A Study of Efficacy/Safety of Intravenous S-649266 Versus Imipenem/Cilastatin in Complicated Urinary Tract Infections

The purpose of this study is to determine the efficacy and safety of intravenous S 649266
versus intravenous imipenem/cilastatin in hospitalized adults with complicated urinary tract
infections with or without pyelonephritis or acute uncomplicated pyelonephritis caused by
Gram-negative pathogens.

Inclusion Criteria:

- Hospitalized male and female patients ≥ 18 years

- Clinical diagnosis of either complicated urinary tract infections (cUTI) with or
without pyelonephritis or acute uncomplicated pyelonephritis

- cUTI diagnosed with a history of ≥ 1 of the following: indwelling urinary catheter or
recent instrumentation of the urinary tract, Urinary retention (caused by benign
prostatic hypertrophy), urinary retention of at least 100 mL or more of residual
urine after voiding (neurogenic bladder), obstructive uropathy, and azotemia caused
by intrinsic renal disease (blood urea nitrogen and creatinine values greater than
normal laboratory values)

- At least 2 of the following signs or symptoms: chills or rigors or warmth associated
with fever (temperature greater than or equal to 38 degrees Celsius), flank pain
(pyelonephritis) or suprapubic/pelvic pain (cUTI), nausea or vomiting, dysuria,
urinary frequency, or urinary urgency, and costo-vertebral angle tenderness on
physical examination

- Urinalysis evidence of pyuria demonstrated by dipstick analysis positive for
leukocyte esterase or ≥10 white blood cells (WBCs) per μL in unspun urine, or ≥ 10
WBCs per high power field in spun urine

- Positive urine culture within 48 hours prior to randomization containing ≥10^5 colony
forming unit (CFU)/mL of a Gram-negative uropathogen likely to be susceptible to
imipenem (IPM)

- Patients who were treated with an effective antibiotic for no more than 24 hours
during the previous 72 hours

- Patients who failed treatment, both clinically and microbiologically, and have an
identified uropathogen which is non-susceptible to the empiric treatment and is a
Gram-negative uropathogen likely to be susceptible to IPM

- Subjects receiving antibiotic prophylaxis for UTI who present with signs and symptoms
consistent with an active new UTI

Exclusion Criteria:

- Urine culture identifies only a Gram-positive pathogen and/or a Gram-negative
uropathogen resistant to IPM

- Urine culture at study entry isolates more than 2 uropathogens or patient has a
confirmed fungal UTI

- Asymptomatic bacteriuria, the presence of >10^5 CFU/mL of a uropathogen and pyuria
but without local or systemic symptoms

- Patient is receiving hemodialysis or peritoneal dialysis