Emblaveo (aztreonam/avibactam) / Pfizer, AstraZeneca, AbbVie - LARVOL DELTA

ICU environment as a reservoir of KPC-ST307-Klebsiella pneumoniae high-risk clone resistant to ceftazidime-avibactam. (PubMed, Sci Rep) - "Regardless of the origin (patients or sinks), KPC-92-, KPC-150 and KPC-62-Kp isolates combining altered porin proteins also exhibited increased/resistant MIC values to cefiderocol, cefepime-taniborbactam, aztreonam-avibactam, meropenem-vaborbactam and/or imipenem-relebactam. A variant calling analysis and plasmid characterization showed possible transmission between patients and sinks. Our results suggest that the patient care environment likely contributed to persistence and spread of last-line antibiotics-resistant KPC-Kp within the ICU during the COVID-19 pandemic."

Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia

Carriage and infections by multi-carbapenemases producing Enterobacterales. (PubMed, Diagn Microbiol Infect Dis) - "Clinical features of patients with MCP-EB are common in the hospital population with chronic diseases and showed high mortality rates both in infected and carriers-only patients. Aztreonam/avibactam and cefiderocol could be promising treatment options against MCP-EB infections."

Journal • Cardiovascular • Chronic Kidney Disease • Infectious Disease • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases

Molecular characteristics and antimicrobial susceptibility of carbapenem-resistant Klebsiella pneumoniae in a multicenter study in Ningbo, China. (PubMed, Front Microbiol) - "ST11 CR-KP exhibited 100% resistance to six antibiotics, including ceftriaxone (CRO), cefotetan (CTT), and cefepime (FEP), and showed susceptibility only to gentamicin (GEN), aztreonam/avibactam (AZA), ceftazidime/avibactam (CZA), polymyxin B (POL), and tigecycline (TGC). ST11 CR-KP strains demonstrate significantly stronger resistance profiles compared to non-ST11 strains. Therefore, stringent control over the use of carbapenem antibiotics is essential, along with measures to prevent the spread of resistance plasmids and the continuous improvement of hospital infection control strategies."

Clinical • Journal • Infectious Disease • Pneumonia

In vivo evolution of ceftazidime-avibactam resistance in bla OXA-244-positive E. coli potentially linked to PBP3 insertion and mutations in acrB and PBP2. (PubMed, JAC Antimicrob Resist) - "Ceftazidime/avibactam resistance emerged during treatment, accompanied by significant increases in aztreonam/avibactam and avibactam MICs. This study shows a complex resistance mechanism involving a YRIK insertion in PBP3, combined with mutations in AcrB and PBP2, as drivers of ceftazidime/avibactam resistance. These findings highlight the importance of monitoring E. coli isolates with YRIK insertions during ceftazidime/avibactam treatment and warrant further investigation into efflux pump-mediated resistance in Enterobacterales."

Journal • Preclinical • Infectious Disease

Amphiphilic nebramine analogs synergize with β-lactam/β-lactamase inhibitor combinations, including cefepime-taniborbactam and meropenem-xeruborbactam against metallo-β-lactamase-carrying Pseudomonas aeruginosa. (PubMed, RSC Med Chem) - "Cefepime-taniborbactam (FEP-TAN) and meropenem-xeruborbactam (MEM-XER) are β-lactam-β-lactamase inhibitor (BL-BLI) combinations currently in development and both projected to treat metallo-β-lactamase (MBL)-producing Gram-negative pathogens. Compound 4 was found to be less toxic than both polymyxin B and its corresponding amphiphilic tobramycin counterpart (compound 7) in human renal cell lines, RPTEC and HK-2. Overall, our study suggests that addition of compound 4 alongside next-generation BL-BLIs such as FEP-TAN, MEM-XER as well as the recently approved ATM-AVI combination can overcome intrinsic and acquired in vitro P. aeruginosa resistance determinants that confer high-level resistance to β-lactam antibiotics."

