Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie - LARVOL DELTA

Evolution of ceftazidime-avibactam resistance driven by variation in bla KPC-2 to bla KPC-190 during treatment of ST11-K64 hypervirulent Klebsiella pneumoniae. (PubMed, Front Cell Infect Microbiol) - "The emergence of Klebsiella pneumoniae carbapenemase (KPC) variants has significantly compromised the efficacy of ceftazidime-avibactam (CZA), a critical antibiotic for treating carbapenem-resistant K. pneumoniae (CRKP) infections. Its association with hypervirulence plasmids and IS26-mediated mobility poses a dual threat for dissemination. These findings highlight the urgent need for genomic surveillance and alternative therapies (e.g., meropenem-vaborbactam) to address KPC-190-mediated resistance."

Journal • Infectious Disease • Pneumonia

Within-Host Resistance Evolution of ST15 Klebsiella pneumoniae in an ICU Immunosuppressed Patient Under Antibiotic Pressure of Polymyxins, Ceftazidime-Avibactam, and Meropenem. (PubMed, Int J Antimicrob Agents) - "All KPC variants originated from a mobile genetic element flanked by IS26, IS26-ISKpn27-blaKPC-2/variants-ISKpn6-TnAs1-IS26, demonstrating its high potential to drive KPC mutations. This study underscores the rapid and diverse evolutionary adaptability of K. pneumoniae under multiple antibiotic pressures in immunocompromised critically ill patients, emphasizing the need for dynamic monitoring of antimicrobial susceptibility testing and resistance gene mutations to guide antibiotic adjustments."

Journal • Critical care • 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

Comparison of the Lifescale Gram Negative Kit to the Microscan Gram Negative Minimum Inhibitor Concentrations Panel Type 56 for Antimicrobial Susceptibility Testing (ASM Microbe 2025) - "14 antibiotics were evaluated: amikacin, ampicillin, aztreonam, cefazolin, cefepime, ceftazidime, ceftazidime/avibactam, ertapenem, gentamicin, levofloxacin, meropenem, meropenem/vaborbactam, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole. In this study, the AST results provided by the LifeScale system were in high agreement with the SOC AST results for the most common Gram-negative bacteria recovered in our patient population. The simplicity and rapid time to results of this novel platform should have a positive impact on implementation of targeted therapy for bacteremic patients."

Gram negative • Infectious Disease • Pneumonia

Evaluation of a Fast vs. Conventional System for Antimicrobial Susceptibility Testing of Gram-Negative Bacteria from Positive Blood Cultures (ASM Microbe 2025) - "We observed 100% CA for amikacin, ceftazidime/avibactam, ertapenem, meropenem, meropenem/vaborbactam, and trimethoprim/sulfamethoxazole. The VITEK® REVEAL™ AST system displayed acceptable CA for all antimicrobials tested except for ampicillin/sulbactam. The VITEK® REVEAL™ average TTR was 20-28 h shorter than MicroScan™'s, allowing for faster assessment of optimal antimicrobial therapy."

Gram negative • Infectious Disease • Pneumonia • Septic Shock

In Vitro Activity of Cefepime-Enmetazobactam against Enterobacterales Isolated from Cancer Patients (ASM Microbe 2025) - "Isolates resistant to third-generation cephalosporins and isolates nonsusceptible to meropenem were screened for the presence of ß-lactamases. Cefepime/enmetazobactam showed excellent activity against most of the Enterobacterales isolates. Excellent activity was seen against third-generation cephalosporin resistant isolates. Cefepime/enmetazobactam exhibited higher activity than Piperacillin-tazobactam and Cefeperazone-sulbactam suggesting a good therapeutic alternative as compared with carbapenems against ESBL producers."

Preclinical • Infectious Disease • Oncology • Pneumonia

Impact of Antimicrobial Stewardship Program Suspension on Antibiotic Use during a Healthcare System Crisis: A Single-Center Experience in South Korea (ASM Microbe 2025) - "Preauthorization antibiotics included carbapenems (meropenem, imipenem/cilastatin, and ertapenem), ceftazidime/avibactam, and ceftolozane/tazobactam. PAF antibiotics included colistin, daptomycin, glycopeptides (vancomycin and teicoplanin), linezolid, and tigecycline... The suspension of antimicrobial stewardship interventions resulted in a significant increase in the use of restricted antibiotics, particularly those requiring preauthorization, highlighting the essential role of ASP in controlling antibiotic overuse and misuse."

