ATM-AVI for Bacterial Infections
Palo Alto (17 mi)Age: < 18
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Pfizer
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Is the drug Avibactam, Aztreonam a promising treatment for bacterial infections?Yes, Avibactam combined with Aztreonam shows promise as a treatment for bacterial infections, especially those caused by difficult-to-treat bacteria like Klebsiella pneumoniae. Studies suggest that this combination can effectively fight infections that are resistant to many other antibiotics.3581012
What safety data exists for ATM-AVI treatment for bacterial infections?Ceftazidime-avibactam (Avycaz) has been evaluated for safety and tolerability in treating complicated urinary tract infections, intra-abdominal infections, and hospital-acquired pneumonia. It was generally well tolerated, with a safety profile consistent with ceftazidime alone. Aztreonam-avibactam, a combination involving ceftazidime-avibactam and aztreonam, is pending phase 3 clinical trials and has shown potent in vitro activity against resistant bacteria, but specific safety data for this combination is not detailed in the provided research.12467
What data supports the idea that ATM-AVI for Bacterial Infections is an effective drug?The available research shows that the combination of ceftazidime-avibactam with aztreonam is promising for treating infections caused by highly resistant bacteria. Specifically, it is effective against infections due to Pseudomonas aeruginosa and other drug-resistant bacteria. This combination helps restore the effectiveness of antibiotics against tough bacterial strains, making it a valuable option for treating complicated infections.146911
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you must stop taking your current medications. However, you cannot use any prohibited medications during the trial, and you must be willing to use Metronidazole if required. It's best to discuss your current medications with the study doctor.
Eligibility Criteria
This trial is for hospitalized children aged 9 months to less than 18 years with suspected or confirmed serious gram-negative infections, requiring IV antibiotics. It's not for those unlikely to respond to the study drugs within 14 days, pregnant/breastfeeding individuals without effective contraception, or those with certain medical conditions.Treatment Details
The trial compares Aztreonam and Avibactam (ATM-AVI) combination against the best available therapy (BAT) in treating complicated infections like abdominal, urinary tract, bloodstream, and lung infections. ATM-AVI dosage depends on weight and kidney function; treatment lasts up to 14 days with possible switch to oral therapy.
2Treatment groups
Experimental Treatment
Active Control
Group I: ATM-AVIExperimental Treatment1 Intervention
ATM-AVI administered iv every 6 or 8 hours and dosed according to participant's weight and kidney function for up to 14 days depending on response. At the investigator's discretion, the participant may be switched to oral therapy after 3 days of iv ATM-AVI therapy
Group II: Best available therapy (BAT)Active Control1 Intervention
BAT will be selected by the investigator and administered iv. At the investigator's discretion, the participant may be switched to oral therapy after 3 days of iv BAT
Avibactam is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Avycaz for:
- Complicated Urinary Tract Infections (cUTI) including Pyelonephritis
- Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP)
🇪🇺 Approved in European Union as Emblaveo for:
- Complicated intra-abdominal infections (cIAI)
- Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP)
- Complicated urinary tract infections (cUTI), including pyelonephritis
Find a clinic near you
Research locations nearbySelect from list below to view details:
Weill Cornell Medicine-New York Presbyterian HospitalNew York, NY
Le Bonheur Children's HospitalMemphis, TN
Rady Children's HospitalSan Diego, CA
Mount Sinai Kravis Children´s HospitalNew York, NY
More Trial Locations
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Who is running the clinical trial?
PfizerLead Sponsor
References
Ceftazidime-Avibactam (Avycaz): For the Treatment of Complicated Intra-Abdominal and Urinary Tract Infections. [2020]Ceftazidime-avibactam (Avycaz) for the treatment of complicated infections.
Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections. [2019]Ceftazidime-avibactam (Zavicefta®) is an intravenously administered combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam. In the EU, ceftazidime-avibactam is approved for the treatment of adults with complicated urinary tract infections (cUTIs) [including pyelonephritis], complicated intra-abdominal infections (cIAIs), hospital-acquired pneumonia (HAP) [including ventilator-associated pneumonia (VAP)], and other infections caused by aerobic Gram-negative organisms in patients with limited treatment options. This article discusses the in vitro activity and pharmacological properties of ceftazidime-avibactam, and reviews data on the agent's clinical efficacy and tolerability relating to use in these indications, with a focus on the EU label. Ceftazidime-avibactam has excellent in vitro activity against many important Gram-negative pathogens, including many extended-spectrum β-lactamase-, AmpC-, Klebsiella pneumoniae carbapenemase- and OXA-48-producing Enterobacteriaceae and drug-resistant Pseudomonas aeruginosa isolates; it is not active against metallo-β-lactamase-producing strains. The clinical efficacy of ceftazidime-avibactam in the treatment of cUTI, cIAI and HAP (including VAP) in adults was demonstrated in pivotal phase III non-inferiority trials with carbapenem comparators. Ceftazidime-avibactam treatment was associated with high response rates at the test-of-cure visit in patients with infections caused by ceftazidime-susceptible and -nonsusceptible Gram-negative pathogens. Ceftazidime-avibactam was generally well tolerated, with a safety and tolerability profile consistent with that of ceftazidime alone and that was generally typical of the injectable cephalosporins. Thus, ceftazidime-avibactam represents a valuable new treatment option for these serious and difficult-to-treat infections.
