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In Vitro Activity of Two Novel Antimicrobial Compounds on MDR-Resistant Clinical Isolates

The development of novel antibiotics is mandatory to curb the growing antibiotic resistance problem resulting in difficult-to-treat bacterial infections. Here, we have determined the spectrum of activity of cystobactamids and chelocardins, two novel and promising classes of molecules with different...

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Autores principales: Rima, Mariam, Pfennigwerth, Niels, Cremanns, Martina, Cirnski, Katarina, Oueslati, Saoussen, Gatermann, Sören G., d’Amélio, Nicola, Herrmann, Jennifer, Müller, Rolf, Naas, Thierry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10451163/
https://www.ncbi.nlm.nih.gov/pubmed/37627685
http://dx.doi.org/10.3390/antibiotics12081265
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author Rima, Mariam
Pfennigwerth, Niels
Cremanns, Martina
Cirnski, Katarina
Oueslati, Saoussen
Gatermann, Sören G.
d’Amélio, Nicola
Herrmann, Jennifer
Müller, Rolf
Naas, Thierry
author_facet Rima, Mariam
Pfennigwerth, Niels
Cremanns, Martina
Cirnski, Katarina
Oueslati, Saoussen
Gatermann, Sören G.
d’Amélio, Nicola
Herrmann, Jennifer
Müller, Rolf
Naas, Thierry
author_sort Rima, Mariam
collection PubMed
description The development of novel antibiotics is mandatory to curb the growing antibiotic resistance problem resulting in difficult-to-treat bacterial infections. Here, we have determined the spectrum of activity of cystobactamids and chelocardins, two novel and promising classes of molecules with different modes of action. A panel of 297 clinically relevant Gram-negative and Gram-positive isolates with different antibiotic susceptibility profiles, going from wild type to multi- or even extremely drug resistant (MDR, XDR) and including carbapenem-resistant isolates, were tested using broth microdilution assays to determine the minimal inhibitory concentrations (MICs), MIC50s and MIC90s of two cystobactamids derivatives (CN-861-2 and CN-DM-861) and two chelocardin derivatives (CHD and CDCHD). Cystobactamids revealed potent activities on the majority of tested Enterobacterales (MIC50s ranging from 0.25 to 4 µg/mL), except for Klebsiella pneumoniae isolates (MIC50s is 128 µg/mL). Pseudomonas aeruginosa and Acinetobacter baumannii showed slightly higher MIC50s (4 µg/mL and 8 µg/mL, respectively) for cystobactamids. Chelocardins inhibited the growth of Enterobacterales and Stenotrophomas maltophilia at low to moderate MICs (0.25–16 µg/mL) and the chemically modified CDCHD was active at lower MICs. A. baumannii and P. aeruginosa were less susceptible to these molecules with MICs ranging from 0.5 to 32 µg/mL. These molecules show also interesting in vitro efficacies on clinically relevant Gram-positive bacteria with MICs of 0.125–8 µg/mL for cystobactamids and 0.5–8 µg/mL for chelocardins. Taken together, the cystobactamid CN-DM-861 and chelocardin CDCHD showed interesting antibiotic activities on MDR or XDR bacteria, without cross-resistance to clinically relevant antibiotics such as carbapenems, fluoroquinolones, and colistin.
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spelling pubmed-104511632023-08-26 In Vitro Activity of Two Novel Antimicrobial Compounds on MDR-Resistant Clinical Isolates Rima, Mariam Pfennigwerth, Niels Cremanns, Martina Cirnski, Katarina Oueslati, Saoussen Gatermann, Sören G. d’Amélio, Nicola Herrmann, Jennifer Müller, Rolf Naas, Thierry Antibiotics (Basel) Article The development of novel antibiotics is mandatory to curb the growing antibiotic resistance problem resulting in difficult-to-treat bacterial infections. Here, we have determined the spectrum of activity of cystobactamids and chelocardins, two novel and promising classes of molecules with different modes of action. A panel of 297 clinically relevant Gram-negative and Gram-positive isolates with different antibiotic susceptibility profiles, going from wild type to multi- or even extremely drug resistant (MDR, XDR) and including carbapenem-resistant isolates, were tested using broth microdilution assays to determine the minimal inhibitory concentrations (MICs), MIC50s and MIC90s of two cystobactamids derivatives (CN-861-2 and CN-DM-861) and two chelocardin derivatives (CHD and CDCHD). Cystobactamids revealed potent activities on the majority of tested Enterobacterales (MIC50s ranging from 0.25 to 4 µg/mL), except for Klebsiella pneumoniae isolates (MIC50s is 128 µg/mL). Pseudomonas aeruginosa and Acinetobacter baumannii showed slightly higher MIC50s (4 µg/mL and 8 µg/mL, respectively) for cystobactamids. Chelocardins inhibited the growth of Enterobacterales and Stenotrophomas maltophilia at low to moderate MICs (0.25–16 µg/mL) and the chemically modified CDCHD was active at lower MICs. A. baumannii and P. aeruginosa were less susceptible to these molecules with MICs ranging from 0.5 to 32 µg/mL. These molecules show also interesting in vitro efficacies on clinically relevant Gram-positive bacteria with MICs of 0.125–8 µg/mL for cystobactamids and 0.5–8 µg/mL for chelocardins. Taken together, the cystobactamid CN-DM-861 and chelocardin CDCHD showed interesting antibiotic activities on MDR or XDR bacteria, without cross-resistance to clinically relevant antibiotics such as carbapenems, fluoroquinolones, and colistin. MDPI 2023-07-31 /pmc/articles/PMC10451163/ /pubmed/37627685 http://dx.doi.org/10.3390/antibiotics12081265 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rima, Mariam
Pfennigwerth, Niels
Cremanns, Martina
Cirnski, Katarina
Oueslati, Saoussen
Gatermann, Sören G.
d’Amélio, Nicola
Herrmann, Jennifer
Müller, Rolf
Naas, Thierry
In Vitro Activity of Two Novel Antimicrobial Compounds on MDR-Resistant Clinical Isolates
title In Vitro Activity of Two Novel Antimicrobial Compounds on MDR-Resistant Clinical Isolates
title_full In Vitro Activity of Two Novel Antimicrobial Compounds on MDR-Resistant Clinical Isolates
title_fullStr In Vitro Activity of Two Novel Antimicrobial Compounds on MDR-Resistant Clinical Isolates
title_full_unstemmed In Vitro Activity of Two Novel Antimicrobial Compounds on MDR-Resistant Clinical Isolates
title_short In Vitro Activity of Two Novel Antimicrobial Compounds on MDR-Resistant Clinical Isolates
title_sort in vitro activity of two novel antimicrobial compounds on mdr-resistant clinical isolates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10451163/
https://www.ncbi.nlm.nih.gov/pubmed/37627685
http://dx.doi.org/10.3390/antibiotics12081265
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