BWC0977, a broad-spectrum antibacterial clinical candidate to treat multidrug resistant infections.

The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC) of 0.

Cefepime-taniborbactam activity against antimicrobial-resistant clinical isolates of Enterobacterales and Pseudomonas aeruginosa: GEARS global surveillance programme 2018-22.

Objectives: Taniborbactam is a boronate-based β-lactamase inhibitor in clinical development in combination with cefepime.

Methods: Cefepime-taniborbactam and comparator broth microdilution MICs were determined for patient isolates of Enterobacterales (n = 20 725) and Pseudomonas aeruginosa (n = 7919) collected in 59 countries from 2018 to 2022. Taniborbactam was tested at a fixed concentration of 4 mg/L.

and activity of cefiderocol against spp. and complex, including carbapenem-non-susceptible isolates.

spp. and complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the antibacterial activity of the siderophore antibiotic cefiderocol against spp.

In vitro activity of cefiderocol against MBL-producing Gram-negative bacteria collected in North America and Europe in five consecutive annual multinational SIDERO-WT surveillance studies (2014-2019).

Objectives: To evaluate the in vitro antibacterial activity of cefiderocol, a siderophore cephalosporin against MBL-producing clinical isolates.

Methods: MBL-producing strains were selected from clinical isolates of Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii complex collected in North America and Europe in five consecutive annual multinational SIDERO-WT surveillance studies from 2014 to 2019. MICs of cefiderocol and comparator agents were determined by the broth microdilution method according to the CLSI guideline.

Relebactam restores susceptibility of resistant Pseudomonas aeruginosa and Enterobacterales and enhances imipenem activity against chromosomal AmpC-producing species: analysis of global SMART 2018-2020.

Background: Carbapenem-resistant bacteria are an increasing problem in clinical practice; thus, it is important to identify β-lactamase inhibitors (e.g., relebactam) that can restore carbapenem susceptibility.

Activity of Cefiderocol Against Meropenem-Nonsusceptible Gram-Negative Bacilli with Defined β-Lactamase Carriage: SIDERO-WT Surveillance Studies, 2014-2019.

We examined the susceptibility of meropenem-nonsusceptible Enterobacterales, , and complex isolates from five consecutive annual SIDERO-WT surveillance studies (2014-2019) to cefiderocol and comparator agents in the context of their carbapenemase carriage. 1,003 Enterobacterales, 1,758 , and 2,809 complex isolates from North America and Europe that were meropenem nonsusceptible (CLSI M100, 2022) were molecularly characterized for β-lactamase content by PCR followed by Sanger sequencing or by whole genome sequencing. Among Enterobacterales, 91.

Multicenter Clinical Performance Evaluation of Omadacycline Susceptibility Testing of on VITEK 2 Systems.

We present the first performance evaluation results for omadacycline on the VITEK 2 and VITEK 2 Compact Systems (bioMérieux, Inc.). The trial was conducted at four external sites and one internal site.

Multidrug-resistant Gram-negative bacilli recovered from respiratory and blood specimens from adults: the ATLAS surveillance program in European hospitals, 2018-2020.

The population of people ≥65 years of age is increasing in Europe. Pneumonia is a prominent cause of infection in this age group. These patients may be at heightened risk of infection caused by multidrug-resistant (MDR) organisms owing to their frequent and prolonged contact with healthcare facilities as well as frequent exposure to antimicrobials and medical devices.

Activity of Ceftibuten-Avibactam against β-Lactamase-Positive Enterobacterales from the ATLAS Global Surveillance Program.

Ceftibuten is an established, oral, third-generation cephalosporin in early clinical development in combination with an oral prodrug of avibactam for the treatment of complicated urinary tract infections, including acute pyelonephritis. We evaluated the activity of ceftibuten-avibactam against 1,165 Enterobacterales isolates selected from the 2016-2020 ATLAS global surveillance program based upon their β-lactamase genotype, β-lactam-susceptible phenotype, species identification, and specimen source (95.8% urine).

In vitro antibacterial activities of cefiderocol against Gram-negative clinical strains isolated from China in 2020.

Objectives: Cefiderocol (CFDC) is a parenteral siderophore cephalosporin that is active against Gram-negative bacteria, including carbapenem-resistant isolates. We report the in vitro activity of CFDC and other antibiotics against 1738 clinical isolates of Gram-negative bacilli (GNB) provided by five medical centres in five provinces of China in 2020 METHODS: Antibiotic susceptibility testing was performed using the Clinical and Laboratory Standards Institute broth microdilution method.

Results: Against Pseudomonas aeruginosa and Acinetobacter Spp.

Antimicrobial activity of ceftazidime-avibactam and comparators against levofloxacin-resistant Escherichia coli collected from four geographic regions, 2012-2018.

Background: Increases in resistance to fluoroquinolones have been correlated with the use of levofloxacin in the treatment of infections caused by Escherichia coli. The analysis presents the in vitro activity of ceftazidime-avibactam and comparator agents against 10,840 levofloxacin-resistant E. coli isolates collected from four geographic regions (Africa/Middle East, Europe, Asia/South Pacific, Latin America) between 2012 and 2018.

