Surfactant treatment in neonatal group B streptococcal pneumonia : experimental and clinical studies

University dissertation from Stockholm : Karolinska Institutet, Department of Women's and Children's Health

Abstract: Surfactant dysfunction is probably involved in the pathophysiology of neonatal group B streptococcal (GBS) pneumonia. Aim of the present studies was to evaluate efficacy and safety of surfactant replacement therapy for term and preterm neonates with severe respiratory failure due to GBS infection. We investigated the effects of surfactant on growth of GBS and on oxidative metabolism of polymorphonuclear neutrophilic granulocytes (PMN) stimulated with GBS, and developed an animal model of GBS pneumonia for studies on lung function, inflammatory response and bacterial proliferation in lung tissue. Surfactant reduced nitroblue tetrazolium-reduction of resting PMN. In contrast, when PMN were stimulated with encapsulated GBS and a specific antibody no suppression in the release of reactive oxygen species from PMN could be observed following incubation with surfactant. We tested the effects of surfactant treatment in tracheotomized, ventilated, near-term newborn rabbits with experimental GBS pneumonia. In this model we found reduced bacterial proliferation following instillation of exogenous surfactant as compared to controls receiving saline. In addition, lung function was significantly improved in preterm rabbits with GBS pneumonia receiving surfactant. The surfactant associated protein A (SP-A) stimulates the phagocytosis of bacteria by alveolar macrophages and is believed to play an important role in the pulmonary antimicrobial defense system. However, inactivation of SP-A by a monoclonal antibody did not influence bacterial proliferation in our model. Furthermore, we could demonstrate that simultaneous instillation of surfactant and specific antibodies against the polysaccharide capsule of GBS reduced bacterial growth in the lungs of GBS infected newborn rabbits more effectively than either treatment alone. We speculate that this might be due to a more homogenous and rapid distribution of the antibodies within the lung. To study the effectiveness of surfactant treatment in neonatal GBS pneumonia, we assessed oxygen requirements and complication rates in 118 neonates with severe respiratory failure due to GBS infection. We could demonstrate a significant improvement in oxygenation within 1 h following surfactant instillation. However, the response to exogenous surfactant was slower than in non-infected infants with respiratory distress syndrome. The use of surfactant for treatment of bacterial pneumonia deserves further experimental evaluation not only in neonates, but also in children and adults.

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