Pathogenic Drug Resistant Fungi: A Review of Mitigation Strategies

Abstract

Fungal pathogens cause significant human morbidity and mortality globally, where there is a propensity to infect vulnerable people such as the immunocompromised ones. There is increasing evidence of resistance to antifungal drugs, which has significant implications for cutaneous, invasive and bloodstream infections. The World Health Organization (WHO) published a priority list of fungal pathogens in October 2022, thus, highlighting that a crisis point has been reached where there is a pressing need to address the solutions. This review provides a timely insight into the challenges and implications on the topic of antifungal drug resistance along with discussing the effectiveness of established disease mitigation modalities and approaches. There is also a need to elucidate the cellular and molecular mechanisms of fungal resistance to inform effective solutions. The established fungal decontamination approaches are effective for medical device processing and sterilization, but the presence of pathogenic fungi in recalcitrant biofilms can lead to challenges, particularly during cleaning. Future design ideas for implantable and reusable medical devices should consider antifungal materials and appropriates for disinfection, and where it is relevant, sterilization. Preventing the growth of mycotoxin-producing fungi on foods through the use of appropriate end-to-end processes is advisable, as mycotoxins are recalcitrant and challenging to eliminate once they have formed.

Medical Device-Associated Healthcare Infections: Sterilization and the Potential of Novel Biological Approaches to Ensure Patient Safety

“…Clinical isolates of ESKAPE pathogens have proven to be MDR, extensively drug-resistant (XDR), and pan-drug-resistant (PDR) [ 16 ]. Similarly, many of the fungal priority pathogens, e.g., Candida , Aspergillus , and Cryptococcus spp., have frighteningly high mortality rates due to the robust and invasive nature and MDR of these species [ 7 ]. Microbial species possess many virulence factors, allowing them to survive, persist, proliferate, and transmit in clinical settings.…”

“…90% of fungal BSIs, resulting in sepsis and with a mortality rate of ca. 40% with treatment [ 7 ]. Aspergillus fumigatus is the most common fungal species infecting the respiratory tract of immunocompromised patients, resulting in severe and fatal invasive infections [ 34 ].…”

“…Single-use devices are terminally sterilized and less prone to contamination. Such devices are classified according to Spaulding’s classification system as critical devices that have direct contact with blood and or internal tissues, semi-critical devices that have contact with mucous membranes, and non-critical devices contacting intact skin [ 7 ].…”

Design, Synthesis, and Activity Evaluation of Novel Dual-Target Inhibitors with Antifungal and Immunoregulatory Properties

“…The incidence of fungal infections has increased significantly due to the overuse of broad-spectrum drugs and the rise in immunodeficiency patients. This has resulted in more attention being given to the issue. , Candida , Cryptococcus , and Aspergillus are currently the representative pathogenic fungal strains that can cause a serious inflammatory reaction by invading subcutaneous, mucous membrane, and splanchnic tissues. , The continuous emergence of drug-resistant strains further increased their treatment difficulty. − According to reports, invasive fungal infections (IFIs) have caused over 1.5–2.0 million direct or indirect deaths annually. At present, the treatment and prevention regimens for fungal infections depend on a limited number of drugs, and it is difficult to meet the clinical management demand. , Therefore, it is necessary to develop novel antifungal agents with highly effective and safe properties.…”

Recent advances in antifungal drug development targeting lanosterol 14α‐demethylase (CYP51): A comprehensive review with structural and molecular insights

“…Preventability of infections from the Candida albicans is low with current drugs and there is no vaccine available in the market (Coordination et al, 2022). Candida species including Candida albicans , Candida tropicalis , Candida krusei , Candida glabrata , Candida parapsilosis , and Candida auris are in the list of WHO priority fungal pathogens that are needed to be tackle immediately and posed global emergency (Garvey & Rowan, 2023; Hoenigl et al, 2021; Jenks et al, 2020; Kidd et al, 2022; Zhang et al, 2021).…”