- |||||||||| Review, Journal, Gram negative: Novel Antibiotics for Gram-Negative Nosocomial Pneumonia. (Pubmed Central) - Jul 27, 2024
We critically present data for the pharmacokinetics/pharmacodynamics, the in vitro spectrum of antimicrobial activity and resistance, and in vivo data for their clinical and microbiological efficacy in trials. Where possible, available data are summarized specifically in patients with nosocomial pneumonia, as this cohort may exhibit 'critical illness' physiology that affects drug efficacy.
- |||||||||| Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
Journal: Resistance to ceftazidime-avibactam and other new ?-lactams in Pseudomonas aeruginosa clinical isolates: a multi-center surveillance study. (Pubmed Central) - Jun 27, 2024 Among non-?-lactams, colistin and amikacin were active against 100% and 85.8% of isolates respectively...With this work, we report that CZA represents a highly active antipseudomonal ?-lactam compound (after cefiderocol), and that metallo-?-lactamases (VIM-type) and extended-spectrum ?-lactamases (GES and PER-type) production is the major factor underlying CZA resistance in isolates from Southern Italian hospitals. In addition, we reported that such resistance mechanisms were mainly carried by the international high-risk clones ST111 and ST235.
- |||||||||| Fetroja (cefiderocol) / Shionogi
Preclinical, Journal: In vitro activity of cefiderocol against European Enterobacterales, including isolates resistant to meropenem and recent?-lactam/?-lactamase inhibitor combinations. (Pubmed Central) - Jun 21, 2024 Cefiderocol susceptibility was higher than approved ?-lactam/?-lactamase inhibitor combinations and largely comparable to cefepime-taniborbactam and aztreonam-avibactam against all Enterobacterales (98.1% vs 78.1%-?97.4% and 98.7%-99.1%, respectively) and Enterobacterales resistant to meropenem (n = 148, including 125 Klebsiella spp.; 87.8% vs 0%-71.6% and 93.2%-98.6%, respectively), ?-lactam/?-lactamase inhibitor combinations (66.7%-?92.1% vs 0%-?88.1% and 66.7%-97.9%, respectively), and to both meropenem and ?-?lactam/?-lactamase inhibitor combinations (61.9%-65.9% vs 0%-?20.5% and 76.2%-97.7%, respectively)...Early susceptibility testing of cefiderocol in parallel with ?-lactam/?-lactamase inhibitor combinations will allow patients to receive the most appropriate treatment option(s) available in a timely manner. This is particularly important when options are more limited, such as against metallo-?-lactamase-producing Enterobacterales.
- |||||||||| Review, Gram negative: Friends or foes? Novel antimicrobials tackling MDR/XDR Gram-negative bacteria: a systematic review. (Pubmed Central) - May 27, 2024
The present review aims to highlight these six antibiotic agents, which have brought hope to clinicians during the past decade, discussing general properties of these substances, as well as mechanisms and patterns of resistance, while also providing a short overview on further directions in the field. https://www.crd.york.ac.uk/prospero/#searchadvanced, Identifier CRD42024505832.
- |||||||||| Zerbaxa (ceftolozane /tazobactam) / Merck (MSD), imipenem/relebactam / Merck (MSD)
Journal, Gram negative: Activity of ceftolozane/tazobactam and imipenem/relebactam against Gram-negative clinical isolates collected in Mexico-SMART 2017-2021. (Pubmed Central) - May 27, 2024 Almost all imipenem/relebactam-non-susceptible E. coli and K. pneumoniae carried MBL or OXA-48-like carbapenemases, whereas among imipenem/relebactam-non-susceptible P. aeruginosa, 56% carried MBL or GES carbapenemases. Ceftolozane/tazobactam and imipenem/relebactam may provide treatment options for patients infected with ?-lactam-non-susceptible Gram-negative bacilli, excluding isolates carrying an MBL- or OXA-48-like carbapenemase.
- |||||||||| Fetroja (cefiderocol) / Shionogi
Preclinical, Journal: In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent ?-lactam/?-lactamase inhibitor combinations. (Pubmed Central) - Apr 8, 2024 inhibitor combinations against P. aeruginosa (98.9% vs 83.3%-91.4%), and P. ?aeruginosa resistant to meropenem (n = 139; 97.8% vs 12.2%-59.7%), ?-lactam/?-lactamase inhibitor combinations (93.6%-98.1% vs 10.7%-71.8%), and both meropenem and ceftazidime-avibactam (96.7% vs 5.0%-??45.0%) or ?ceftolozane-tazobactam (98.4% vs 8.1%-54.8%), respectively...(n = 227; 85.0% and 93.8%) but lower against sulbactam-durlobactam- (n ?= 15; 13.3%) and cefiderocol- (n = 38; 65.8%) resistant isolates, respectively...and indicate how early susceptibility testing of cefiderocol in parallel with ?-lactam/?-lactamase inhibitor combinations will allow clinicians to choose the effective treatment(s) from all available options. This is particularly important as current treatment options against non-fermenters are limited.
- |||||||||| relebactam (MK-7655) / Merck (MSD)
Preclinical, Journal: Aztreonam Combinations with Avibactam, Relebactam, and Vaborbactam as Treatment for New Delhi Metallo-?-Lactamase-Producing Enterobacterales Infections-In Vitro Susceptibility Testing. (Pubmed Central) - Mar 28, 2024 We investigated 21 NDM isolates-including Klebsiella pneumoniae, Escherichia coli, and Citrobacter freundii-which are simultaneously resistant to aztreonam, ceftazidime/avibactam, imipenem/relebactam, and meropenem/vaborbactam...The most effective combination was aztreonam/avibactam, active in 80.95% strains, while combinations with relebactam and vaborbactam were effective in 61.90% and 47.62%, respectively...However, combinations with other inhibitors should not be rejected in advance because we identified strain susceptible only to tested combinations with inhibitors other than avibactam. Standardization committees should, as soon as possible, develop official methodology for antimicrobial susceptibility testing for aztreonam with ?-lactamase inhibitors.
