Manual of Clinical Microbiology


Mechanisms of Resistance to Antifungal Agents

Last Updated:2023

Invasive fungal infections cause extensive morbidity and mortality, and 1.5 million cases occur worldwide each year with mortality rates as high as 30 to 80% across infection types…

Defining Clinical and Microbiological Resistance

The development of antifungal resistance is complex and relies on multiple host and microbial factors. A discussion of drug resistance must distinguish between multifaceted clinical resistance and microbial resistance to…

Resistance to Azoles

Azoles inhibit the biosynthesis of ergosterol, the principal sterol in fungal cell membranes, by interfering with the action of lanosterol 14α‐demethylase, which is encoded by ERG11 (Cyp51A in Aspergillus)…

Mechanisms of Azole Resistance

The underlying molecular mechanisms responsible for acquired azole resistance have been extensively studied over the past several decades. Early studies elucidating the biological machinery central to resistance have evolved into…

Mechanisms of Echinocandin and Enfumafungin Resistance

Cell wall‐active inhibitors of glucan synthase, which catalyzes the biosynthesis of β‐1,3‐d‐glucan, include echinocandins and a newly approved drug, enfumafungin. The echinocandin drugs anidulafungin, caspofungin, and micafungin are lipopeptides that…

Mechanisms of Polyene Resistance

The polyene amphotericin B was the first antifungal agent approved in the United States (1957) to treat life‐threatening invasive fungal infections (193). Polyene drugs bind the fungal‐specific sterol…

Mechanisms of Flucytosine Resistance

Flucytosine (5‐fluorocytosine or 5FC) is a prodrug that when taken up by cells is metabolized by organisms expressing cytosine deaminase to a toxic form, 5‐fluorouracil, which disrupts DNA and protein…

Microbial Drivers of Resistance: Drug Adaptation, Tolerance, and Escape

The conversion of a drug‐sensitive cell to a drug‐resistant mutant requires acquisition of one or more resistance mechanisms. The pathway leading to genetically stable escape mutants is a multiphase process…

Summary and Perspective

As the global burden of invasive fungal infections rises, antifungal therapy remains a critical element of patient management. Yet, treatment choices are restricted due to the limited classes of antifungal…

Section Editor: Sean Zhang

Volume Editor: Bobbi S. Pritt

Editors in Chief: Karen C. Carroll and Michael A. Pfaller

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