Objectives: The FOSFO-MIC study assessed the clinical and microbiological effectiveness, and safety of intravenous fosfomycin in treating complicated urinary tract infections (cUTIs) caused by Escherichia coli, in comparison with other intravenous antimicrobials.
Methods: A prospective, multinational matched-cohorts study involving adults with community-acquired cUTIs and receiving targeted therapy with intravenous fosfomycin or other first-line drugs (beta-lactams or fluoroquinolones) was conducted from November 2019 to May 2023 in 10 centres from Spain, Italy, and Türkiye. Matching criteria included healthcare-relation, Charlson and Pitt scores.
Purpose: A analysis of data from a previously published clinical trial was conducted using the desirability of outcome ranking (DOOR) methodology with the aim provide additional information on the use of fosfomycin for the treatment of bacteraemic urinary tract infection (BUTI) caused by multi-drug-resistant (MDR) .
Methods: Three DOOR systems with five, six and seven categories, respectively were developed. Safety and efficacy were prioritised in all rankings, but step down to oral therapy and exposure to antibiotics with lower ecological impact were also considered in DOOR-6 and DOOR-7.
In recent years, new evidence has shown that the SOS response plays an important role in the response to antimicrobials, with involvement in the generation of clinical resistance. Here we evaluate the impact of heterogeneous expression of the SOS response in clinical isolates of Escherichia coli on response to the fluoroquinolone, ciprofloxacin. In silico analysis of whole genome sequencing data showed remarkable sequence conservation of the SOS response regulators, RecA and LexA.
View Article and Find Full Text PDFIntroduction/objective: Suppression of the SOS response in combination with drugs damaging DNA has been proposed as a potential target to tackle antimicrobial resistance. The SOS response is the pathway used to repair bacterial DNA damage induced by antimicrobials such as quinolones. The extent of -regulated protein expression and other associated systems under pressure of agents that damage bacterial DNA in clinical isolates remains unclear.
View Article and Find Full Text PDFBackground: Temocillin is an old antimicrobial that is resistant to hydrolysis by ESBLs but has variable activity against carbapenemase-producing Enterobacteriaceae. The current EUCAST susceptibility breakpoints for Enterobacterales are set at ≤16 mg/L (susceptible with increased exposure) based on a dose of 2 g q8h, but there is limited information on the efficacy of this dose against temocillin-susceptible carbapenemase-producing Klebsiella pneumoniae isolates.
Objectives: To evaluate the efficacy of this dose using a hollow-fibre infection model (HFIM) against six KPC-2-producing clinical isolates of K.