In Vitro Screening of a 1280 FDA-Approved Drugs Library against Multidrug-Resistant and Extensively Drug-Resistant Bacteria
Abstract
:1. Introduction
2. Results
2.1. Antibiotic Resistance Profile and Genomic Support of Selected Strains Panel
2.2. General High-Throughput Screening Results
2.3. Main Hits by Species
2.4. Comparison with Data from the Literature
3. Discussion
3.1. What Are the Potential Therapeutic Options for Treating These MDR Bacteria?
3.2. To Find a Common Hit
3.3. To Repurpose a Molecule
3.4. Using Drug Associations
3.5. Damaging Basic Mechanisms of Bacteria
3.6. Personalizing the Treatment in a Compassionnal Approach
4. Materials and Methods
4.1. Collection and Susceptibility of Bacterial Strains
4.2. Preparation of Isolates
4.3. High-Throughput Screening Assay
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Strain and No. | Characterization [3] | Non-Susceptibility to at Least One Agent in All Those Classes | Known Resistance Genes |
---|---|---|---|
S. aureus P1943 [20] | MDR | Fluoroquinolones, anti-staphylococcal β-lactams, glycopeptides, and macrolides | mecA, gyrA, aaD, bleO, and ermC |
E. faecium P5015 | MDR | Aminoglycosides, glycopeptides, and tetracyclines | vanA |
E. coli DSM 105182 [21] | MDR | Polymyxins, tetracyclins, and fluoroquinolones | mcr-1 |
K. pneumoniae P9495 | MDR | Aminoglycosides, penicillins + β-lactamase inhibitors, carbapenems, extended-spectrum cephalosporins, fluoroquinolones, folate pathway inhibitors, monobactacms, and polymyxins | blaOXA-48 |
A. baumannii P1887 [22] | MDR | Aminoglycosides, carbapenems, fluoroquinolones, penicillins + β-lactamase inhibitors, extended-spectrum cephalosporins, and folate pathway inhibitors | blaOXA-51, blaOXA-23, and blaNDM-1 |
P. aeruginosa P6540 | XDR | Aminoglycosides, antipseudomonal cephalosporins, antipseudomonal fluoroquinolones, penicillins + β-lactamase inhibitors, monobactacms, and polymyxins | |
B. multivorans P6539 | XDR | Aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, penicillins + β-lactamase inhibitors, monobactacms, folate pathways inhibitors, glycylcyclines, and polymyxins | |
P. nosoerga P8103 | XDR | Aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, penicillins + β-lactamase inhibitors, rifamycins, folate pathways inhibitors, tetracyclins, phosphonic acids, and polymyxins | blaOXA-158 |
Name of Strain | Hits Except “Infectiology” Class |
---|---|
S. aureus P1943 | Dronedarone hydrochloride (cardiovascular); thonzonium bromide (dermatology); auranofin (metabolism); pinaverium bromide (neuromuscular); and 5-fluorouracil, carmofur, and gemcitabine (oncology) |
E. faecium P5015 | Amiodarone and dronedarone hydrochloride (cardiovascular); clomiphene citrate (Z and E) (endocrinology); auranofin (metabolism); tamoxifen citrate, gemcitabine, carmofur, floxuridine, pemetrexed disodium, raltitrexed, 5-fluorouracil, and methotrexate (oncology) |
E. coli DSM 105182 | Azaperone and lomerizine hydrochloride (central nervous system) |
P. nosoerga P8103 | Deferoxamine mesylate (hematology) |
Combination Therapy | Drug Repurposing | Increased Dosages | |
---|---|---|---|
P. aeruginosa | Rifampicin + imipenem Colistin + imipenem | Auranofin (+ colistin ± ceftazidime) | Colistin |
P. nosoerga | Rifampicin + minocyclin | Deferoxamine + ascorbic acid (+ gentamicin) | Rifampicin |
B. multivorans | Fluoroquinolones + β-lactams | - | Fluoroquinolones |
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Peyclit, L.; Baron, S.A.; Hadjadj, L.; Rolain, J.-M. In Vitro Screening of a 1280 FDA-Approved Drugs Library against Multidrug-Resistant and Extensively Drug-Resistant Bacteria. Antibiotics 2022, 11, 291. https://doi.org/10.3390/antibiotics11030291
Peyclit L, Baron SA, Hadjadj L, Rolain J-M. In Vitro Screening of a 1280 FDA-Approved Drugs Library against Multidrug-Resistant and Extensively Drug-Resistant Bacteria. Antibiotics. 2022; 11(3):291. https://doi.org/10.3390/antibiotics11030291
Chicago/Turabian StylePeyclit, Lucie, Sophie Alexandra Baron, Linda Hadjadj, and Jean-Marc Rolain. 2022. "In Vitro Screening of a 1280 FDA-Approved Drugs Library against Multidrug-Resistant and Extensively Drug-Resistant Bacteria" Antibiotics 11, no. 3: 291. https://doi.org/10.3390/antibiotics11030291