Evaluation of Safety, Pharmacokinetics and Efficacy of Ceftazidime and Avibactam (CAZ-AVI ) Compared With Cefepime in Children From 3 Months to Less Than 18 Years of Age With Complicated Urinary Tract Infections (cUTIs)

Inclusion Criteria

• Must be ≥3 calendar months to 38.5°C (or equivalent by other methods) with or without patient symptoms of rigor, chills, warmth Nausea Vomiting Irritability Loss of appetite Flank pain
• Or patients considered to have complicated UTI as indicated by 2 of the previous qualifying signs/symptoms in (a) plus at least 1 complicating factor from the following:

Recurrent UTI (2 or more within 12 months period) Obstructive uropathy that is scheduled to be surgically relieved during IV study therapy and before the EOT Functional or anatomical abnormality of the urogenital tract, including anatomic malformations or neurogenic bladder Vesicoureteral reflux Use of intermittent bladder catheterisation or presence of an indwelling bladder catheter for >48 hours prior to the diagnosis of cUTI Urogenital procedure (eg, cystoscopy or urogenital surgery) within the 7 days prior to study entry

Exclusion Criteria

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Previous enrolment or randomisation in the present study
• Participation in another clinical study with an investigational product (IP) during the last 30 days before the first dose of IV study drug or have previously participated in the current study or in another study of CAZ-AVI (in which an active agent was received)
• History of hypersensitivity reactions to carbapenems, cephalosporins, penicillins or other β-lactam antibiotics
• Concurrent infection, including, but not limited to, central nervous system infection requiring systemic antibiotics in addition to the IV study drug therapy at the time of randomisation
• Receipt of more than 24 hours of any systemic antibiotics after culture and before study drug therapy
• Receipt of systemic antibiotics within 24 hours before obtaining the study qualifying pre-treatment baseline urine sample and before study drug therapy
• The child is suspected or documented to have an infection caused by organisms resistant to the prophylactic antibiotics
• A permanent indwelling bladder catheter or instrumentation including nephrostomy or current urinary catheter that will not be removed or anticipation of urinary catheter placement that will not be removed during the course of IV study drug therapy administration
• Patient has suspected or known complete obstruction of any portion of the urinary tract, perinephric abscess, or ileal loops
• Patient has had trauma to the pelvis or urinary tract
• Patient has undergone renal transplantation
• Patient has a condition or history of any illness that, in the opinion of the Investigator, would make the patient unsuitable for the study (eg, may confound the results of the study or pose additional risk in administering the study therapy to the patient)
• Patient is considered unlikely to survive the 6 to 8 week study period or have a rapidly progressive illness, including septic shock that is associated with a high risk of mortality
• At the time of randomisation, patient is known to have a cUTI caused by pathogens resistant to the antimicrobials planned to be used in the study
• Presence of any of the following clinically significant laboratory abnormalities:
• Haematocrit 3×the age-specific upper limit of normal (ULN), or total bilirubin >2×ULN (except known Gilbert's disease) For a) to b): unless if these values are acute and directly related to the infectious process being treated.
• Creatinine clearance <30 mL/min/1.73 m2 calculated using the child's measured height (length) and serum creatinine within the updated "bedside" Schwartz formula (Schwartz et al 2009):

CrCl (mL/min/1.73m2)=0.413×height (length) (cm)/serum creatinine (mg/dL)

• History of seizures, excluding well-documented febrile seizure of childhood
• If female, currently pregnant or breast feeding