Antimicrobial susceptibility of enterobacterales causing bloodstream infection in United States medical centres: comparison of aztreonam-avibactam with beta-lactams active against carbapenem-resistant enterobacterales.

Background: Bloodstream infection (BSI) is associated with poor outcomes especially when effective antimicrobial therapy and control of infection source are delayed. As the frequency of Enterobacterales producing metallo-β-lactamases (MBL) and/or OXA-48-like carbapenemases is increasing in some United States (US) medical centres, effective antimicrobials to treat the infections caused by these organisms are urgently needed. Aztreonam-avibactam is under clinical development for treatment of infections caused by Gram-negative bacteria, including MBL producers.

Intermethod comparability analyses of gepotidacin antimicrobial susceptibility tests using a large collection of globally collected Escherichia coli and Staphylococcus saprophyticus clinical isolates.

Gepotidacin (GSK2140944) is a novel, bactericidal, first in class triazaacenaphthylene bacterial type II topoisomerase inhibitor in development for the treatment of uncomplicated urinary tract infections and gonorrhea. The performance of several antimicrobial susceptibility methods (broth microdilution, gradient diffusion, and disk diffusion) for gepotidacin were evaluated using over 5800 recent Escherichia coli and Staphylococcus saprophyticus clinical isolates. Reference broth microdilution gepotidacin MICs showed an essential agreement of 95.

In Vitro Activity of Isavuconazole and Other Mould-Active Azoles against with and without CYP51 Alterations.

Azole resistance in (AFM) is mainly associated with mutations in CYP51A and its promoter region or its homologue CYP51B. We evaluated the in vitro activity of isavuconazole, itraconazole, posaconazole, and voriconazole against 660 AFM collected during 2017-2020. Isolates were tested via CLSI broth microdilution.

In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program.

Objectives: Physicians must leverage several factors when making antibiotic therapy decisions, including route of administration and duration of therapy. Oral administration provides several potential advantages including increased accessibility, prevention of hospitalizations and earlier discharges. Sulopenem-a broad-spectrum, synthetic penem β-lactam agent-uniquely possesses both oral and IV formulations along with noted stability among antimicrobial-resistant subsets.

Aztreonam/avibactam activity against a large collection of carbapenem-resistant Enterobacterales (CRE) collected in hospitals from Europe, Asia and Latin America (2019-21).

Background: Aztreonam/avibactam is under development to treat infections caused by Gram-negative bacteria. We evaluated the activities of aztreonam/avibactam and comparators against a global collection of carbapenem-resistant Enterobacterales (CRE), including ceftazidime/avibactam-resistant isolates.

Methods: Isolates were consecutively collected (24 924; 1/patient) from 69 medical centres in 36 countries during 2019-21.

Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific.

Isavuconazole is the only US FDA-approved antifungal for treating invasive mucormycosis. We evaluated isavuconazole activity against a global collection of Mucorales isolates. Fifty-two isolates were collected during 2017-2020 from hospitals located in the USA, Europe, and the Asia-Pacific.

Antimicrobial activity of ceftibuten-avibactam against a global collection of Enterobacterales from patients with urinary tract infections (2021).

We evaluated the in vitro activity of ceftibuten-avibactam against Enterobacterales causing urinary tract infection (UTI). A total of 3216 isolates (1/patient) were consecutively collected from patients with UTI in 72 hospitals from 25 countries in 2021 then susceptibility tested by CLSI broth microdilution. Ceftibuten-susceptible breakpoints currently published by EUCAST (≤ 1 mg/L) and CLSI (≤ 8 mg/L) were applied to ceftibuten-avibactam for comparison.

Prevalence of carbapenemase genes among carbapenem-nonsusceptible collected in US hospitals in a five-year period and activity of ceftazidime/avibactam and comparator agents.

Objectives: To evaluate the prevalence of acquired β-lactamase genes and susceptibility profiles of carbapenem-nonsusceptible (CNSE) clinical isolates collected in US hospitals during a 5-year period.

Methods: Isolates were susceptibility tested by reference broth microdilution methods. Results were interpreted using CLSI breakpoints.

In Vitro and In Vivo Antimicrobial Activity of the Novel Peptide OMN6 against Multidrug-Resistant .

The rapid worldwide spread of antimicrobial resistance highlights the significant need for the development of innovative treatments to fight multidrug-resistant bacteria. This study describes the potent antimicrobial activity of the novel peptide OMN6 against a wide array of drug-resistant clinical isolates. OMN6 prevented the growth of all tested isolates, regardless of any pre-existing resistance mechanisms.

