Repurposing the anti-viral drug zidovudine (AZT) in combination with meropenem as an effective treatment for infections with multi-drug resistant, carbapenemase-producing strains ofKlebsiella pneumoniae
| Autor: | Benjamin J. Parcell, Peter J. Coote, Alexandra E DeSarno |
|---|---|
| Přispěvatelé: | University of St Andrews. Infection and Global Health Division, University of St Andrews. School of Medicine, University of St Andrews. Biomedical Sciences Research Complex, University of St Andrews. School of Biology |
| Rok vydání: | 2020 |
| Předmět: |
Klebsiella pneumoniae
Antibiotics Drug Resistance Multiple Bacterial polycyclic compounds Immunology and Allergy Medicine media_common 0303 health sciences biology Drug Synergism QR Microbiology 3rd-DAS General Medicine Anti-Bacterial Agents Galleria mellonella Infectious Diseases NDM1 Drug Therapy Combination Zidovudine medicine.drug Microbiology (medical) Drug RM Combination therapy medicine.drug_class media_common.quotation_subject Microbial Sensitivity Tests KPC3 Meropenem beta-Lactamases 03 medical and health sciences Bacterial Proteins Humans 030304 developmental biology General Immunology and Microbiology 030306 microbiology business.industry Drug Repositioning biochemical phenomena metabolism and nutrition biology.organism_classification Virology In vitro RM Therapeutics. Pharmacology QR Klebsiella Infections Wax-moth larvae business |
| Zdroj: | Pathogens and Disease. 78 |
| ISSN: | 2049-632X |
| Popis: | Funding: University of St Andrews. Multi-drug resistant (MDR) Klebsiella pneumoniae represent a global threat to healthcare due to lack of effective treatments and high mortality rates. The aim of this research was to explore the potential of administering zidovudine (AZT) in combination with an existing antibiotic to treat resistant K. pneumoniae infections. Two MDR K. pneumoniae strains were employed, producing either the NDM-1 or KPC-3 carbapenemase. Efficacy of combinations of AZT with meropenem were compared with monotherapies against infections in Galleria mellonella larvae by measuring larval mortality and bacterial burden. The effect of the same combinations in vitro was determined via checkerboard and time-kill assays. In vitro, both K. pneumoniae strains were resistant to meropenem but were susceptible to AZT. In G. mellonella, treatment with either AZT or meropenem alone offered minimal therapeutic benefit against infections with either strain. In contrast, combination therapy of AZT with meropenem presented significantly enhanced efficacy compared to monotherapies. This was correlated with prevention of bacterial proliferation within the larvae but not elimination. Checkerboard assays showed that the interaction between AZT and meropenem was not synergistic but indifferent. In summary, combination therapy of AZT with meropenem represents a potential treatment for carbapenemase-producing MDR K. pneumoniae and merits further investigation. Postprint |
| Databáze: | OpenAIRE |
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