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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...

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Autores principales: Maher, Joshua M, Huband, Michael D, Blankers, Christopher G, Puttagunta, Sailaja, Aronin, Steven I, Castanheira, Mariana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232259/
https://www.ncbi.nlm.nih.gov/pubmed/37042351
http://dx.doi.org/10.1093/jac/dkad099
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author Maher, Joshua M
Huband, Michael D
Blankers, Christopher G
Puttagunta, Sailaja
Aronin, Steven I
Castanheira, Mariana
author_facet Maher, Joshua M
Huband, Michael D
Blankers, Christopher G
Puttagunta, Sailaja
Aronin, Steven I
Castanheira, Mariana
author_sort Maher, Joshua M
collection PubMed
description 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. This study evaluated the in vitro activity of sulopenem and comparator agents against contemporary Enterobacterales and anaerobic clinical isolates predominantly from patients with bloodstream, intra-abdominal and urinary tract infections. METHODS: A contemporary collection of 1647 Enterobacterales and 559 anaerobic isolates was assembled from medical centres in Europe and the USA. Isolates were susceptibility tested using the CLSI reference methods: broth microdilution for Enterobacterales and agar dilution for anaerobes. RESULTS: Sulopenem demonstrated potent in vitro antimicrobial activity (MIC(50/90), 0.03/0.25 mg/L) against Enterobacterales isolates regardless of infection type, inhibiting 99.2% of isolates at ≤1 mg/L. This activity was conserved against resistant phenotypes including ESBL-phenotype Escherichia coli (MIC(50/90), 0.03/0.06 mg/L) and ESBL-phenotype Klebsiella pneumoniae (MIC(50/90), 0.06/1 mg/L). Sulopenem maintained activity against ciprofloxacin-, nitrofurantoin- and trimethoprim/sulfamethoxazole-non-susceptible subsets (MIC(50/90), 0.03–0.06/0.12–0.5 mg/L). Against anaerobic isolates, sulopenem (98.9% inhibited at ≤4 mg/L) and meropenem [98.4% susceptible (CLSI)] were the most active compounds tested. CONCLUSIONS: The potent in vitro activity of sulopenem against this large collection of recent Enterobacterales and anaerobic clinical isolates from multiple infection types supports its further clinical evaluation in the treatment of intra-abdominal and urinary tract infections.
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spelling pubmed-102322592023-06-01 In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program Maher, Joshua M Huband, Michael D Blankers, Christopher G Puttagunta, Sailaja Aronin, Steven I Castanheira, Mariana J Antimicrob Chemother Original Research 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. This study evaluated the in vitro activity of sulopenem and comparator agents against contemporary Enterobacterales and anaerobic clinical isolates predominantly from patients with bloodstream, intra-abdominal and urinary tract infections. METHODS: A contemporary collection of 1647 Enterobacterales and 559 anaerobic isolates was assembled from medical centres in Europe and the USA. Isolates were susceptibility tested using the CLSI reference methods: broth microdilution for Enterobacterales and agar dilution for anaerobes. RESULTS: Sulopenem demonstrated potent in vitro antimicrobial activity (MIC(50/90), 0.03/0.25 mg/L) against Enterobacterales isolates regardless of infection type, inhibiting 99.2% of isolates at ≤1 mg/L. This activity was conserved against resistant phenotypes including ESBL-phenotype Escherichia coli (MIC(50/90), 0.03/0.06 mg/L) and ESBL-phenotype Klebsiella pneumoniae (MIC(50/90), 0.06/1 mg/L). Sulopenem maintained activity against ciprofloxacin-, nitrofurantoin- and trimethoprim/sulfamethoxazole-non-susceptible subsets (MIC(50/90), 0.03–0.06/0.12–0.5 mg/L). Against anaerobic isolates, sulopenem (98.9% inhibited at ≤4 mg/L) and meropenem [98.4% susceptible (CLSI)] were the most active compounds tested. CONCLUSIONS: The potent in vitro activity of sulopenem against this large collection of recent Enterobacterales and anaerobic clinical isolates from multiple infection types supports its further clinical evaluation in the treatment of intra-abdominal and urinary tract infections. Oxford University Press 2023-04-12 /pmc/articles/PMC10232259/ /pubmed/37042351 http://dx.doi.org/10.1093/jac/dkad099 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research
Maher, Joshua M
Huband, Michael D
Blankers, Christopher G
Puttagunta, Sailaja
Aronin, Steven I
Castanheira, Mariana
In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program
title In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program
title_full In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program
title_fullStr In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program
title_full_unstemmed In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program
title_short In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program
title_sort in vitro activity of sulopenem and comparator agents against enterobacterales and anaerobic clinical isolates collected during the sentry antimicrobial surveillance program
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232259/
https://www.ncbi.nlm.nih.gov/pubmed/37042351
http://dx.doi.org/10.1093/jac/dkad099
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