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

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

The Fair, the Foul, and the Filamentous: Aztreonam/Avibactam Overcomes Strain-Specific Phenotypic Variability in Klebsiella pneumoniae When Targeting PBP-2 and PBP-3 (ASM Microbe 2025) - "Here, we assessed the pharmacodynamics and phenotypic responsiveness to mono and combination therapies involving aztreonam (ATM), ceftibuten (CBT), and avibactam (AVI) in several resistant isolates. ATM-induced filamentation is not consistent across resistant Kp isolates. Independent of strain-specific responses to monotherapy, ATM+AVI proved to be the superior combination as it produces a universal bulging elongated rod/filament intermediary phenotype that gives way to a "pop and kill mechanism"."

Infectious Disease • Pneumonia

β-Lactam Susceptibility and Fitness of Thirty Clinically Derived and In Vitro Selected Ceftazidime-Avibactam-Resistant KPC Variants (ASM Microbe 2025) - "The susceptibility of these variants to other β-lactam antibiotics, including novel β-lactam-β-lactamase inhibitors and cefiderocol (FDC), as well as their relative fitness, remain poorly characterized...MICs of 19 β-lactam agents, including ceftolozane-tazobactam (C/T), imipenem-relebactam (I/R), meropenem-vaborbactam (M/V), aztreonam-avibactam (AZA), and FDC, were determined using the broth microdilution method...Additional mutations on the D179Y background variably affected susceptibility to other β-lactams, resulting in scattered MIC distributions for cefotaxime, cefepime, and C/T... CZA-resistant KPC variants exhibit diverse susceptibility profiles to other β-lactams. Reduced susceptibility to FDC, even within the susceptible range, warrants careful monitoring in clinical practice."

Preclinical • Infectious Disease • Pneumonia

Population pharmacokinetic/pharmacodynamic modeling to optimize aztreonam-avibactam dose regimens for adult patients. (PubMed, Antimicrob Agents Chemother) - P3 | "Ceftazidime-avibactam + aztreonam dose regimens proposed by the Infectious Diseases Society of America (IDSA) achieved joint PTA <85% due to insufficient avibactam exposures. Approved aztreonam-avibactam dose regimens (single loading dose and regular maintenance doses, all 3 h intravenous infusions) are optimized for joint PTA across renal function groups and infection types.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT03329092 and NCT03580044."

Journal • PK/PD data • Chronic Kidney Disease • Infectious Disease • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases

Aztreonam/avibactam activity against Enterobacterales from European medical centres: summary of 5 years of surveillance prior to approval for clinical use (2019-2023). (PubMed, J Antimicrob Chemother) - "The results of this investigation provide a valuable benchmark for monitoring the in vitro activity of aztreonam/avibactam after its clinical approval in Europe and emphasizes the importance of comprehensive surveillance programmes to monitor the emergence of high-risk clones and resistance mechanisms to newly approved antimicrobial agents."

Journal

Carbapenemase type and mortality in blood-stream infections caused by carbapenemase-producing enterobacterales: a multicenter retrospective cohort study. (PubMed, Infection) - "After controlling for antimicrobial therapy, we did not find evidence of an association between carbapenemase type and mortality. Ceftazidime/avibactam was associated with a greater than 80% reduction in mortality as compared with colistin."

Journal • Retrospective data • Infectious Disease

From genomics to treatment: overcoming pan-drug-resistant Klebsiella pneumoniae in clinical settings. (PubMed, Front Pharmacol) - "We report pan-drug resistant Klebsiella pneumoniae isolates from five patients in a single hospital, including resistance to cefiderocol and cefepime-zidebactam in one isolate...Genomic and phenotypic characterization guided successful compassionate treatment using aztreonam, ceftazidime-avibactam, and amoxicillin-clavulanate at maximum doses. Dissection of the roles of the substitutions present in blaSHV-231 revealed that this variant was responsible for the reduced susceptibility to aztreonam-avibactam, at the expense of a higher susceptibility to clavulanate. Targeted therapy can be successful upon dissection of unexpected mechanisms of resistance that enhance the contribution of endemic β-lactamase."

Journal • Infectious Disease • Pneumonia

Activity of Aztreonam-avibactam and Ceftazidime-avibactam against β-lactamase-producing Enterobacterales Isolates from United States Hospitals. (PubMed, J Glob Antimicrob Resist) - "New β-lactam/β-lactamase inhibitors were active against common β-lactamase-producing isolates from US hospitals, including carbapenemase-producing isolates for which therapeutic options are limited. Aztreonam-avibactam was the most active agent against carbapenemase producers, including MBL-carrying isolates."

Journal • Infectious Disease • Pneumonia

TREAT-GNB: Optimising TREATment for Severe Gram-Negative Bacterial Infections (clinicaltrials.gov) - P4 | N=600 | Recruiting | Sponsor: National University of Singapore

New P4 trial • Infectious Disease • Pneumonia • Respiratory Diseases

Aztreonam plus ceftazidime-avibactam for post-neurosurgical meningitis due to Stenotrophomonas maltophilia. (PubMed, Antimicrob Agents Chemother) - "Clinical evidence is lacking regarding the efficacy of aztreonam-avibactam in severe infections involving Stenotrophomonas maltophilia. We report a case of post-neurosurgical meningitis due to S. maltophilia (minimal inhibitory concentration of aztreonam plus avibactam, 4/4 µg/mL) clinically and microbiologically cured with a combination of aztreonam and ceftazidime-avibactam (2 g and 2 g/500 mg q8h, 3 h simultaneous infusions). Therapeutic drug monitoring showed adequate concentrations of aztreonam and avibactam in the cerebrospinal fluid at each time point over the 14-day treatment duration."

Journal • CNS Disorders • Infectious Disease

Molecular characterization of carbapenem resistance mechanisms and phenotypic correlations in clinical Klebsiella pneumoniae isolates from Ningbo, China. (PubMed, Front Microbiol) - "The tested agents included: (1) basic antimicrobials (tigecycline, polymyxin B, ceftazidime-avibactam); and (2) combination therapy candidates (ertapenem, imipenem, levofloxacin, piperacillin-tazobactam, ceftriaxone, cefepime, trimethoprim-sulfamethoxazole, fosfomycin, amikacin, aztreonam, chloramphenicol, amoxicillin-clavulanate, ceftazidime)...The 150 strains of CRKP exhibit high resistance rates to various conventional drugs; The sensitivity rates to tigecycline, polymyxin B, and ceftazidime-avibactam were 98.7, 98.0, and 68%, respectively; Conversely, the sensitivity rates to fosfomycin, amikacin, and chloramphenicol were 72.0, 40.0, and 16.7%, respectively; The main proportions of carbapemen genes producing in CRKP are as follows: KPC-2 (61.3%), NDM-5 (14.7%), IMP-4 (8.0%), OXA-232 (6.0%), and OXA-181 (1.3%); The main proportions of β-lactamase resistance genes are as follows: CTX-M-1 (13.33%), CTX-M-3 (25.33%), CTX-M-9 (17.33%), CTX-M-14 (34.67%), SHV-1 (26.66%),..."

Journal • Infectious Disease • Pneumonia

Breaking Through Resistance: A Comparative Review of New Beta-Lactamase Inhibitors (Avibactam, Vaborbactam, Relebactam) Against Multidrug-Resistant Superbugs. (PubMed, Antibiotics (Basel)) - "The introduction of new β-lactam-β-lactamase inhibitors (BLBLIs), such as ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/cilastatin/relebactam, expands our therapeutic options against carbapenem-resistant Gram-negative bacteria, including those pathogens for which therapeutic options are limited...The recent introduction of aztreonam/avibactam marks a significant advancement in our therapeutic armamentarium against metallo-β-lactamase-producing pathogens...The present review aims to provide clinicians with a detailed understanding of each BLBLI treatment option to guide the optimal use of these new agents for the effective treatment of difficult infections caused by carbapenemase-producing Enterobacterales infections. This review is based on literature retrieved from PubMed, Scopus, Web of Science, and the Cochrane Library."

Journal • Review • Infectious Disease

Combined resistance mechanisms leading to high-level of cefiderocol resistance among NDM-like producing E. coli ST167 clinical isolates. (PubMed, Eur J Clin Microbiol Infect Dis) - "We identified a variety of NDM-producing E. coli isolates exhibiting high level of resistance to FDC as a result of the combined effect of CirA deficiency, along with production of NDM-type enzymes. The spread of such resistance phenotype across Europe poses great concern on the clinical efficacy of this novel drug. Additionally, the identification of an FDC- and AZA-resistant NDM-5 producing E. coli isolate represents one of the ultimate evolutions with a possible step towards pan-resistance."

Journal

AN INFECTION HARD TO TREAT WITH A BACTERIA HARD TO KILL: A PEDIATRIC CASE OF MULTIDRUG-RESISTANT PSEUDOMONAS AERUGINOSA ENDOCARDITIS (ESPID 2025) - "The patient was initially treated with a combination of five antibiotics: ceftazidime-avibactam, aztreonam, tobramycin, ciprofloxacin, and colistin (day 0). Available evidences to guide such treatment are limited, particularly when first-line antibiotics show resistance. A maximalist therapeutic approach is frequently adopted given the poor prognosis of such complicated infections."

Clinical • Infectious Disease • Septic Shock

CEFIDEROCOL AS SALVAGE THERAPY IN DIFFICULT-TO-TREAT RESISTANT (DTR) PSEUDOMONAS AERUGINOSA COMPLICATED CENTRAL NERVOUS SYSTEM INFECTION (ESPID 2025) - "Cultures of CSF with debris and frank pus were positive for NDM and OXA-48 producing Klebsiella pneumoniae, and DTR Pseudomonas aeruginosa with in-vitro susceptibility only to colistin (MIC 2mg/L) and cefiderocol (disk zone diameter 21mm). He was initially treated with ceftazidime-avibactam, aztreonam, and polymyxin B. Intravenous cefiderocol 60mg/kg 3-hour infusions 8-hourly was started 1 week later on compassionate basis; mild transaminitis<5x ULN developed...Cefiderocol was well-tolerated. A phase 2 paediatric study on cefiderocol dosing for non-CNS infections has been reported; more data is needed for optimal dosing in CNS infections."

