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

TY - JOUR

T1 - Mutational change of CTX-M-15 to CTX-M-127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient

AU - Nielsen, Karen Leth

AU - Hansen, Katrine Hartung

AU - Nielsen, Jesper Boye

AU - Knudsen, Jenny Dahl

AU - Schønning, Kristian

AU - Frimodt-Møller, Niels

AU - Hertz, Frederik Boëtius

AU - Jansåker, Filip

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

U2 - 10.1002/mbo3.941

DO - 10.1002/mbo3.941

M3 - Journal article

C2 - 31573735

SN - 2045-8827

JO - MicrobiologyOpen

JF - MicrobiologyOpen

M1 - e941

ER -