Journal • Infectious Disease

Antimicrobial Susceptibility Testing of the Combination of Aztreonam and Avibactam in NDM-Producing Enterobacterales: A Comparative Evaluation Using the CLSI and EUCAST Methods. (PubMed, Antibiotics (Basel)) - "Four antimicrobial susceptibility testing methods of the combination of ATM and AVI were evaluated on these isolates, including the CLSI broth disk elution (BDE) method, the disk diffusion (DD) method of aztreonam-avibactam (AZA) following the EUCAST breakpoints, the MIC test strip (MTS) method of AZA following the EUCAST breakpoints, and the gradient strip stacking (SS) method. The AZA DD, AZA MTS, and the SS methods showed complete concordance with the BDE method. However, the MICs obtained from the AZA MTS and SS were not comparable."

Journal • Infectious Disease • Pneumonia

Aztreonam-avibactam for the treatment of serious infections caused by metallo-β-lactamase-producing Gram-negative pathogens: a Phase 3 randomized trial (ASSEMBLE). (PubMed, JAC Antimicrob Resist) - "Aztreonam-avibactam was generally well-tolerated, with no treatment-related serious adverse events. These Phase 3 data provide support for aztreonam-avibactam as a potential therapeutic option for difficult-to-treat infections caused by MBL-producing Gram-negative bacteria."

Journal • P3 data • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

Emergence of transferable aztreonam-avibactam resistance in the high-risk ST44 subclade of carbapenemase-producing Providencia hangzhouensis, 2012-2023. (PubMed, J Infect) - No abstract available

Journal

Estimating the Value of Aztreonam-Avibactam in Treating Metallo-beta-Lactamase-Producing Enterobacterales Infections in Spain Using the STEDI AMR Value Framework. (PubMed, Infect Dis Ther) - "In Spain, ATM-AVI is a highly cost-effective and urgently needed treatment option for patients with MBL-EB including HAP/VAP and cIAI infections. Using the novel STEDI framework unlocks the considerable value of a new antibiotic which is essential to support incentives for the development of new antimicrobials."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Nephrotoxicity of New Antibiotics: A Systematic Review. (PubMed, Toxics) - "The agents assessed included aztreonam/avibactam, cefepime/enmetazobactam, cefiderocol, ceftobiprole, contezolid, gepotidacin, imipenem/cilastatin/relebactam, lascufloxacin, lefamulin, levonadifloxacin, plazomicin, and sulbactam/durlobactam. There is a need for post-marketing studies to better characterize renal safety. Clinicians should remain vigilant and continue to monitor for and report renal-related adverse events."

Journal • Review

Broad spectrum of β-lactamase coverage and potent antimicrobial activity of xeruborbactam in combination with meropenem against carbapenemase-producing Enterobacterales, including strains resistant to new β-lactam/β-lactamase inhibitor combinations. (PubMed, Antimicrob Agents Chemother) - "The MICs of meropenem, meropenem/xeruborbactam, meropenem/vaborbactam, imipenem, imipenem/relebactam, cefepime, cefepime/taniborbactam, ceftazidime, ceftazidime/avibactam, aztreonam, and aztreonam/avibactam were determined by reference broth microdilution and interpreted following the European Committee on Antimicrobial Susceptibility Testing guidelines, using the breakpoint of the β-lactam alone for not yet approved combinations. Xeruborbactam restored meropenem activity against the strains carrying resistance mechanisms to β-lactam/β-lactamase inhibitor combinations, including strains producing KPC variants or MBLs in combination with additional chromosomal alterations (MIC range: ≤0.06-0.25 and ≤0.06-4 mg/L, respectively). Our findings highlight the potential of xeruborbactam in combination with meropenem as a promising treatment against carbapenemase-producing Enterobacterales, including strains with emerging resistance to other β-lactam/β-lactamase inhibitor..."

Journal

Whole-Genome Analysis of NDM-Producing Providencia hangzhouensis Associated With Recurrent Bacteraemia with Rapid Development of Aztreonam-Avibactam Resistance. (PubMed, Emerg Microbes Infect) - "This study identifies a glycine insertion in PBP3 as a novel mechanism driving aztreonam-avibactam resistance in Providencia, supported by structural modeling and additional mutations in OmpC. This study provides evidence of a novel resistance mechanism to aztreonam-avibactam in Providencia, driven by a glycine insertion in PBP3 and supported by alterations in OmpC."

