Effect of different surfactants on pulmonary group B streptococcal infection in premature rabbits,☆☆,,★★

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Abstract

Objectives: To evaluate the effects of different surfactants on pulmonary infection with group B streptococci in premature rabbits and to examine the effects of different surfactants on pulmonary alveolar macrophage function of newborn rabbits. Model: Preterm and term rabbit pups. Methods: Rabbit pups were infected with GBS aerosols followed by intratracheal administration of either calf lung surfactant extract, minced porcine lung surfactant (Curosurf), synthetic surfactant (Exosurf Neonatal), minced bovine lung surfactant (Survanta), human amniotic fluid-derived surfactant, rabbit surfactant, saline vehicle, or no treatment. Intrapulmonary clearance of GBS was determined by comparing bacterial counts in left lungs cultured immediately after aerosol infection with similarly infected lungs analyzed 4 hours after surfactant therapy. Phagocytosis of streptococci was ascertained by microscopic examination of the right lungs fixed in situ at 4 hours. For comparison, an in vitro method was used to measure growth of GBS in the different surfactants. Results: Preterm animals had a sixfold increase in pulmonary bacterial growth compared with a slight decrease in intrapulmonary GBS in term animals when all were delivered by cesarean section (p <0.05). In premature rabbits, GBS proliferation was lowest in animals treated with Exosurf Neonatal and highest in animals receiving Curosurf and human amniotic fluid-derived surfactant (p <0.05). None of the surfactants promoted accelerated growth of GBS in comparison with control animals. Similar growth of GBS was seen in in vitro cultures. Intrapulmonary phagocytosis of GBS in premature pups was not altered by any of the surfactants. In term rabbit pups, the following measures of macrophage population kinetics remained normal at 1 and 24 hours after surfactant administration: viability, cell numbers based on lung lavage, and in vivo incorporation of thymidine. Conclusions: Surfactants used in clinical practice do not accelerate the in vivo growth of group B streptococci in the lungs of preterm rabbits. Some surfactants inhibit streptococcal proliferation. The effects of different surfactants are not explained by changes in macrophage function. (J PEDIATR 1994;125:939-47)

Section snippets

Animals

The animal procedures used in this study were approved by the Chancellor's Animal Research Committee of the University of California, Los Angeles, and met the standards of the National Institutes of Health. Time-dated, pregnant New Zealand white rabbits (Irish Farms, Norco, Calif.) underwent cesarean section on day 28 or 29 of gestation. Immediately thereafter, preterm pups were placed in warmed (37° C), humidified (75% relative humidity) incubators. Sufficient inspired oxygen was provided to

Group B streptococcal clearance in premature versus term neonatal lung

Birth weights, infective doses of GBS in the left lung at 0 hour, and the numbers of GBS present in the left lung at 4 hours after surfactant therapy are shown in Table II. The different groups of preterm rabbits did not differ in birth weight or initial inoculum of GBS after aerosol infection. Untreated premature rabbits inhaled fewer streptococci than did rabbits born by cesarean section at term. Nevertheless, these premature rabbits had nearly a sixfold increase in intrapulmonary GBS after 4

DISCUSSION

Although group B streptococcal pneumonia is a common cause of congenital pulmonary infection,22 it is infrequently responsible for nosocomial lung infections in intensive care nurseries.23 The growth of GBS in the lungs of preterm rabbits versus the progressive inactivation of this bacterium in the lungs of term and postnatal rabbits offers a rationale for the relative absence of group B streptococcal pneumonia in human beings beyond 3 days of age. Several factors explain the timely maturation

References (40)

  • MP Sherman et al.

    Hyperoxia damages phagocytic defenses of neonatal rabbit lung

    J Appl Physiol

    (1987)
  • MP Sherman et al.

    Surfactant therapy of newborn rabbits impairs lung macro-phage bactericidal activity

    J Appl Physiol

    (1988)
  • M Hallman et al.

    Isolation of human surfactant from amniotic fluid and a pilot study of its efficacy in respiratory distress syndrome

    Pediatrics

    (1983)
  • DL Shapiro et al.

    Double-blind, randomized trial of a calf lung surfactant extract administered at birth to very premature infants for prevention of respiratory distress syndrome

    Pediatrics

    (1985)
  • WH Tooley et al.

    Lung function in prematurely delivered rabbits treated with a synthetic surfactant

    Am Rev Respir Dis

    (1987)
  • JD Gitlin et al.

    Randomized, controlled trial of exogenous surfactant for the treatment of hyaline membrane disease

    Pediatrics

    (1987)
  • B Robertson et al.

    Structural and functional characterization of porcine surfactant isolated by liquid-gel chromatography

  • M Sherman et al.

    Growth of neonatal bacterial pathogens in clinically relevant surfactants

    Pediatr Res

    (1989)
  • DW. Nielson

    Electrolyte composition of pulmonary alveolar subphase in anesthetized rabbits

    J Appl Physiol

    (1986)
  • S. Matalon

    Mechanisms and regulation of ion transport in adult mammalian alveolar type II pneumocytes

    Am J Physiol

    (1991)
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    From the Department of Pediatrics, University of California, Los Angeles, Medical Center, the Department of Pediatrics, University of California, Davis, Medical Center, the Clinical Research Division, Burroughs Wellcome Co., Research Triangle Park, North Carolina, the Department of Pediatrics, University of North Carolina at Chapel Hill, Ross Laboratories, Division of Abbott Laboratories, Columbus, Ohio, the Department of Clinical Chemistry, Danderyd Hospital, Danderyd, Sweden, and the Research Unit for Experimental Pathology, Karolinska Hospital, Stockholm, Sweden.

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    Supported by National Institutes of Health grants HL40675 and HL/H35036, American Lung Association of California grant R-S900425, Food and Drug Administration grant 00012, and the Swedish Medical Research Council (project No. 3351) and Oscar II:s Jubileumsfond.

    Reprint requests: Michael P. Sherman, MD, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7330.

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