Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum β-lactamase producing, Enterobacteriaceae infections: a systematic review

SummaryRising rates of resistance to antimicrobial drugs among Enterobacteriaceae limit the choice of reliably active forms of these drugs. We evaluated the evidence on fosfomycin as a treatment option for infections caused by members of the family Enterobacteriaceae with advanced resistance to antimicrobial drugs, including producers of extended-spectrum β-lactamase (ESBL). We systematically reviewed studies evaluating the antimicrobial activity, or the clinical effectiveness of fosfomycin. 17 antimicrobial-susceptibility studies were found and included in our Review, accounting for 5057 clinical isolates of Enterobacteriaceae with advanced resistance to antimicrobial drugs (4448 were producers of ESBL); 11 of the 17 studies reported that at least 90% of the isolates were susceptible to fosfomycin. Using a provisional minimum inhibitory concentration susceptibility breakpoint of 64 mg/L or less, 1604 (96·8%) of 1657 Escherichia coli isolates producing ESBL were susceptible to fosfomycin. Similarly, 608 (81·3%) of 748 Klebsiella pneumoniae isolates producing ESBL were susceptible to fosfomycin. In two clinical studies, oral treatment with fosfomycin–trometamol was clinically effective against complicated or uncomplicated lower urinary tract infections caused by ESBL-producing E coli in, cumulatively, 75 (93·8%) of the 80 patients evaluated. Initial clinical data support the use of fosfomycin for the treatment of urinary tract infections caused by these pathogens, although further research is needed.