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Antimicrobial activity of POL7306 tested against clinical isolates of Gram-negative bacteria collected worldwide
Helio S Sader1, Paul R Rhomberg1, Leonard R Duncan1
1JMI Laboratories, North Liberty, IA, USA.
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. Susceptibility testing was performed using the reference broth microdilution method and the medium was supplemented with 0.002% polysorbate-80 for testing POL7306. Resistant subsets were characterized by WGS.
Results:
POL7306 demonstrated potent in vitro activity against Enterobacterales [including carbapenem-resistant (MIC50/90, 0.06/0.25 mg/L), ESBL-producing (MIC50/90, 0.06/0.12 mg/L), KPC-producing (MIC50/90, 0.12/0.25 mg/L), MBL-producing (MIC50/90, 0.06/0.25 mg/L), colistin-non-susceptible, mcr-negative (MIC50/90, 0.5/2 mg/L) and mcr-positive (MIC50/90, 0.12/0.25 mg/L) Enterobacterales], Pseudomonas aeruginosa (MIC50/90, 0.25/0.25 mg/L), Acinetobacter baumannii (MIC50/90, 0.06/0.12 mg/L) and Stenotrophomonas maltophilia (MIC50/90, 0.06/0.25 mg/L).
Conclusions:
POL7306 demonstrated potent activity against a large collection of Gram-negative organisms collected worldwide that included colistin-resistant, XDR and ESBL- and carbapenemase-producing isolates for which there are currently limited treatment options.
Insights
POL7306, a novel peptidomimetic antibiotic, shows potent activity against challenging Gram-negative bacterial infections. This new drug class offers a promising option for treating resistant infections with low toxicity.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- POL7306 represents a new class of peptidomimetic antibiotics targeting bacterial outer membrane proteins.
- It is under development for treating infections caused by Gram-negative bacteria resistant to existing antibiotics.
- POL7306 exhibits low cytotoxicity and nephrotoxicity in preliminary assessments.
Purpose of the Study:
- To evaluate the in vitro activity of POL7306 against a diverse collection of Gram-negative bacterial isolates.
- To assess the efficacy of POL7306 against resistant strains, including those producing extended-spectrum beta-lactamases (ESBLs) and carbapenemases.
- To determine the activity spectrum of POL7306 against key Gram-negative pathogens.
Main Methods:
- A total of 891 Gram-negative bacterial isolates were collected globally through the SENTRY Antimicrobial Surveillance Program.
- Susceptibility testing for POL7306 was performed using the reference broth microdilution method, with medium supplemented with polysorbate-80.
- Whole Genome Sequencing (WGS) was utilized to characterize resistant isolates.
Main Results:
- POL7306 demonstrated potent in vitro activity against Enterobacterales, including carbapenem-resistant, ESBL-producing, KPC-producing, and MBL-producing strains.
- The antibiotic was also highly active against Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia.
- Potent activity was observed against colistin-non-susceptible and colistin-resistant isolates, including mcr-negative and mcr-positive strains.
Conclusions:
- POL7306 exhibits potent activity against a wide range of Gram-negative bacteria, including multidrug-resistant strains.
- The findings highlight POL7306 as a potential therapeutic option for infections caused by pathogens with limited current treatment alternatives.
- This novel antibiotic class shows promise in addressing the growing threat of antimicrobial resistance.
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