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.

Ceftobiprole activity against Gram-positive and Gram-negative pathogens causing bone and joint infections in the United States from 2016 to 2020.

Bone and joint infections (BJIs) present significant treatment challenges. Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus, is approved in many European and other countries for the treatment of adults with community- and hospital-acquired pneumonia, excluding ventilator-associated pneumonia. In this study, the in vitro activity of ceftobiprole and comparators was evaluated against clinical isolates collected from BJIs in the USA from 2016 to 2020.

Surveillance of omadacycline activity tested against clinical isolates from the USA: report from the SENTRY Antimicrobial Surveillance Program, 2019.

Objectives: Omadacycline was tested against 7000 bacterial isolates collected prospectively from medical centres in the USA during 2019.

Methods: Antimicrobial susceptibility testing was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines.

Results: Omadacycline was active against: Staphylococcus aureus (MIC, 0.

Antimicrobial activity of manogepix, a first-in-class antifungal, and comparator agents tested against contemporary invasive fungal isolates from an international surveillance programme (2018-2019).

Objectives: Manogepix, the active moiety of the prodrug fosmanogepix, is a novel antifungal with activity against major fungal pathogens including Candida (except Candida krusei), Aspergillus and difficult-to-treat/rare moulds. We tested manogepix and comparators against 2669 contemporary (2018-2019) fungal isolates collected from 82 medical centres in North America (42.3%), Europe (37.

In vitro activity of iclaprim and comparator agents against Listeria monocytogenes clinical isolates from 2012 to 2018.

Objectives: This study examined the in vitro activity of iclaprim and comparators against 40 Listeria monocytogenes clinical isolates mostly (95%) from patients with bloodstream infection (BSI) from the USA, Australia/New Zealand, Latin America and Europe collected between 2012-2018.

Methods: Antimicrobial susceptibility testing was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum inhibitory concentration (MIC) interpretations were based on CLSI criteria.

Susceptibility trends of ceftolozane/tazobactam and comparators when tested against U.S. gram-negative bacterial surveillance isolates (2012-2018).

Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. Ceftolozane/tazobactam has been approved in >60 countries for treating complicated urinary tract infections, acute pyelonephritis, complicated intra-abdominal infections (with metronidazole), and hospital-acquired pneumonia, including ventilator-associated pneumonia in adults. We analyzed susceptibilities for 35,882 gram-negative isolates collected from patients in 35 US medical centers from 2012 to 2018.

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.

In vitro activity of KHP-3757 (a novel LpxC inhibitor) and comparator agents against recent and molecularly characterized Pseudomonas aeruginosa isolates from a global surveillance program (2017-2018).

This study evaluated the in vitro activity of KHP-3757 (a novel LpxC inhibitor) and comparator agents against recent, geographically diverse, Pseudomonas aeruginosa isolates from a global surveillance program as well as molecularly characterized extended-spectrum-β-lactamase-positive, metallo-β-lactamase-positive, and colistin-resistant strains. KHP-3757 (MIC, 0.25/0.

Comparison of minimum inhibitory concentration results for gepotidacin obtained using agar dilution and broth microdilution methods.

Gepotidacin (GSK2140944) is a first in class, novel triazaacenaphthylene bacterial type II topoisomerase inhibitor in Phase 3 clinical development for the treatment of gonorrhea and uncomplicated urinary tract infections (acute cystitis). This study tested the equivalency of minimal inhibitory concentrations (MICs) obtained by two reference susceptibility testing methods, agar dilution and broth microdilution, for gepotidacin when tested against various gram-positive and gram-negative organisms. Equivalency, measured as the essential agreement >89.

Old In Vitro Antimicrobial Breakpoints Are Misleading Stewardship Efforts, Delaying Adoption of Innovative Therapies, and Harming Patients.

The current antimicrobial market and old (pre-2000) in vitro antimicrobial susceptibility test interpretative criteria (STIC) are not working properly. Malfunctioning susceptibility breakpoints and antimicrobial markets have serious implications for both patients (ie, from a safety and efficacy perspective) and antibiotic-focused pharmaceutical and biotechnology company economic viability. Poorly functioning STIC fail both patients and clinicians since they do not discriminate between likely effective and ineffective antimicrobial regimens.

Susceptibility trends of ceftolozane/tazobactam and comparators when tested against European Gram-negative bacterial surveillance isolates collected during 2012-18.

Background: The Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) monitors the in vitro activity of ceftolozane/tazobactam and numerous antimicrobial agents against Gram-negative bacteria worldwide.

Objectives: To evaluate the activity of ceftolozane/tazobactam and resistance trends among Pseudomonas aeruginosa and Enterobacterales isolates in Europe between 2012 and 2018.

Methods: P.

Activity of ceftolozane-tazobactam and comparators when tested against bacterial surveillance isolates collected from patients at risk of infections caused by resistant gram-negative pathogens.

Ceftolozane-tazobactam is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. Ceftolozane-tazobactam has been approved for treatment of complicated urinary tract infections and acute pyelonephritis, for complicated intra-abdominal infections (with metronidazole) in adults, and for hospital-acquired bacterial pneumonia including ventilator-associated bacterial pneumonia. This study analyzed gram-negative pathogen susceptibility in US and European patients who are considered at risk for infections caused by pathogens resistant to commonly used antimicrobials: patients in the intensive care unit (ICU), patients on the hematology/oncology or transplant service who may be immunocompromised, and patients >65 years old (yo).

Omadacycline invitro activity against a molecularly characterized collection of clinical isolates with known acquired tetracycline resistance mechanisms.

Omadacycline and tigecycline MIC values were 2 μg/mL and 0.25 μg/mL, respectively, against Staphylococcus aureus carrying tet(M), whereas the minocycline, tetracycline, and doxycycline values were > 8 μg/mL. Similarly, omadacycline and tigecycline remained active against Enterococcus faecalis and Streptococcus pneumoniae harboring tet(L)and/or tet(M)(MIC, 0.

