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Pharmacodynamics of colistin against Acinetobacter baumannii

Nosocomial infection caused by Acinetobacter baumannii is endemic in hospital settings especially among immunocompromised patients. Treatment strategy is limited due to rapid emergence of extensively drug resistance and lack of novel agent in the antibiotic development pipeline. Colistin has been th...

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Egile nagusia: Mohd Rasidin, Rashizal Sazli
Formatua: Thesis
Hizkuntza:English
Argitaratua: 2017
Sarrera elektronikoa:http://ethesis.upm.edu.my/id/eprint/12307/1/FPSK%28M%29%202017%2013%20-%20T.pdf
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spelling oai:ethesis.upm.edu.my:12307 http://ethesis.upm.edu.my/id/eprint/12307/ Pharmacodynamics of colistin against Acinetobacter baumannii Mohd Rasidin, Rashizal Sazli Nosocomial infection caused by Acinetobacter baumannii is endemic in hospital settings especially among immunocompromised patients. Treatment strategy is limited due to rapid emergence of extensively drug resistance and lack of novel agent in the antibiotic development pipeline. Colistin has been the last line therapy with good in vitro activity. However, updates in the pharmacological aspects are required to support dosing optimisation. The current study descriptively explained high proportion (89%) of extensively drug resistance among 72 multidrug resistance strains of A. baumannii collected from Hospital Serdang. The clinical strains were mainly isolated from elderly patients (median age 61 [IQR 25]) admitted to medical ward (35%) while common isolation site was respiratory sample (60%). Antibiogram profile showed 100% in vitro susceptibility of the strains to colistin with 54% of isolates exhibit MIC 1.0 μg/mL. The in vitro static time-kill kinetic and post-antibiotic effect experiments were conducted against two clinical isolates (colistin MIC 1.0 μg/mL and 0.75 μg/mL) as well as one reference isolate ATCC 19606 (colistin MIC 1.0 μg/mL). The development of colistin resistance was also examined after colistin exposure in time-kill study. The post-antibiotic effect was determined at colistin concentration based on the achievable plasma level after parenteral administration. Concentration-dependent killing activity was observed in time-kill experiment against all studied isolates. However, delayed bactericidal activity indicates tolerance or persistence of the strains against colistin. Development of colistin resistance after colistin exposure was not detected except for the known colistin heteroresistance ATCC 19606 strain. Meanwhile, the post-antibiotic effect was significant in a concentration-dependent manner for all studied isolates. Dosing suggestion based on observations from this study include administration of a supplemental dose 3 MIU at 12 hours after loading dose, administration of maintenance dose 9 MIU in two divided doses and the application of extended interval in dosing adjustment for patients with renal impairment. However, information of the current study is applicable for non-colistin-heteroresistance A. baumannii with colistin MIC ≤ 1 μg/mL. As for heteroresistance and strain with colistin MIC > 1.0 μg/mL, combination therapy would be the more appropriate treatment strategy. 2017-04 Thesis NonPeerReviewed application/pdf en http://ethesis.upm.edu.my/id/eprint/12307/1/FPSK%28M%29%202017%2013%20-%20T.pdf Mohd Rasidin, Rashizal Sazli (2017) Pharmacodynamics of colistin against Acinetobacter baumannii. Masters thesis, Universiti Putra Malaysia. (FPSK(m) 2017 13).
institution UPM eTHESES
collection UPM eTHESES
language English
description Nosocomial infection caused by Acinetobacter baumannii is endemic in hospital settings especially among immunocompromised patients. Treatment strategy is limited due to rapid emergence of extensively drug resistance and lack of novel agent in the antibiotic development pipeline. Colistin has been the last line therapy with good in vitro activity. However, updates in the pharmacological aspects are required to support dosing optimisation. The current study descriptively explained high proportion (89%) of extensively drug resistance among 72 multidrug resistance strains of A. baumannii collected from Hospital Serdang. The clinical strains were mainly isolated from elderly patients (median age 61 [IQR 25]) admitted to medical ward (35%) while common isolation site was respiratory sample (60%). Antibiogram profile showed 100% in vitro susceptibility of the strains to colistin with 54% of isolates exhibit MIC 1.0 μg/mL. The in vitro static time-kill kinetic and post-antibiotic effect experiments were conducted against two clinical isolates (colistin MIC 1.0 μg/mL and 0.75 μg/mL) as well as one reference isolate ATCC 19606 (colistin MIC 1.0 μg/mL). The development of colistin resistance was also examined after colistin exposure in time-kill study. The post-antibiotic effect was determined at colistin concentration based on the achievable plasma level after parenteral administration. Concentration-dependent killing activity was observed in time-kill experiment against all studied isolates. However, delayed bactericidal activity indicates tolerance or persistence of the strains against colistin. Development of colistin resistance after colistin exposure was not detected except for the known colistin heteroresistance ATCC 19606 strain. Meanwhile, the post-antibiotic effect was significant in a concentration-dependent manner for all studied isolates. Dosing suggestion based on observations from this study include administration of a supplemental dose 3 MIU at 12 hours after loading dose, administration of maintenance dose 9 MIU in two divided doses and the application of extended interval in dosing adjustment for patients with renal impairment. However, information of the current study is applicable for non-colistin-heteroresistance A. baumannii with colistin MIC ≤ 1 μg/mL. As for heteroresistance and strain with colistin MIC > 1.0 μg/mL, combination therapy would be the more appropriate treatment strategy.
format Thesis
author Mohd Rasidin, Rashizal Sazli
spellingShingle Mohd Rasidin, Rashizal Sazli
Pharmacodynamics of colistin against Acinetobacter baumannii
author_facet Mohd Rasidin, Rashizal Sazli
author_sort Mohd Rasidin, Rashizal Sazli
title Pharmacodynamics of colistin against Acinetobacter baumannii
title_short Pharmacodynamics of colistin against Acinetobacter baumannii
title_full Pharmacodynamics of colistin against Acinetobacter baumannii
title_fullStr Pharmacodynamics of colistin against Acinetobacter baumannii
title_full_unstemmed Pharmacodynamics of colistin against Acinetobacter baumannii
title_sort pharmacodynamics of colistin against acinetobacter baumannii
publishDate 2017
url http://ethesis.upm.edu.my/id/eprint/12307/1/FPSK%28M%29%202017%2013%20-%20T.pdf
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score 13.4562235

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