A Study of Efficacy and Safety of Intravenous Cefiderocol (S-649266) Versus Imipenem/Cilastatin in Complicated Urinary Tract Infections
Condition: Urinary Tract Infections
MeSH terms: Infections; Communicable Diseases; Urinary Tract Infections; Pyelonephritis
Intervention: Cefiderocol; Imipenem/cilastatin
Intervention description: 2000 mg intravenously every 8 hours for 7 to 14 days; dose adjustments for participants with reduced renal function (estimated CrCl ≤ 70 mL/minute) and/or body weight (< 70 kg) included every 6-hour dosing intervals and/or reduced doses.; 1000 mg of each intravenously every 8 hours for 7 to 14 days; dose adjustments for participants with reduced renal function (estimated CrCl ≤ 70 mL/minute) and/or body weight (< 70 kg) included every 6-hour dosing intervals and/or reduced doses.
Intervention MeSH terms: Imipenem; Cilastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 452.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: S-649266; complicated urinary tract infection; cefiderocol; acute uncomplicated pyelonephritis; Gram-negative pathogens; imipenem/cilastatin

Summary:

      The purpose of this study was to determine the efficacy and safety of intravenous cefiderocol
      (S-649266) in hospitalized adults with complicated urinary tract infections caused by
      Gram-negative pathogens.
    

Eligibility criteria:

        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

               -  Azotemia caused by intrinsic renal disease (blood urea nitrogen and creatinine
                  values greater than normal laboratory values) OR Pyelonephritis and normal
                  urinary tract anatomy, ie, acute uncomplicated pyelonephritis AND

        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

          -  Costo-vertebral angle tenderness on physical examination AND

        All subjects had to have urinalysis evidence of pyuria demonstrated by 1 of the following:

          -  Dipstick analysis positive for leukocyte esterase

          -  ≥ 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 previously with an empiric antibiotic other than the
                  study drugs but failed treatment, both clinically and microbiologically, were
                  eligible for the study if they had an identified Gram-negative uropathogen that
                  was not susceptible to the previously used empiric treatment and 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