Antimicrobial activity of POL7306 tested against clinical isolates of Gram-negative bacteria collected worldwide.

Background: POL7306 belongs to a new class of peptidomimetic outer-membrane-protein-targeting antibiotics with a novel mechanism of action. POL7306 is in development for the treatment of infections caused by antimicrobial-resistant Gram-negative bacteria and has demonstrated low cytotoxicity and nephrotoxicity.

Methods: A total of 891 isolates were collected by the SENTRY Antimicrobial Surveillance Program from 134 medical centres in Europe (n = 424; 41 centres in 18 nations), the USA (n = 411 isolates from 67 centres), the Asia-Pacific region (n = 24; 15 centres in 6 nations) and Latin America (n = 32; 11 centres in 9 nations) and included 558 Enterobacterales, 310 non-fermenters and 23 fastidious organisms.

Surveillance of Omadacycline Activity Tested against Clinical Isolates from the United States and Europe: Report from the SENTRY Antimicrobial Surveillance Program, 2016 to 2018.

Omadacycline is a broad-spectrum aminomethylcycline approved in October 2018 by the U.S. Food and Drug Administration for treating acute bacterial skin and skin structure infections and community-acquired pneumonia as both an oral and intravenous once-daily formulation.

Activity of KBP-7072, a Novel Third-Generation Tetracycline, against 531 Recent Geographically Diverse and Molecularly Characterized Acinetobacter baumannii Species Complex Isolates.

KBP-7072 is a novel third-generation tetracycline (aminomethylcycline) antibacterial that overcomes common efflux and ribosomal protection resistance mechanisms that cause resistance in older-generation tetracyclines. KBP-7072 completed phase 1 clinical development studies for safety, tolerability, and pharmacokinetics (ClinicalTrials.gov identifier NCT02454361) and multiple ascending doses in healthy subjects (ClinicalTrials.

Antimicrobial Activity of Telavancin Tested Against a Global Collection of Gram-Positive Pathogens, Including Multidrug-Resistant Isolates (2015-2017).

This study evaluated the antimicrobial activity of telavancin against a large collection of Gram-positive pathogens of clinical importance, which were collected worldwide from 2015 through 2017, including methicillin-resistant (MRSA), coagulase-negative staphylococci, spp., β-hemolytic streptococci (BHS), , and viridans group streptococci (VGS). This report completes 7 years of continuous surveillance data for telavancin using the approved reference method for testing methodology that includes the addition of polysorbate 80.

Assessment of Tedizolid Activity and Resistance Mechanisms against a Collection of spp. Causing Invasive Infections, Including Isolates Requiring an Optimized Dosing Strategy for Daptomycin from U.S. and European Medical Centers, 2016 to 2018.

High-level aminoglycoside resistance was noted in 30.0% of and 25.2% of isolates.

Comparison of ceftazidime-avibactam and ceftolozane-tazobactam in vitro activities when tested against gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2017-2018).

Clinical isolates were consecutively collected from 70 United States medical centers in 2017-2018 and susceptibility tested by reference broth microdilution methods at a central laboratory. The most active agents against Enterobacterales (n = 3269) were ceftazidime-avibactam (99.9% susceptible), amikacin (98.

Polymyxin Susceptibility Testing and Interpretive Breakpoints: Recommendations from the United States Committee on Antimicrobial Susceptibility Testing (USCAST).

The polymyxins are important agents for carbapenem-resistant Gram-negative bacilli. The United States Committee on Antimicrobial Susceptibility Testing breakpoint recommendations for colistin and polymyxin B are that isolates of , , and are considered susceptible at MIC values of ≤2 mg/liter. These recommendations are contingent upon dosing and testing strategies that are described in this commentary.

Antimicrobial activity of cefoperazone-sulbactam tested against Gram-Negative organisms from Europe, Asia-Pacific, and Latin America.

Objectives: To evaluate the antimicrobial activities of cefoperazone-sulbactam and comparator agents tested against a large collection of clinical isolates of Gram-negative organisms.

Methods: A total of 19545 Gram-negative organisms were collected from medical centers located in western Europe (W-EUR; n=10626), eastern Europe and the Mediterranean region (E-EUR; n=4029), the Asia-Pacific region (APAC; n=2491), and Latin America (LATAM; n=2399) in 2015-2016 and susceptibility tested by reference broth microdilution methods.

Results: Overall, 91.

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.

Evaluation of Antimicrobial Effects of a New Polymyxin Molecule (SPR741) When Tested in Combination with a Series of β-Lactam Agents Against a Challenge Set of Gram-Negative Pathogens.

The antimicrobial activities of several β-lactam agents were tested by broth microdilution alone and in combination with a new polymyxin analog, SPR741 (at a fixed concentration of 8 mg/L), against a challenge set of clinical isolates (202 and 221 isolates). Using Clinical and Laboratory Standards Institute (CLSI) or European Committee on Antimicrobial Susceptibility Testing (EUCAST) susceptibility criteria for each partner antibiotic, mecillinam-SPR741, temocillin-SPR741, and piperacillin-tazobactam-SPR741 combinations had susceptibility rates higher (85.6-100.

Activity of Minocycline against U.S. Isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus Species Complex, Stenotrophomonas maltophilia, and Burkholderia cepacia Complex: Results from the SENTRY Antimicrobial Surveillance Program, 2014 to 2018.

We evaluated the activity of minocycline and comparator agents against a large number of ( = 1,289), - species complex ( = 1,081), and complex ( = 101) isolates collected from 2014 to 2018 from 87 U.S. medical centers spanning all 9 census divisions.