title: Inhaled Antibiotics for Gram-Negative Respiratory Infections.
abstract: Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.
authors.affiliation: University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois, USA.
authors.forename: Eric
authors.identifier: http://orcid.org/0000-0003-3914-8400
authors.initials: E
authors.lastname: Wenzler
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Dustin R
authors.initials: DR
authors.lastname: Fraidenburg
authors.affiliation: Loyola University Medical Center, Chicago, Illinois, USA.
authors.forename: Tonya
authors.initials: T
authors.lastname: Scardina
authors.affiliation: University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois, USA University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA danziger@uic.edu.
authors.forename: Larry H
authors.initials: LH
authors.lastname: Danziger
mesh_terms: D006801:Humans; D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents