720. Efficacy of Fosfomycin for Injection (FOS) vs. Piperacillin–Tazobactam (PIP-TAZ) in Adults with Complicated Urinary Tract Infection (cUTI) and Acute Pyelonephritis (AP): ZEUS Study Outcomes in Patients With Reduced Study Drug Susceptibility

Abstract Background FOS is being pursued for US registration in cUTI/AP. Safety and efficacy of FOS vs. PIP-TAZ were demonstrated in the noninferiority ZEUS trial in hospitalized patients with cUTI/AP. Although FOS resistance has been observed in several in vitro studies, resistance rates in clinical settings have remained relatively stable despite >40 years of clinical use of FOS outside of the United States. Here we report outcomes in patients who developed reduced susceptibility to study drug (FOS or PIP-TAZ) after enrollment in ZEUS. Methods Patients received IV FOS 6g q8h or PIP-TAZ 4.5g q8h for 7 days (no oral switch allowed). The primary endpoint was overall success (clinical cure + microbiologic eradication) in microbiologic modified intent-to-treat (m-MITT) population at test-of-cure (TOC; Day 19–21). Reduced susceptibility to FOS or PIP-TAZ was defined as a ≥4-fold increase from baseline in minimum inhibitory concentration (MIC) at Day 5, end of treatment (EOT; Day 7–8), TOC, or late follow-up (LFU; Day 26 ± 2). Microbiologic eradication/persistence of baseline and postbaseline pathogens was confirmed post hoc by pulsed-field gel electrophoresis (PFGE). Results In all m-MITT patients, overall success/clinical cure/microbiologic eradication rates (with PFGE) at TOC were 69.0/90.8/70.7% (FOS) and 57.3/91.6/60.1% (PIP-TAZ). Reduced study drug susceptibility was identified in 7/184 (3.8%) FOS and 8/178 (4.5%) PIP-TAZ patients; all had monomicrobial infections (Table 1). Of these patients, almost all were aged ≥50 years (93%), male (73%), white (100%), and had a screening diagnosis of cUTI (93%). At TOC, 7/7 FOS patients and 7/8 PIP-TAZ patients had microbiologic persistence but all patients were clinical cures; these responses were all sustained through LFU (Table 1). Conclusion In the ZEUS study, few patients had urine isolates with reduced postbaseline susceptibility to either FOS or PIP-TAZ. No trend was observed in isolate species associated with decreased susceptibility to FOS or PIP-TAZ, including various Enterobacteriaceae species and Pseudomonas aeruginosa. Despite microbiologic persistence at TOC in a small number of patients, all of these patients were clinical cures at TOC and sustained cures at LFU. Disclosures All authors: No reported disclosures.