Activity of Gepotidacin against Gram-Negative and Gram-Positive Anaerobes.

Gepotidacin (formerly GSK2140944) is a first-in-class triazaacenaphthylene antibacterial currently in phase III clinical trials. When tested against Gram-negative (= 333) and Gram-positive (= 225) anaerobes by agar dilution, gepotidacin inhibited 90% of isolates at concentrations of 4 and 2 μg/mL, respectively. Given gepotidacin's activity against the anaerobic isolates tested, further study is warranted to better understand the utility of gepotidacin in the treatment of infections caused by clinically relevant anaerobic organisms.

Susceptibility of Gram-Negative Pathogens to Cefiderocol in Five Consecutive Annual Multinational SIDERO-WT Surveillance Studies, 2014 to 2019.

We report susceptibility data from five consecutive annual SIDERO-WT surveillance studies (2014 to 2019) for cefiderocol and comparators tested against Gram-negative clinical isolates from North America and Europe. CLSI broth microdilution was used to determine MICs for (= 31,896), Pseudomonas aeruginosa (= 7,700), Acinetobacter baumannii complex (= 5,225), Stenotrophomonas maltophilia (= 2,030), and Burkholderia cepacia complex (= 425). MICs were interpreted by CLSI-approved clinical breakpoints (February 2021).

Activity of Ceftibuten/VNRX-5236 against Urinary Tract Infection Isolates of Antimicrobial-Resistant .

Ceftibuten/VNRX-7145 is a cephalosporin/boronate β-lactamase inhibitor combination under development as an oral treatment for complicated urinary tract infections caused by producing serine β-lactamases (Ambler class A, C, and D). , VNRX-7145 (VNRX-5236 etzadroxil) is cleaved to the active inhibitor, VNRX-5236. We assessed the activity of ceftibuten/VNRX-5236 against 1,066 urinary isolates of from a 2014-2016 global culture collection.

Collective assessment of antimicrobial susceptibility among the most common Gram-negative respiratory pathogens driving therapy in the ICU.

Objectives: To describe the pathogen predominance and to evaluate the probability of covering the most common Gram-negative pathogens collectively in both empirical and early adjustment prescribing scenarios in ICU patients with respiratory infections.

Methods: Data were collected from an international cohort of hospitals as part of the SMART Surveillance Program (2018). Susceptibility testing (mg/L) was performed by broth microdilution methods.

strains possessing a four amino acid YRIN insertion in PBP3 identified as part of the SIDERO-WT-2014 surveillance study.

Background: In addition to carbapenemases, dissemination of recently reported lineages possessing a four amino acid insertion in PBP3 (encoded by ) that confers reduced susceptibility to PBP3-targeted β-lactams, such as ceftazidime, can pose a threat of antimicrobial resistance.

Objectives: To evaluate genotypic and phenotypic characteristics of possessing the mutated PBP3 collected during SIDERO-WT-2014 surveillance.

Methods: A subset of 65 clinical isolates with MICs ≥2 mg/L for ceftazidime/avibactam, ceftolozane/tazobactam or cefiderocol, among a total of 1529 isolates from the multinational surveillance study, were subjected to gene analysis and antimicrobial susceptibility testing.

Activity of imipenem/relebactam and comparators against gram-negative pathogens from patients with bloodstream infections in the United States and Canada - SMART 2018-2019.

Bloodstream infections (BSI) are often caused by drug-resistant pathogens, and novel antimicrobials are needed. We examined the activity of imipenem/relebactam against BSI pathogens from US and Canada: >99% of non-Morganellaceae Enterobacterales, including 100% of MDR isolates, and >94% of Pseudomonas aeruginosa were imipenem/relebactam-susceptible. Imipenem/relebactam could provide an important treatment option.

In vitro activity of ceftaroline against bacterial pathogens isolated from patients with skin and soft tissue and respiratory tract infections in the Middle East and Africa: AWARE global surveillance programme 2015-2018.

Objectives: To report antimicrobial susceptibility testing surveillance data for ceftaroline and comparative agents from the AWARE global surveillance programme for bacterial pathogens causing skin and soft tissue infections (SSTIs) and lower respiratory infections (RTIs) in Middle East and African countries from 2015 to 2018.

Methods: Pathogens were identified by MALDI-TOF/MS. Antimicrobial susceptibility testing was performed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method.

Activity of WCK 5222 (Cefepime-Zidebactam) against Worldwide Collected Gram-Negative Bacilli Not Susceptible to Carbapenems.

WCK 5222 (cefepime-zidebactam, 2 g + 1g, every 8 h [q8h]) is in clinical development for the treatment of infections caused by carbapenem-resistant and multidrug-resistant (MDR) Gram-negative bacilli. We determined the susceptibility of 1,385 clinical isolates of non-carbapenem-susceptible , MDR (also non-carbapenem susceptible), , and spp. collected worldwide (49 countries) from 2014 to 2016 to cefepime-zidebactam (1:1 ratio), ceftazidime-avibactam, imipenem-relebactam, ceftolozane-tazobactam, and colistin using the CLSI broth microdilution method.