In Vitro Activity of Fosfomycin and Nitrofurantoin Against Contemporary Enterobacterales Pathogens Isolated from Indian Tertiary Care Hospitals

Background: In India, multidrug resistance in community and hospital associated Gram-negative pathogens has increased sharply over the past few years. In the absence of novel oral multidrug resistant-pathogen active therapies, the therapeutic situation with regard to community infections is even more challenging. Hence, the focus is now shifting toward potentially expanding the utility of older antibiotics such as fosfomycin and nitrofurantoin beyond their approved pathogen coverage. The current study was undertaken to assess the activity of fosfomycin and nitrofurantoin against Enterobacterales pathogens through minimum inhibitory concentration (MIC) determination to facilitate monitoring future shifts in susceptibility to these agents. Materials and Methods: The present study used 1,350 Enterobacterales, recently collected from various Indian tertiary care hospitals and preserved at Wockhardt Strain Repository. The MIC50/90 for fosfomycin and nitrofurantoin and the comparator antibiotics was determined for Escherichia coli (N = 470), Klebsiella pneumoniae (N = 429), Enterobacter spp., (N = 144), Proteus spp. (N = 262), and Citrobacter spp. (N = 45), using Clinical and Laboratory Standards Institute recommended agar dilution method. Results: Applying E. coli breakpoints, the susceptibility rates of fosfomycin for E. coli, K. pneumoniae, Enterobacter spp., Proteus spp., and Citrobacter spp., were 95.5%, 53.2%, 71.5%, 76.7%, and 91.1%, respectively. Applying respective breakpoints, the susceptibility rates of comparator drugs, including meropenem, were lower than fosfomycin. Susceptibility of nitrofurantoin for E. coli and Citrobacter isolate was 83%, while limited coverage (<13.2% susceptibility) was observed for other genera. Conclusion: Amidst widespread resistance, a > 70% fosfomycin susceptibility observed for clinical isolates, including strains expressing carbapenemases, is encouraging and supports conducting additional susceptibility and pharmacokinetic/pharmacodynamic studies to explore its potential for expanded therapeutic use. Nitrofurantoin activity spectrum was restricted to E. coli and Citrobacter spp. and, therefore, offers a relatively limited therapeutic scope.