Adaptation of an in vitro one-compartment pharmacodynamic chemostat for testing efficacy of ceftazidime against Burkholderia pseudomallei outside a BSL3 facility

Non-clinical pharmacokinetic-pharmacodynamic (PKPD) models are crucial in the initial design of drug-dosage regimens and in drug development but has rarely been employed for testing high-risk organisms due to stringent handling procedures. Burkholderia pseudomallei is classified as a Tier 1 select agent with international guidelines recommending this organism to be handled within a biosafety level 3 (SL3) facility. Unfortunately, BS13 facilities are not widely available in low- resource settings. This paper describes a detailed guide for setting up an in vitro pharmacodynamic infection model specific for testing 8. pseudomallei outside BSI. 3 laboratory. Briefly in this study. All procedures involving active handling of live H. pseudomallei cultures were performed strictly inside class II BSC in BSL-2 plus negative airflow laboratory. The model was set to simulate II. pseudomallei-bacteremia treated with ceftazidime, a 1st-line anti-melioidos drug with an approximate 2-hour half-life. Model validation was performed by simulating-ftazidime half-life. For the pharmacodynamic study, ceftazidime was given as bolus injections at 8-hour intervals into the central culture chamber containing actively growing B. pseudomallei.