Comparative studies of intermittent and continuous administration of aminoglycosides in the treatment of bronchopulmonary infections due to gram-negative bacteria.

The positive correlation between the protein concentration in bronchial secretions and the penetration of amikacin and tobramycin in the present study suggests that inflammation favorably affects the penetration of aminoglycosides into these secretions. As shown in this and other studies, local inactivation of aminoglycosides might counterbalance this effect to some extent. The relatively low penetration of aminoglycosides into the bronchial secretions (approximately 20%) probably accounts for the poor antibacterial activity of bronchial secretions of aminoglycoside-treated patients and, possibly, for the poor clinical outcome of bronchopneumonia due to gram-negative bacteria. Continuous infusion of these antibiotics, even at high dosage, does not appear to solve the problem; it does not achieve at any time satisfactory inhibitory activity against Enterobacteriaceae or Pseudomonas aeruginosa in the bronchial secretions. Although intermittent injections can result in higher levels of aminoglycosides within the bronchial secretions, such levels cannot be maintained for prolonged periods unless the dosage is increased. Thus endotracheal administration of aminoglycosides might still be indicated as an adjunct for therapy of severe bronchial infections due to gram-negative bacteria.