Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection
Derek S Sarovich,1,2,* Erin P Price,1,2,* Direk Limmathurotsakul,3 James M Cook,1 Alex T Von Schulze,1 Spenser R Wolken,1 Paul Keim,1 Sharon J Peacock,3,4 Talima Pearson1 1Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, USA; 2Tropical and Emerging Infectious D...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2012-08-01
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| Series: | Infection and Drug Resistance |
| Online Access: | http://www.dovepress.com/development-of-ceftazidime-resistance-in-an-acute-burkholderia-pseudom-a10785 |
| _version_ | 1818021168091758592 |
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| author | Sarovich DS Price EP Limmathurotsakul D Cook JM Von Schulze AT Wolken SR Keim P Peacock SJ Pearson T |
| author_facet | Sarovich DS Price EP Limmathurotsakul D Cook JM Von Schulze AT Wolken SR Keim P Peacock SJ Pearson T |
| author_sort | Sarovich DS |
| collection | DOAJ |
| description | Derek S Sarovich,1,2,* Erin P Price,1,2,* Direk Limmathurotsakul,3 James M Cook,1 Alex T Von Schulze,1 Spenser R Wolken,1 Paul Keim,1 Sharon J Peacock,3,4 Talima Pearson1 1Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, USA; 2Tropical and Emerging Infectious Diseases Division, Menzies School of Health Research, Darwin, Australia; 3Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 4Department of Medicine, University of Cambridge, Cambridge, United Kingdom*These authors contributed equally to this workAbstract: 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.Keywords: Burkholderia pseudomallei, ceftazidime, antibiotic resistance, melioidosis, β-lactamase, penA |
| first_indexed | 2024-04-14T08:15:15Z |
| format | Article |
| id | doaj.art-0f5f53235d47431493244c322fcc21c3 |
| institution | Directory Open Access Journal |
| issn | 1178-6973 |
| language | English |
| last_indexed | 2024-04-14T08:15:15Z |
| publishDate | 2012-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Infection and Drug Resistance |
| spelling | doaj.art-0f5f53235d47431493244c322fcc21c32022-12-22T02:04:25ZengDove Medical PressInfection and Drug Resistance1178-69732012-08-012012default129132Development of ceftazidime resistance in an acute Burkholderia pseudomallei infectionSarovich DSPrice EPLimmathurotsakul DCook JMVon Schulze ATWolken SRKeim PPeacock SJPearson TDerek S Sarovich,1,2,* Erin P Price,1,2,* Direk Limmathurotsakul,3 James M Cook,1 Alex T Von Schulze,1 Spenser R Wolken,1 Paul Keim,1 Sharon J Peacock,3,4 Talima Pearson1 1Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, USA; 2Tropical and Emerging Infectious Diseases Division, Menzies School of Health Research, Darwin, Australia; 3Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 4Department of Medicine, University of Cambridge, Cambridge, United Kingdom*These authors contributed equally to this workAbstract: 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.Keywords: Burkholderia pseudomallei, ceftazidime, antibiotic resistance, melioidosis, β-lactamase, penAhttp://www.dovepress.com/development-of-ceftazidime-resistance-in-an-acute-burkholderia-pseudom-a10785 |
| spellingShingle | Sarovich DS Price EP Limmathurotsakul D Cook JM Von Schulze AT Wolken SR Keim P Peacock SJ Pearson T Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection Infection and Drug Resistance |
| title | 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_short | Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection |
| title_sort | development of ceftazidime resistance in an acute burkholderia pseudomallei infection |
| url | http://www.dovepress.com/development-of-ceftazidime-resistance-in-an-acute-burkholderia-pseudom-a10785 |
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