Clinical

Biochemical Impact of Insertion Mutations in the 266-275 Loop of KPC-2 β-Lactamase on the Efficacy of Ceftazidime-Avibactam (ASM Microbe 2025) - "The combinations of ceftazidime-avibactam (CZA) and imipenem-relebactam (IMR) are effective options for treating infections caused by Klebsiella pneumoniae strains producing KPC-2 β-lactamase. Unlike other KPC variants with substitutions in the Ω-loop (e.g., D179), the insertions in these variants may preserve critical interactions within the Ω-loop, allowing both enzymes to retain imipenem hydrolysis activity while also exhibiting higher hydrolysis efficiency for CAZ. In conclusion, this work provides relevant insights into the biochemical impact of insertions in the 266-275 loop of KPC-2 on CZA activity and β-lactam hydrolysis."

Clinical • 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

Understanding the Catalytic Mechanism of CAZ Hydrolysis by Beta-Lactamase Variants from Clinical Isolates (ASM Microbe 2025) - "Although the FDA approved Ceftazidime-Avibactam (CAZ-Avi) in 2015 to combat resistant infections, Klebsiella pneumoniae carbapenemase (KPC) variants resistant to CAZ are emerging...In contrast, most mutants exhibit a lower KM, suggesting an adaptive advantage for survival at lower CAZ concentrations, though all mutants retain high KM (>500), reflecting continued selective pressure. Future work will integrate pre-steady-state kinetics and structural analysis to further elucidate the mechanisms behind these mutants and provide insights for designing more effective β-lactam therapies."

Clinical • Infectious Disease • Pneumonia

In Vitro Activity of Fosfomycin Against Ceftazidime/Avibactam-Resistant KPC-Producing Klebsiella pneumoniae (ASM Microbe 2025) - "FOS susceptibility was performed by agar dilution method whereas for CZA, MEM and meropenem/vaborbactam (MVB) susceptibility, gradient strips were used. FOS+MEM may represent a possible therapeutic option for infections due to CZA-resistant and MEM-susceptible strains. The analysis of the mgrB gene shows that two strains have a mutation which generally confers resistance to colistin while the genes encoding the two main porins, OmpK35 and OmpK36, showed structural alterations and several mutations in almost all the strains."

Preclinical • Infectious Disease • Pneumonia

Multi-Center Evaluation of the Pattern Single-Cell Microbiology Platform for Microorganism Identification and Antimicrobial Susceptibility Testing Directly from Lower Respiratory Tract Specimens (ASM Microbe 2025) - "For S. aureus, there was 100% accuracy in predicting methicillin and vancomycin susceptibility (Figure 1). For Enterobacterales and P. aeruginosa, there was 100% accuracy in predicting susceptibility to cefepime, ceftolozane-tazobactam, and meropenem. For Enterobacterales, there was 100% and 86% category agreement for ceftazidime-avibactam and ceftriaxone, respectively... This pilot study highlights the accuracy of the Pattern single-cell microbiology approach for pathogen ID and phenotypic AST directly from complex LRT specimens. Phenotypic AST in <7 hours enables second-dose antimicrobial optimization, enhancing clinical outcomes and stewardship."

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Evaluation of the ASTar® System for Rapid Susceptibility Testing Directly from Positive Blood Cultures from Oncology Patients with Bloodstream Infections (ASM Microbe 2025) - "The ASTar® panel was performed according to manufacturer's instructions and organisms were tested across 18 antimicrobials: amikacin, ampicillin, ampicillin/sulbactam, aztreonam, cefazolin, cefepime, ceftazidime, cefuroxime, ceftazidime/avibactam, ciprofloxacin, gentamicin, levofloxacin, meropenem, meropenem/vaborbactam, piperacillin/tazobactam, tobramycin, tigecyline, and trimethoprim/sulfamethoxazole. The ASTar® system yields reliable AST results with an overall CA of 94% and 99% EA. The ASTar® system combined with direct from positive blood rapid identification can help in the optimization of early antimicrobial therapy in patients with bloodstream infections."

