Retracted: In vivo mecillinam resistance in Escherichia coli after pivmecillinam treatment of a urinary tract infection

Retraction: Nielsen, KL, Hansen, KH, Knudsen, JD, Frimodt‐Møller, N, Hertz, FB, Jansåker, F., In vivo mecillinam resistance in Escherichia coli after pivmecillinam treatment of a urinary tract infection, MicrobiologyOpen, 2019; e770 (https://doi.org/10.1002/mbo3.770). The above article, published online on 6 January 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors and John Wiley & Sons Ltd. The retraction has been agreed due to the authors’ self‐reported errors in their data rendering the article’s conclusions incorrect.


Abstract
Pivmecillinam (amdinocillin pivoxil) is the recommended first choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. Yet, in laboratory settings the frequency of mutation to mecillinam resistance has been found to be very high.
Treatment of UTI has a good clinical response, but low bacteriological cure rates.
Prevalence of mecillinam resistance in Escherichia coli remains low in spite of many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of extended-spectrum β-lactamase producing E. coli following pivmecillinam treatment. The only identified phenotypic differences in MEC-R compared to the original MEC-S isolate were full-length lipopolysaccharides with O-antigen (O25), mecillinam resistance, and a lower minimum inhibitory concentration for ceftazidime.
Whether the serotype change and mutation in fhlA is the cause of the mecillinam resistance is unknown. Further studies are required to elucidate this possible mechanism. We continue to recommend the use of pivmecillinam as first-line treatment for UTI, yet mecillinam treatment for other foci should be investigated.

R E T R
A C T E D SNP differences between the two isolates were identified with Geneious R9 using MEC-S as reference for the SNP call followed by verification by inspection of reference mapping with parameters previously described (Nielsen et al., 2016). Whole-genome alignments were analyzed with Mauve in Geneious followed by verification with reference mapping (>10× coverage with unique mapping).
For further depiction of the isolates, we used the following genomic The genomic analyses revealed no differences between the two isolates with respect to MLST (ST131) and phylotype (B2), prophage content, and plasmid Inc-groups (Table 1). Regarding serotype, SeroTypeFinder identified O25:K-:H2 in both MEC-S and MEC-R.
However, from the phenotypic serotype it was evident that MEC-S was a rough isolate that did not produce the O25 antigen, but genetically, it belonged to the O25:K-:H2 group. SeroTypeFinder does not identify rough phenotypes.
The genomic investigations revealed that the two isolates dif-  (Antón, 1995). In this perspective, it could be hypothesized that the reversion of the premature stop codon in fhlA to the fully translational fhlA of MEC-R could be correlated with the LPS production and mecillinam resistance by a serotype change from rough to O25, through yet unknown mechanisms.
Whether the bla TEM-1B deletion contributed to changed MIC for ceftazidime is not conclusive from these results, however should be investigated further. Alternatively, the changed ceftazidime MIC could be caused by minority variants of TEM, which cannot be detected by ResFinder but could differ undetected between the two isolates.
In this paper, we describe the clinical occurrence of mecillinam resistance, which has rarely been described with respect to genomic analyses on resistance in a patient. The observed mecillinam resistance is in accordance with previous laboratory findings (Thulin et al., 2015). The data indicate that a spontaneous mutation rather than horizontal gene transfer caused the resistance, contributing to the previously described mutations identified in the laboratory.
The clinical significance of such resistance is unknown; we are planning further studies to investigate the in vivo fitness in mice as well as susceptibility in urine for MEC-R to answer these questions. We continue to recommend the use of pivmecillinam as first-line treatment for UTI, yet mecillinam treatment for other foci should be investigated.

ACKNOWLEDG EMENTS
The authors would like to thank Jesper Boye Nielsen for his valuable contributions to this study. During JBNs employment at Department of Clinical Microbiology, Hvidovre University Hospital, Copenhagen, JBN functioned as a scientific advisor in regards to methods and analyses.

CO N FLI C T O F I NTE R E S T
All authors declare no conflict of interests.

E TH I C S S TATEM ENT
The study was approved by the Danish Data Protection Agency (I -suitnr. 01755 and id.nr. HVH-2012-022) for a previously published study (Jansåker et al., 2014). Included patients were asked to participate and gave written consent prior to inclusion.