Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection

Burkholderia pseudomallei, a bacterium that causes the disease melioidosis, is intrinsically resistant to many antibiotics. First-line antibiotic therapy for treating melioidosis is usually the synthetic β-lactam, ceftazidime (CAZ), as almost all B. pseudomallei strains are susceptible to this drug....

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Main Authors: Sarovich, Derek S, Price, Erin P, Limmathurotsakul, Direk, Cook, James M, Von Schulze, Alex T, Wolken, Spenser R, Keim, Paul, Peacock, Sharon J, Pearson, Talima
Format: Online
Language:English
Published: Dove Medical Press 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430440/
id pubmed-3430440
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spelling pubmed-34304402012-09-13 Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection Sarovich, Derek S Price, Erin P Limmathurotsakul, Direk Cook, James M Von Schulze, Alex T Wolken, Spenser R Keim, Paul Peacock, Sharon J Pearson, Talima Case Report Burkholderia pseudomallei, a bacterium that causes the disease melioidosis, is intrinsically resistant to many antibiotics. First-line antibiotic therapy for treating melioidosis is usually the synthetic β-lactam, ceftazidime (CAZ), as almost all B. pseudomallei strains are susceptible to this drug. However, acquired CAZ resistance can develop in vivo during treatment with CAZ, which can lead to mortality if therapy is not switched to a different drug in a timely manner. Serial B. pseudomallei isolates obtained from an acute Thai melioidosis patient infected by a CAZ susceptible strain, who ultimately succumbed to infection despite being on CAZ therapy for the duration of their infection, were analyzed. Isolates that developed CAZ resistance due to a proline to serine change at position 167 in the β-lactamase PenA were identified. Importantly, these CAZ resistant isolates remained sensitive to the alternative melioidosis treatments; namely, amoxicillin-clavulanate, imipenem, and meropenem. Lastly, real-time polymerase chain reaction-based assays capable of rapidly identifying CAZ resistance in B. pseudomallei isolates at the position 167 mutation site were developed. The ability to rapidly identify the emergence of CAZ resistant B. pseudomallei populations in melioidosis patients will allow timely alterations in treatment strategies, thereby improving patient outcomes for this serious disease. Dove Medical Press 2012-08-22 /pmc/articles/PMC3430440/ /pubmed/22977307 http://dx.doi.org/10.2147/IDR.S35529 Text en © 2012 Sarovich et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Sarovich, Derek S
Price, Erin P
Limmathurotsakul, Direk
Cook, James M
Von Schulze, Alex T
Wolken, Spenser R
Keim, Paul
Peacock, Sharon J
Pearson, Talima
spellingShingle Sarovich, Derek S
Price, Erin P
Limmathurotsakul, Direk
Cook, James M
Von Schulze, Alex T
Wolken, Spenser R
Keim, Paul
Peacock, Sharon J
Pearson, Talima
Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection
author_facet Sarovich, Derek S
Price, Erin P
Limmathurotsakul, Direk
Cook, James M
Von Schulze, Alex T
Wolken, Spenser R
Keim, Paul
Peacock, Sharon J
Pearson, Talima
author_sort Sarovich, Derek S
title Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection
title_short Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection
title_full Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection
title_fullStr Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection
title_full_unstemmed Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection
title_sort development of ceftazidime resistance in an acute burkholderia pseudomallei infection
description Burkholderia pseudomallei, a bacterium that causes the disease melioidosis, is intrinsically resistant to many antibiotics. First-line antibiotic therapy for treating melioidosis is usually the synthetic β-lactam, ceftazidime (CAZ), as almost all B. pseudomallei strains are susceptible to this drug. However, acquired CAZ resistance can develop in vivo during treatment with CAZ, which can lead to mortality if therapy is not switched to a different drug in a timely manner. Serial B. pseudomallei isolates obtained from an acute Thai melioidosis patient infected by a CAZ susceptible strain, who ultimately succumbed to infection despite being on CAZ therapy for the duration of their infection, were analyzed. Isolates that developed CAZ resistance due to a proline to serine change at position 167 in the β-lactamase PenA were identified. Importantly, these CAZ resistant isolates remained sensitive to the alternative melioidosis treatments; namely, amoxicillin-clavulanate, imipenem, and meropenem. Lastly, real-time polymerase chain reaction-based assays capable of rapidly identifying CAZ resistance in B. pseudomallei isolates at the position 167 mutation site were developed. The ability to rapidly identify the emergence of CAZ resistant B. pseudomallei populations in melioidosis patients will allow timely alterations in treatment strategies, thereby improving patient outcomes for this serious disease.
publisher Dove Medical Press
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430440/
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