Infectious Disease • Oncology • Pneumonia • Septic Shock

In Vitro Activity of Newer β-Lactam-β-Lactamase Inhibitor Combination Agents Against Difficult-to-Treat Resistance (DTR) Phenotype Enterobacterales and Pseudomonas aeruginosa Isolated from Clinical Specimens of Patients Receiving Care at Canadian Hospitals (CANWARD 2016-2023) (ASM Microbe 2025) - "DTR isolates were defined as those testing not susceptible to all carbapenems (ertapenem [Enterobacterales only], imipenem, and meropenem), all oxyiminocephalosporins (ceftazidime, ceftriaxone [Enterobacterales only], and cefepime), piperacillin-tazobactam, and ciprofloxacin. From 2016 to 2023, 0.2% of Enterobacterales and 7.7% of P. aeruginosa isolated from Canadian hospital patients displayed a DTR phenotype. >60% of DTR Enterobacterales were susceptible to ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam and gentamicin. Ceftolozane-tazobactam (65.1% susceptible) was the most active agent against DTR P. aeruginosa."

Preclinical • Infectious Disease

First Report of KPC-31 in Florida: Redefining Detection of KPC Producing Isolates with ESBL-Like Resistance Pattern (ASM Microbe 2025) - "Conventional screening methods relying on carbapenem resistance would have failed to identify this variant. The "ESBL-like" resistance pattern of KPC-31 highlights the critical need to revise current carbapenem-resistant Enterobacterales (CRE) screening protocols. Including ceftazidime/avibactam as a key agent in routine testing is essential for accurate phenotypical detection of this variant."

Infectious Disease • Pneumonia

Defining the Interplay Between Antibiotic Activity and the Presence of Hypervirulence Plasmids in Hypervirulent Klebsiella pneumoniae (ASM Microbe 2025) - "Antibiotic activity was evaluated using 48-hour time-kill assays in the presence of clinically relevant concentrations of polymyxin B (0.5 and 2 mg/L), gentamicin (2 and 8 mg/L), meropenem (16 and 64 mg/L), and ceftazidime/avibactam (16/4 and 4/4 mg/L). Removing the hypervirulence plasmid from hvKp led to increased activity of ceftazidime/avibactam. Strategies that aim to inhibit virulence factors in hvKp, such as CPS, may also enhance the activity of certain antibiotics."

Infectious Disease • Pneumonia

Validation of VITEK 2 AST-N807 and AST-XN30 Susceptibility Cards for Gram-Negative Antimicrobial Susceptibility Testing (ASM Microbe 2025) - "The final VME rate was 0.6% (3/536), with aztreonam at 5.9% (1/17), imipenem/relebactam at 11.1% (1/9), and ceftazidime/avibactam at 10.0% (1/10). Overall ME rate was 0.7% (3/430), with cefepime at 5.6% (2/36) and ciprofloxacin at 2.8% (1/36). The overall minor error (mE) rate was 7.0% (71/1017), with higher mE rates observed with ceftazidime (18.3%: 13/71), tigecycline (19.0%: 4/21), and nitrofurantoin (30.0%: 3/10)...The VITEK® 2 AST-N807 and AST-XN30 susceptibility cards demonstrated acceptable performance for most antibiotics tested, meeting FDA criteria for CA, EA, and error rates. This validation supports the use of these cards for routine clinical use, with considerations for specific antibiotic limitations."

Gram negative • Infectious Disease

Defining the Interplay Between Antibiotic Activity and the Presence of Hypervirulence Plasmids in Hypervirulent Klebsiella pneumoniae (ASM Microbe 2025) - "Antibiotic activity was evaluated using 48-hour time-kill assays in the presence of clinically relevant concentrations of polymyxin B (0.5 and 2 mg/L), gentamicin (2 and 8 mg/L), meropenem (16 and 64 mg/L), and ceftazidime/avibactam (16/4 and 4/4 mg/L). Removing the hypervirulence plasmid from hvKp led to increased activity of ceftazidime/avibactam. Strategies that aim to inhibit virulence factors in hvKp, such as CPS, may also enhance the activity of certain antibiotics."

