10th International Aerosol Conference
September 2 - September 7, 2018
America's Center Convention Complex
St. Louis, Missouri, USA

Abstract View


Pulmonary Delivery of Ceftazidime for the Treatment of Melioidosis in a Murine Model

SARA RUIZ, Larry Bowen, Mark Bailey, Cory Berkland, USAMRIID

     Abstract Number: 370
     Working Group: Infectious Bioaerosol

Abstract
Interest in Burkholderia pseudomallei, the causative agent of melioidosis, has increased over the years given its status as a select agent. This is due to its inherent ease of aerosol transmission, resistance to common antibiotics, and ability to establish both an acute and chronic infection. Clinical manifestations range from pneumonia to acute sepsis with chronic individuals being asymptomatic for a number of years before progressing to acute disease. To date, there is no vaccine available for melioidosis and even with the proper antibiotic course of treatment, therapy fails in approximately 10% of patients. In vitro studies have shown that B. pseudomallei is able to form biofilms readily. Other medically important bacteria, including Staphylococcus aureus, have shown biofilm formation as a contributing factor to overall virulence including antibiotic resistance and chronic disease. We have demonstrated that biofilms can be visualized in non-human primate lungs infected with B. pseudomallei upon staining with fluorescent markers. In addition, all strains secrete known quorum sensing effectors that influence biofilm formation as determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). The presence of a biofilm during the natural course of disease implies that it is an important bacterial state to consider in assessing novel treatment options. Inhaled antibiotics are a promising avenue to pursue for pulmonary diseases, including biofilm infections. Ceftazidime was delivered via a nose-only system to BALB/c mice challenged with B. pseudomallei. Mice treated with nebulized ceftazidime became symptomatic but survived until study end, which was comparable to those treated intraperitoneally. Upon necropsy, bacteria remained within the spleens of the majority of the experimental animals. The effectiveness of nebulized ceftazidime warrants additional studies to improve the treatment regimen and to test as a prophylactic therapy against B. pseudomallei.