- |||||||||| imipenem/relebactam / Merck (MSD)
PK/PD data, Journal: Imipenem/relebactam pharmacokinetics in critically ill patients supported on extracorporeal membrane oxygenation. (Pubmed Central) - Mar 22, 2024 This framework could also be expanded to incorporate other new antimicrobials, such as cefiderocol, or currently unavailable BL/BLIs such as aztreonam/avibactam and cefepime/taniborbactam. Imipenem/cilastatin/relebactam dosed according to package insert in patients supported on ECMO is predicted to achieve exposures sufficient to treat susceptible Gram-negative isolates, including Pseudomonas aeruginosa.
- |||||||||| imipenem/relebactam / Merck (MSD), Vabomere (meropenem/vaborbactam) / Melinta Therap, Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
Journal: Rates of resistance and heteroresistance to newer ?-lactam/?-lactamase inhibitors for carbapenem-resistant Enterobacterales. (Pubmed Central) - Mar 22, 2024 Twenty-four percent of CRE isolates tested were either resistant or heteroresistant (HR) to newer BL/BLIs, with an overall decrease of ?10% susceptibility over 6?years. While newer BL/BLIs remain active against most CRE, these findings support the need for ongoing antibiotic stewardship and a better understanding of the clinical implications of HR in CRE.
- |||||||||| ANT3310 / Antabio
Journal, Gram negative: Meropenem-ANT3310, a unique ?-lactam-?-lactamase inhibitor combination with expanded antibacterial spectrum against Gram-negative pathogens including carbapenem-resistant Acinetobacter baumannii. (Pubmed Central) - Jan 30, 2024 However, tolerability of the HFS-Mab identified dose could be an issue. MEM was poorly active against A. baumannii, as were MEM-vaborbactam, ceftazidime-avibactam, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and imipenem-relebactam (MIC values of ?32
- |||||||||| Zerbaxa (ceftolozane /tazobactam) / Merck (MSD), imipenem/relebactam / Merck (MSD), Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
Journal: Moving towards a standardized definition of antimicrobial resistance: a comparison of the antimicrobial susceptibility profile of difficult-to-treat resistance (DTR) versus multidrug-resistant (MDR) Pseudomonas aeruginosa clinical isolates (CANWARD, 2016-2021). (Pubmed Central) - Jan 22, 2024 Susceptibility was lower for all antimicrobials versus DTR relative to MDR isolates. Ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam susceptibility was 35.9%, 64.5%, and 47.0% for DTR isolates and 60.5%, 80.6%, and 71.5% for MDR isolates.
- |||||||||| Review, Journal: Approaches to Testing Novel ?-Lactam and ?-Lactam Combination Agents in the Clinical Laboratory. (Pubmed Central) - Dec 23, 2023
While their introduction offers a beacon of hope, clinical microbiology laboratories must navigate the complexities of susceptibility testing for these agents due to their diverse activity profiles against specific ?-lactamases and the possibility of acquired resistance mechanisms in some bacterial isolates. This review explores the complexities of these novel antimicrobial agents detailing the intricacies of their application, providing guidance on the nuances of susceptibility testing, interpretation, and result reporting in clinical microbiology laboratories.
- |||||||||| imipenem/relebactam / Merck (MSD)
Preclinical, Journal: In vitro activity of imipenem/relebactam against Pseudomonas aeruginosa isolated from patients with cystic fibrosis. (Pubmed Central) - Dec 17, 2023 Imipenem/relebactam, imipenem, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam susceptibilities were 77%, 55%, 58%, 90%, and 92%, respectively. Relebactam potentiates imipenem against CF P. aeruginosa by fourfold leading imipenem/relebactam to retain susceptibility against most isolates in this cohort.
- |||||||||| Review, Journal: What are the most relevant publications in Clinical Microbiology in the last two years? (Pubmed Central) - Nov 28, 2023
This minireview describes some of the articles published in the last two years related to innovative technologies including CRISPR-Cas, surface-enhanced Raman spectroscopy, microfluidics, flow cytometry, Fourier transform infrared spectroscopy, and artificial intelligence and their application to microbiological diagnosis, molecular typing and antimicrobial susceptibility testing. In addition, some articles related to resistance to new antimicrobials (ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and cefiderocol) are also described.
- |||||||||| relebactam (MK-7655) / Merck (MSD)
Preclinical, Journal: Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study. (Pubmed Central) - Nov 24, 2023 The addition of relebactam delays the generation of resistance to imipenem and limits the cross-resistance to other beta-lactams. The clinical relevance of this phenomenon, which has the limitation that it has been performed in vitro, should be evaluated by stewardship programs in clinical practice, as it could be useful in controlling multi-drug resistance in P. aeruginosa.
- |||||||||| imipenem/relebactam / Merck (MSD), Vabomere (meropenem/vaborbactam) / Melinta Therap, Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
Review, Journal: Klebsiella pneumoniae carbapenemase variants: the new threat to global public health. (Pubmed Central) - Nov 8, 2023 In addition, meropenem-vaborbactam, imipenem-relebactam, and other new ?-lactam-?-lactamase inhibitor combinations have little discussion on KPC variants. This review aims to discuss the clinical characteristics, risk factors, epidemiological characteristics, antimicrobial susceptibility profiles, methods for detecting bla variants, treatment options, and future perspectives of bla variants worldwide to alert this new great public health threat.
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