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 a...
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2025-06-01
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author | Hana Farizah Zamri Mohammad Ridhuan Mohd Ali Ahmad Izzan Irfan Sha'ari Nurul Husna Mohd Mazalan Norazah Ahmad Nur Asyura Nor Amdan Nusaibah Abdul Rahim Zakuan Zainy Deris |
author_facet | Hana Farizah Zamri Mohammad Ridhuan Mohd Ali Ahmad Izzan Irfan Sha'ari Nurul Husna Mohd Mazalan Norazah Ahmad Nur Asyura Nor Amdan Nusaibah Abdul Rahim Zakuan Zainy Deris |
author_sort | Hana Farizah Zamri |
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description | 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 (BSL3) facility. Unfortunately, BSL3 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 B. pseudomallei outside BSL 3 laboratory. Briefly in this study, • All procedures involving active handling of live B. pseudomallei cultures were performed strictly inside a class II BSC in BSL-2 plus negative airflow laboratory. • The model was set to simulate B. pseudomallei-bacteremia treated with ceftazidime, a 1st-line anti-melioidosis drug with an approximate 2-hour half-life. Model validation was performed by simulating ceftazidime 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. |
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institution | Kabale University |
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language | English |
publishDate | 2025-06-01 |
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spelling | doaj-art-ca48c0d35bfa45b285949d65ad8b6d032025-01-16T04:28:45ZengElsevierMethodsX2215-01612025-06-0114103167Adaptation of an in vitro one-compartment pharmacodynamic chemostat for testing efficacy of ceftazidime against Burkholderia pseudomallei outside a BSL3 facilityHana Farizah Zamri0Mohammad Ridhuan Mohd Ali1Ahmad Izzan Irfan Sha'ari2Nurul Husna Mohd Mazalan3Norazah Ahmad4Nur Asyura Nor Amdan5Nusaibah Abdul Rahim6Zakuan Zainy Deris7Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia; Bacteriology Unit, Institute for Medical Research (IMR), Malaysian Ministry of Health, Seksyen U13 Setia Alam, Shah Alam, Selangor 40170, MalaysiaBacteriology Unit, Institute for Medical Research (IMR), Malaysian Ministry of Health, Seksyen U13 Setia Alam, Shah Alam, Selangor 40170, Malaysia; Corresponding authors.Bacteriology Unit, Institute for Medical Research (IMR), Malaysian Ministry of Health, Seksyen U13 Setia Alam, Shah Alam, Selangor 40170, MalaysiaBacteriology Unit, Institute for Medical Research (IMR), Malaysian Ministry of Health, Seksyen U13 Setia Alam, Shah Alam, Selangor 40170, MalaysiaBacteriology Unit, Institute for Medical Research (IMR), Malaysian Ministry of Health, Seksyen U13 Setia Alam, Shah Alam, Selangor 40170, MalaysiaBacteriology Unit, Institute for Medical Research (IMR), Malaysian Ministry of Health, Seksyen U13 Setia Alam, Shah Alam, Selangor 40170, MalaysiaDepartment of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia; Corresponding authors.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 (BSL3) facility. Unfortunately, BSL3 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 B. pseudomallei outside BSL 3 laboratory. Briefly in this study, • All procedures involving active handling of live B. pseudomallei cultures were performed strictly inside a class II BSC in BSL-2 plus negative airflow laboratory. • The model was set to simulate B. pseudomallei-bacteremia treated with ceftazidime, a 1st-line anti-melioidosis drug with an approximate 2-hour half-life. Model validation was performed by simulating ceftazidime 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.http://www.sciencedirect.com/science/article/pii/S2215016125000159In vitro one-compartment chemostat for evaluating ceftazidime PK/PD against B. pseudomallei |
spellingShingle | Hana Farizah Zamri Mohammad Ridhuan Mohd Ali Ahmad Izzan Irfan Sha'ari Nurul Husna Mohd Mazalan Norazah Ahmad Nur Asyura Nor Amdan Nusaibah Abdul Rahim Zakuan Zainy Deris Adaptation of an in vitro one-compartment pharmacodynamic chemostat for testing efficacy of ceftazidime against Burkholderia pseudomallei outside a BSL3 facility MethodsX In vitro one-compartment chemostat for evaluating ceftazidime PK/PD against B. pseudomallei |
title | Adaptation of an in vitro one-compartment pharmacodynamic chemostat for testing efficacy of ceftazidime against Burkholderia pseudomallei outside a BSL3 facility |
title_full | Adaptation of an in vitro one-compartment pharmacodynamic chemostat for testing efficacy of ceftazidime against Burkholderia pseudomallei outside a BSL3 facility |
title_fullStr | Adaptation of an in vitro one-compartment pharmacodynamic chemostat for testing efficacy of ceftazidime against Burkholderia pseudomallei outside a BSL3 facility |
title_full_unstemmed | Adaptation of an in vitro one-compartment pharmacodynamic chemostat for testing efficacy of ceftazidime against Burkholderia pseudomallei outside a BSL3 facility |
title_short | Adaptation of an in vitro one-compartment pharmacodynamic chemostat for testing efficacy of ceftazidime against Burkholderia pseudomallei outside a BSL3 facility |
title_sort | adaptation of an in vitro one compartment pharmacodynamic chemostat for testing efficacy of ceftazidime against burkholderia pseudomallei outside a bsl3 facility |
topic | In vitro one-compartment chemostat for evaluating ceftazidime PK/PD against B. pseudomallei |
url | http://www.sciencedirect.com/science/article/pii/S2215016125000159 |
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