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Efficacy of mecillinam against clinical multidrug-resistant Escherichia coli in a murine urinary tract infection model

Permanent lenke
https://hdl.handle.net/10037/17908
DOI
https://doi.org/10.1016/j.ijantimicag.2019.11.008
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article.pdf (782.3Kb)
Publisert versjon (PDF)
Dato
2019-11-23
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Zykov, Ilya Nikolaevich; Frimodt-Møller, Niels; Småbrekke, Lars; Sundsfjord, Arnfinn; Samuelsen, Ørjan
Sammendrag
Pivmecillinam, a pro-drug of mecillinam, has been used extensively in Scandinavia for the treatment of acute lower urinary tract infections (UTIs) caused by Enterobacterales. It is still an attractive first-line drug for the empirical treatment of UTIs owing to the low prevalence of resistance as well as its favourable impact on the intestinal microbiota as a pro-drug and good in vitro efficacy against extended-spectrum β-lactamase (ESBL)- and plasmid-mediated AmpC β-lactamase-producing Escherichia coli. However, optimal dosing of pivmecillinam as well as its in vivo efficacy against UTIs caused by multidrug-resistant (MDR) broad-spectrum β-lactamase-producing E. coli has not been thoroughly studied. In this study, the efficacy of two mimicked human dosing regimens of pivmecillinam (200 mg and 400 mg three times daily) against clinical E. coli strains, including isolates producing ESBLs (CTX-M-14 and CTX-M-15), plasmid-mediated AmpCs (CMY-4 and CMY-6) and carbapenemases (NDM-1 and VIM-29), in a murine UTI model was compared. Both dosing regimens reduced the number of CFU/mL in urine for all strains, including mecillinam-resistant strains. Combining the effect for all six strains showed no significant differences in effect between doses for all three fluids/organs, but for each dose there was a highly significant effect in urine, kidney and bladder compared with vehicle-treated mice. Overall, this highlights the need for further studies to elucidate the role of mecillinam in the treatment of infections caused by MDR E. coli producing broad-spectrum β-lactamases, including specific carbapenemases.
Er en del av
Zykov, I.N. (2020). Old antibiotics as alternative treatment options for urinary tract infections caused by ESBL-, AmpC- and carbapenemase-producing Escherichia coli. (Doctoral thesis). https://hdl.handle.net/10037/18260
Forlag
Elsevier
Sitering
Zykov IN, Frimodt-Møller N, Småbrekke L, Sundsfjord A, Samuelsen Ø. Efficacy of mecillinam against clinical multidrug-resistant Escherichia coli in a murine urinary tract infection model. International Journal of Antimicrobial Agents. 2019;55(2)
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  • Artikler, rapporter og annet (medisinsk biologi) [1103]
Copyright 2019 The Author(s)

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