Antimicrobial activity of dalbavancin against Gram-positive bacteria isolated from patients hospitalized with bloodstream infection in United States and European medical centers (2018-2020).

Dalbavancin and comparators were susceptibility tested against 8643 Gram-positive bacteria from 74 hospitals located in Europe and the United States by broth microdilution method. The most common organisms were Staphylococcus aureus (45.2%), Enterococcus faecalis (12.

Antimicrobial activities of aztreonam-avibactam and comparator agents tested against Enterobacterales from European hospitals analysed by geographic region and infection type (2019-2020).

The purpose of this study is to evaluate the activities of aztreonam-avibactam and comparator agents against Enterobacterales isolates from European medical centres as well as the occurrence of carbapenemases (CPEs). A total of 11,655 Enterobacterales isolates were collected consecutively in 2019-2020 from 38 medical centres located in Western Europe (W-EU; n = 8,784; 25 centres in 10 countries) and the Eastern European and Mediterranean region (E-EU; n = 2,871; 13 centres in 10 countries). Isolates were susceptibility tested by broth microdilution methods in a monitoring laboratory.

Comparative activity of newer β-lactam/β-lactamase inhibitor combinations against Pseudomonas aeruginosa from patients hospitalized with pneumonia in European medical centers in 2020.

Pseudomonas aeruginosa isolates were consecutively collected from patients with pneumonia in 29 medical centers in 2020 and susceptibility tested by broth microdilution method. Ceftazidime-avibactam (95.5% susceptible), imipenem-relebactam (94.

Activity of ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam against carbapenemase-negative carbapenem-resistant Enterobacterales isolates from US hospitals.

We investigated the prevalence, resistance mechanisms and activity of ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam and comparator agents against carbapenem-resistant Enterobacterales (CRE) that did not carry carbapenemase genes. Among 304 CRE isolates collected in US hospitals during 2016-2018 (1.1% of the overall Enterobacterales), 45 (14.

Comparative activity of posaconazole and systemic azole agents against clinical isolates of filamentous fungi from a global surveillance programme.

Objectives: The activity of mould-active azoles was evaluated against 397 filamentous fungi causing invasive mould infections (IMI) worldwide. In addition, a tentative posaconazole epidemiological cut-off value (ECV) against was investigated.

Methods: Isolates were susceptibility tested by the CLSI reference broth microdilution methods.

Update on the activity of delafloxacin against acute bacterial skin and skin-structure infection isolates from European hospitals (2014-2019).

Objectives: Delafloxacin is a broad-spectrum anionic fluoroquinolone with activity against Gram-positive and Gram-negative organisms, including methicillin-resistant Staphylococcus aureus. Both oral and intravenous formulations were approved for use in the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) due to Gram-positive and Gram-negative organisms by the US Food and Drug Administration (2017) and European Medicines Agency (2019), and for community-acquired bacterial pneumonia by the FDA (2019). The SENTRY Antimicrobial Surveillance Program has monitored the susceptibility of delafloxacin in the USA and Europe since 2014.

Antimicrobial activity of ceftolozane/tazobactam tested against contemporary (2015-2017) Pseudomonas aeruginosa isolates from a global surveillance programme.

Objectives: Ceftolozane/tazobactam (C-T) is an antimicrobial combination of an antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T has been approved in >60 countries for complicated urinary tract infections, acute pyelonephritis, complicated intra-abdominal infections in combination with metronidazole, and was recently approved for hospital-acquired bacterial pneumonia. In this study, data for Pseudomonas aeruginosa isolates consecutively collected from various infection types in hospitalised patients from 2015 to 2017 were analysed.

Analysis of global antifungal surveillance results reveals predominance of Erg11 Y132F alteration among azole-resistant Candida parapsilosis and Candida tropicalis and country-specific isolate dissemination.

This study evaluated the activity of echinocandins, azoles and amphotericin B against Candida spp. isolates and other yeasts and characterised azole resistance mechanisms in Candida parapsilosis and Candida tropicalis. Invasive Candida spp.

Frequency and antimicrobial susceptibility of bacterial isolates from patients hospitalised with community-acquired skin and skin-structure infection in Europe, Asia and Latin America.

