Synergistic interactions of sulfamethoxazole and azole antifungal drugs against emerging multidrug-resistant Candida auris

International Journal of Antimicrobial Agents
Hassan E EldesoukyMohamed N Seleem

Abstract

Candida auris is an emerging multidrug-resistant pathogen implicated in numerous outbreaks worldwide, with a notably high mortality rate (ca. 60%). A significant challenge with treatment of these infections is the resistance of C. auris to most antifungal drugs used clinically. Thus, finding co-drugs capable of overcoming resistance to frontline antifungals is of prime clinical importance. In this study, the ability of the combination of different sulfa drugs with azole antifungals to inhibit the growth of azole-resistant C. auris isolates was evaluated. Among the active sulfa drugs, sulfamethoxazole exhibited the most potent in vitro synergistic interactions with voriconazole and itraconazole. The sulfamethoxazole-voriconazole combination restored voriconazole's fungistatic activity against three of eight voriconazole-resistant clinical isolates. Similarly, the sulfamethoxazole-itraconazole combination restored itraconazole's fungistatic activity against three of four itraconazole-resistant clinical isolates. This activity was further confirmed in vivo in a Caenorhabditis elegans model of C. auris infection. The sulfamethoxazole-voriconazole combination enhanced survival of nematodes infected with C. auris by nearly 70%. Notab...Continue Reading

Citations

Feb 19, 2019·Mycoses·Shabir A Lone, Aijaz Ahmad
Sep 27, 2019·Medical Microbiology and Immunology·Moses MadendeCarolina H Pohl
Oct 2, 2019·Antimicrobial Agents and Chemotherapy·Marwa AlhashimiMohamed N Seleem
May 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·George A NaclerioHerman O Sintim
Aug 20, 2019·Internal Medicine Journal·Chong W OngUNKNOWN Australian and New Zealand Mycoses Interest Group (ANZMIG); and the Healthcare Infection Control Special Interest Group (HIC
Oct 23, 2020·PLoS Pathogens·Han DuGuanghua Huang
Oct 14, 2020·Antimicrobial Agents and Chemotherapy·Hassan E EldesoukyMohamed N Seleem
Nov 20, 2020·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Heather R DavisGeorge A Pankey
Jan 20, 2020·International Journal of Antimicrobial Agents·A L BidaudE Dannaoui
May 1, 2021·International Journal of Molecular Sciences·Lucia ČernákováCélia F Rodrigues
Jun 29, 2021·Expert Review of Clinical Pharmacology·Daniele R GiacobbeMatteo Bassetti

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