
Mutational change of CTX‐M‐15 to CTX‐M‐127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient
Author(s) -
Nielsen Karen Leth,
Hansen Katrine Hartung,
Nielsen Jesper Boye,
Knudsen Jenny Dahl,
Schønning Kristian,
FrimodtMøller Niels,
Hertz Frederik Boëtius,
Jansåker Filip
Publication year - 2019
Publication title -
microbiologyopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.881
H-Index - 36
ISSN - 2045-8827
DOI - 10.1002/mbo3.941
Subject(s) - mecillinam , microbiology and biotechnology , escherichia coli , ceftazidime , antibiotics , biology , medicine , enterobacteriaceae , genetics , bacteria , pseudomonas aeruginosa , gene
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 bla CTX‐M‐15 to bla CTX‐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 bla CTX‐M‐15 with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first‐line treatment for UTI.