Microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections caused by ESBL‐producing Escherichia coli

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica Vol. 128; no. 3; pp. 232 - 241
• Main Authors: Syre, Heidi, Hetland, Marit Andrea Klokkhammer, Bernhoff, Eva, Bollestad, Marianne, Grude, Nils, Simonsen, Gunnar Skov, Löhr, Iren Høyland
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.03.2020; Wiley
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amdinocillin; Amdinocillin Pivoxil - therapeutic use; Anti-Bacterial Agents - therapeutic use; Basale medisinske, odontologiske og veterinærmedisinske fag: 710; Basic medical, dental and veterinary science disciplines: 710; beta-Lactamases - metabolism; Community-Acquired Infections - drug therapy; Community-Acquired Infections - microbiology; E coli; ESBL; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - metabolism; Escherichia coli Infections - drug therapy; Escherichia coli Infections - microbiology; Escherichia coli Proteins - metabolism; Female; Gene sequencing; Genomes; Genotypes; Humans; Infections; Medical disciplines: 700; Medisinske Fag: 700; Microbial Sensitivity Tests - methods; Microorganisms; Middle Aged; Molecular microbiology; Patients; Pivmecillinam; Risk analysis; Risk Factors; Strains (organisms); Treatment Failure; Treatment Outcome; Urinary tract; Urinary Tract - microbiology; Urinary tract diseases; urinary tract infection; Urinary tract infections; Urinary Tract Infections - drug therapy; Urinary Tract Infections - microbiology; Urogenital system; VDP; Whole genome sequencing; Young Adult; ESBL; Molecular microbiology; pivmecillinam; Escherichia coli; urinary tract infection
• ISSN: 0903-4641; 1600-0463; 1600-0463
• DOI: 10.1111/apm.13013

The aim of this study was to identify microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections (ca‐UTIs) caused by ESBL‐producing Escherichia coli. Eighty‐nine ESBL‐producing E. coli isolated from women suffering from ca‐UTIs were included. The susceptibilities to mecillinam were determined using MIC gradient strip. Whole genome sequencing was performed on a MiSeq platform, and genome assembly was performed using SPAdes v3.11.0. Neither mecillinam MICs nor ESBL genotypes were associated with treatment outcome of patients treated with pivmecillinam. Specific STs, however, showed significant differences in treatment outcome. Patients infected with ST131 were more likely to experience treatment failure compared to patients infected with non‐ST131 (p 0.02) when adjusted for pivmecillinam dose, mecillinam MIC and severity of infection. Patients infected with ST69 were more often successfully treated compared to patients infected with non‐ST69 (p 0.04). Patients infected with blaCTX‐M‐15 ST131 strains were more likely to experience treatment failure than those infected with non‐blaCTX‐M‐15 ST131 strains (p 0.02). The results suggest that specific STs are associated with the clinical efficacy of pivmecillinam. Further studies with a larger number of strains, including a larger number of mecillinam resistant strains, are needed to confirm these results.