Evaluation of the Efficacy and Safety of Intravenous Imipenem/Cilastatin/XNW4107 in Comparison With Meropenem in Hospitalized Adults With cUTI Including AP (EudraCT no. 2022-000061-40)

Inclusion Criteria:

1. Patients willing and able to provide written informed consent.
2. Willing and able to comply with all study assessments and adhere to the protocolschedule.
3. Hospitalized or requiring hospitalization for cUTI or AP in male or female patients ≥18 years on the day of signing informed consent.
4. Requiring treatment with IV antibiotic therapy.
5. Evidence of AP or cUTI At least 1 of the following:

• Nausea or vomiting.
• Chills or rigors or warmth associated with fever (temperature >38°C).
• Peripheral white blood cell count (WBC) >10,000/mm³ or bandemia , regardless ofWBC count.

6. Having at least 1 of the following complicated factors for cUTI (not required for AP):
7. Indwelling catheter of the urinary tract.
8. Urinary retention.
9. Any functional or anatomical abnormality of the urogenital tract resulting in atleast 100 mL or more of residual urine after voiding.
10. Obstructive uropathy .
11. Evidence of pyuria demonstrated by 1 of the following methods:
12. Dipstick analysis positive for leukocyte esterase.
13. ≥10 WBCs per µL in unspun urine, or ≥10 WBCs per high power field in spun urine.

Exclusion Criteria:

1. Patients with any of the following conditions:
2. Suspected or confirmed perinephric abscess
3. Suspected or confirmed renal corticomedullary abscess
4. Suspected or confirmed acute or chronic bacterial prostatitis, orchitis, orepididymitis, as determined by history and/or physical examination
5. Known polycystic kidney disease or only 1 functional kidney
6. Known chronic vesicoureteral reflux
7. Previous renal transplantation or planned renal transplantation within 2 weeks ofstudy entry
8. Patients receiving renal replacement therapy
9. Complete, permanent obstruction of the urinary tract
10. Urinary tract symptoms attributable to a sexually transmitted disease.
11. Gross hematuria requiring intervention other than administration of study drug.
12. Urinary tract surgery within 7 days prior to randomization or urinary tract surgeryplanned during the study period (except surgery required to relieve an obstruction orplace a stent or nephrostomy).
13. Patient has any urinary catheter or device that will not be removed or replaced (ifremoval is not clinically acceptable) during IV therapy, including but NOT limited toindwelling bladder catheters, ureteral catheters, suprapubic catheters, J stents, andnephrostomy tubes.
14. Renal function at Screening as estimated glomerular filtrated rate <15 mL/min/1.73㎡,calculated using Modification of Diet in Renal Disease.
15. Known non-urinary tract source of infection such as endocarditis, osteomyelitis,abscess, meningitis, or pneumonia diagnosed within 7 days prior to randomization.
16. Any rapidly progressing disease or immediately life-threatening illness, including,but not limited to, current or impending respiratory failure, septic shock, acuteheart failure, acute coronary syndrome, unstable arrhythmias, hypertensive emergency,acute hepatic failure, active gastrointestinal bleeding, profound metabolicabnormalities (e.g., diabetic ketoacidosis), or acute cerebrovascular events.
17. If the culture result is available prior to randomization and identifies only aGram-positive pathogen and/or only a Gram negative pathogen (>10^5 CFU/mL) known to beresistant to meropenem
18. If the culture result is available prior to randomization and identifies isolates >2pathogens or no pathogens with >10^5 CFU/mL identified or patient has a confirmedfungal UTI.
19. Receipt of more than 24 hours of a potentially effective systemic antibacterialswithin 72 hours prior to start of study therapy.
20. History of a seizure disorder.
21. Female patients of childbearing potential, who are unable or unwilling to use a highlyeffective method of birth control during the study and for at least 30 days followingthe last dose of study medication.
22. A female who is pregnant or breastfeeding, or have a positive pregnancy test atScreening.
23. Patient is participating in any clinical study of any investigational medication (i.e., non-licensed medication) during the 30 days prior to randomization. COVID-19vaccines that are given under emergency use authorization are not consideredinvestigational agents.
24. Documented presence of immunodeficiency or an immunocompromised condition includinghematologic malignancy, bone marrow transplant, known human immunodeficiency virusinfection with a CD4 count <200/mm³, or requiring frequent or prolonged use ofsystemic corticosteroids or other immunosuppressive drugs.
25. Patients with 1 or more of the following laboratory abnormalities in baselinespecimens: aspartate aminotransferase, alanine aminotransferase >3 × the upper limitof normal (ULN), total bilirubin level >2 × ULN (except for isolatedhyperbilirubinemia due to known Gilbert's disease), neutrophils <500 cells/mm³,platelet count <40,000/mm³
26. Patients requires concomitant medication with valproic acid or divalproex.
27. History of active liver disease, cirrhosis.
28. Documented or severe hypersensitivity or previous severe adverse drug reaction,especially to any beta-lactam antibiotics, or any of the excipients used in the studydrug formulations.
29. Any other condition or prior therapy, which, in the opinion of the investigator, wouldmake the patient unsuitable for this study.