Efficacy of Ceftazidime-avibactam Plus Aztreonam in Patients With Bloodstream Infections Caused by Metallo-β-lactamase-Producing Enterobacterales. [2021]In vitro data support the use of combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI), but clinical studies are lacking. The aim of our study was to compare the outcome of patients with bloodstream infections (BSIs) due to metallo-β-lactamase (MBL)-producing Enterobacterales treated either with CAZ-AVI plus ATM or other active antibiotics (OAAs).
Phenotypic synergy testing of ceftazidime-avibactam with aztreonam in a university hospital having high number of metallobetalactamase producing bacteria. [2021]Ceftazidime-avibactam combination with aztreonam and role of rapid synergy reporting has not been widely evaluated. Also the synergy correlation with various betalactamases has not been widely studied.
In vitro activity of aztreonam/avibactam against a global collection of Klebsiella pneumoniae collected from defined culture sources in 2016 and 2017. [2021]This study reports on the activity of aztreonam/avibactam (ATM-AVI) against a collection of Klebsiella pneumoniae collected in 2016 and 2017.
Assessing the in vitro impact of ceftazidime on aztreonam/avibactam susceptibility testing for highly resistant MBL-producing Enterobacterales. [2021]Aztreonam/avibactam is a combination agent that shows promise in treating infections caused by highly antibiotic-resistant MBL-producing Enterobacterales. This combination can be achieved by combining two FDA-approved drugs: ceftazidime/avibactam and aztreonam. It is unknown whether ceftazidime in the combination ceftazidime/aztreonam/avibactam has a synergistic or antagonistic effect on the in vitro activity of aztreonam/avibactam by significantly increasing or decreasing the MIC.
Aztreonam-Avibactam Susceptibility Testing Program for Metallo-Beta-Lactamase-Producing Enterobacterales in the Antibiotic Resistance Laboratory Network, March 2019 to December 2020. [2022]Aztreonam-avibactam is a drug combination pending phase 3 clinical trials and is suggested for treatment of severe infections caused by metallo-beta-lactamase (MBL)-producing Enterobacterales by combining ceftazidime-avibactam and aztreonam. Beginning in 2019, four Antibiotic Resistance Laboratory Network regional laboratories offered aztreonam-avibactam susceptibility testing by broth microdilution. For 64 clinical isolates tested, the MIC50 and MIC90 values of aztreonam-avibactam were 0.5/4 μg/ml and 8/4 μg/ml, respectively. Aztreonam-avibactam displayed potent in vitro activity against the MBL-producing Enterobacterales tested.
Suboptimal drug exposure leads to selection of different subpopulations of ceftazidime-avibactam-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae in a critically ill patient. [2022]Ceftazidime-avibactam (CAZ-AVI) is a promising novel agent with activity against carbapenem-resistant Enterobacteriaceae. Here, we describe the dynamic evolution of a Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infection in a critically ill patient treated with CAZ-AVI-tigecycline combination therapy.
[Several key points that need to be concerned in the clinical application of ceftazidime/avibactam]. [2021]Ceftazidime/avibactam is a new enzyme inhibitor combination medication composed of ceftazidime and avibactam. It forms an enzyme-inhibitor complex by covalently binding β-lactamase, which can effectively restore the antibacterial activity of ceftazidime against a variety of carbapenemase-producing enterobacteriaceae strains, covering Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Klebsiella pneumonia (CRKP) and other common drug-resistant gram-negative bacteria infections. The related issues of anti-infective effects of ceftazidime/avibactam on lung infections, abdominal infections, bloodstream infections, urinary tract infections and other different infections were discussed in this article. The clinical safety and indications of ceftazidine/avibatan were referred in the article.
A simple disk pre-diffusion test to predict in vitro aztreonam/avibactam activity against NDM-producing Klebsiella pneumoniae complex. [2022]The aim of this study was to describe a simple test to predict in vitro efficacy of aztreonam/avibactam (ATM-AVI) combination based on a pre-diffusion assay involving routinely available ceftazidime/avibactam (CAZ-AVI) and aztreonam (ATM) disks.
Effectiveness of ceftazidime-avibactam for the treatment of infections due to Pseudomonas aeruginosa. [2022]Clinical experience with ceftazidime-avibactam (CAZ-AVI) for treatment of infections due to multidrug or extremely resistant (MDR/XDR) Pseudomonas aeruginosa (P. aeruginosa) is limited.
A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)-producing Enterobacterales infection. [2023]In response to infection with New Delhi metallo-beta-lactamase (NDM)-producing Enterobacterales, combination antimicrobial therapy with ceftazidime/avibactam (CAZ/AVI) plus aztreonam (ATM) has been explored. This study evaluated a practical laboratory method of testing for clinically significant synergy between CAZ/AVI+ATM in NDM-producing Enterobacterales.