Journal • Pancreatitis

Evaluation of imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam and cefepime-zidebactam activities on a wide collection of French clinical Enterobacterales isolates. (PubMed, Diagn Microbiol Infect Dis) - "This work confirmed the interest of C/Z and A/A combinations against carbapenem-resistant Enterobacterales isolates compared with M/V and I/R. Additionally, the findings indicate that the E-test method can be used for the determination of M/V and I/R MIC for E. coli and K. pneumoniae strains."

Journal • Infectious Disease • Pneumonia

Cefepime-zidebactam therapy for extensively drug-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae infection as a bridge to liver transplantation. (PubMed, JAC Antimicrob Resist) - "Serial clinical isolates recovered from biliary fluid and ascitic fluid were tested for susceptibility to cefiderocol, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and cefiderocol-xeruborbactam by broth microdilution...The patient was treated with a regimen of cefiderocol and eravacycline, with persistent fever and development of hepatic microabscesses on imaging...Antimicrobial therapy with cefepime-zidebactam along with source control allowed successful liver transplantation in a patient with cefiderocol-resistant K. pneumoniae and P. aeruginosa. Cefepime-zidebactam may be a therapeutic option for extensively drug-resistant Gram-negative organisms."

Journal • Infectious Disease • Pneumonia • Transplantation

Clinical and microbiological analysis of bloodstream infections by four cefiderocol-resistant and not previously exposed NDM-producing Klebsiella pneumoniae. (PubMed, J Antimicrob Chemother) - "This case series highlights the urgent need of new therapeutic agents that will overcome the diffusion of NDM-KP resistant to FDC. The emergence of NDM-KP with an acquired fec operon in nosocomial settings, even without a previous drug exposure, may further compromise cefiderocol efficacy. Further studies will be necessary to assess the in vivo activity of xeruborbactam, a new cyclic boronate β-lactamase inhibitor, which may restore cefiderocol susceptibility in NDM-KP isolates."

Journal • CNS Disorders • Infectious Disease • Pneumonia • Psychiatry • ST14

Aztreonam-avibactam resistance rates and resistance mechanisms of NDM and NDM/OXA48-like dual-carbapenemase-producing Enterobacterales in Singapore. (PubMed, Pathology) - "Higher resistance rates were seen in NDM-OXA-48-like dual-carbapenemase-producing E. coli, driven by ST361 isolates. Aztreonam-avibactam susceptibility testing should be performed as part of routine diagnostic testing for invasive NDM-CPE infections."

Journal • Infectious Disease • Pneumonia

Case Commentary: Overcoming intrinsic resistance-the successful use of aztreonam and avibactam for Stenotrophomonas maltophilia meningitis. (PubMed, Antimicrob Agents Chemother) - "Wong-So and colleagues describe a case of post-neurosurgical Stenotrophomonas maltophilia meningitis successfully managed with ceftazidime-avibactam and aztreonam...Simultaneous peak and trough levels in cerebrospinal fluid (CSF) and plasma demonstrated favorable CSF-to-plasma ratios for both aztreonam and avibactam. This case highlights aztreonam-avibactam as a rational therapeutic strategy for S. maltophilia meningitis."

Journal • CNS Disorders • Infectious Disease

Evaluation of the in vitro efficacy of antimicrobials against Enterobacterales with multiple carbapenemase enzymes. (PubMed, Iran J Microbiol) - "Ceftazidime -avibactam/aztreonam combination displayed good in vitro activity against dual carbapenemase producers of E. coli isolates (NDM with OXA-48 and NDM with VIM genes) and Klebsiella pneumoniae (combination of NDM, VIM and OXA-48 genes). Ceftazidime/avibactam/aztreonam, aminoglycosides and tigecycline displayed in vitro activity against dual carbapenemase producers of E. coli and K. pneumoniae."

