Drug Resistance and Novel Therapeutic Approaches in Invasive Candidiasis

被引:58
作者
Murphy, Sarah E. [1 ]
Bicanic, Tihana [1 ,2 ]
机构
[1] St Georges Univ London, Inst Infect & Immun, London, England
[2] St Georges Univ Hosp Natl Hlth Serv NHS Fdn Trust, Clin Acad Grp Infect & Immun, London, England
关键词
Candida; invasive candidiasis; candidaemia; antifungal resistance; antifungal drugs; drug therapy; drug resistance; antimicrobial resistance; BROAD-SPECTRUM ANTIFUNGAL; GLUCAN SYNTHASE INHIBITOR; LONG-ACTING ECHINOCANDIN; IN-VITRO ACTIVITY; INFECTIOUS-DISEASES SOCIETY; CELECOXIB DERIVATIVE AR-12; HIGHLY POTENT INHIBITOR; AMPHOTERICIN-B; MURINE MODEL; TREHALOSE-6-PHOSPHATE PHOSPHATASE;
D O I
10.3389/fcimb.2021.759408
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Candida species are the leading cause of invasive fungal infections worldwide and are associated with acute mortality rates of ~50%. Mortality rates are further augmented in the context of host immunosuppression and infection with drug-resistant Candida species. In this review, we outline antifungal drugs already in clinical use for invasive candidiasis and candidaemia, their targets and mechanisms of resistance in clinically relevant Candida species, encompassing not only classical resistance, but also heteroresistance and tolerance. We describe novel antifungal agents and targets in pre-clinical and clinical development, including their spectrum of activity, antifungal target, clinical trial data and potential in treatment of drug-resistant Candida. Lastly, we discuss the use of combination therapy between conventional and repurposed agents as a potential strategy to combat the threat of emerging resistance in Candida.
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页数:22
相关论文
共 235 条
[101]   Penetration of Ibrexafungerp (Formerly SCY-078) at the Site of Infection in an Intra-abdominal Candidiasis Mouse Model [J].
Lee, Annie ;
Prideaux, Brendan ;
Zimmerman, Matthew ;
Carter, Claire ;
Barat, Stephen ;
Angulo, David ;
Dartois, Veronique ;
Perlin, David S. ;
Zhao, Yanan .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2020, 64 (03)
[102]   Elevated Cell Wall Chitin in Candida albicans Confers Echinocandin Resistance In Vivo [J].
Lee, Keunsook K. ;
MacCallum, Donna M. ;
Jacobsen, Mette D. ;
Walker, Louise A. ;
Odds, Frank C. ;
Gow, Neil A. R. ;
Munro, Carol A. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2012, 56 (01) :208-217
[103]   In Vitro and In Vivo Assessment of FK506 Analogs as Novel Antifungal Drug Candidates [J].
Lee, Yeonseon ;
Lee, Kyung-Tae ;
Lee, Soo Jung ;
Beom, Ji Yoon ;
Hwangbo, Areum ;
Jung, Jin A. ;
Song, Myoung Chong ;
Yoo, Young Ji ;
Kang, Sang Hyeon ;
Averette, Anna F. ;
Heitman, Joseph ;
Yoon, Yeo Joon ;
Cheong, Eunji ;
Bahn, Yong-Sun .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2018, 62 (11)
[104]  
Lepak AJ, 2018, ANTIMICROB AGENTS CH, V62, DOI [10.1128/AAC.01572-18, 10.1128/aac.01572-18]
[105]   Pharmacodynamics of a Long-Acting Echinocandin, CD101, in a Neutropenic Invasive-Candidiasis Murine Model Using an Extended-Interval Dosing Design [J].
Lepak, Alexander J. ;
Zhao, Miao ;
VanScoy, Brian ;
Ambrose, Paul G. ;
Andes, David R. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2018, 62 (02)
[106]   Antifungal Pharmacokinetics and Pharmacodynamics [J].
Lepak, Alexander J. ;
Andes, David R. .
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2015, 5 (05)
[107]   Pharmacodynamic Target Evaluation of a Novel Oral Glucan Synthase Inhibitor, SCY-078 (MK-3118), Using an In Vivo Murine Invasive Candidiasis Model [J].
Lepak, Alexander J. ;
Marchillo, Karen ;
Andes, David R. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2015, 59 (02) :1265-1272
[108]   Caspofungin: the first representative of a new antifungal class [J].
Letscher-Bru, V ;
Herbrecht, R .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2003, 51 (03) :513-521
[109]   Bet Hedging in Yeast by Heterogeneous, Age-Correlated Expression of a Stress Protectant [J].
Levy, Sasha F. ;
Ziv, Naomi ;
Siegal, Mark L. .
PLOS BIOLOGY, 2012, 10 (05)
[110]   Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility [J].
Liston, Sean D. ;
Whitesell, Luke ;
Kapoor, Mili ;
Shaw, Karen Joy ;
Cowen, Leah E. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2020, 64 (05)