Yeast infections: the unexpected facts

It is only for medical professionals to read for reference.
The detection rate of resistant bacteria/rare bacteria in yeast is increasing, and the high-risk population is constantly changing
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1.
5 billion years ago, fungi existed extensively on this blue planet, and fungi continued to thrive along with the evolution of life
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Perhaps you have never noticed that your life has been surrounded by fungi; these inconspicuous microorganisms hold the key to survival and even change the development process of human civilization! About 300 of the 400,000 species of fungi [1] that have been identified [2] are "hidden deadly killers", which can not only cause disease, but can even lead to death
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Invasive mycosis (IFD) is an important type of fungal infection, with an increasing incidence [3]; and from "super fungi" to "COVID-19 related fungal infections", IFD has become a global fatal threat, triggering clinical trials The widespread attention [4-5]
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With the change of the environment and the development of diagnostic technology, the epidemiology of IFD continues to change, and the increase in the detection rate of drug-resistant fungi and rare fungi makes the diagnosis and treatment of IFD face new challenges [3,6]
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Although yeast is a common pathogenic fungus in clinical practice, there are many "changes" in these "usually": Therefore, the current IFD treatment should be comprehensively evaluated based on a variety of factors such as the patient's immune status and infectious strains.

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 Candidiasis: Faced with the dual pressure of bacterial spectrum changes and drug resistance, it is time to consider adjusting the best clinical management strategy.
The incidence of invasive candidiasis on a global scale is increasing significantly
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In the past, Candida albicans was the most common Candida strain, but the detection rate of non-Albicans has gradually increased in recent years, which has led to decreased drug sensitivity and outbreaks of drug-resistant bacteria
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The diagnosis of invasive candidiasis is difficult, and early experience of antifungal therapy is an important measure to improve the prognosis of patients [7-8]
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1.
The detection rate of non-albicans and drug-resistant candida is worrying; the detection rate of rare candida is increasing, and the epidemiological change of non-albicans has reached a worrying trend
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The incidence of different Candida species is different due to different regions, ages, patient susceptibility factors, local hospital epidemiology and the application of antifungal drugs
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Candida albicans accounts for a higher proportion in Northern Europe, Central Europe and the United States, while non-candida albicans is more common in South America, Asia and Southern Europe [1,9]; in China, nearly 70% of the detected Candida are non-candida Candida albicans [10-11]
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In the current COVID-19 epidemic, non-albicans candida has even become the main strain of Candida in the world [12]
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Candida parapsilosis, Candida tropicalis and Candida glabrata are the top three non-Albicans detected [9-11]
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Figure 1.
SENTRY and CHIF-NET monitoring data: the detection rate of Candida albicans and non-candida albicans[9-10] Figure 2.
SENTRY and CHIF-NET monitoring data: the proportion of non-candida albicans detected in Candida[9-10] 9-11] The problem of Candida resistance is severe
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The massive application of azoles and echinocandin drugs has led to selective pressure on Candida, leading to a significant increase in the detection rate of drug-resistant bacteria (including multi-drug-resistant bacteria) [13-15]
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Different studies have shown that the resistance rate of Candida parapsilosis, Candida tropicalis, and Candida glabrata to azole drugs is about 15%-33% [14-16]; the resistance rate of Candida glabrata to echinocandin is up to More than 10% [15], and even Candida tropicalis and Candida glabrata resistant to pan-echinocandin have been detected in recent years [10]
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Figure 3.
The resistance rate of different Candida strains to azoles and echinocandin drugs.
Rare Candida has caused widespread concern
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The detection rate of rare Candida is increasing, and the minimum inhibitory concentration (MIC) of azoles and echinocandin drugs is higher, and the antibacterial spectrum and antibacterial activity of amphotericin B are the best [17]
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Candida auris, as the most famous and rare Candida, has appeared worldwide and caused multiple outbreaks of "super fungi"
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Candida auris has a high resistance rate to current commonly used antifungal drugs, and even exhibits abnormal growth when exposed to high-concentration echinocandin drugs, which brings great challenges to treatment [18-20]
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 Table 1.
Compared with common clinical Candida breakpoints, the MIC value of commonly used antifungal drugs against rare yeasts [17] 2.
Diagnosis of invasive candidiasis is difficult, and empirical treatment should be based on epidemiological status to choose appropriate antifungal drugs At present, the diagnosis of Candida is still difficult, and there are certain shortcomings in blood culture, G test, etc.
, but a variety of new diagnostic techniques are constantly being explored and researched [19]
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T2 Candida nano-diagnosis, Candida albicans tube antibody assay (CAGTA), direct PCR detection of clinical specimens, metagenomic detection, etc.
have gradually been used for the diagnosis of invasive candidiasis, and have even been recommended as a clinical diagnostic method by the guidelines [ 21-23]
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Early recognition and rapid initiation of appropriate systemic antifungal therapy is the key to reducing the mortality of invasive candidiasis [8]
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The current guidelines recommend echinocandin, fluconazole, and amphotericin B liposomes for the treatment of invasive candidiasis [24-27]
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However, a number of studies have found that most of the patients with candidaemia who initially received fluconazole treatment were improperly treated (56% were non-albicans infections, 10.
6% were fluconazole-resistant bacteria infections) [28] In addition, in ICU non-granules patients who received empirical treatment with fluconazole or echinocandin, no significant survival benefit was finally obtained [8]
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In view of the current epidemiological characteristics of invasive candidiasis, it is time to consider new strategies for adjusting the best clinical management of patients [8]: 1.
