Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie 
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  • ||||||||||  Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
    Journal:  Alternative drugs against multiresistant Gram-negative bacteria. (Pubmed Central) -  Jun 24, 2021   
    Further analyses need to be carried out to confirm these results before extending them to clinical practice. This study involving genetically distinct bacteria showed promising results for tigecycline for all Gram-negative (except P. aeruginosa), and there was good activity of minocycline against A. baumannii, of ceftazidime/avibactam against Enterobacterales, and of fosfomycin against S. marcescens.
  • ||||||||||  Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
    Journal:  Ceftazidime-avibactam resistance mediated by the NY substitution in various AmpC β-lactamases. (Pubmed Central) -  Jun 22, 2021   
    For FOX-3, the IY substitution did not reduce the inactivation efficacy of avibactam and the substitution was highly deleterious for β-lactam hydrolysis, including ceftazidime, preventing CAZ-AVI resistance. Since AmpCand DHA-1 display substantial sequence diversity, our results suggest that loss of hydrogen interaction between Asn and avibactam could be a common mechanism of acquisition of CAZ-AVI resistance.
  • ||||||||||  Fetroja (cefiderocol) / Shionogi, Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
    Journal:  Structural basis of reduced susceptibility to ceftazidime-avibactam and cefiderocol in Enterobacter cloacae due to AmpC R2 loop deletion. (Pubmed Central) -  Jun 22, 2021   
    By crystallographic studies of free and drug-bound forms of enzyme, we demonstrate that this deletion in AmpC induces slanting of the H-9 helix that is directly connected with the R2 loop, and disappearance of the H-10 helix, is directly responsible for increased hydrolysis of ceftazidime and cefiderocol. These findings provide novel insights into how MDR Gram-negative bacteria may evolve their β-lactamases to survive selective pressure from these newly developed β-lactam agents.
  • ||||||||||  Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
    Journal:  KPC-50 confers resistance to ceftazidime-avibactam associated with reduced carbapenemase activity. (Pubmed Central) -  Jun 22, 2021   
    KPC-50 is a KPC-3 variant identified from a Klebsiella pneumoniae clinical isolate recovered in Switzerland in 2019. As compared to KPC-3, KPC-50 shows i) a three amino-acid insertion (Glu-Ala-Val) between amino acids 276 and 277 amino acid sequence, (ii) an increased affinity to ceftazidime, (iii) a decreased sensitivity to avibactam, explaining the ceftazidime-avibactam resistance, and (iv) associated to a sharp reduction of its carbapenemase activity.
  • ||||||||||  cefepime/zidebactam IV (WCK 5222) / Wockhardt
    Preclinical, Journal:  In Vitro Activity of WCK 5222 (Cefepime-Zidebactam) against Worldwide Collected Gram-Negative Bacilli Not Susceptible to Carbapenems. (Pubmed Central) -  Jun 22, 2021   
    The activity of cefepime-zidebactam against carbapenem-resistant Gram-negatives is ascribed to its β-lactam enhancer mechanism of action (i.e., zidebactam binding to PBP2 and its universal stability to both serine β-lactamases and MBLs). The results from this study support the continued development of cefepime-zidebactam as a potential therapy for infections caused by Enterobacterales, P. aeruginosa, and other non-fermentative Gram-negative bacilli where resistance to marketed antimicrobial agents is a limiting factor.
  • ||||||||||  Fetroja (cefiderocol) / Shionogi
    Journal:  Cefiderocol Retains Anti-Biofilm Activity in Multi-Drug Resistant Gram-Negative Pathogens. (Pubmed Central) -  Jun 22, 2021   
    There was a trend towards greater biofilm reduction when the antibiotic dose was increased or with increased frequency of antibiotic treatment. We conclude that cefiderocol effectively reduces biofilm and is a potent inhibitor of planktonic growth across a range of Gram-negative medically important pathogens.
  • ||||||||||  Clinical, PK/PD data, Journal:  Pharmacokinetic/pharmacodynamic target attainment in critically ill renal patients on antimicrobial usage: focus on novel beta-lactams and beta lactams/beta-lactamase inhibitors. (Pubmed Central) -  Jun 22, 2021   
    Suboptimal clinical response rate with ceftazidime-avibactam and ceftolozane-tazobactam was reported in phase II-III trials in patients with moderate kidney injury; data on patients undergoing renal replacement therapy are limited to some case reports; dose adjustment in augmented renal clearance is provided only for cefiderocol. Implementation of altered dosing strategies (prolonged infusion and/or higher dosage) coupled with adaptive real-time therapeutic drug monitoring could represent the most effective approach in warranting optimal pharmacokinetic/pharmacodynamic targets with novel BLs and/or BL/BLIs in challenging scenarios, thus minimizing the risk of clinical failure and/or of resistance selection.
