Novel Approaches to Multidrug-Resistant Infections in Cystic Fibrosis

Thomas S Murray; Gail Stanley; Jonathan L Koff

doi:10.1016/j.idc.2023.12.002

Novel Approaches to Multidrug-Resistant Infections in Cystic Fibrosis

Infect Dis Clin North Am. 2024 Mar;38(1):149-162. doi: 10.1016/j.idc.2023.12.002.

Authors

Thomas S Murray¹, Gail Stanley², Jonathan L Koff³

Affiliations

¹ Department of Pediatrics, Section Infectious Diseases and Global Health, Yale University School of Medicine, PO Box 208064, 333 Cedar Street, New Haven, CT 06520-8064, USA. Electronic address: [email protected].
² Department of Internal Medicine, Section Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, PO Box 208057, 300 Cedar Street TAC-441 South, New Haven, CT 06520-8057, USA; Adult Cystic Fibrosis Program; Yale University Center for Phage Biology & Therapy. Electronic address: [email protected].
³ Adult Cystic Fibrosis Program; Yale University Center for Phage Biology & Therapy; Department of Internal Medicine, Section Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, PO Box 208057, 300 Cedar Street TAC-455A South, New Haven, CT 06520-8057, USA. Electronic address: [email protected].

PMID: 38280761
DOI: 10.1016/j.idc.2023.12.002

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.

Publication types

Review

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Anti-Infective Agents* / therapeutic use
Cystic Fibrosis* / complications
Cystic Fibrosis* / drug therapy
Cystic Fibrosis* / microbiology
Humans
Methicillin-Resistant Staphylococcus aureus*
Respiratory Tract Infections* / drug therapy
Respiratory Tract Infections* / microbiology
Stenotrophomonas maltophilia*

Substances

Anti-Infective Agents
Anti-Bacterial Agents