Mutational change of CTX‐M‐15 to CTX‐M‐127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient

Abstract Pivmecillinam (amdinocillin pivoxil) is the recommended first‐choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and preval...

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Main Authors: Karen Leth Nielsen, Katrine Hartung Hansen, Jesper Boye Nielsen, Jenny Dahl Knudsen, Kristian Schønning, Niels Frimodt‐Møller, Frederik Boëtius Hertz, Filip Jansåker
Format: Article
Language:English
Published: Wiley 2019-12-01
Series:MicrobiologyOpen
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Online Access:https://doi.org/10.1002/mbo3.941
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author Karen Leth Nielsen
Katrine Hartung Hansen
Jesper Boye Nielsen
Jenny Dahl Knudsen
Kristian Schønning
Niels Frimodt‐Møller
Frederik Boëtius Hertz
Filip Jansåker
author_facet Karen Leth Nielsen
Katrine Hartung Hansen
Jesper Boye Nielsen
Jenny Dahl Knudsen
Kristian Schønning
Niels Frimodt‐Møller
Frederik Boëtius Hertz
Filip Jansåker
author_sort Karen Leth Nielsen
collection DOAJ
description Abstract Pivmecillinam (amdinocillin pivoxil) is the recommended first‐choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and prevalence of mecillinam resistance in Escherichia coli remains low despite many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of ESBL‐producing E. coli following pivmecillinam treatment. The identified phenotypic differences in the mecillinam resistant isolate compared with the original mecillinam susceptible isolate were a full‐length LPS with O‐antigen (O25), mecillinam resistance and a lower MIC for ceftazidime. Regarding genotype, the resistant isolate differed with a mutation in blaCTX‐M‐15 to blaCTX‐M‐127, loss of a part of a plasmid and a genomic island, respectively, and insertion of a transposase in wbbL, causing the rough phenotype. The observed mecillinam resistance is expected to be caused by the mutation in blaCTX‐M‐15 with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first‐line treatment for UTI.
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spelling doaj.art-28ed3dfe9a624fc3916e025cd07bd4702022-12-21T22:58:17ZengWileyMicrobiologyOpen2045-88272019-12-01812n/an/a10.1002/mbo3.941Mutational change of CTX‐M‐15 to CTX‐M‐127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patientKaren Leth Nielsen0Katrine Hartung Hansen1Jesper Boye Nielsen2Jenny Dahl Knudsen3Kristian Schønning4Niels Frimodt‐Møller5Frederik Boëtius Hertz6Filip Jansåker7Department of Clinical Microbiology Rigshospitalet Copenhagen DenmarkDepartment of Clinical Microbiology Rigshospitalet Copenhagen DenmarkDepartment of Clinical Microbiology Hvidovre Hospital Hvidovre DenmarkDepartment of Clinical Microbiology Rigshospitalet Copenhagen DenmarkDepartment of Clinical Microbiology Hvidovre Hospital Hvidovre DenmarkDepartment of Clinical Microbiology Rigshospitalet Copenhagen DenmarkDepartment of Clinical Microbiology Herlev Hospital Herlev DenmarkDepartment of Clinical Microbiology Rigshospitalet Copenhagen DenmarkAbstract Pivmecillinam (amdinocillin pivoxil) is the recommended first‐choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and prevalence of mecillinam resistance in Escherichia coli remains low despite many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of ESBL‐producing E. coli following pivmecillinam treatment. The identified phenotypic differences in the mecillinam resistant isolate compared with the original mecillinam susceptible isolate were a full‐length LPS with O‐antigen (O25), mecillinam resistance and a lower MIC for ceftazidime. Regarding genotype, the resistant isolate differed with a mutation in blaCTX‐M‐15 to blaCTX‐M‐127, loss of a part of a plasmid and a genomic island, respectively, and insertion of a transposase in wbbL, causing the rough phenotype. The observed mecillinam resistance is expected to be caused by the mutation in blaCTX‐M‐15 with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first‐line treatment for UTI.https://doi.org/10.1002/mbo3.941Escherichia coliLPSmecillinammetabolismmutationO‐antigen
spellingShingle Karen Leth Nielsen
Katrine Hartung Hansen
Jesper Boye Nielsen
Jenny Dahl Knudsen
Kristian Schønning
Niels Frimodt‐Møller
Frederik Boëtius Hertz
Filip Jansåker
Mutational change of CTX‐M‐15 to CTX‐M‐127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient
MicrobiologyOpen
Escherichia coli
LPS
mecillinam
metabolism
mutation
O‐antigen
title Mutational change of CTX‐M‐15 to CTX‐M‐127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient
title_full Mutational change of CTX‐M‐15 to CTX‐M‐127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient
title_fullStr Mutational change of CTX‐M‐15 to CTX‐M‐127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient
title_full_unstemmed Mutational change of CTX‐M‐15 to CTX‐M‐127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient
title_short Mutational change of CTX‐M‐15 to CTX‐M‐127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient
title_sort mutational change of ctx m 15 to ctx m 127 resulting in mecillinam resistant escherichia coli during pivmecillinam treatment of a patient
topic Escherichia coli
LPS
mecillinam
metabolism
mutation
O‐antigen
url https://doi.org/10.1002/mbo3.941
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