Susceptibility of carbapenemase-producing Enterobacterales (CPE) to nitroxoline

Background Infections caused by carbapenemase-producing Enterobacterales (CPE) constitute a major global health concern and are associated with increased morbidity and mortality. Nitroxoline is an old antibiotic, which has recently been re-launched for the treatment of uncomplicated urinary tract infection. Because of low resistance rates it could be an interesting option for treatment of MDR isolates, yet data on CPE susceptibility are scarce. Objectives To analyse the in vitro activity of nitroxoline against CPE. Methods MICs of nitroxoline were determined by agar dilution for a collection of well-characterized carbapenemase producers (n=105), producing OXA-48-like (n=36), VIM (n=21), IMI (n=9), IMP (n=6), NDM (n=22), KPC (n=11), OXA-58 (n=2) and GES (n=2). For comparison, MICs of ertapenem, imipenem and meropenem were determined by agar gradient diffusion. Results For all 105 isolates, the MIC50/90 of nitroxoline was 8/16mg/L. All Escherichia coli isolates (30/30, 100%) showed low MICs of 2-8mg/L and were susceptible to nitroxoline. MICs of 32mg/L were recorded for five isolates of VIM- and IMI-producing Enterobacter cloacae (n=3) and OXA- and VIM-producing Klebsiella pneumoniae (n=2). Conclusions Nitroxoline exhibited excellent in vitro activity against most isolates producing common and rare carbapenemases. If the current EUCAST susceptibility breakpoint of <= 16mg/L for E. coli in uncomplicated urinary tract infections was applied, 95.2% (100/105) of isolates would be classified as susceptible. Nitroxoline could therefore be an alternative oral option for treatment of uncomplicated urinary tract infections caused by CPE.