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 responsea was defined as a composite of clinical cure and microbiologic eradication at TOC in the m-MITT population (N) | (i) Clinical cureb rates in the 2 treatment groups in MITT, m-MITT, CE, and ME populations (N) at TOC (ii) Microbiological eradicationc 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%) |
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| 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%) |
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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.