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In vitro activity of sulopenem against 1880 bacterial pathogens isolated from Canadian patients with urinary tract
Andrew J Walkty1,2, James A Karlowsky1,2, Melanie R Baxter1
1Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
Introduction:
There are limited oral antimicrobial options for the treatment of urinary infections caused by ESBL-producing and MDR Enterobacterales. Sulopenem is an investigational thiopenem antimicrobial that is being developed as both an oral and IV formulation. The purpose of this study was to evaluate the in vitro activity of sulopenem versus bacterial pathogens recovered from the urine of patients admitted to or assessed at hospitals across Canada (CANWARD).
Materials And Methods:
The in vitro activity of sulopenem and clinically relevant comparators was determined for 1880 Gram-negative and Gram-positive urinary isolates obtained as part of the CANWARD study (2014 to 2021) using the CLSI broth microdilution method.
Results:
Sulopenem demonstrated excellent in vitro activity versus members of the Enterobacterales, with MIC90 values ranging from 0.06 to 0.5 mg/L for all species tested. Over 90% of ESBL-producing, AmpC-producing and MDR (not susceptible to ≥1 antimicrobial from ≥3 classes) Escherichia coli were inhibited by ≤0.25 mg/L of sulopenem. Sulopenem had an identical MIC90 to meropenem for ESBL-producing and MDR E. coli. The MIC90 of sulopenem and meropenem versus MSSA was 0.25 mg/L. Sulopenem was not active in vitro versus Pseudomonas aeruginosa (similar to ertapenem), and it demonstrated poor activity versus Enterococcus faecalis (similar to meropenem).
Conclusions:
Sulopenem demonstrated excellent in vitro activity versus bacterial pathogens recovered from the urine of Canadian patients. These data suggest that sulopenem may have a role in the treatment of urinary infections caused by antimicrobial-resistant Enterobacterales, but additional clinical studies are required.
Insights
Sulopenem shows promising in vitro activity against common urinary tract infection pathogens, including multidrug-resistant strains. Further clinical studies are needed to confirm its effectiveness for treating resistant bacterial infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Limited oral antimicrobial options exist for urinary infections caused by extended-spectrum beta-lactamase (ESBL)-producing and multidrug-resistant (MDR) Enterobacterales.
- Sulopenem, a novel thiopenem, is under development in oral and intravenous formulations.
Purpose of the Study:
- To evaluate the in vitro activity of sulopenem against bacterial pathogens commonly found in urinary tract infections (UTIs) in Canada.
Main Methods:
- The study analyzed 1880 Gram-negative and Gram-positive urinary isolates collected from Canadian hospitals between 2014 and 2021.
- In vitro activity was assessed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, comparing sulopenem to relevant antimicrobial agents.
Main Results:
- Sulopenem exhibited potent in vitro activity against Enterobacterales, with MIC90 values ranging from 0.06 to 0.5 µg/mL.
- Over 90% of ESBL-producing, AmpC-producing, and MDR Escherichia coli isolates were inhibited by sulopenem at ≤0.25 µg/mL, showing comparable activity to meropenem.
- Sulopenem demonstrated limited activity against Pseudomonas aeruginosa and Enterococcus faecalis.
Conclusions:
- Sulopenem shows excellent in vitro efficacy against key urinary pathogens, including resistant Enterobacterales.
- These findings suggest a potential role for sulopenem in treating UTIs caused by antimicrobial-resistant bacteria.
- Further clinical investigation is warranted to establish sulopenem's therapeutic utility.
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