<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>The contribution of fluconazole-resistant <italic>Candida</italic> spp. isolates to urinary tract infections in Egypt has become a nationwide problem. A recent approach to overcome such disaster is combining conventional antifungals with non-antifungals. This study investigated the interaction of amikacin with fluconazole against resistant <italic>Candida</italic> strains isolated from the urine culture of patients admitted to Alexandria Main University Hospital. Among the collected <italic>Candida</italic> spp. isolates, 42.9% were resistant to fluconazole with MICs ranging between 128 and 1,024 μg/ml. The resistance-modifying activity of amikacin (4,000 μg/ml) was studied against fluconazole-resistant isolates where amikacin sensitized 91.7 % of resistant <italic>Candida</italic> spp. isolates to fluconazole with a modulation factor ranging between 32 and 256. The rhodamine efflux assay was performed to examine the impact of amikacin on efflux pump activity. After 120 minutes of treatment, amikacin affected the efflux pump activity of the isolates tested with a percentage of reduction in the fluorescence intensity of 8.9%. Quantitative real-time PCR was applied to assess the amikacin effect on the expression of the efflux pump genes <italic>MDR1, CDR1</italic>, and <italic>CDR2</italic>. The downregulatory effect of amikacin on the expression of the studied genes caused a percentage of reduction in the expression level ranging between 42.1 and 94%. In conclusion, amikacin resensitized resistant <italic>Candida</italic> spp. isolates to fluconazole and could be used in combination in the management of candiduria with a higher efficiency or at lower administration doses. To the best of our knowledge, this is the first study evaluating the enhancement of fluconazole activity in combination with amikacin against <italic>Candida</italic> spp.</p>
</abstract>

The contribution of fluconazole-resistant Candida spp. isolates to urinary tract infections in Egypt has become a nationwide problem. A recent approach to overcome such disaster is combining conventional antifungals with non-antifungals. This study investigated the interaction of amikacin with fluconazole against resistant Candida strains isolated from the urine culture of patients admitted to Alexandria Main University Hospital. Among the collected Candida spp. isolates, 42.9% were resistant to fluconazole with MICs ranging between 128 and 1,024 μg/ml. The resistance-modifying activity of amikacin (4,000 μg/ml) was studied against fluconazole-resistant isolates where amikacin sensitized 91.7 % of resistant Candida spp. isolates to fluconazole with a modulation factor ranging between 32 and 256. The rhodamine efflux assay was performed to examine the impact of amikacin on efflux pump activity. After 120 minutes of treatment, amikacin affected the efflux pump activity of the isolates tested with a percentage of reduction in the fluorescence intensity of 8.9%. Quantitative real-time PCR was applied to assess the amikacin effect on the expression of the efflux pump genes MDR1, CDR1, and CDR2. The downregulatory effect of amikacin on the expression of the studied genes caused a percentage of reduction in the expression level ranging between 42.1 and 94%. In conclusion, amikacin resensitized resistant Candida spp. isolates to fluconazole and could be used in combination in the management of candiduria with a higher efficiency or at lower administration doses. To the best of our knowledge, this is the first study evaluating the enhancement of fluconazole activity in combination with amikacin against Candida spp.

Resensitization of Fluconazole-Resistant Urinary <italic>Candida</italic> spp. Isolates by Amikacin through Downregulation of Efflux Pump Genes

Polish Journal of Microbiology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Resensitization of Fluconazole-Resistant Urinary  spp. Isolates by Amikacin through Downregulation of Efflux Pump Genes

The contribution of fluconazole-resistant Candida spp. isolates to urinary tract infections in Egypt has become a nationwide problem. A recent approach to...

Resensitization of Fluconazole-Resistant Urinary Candida spp. Isolates by Amikacin through Downregulation of Efflux Pump Genes

Article Category: original-paper

Published Online: Mar 11, 2020

Page range: 73 - 84

Received: Nov 12, 2019

Accepted: Feb 06, 2020

DOI: https://doi.org/10.33073/pjm-2020-010

Keywords
spp., amikacin, fluconazole, rhodamine efflux assay, quantitative real-time PCR

© 2020 Eva A. Edward et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Resensitization of Fluconazole-Resistant Urinary Candida spp. Isolates by Amikacin through Downregulation of Efflux Pump Genes

Article Category: original-paper

Published Online: Mar 11, 2020

Page range: 73 - 84

Received: Nov 12, 2019

Accepted: Feb 06, 2020

DOI: https://doi.org/10.33073/pjm-2020-010

Keywordsspp., amikacin, fluconazole, rhodamine efflux assay, quantitative real-time PCR

© 2020 Eva A. Edward et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
spp., amikacin, fluconazole, rhodamine efflux assay, quantitative real-time PCR