Safety and Efficacy of ZTI-01 (IV Fosfomycin) vs Piperacillin/Tazobactam for Treatment cUTI/AP Infections

Inclusion Criteria:

1. A signed informed consent form (ICF);

2. Male or female, at least 18 years of age;

3. Diagnosis requires hospitalization and treatment with intravenous (IV) antibiotics;

4. Documented or suspected cUTI or AP including at least 2 protocol defined signs andsymptoms and a urine specimen with evidence of pyuria plus at least one protocoldefined associated risk

5. Pretreatment baseline urine culture specimen

6. Expectation that any implanted urinary instrumentation will be removed or replaced notlonger than 24 hours, after randomization;

7. Expectation that patient will survive anticipated duration of the study;

8. Patient requires initial hospitalization to manage the cUTI or AP;

9. Women of childbearing potential have had a negative pregnancy test beforerandomization and be willing to consistently use a highly effective method ofcontraception

10. Male study participants will be required to use condoms with a spermicide throughoutstudy

Exclusion Criteria:

1. Presence of any of the following conditions: perinephric abscess, renalcorticomedullary abscess, uncomplicated urinary tract infection, recent history oftrauma to the pelvis or urinary tract, polycystic kidney disease, chronicvesicoureteral reflux, previous or planned renal transplantation; patients receivingdialysis/hemodialysis/CVVH, previous or planned cystectomy or ileal loop surgery;known or suspected infection; caused by pathogen resistant to study treatmentantibiotics

2. Presence of suspected or confirmed acute bacterial prostatitis, orchitis,epididymitis, or chronic bacterial prostatitis as determined by history and/orphysical examination;

3. Gross hematuria requiring intervention;

4. Urinary tract surgery within 7 days prior to randomization or urinary tract surgeryplanned during the study period;

5. Creatinine clearance <20 mL/min using the Cockcroft-Gault formula;

6. Non-renal source of infection such as endocarditis, osteomyelitis, abscess,meningitis, or pneumonia diagnosed within 7 days prior to randomization;

7. Signs of severe sepsis as defined per protocol;

8. Pregnant or breastfeeding women;

9. Known seizure disorder requiring current treatment with anti-seizure medication whichwould prohibit the patient from complying with the protocol;

10. Cancer chemotherapy, immunosuppressive medications for transplantation, or medicationsfor rejection of transplantation with 30 days of randomization;

11. Significant hepatic disease or dysfunction, including known acute viral hepatitis orhepatic encephalopathy;

12. ALT/AST >5 × ULN or total bilirubin >3 × ULN at Screening;

13. Receipt of any potentially-effective systemic antibiotic with activity againstGram-negative uropathogens for more than 24 hours within the 72-hour window prior torandomization (exceptions defined in protocol);

14. Requirement for additional systemic antibiotic therapy (other than study drug) orantifungal therapy for vaginal candidiasis;

15. Likely to require the use of an antibiotic for cUTI or AP prophylaxis during thestudy;

16. Known history of HIV virus infection and known recent CD4 count <200/mm3;

17. Presence of significant immunodeficiency or an immunocompromised condition andlong-term use of systemic corticosteroids;

18. Presence of neutropenia;

19. Presence of thrombocytopenia;

20. A QT interval corrected using Fridericia's formula >480 msec;

21. History of significant hypersensitivity or allergic reaction to fosfomycin, anycontraindication to the use of piperacillin/tazobactam;

22. Participation in a clinical study involving investigational medication orinvestigational device within the last 30 days prior to randomization;

23. Inability, in the judgment of the Investigator, to tolerate the salt load required forstudy drug administration;

24. Unable or unwilling, in the judgment of the Investigator, to comply with the protocol;

25. Any patients previously randomized in this study.