Characteristics of gram-negative urinary tract infections caused by extended spectrum beta lactamases: pivmecillinam as a treatment option within South Dublin, Ireland

Abstract

BackgroundThe prevalence of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is increasing and the therapeutic options are limited, especially in primary care. Recent indications have suggested pivmecillinam to be a suitable option. This pilot study aimed to assess the viability of pivmecillinam as a therapeutic option in a Dublin cohort of mixed community and healthcare origin.MethodsA prospective measurement of mean and fractional inhibitory concentrations of antibiotic use in 95 patients diagnosed with UTI caused by ESBL-producing Enterobacteriaceae was carried out. 36 % patients were from general practice, 40 % were admitted to hospital within south Dublin, and 25 % samples arose from nursing homes. EUCAST breakpoints were used to determine if an isolate was sensitive or resistant to antibiotic agents.ResultsSixty-nine percent of patients (N = 66) with urinary ESBL isolates were female. The mean age of females was 66 years compared with a mean age of 74 years for males. Thirty-six percent of isolates originated from primary care, hospital inpatients (26 %), and nursing homes (24 %). The vast majority of ESBL isolates were E. coli (80 %). The E tests for mecillinam and co-amoxiclav had concentration ranges from 0.16 mg/L up to 256 mg/L. The mean inhibitory concentration (MIC) of mecillinam ranged from 0.25 to 256 mg/L, while co-amoxiclav MICs ranged from 6 to 256 mg/L. The percentage of isolates resistant to mecillinam and co-amoxiclav was found to be 5.26 and 94.74 % respectively.ConclusionsThis is the first study exploring the use of pivmecillinam in an Irish cohort and has demonstrated that its use in conjunction with or without co-amoxiclav is an appropriate and useful treatment for urinary tract infections caused by ESBL-producing organisms.

Emerging clinical role of pivmecillinam in the treatment of urinary tract infections caused by Extended Spectrum βeta‐lactamase (ESBL) producing Enterobacteriaceae

“…The infections because of ESBL‐producing organisms are a major burden on clinical practice and a public health concern worldwide. These infections are increasing and are associated with increased morbidity, mortality and healthcare costs, as well as there is growing need to for broad‐spectrum antibiotics . UTIs are the most common infections caused by ESBL‐producing Enterobacteriaceae .…”

“…ESBL are a group of plasmid mediated enzymes which destroy the beta‐lactams such as penicillins, cephalosporins, and monbactam antimicrobials and ESBL‐producing Enterobacteriaceae are also resistant to quinolones and trimethoprim. This means that there are limited options to treat uncomplicated UTIs caused by ESBL‐producing organisms . These factors have initiated an idea to consider older antibiotics as an alternate option to treat uncomplicated UTIs …”

“…Several risk factors have been associated with ESBL organisms causing UTIs such as recurrent UTIs, prostatic disease, recent hospital admission, travel to high prevalence countries, recent antibiotic exposure including fluoroquinolone exposure, diabetes, previous instrumentation, old age and recreational fresh water swimming . One study from Denmark that confirmed antibiotic exposure within 30 days of UTI because of ESBL‐producing organism and multiple hospital admissions are linked with community UTIs especially ESBL‐producing Escherichia coli ( E coli ) .…”

“…ESBL‐producing Enterobacteriaceae are usually linked with nosocomial infection but they are also widespread in the community settings. Most patients with UTIs do not require hospital admission and they can be treated with suitable oral antibiotic in the community …”

PMQR Determinants Expression in Gram-negative Uropathogens Clinically Isolated from Hospitalized Patients with Pyelonephritis in Kharkiv, Ukraine

“…According to the published data, acquirеd rеsistance to beta-lactams is predоminantly mediated by extended spectrum beta-lactamases (ESBLs) that cоmpromise the efficаcу of all known betа-lactams, excеpt cephаmycine and carbаpеnems [8]. ESBLs are оften еncoded by genеs lоcated on lаrgе plаsmids, which аlsо cаrry gеnes related with resistance to other аntimicrobial аgents suсh as аminоglуcosides, trimеthoprim, sulphonаmides, tetrаcyclines and chloramphenicol [9].…”