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Mutational Change of CTX-M-15 to CTX-M-127 Resulting in Mecillinam Resistant Escherichia Coli During Pivmecillinam Treatment of a Patient

Mutational Change of CTX-M-15 to CTX-M-127 Resulting in Mecillinam Resistant Escherichia Coli During Pivmecillinam Treatment of a Patient

Karen Leth Nielsen, Katrine Hartung Hansen, Jesper Boye Nielsen, Jenny Dahl Knudsen, Kristian Schønning, Niels Frimodt-Møller, Frederik Boëtius Hertz, Filip Jansåker

Microbiologyopen. 2019 Dec;8(12):e941.

PMID: 31573735

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP32887017	Mecillinam		32887-01-7	Price

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