A Study to Investigate PK, Safety, Tolerability of Cefepime-enmetazobactam in Pediatric Participants With cUTI

Inclusion Criteria:

• Participant must be from birth to <18 years of age. Participants up to 2 months musthave been born at term or preterm with a gestational age ≥32 weeks.
• Written informed consent from parent(s) or other legally acceptable representative(s),and informed assent from participant (if age appropriate according to localregulations).
• If female and has reached menarche, or has reached Tanner stage 3 development, (evenif not having reached menarche) the participant is authorized to participate in thisclinical study if the following criteria are met:

1. Participant has a negative urine and/or serum human chorionic gonadotropin testat screening visit. As serum tests may miss an early pregnancy, relevantmenstrual history, and sexual history, including methods of contraception, shouldbe considered
2. Participant agrees to avoid conception from the time of screening until 7 daysafter receipt of study intervention and agrees not to attempt pregnancy from thetime of screening until 7 days after EOT with study intervention, and participantagrees to follow guidelines received regarding continuation of abstinence,initiation of abstinence or about allowed contraception, and
3. Participant reports sexual abstinence for the prior 3 months or reported the useof at least 1 of the acceptable methods of contraception, including anintrauterine device (with copper banded coil), levonorgestrel intrauterine systemor regular medroxyprogesterone injections, or participant agrees to initiatesexual abstinence from the time of screening until 7 days after end of treatment (EOT) with study intervention.

• Participant has a clinically suspected and/or bacteriologically documented complicatedurinary tract infection (cUTI) or acute pyelonephritis judged by the investigator torequire the participant to be hospitalized for treatment with intravenous (i.v.)therapy.
• The causative pathogen is confirmed or suspected to be susceptible tocefepime-enmetazobactam.
• Participant has pyuria, defined as dipstick analysis positive for leukocyte esteraseOR:

1. If ≥1 year of age: White blood cell (WBC) count >10 cells/µL in unspun urine or ≥10 cells/high power field in spun urine.
2. If <1 year of age: WBC count >5 cells/µL in unspun urine or ≥5 cells/high powerfield in spun urine.

• Participant demonstrates clinical signs and/or symptoms of either acute pyelonephritisor cUTI at the Screening Visit, as defined by the following criteria: a. For pyelonephritis, participants must have at least 2 of the following new orworsening signs and/or symptoms: i. If 0 to <2 years of age:
• Fever (as defined by the investigator)
• Failure to thrive
• Recent weight loss
• Irritability
• Poor feeding
• Lack of normal level of activity
• Abdominal tenderness on physical examination
• Vomiting ii. If 2 to <18 years of age:
• Fever (as defined by the investigator)
• Dysuria
• Urinary urgency
• Urinary frequency
• New-onset urinary incontinence
• Suprapubic pain, flank pain, or abdominal pain
• Suprapubic tenderness or CVA tenderness on physical examination
• Nausea or vomiting OR b. For cUTI, participants must have at least 2 of the new or worsening signsand/or symptoms listed above AND must have at least 1 of the followingcomplicating factors:
• Obstructive uropathy
• Congenital, functional, or anatomic abnormality of the urogenital tract
• Temporary indwelling urinary catheter
• Bladder instrumentation within <24 hours
• Recurrent UTI (≥2 events within a 12-month period)
• Have a baseline urine culture specimen obtained within 48 hrs prior to the first doseof the study intervention. (Participants may be enrolled in this study and start i.v.study intervention therapy before the Investigator knows the results of the baselineurine culture in the event the causative pathogen is suspected to be susceptible tocefepime-enmetazobactam). Specimen is to be obtained by suprapubic aspiration, clean intermittent urethralcatheterization, indwelling urethral catheter, or mid- stream clean catch.
• Likely to survive the current illness or hospitalization.
• Sufficient intravascular access (peripheral or central) to receive study intervention

Exclusion Criteria:

• History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any seriousreaction to cefepime, any cephalosporin, penicillins, β-lactamase inhibitors (e.g.,tazobactam, sulbactam, or clavulanic acid), or other β-lactam agents.
• Previous enrolment in this study, or in another interventional study ≤30 days beforei.v. administration of study intervention.
• Concurrent infection requiring systemic antibiotics in addition to the i.v. studyintervention therapy at the time of first study intervention administration.
• Receipt of systemic antibiotics within 24 hours before obtaining the study qualifyingpre-treatment baseline urine sample and before study intervention therapy. Exceptionsare:
• Receipt up to 24 hours of short-acting antibacterial agent with a daily dose notcompleted. (Refer protocol ► Section 10.5, Appendix 5 for the list of allowed anddisallowed antibiotics).
• Patients who received prior antimicrobial therapy for the current cUTI/AP, and 1)in the Investigator's opinion, failed that prior antibiotic therapy (i.e.,presented with worsening signs and symptoms), AND 2) were documented that thepathogen is non-susceptible to the prior antibiotic therapy.
• Patients who have received antimicrobial prophylaxis for recurrent cUTI and thenpresented signs and symptoms consistent with an active new cUTI or AP.
• A permanent indwelling bladder catheter or instrumentation including nephrostomy orcurrent urinary catheter or anticipation of urinary catheter placement that would notbe removed during the course of i.v. study intervention therapy administration.
• Participant has suspected or known complete obstruction of any portion of the urinarytract, perinephric abscess, or ileal loops.
• Participant has trauma to the pelvis or urinary tract.
• Participant has undergone renal transplantation.
• Participant has a condition or history of any illness that, in the opinion of theinvestigator, would have made the participant unsuitable for the study (e.g., may haveconfounded the results of the study or posed additional risk in administering thestudy therapy to the participant).
• Participant is considered unlikely to survive the 6-week study period or had a rapidlyprogressive illness, including septic shock, that was associated with a high risk ofmortality.
• At the time of first study intervention administration, known presence of a cUTIcaused by pathogens resistant to Cefepime - enmetazobactam.
• Presence of any of the following clinically significant laboratory abnormalities:

1. Haematocrit <25% or haemoglobin <8 g/dL (<80 g/L, <4.9 mmol/L) for children ≥ 1month, or <13 g/dL (<130 g/L, <8.0 mmol/L) for children < 1 month.
2. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST)>3 timesthe age-specific upper limit of normal (ULN), or total bilirubin >2 times ULN (except known Gilbert's disease) and Absolute Neutrophil count<1000/ mm3.
3. eGFR <30 mL/min/1.73m2. (updated creatinine-based "Bedside Schwartz" equation (Schwartz et al. 2009))

• Participant has baseline QTcB (corrected Bazett's formula) of greater than 450 msec.
• History of seizures, excluding well-documented febrile seizures of childhood.
• If female, currently pregnant or breast feeding.