[Antibiotic strategy in pleural empyema in children: Consensus by the DELPHI method]. / Stratégie antibiotique dans les pleurésies en pédiatrie : consensus par méthode DELPHI.

INTRODUCTION: The evolution of the microbial epidemiology of pleuropulmonary infections complicating community-acquired pneumonia has resulted in a change in empirical or targeted antibiotic therapy in children in the post Prevenar 13 era. The three main pathogens involved in pleural empyema in children are Streptococcus pneumoniae, Staphylococcus aureus and group A Streptococcus. METHODS: A questionnaire according to the DELPHI method was sent to experts in the field (paediatric pulmonologists and infectious disease specialists) in France with the purpose of reaching a consensus on the conservative antibiotic treatment of pleural empyema in children. Two rounds were completed as part of this DELPHI process. RESULTS: Our work has shown that in the absence of clinical signs of severity, the prescription of an intravenous monotherapy is consensual but there is no agreement on the choice of drug to use. A consensus was also reached on treatment adjustment based on the results of blood cultures, the non-systematic use of a combination therapy, the need for continued oral therapy and the lack of impact of pleural drainage on infection control. On the other hand, after the second round of DELPHI, there was no consensus on the duration of intravenous antibiotic therapy and on the treatment of severe pleural empyema, especially when caused by Staphylococci. CONCLUSIONS: The result of this work highlights the needed for new French recommendations based on the evolution of microbial epidemiology in the post PCV13 era.

Bacterial killing is enhanced by exogenous administration of lysozyme in the lungs.

OBJECTIVE: Lysozyme, a 14-kDa protein, is one of the most abundant antimicrobials in the lungs. Its concentration in airway surface sufficient to kill several bacterial pathogens in vitro. The purpose of this study was to determine if administration of exogenous lysozyme would further enhance bacterial killing in vivo. METHODS: To assess the effect of acute lung infection on endogenous lysozyme protein levels, mice were infected by intratracheal instillation of Pseudomonas aeruginosa and bronchoalveolar (BAL) fluid assessed for lysozyme concentration and for muramidase activity. In order to inform in vivo testing, species-specific bacterial killing efficacy was determined by incubating mucoid P. aeruginosa with 2×105 units of chicken lysozyme, human lysozyme or with vehicle at 37°C for 2hours. Subsequently, mice challenged with intratracheally-administered mucoid P. aeruginosa, were reintubated and injected with 2×105 Units of native human lysozyme, recombinant human lysozyme or with vehicle. Lung bacterial burden was enumerated subsequently. RESULTS: The concentration of lysozyme protein in BAL fluid from mice challenged with mucoid clinical isolate of P. aeruginosa was increased 4-fold at 6hours post-infection. Quantitative culture showed that the number of recoverable bacteria was significantly decreased by both chicken and human lysozyme compared to vehicle but human lysozyme was significantly more effective than chicken egg lysozyme. In vivo, 24hours post-infection quantitative culture of lung homogenates showed that the number of viable bacteria recovered from mice treated with either native or recombinant lysozyme was decreased with 0.76±0.25×104 and 0.84±0.16×104, respectively, vs. 7.0±2.52×104 CFU/g protein in mice treated with HBSS, both P<0.05. CONCLUSIONS: These results indicate that endogenous lysozyme is increased during acute lung infection and that early administration of exogenous lysozyme further enhances bacterial killing in vivo.

[Lung diseases in children associated with inherited disorders of surfactant metabolism]. / Pathologies respiratoires de l'enfant associées à des anomalies héréditaires du métabolisme du surfactant.

Pulmonary surfactant is a unique mixture of lipids and specific proteins that reduces surface tension at the air-liquid interface, preventing collapse of the lung at the end of expiration. Recessive loss-of-function mutations of pulmonary surfactant protein B (SP-B) was initially described in infants who develop respiratory failure at birth. More recently, mutations in other constitutive surfactant proteins like surfactant protein C or implied in its metabolism like ATP-binding cassette, sub-family A, member 3 (ABCA3) or NK2 homeobox (NKX2-1) were identified in newborn with respiratory distress but also in children with diffuse infiltrative pneumonia. Intra-alveolar accumulation of protein related to surfactant dysfunction leads to cough, hypoxemia and radiological abnormalities including ground-glass opacities and lung cysts. The clinical and radiological features associated with these genetic disorders, along with their treatment and outcome, are reviewed.

[Genetic disorders of surfactant]. / Pathologies génétiques du surfactant.

Lung diseases associated with surfactant metabolism disorders represent a significant but heterogeneous group of rare disorders. Intra-alveolar accumulation of protein related to surfactant dysfunction leads to cough, hypoxemia and radiological diffuse infiltration. Inherited deficiency of pulmonary surfactant protein B (SP-B) was initially described in term newborns who develop severe respiratory failure at birth. More recently, mutations in surfactant protein C (SP-C) or in proteins required for surfactant synthesis such as ATP-binding cassette, sub-family A, member 3 (ABCA3) or NK2 homeobox 1 (NKX2-1) were identified in newborns with respiratory distress but also in children with diffuse infiltrative pneumonia. The aim of this review is to describe the clinical presentation of these diseases but also the diagnostic tools and the treatments options available.