necrotizing pneumonia in children: report of 41 cases between 2006 and 2011 in a French tertiary care center.

Forty-one children hospitalized for necrotizing pneumonia were retrospectively analyzed. Necrotizing pneumonia represented 0.8% of community-acquired pneumonia and 6% of hospitalized community-acquired pneumonia. The chest radiograph revealed necrosis on admission in onethird of cases. Twenty-one cases (51%) were documented, including 13 Staphylococcus aureus, all Panton-Valentine leukocidin positive, 7 Streptococcus pneumoniae and 1 Fusobacterium nucleatum.

Effect of Nebulized Hypertonic Saline Treatment in Emergency Departments on the Hospitalization Rate for Acute Bronchiolitis: A Randomized Clinical Trial

Importance Acute bronchiolitis is the leading cause of hospitalization among infants. Previous studies, underpowered to examine hospital admission, have found a limited benefit of nebulized hypertonic saline (HS) treatment in the pediatric emergency department (ED). Objective To examine whether HS nebulization treatment would decrease the hospital admission rate among infants with a first episode of acute bronchiolitis. Design, Setting, and Participants The Efficacy of 3% Hypertonic Saline in Acute Viral Bronchiolitis (GUERANDE) study was a multicenter, double-blind randomized clinical trial on 2 parallel groups conducted during 2 bronchiolitis seasons (October through March) from October 15, 2012, through April 15, 2014, at 24 French pediatric EDs. Among the 2445 infants (6 weeks to 12 months of age) assessed for inclusion, 777 with a first episode of acute bronchiolitis with respiratory distress and no chronic medical condition were included. Interventions Two 20-minute nebulization treatments of 4 mL of HS, 3%, or 4 mL of normal saline (NS), 0.9%, given 20 minutes apart. Main Outcomes and Measures Hospital admission rate in the 24 hours after enrollment. Results Of the 777 infants included in the study (median age, 3 months; interquartile range, 2-5 months; 468 [60.2%] male), 385 (49.5%) were randomized to the HS group and 387 (49.8%) to the NS group (5 patients did not receive treatment). By 24 hours, 185 of 385 infants (48.1%) in the HS group were admitted compared with 202 of 387 infants (52.2%) in the NS group. The risk difference for hospitalizations was not significant according to the mixed-effects regression model (adjusted risk difference, –3.2%; 95% CI, –8.7% to 2.2%; P = .25). The mean (SD) Respiratory Distress Assessment Instrument score improvement was greater in the HS group (–3.1 [3.2]) than in the NS group (–2.4 [3.3]) (adjusted difference, –0.7; 95% CI, –1.2 to –0.2; P = .006) and similarly for the Respiratory Assessment Change Score. Mild adverse events, such as worsening of cough, occurred more frequently among children in the HS group (35 of 392 [8.9%]) than among those in the NS group (15 of 384 [3.9%]) (risk difference, 5.0%; 95% CI, 1.6%-8.4%; P = .005), with no serious adverse events. Conclusions and Relevance Nebulized HS treatment did not significantly reduce the rate of hospital admissions among infants with a first episode of acute moderate to severe bronchiolitis who were admitted to the pediatric ED relative to NS, but mild adverse events were more frequent in the HS group. Trial Registration clinicaltrials.gov Identifier: NCT01777347

Validation of a Novel Assay to Distinguish Bacterial and Viral Infections

A novel 3-protein host-assay’s diagnostic performance for distinguishing between bacterial and viral etiologies is validated in a double-blind, investigator-driven study in febrile children. BACKGROUND: Reliably distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse. A novel assay that integrates measurements of blood-borne host-proteins (tumor necrosis factor-related apoptosis-inducing ligand, interferon γ-induced protein-10, and C-reactive protein [CRP]) was developed to assist in differentiation between bacterial and viral disease. METHODS: We performed double-blind, multicenter assay evaluation using serum remnants collected at 5 pediatric emergency departments and 2 wards from children ≥3 months to ≤18 years without (n = 68) and with (n = 529) suspicion of acute infection. Infectious cohort inclusion criteria were fever ≥38°C and symptom duration ≤7 days. The reference standard diagnosis was based on predetermined criteria plus adjudication by experts blinded to assay results. Assay performers were blinded to the reference standard. Assay cutoffs were predefined. RESULTS: Of 529 potentially eligible patients with suspected acute infection, 100 did not fulfill infectious inclusion criteria and 68 had insufficient serum. The resulting cohort included 361 patients, with 239 viral, 68 bacterial, and 54 indeterminate reference standard diagnoses. The assay distinguished between bacterial and viral patients with 93.8% sensitivity (95% confidence interval: 87.8%–99.8%) and 89.8% specificity (85.6%–94.0%); 11.7% had an equivocal assay outcome. The assay outperformed CRP (cutoff 40 mg/L; sensitivity 88.2% [80.4%–96.1%], specificity 73.2% [67.6%–78.9%]) and procalcitonin testing (cutoff 0.5 ng/mL; sensitivity 63.1% [51.0%–75.1%], specificity 82.3% [77.1%–87.5%]). CONCLUSIONS: Double-blinded evaluation confirmed high assay performance in febrile children. Assay was significantly more accurate than CRP, procalcitonin, and routine laboratory parameters. Additional studies are warranted to support its potential to improve antimicrobial treatment decisions.

Aetiology and epidemiology of fever in children presenting to the emergency department of a French paediatric tertiary care centre after international travel

Objective As few data are available on the causes of fever in children returning from international travel, the authors studied children presenting to a French tertiary care centre with fever. Methods Children presenting to the emergency department of the Robert Debré Paediatric Hospital, Paris, France between July and December 2007 with fever that occurred within 3 months of a stay abroad were included in this retrospective study. Results The children (n=538) had most commonly visited North Africa (NA) (n=214), sub-Saharan Africa (SSA) (n=185) and Europe (n=67). Their median age was 2.8 years (IQR 1.4–5.8). The median time between their return to France and the onset of fever was 5 days (IQR 0–18). Cosmopolitan infections represented 85% of the established diagnoses (97.8% and 63.9% in the children returning from NA and SSA, respectively). Fever of unknown origin accounted for 19.3% of cases. Malaria was the leading tropical infection. Excluding malaria, diarrhoeal diseases were more frequent in the children returning from NA (38.5%) than in those returning from SSA (24.5%). Malaria was associated with stays in endemic countries that exceeded 30 days (OR 3.13, 95% CI 1.02 to 9.59). Conclusion Cosmopolitan infections are the leading cause of fever in French children returning from tropical and subtropical areas. However, all febrile children who have returned from an endemic area should be tested for malaria.

Impact of unlabeled French antibiotic guidelines on antibiotic prescriptions for acute respiratory tract infections in 7 Pediatric Emergency Departments, 2009-2012.

From November 2009 to October 2012, implementation of guidelines, unlabeled by the French Agency of Health Products, changed the categories of antibiotics prescribed for acute respiratory tract infections in 7 pediatric emergency departments. During the study, 36,413 acute respiratory tract infections-related antibiotic prescriptions were prescribed. Amoxicillin prescriptions rose from 30.0% to 84.7%, while amoxicillin-clavulanate and cefpodoxime prescriptions decreased to 10.2% and 2.5%, respectively.