High Rate of Per Oral Mecillinam Treatment Failure in Community-Acquired Urinary Tract Infections Caused by ESBL-Producing Escherichia coli

Abstract

A population-based study was performed to investigate the efficacy of mecillinam treatment of community-acquired urinary tract infections (CA-UTI) caused by extended-spectrum β-lactamase (ESBL) producing Escherichia coli. The study was conducted in South-Eastern Norway. Data from patients with CA-UTI caused by ESBL-producing and non-producing (random controls) E. coli were collected through interviews, questionnaires, medical records and the Norwegian Prescription Database. Treatment failure was defined as a new antibiotic prescription appropriate for UTI prescribed within two weeks after the initial antimicrobial therapy. Multivariable logistic regression analysis was performed to identify treatment agents and patient- or bacterial traits associated with treatment failure. A total of 343 patients (mean age 59) were included, of which 158 (46%) were treated with mecillinam. Eighty-one patients (24%, mean age 54) had infections caused by ESBL producing E. coli, and 41 of these patients (51%) received mecillinam as the primary treatment. Mecillinam treatment failure was observed in 18 (44%) of patients infected by ESBL-producing strains and in 16 (14%) of patients with a CA-UTI caused by ESBL non-producing strains. Multivariable analysis showed that ESBL status (odds ratio (OR) 3.2, 95% confidence interval (CI) 1.3–7.8, p = 0.009) and increased MIC of mecillinam (OR 2.0 for each doubling value of MIC, CI 1.4–3.0, p<0.001) were independently associated with mecillinam treatment failure. This study showed a high rate of mecillinam treatment failure in CA-UTIs caused by ESBL producing E. coli. The high failure rate could not be explained by the increased MIC of mecillinam alone. Further studies addressing the use of mecillinam against ESBL-producing E. coli, with emphasis on optimal dosing and combination therapy with β-lactamase inhibitors, are warranted.

The antimicrobial activity of mecillinam, nitrofurantoin, temocillin and fosfomycin and comparative analysis of resistance patterns in a nationwide collection of ESBL-producing Escherichia coli in Norway 2010–2011

“…This observation indicates the possible presence of an acquired reduced susceptibility to mecillinam in the ESBL group of strains that should be further investigated. A high rate of mecillinam treatment failure for UTI caused by ESBL-producing E. coli has been reported in Norway using 200 mg/TID, and the proportion of failures increased as the mecillinam MIC increased above the ECOFF [23]. However, authors did not clarify if the study included lower UTIs or upper UTIs; mecillinam is not indicated for pyelonephritis and treatment failures in this case are expected.…”

Antimicrobial susceptibility of uropathogens isolated from Cambodian children

“…13 The resistance to mecillinam, not seen in other studies, suggests that this antibiotic should be used with caution in our setting. [14][15][16] For children with urosepsis, gentamicin, ESC and ciprofloxacin would not be reliable empirical choices. The carbapenems and amikacin would be more predictably active, but these are not widely available in most local health-care settings.…”

Antimicrobial susceptibility of uropathogens isolated from Cambodian children

“…13 The resistance to mecillinam, not seen in other studies, suggests that this antibiotic should be used with caution in our setting. [14][15][16] For children with urosepsis, gentamicin, ESC and ciprofloxacin would not be reliable empirical choices. The carbapenems and amikacin would be more predictably active, but these are not widely available in most local health-care settings.…”