In Vitro Screening of a 1280 FDA-Approved Drugs Library against Multidrug-Resistant and Extensively Drug-Resistant Bacteria
Alternative strategies against multidrug-resistant (MDR) bacterial infections are suggested to clinicians, such as drug repurposing, which uses rapidly available and marketed drugs. We gathered a collection of MDR bacteria from our hospital and performed a phenotypic high-throughput screening with a...
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| Main Authors: | , , , |
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| Format: | Book |
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MDPI AG,
2022-02-01T00:00:00Z.
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| Summary: | Alternative strategies against multidrug-resistant (MDR) bacterial infections are suggested to clinicians, such as drug repurposing, which uses rapidly available and marketed drugs. We gathered a collection of MDR bacteria from our hospital and performed a phenotypic high-throughput screening with a 1280 FDA-approved drug library. We used two Gram positive (<i>Enterococcus faecium</i> P5014 and <i>Staphylococcus aureus</i> P1943) and six Gram negative (<i>Acinetobacter baumannii</i> P1887, <i>Klebsiella pneumoniae</i> P9495, <i>Pseudomonas aeruginosa</i> P6540, <i>Burkholderia multivorans</i> P6539, <i>Pandoraea nosoerga</i> P8103, and <i>Escherichia coli</i> DSM105182 as the reference and control strain). The selected MDR strain panel carried resistance genes or displayed phenotypic resistance to last-line therapies such as carbapenems, vancomycin, or colistin. A total of 107 compounds from nine therapeutic classes inhibited >90% of the growth of the selected Gram negative and Gram positive bacteria at a drug concentration set at 10 µmol/L, and 7.5% were anticancer drugs. The common hit was the antiseptic chlorhexidine. The activity of niclosamide, carmofur, and auranofin was found against the selected methicillin-resistant <i>S. aureus</i>. Zidovudine was effective against colistin-resistant <i>E. coli</i> and carbapenem-resistant <i>K. pneumoniae</i>. Trifluridine, an antiviral, was effective against <i>E. faecium</i>. Deferoxamine mesylate inhibited the growth of XDR <i>P. nosoerga</i>. Drug repurposing by an in vitro screening of a drug library is a promising approach to identify effective drugs for specific bacteria. |
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| Item Description: | 10.3390/antibiotics11030291 2079-6382 |