The purpose of this study is to evaluate how Aztreonam (ATM) and Avibactam (AVI) are processed in pediatric participants. This study also aims to understand participant safety and effects in pediatric participants.
The study is seeking participants who are:
* 9 months to less than 18 years of age * Hospitalized * Suspected/known to have a gram-negative infection * Receiving intravenous (iv, given directly into a vein) antibiotics * Being treated for complicated infections of various body parts that includes the abdomen, urinary tract, blood stream, and lungs. * Participants will receive either ATM-AVI or best available therapy (BAT). * Both therapies will be given through a vein. * Participants with complicated abdominal infections will also receive iv Metronidazole (MTZ). Patients with cIAI and Cockayne Syndrome are excluded due to a risk of severe hepatotoxicity with the use of MTZ. - Participants on ATM-AVI treatment who have anaerobic infections will also receive iv MTZ at the study doctor's discretion. * The iv dose of ATM-AVI will be based on the participant's weight and kidney function. * The study doctor will determine the iv dose of BAT. * During the first 2 study days, participants on ATM-AVI therapy will have 5 blood draws in small quantities. * Starting on day 4, the study doctor will decide if participants may be switched to oral therapy. * Participants will receive a maximum of 14 days of ATM-AVI treatment. * After discharge from the hospital, 1 study visit may be required. * Depending on the participant's response, the study duration will be from 33 to 50 days. * The investigator will contact participants by phone 28 to 35 days after the last study treatment to check participants health status.
Participants ≥9 months to <18 years of age at Screening; Female (post-menarchal) participants must have a negative serum/urine pregnancy test (β hCG sensitivity ≥25 mIU/mL).
Suspected/confirmed cIAI, cUTI, HAP/VAP, or BSI with gram-negative pathogens.
Require hospitalization and IV antibiotic treatment.
Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
Gram-negative species not expected to respond to ATM AVI ≤14 days.
Pregnant or breastfeeding; fertile male/female unwilling/unable to use effective contraception for at ≥7 days (males) or ≥28 days (females) after last ATM-AVI infusion.
Microbiologically known or high likelihood of monomicrobial infection with a gram-positive organism, lung abscess, pleural empyema, or post-obstructive pneumonia, lung or heart transplant.
Parallel
ATM-AVI
DrugA drug specifically designed to treat resistant gam-negative bacterial infections
BAT
DrugBAT will be selected by the investigator and administered iv as appropriate for the selected drug(s)
Maximum Predicted Plasma Concentration (Cmax) of ATM and AVI
Cmax is the maximum plasma concentration of ATM and AVI as population pharmacokinetic (popPK) analysis predicts.
Minimum Predicted Trough Plasma Concentration (Cmin) of ATM and AVI
Cmin is the minimum trough plasma concentration of ATM and AVI as popPK analysis predicts.
Area under the Concentration-Time Curve (AUC) of ATM-AVI
AUC is a measure of the plasma concentration of ATM and AVI overtime as popPK analysis predicts.
Plasma Decay Half-Life (t1/2)
Half-life is the time measured for the plasma concentration of ATM and AVI to decrease by one half as popPK analysis predicts.
Perentage of participants with favorable clinical response (CR) at end of iv study treatment (EOIV)
EOIV favorable CR is baseline signs and symptoms have improved such that with in 24hours after iv study treatment stopped, or premature discontinuation of the study drug or early withdrawal from the study no further antimicrobial treatment for the index infection is required. In addition, for cIAI participants, no unplanned drainage or surgical intervention is necessary since the initial procedure.
Percentage of Participants With Favorable Clinical Response (CR) at End of Treatment (EOT)
EOT is only for those that were switched to oral therapy a favorable CR is baseline signs and symptoms have improved such that after study treatment, no further antimicrobial treatment for the index infection is required. In addition for cIAI participants, no unplanned drainage or surgical intervention is necessary since the initial procedure.
Percentage of Participants With Favorable Clinical Response (CR) at Test of Cure (TOC)
A TOC favorable CR is baseline signs and symptoms have improved such that after up to 14 days of study treatment, no further antimicrobial treatment for the index infection is required. In addition for cIAI participants, no unplanned drainage or surgical intervention is necessary since the initial procedure.
Percentage of participants with Favorable Microbiological Response at end of iv study drug treatment (EOIV)
Eradication (or urine quantification \<103 CFU/mL for cUTI participants) of causative pathogen from an appropriately obtained specimen at the site of infection and presumed eradication specific to cIAI and HAP/VAP participants when repeat culture of specimens were not performed or clinically indicated in a participant who had a clinical response of cure
