Daily fosfomycin versus levofloxacin for complicated urinary tract infections

ABSTRACT Fosfomycin, approved in the United States only for cystitis, is an attractive alternative for oral treatment of outpatient complicated urinary tract infections (cUTIs) as it has antimicrobial activity against most common uropathogens. The study was a multicenter, randomized, open-label pragmatic superiority clinical trial evaluating the efficacy of oral fosfomycin versus oral levofloxacin strategies in cUTIs (FOCUS study). The trial compared two strategies for initial or step-down oral therapy of cUTI without bacteremia after 0–48 hours of parenteral antibiotic therapy. Subjects were assigned to 3 g of fosfomycin or 750 mg (or dose adjusted for kidney function) of levofloxacin daily for 5–7 days. Clinical and microbiological cures were assessed at the end of therapy (EOT) and test of cure (TOC) (approximately 21 days from the start of antibiotics). The trial did not meet accrual goals; thus, the results were descriptive. Only 51 subjects were included in the microbiological intention-to-treat population. The subjects were mainly females (76%), with a mean age of 46.7 years (standard deviation [SD] = 20.8) and acute pyelonephritis (88%). At the end of therapy, clinical cure remained similar (69% and 68% for fosfomycin and levofloxacin strategies, respectively), and microbiological success was 100% for both strategies. At the test of cure, clinical cure was similar (84% and 86% in the fosfomycin and levofloxacin strategies, respectively); however, a numerically lower microbiological success was observed for fosfomycin (69% compared to 84% for levofloxacin). These limited data suggest that fosfomycin could be an oral alternative as a step-down therapy for the treatment of cUTIs (registry number NCT 03697993). IMPORTANCE Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics.