Delving into the Latest Updates on Avibactam Sodium/Ceftazidime with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

AVE 1330/ceftazidime, AVE 1330A/ceftazidime, Avibactam/ceftazidime

+ [20]

Target

β-lactamase

Action

inhibitors

Mechanism

β-lactamase inhibitors(Beta Lactamase inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System DisordersRespiratory Diseases+ [2]

Active Indication

Abdominal AbscessCholecystitisCystitis+ [13]

Inactive Indication

Acute pyelonephritisFebrile NeutropeniaNeoplasms

Originator Organization

Allergan UC

Active Organization

AbbVie, Inc.Pfizer Biotechnology Ireland Unlimited Co.Pfizer Manufacturing Ireland Unlimited Co.

+ [2]

Inactive Organization

Forest Laboratories LLC

Pfizer Investment Co. Ltd.

AstraZeneca Pharmaceuticals Co. Ltd.

+ [3]

Drug Highest PhaseApproved

First Approval Date

United States (25 Feb 2015),

Complicated intra-abdominal infectionComplicated urinary tract infectionPyelonephritis

RegulationFast Track (United States), Priority Review (China)

Login to view timeline

Structure/Sequence

Molecular FormulaC7H11N3NaO6S

InChIKeyAXVUNLXMABVHIF-JBUOLDKXSA-N

CAS Registry1192491-61-4

View All Structures (2)

The purpose of this study is to learn about the safety and how effective is Zavicefta under actual clinical practice in Japan.
Zavicefta is a combination of Avibactam sodium and Ceftazidime hydrate.
This study is seeking for patients with:
* sepsis (A very serious infection in your blood caused by germ (a bacteria)) or
* renal impairment (loss of kidney function) who are administrated with Zavicefta for the first time.
Subjects will take part in this study from the start date of receiving Zavicefta (Day 1) to Day 28.

Start Date13 Mar 2025

Sponsor / Collaborator

Pfizer Inc.

NCT06811727

/ Not yet recruitingPhase 4IIT

CONTinuous Infusion Versus Intermittent Dosing of ceftaZidime/AVIbactam in Critically Ill Patients With Klebsiella Pneumoniae OXA-48 or Pseudomonas Aeruginosa Infections: A Single-centre Randomized Open-label Trial (ZAVICONT)

Ceftazidime/avibactam (CZA) is an essential treatment option for managing infections caused by multidrug-resistant (MDR) gram-negative (G-) bacteria, including Klebsiella pneumoniae OXA-48 and carbapenem-resistant Pseudomonas aeruginosa. Critically ill intensive care unit (ICU) patients frequently exhibit altered pharmacokinetics (PK) of CZA, potentially compromising optimal PK/pharmacodynamic (PD) target attainment with standard dosing regimens. This study compares the efficacy of continuous infusion (CI) versus conventional intermittent dosing (ID) of CZA in critically ill ICU patients with severe infections caused by K. pneumoniae OXA-48 or P. aeruginosa.
This single-centre, randomized, open-label trial will be conducted at a tertiary care hospital within the University Hospital Centre in Zagreb, Croatia, with a 1:1 allocation ratio. One hundred forty critically ill ICU patients requiring CZA treatment will be randomized to receive either ID (2 g/0.5 g every 8 hours over 2 hours) or an equivalent dose in CI (6 g/1.5 g continuously over 24 hours).
The primary outcome is the microbiological success rate. Secondary outcomes include clinical success rate, time to symptom improvement, length of ICU and hospital stay, 28-day all-cause mortality, pathogen recurrence rate, time to weaning from mechanical ventilation, cumulative vasoactive-inotropic score, adverse events, and the ratio of ceftazidime plasma concentration to the pathogen's minimum inhibitory concentration (C/MIC).
This trial seeks to provide evidence on the optimal administration strategy for CZA in critically ill ICU patients with severe infections due to MDR G- pathogens.

Start Date01 Mar 2025

Sponsor / Collaborator-

NCT06818565

/ Not yet recruitingNot ApplicableIIT

Comparison of Efficacy and Safety of Ceftazidime Avibactam Versus Extended Infusions of High Dose Meropenem in Patients of ACLF With Nosocomial Infections.

Acute on chronic liver failure patients are at high risk for nosocomial infections due to liver dysfunction, which impairs immune responses and increases vulnerability to infections. Key factors contributing to nosocomial infections in ACLF patients include ascites, use of invasive devices, and recent hospitalization, frequent need for broad spectrum antibiotics. Multidrug resistance is a growing issue, making treatment more challenging, common pathogens involved are gram negative bacteria such as Escherichia Coli and Klebsiella pneumoniae. Surveillance data show increasing carbapenem resistant enterobacterales (CRE) infection rates in cirrhotics, with high morbidity and mortality rates. The impact of these nosocomial infections is profound, significantly worsen outcomes in ACLF patients, leading to prolonged hospitalizations, increased health care costs and higher mortality rates. Early detection and effective antibiotic stewardship are essential to manage antibiotic resistance and improve patient outcomes. In this study we aim to compare efficacy and safety of Ceftazidime avibactam versus extended infusions of high dose Meropenem in patients of ACLF with nosocomial infections.

Start Date10 Feb 2025

Sponsor / Collaborator

Institute of Liver & Biliary Sciences

100 Clinical Results associated with Avibactam Sodium/Ceftazidime

Login to view more data

100 Translational Medicine associated with Avibactam Sodium/Ceftazidime

Login to view more data

100 Patents (Medical) associated with Avibactam Sodium/Ceftazidime

Login to view more data

527

Literatures (Medical) associated with Avibactam Sodium/Ceftazidime

01 Mar 2025·JOURNAL OF INFECTION AND CHEMOTHERAPY

Efficacy and safety of ceftazidime-avibactam in combination with metronidazole in Japanese patients with complicated intra-abdominal infection: A phase 3, multicentre, open-label study

Article

Author: Nagashima, Masahito ; Tabuchi, Riko ; Mikamo, Hiroshige ; Tawadrous, Margaret ; Wible, Michele ; Nakazuru, Yoshiomi ; Suzuki, Misaki ; Ohta, Makoto

BACKGROUND:

This phase 3 open-label study evaluated the efficacy and safety of ceftazidime-avibactam in Japanese patients with complicated intra-abdominal infections (cIAIs).

METHODS:

Hospitalised adults with cIAI received ceftazidime-avibactam + metronidazole for 5-14 days. The primary efficacy endpoint was clinical cure at the test-of-cure (TOC) visit in the clinically evaluable (CE) analysis set. Efficacy was evaluated against a pre-defined point estimate criterion of ≥78 %. Microbiological responses, safety and pharmacokinetics were assessed as secondary objectives.

RESULTS:

Sixty patients were enrolled at 27 Japanese study sites; 59 (mean age 57 years, 42 % female) were included in the modified intent-to-treat (MITT) analysis set. The most common baseline pathogens (microbiological MITT analysis set; n = 42) were Escherichia coli (n = 31; 74 %), Pseudomonas aeruginosa (n = 6; 14 %) and Klebsiella pneumoniae (n = 5; 12 %); all were susceptible to ceftazidime-avibactam. In the CE analysis set (n = 40), 36 patients (90.0 %; 95 % confidence interval: 76.3, 97.2) achieved clinical cure at TOC. Favourable per-pathogen microbiological responses at TOC were >90 % for common Gram-negative pathogens, including E. coli, K. pneumoniae, and P. aeruginosa. Adverse events were generally mild; the most common were constipation (12 %), diarrhoea (12 %), and insomnia (10 %). Pharmacokinetic observations of ceftazidime and avibactam were consistent with previous reports.

CONCLUSION:

The proportion of patients with clinical cure at TOC was greater than the pre-defined threshold of 78.0 %. These findings in Japanese patients are consistent with multi-regional phase 3 non-inferiority trials demonstrating the efficacy and safety of ceftazidime-avibactam in patients with cIAIs.

CLINICALTRIALS GOV IDENTIFIER:

NCT04927312.

01 Mar 2025·Journal of Global Antimicrobial Resistance

Genomic Insights into a Multidrug-Resistant Escherichia Coli of sequence type 155: A Ceftazidime-Avibactam Resistant Strain Harboring Four Classes of β-Lactamases

Article

Author: Li, Jia ; Zhou, Wanqing ; Wang, Danwei ; Han, Mei ; Zhang, Zhifeng ; Meng, Lingning ; Liu, Wenjing ; Gao, Zixin ; Zhang, Yan ; Liu, Chang

OBJECTIVE:

The emergence of multidrug-resistant (MDR) Escherichia coli strains has significantly constrained antibiotic treatment options, while the spread of antimicrobial resistance genes (ARGs) and mobile genetic elements exacerbates the situation. This study delves into an MDR E. coli strain, QMM-01, which uniquely co-expresses β-lactamases from all four recognized classes, aiming to uncover the underlying mechanisms of its resistance and assess its potential for global spread.

METHODS:

E. coli QMM-01, isolated from a burn patient, underwent antibiotic susceptibility testing through standard automated procedures commonly employed in clinical settings, with further test by immunochromatographic tests for carbapenemases. For genomic insights, whole-genome sequencing (WGS) was performed using both PacBio Sequel and Illumina NovaSeq platforms, supplemented by bioinformatics analyses to predict antimicrobial resistance genes, determining serotypes, performing multilocus sequence typing, and conducting comparative genomic analysis.

RESULTS:

QMM-01 exhibited resistance to a broad spectrum of β-lactam antibiotics, including carbapenems and ceftazidime-avibactam, with aztreonam being the sole exception. The resistance profile of the strain might primarily be due to the production of class B metallo-β-lactamases. WGS revealed the presence of a chimeric plasmid, pQMM-2-NDM-5, carrying the blaNDM-5 gene and exhibiting similarities with plasmids from diverse geographical regions. This plasmid contains 161 predicted coding sequences and harbors resistance genes for 13 different antibiotics, forming a resistance island with a complex genetic environment.

CONCLUSION:

This study underscores the global challenge posed by antibiotic resistance and emphasizes the need for international collaboration in antibiotic stewardship to mitigate the spread of resistance genes.

01 Mar 2025·INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS

Characterization of a novel KPC-2 variant, KPC-228, conferring resistance to ceftazidime–avibactam in an ST11-KL64 hypervirulent Klebsiella pneumoniae

Article

Author: Zhou, Ying ; Wan, Cailing ; Huang, Yu ; Lv, Jianbo ; Shi, Junhong ; Yu, Fangyou ; Yuan, Xinru ; Gao, Haojin ; Han, Weihua ; Shen, Li ; Li, Meilan ; Zhou, Peiyao ; Wu, Chunyang

BACKGROUND:

With the widespread clinical use of ceftazidime-avibactam (CZA), reports of resistance have increased continuously, posing immense threats to public health worldwide. In this study, we explored the underlying mechanisms leading to the development of CZA resistance in an ST11-KL64 hypervirulent Klebsiella pneumoniae CRE146 that harbored the bla_KPC-228 gene.

METHODS:

Twelve carbapenem-resistant Klebsiella pneumoniae (CRKP) strains were isolated from the same patient, including K. pneumoniae CRE146. Whole-genome sequencing (WGS), phylogenetic analysis, bla_KPC gene cloning and pACYC-KPC construction assays were conducted to further explore the molecular mechanisms of CZA resistance. Quantitative siderophore production assay, string test, capsule quantification and Galleria mellonella in vivo infection model were applied to verify the level of pathogenicity of K. pneumoniae CRE146.

RESULTS:

This strain carried key virulence factors, iutA-iucABCD operon and rmpA gene. Compared to the wild-type KPC-2 carbapenemase, the novel KPC-228 enzyme exhibited a deletion of four amino acids in the Ω-loop (del_167-170_ELNS). In addition, the emergence of CZA resistance appeared to be associated with drug exposure, and we observed the in vivo evolution of wild-type KPC-2 to KPC-228 and then the reversion to its original wild-type KPC-2. The bla_KPC-228 gene was located within the double IS26 flanking the ISKpn6-bla_KPC-228-ISKpn27 core structure and carried on an IncFII/IncR-type plasmid. Notably, CRE146 exhibited high-level resistance to CZA (64/4 mg/L) but increased susceptibility to meropenem (1 mg/L) and imipenem (0.5 mg/L) respectively. PACYC-KPC plasmids were constructed and expressed in K. pneumoniae ATCC13883. Compared to K. pneumoniae ATCC13883 harboring bla_KPC-2, K. pneumoniae ATCC13883 harboring bla_KPC-228 exhibited a high-level resistance to CZA (32/4 mg/L) and increased susceptibility to meropenem (1 mg/L) and imipenem (0.5 mg/L). Interestingly, K. pneumoniae ATCC13883 harboring bla_KPC-228 showed a significant decrease in their resistance to all β-lactamases tested except CZA and ceftazidime.

CONCLUSIONS:

In conclusion, we reported a novel KPC variant, KPC-228, in a clinical ST11-KL64 hypervirulent K. pneumoniae strain, which conferred CZA resistance, possibly through enhancing ceftazidime affinity and reducing avibactam binding. The bla_KPC-228 can mutate back to bla_KPC-2 under carbapenem pressure, which was very detrimental to clinical treatment. This strain carried both resistance and virulence genes, posing a major challenge in clinical management.

28

News (Medical) associated with Avibactam Sodium/Ceftazidime

08 Oct 2024

·www.biospace.com

Pfizer to Showcase Scientific Advancements in Respiratory and Other Infectious Diseases at IDWeek 2024

Presentations highlight momentum of Pfizer’s portfolio of infectious disease prevention and treatment options NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) will present data across its infectious disease portfolio at the upcoming IDWeek 2024 congress, held in Los Angeles from October 16-19, 2024. Data in 49 abstracts from company- and collaborator-led studies, will highlight the advances Pfizer is making in helping prevent and treat infectious diseases. “Pfizer is at the forefront of vaccine and therapeutic development in respiratory and infectious diseases,” said Annaliesa Anderson, Ph.D., Senior Vice President and Head, Vaccine Research and Development, Pfizer. “IDWeek 2024 provides a crucial platform to showcase our innovative advancements and engage with the scientific community, as we work to effectively tackle the ongoing challenge posed by infectious diseases.” “As we approach another respiratory virus season, the importance of preventive vaccines and treatments to help keep us healthy is more apparent than ever,” said Luis Jodar, Ph.D., Chief Medical Affairs Officer, Vaccines/Antivirals, Pfizer. “We’re excited to present new, meaningful data that we hope will help further inform healthcare providers.” Pfizer will present research from its robust infectious disease portfolio, covering RSV, COVID-19, pneumococcal disease, Lyme disease, meningococcal disease, and serious bacterial and fungal infections. Details for Pfizer-sponsored, investigator-sponsored and collaborative research oral and poster presentations are below: Title/Abstract Number Presenting Name/Type Date/Time (PDT) Location ORAL & LATE-BREAKING PRESENTATIONS 580 - Pharmacokinetics (PK) and Safety of Nirmatrelvir/Ritonavir (NMV/r) in Non-Hospitalized Symptomatic Pediatric Patients Ages 6 Years and Older with COVID-19 Who Are at Increased Risk of Progression to Severe Disease (EPIC-Peds) Jacqueline Gerhart, PhD Oct 19 2:45 – 2:57 PM US PT 403 A 88 - Efficacy of Nirmatrelvir/Ritonavir in High-Risk Trial Participants With Prior SARS-CoV-2 Infection or Vaccination: A Pooled Analysis John M. McLaughlin, PhD Oct 17 10:42 – 10:54 AM US PT 411 165 - Real-world Abrysvo vaccine effectiveness (VE) against Respiratory Syncytial Virus (RSV)-related severe acute respiratory infection (ARI) hospitalizations and emergency department (ED) visits—Kaiser Permanente of Southern California (KPSC), November 2023-April 2024 Sara Tartof, PhD, MPH, (KPSC)* Oct 17 1:45 – 3:00 PM US PT 403A 571 – Safety and Immunogenicity of Coadministered Bivalent BNT162b2 COVID-19 Vaccine and Bivalent RSVpreF Respiratory Syncytial Virus Vaccine With and Without Quadrivalent Influenza Vaccine in Adults ≥ 65 Years of Age Rahsan Erdem, MD Oct 19 1:45 – 2:03 PM US PT 408 A POSTER PRESENTATIONS COVID-19 P - 1194 - Comparison of COVID-19 Inpatient Burden in Hospitalized Children Age < 5years, by SARS-CoV-2 Variant Kathleen M. Andersen, PhD MSc Oct 18 12:15 – 1:30 PM US PT Hall J & K P - 1906 - Early COVID-19 and Severity of Subsequent Omicron Infection in Ontario, Canada Caroline Kassee, MPH (Sinai Health)* Oct 19 12:15 – 1:30 PM US PT Hall J & K P - 1977 - Six-Month Trajectory of Symptoms of COVID-19 Fatigue by Age and BNT162b2 COVID-19 Vaccination Status: A Prospective Study Among Symptomatic US Adults Testing Positive for SARS-CoV-2 at a National Retail Pharmacy Manuela Di Fusco, PhD Oct 19 12:15 – 1:30 PM US PT Hall J & K P - 2047 - Public Health Impact and Economic Value of an Additional Dose of Pfizer-BioNTech XBB.1.5-adapted COVID-19 Vaccine for Older Adults in the United States Alon Yehoshua, PharmD, MS Oct 19 12:15 – 1:30 PM US PT Hall J & K P - 2048 - COVID-19 XBB.1.5 vaccine uptake based on state vaccine registries compared to national survey data Angela Cook, MS Oct 19 12:15 – 1:30 PM US PT Hall J & K P - 2054 - Effectiveness of a Single COVID-19 mRNA Vaccine Dose in Individuals Previously Infected with SARS-CoV-2: A Systematic Review Hannah R. Volkman, PhD, MPH Oct 19 12:15 – 1:30 PM US PT Hall J & K P - 2060 - Effectiveness of BNT162b2 COVID-19 Vaccination Against Long COVID Among Older Adults: A Nationwide Study Manuela Di Fusco, PhD Oct 19 12:15 – 1:30 PM US PT Hall J & K P - 2062 - COVID-19 XBB.1.5-adapted vaccine uptake in immunocompromised individuals using tokenized state vaccine registries Matthew A. Brouillette, MPH Oct 19 12:15 – 1:30 PM US PT Hall J & K P - 2017 - Patient Reported Outcomes of Nirmatrelvir/Ritonavir Treatment for High-risk, Nonhospitalized Adults with Symptomatic COVID-19 Ashley S. Cha-Silva, PharmD, MS Oct 19 12:15 – 1:30 PM US PT Hall J & K Lyme Disease P - 599 - 6-Valent, OspA-Based VLA15 Lyme Disease Vaccine Candidate Against Lyme Borreliosis in a Healthy Pediatric and Adult Study Population: A Phase 2 Study Update James H. Stark, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 1287 - Incidence of Symptomatic Lyme Borreliosis in Nine European Countries, 2018−2022 Frederick Angulo, DVM PhD Oct 18 12:15 – 1:30 PM US PT Hall J & K P - 1291 - Racial disparities in Lyme disease among beneficiaries of US Medicaid and Medicare L. Hannah Gould, PhD, MS, MBA Oct 18 12:15 – 1:30 PM US PT Hall J & K P - 1293 - Healthcare Costs Associated with Lyme Disease in a U.S. Insured Population Holly Yu, MSPH Oct 18 12:15 – 1:30 PM US PT Hall J & K Meningococcal Disease P - 1299 - Epidemiology of Invasive Meningococcal Disease in the United States: Review of Recent Data and Identified Risk Factors Jessica Presa, MD Oct 18 12:15 – 1:30 PM US PT Hall J & K P - 1304 - Public Health Impact of changes to Meningococcal vaccination platform in the United States Katharina Schley, Dr. rer pol. Oct 18 12:15 – 1:30 PM US PT Hall J & K Pneumococcal disease P - 8 - Assessment of 13-valent pneumococcal conjugate vaccine effectiveness among people living with HIV in the United States Amanda C. Miles, MPH Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 628 - Real-world impact of pneumococcal conjugate vaccines on vaccine serotypes and cross-reacting non-vaccine serotypes Kevin Apodaca, MPH Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 629 - The health and economic impact of the PCV15 and PCV20 priming series during the first year of life in the US Mark Rozenbaum, PhD, M.B.A Oct 17 12:15 – 1:30 PM US PT Hall J & K Respiratory Syncytial Virus (RSV) P - 673 - Respiratory Syncytial Virus (RSV) Hospitalizations During Off-Season Months Among Infants in US Amy W. Law, PharmD Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 674 - The Economic Burden of Infant RSV Among US Caregivers Amy W. Law, PharmD Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 40 - Impact of case and control selection on influenza vaccine effectiveness (VE) among adults aged 40 years and older hospitalized with acute respiratory illness (ARI) during 2022-2023 using a test negative design (TND): secondary analysis of the North America Multi-Specimen Study Negar Aliabadi, MD, MS Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 1204 - Hospitalizations Associated with Respiratory Syncytial Virus (RSV) Illness Among Children and Adolescents in Ontario, Canada Sazini Nzula, PhD Oct 18 12:15 – 1:30 PM US PT Hall J & K P - 1205 - Impact of the COVID-19 Pandemic on Hospitalizations Associated with Respiratory Syncytial Virus (RSV) Illness Among Children and Adolescents in Ontario, Canada Sazini Nzula, PhD Oct 18 12:15 – 1:30 PM US PT Hall J & K P - 677 - Estimation of Respiratory Syncytial Virus-Attributable Hospitalizations Among Older Adults in Japan between 2015 and 2018: An Administrative Health Claims Database Analysis Asuka Yoshida, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 680 - Estimated Respiratory Syncytial Virus (RSV)-Related Hospitalizations and Deaths Among Adults in Norway between 2010–2019 Caihua Liang, MD, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 682 - The Risk of Cardiorespiratory Events for Up to 180 days Following Respiratory Syncytial Virus (RSV) Infection Hospitalization: A Self-Controlled Case Series Analysis Caihua Liang, MD, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K P – 683 – Estimation of RSV-Attributable Cardiovascular and Respiratory Hospitalizations in Adults in Germany, Between 2015-2019 Caroline Beese Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 604 - Preliminary real-world Abrysvo vaccine effectiveness (VE) against Respiratory Syncytial Virus (RSV)-related lower respiratory tract disease (LRTD) hospitalizations and emergency department (ED) visits—Kaiser Permanente of Southern California (KPSC) November 2023-April 2024 Negar Aliabadi, MD, MS Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 53 - Trends in Co-administration of Adult Vaccinations in the US Retail Pharmacy Setting Reiko Sato, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 603 - Potential Public Health Impact of Respiratory Syncytial Virus (RSV) Vaccines for Prevention of RSV Among Older Adults in the United States Reiko Sato, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 600 - Efficacy Of a Bivalent RSVpreF Vaccine in Older Adults Across a Second RSV Season John Woodside, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 596 - Immunobridging Demonstrating Effectiveness of the Bivalent Respiratory Syncytial Virus (RSV) Prefusion F Subunit Vaccine in Adults 18-59 Years of Age at High Risk of Severe RSV Disease in a Phase 3 Trial: The C3671023 MONeT Study Results Elliot N. DeHaan, MD Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 681 - Estimated Incidence of Respiratory Syncytial Virus (RSV)-Related Hospitalizations for Acute Respiratory Infections (ARIs), including Community Acquired Pneumonia (CAP), in Adults in Germany Caihua Liang, MD, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 605 - Bivalent RSV Prefusion F-Based Subunit Vaccine Generates High and Durable Neutralizing Titers Across an Entire RSV Season Among Older Adults Tarek Mikati, MD, MPH Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 595 - Public Health Impact of RSVpreF Vaccination on Older Adult Disease Outcomes Daniel Eiras, MD, MPH Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 21 - Comparison of Three RSV Vaccine Lower Respiratory Tract Disease Primary Endpoint Definitions for Adult Vaccine Sarah E. Williams, MD. MPH Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 2357 - Respiratory Syncytial Virus (RSV) Disease Burden Among Adults in Primary Care Settings in High-Income Countries: A Systematic Review and Modelling Study You Li; multiple Pfizer co-authors Oct 19 12:15 – 1:30 PM US PT Hall J & K Aztreonam-Avibactam P - 105 - Aztreonam-Avibactam Compared with Adjunctive Colistin Combined with Meropenem for the Treatment of Serious Gram-Negative Bacterial Infections: Subgroup Analysis of the Phase 3 REVISIT Study Heidi Leister-Tebbe, BSN Oct 17 12:15-1:30 PM US PT Hall J & K P - 1080 Aztreonam-Avibactam Activity Against Gram-negative Bacteria Isolated From Patients with Pneumonia from Europe, Asia, and Latin America (2021–2023) Helio S. Sader, MD, PhD, FIDSA Oct 18 12:15 – 1:30 PM US PT Hall J & K P - 1256 - Pharmacokinetic/Pharmacodynamic (PK/PD) Target Attainment Analyses for Aztreonam-Avibactam Dosing Regimens Susan Raber*, PharmD, MPH Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 1508 - In Vitro Activity of Aztreonam-Avibactam Against Enterobacterales Isolates Producing Multiple β-lactamases Collected Globally as a Part of the ATLAS Global Surveillance Program From 2018-2022 Mark Estabrook*, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K P - 1509 - In Vitro Activity of Aztreonam-Avibactam Against Enterobacterales Isolated From Pediatric and Adult Patients Collected During the ATLAS Global Surveillance Program, 2018-2022 Mark Estabrook*, PhD Oct 18 12:15 – 1:30 PM US PT Hall J & K Isavuconazole P - 1168 - Activity of Isavuconazole and Comparator Agents Against Pediatric Fungal Isolates Collected from 2017–2023 in a Global Surveillance Program Marisa Winkler, MD, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K Ceftazidime-Avibactam P- 1506 - In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Pseudomonas aeruginosa Collected from Patients with Presumed Hospital- and Community-Acquired Respiratory Tract Infections as a Part of the ATLAS Global Surveillance Program 2018-2022 Mark Estabrook, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K P- 1507 - In Vitro Activity of Ceftazidime-Avibactam Against Enterobacterales Isolates Producing Multiple β-lactamases Collected Globally as a Part of the ATLAS Global Surveillance Program from 2018-2022 Mark Estabrook, PhD Oct 17 12:15 – 1:30 PM US PT Hall J & K * =multiple Pfizer co-authors Prescribing Information for Pfizer Medicines Please see full Prescribing Information for ABRYSVO ® (Respiratory Syncytial Virus Vaccine) or visit and . Please see full Prescribing Information for COMIRNATY ® (COVID-19 Vaccine, mRNA) or visit . Please see full Prescribing Information for CRESEMBA ® (Isavuconazonium Sulfate) or visit Please see full Prescribing Information for PAXLOVID TM (Nirmatrelvir and Ritonavir) or visit . Please see full Prescribing Information for PREVNAR 20 TM (Pneumococcal 20-valent Conjugate Vaccine) or visit . Please see full Prescribing Information for PREVNAR 13 ® (Pneumococcal 13-valent Conjugate Vaccine). Please see full Prescribing Information for ZAFICEFTA ® (Ceftazidime-Avibactam). About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at . In addition, to learn more, please visit us on and follow us on X at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer . DISCLOSURE NOTICE: The information contained in this release is as of October 8, 2024. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about Pfizer’s infectious disease pipeline, in-line products and product candidates, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risk and uncertainties include, among other things, uncertainties regarding the commercial success of Pfizer’s infectious disease products and product candidates; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; risks associated with interim and preliminary data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any drug applications, biologics license applications and/or emergency use authorization applications may be filed in any jurisdictions for any potential indication for Pfizer’s product candidates; whether and when any such applications that may be pending or filed for any of Pfizer’s product candidates may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether any such product candidates will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of Pfizer’s products or product candidates, including development of products or therapies by other companies; manufacturing capabilities or capacity; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at and . Contacts Media Contact: PfizerMediaRelations@Pfizer.com +1 (212) 733-1226 Investor Contact: IR@Pfizer.com +1 (212) 733-4848

VaccinePhase 3Phase 2Clinical Result

08 Oct 2024

·www.pfizer.com

Pfizer to Showcase Scientific Advancements in Respiratory and Other Infectious Diseases at IDWeek 2024

Presentations highlight momentum of Pfizer’s portfolio of infectious disease prevention and treatment options NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) will present data across its infectious disease portfolio at the upcoming IDWeek 2024 congress, held in Los Angeles from October 16-19, 2024. Data in 49 abstracts from company- and collaborator-led studies, will highlight the advances Pfizer is making in helping prevent and treat infectious diseases. “Pfizer is at the forefront of vaccine and therapeutic development in respiratory and infectious diseases,” said Annaliesa Anderson, Ph.D., Senior Vice President and Head, Vaccine Research and Development, Pfizer. “IDWeek 2024 provides a crucial platform to showcase our innovative advancements and engage with the scientific community, as we work to effectively tackle the ongoing challenge posed by infectious diseases.” "As we approach another respiratory virus season, the importance of preventive vaccines and treatments to help keep us healthy is more apparent than ever,” said Luis Jodar, Ph.D., Chief Medical Affairs Officer, Vaccines/Antivirals, Pfizer. “We’re excited to present new, meaningful data that we hope will help further inform healthcare providers.” Pfizer will present research from its robust infectious disease portfolio, covering RSV, COVID-19, pneumococcal disease, Lyme disease, meningococcal disease, and serious bacterial and fungal infections. Details for Pfizer-sponsored, investigator-sponsored and collaborative research oral and poster presentations are below: * =multiple Pfizer co-authors Prescribing Information for Pfizer Medicines Please see full Prescribing Information for ABRYSVO ® (Respiratory Syncytial Virus Vaccine) or visit https://abrysvoadult.pfizerpro.com/ and https://abrysvomaternal.pfizerpro.com/. Please see full Prescribing Information for COMIRNATY ® (COVID-19 Vaccine, mRNA) or visit https://comirnatyhcp.com. Please see full Prescribing Information for CRESEMBA ® (Isavuconazonium Sulfate) or visit www.cresemba.com. Please see full Prescribing Information for PAXLOVID TM (Nirmatrelvir and Ritonavir) or visit https://paxlovid.pfizerpro.com. Please see full Prescribing Information for PREVNAR 20 TM (Pneumococcal 20-valent Conjugate Vaccine) or visit https://prevnar20.pfizerpro.com/. Please see full Prescribing Information for PREVNAR 13 ® (Pneumococcal 13-valent Conjugate Vaccine). Please see full Prescribing Information for ZAFICEFTA ® (Ceftazidime-Avibactam). About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer. DISCLOSURE NOTICE: The information contained in this release is as of October 8, 2024. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about Pfizer’s infectious disease pipeline, in-line products and product candidates, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risk and uncertainties include, among other things, uncertainties regarding the commercial success of Pfizer’s infectious disease products and product candidates; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; risks associated with interim and preliminary data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any drug applications, biologics license applications and/or emergency use authorization applications may be filed in any jurisdictions for any potential indication for Pfizer’s product candidates; whether and when any such applications that may be pending or filed for any of Pfizer’s product candidates may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether any such product candidates will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of Pfizer’s products or product candidates, including development of products or therapies by other companies; manufacturing capabilities or capacity; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com. Media Contact: PfizerMediaRelations@Pfizer.com +1 (212) 733-1226 Investor Contact: IR@Pfizer.com +1 (212) 733-4848

VaccineClinical Study

22 Oct 2023

·synapse.patsnap.com

Analysis on the Clinical Research Progress of β-lactamase inhibitor

β-lactamase is an enzyme found in the human body that plays a crucial role in the defense against bacterial infections. It is responsible for breaking down β-lactam antibiotics, a class of drugs commonly used to treat bacterial infections. By targeting and degrading these antibiotics, β-lactamase helps bacteria develop resistance mechanisms, making them less susceptible to treatment. This enzyme is produced by certain bacteria as a defense mechanism, allowing them to survive and multiply in the presence of β-lactam antibiotics. Understanding the role of β-lactamase is essential in developing strategies to combat antibiotic resistance and improve the effectiveness of antibiotic therapies. β-lactamase Competitive LandscapeAccording to Patsnap Synapse, as of 27 Sep 2023, there are a total of 134 β-lactamase drugs worldwide, from 145 organizations, covering 110 indications, and conducting 766 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The analysis of the target β-lactamase in the pharmaceutical industry reveals a competitive landscape with multiple companies actively developing drugs. Pfizer Inc. and Merck & Co., Inc. are leading in terms of the number of drugs in various development phases. Bacterial infections are the most common approved indication for drugs targeting β-lactamase. Small molecule drugs dominate the drug type analysis, indicating intense competition and potential for biosimilars. China is the country with the highest number of approved drugs, indicating significant progress in the field. Overall, the target β-lactamase presents a promising area for future development in the pharmaceutical industry. Key drug: Avibactam Sodium/CeftazidimeAvibactam Sodium/Ceftazidime is a small molecule drug that targets β-lactamase, an enzyme responsible for antibiotic resistance in bacteria. It is primarily used in the treatment of infectious diseases, respiratory diseases, and urogenital diseases. The drug has been approved for various indications, including ventilator-associated pneumonia, bacteremia, hospital-acquired pneumonia, gram-negative bacterial infections, intraabdominal infections, pyelonephritis, etc. The originator organization of Avibactam Sodium/Ceftazidime is Allergan Ltd., based in Ireland. The drug has achieved the highest phase of approval both globally and in China. It received its first approval in the United States in February 2015. The regulatory status of Avibactam Sodium/Ceftazidime includes priority review and fast track, indicating that it has undergone expedited evaluation processes due to its potential to address unmet medical needs. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Avibactam Sodium/Ceftazidime is a significant development in the field of biomedicine, particularly in the fight against antibiotic resistance. By targeting β-lactamase, it helps to overcome one of the major mechanisms through which bacteria develop resistance to antibiotics. This drug offers a promising solution for the treatment of various infectious diseases caused by gram-negative bacteria. The approval of Avibactam Sodium/Ceftazidime in multiple indications highlights its broad therapeutic potential. It can be used to treat serious infections such as pneumonia, bacteremia, and urinary tract infections, including complicated cases. The drug's approval in the United States and China, two major pharmaceutical markets, further emphasizes its global significance. The regulatory designations of priority review and fast track indicate that Avibactam Sodium/Ceftazidime has undergone an accelerated evaluation process. This suggests that regulatory authorities recognize the urgent need for effective treatments in the indicated therapeutic areas. The fast track designation also implies that the drug has demonstrated promising results in early clinical trials, warranting expedited development and review. In summary, Avibactam Sodium/Ceftazidime is a small molecule drug developed by Allergan Ltd. It targets β-lactamase and has been approved for various indications in the treatment of infectious diseases, respiratory diseases, and urogenital diseases. Its approval in the United States and China, along with priority review and fast track designations, highlights its potential to address unmet medical needs and combat antibiotic resistance.

100 Deals associated with Avibactam Sodium/Ceftazidime

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	Avibactam Sodium/Ceftazidime	J01	-

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Abdominal Abscess	Japan	Pfizer Japan, Inc.	24 Jun 2024
Cholecystitis	Japan	Pfizer Japan, Inc.	24 Jun 2024
Cystitis	Japan	Pfizer Japan, Inc.	24 Jun 2024
Hemorrhagic Septicemia	Japan	Pfizer Japan, Inc.	24 Jun 2024
Liver Abscess	Japan	Pfizer Japan, Inc.	24 Jun 2024
Peritonitis	Japan	Pfizer Japan, Inc.	24 Jun 2024
Pneumonia	Japan	Pfizer Japan, Inc.	24 Jun 2024
Ventilator associated bacterial pneumonia	United States	AbbVie, Inc.	20 Dec 2022
Intraabdominal Infections	China	Pfizer Manufacturing Ireland Unlimited Co.	21 May 2019
Bacteremia	European Union	Pfizer Biotechnology Ireland Unlimited Co.	23 Jun 2016
Bacteremia	Iceland	Pfizer Biotechnology Ireland Unlimited Co.	23 Jun 2016
Bacteremia	Liechtenstein	Pfizer Biotechnology Ireland Unlimited Co.	23 Jun 2016
Bacteremia	Norway	Pfizer Biotechnology Ireland Unlimited Co.	23 Jun 2016
Gram-Negative Bacterial Infections	European Union	Pfizer Biotechnology Ireland Unlimited Co.	23 Jun 2016
Gram-Negative Bacterial Infections	Iceland	Pfizer Biotechnology Ireland Unlimited Co.	23 Jun 2016
Gram-Negative Bacterial Infections	Liechtenstein	Pfizer Biotechnology Ireland Unlimited Co.	23 Jun 2016
Gram-Negative Bacterial Infections	Norway	Pfizer Biotechnology Ireland Unlimited Co.	23 Jun 2016
Hospital-acquired pneumonia	European Union	Pfizer Biotechnology Ireland Unlimited Co.	23 Jun 2016
Hospital-acquired pneumonia	Iceland	Pfizer Biotechnology Ireland Unlimited Co.	23 Jun 2016
Hospital-acquired pneumonia	Liechtenstein	Pfizer Biotechnology Ireland Unlimited Co.	23 Jun 2016

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Acute pyelonephritis	Phase 3	United States	Pfizer Inc.	01 Oct 2012
Acute pyelonephritis	Phase 3	United States	Forest Laboratories LLC	01 Oct 2012
Acute pyelonephritis	Phase 3	Japan	Forest Laboratories LLC	01 Oct 2012
Acute pyelonephritis	Phase 3	Japan	Pfizer Inc.	01 Oct 2012
Acute pyelonephritis	Phase 3	Argentina	Pfizer Inc.	01 Oct 2012
Acute pyelonephritis	Phase 3	Argentina	Forest Laboratories LLC	01 Oct 2012
Acute pyelonephritis	Phase 3	Brazil	Pfizer Inc.	01 Oct 2012
Acute pyelonephritis	Phase 3	Brazil	Forest Laboratories LLC	01 Oct 2012
Acute pyelonephritis	Phase 3	Bulgaria	Forest Laboratories LLC	01 Oct 2012
Acute pyelonephritis	Phase 3	Bulgaria	Pfizer Inc.	01 Oct 2012

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04927312 (Pubmed \| J Infect Chemother)	Phase 3	Complicated intra-abdominal infection	-	Ceftazidime-avibactam + Metronidazole	nuwdtcqqfj(kbkebaalfd) = mdjkcfwrol vcsnabzqjt (zaptkiefkn, 76.3 - 97.2)	Positive	01 Dec 2024
NCT04882085 (CTgov)	Phase 4	Urinary Tract Infections \| Acute pyelonephritis \| Bacteremia ... View more	60	Best Available Treatment	mzbiftcoaz = ptgbhjxsrb shteognaau (hlrgnbqfwf, fsrmhybgbx - xwfseykqwr) View more	-	21 Oct 2024
NCT04774094 (CTgov)	Phase 4	Pneumonia, Ventilator-Associated \| Hospital-acquired pneumonia	235	Zavicefta, Ceftazidime-Avibactam	tohegqedcp = gthkrpvolg mijatwmptt (tqnbwmhrgy, iapuzvzshy - blnlmcuuge) View more	-	19 Sep 2024
NCT04126031 (NOOR, CTgov)	Phase 2	Gram-Negative Bacterial Infections	48	ceftazidime-avibactam (CAZ-AVI)+CAZ (Part A: Cohort 1)	bllzcsokze(wwpwsqezgw) = cxbyaxsfgd xpzdffhktw (asqlveekuu, 113161.34) View more	-	26 Mar 2024
NCT04126031 (NOOR, CTgov)	Phase 2	Gram-Negative Bacterial Infections	48	AVI+CAZ (Part A: Cohort 2)	bllzcsokze(wwpwsqezgw) = ycddmoltus xpzdffhktw (asqlveekuu, 13473.88) View more	-	26 Mar 2024
NCT04927312 (CTgov)	Phase 3	Complicated intra-abdominal infection	60	PF-06947386+Metronidazole	nwwwsdbojd = asnriuumal whzskyyuun (xmdlhztokv, bwaowyoplm - agiqrpycfi) View more	-	08 Mar 2024
NCT01808092 \| NCT01499290 \| NCT01595438 \| NCT01726023 \| NCT01644643 (Phase 3 clinical trial programme, Pubmed \| J Antimicrob Chemother)	Phase 3	Gram-Negative Bacterial Infections ESBLs \| AmpC \| serine carbapenemase-producing Gram-negative pathogens	813	Ceftazidime/avibactam	gfqtpajglx(niufyvtfmd) = ybsznihkjl nsbexgftrw (swoaoildnk )	Positive	06 Nov 2023
	Phase 3		813	Comparators (carbapenems)	gfqtpajglx(niufyvtfmd) = yicgdgjuyi nsbexgftrw (swoaoildnk )	Positive	06 Nov 2023
NCT03923426 (EZTEAM STUDY, Pubmed \| Infect Dis Ther)	Not Applicable	Infectious Diseases	569	Ceftazidime-avibactam	djprcggwkf(frwogdptla) = Adverse events were reported for six of the 569 patients enrolled. hcslaslsek (jdxljbgyul )	-	10 Feb 2023
NCT04040621 (CTgov)	Phase 1	Pneumonia, Ventilator-Associated \| Hospital-acquired pneumonia	4	Ceftazidime-Avibactam (CAZ-AVI)	fdovorbvky(varwvmspzh) = rtgfkbkybx nhrfzsddpt (qrfsfbzfhu, pokwahbxnq - blvabjpntk) View more	-	09 Sep 2022
EHA2022	Not Applicable	Carbapenem Resistant Bacterial Infection	47	Ceftazidime-avibactam	qbnxvgqusn(npdbugwoxw) = hnkydwhlyn orviqrfqrp (dewsbqbsjc ) View more	-	10 Jun 2022
NCT03978091 (CTgov)	Phase 1/2	Bacterial Infections	48	AVYCAZ IV (AVYCAZ IV)	ffnrmtzndw = sduaqpqdrs wbybaybdbs (lbqirmjmna, wldqassyoi - ylrqenfwrz) View more	-	23 Dec 2021
NCT03978091 (CTgov)	Phase 1/2	Bacterial Infections	48	AVYCAZ (AVYCAZ CI)	ffnrmtzndw = fchidoloae wbybaybdbs (lbqirmjmna, hxgmcfpugg - wzvtxtzerb) View more	-	23 Dec 2021