In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated Pathways
Two pairs of ceftolozane/tazobactam susceptible/resistant P. aeruginosa were isolated from 2 patients after exposure to β-lactams. The genetic basis of ceftolozane/tazobactam resistance was evaluated, and β-lactam-resistant mechanisms were assessed by phenotypic assays. Whole genome sequencing ident...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Case Reports in Infectious Diseases |
| Online Access: | http://dx.doi.org/10.1155/2018/9095203 |
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| author | Erik Skoglund Henrietta Abodakpi Rafael Rios Lorena Diaz Elsa De La Cadena An Q. Dinh Javier Ardila William R. Miller Jose M. Munita Cesar A. Arias Vincent H. Tam Truc T. Tran |
| author_facet | Erik Skoglund Henrietta Abodakpi Rafael Rios Lorena Diaz Elsa De La Cadena An Q. Dinh Javier Ardila William R. Miller Jose M. Munita Cesar A. Arias Vincent H. Tam Truc T. Tran |
| author_sort | Erik Skoglund |
| collection | DOAJ |
| description | Two pairs of ceftolozane/tazobactam susceptible/resistant P. aeruginosa were isolated from 2 patients after exposure to β-lactams. The genetic basis of ceftolozane/tazobactam resistance was evaluated, and β-lactam-resistant mechanisms were assessed by phenotypic assays. Whole genome sequencing identified mutations in AmpC including the mutation (V213A) and a deletion of 7 amino acids (P210–G216) in the Ω-loop. Phenotypic assays showed that ceftolozane/tazobactam resistance in the strain with AmpCV213A variant was associated with increased β-lactamase hydrolysis activity. On the other hand, the deletion of 7 amino acids in the Ω-loop of AmpC did not display enhanced β-lactamase activity. Resistance to ceftolozane/tazobactam in P. aeruginosa is associated with changes in AmpC; however, the apparent loss of β-lactamase activity in AmpC∆7 suggests that non-AmpC mechanisms could play an important role in resistance to β-lactam/β-lactamase inhibitor combinations. |
| format | Article |
| id | doaj-art-47ed234790a04dd889c2fbfca540c2a7 |
| institution | Kabale University |
| issn | 2090-6625 2090-6633 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Infectious Diseases |
| spelling | doaj-art-47ed234790a04dd889c2fbfca540c2a72025-02-03T01:24:19ZengWileyCase Reports in Infectious Diseases2090-66252090-66332018-01-01201810.1155/2018/90952039095203In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated PathwaysErik Skoglund0Henrietta Abodakpi1Rafael Rios2Lorena Diaz3Elsa De La Cadena4An Q. Dinh5Javier Ardila6William R. Miller7Jose M. Munita8Cesar A. Arias9Vincent H. Tam10Truc T. Tran11University of Houston College of Pharmacy, Houston, TX, USAUniversity of Houston College of Pharmacy, Houston, TX, USAMolecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, ColombiaMolecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, ColombiaGrupo de Investigación en Resistencia Antimicrobiana y Epidemiología Hospitalaria – RAEH, Universidad El Bosque, Bogotá, ColombiaCenter for Antimicrobial Resistance and Microbial Genomics, UTHealth McGovern Medical School, Houston, TX, USAMolecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, ColombiaCenter for Antimicrobial Resistance and Microbial Genomics, UTHealth McGovern Medical School, Houston, TX, USACenter for Antimicrobial Resistance and Microbial Genomics, UTHealth McGovern Medical School, Houston, TX, USAMolecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, ColombiaUniversity of Houston College of Pharmacy, Houston, TX, USACenter for Antimicrobial Resistance and Microbial Genomics, UTHealth McGovern Medical School, Houston, TX, USATwo pairs of ceftolozane/tazobactam susceptible/resistant P. aeruginosa were isolated from 2 patients after exposure to β-lactams. The genetic basis of ceftolozane/tazobactam resistance was evaluated, and β-lactam-resistant mechanisms were assessed by phenotypic assays. Whole genome sequencing identified mutations in AmpC including the mutation (V213A) and a deletion of 7 amino acids (P210–G216) in the Ω-loop. Phenotypic assays showed that ceftolozane/tazobactam resistance in the strain with AmpCV213A variant was associated with increased β-lactamase hydrolysis activity. On the other hand, the deletion of 7 amino acids in the Ω-loop of AmpC did not display enhanced β-lactamase activity. Resistance to ceftolozane/tazobactam in P. aeruginosa is associated with changes in AmpC; however, the apparent loss of β-lactamase activity in AmpC∆7 suggests that non-AmpC mechanisms could play an important role in resistance to β-lactam/β-lactamase inhibitor combinations.http://dx.doi.org/10.1155/2018/9095203 |
| spellingShingle | Erik Skoglund Henrietta Abodakpi Rafael Rios Lorena Diaz Elsa De La Cadena An Q. Dinh Javier Ardila William R. Miller Jose M. Munita Cesar A. Arias Vincent H. Tam Truc T. Tran In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated Pathways Case Reports in Infectious Diseases |
| title | In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated Pathways |
| title_full | In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated Pathways |
| title_fullStr | In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated Pathways |
| title_full_unstemmed | In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated Pathways |
| title_short | In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated Pathways |
| title_sort | in vivo resistance to ceftolozane tazobactam in pseudomonas aeruginosa arising by ampc and non ampc mediated pathways |
| url | http://dx.doi.org/10.1155/2018/9095203 |
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