Urinary tract infections (UTIs) are incredibly common for women and they often lead to recurrence. Nitrofurantoin (NIT) is a nitrofuran antibiotic that has been on the front-line to treat uncomplicated UTIs. We discovered that certain metabolites could resensitize tolerant E. coli to NIT, even while they remain non-growing, and demonstrated that tolerance was due to insufficient reducing equivalents for NIT activation. We further extended our findings to another nitrofuran antibiotic, nitrofurazone, and a strain of uropathogenic E. coli. Our findings suggest that a cotreatment of NIT and metabolites, such as mannitol, may enhance its bactericidal activity and reduce the recurrence of UTIs.