Oral and Intravenous Fosfomycin for the Treatment of Complicated Urinary Tract Infections

Table 2

Randomized comparative trial data of ZTI-01 (IV fosfomycin) versus piperacillin-tazobactam in the treatment of patients with complicated urinary tract infection (cUTI) and acute pyelonephritis (AP).

Trial description	Study type	Total subjects	Treatment regimens	Primary outcome measure	Secondary outcome measure
Author: Kaye et al. [3]; Clinical Trial Registration. NCT02753946	Phase 2/3 randomized trial	465	Experimental: Fosfomycin; 6 grams IV (t’ 1 h) every 8 hours for 7–14 days	(i) Overall response^a was defined as a composite of clinical cure and microbiologic eradication at TOC in the m-MITT population (N)	(i) Clinical cure^b rates in the 2 treatment groups in MITT, m-MITT, CE, and ME populations (N) at TOC; (ii) Microbiological eradication^c rates in m-MITT and ME population at TOC
			Comparator: Piperacillin-tazobactam; 4 grams piperacillin/0.5 grams tazobactam IV (infused over 1 hour) every 8 hours for 7–14 days	Results n/N (%); Fosfomycin: cUTI: 52/85 (61.2%); AP: 67/99 (67.7%); Total: 119/184 (64.7%); Piperacillin-tazobactam: cUTI: 35/84 (41.7%); AP: 62/94 (66.0%); Total: 97/178 (54.5%)	Results n/N (%); Clinical cure overall	Fosfomycin: 167/184 (90.8%); Piperacillin-tazobactam: 163/178 (91.6%)
					Clinical cure per pathogen; E. coli; K. pneumoniae; Proteus mirabilis; Enterobacter cloacae species complex; P. aeruginosa; Microbiological eradication; Microbiological eradication per pathogen; E. coli; K. pneumoniae; P. mirabilis; E. cloacae species complex; P. aeruginosa	Fosfomycin: 120/133 (90.2%); Piperacillin-tazobactam: 120/133 (90.2%); Fosfomycin: 25/27 (92.6%); Piperacillin-tazobactam: 25/25 (100%); Fosfomycin: 8/9 (88.9%); Piperacillin-tazobactam: 3/5 (60.0%); Fosfomycin: 8/9 (88.9%); Piperacillin-tazobactam: 3/3 (100%); Fosfomycin: 8/8 (100%); Piperacillin-tazobactam: 9/9 (100%); Fosfomycin: 121/184 (65.8%); Piperacillin-tazobactam: 100/178 (56.2%); Fosfomycin: 87/133 (72.9%); Piperacillin-tazobactam: 84/133 (63.2%); Fosfomycin:18/27 (66.7%); Piperacillin-tazobactam: 14/25 (56.0%); Fosfomycin: 8/9 (88.9%); Piperacillin-tazobactam: 1/5 (20.0%); Fosfomycin: 6/9 (66.7%); Piperacillin-tazobactam: 3/3 (100%); Fosfomycin: 3/8 (37.5%); Piperacillin-tazobactam: 4/9 (44.4%)

Table adapted from reference [3]. TOC, test of cure (day 19–21); m-MITT, microbiologic modified intent to treat population; MITT, microbiological intent to treat; CE, clinically evaluable; ME, microbiologically evaluable; N, total number of patients in specified cohort; n, number of patients achieving specified outcome. ^aOverall response measure defined as complete resolution or significant improvement of signs and symptoms such that no further antimicrobial therapy is warranted; baseline pathogen reduction to <10⁴ CFU/mL on urine culture, if applicable on repeat blood culture. ^bClinical cure defined as complete resolution or significant improvement of signs and symptoms such that no further antimicrobial therapy is warranted. ^cMicrobiological eradication defined as a urine culture or blood culture, if applicable, demonstrating that the bacterial pathogen identified at baseline has decreased from ≥10⁵ CFU/mL to <10⁴ CFU/mL.