  • ||||||||||  QPX7728 / Qpex Biopharma, Brii Biosci
    Preclinical, Journal, Combination therapy:  In Vitro Activity of the Ultra-Broad-Spectrum Beta-lactamase Inhibitor QPX7728 in Combination with Multiple Beta-Lactam Antibiotics against Pseudomonas aeruginosa. (Pubmed Central) -  Jun 22, 2021   
    Seven hundred ninety clinical isolates were included in this study; 500 isolates, termed a "representative panel," were selected to be representative of the MIC distribution of meropenem (MEM), ceftazidime-avibactam (CAZ-AVI), and ceftolozane-tazobactam (TOL-TAZ) resistance for clinical isolates according to 2017 SENTRY surveillance data...For the challenge panel, QPX-ceftolozane (TOL) was the most active combination (78.6% susceptible) followed by equipotent QPX-piperacillin (PIP) and QPX-cefepime (FEP), restoring susceptibility in 70.3% of strains (CLSI breakpoints for the beta-lactam compound alone)...Increased efflux and impaired OprD had varying effect on QPX7728 combination depending on the partner beta-lactam tested. QPX7728 enhanced the potency of multiple beta-lactams against P. aeruginosa, with varying results according to the beta-lactamase production and other intrinsic resistance mechanisms.
  • ||||||||||  Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
    Clinical, Journal:  Global trends and hotspots in research of carbapenem-resistant Enterobacteriaceae (CRE): a bibliometric analysis from 2010 to 2020. (Pubmed Central) -  Jun 16, 2021   
    Eighty-one percent (12/16) of ceftolozane-tazobactam resistant isolates with ampC mutations were susceptible to imipenem-relebactam. The bibliometric analysis revealed that development of antibacterial agents, early etiological detection and genome sequencing techniques were the hotspots and would probably direct the future research directions which would also facilitate a better understanding of the epidemiology of drug-resistant bacteria and implementing the antibiotic stewardship program.
  • ||||||||||  Teflaro (ceftaroline fosamil) / Sumitomo Dainippon, AstraZeneca, AbbVie, Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
    Clinical, Journal:  Investigation of an outbreak of Elizabethkingia meningoseptica on a pediatric intensive care unit. (Pubmed Central) -  Jun 12, 2021   
    Resistance was found to the relatively new antibiotics ceftaroline and ceftazidime-avibactam...Investigation of the outbreak source and continuation of intensive infection control precautions are vital to handle E. meningoseptica outbreaks in PICUs. Using quinolones according to testing results of automated AST systems may lead to inadequate treatment and foster the selection of resistant strains.
  • ||||||||||  Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
    Preclinical, Journal:  Safety and Efficacy of a Phage, kpssk3, in an in vivo Model of Carbapenem-Resistant Hypermucoviscous Klebsiella pneumoniae Bacteremia. (Pubmed Central) -  Jun 8, 2021   
    Phage kpssk3 was shown to not be cytotoxic to mammalian cells in vitro or in vivo. Fecal samples were collected from the phage-treated mice at 3 time points before (0 day) and after (3 and 10 days) phage therapy to study the change in the gut microbiome via high-throughput 16S rDNA sequence analysis, which revealed no notable alterations in the gut microbiota except for decreases in the Chao1 and ACE indexes.
  • ||||||||||  Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
    Journal:  Emergence of ceftazidime-avibactam resistance in KPC-8-producing Klebsiella pneumoniae in South America. (Pubmed Central) -  Jun 4, 2021   
    Fecal samples were collected from the phage-treated mice at 3 time points before (0 day) and after (3 and 10 days) phage therapy to study the change in the gut microbiome via high-throughput 16S rDNA sequence analysis, which revealed no notable alterations in the gut microbiota except for decreases in the Chao1 and ACE indexes. No abstract available
  • ||||||||||  Fetroja (cefiderocol) / Shionogi
    [VIRTUAL] COMPASSIONATE USE OF CEFIDEROCOL FOR VIM METALLO-BETA-LACTAMASE-PRODUCING PSEUDOMONAS AERUGINOSA INFECTION IN A TODDLER WITH BURKITT LYPHOMA () -  Jun 2, 2021 - Abstract #ESPID2021ESPID_1447;    
    She was receiving chemotherapy and tuberculostatic treatment (isoniazid, pyrazinamide, ethambutol and levofloxacin; rifampicin was discontinued due to liver toxicity)...Despite in-vitro resistance to all antibiotics tested (cephalosporins, piperacillin/tazobactam, quinolones, aminoglycosides, colistin, carbapenems, and also the combination of aztreonam with ceftazidime-avibactam), the patient received high-dose colistin for 14 days and the infection was controlled...After 5 days, fever persisted so cefepime was switched to high-dose meropenem and teicoplanin...In this case, ecthyma was controlled when cefiderocol was started, but coincident with neutrophil recovery. More information is needed about novel antibiotics in pediatrics.
  • ||||||||||  Clinical, Journal:  Novel Cephalosporins in Septic Subjects and Severe Infections: Present Findings and Future Perspective. (Pubmed Central) -  May 25, 2021   
    Moreover, new cephalosporins are the basis for the actual indications to open up new and exciting prospects for serious infections in the future. In future, patients will be addressed with the desirable approach to sepsis and serious infections in terms of their clinical situation, inherent features of the host, the sensitivity profile, and local epidemiology, for which evidence of the use of new cephalosporin in the treatment of severe infections will fill the remaining gaps.