Feedback

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

Affiliation
Team “Resist”, UMR1184 “Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)”, INSERM, Faculty of Medicine, Université Paris-Saclay, CEA, LabEx LERMIT, 94270 Le Kremlin-Bicêtre, France;(M.R.);(S.O.)
Rima, Mariam;
ORCID
0000-0002-6403-5646
Affiliation
Department of Clinical Microbiology, Ruhr-University, 44801 Bochum, Germany;(N.P.);(M.C.);(S.G.G.)
Pfennigwerth, Niels;
Affiliation
Department of Clinical Microbiology, Ruhr-University, 44801 Bochum, Germany;(N.P.);(M.C.);(S.G.G.)
Cremanns, Martina;
Affiliation
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research and Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrücken, Germany;(K.C.);(J.H.);(R.M.)
Cirnski, Katarina;
ORCID
0000-0001-5766-3831
Affiliation
Team “Resist”, UMR1184 “Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)”, INSERM, Faculty of Medicine, Université Paris-Saclay, CEA, LabEx LERMIT, 94270 Le Kremlin-Bicêtre, France;(M.R.);(S.O.)
Oueslati, Saoussen;
Affiliation
Department of Clinical Microbiology, Ruhr-University, 44801 Bochum, Germany;(N.P.);(M.C.);(S.G.G.)
Gatermann, Sören G.;
ORCID
0000-0002-4400-2222
Affiliation
Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne, 80039 Amiens, France;
d’Amélio, Nicola;
ORCID
0000-0003-3398-9938
Affiliation
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research and Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrücken, Germany;(K.C.);(J.H.);(R.M.)
Herrmann, Jennifer;
ORCID
0000-0002-1042-5665
Affiliation
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research and Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrücken, Germany;(K.C.);(J.H.);(R.M.)
Müller, Rolf;
ORCID
0000-0001-9937-9572
Affiliation
Team “Resist”, UMR1184 “Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)”, INSERM, Faculty of Medicine, Université Paris-Saclay, CEA, LabEx LERMIT, 94270 Le Kremlin-Bicêtre, France;(M.R.);(S.O.)
Naas, Thierry

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.

Cite

Citation style:
Could not load citation form.

Access Statistic

Total:
Downloads:
Abtractviews:
Last 12 Month:
Downloads:
Abtractviews:

Rights

License Holder: © 2023 by the authors.

Use and reproduction: