Novel Approaches to Multidrug-Resistant Infections in Cystic Fibrosis

Abstract

Patients with cystic fibrosis (CF) often develop respiratory tract infections with pathogenic multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus, and a variety of gram-negative organisms that include Pseudomonas aeruginosa, Burkholderia sp., Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM). Despite the introduction of new therapies to address underlying cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, MDRO infections remain a problem and novel antimicrobial interventions are still needed. Therapeutic approaches include improving the efficacy of existing drugs by adjusting the dose based on differences in CF patient pharmacokinetics/pharmacodynamics, the development of inhaled formulations to reduce systemic adverse events, and the use of newer beta-lactam/beta-lactamase combinations. Alternative innovative therapeutic approaches include the use of gallium and bacteriophages to treat MDRO pulmonary infections including those with extreme antibiotic resistance. However, additional clinical trials are required to determine the optimal dosing and efficacy of these different strategies and to identify patients with CF most likely to benefit from these new treatment options.

Keywords: Bacteriophage; Cystic fibrosis; Gallium; Multidrug-resistant organisms.