Journal • Preclinical • Infectious Disease • Pneumonia

Tracking international and regional dissemination of the KPC/NDM co-producing Klebsiella pneumoniae. (PubMed, Nat Commun) - "Aztreonam/avibactam and cefiderocol were promising antimicrobial agents against KN-CRKP. The global KN-CRKP research, spanning from 2005 to 2024, provides valuable insights into the global transmission, dynamics, and treatment of KN-CRKP."

Journal • Infectious Disease • Pneumonia

Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review. (PubMed, JAC Antimicrob Resist) - "A total of 191 articles addressing clinical research regarding the efficacy, safety, tolerability, and PK of new BL/BLI combinations with avibactam, durlobactam, enmetazobactam, nacubactam, relebactam, taniborbactam, tazobactam, vaborbactam and zidebactam were included...In spite of that, the development of new BLI effective for class B metallo-β-lactamases (MBL) is still challenging, being aztreonam/avibactam the only approved combination active against MBL-producing bacteria. Although there has been extensive research to develop new BLI and BL/BLI combinations, only a few have reached the market. More evidence of its usefulness in the real world is still needed."

Journal • PK/PD data • Review • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

A Study to Learn About the Study Medicine Aztreonam-Avibactam (ATM-AVI) in Infants and Newborns Admitted in Hospitals With Bacterial Infection (CHERISH) (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Pfizer | Trial completion date: Sep 2027 ➔ Jul 2028 | Trial primary completion date: Sep 2027 ➔ Jul 2028

Trial completion date • Trial primary completion date • Infectious Disease

Activity of β-Lactamase Inhibitor Combinations Against Enterobacterales Isolated from Patients with Intra-Abdominal Infection from United States Medical Centres (2019-2023). (PubMed, Antibiotics (Basel)) - "Only 51.6% of Enterobacterales were susceptible to ampicillin-sulbactam. Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam exhibited almost complete activity (99.9% susceptibility) against Enterobacterales causing IAI in US hospitals. In contrast, piperacillin-tazobactam exhibited limited activity against these organisms, especially those with a MDR phenotype."

Journal • Infectious Disease • Pneumonia

Advanced Combination Antimicrobial Resistance Testing for Hard-to-treat Carbapenem-Resistant Enterobacterales Carrying Metallo-Beta-Lactamases Offers Additional Treatment Options (ASM Microbe 2025) - "The drug combinations include TAZ-AVI, ATM-AVI, and Aztreonam-Ceftazidime-Avibactam (ATM-TAZ-AVI). pneumoniae, blaNDM-1, ST 4843 and E. coli blaNDM-5, ST 167/2 were the strains most frequently submitted for testing. The ExAST program provides testing not widely available and has been successful in expanding the characterization and additional treatment options for these hard-to-treat infections."

Metastases • Infectious Disease • Pneumonia

Global Trends in Resistance Rates of Ceftazidime-Avibactam (CZA) in Citrobacter freundii, Serratia marcescens, and Providencia spp.: Data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) Programme, 2015-2022 (ASM Microbe 2025) - "In CRE isolates, MIC > 4 mg/liter for aztreonam-avibactam was observed in Providencia spp. The emergence of high ceftazidime-avibactam resistance in these bacterial isolates underscores the need for ongoing surveillance and further monitoring."

Clinical

In Vitro Activity of Minocycline in Combination with Biapenem Against Cefiderocol-Resistant NDM-Producing Enterobacterales (ASM Microbe 2025) - "In addition, the cMIC90 and susceptible rate of aztreonam/avibactam, used as a comparator, were 4 μg/mL and 90.6%, respectively. MINO has been suggested to exhibit an ability to cell wall damage in addition to inhibiting protein synthesis, and its bactericidal effect has been confirmed when used in high concentrations. Therefore, it was considered that the cell wall damage caused by BIPM increased the intracellular internalization of MINO, resulting in a more effective bactericidal effect even at low concentrations of MINO against NDME."

Combination therapy • Preclinical • Infectious Disease • Pneumonia