Objectives: Ceftaroline fosamil is approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs), including those caused by methicillin-resistant Staphylococcus aureus (MRSA). This study evaluated the frequency and antimicrobial susceptibility of organisms isolated from patients hospitalised with community-acquired (CA) SSSI in Europe, the Asia-Pacific region (APAC) and Latin America (LATAM).

Methods: Isolates (n=5120) were consecutively collected from patients hospitalised with CA-SSSI in 2014-2016 from 63 medical centres in 41 nations, stratified as Western Europe (20 centres/10 nations), Eastern Europe and the Mediterranean region (E-EUR; 16 centres/12 nations), APAC (16 centres/10 nations) and LATAM (11 centres/9 nations).

Aminoglycoside-modifying enzyme and 16S ribosomal RNA methyltransferase genes among a global collection of Gram-negative isolates.

Objectives: The prevalence of genes encoding aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methyltransferases among 200 Gram-negative clinical isolates resistant to different aminoglycosides and collected worldwide during 2013 was evaluated.

Methods: Selected AMEs and 16S rRNA methyltransferase genes were screened by PCR/sequencing among 49 Acinetobacter spp., 52 Pseudomonas aeruginosa and 99 Enterobacterales.

Antimicrobial activity of ceftaroline and comparator agents tested against organisms isolated from patients with community-acquired bacterial pneumonia in Europe, Asia, and Latin America.

Objective: To evaluate the potency and spectrum of ceftaroline and comparator agents tested against contemporary bacteria isolated from patients with community-acquired bacterial pneumonia (CABP) in Europe (EUR), Asia-Pacific (APAC), and Latin America (LATAM).

Methods: A total of 4321 bacterial isolates were collected consecutively by the SENTRY Antimicrobial Surveillance Program in 2015-2017 from 65 medical centers located in Western Europe (W-EUR; 21 centers in 10 nations), Eastern Europe and the Mediterranean region (E-EUR; 15 centers in 11 nations), APAC (18 centers in nine nations), and LATAM (11 centers in nine nations). Isolates were collected from lower respiratory tract specimens, and an isolate obtained from an outpatient or earlier than 48h after hospitalization was considered community-acquired.

Molecular β-lactamase characterization of Gram-negative pathogens recovered from patients enrolled in the ceftazidime-avibactam phase 3 trials (RECAPTURE 1 and 2) for complicated urinary tract infections: Efficacies analysed against susceptible and resistant subsets.

This study characterized the β-lactamase content of baseline pathogens recovered from patients with complicated urinary tract infections (cUTI), including acute pyelonephritis, who were enrolled in two phase 3 clinical trials of ceftazidime-avibactam (RECAPTURE 1 and 2), and correlated the clinical efficacy of ceftazidime-avibactam and the comparator doripenem according to resistance mechanisms. A total of 26.2% (93/355) ceftazidime-avibactam and 26.

Surveillance of tigecycline activity tested against clinical isolates from a global (North America, Europe, Latin America and Asia-Pacific) collection (2016).

Tigecycline and comparators were tested by the reference broth microdilution method against 33 348 non-duplicate bacterial isolates collected prospectively in 2016 from medical centres in the Asia-Pacific (3443 isolates), Europe (13 530 isolates), Latin America (3327 isolates) and the USA (13 048 isolates). Among 7098 Staphylococcus aureus isolates tested, >99.9% were inhibited by ≤0.

Telavancin activity in vitro tested against a worldwide collection of Gram-positive clinical isolates (2014).

Objectives: Telavancin activity was measured against Gram-positive pathogens collected worldwide during 2014 using the revised broth microdilution testing method. The results were compared with previous reports.

Methods: A total of 10552 isolates from 86 sites located in 32 countries were included as part of the Telavancin International Surveillance Program for the Americas, Europe and Asia-Pacific.

Update of the activity of telavancin against a global collection of Staphylococcus aureus causing bacteremia, including endocarditis (2011-2014).

The efficacy and safety of telavancin is under evaluation for the treatment of subjects with complicated Staphylococcus aureus bacteremia and S. aureus right-sided infective endocarditis. This study evaluated the telavancin activity against a global collection of S.

Tigecycline antimicrobial activity tested against clinical bacteria from Latin American medical centres: results from SENTRY Antimicrobial Surveillance Program (2011-2014).

Bacterial organisms (n = 13,494) were consecutively collected in 2011-2014 from 21 Latin American medical centres (11 nations). Antimicrobial susceptibility was determined by broth microdilution at a central laboratory. Tigecycline was very active against Gram-positive organisms, with MIC50/90 values of 0.