Infectious Disease

CEFTAZIDIME-AVIBACTAM PLUS AZTREONAM IN MANAGING MULTIDRUG-RESISTANT GRAM-NEGATIVE INFECTIONS IN PAEDIATRICS: A SINGLE-CENTRE CASE SERIES. (ESPID 2025) - "Background Aztreonam-avibactam targets multidrug-resistant (MDR) Gram-negative pathogens, including those producing metallo-β-lactamases (MBL). Combination of aztreonam-avibactam has recently been licensed to use in adults and may soon be available in children. Larger trials are needed to establish its efficacy and place in paediatric guidelines."

Clinical • Gram negative • Infectious Disease

Aztreonam-avibactam Demonstrates Potent Activity Against Carbapenem-resistant Enterobacterales Collected From US Medical Centers Over a 6-year Period (2017-2022). (PubMed, Open Forum Infect Dis) - "Antimicrobial susceptibility testing for aztreonam-avibactam, ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, cefiderocol, tigecycline, and colistin was conducted using the reference broth microdilution method. Aztreonam-avibactam demonstrates potent activity toward CREs with different carbapenem-resistance mechanisms. The combination is an anticipated welcome addition to the clinician's toolbox giving physicians another option to treat CREs."

Journal

l-2,3-Diaminopropionate Binding Mode of the SulM Adenylation Domain Limits Engineering Monobactam Analogue Biosynthesis with Larger Substrates. (PubMed, JACS Au) - "The recent FDA approval of Emblaveo to treat serious bacterial infections combines an established synthetic monobactam aztreonam and avibactam, which additionally blocks serine β-lactamases, to create a broadly effective antibacterial therapeutic. Comparisons with the structures of other diamino acid-activating adenylation domains identify alternate binding modes that may be more suitable for the production of sulfazecin analogues. The impact of these structures on the further engineering of the SulA3 domain and its relation to monobactam synthesis in the recently structurally characterized SulTE are discussed."

Journal • Infectious Disease

New β-Lactam/β-Lactamase Inhibitor Combination Antibiotics. (PubMed, Pathogens) - "During the last 2 years from the writing of this article, cefepime/enmetazobactam, aztreonam/avibactam, and sulbactam/durlobactam were approved for use in clinical practice. Aztreonam/avibactam is indicated for the treatment of adult patients who suffer from complicated intra-abdominal infections, complicated urinary tract infections including pyelonephritis, hospital-acquired pneumonia, and ventilator-associated pneumonia due to aerobic Gram-negative infections with limited therapeutic options. Sulbactam/durlobactam, a combination of 2 β-lactamase inhibitors, is indicated for the treatment of adult patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia due to the Acinetobacter baumannii-calcoaceticus complex [including carbapenem-resistant Acinetobacter baumannii (CRAB) infections]."

Journal • Review • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

In vitro susceptibility of aztreonam/avibactam against metallo-β-Lactamase-producing Enterobacterales in a Croatian tertiary care hospital. (PubMed, Infect Dis Now) - No abstract available

Journal • Preclinical

Estimating the Magnitude of a Pull Incentive for Antibiotic Development Using the STEDI Value Framework: An Example From Spain (ISPOR 2025) - "Using only transmission and diversity elements of the STEDI framework, this analysis shows that a novel antibiotic (ATM-AVI) provides substantial value to the Spanish healthcare system. Unlocking the value of novel antimicrobials in the context of existing antimicrobial resistance supports policy decisions that incentivize novel antimicrobial development."

Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

Characterization of Enterobacter cloacae and Citrobacter freundii Species Complex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam-Avibactam and Comparator Agents (2019-2023). (PubMed, Antibiotics (Basel)) - "Aztreonam-avibactam was highly active against cephalosporin-nonsusceptible ECLC and CFC, including MBL producers. The activities of ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol were compromised against CB-R isolates due to the high frequency of NDM producers."

Journal • Infectious Disease

Analysis of intrahospital and global dissemination and resistome dynamics of NDM-1-producing ST773 Pseudomonas aeruginosa high-risk clone. (PubMed, JAC Antimicrob Resist) - "Lastly, HCB isolates evolved further resistome mutations during intrahospital dissemination, including regulators of AmpC (mpl) and MexAB-OprM (nalD), linked to the acquisition of aztreonam/avibactam resistance, and thus remaining only susceptible to cefiderocol and colistin. This work evidences the transborder spread and intrahospital dissemination and evolution of the emerging ST773-NDM-1 P. aeruginosa high-risk clone."

Journal • Breast Cancer • Oncology • Solid Tumor