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

In reply to the Letter to Editor Regarding "Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48- or KPC-producing Enterobacterales infections in Turkiye: A multi-centre retrospective matched-cohort study". (PubMed, Int J Antimicrob Agents) - No abstract available

Journal • Retrospective data • Infectious Disease

Reversible Evolution of Ceftazidime-Avibactam Resistance Driven by bla KPC-71 and Aerobactin Loss in ST11-KL64 Hypervirulent Klebsiella Pneumoniae. (PubMed, Infect Drug Resist) - "This study provides the first clinical evidence of the reversible in vivo evolution of an insertional KPC-71 variant under antibiotic pressure. The findings reveal a dynamic balance between resistance and virulence mediated by bla KPC mutations and plasmid remodeling, highlighting the risk of resistance cycling during CZA treatment and the need for genomic surveillance in managing CRKP infections."

Journal • Infectious Disease • Pneumonia

Evaluation of aztreonam/avibactam gradient test strip and aztreonam-ceftazidime/avibactam broth disk elution method for susceptibility testing of metallo-β-lactamase positive carbapenemase-producing bacteria. (PubMed, Diagn Microbiol Infect Dis) - "Whole-genome sequencing was used for discrepancy analysis. Based on accuracy, reproducibility, and ease of use, the ATM/AVI gradient strip was selected as the preferred method for clinical laboratory testing."

Journal

Synergistic Antibacterial Effects of Ceftazidime/Avibactam and Auranofin Combination against Carbapenem-Resistant Klebsiella pneumoniae: In Vitro and in Vivo Evaluation. (PubMed, Curr Microbiol) - "AUR synergizes with CZA on killing a broad spectrum of carbapenem or CZA resistant Klebsiella pneumoniae both in vitro and in vivo, and slows down the development of CZA resistance. The combination of CZA and AUR might be a potential therapeutic strategy for combating superbugs CZA resistant CRKP."

Journal • Preclinical • Infectious Disease • Pneumonia

Analysis of Carbapenem-Resistant Enterobacterales Resistance in a Hospital in Kunming Over the Past Two Years. (PubMed, Infect Drug Resist) - "Conversely, the resistance rates to tigecycline, ceftazidime/avibactam, and polymyxin B were 1.26%, 24.24%, and 5.43%, respectively. CRE infections are difficult to treat and have a high mortality rate. Therefore, to meet the needs of Infection Prevention and Control, it is necessary to strengthen the monitoring of CRE resistance in this institution, contributing to the prevention, control, and clinical management capabilities for infections."

Journal • Critical care • Infectious Disease • Pneumonia

Current Management Strategies of Difficult-to-Treat Resistant Pseudomonas aeruginosa Infections. (PubMed, Infect Dis Clin North Am) - "Although new active therapeutic options such as ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam and cefiderocol are currently available, lack of randomized control trials, drug access limitations, and emerging resistance have a negative impact on the management of these infections. This review discusses the mechanisms of resistance, molecular epidemiology, clinical management, and current and future therapeutic strategies for DTR P aeruginosa infections."

Journal • Review • Infectious Disease

Novel KPC-2 variants and epidemic ST463 clones underlie ceftazidime/avibactam resistance in carbapenem-resistant Pseudomonas aeruginosa. (PubMed, Microbiol Spectr) - "Whole-genome sequencing revealed that resistant strains were highly resistant to carbapenems, cephalosporins, and aztreonam but retained partial susceptibility to aminoglycosides and polymyxins. By combining clinical, microbiological, and genomic data, our findings highlight an urgent need for ongoing surveillance and careful antibiotic use to preserve the usefulness of last-resort drugs like CZA. This work informs both clinicians and public health experts on emerging resistance threats."

Journal • Infectious Disease

In vitro sulbactam/avibactam synergy against carbapenem-resistant Acinetobacter baumannii from hospitals in Peru. (PubMed, JAC Antimicrob Resist) - "The presence of metallo-β-lactamase producers (all bla NDM) was observed in three isolates (1.6%). These findings demonstrate high levels of synergistic activity between ampicillin/sulbactam and ceftazidime/avibactam and their potential use as a treatment for CR-Ab."

Journal • Preclinical

Cerebrospinal fluid and plasma pharmacokinetics of ceftazidime/avibactam in a neurocritical patient with CRKP intracranial infection and augmented renal clearance. (PubMed, JAC Antimicrob Resist) - "Our findings advocate for therapeutic drug monitoring-guided dose optimization incorporating extended infusions to achieve therapeutic targets. These results emphasize the critical need for personalized dosing algorithms in the neurocritical care setting."

Journal • PK/PD data • CNS Disorders • Infectious Disease • Pneumonia • Vascular Neurology

Synergistic effect of ceftazidime-avibactam and aztreonam combination against carbapenem resistant Klebsiella spp., E.coli and Pseudomonas spp. (PubMed, Diagn Microbiol Infect Dis) - "Compared to the E-strip disk diffusion method, BDE method showed an agreement of 78.4 %, while DSE method exhibited an agreement of 89.7 %. The in vitro evaluation of the CZA-ATM combination highlights its potential as a therapeutic option for treating carbapenemase producing organisms."

