Local administration of polymyxins into the respiratory tract for the prevention and treatment of pulmonary infections in patients without cystic fibrosis

The increasing problem of antimicrobial resistance has forced the medical community to evaluate alternative preventive and therapeutic strategies for nosocomial pneumonia, infection that is associated with considerable morbidity and mortality. Among them, local administration of polymyxins into the respiratory tract represents a promising strategy. This review highlights recent evidence regarding the effectiveness and safety of this intervention in the prevention and treatment of patients with multidrug-resistant Gram-negative bacterial infections. Polymyxins can be administered directly to the respiratory tract through jet or ultrasonic nebulizers, dry powder inhalers, or by endotracheal instillation. Data from limited studies on pharmacokinetic and pharmacodynamic properties of aerosolized polymyxins suggest that while high sputum concentrations are achievable systemic exposure is limited. The incidence of colonization of the upper respiratory tract with Gramnegative bacteria, especially Pseudomonas aeruginosa was considerably reduced in two trials that assessed the effect of prophylactic administration of aerosolized polymyxins on the colonization of the respiratory tract of critically ill patients. Clinical trials that examined the value of aerosolized polymyxins in the prevention of lung infections resulted in conflicting findings. Although the incidence of Gram-negative bacterial pneumonia was decreased in the majority of the studies, no improvement in mortality was found. Possible selection of polymyxin-resistant microorganisms has been the major limitation. Treatment of Gram-negative bacterial nosocomial pneumonia with aerosolized polymyxins may be a beneficial supplemental to the conventional therapy; however, its value remains to be proved. The available evidence supports that the local administration of polymyxins into the respiratory tract for the prevention and treatment of multidrug-resistant (MDR) Gram-negative bacterial infections deserves further investigation.