Infectious Disease • Pneumonia

Evaluation of the VITEK 2 AST-N439 Card for Susceptibility Testing of New β-lactam/β-lactamase Inhibitor Combinations and Colistin in Carbapenem-Non-Susceptible Gram-Negative Bacilli (ASM Microbe 2025) - "This card includes new β-lactam/β-lactamase inhibitor (BL/BLI) combinations: ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam, and meropenem/vaborbactam. Our findings suggest that VITEK 2 has suboptimal performance for new BL/BLI combinations in carbapenem-non-susceptible Gram-negative isolates, and caution is warranted as VITEK 2 demonstrates low sensitivity in detecting ceftolozane/tazobactam heteroresistance. Furthermore, despite changes to the colistin formulation used in the VITEK 2 card, it remains an unreliable method for detecting colistin resistance.Table 1. Performance of VITEK 2 for new BL/BLI combinations in carbapenem-non-susceptible Gram-negative isolatesTable 2."

Gram negative • Infectious Disease

Multi-Center Evaluation of the Pattern Single-Cell Microbiology Platform for Microorganism Identification and Antimicrobial Susceptibility Testing Directly from Positive Blood Culture Broth (ASM Microbe 2025) - "For the Enterobacterales, there was 100% accuracy in predicting susceptibility to ceftazidime-avibactam, ceftriaxone, and meropenem, and 88% categorical agreement for cefepime (all minor errors) and 88% categorical agreement for ceftolozane-tazobactam (Figure 1). Our pilot study demonstrates the accuracy of the Pattern single-cell approach for rapid ID and phenotypic AST from positive blood culture broths. A rapid, combined ID/AST assay can reduce testing costs and complexity while enabling early antimicrobial optimization and improved clinical outcomes."

Infectious Disease • Pneumonia

The Environmental Resistome: Phenotypic and Biochemical Characterization of Chromosome-Encoded Per-Like Β-Lactamases (ASM Microbe 2025) - "Class A PER β-lactamases have distinctive features compared to other class A enzymes (e.g., high catalytic efficiency on oxyimino-cephalosporins and an enlarged omega-loop) and were associated with resistance to ceftazidime-avibactam (CZA)...In contrast, for ceftriaxone, the relative kcat/Km is higher compared to PER-2 (5.0 vs 1.8 µM⁻¹ s⁻¹)...For penicillin G and ampicillin, the kcat/Km values were comparable to those of PER-2...The same scenario could be possible for the other chromosome encoded PER enzymes. Whether theses enzymes and particularly PER-YR1 will have a reduced response against avibactam remains to be evaluated."

Real-world study of Ceftazidime-Avibactam for the treatment of disease caused by bacteria: a plain language summary. (PubMed, Future Microbiol) - No abstract available

Journal • Real-world evidence

Improved diagnostic stewardship in carbapenem-resistant Enterobacterales gene detection helps in early initiation of targeted therapy. (PubMed, J Med Microbiol) - "Synergy test guided effective combination therapy of ceftazidime-avibactam and aztreonam for MBL-producing CRE isolates.Conclusion. However, discrepancies between phenotypic and genotypic methods and the high cost of certain therapies are notable limitations. Enhanced infection control and early initiation of targeted therapy are crucial to combat AMR."

Journal • Infectious Disease • Pneumonia

Molecular and epidemiological characterization of carbapenem-resistant hypervirulent Klebsiella pneumoniae in Huaian, China (2022-2024): a retrospective study. (PubMed, Front Cell Infect Microbiol) - "The CR-hvKP strains showed significantly higher resistance to the tested antibiotics, except for ceftazidime/avibactam and colistin. Resistance rates of CR-hvKP to the three tested antibiotics (minocycline, cotrimoxazole, and amikacin) were higher than those of CRnon-hvKP...Notably, the ST11 lineage carrying blaKPC-2 has emerged as a dominant high-risk clone in Huaian. Given the wide distribution of these novel CR-hvKP isolates, global monitoring and stricter control measures should be implemented to prevent their further spread in hospital settings."

Journal • Retrospective data • Diabetes • Infectious Disease • Metabolic Disorders • Pneumonia