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

Burkholderia pseudomallei, the etiological agent responsible for melioidosis, exhibits a great public health toll in its endemic regions. The elevation of B. pseudomallei to a Tier I select agent underscores the urgent need for effective therapeutics and preventatives. The current treatment regimen for melioidosis is suboptimal, requiring an intensive phase of intravenous antibiotic followed by months of oral antibiotics. Inhaled antibiotics are a promising avenue to pursue for pulmonary diseases, including melioidosis, since this mode of delivery mimics the likely exposure route and can provide high drug doses directly to the infected tissue. 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.