Journal • Infectious Disease

Case Report of Treatment of Polymicrobial Bacteremia Caused by Carbapenem-Resistant Klebsiella pneumoniae, and Bacillus Species in an Immunocompetent Patient With Meropenem-Vaborbactam. (PubMed, J Pharm Pract) - "The Infectious Disease Society of America (IDSA) recommends meropenem-vaborbactam, ceftazidime-avibactam, or imipenem-cilastatin-relebactam as preferred options with cefiderocol as an alternative, all of which are also alternative options for CTX-M Enterobacterales...This case report illustrates the treatment course of CTX-M and KPC-producing Klebsiella pneumoniae, and Bacillus species bacteremia that included cefiderocol, followed by vancomycin and meropenem-vaborbactam, and then meropenem-vaborbactam monotherapy...In our report, an immunocompetent patient developed a polymicrobial bloodstream infection caused by an MDR Klebsiella pneumoniae, and Bacillus species, which was successfully treated with meropenem-vaborbactam. This unusual infection and treatment course also serves to promote awareness of another treatment option for invasive Bacillus species infection and furthermore encourages providers to request testing & sensitivities to consolidate therapy,..."

Journal • Infectious Disease • Pneumonia

One-year surveillance of last-resort antimicrobial resistance patterns in carbapenemase-producing Klebsiella pneumoniae strains isolated in a Romanian tertiary care hospital: a prospective study. (PubMed, Germs) - "Strains presenting a minimum inhibitory concentration to meropenem of >0.125 μg/mL underwent phenotypic enzyme production testing, followed by synergistic testing to identify antimicrobial salvage therapy options...Forty-six strains were resistant to cefiderocol (35.7%), 108 (83.7%) to ceftazidime/avibactam, 127 (98.4%) to ceftolozane/tazobactam, 116 (90.0%) to imipenem/relebactam and 127 (98.4%) to aztreonam. The association of aztreonam with ceftazidime/avibactam demonstrated a synergistic effect in 127 (98.5%) strains, while aztreonam with imipenem/relebactam was efficient in vitro against 103 (79.8%) strains. Antimicrobial resistance remains a concerning phenomenon among Enterobacterales, especially when considering the increasing resistance rates even against salvage therapy antimicrobials."

Journal • Infectious Disease • Pneumonia

Emergence of mutH V76G among longitudinal carbapenem resistant Klebsiella pneumoniae causing long-term colonization and recurrent infection disrupts DNA mismatch repair and results in a hypermutator phenotype. (PubMed, bioRxiv) - "Clinical mutH V76G isolates and CRISPR-engineered mutH V76G mutants were hypermutators based on rifampin mutational frequencies...Both clinical and lab-engineered mutH V76G mutant strains rapidly acquire resistance or reduced susceptibility to new antibiotics like ceftazidime-avibactam, meropenem-vaborbactam and cefiderocol, due to mutations in carbapenemase ( bla KPC-3 ), porin ( ompK36 ) and other genes. mutH V76G -driven hypermutation also enhances horizontal transfer of resistance plasmids and improves K. pneumoniae fitness during mouse infections. This study is important for understanding K. pneumoniae hypermutation as a potent mediator of antibiotic resistance and other phenotypes relevant to human infections."

Journal • Mismatch repair • Infectious Disease • Pneumonia

Evolution and high transferability of an IncN/FII plasmid harboring blaKPC-2/blaKPC-33 in Enterobacter intestinihominis under ceftazidime pressure. (PubMed, BMC Microbiol) - No abstract available

Journal

Single - molecule, real - time sequencing of ceftazidime - avibactam - resistant Pseudomonas aeruginosa and the mechanism of resistance to ceftazidime - avibactam (PubMed, Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi) - "Mutation or downregulation of oprD gene may lead to CAZ-AVI resistance in P. aeruginosa."

Journal • VIM

Sphingobacterium spp. as intrinsic producers of SPI Ambler class B metallo-β-lactamases. (PubMed, J Antimicrob Chemother) - "S. spiritivorum was the most prevalent species of Sphingobacterium identified in clinical samples. All S. spiritivorum-like species produced a chromosomally encoded SPI-like MBL that might be challenging for the treatment of infections caused by this bacterial species."

Journal • Infectious Disease

Molecular Characterization of KPC-2 and CMY AmpC Beta Lactamases in Ceftazidime-Avibactam Resistant Klebsiella pneumoniae in a Tertiary Care Hospital. (PubMed, Cureus) - "Introduction Multidrug-resistant (MDR) Klebsiella pneumoniae poses significant treatment challenges, particularly in intensive care settings. Sanger sequencing confirmed 99.3% similarity with bla CMY-2. Conclusion CMY AmpC β-lactamase emerged as the predominant mechanism of CZA resistance in K. pneumoniae, highlighting the need for routine AmpC screening, prudent use of alternatives such as cefiderocol, tigecycline, or fosfomycin, and sustained genomic surveillance to guide therapy and infection control."

Journal • Critical care • Infectious Disease • Pneumonia

Conformational dynamics and substrate selectivity in KPC-33: Molecular mechanisms of resistance to ceftazidime-avibactam revealed by multiscale molecular dynamics simulations. (PubMed, J Pharm Biomed Anal) - "Together, these findings explain how D179Y substitution reshapes KPC-33's conformational landscape, favoring CAZ accommodation while evading avibactam inhibition. This study highlights the Ω-loop-H6 interface as a potential target to restore CAZ-AVI efficacy against resistant β-lactamases."

Journal • Infectious Disease • Pneumonia

Genomic characterization of two distinct Klebsiella pneumoniae strains in a fatal case of relapsed acute myelogenous leukemia: a case report. (PubMed, BMC Infect Dis) - "This case highlights the importance of genome-based diagnostics in identifying mixed-strain infections and uncovering resistance mechanisms that may not be apparent in routine phenotypic assays. The presence of the high-risk clone ST147 and the emerging ST967 lineage in a single host highlights the complexity of managing infections in immunocompromised patients and the urgent need for real-time genomic surveillance to guide antimicrobial stewardship and infection control."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases

Clinical performance of the VITEK REVEAL fast antimicrobial susceptibility test within a real-world workflow for gram-negative bacteremia: comparison with QMAC-dRAST and conventional methods. (PubMed, Microbiol Spectr) - "For ceftazidime/avibactam and ceftolozane/tazobactam, REVEAL showed 100% and 98.6% CA, respectively, compared to ETEST. The volatile organic compounds-based system demonstrated high concordance, shorter time-to-results, and reliable performance for newer antimicrobial agents. By directly comparing its performance with established clinical diagnostic tools, this study provides relevant support for the potential integration of this approach into real-world laboratory workflows, with implications for improved patient management and antimicrobial stewardship."

Journal • Real-world evidence • Infectious Disease

Co-occurrence of mcr-1.1, mcr-3.40, and tmexCD1-toprJ1 on a hybrid IncFIB/IncHI1B plasmid in Klebsiella pneumoniae from pork in Hainan, China. (PubMed, Int J Food Microbiol) - "All isolates exhibited resistance to tigecycline (MIC = 4-32 mg/L), cefotaxime and ciprofloxacin, while remaining susceptible to meropenem and ceftazidime/avibactam. Conjugation assays showed that six isolates successfully transferred tigecycline resistance to recipients, and two of these isolates also transferred colistin resistance...This is the first report of the co-occurrence of mcr-1.1, mcr-3.40, and tmexCD1-toprJ1 on a hybrid IncFIB/IncHI1B plasmid in K. pneumoniae. The convergence of last-resort antibiotic resistance highlights the urgent need for integrated One Health surveillance to limit the dissemination of clinically important pathogens in the food chain."

Journal • Infectious Disease • Pneumonia

Cefiderocol Resistance in Pseudomonas aeruginosa ST175: A Case Report with Genomic Analysis. (PubMed, Antibiotics (Basel)) - "Cefiderocol resistance can emerge rapidly in vivo during treatment of infections caused by P. aeruginosa ST175. Continuous surveillance, molecular characterization of resistance mechanisms, and cautious use of cefiderocol-preferably in combination regimens-are warranted to preserve its clinical utility."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases • Septic Shock

Antimicrobial Activity of Aztreonam-Avibactam and Other β-Lactamase Inhibitor Combinations Tested Against Enterobacterales Isolates from Pediatric Patients from United States Medical Centers (2019-2023). (PubMed, Antibiotics (Basel)) - "Susceptibility to imipenem-relebactam varied from 97.1% (ceftriaxone-nonsusceptible) to 100.0% (ESBL producers). Ceftolozane-tazobactam showed good activity against ESBL producers (91.8% susceptible), but limited activity against ceftriaxone-nonsusceptible (75.8% susceptible) and MDR isolates (80.9% susceptible)...ESBL-producing Enterobacterales, mainly CTX-M, remain an important cause of infection in children. Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam were highly active against isolates from both pediatric and adult population."

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

Ceftazidime/Avibactam Monotherapy Versus Other Antibiotics: Where Do We Stand? (PubMed, Pathogens) - "The non-inferiority of CAZ-AVI with respect to carbapenems and superiority over polymyxins in terms of both clinical outcomes and safety are outlined, along with evidence supporting the use of CAZ/AVI in high-risk populations such as immunocompromised and critically ill patients. Overall, CAZ/AVI represents a compelling therapeutic option with favorable efficacy and safety, thus appearing as a reasonable frontline treatment for resistant Gram-negative infections."

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

Ceftazidime-Avibactam Resistance in Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections: Risk Factors and Clinical Outcomes. (PubMed, Antibiotics (Basel)) - "CAZ-AVI resistance in CRKP bacteremia is associated with specific clinical risk profiles and contributes to high mortality. Identifying high-risk patients and optimizing antimicrobial stewardship are essential to improve prognosis."

Clinical data • Journal • Infectious Disease • Pneumonia