Drug-resistant candida infection: amphotericin B or voriconazole should be selected for treatment [27]
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2.
Rare yeast infections: Amphotericin B liposomes should be selected for the first-line treatment, with voriconazole as an alternative; for the second-line treatment, antifungal drugs different from the first-line treatment should be selected; for a variety of rare yeast infections, the use of spinal cord should be avoided White bacteria drugs [29]
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Cryptococcal disease: respond to the huge challenge of increasing incidence and practice comprehensive management focusing on bacterial species.
Since the epidemic of acquired immunodeficiency syndrome (AIDS), cryptococcosis has become a pathogen with an increasing incidence; With the increase of other immunodeficiency hosts such as solid organ transplantation, the incidence of Cryptococcus in non-human immunodeficiency virus (HIV) infection patients is also increasing [30-32]
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Cryptococcus gordonii and Cryptococcus neoformans are the main clinical strains, but in recent years, rare Cryptococcus strains have also continued to appear [30]
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Long-term and appropriate antifungal treatment, combined with intracranial pressure management and improvement of host immune function are the main methods for the treatment of cryptococcosis [31]
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1.
It occurs more frequently in patients with no significant recognizable immunodeficiency, and the problem of drug resistance has occurred.
Cryptococcosis can occur in more patients with no significant recognizable immunodeficiency
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Cryptococcosis is the most common lethal fungal disease in the world; there are more than 1 million patients with cryptococcal infection each year, of which about 650,000 patients with cryptococcal infection die [33]
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Past HIV infection is an important risk factor for cryptococcosis; there are reports that about 181,100 people die from human immunodeficiency virus (also known as HIV, HIV)-related cryptococcal meningitis each year, accounting for 15% of all HIV deaths [31]
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In recent years, more studies have found that cryptococcosis is equally high in non-HIV infected patients, such as organ transplantation, malignant tumors, diabetes, and diseases that require immunosuppressive therapy [33]
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With the improvement of the understanding of the disease, more data confirm that cryptococcosis (especially independent lung infection) can occur in patients without any recognizable immunodeficiency (non-HIV non-transplant patients) [33]
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Recent studies have shown that only 20% and 10% of patients with confirmed cryptococcosis have HIV infection and organ transplantation, while 70% of cryptococcosis patients are non-HIV non-transplant populations[30]; diabetes, chronic liver disease, chronic Kidney disease and chronic lung disease are common underlying diseases in patients with cryptococcosis [33]
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Figure 4.
Risk factors for non-HIV non-transplanting cryptococcosis patients [32-33] The problem of drug resistance of cryptococcal bacteria has emerged
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Cryptococcus gordonii and Cryptococcus neoformans are the main clinical strains.
Past data suggest that Cryptococcus neoformans maintains a high sensitivity rate to fluconazole, voriconazole, and amphotericin B; however, in recent years, cryptococcus strains and drug resistance have been rare in the past Strains continue to appear [30,34]
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A recent study in China found that there have been 7 previously unreported Cryptococcus strains in the Yangtze River Delta, and cryptococcal strains resistant to fluconazole and itraconazole are still being detected [34]
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 2.
The treatment should focus on bacterial species.
The diagnosis of cryptococcosis including the site of infection, severity of the disease, and immune status of the patient includes microscopic examination, serological examination and culture; among them, cryptococcal capsular polysaccharide antigen detection has High sensitivity and specificity are currently commonly used clinical diagnostic methods [30-31]
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In addition, PCR-fingerprinting, AFLP genotyping, microsatellite typing, multi-site sequencing typing and whole-genome sequencing are also widely used in cryptococcal molecular epidemiological surveillance research [30]
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The treatment of cryptococcosis needs to consider the site of infection, the severity of the disease, and the patient's potential immune status [31]
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In addition, due to the differences in the sensitivity of different Cryptococcus strains; therefore, future treatments should focus on strains rather than complexes [30-31]
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1) Cryptococcosis in HIV-infected patients: 2 weeks of amphotericin B (including amphotericin B liposomes, amphotericin B deoxycholate) + 5-fluorocytosine as an induction regimen, followed by fluconazole maintenance treatment [30-31]
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2) Cryptococcosis in transplant patients: Amphotericin B liposome + 5-flucytosine as an induction program, followed by fluconazole maintenance treatment [31]
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3) Cryptococcosis in non-HIV non-transplant patients: There are currently few prospective studies to guide the treatment of such patients, and clinical adjustments are often made based on the results of HIV-infected patients [31]
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 Advances in medical technology have continuously increased the number of high-risk patients with IFD.
As the most common pathogenic fungus, the incidence of yeast infections has also increased significantly
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However, the changes in high-risk patient groups and the large-scale application of antifungal drugs have brought unexpected changes at the same time-the detection rate of drug-resistant yeast and rare yeast has continued to increase
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In view of the above-mentioned unexpected epidemiological status of yeast infections, clinical management strategies should also be adjusted in time.
The current treatment of yeasts should be based on bacterial species, and antifungals that can effectively cover drug-resistant, rare bacteria and have strong activity should be selected.
Drugs
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Investigation at the end of the article: 1.
In your opinion, which of the following descriptions of the current yeast epidemiology are correct? (Multiple choice questions) Analysis: 1.
Candida: China’s 2017 CHIF-NET monitoring data suggest that the detection rate of non-albicans candida accounts for 69.
6% of all Candida strains[10-11]
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Different studies of Candida have shown that Candida parapsilosis, Candida tropicalis, and Candida glabrata have a resistance rate of 15%-33% to azole drugs, and Candida glabrata has a resistance rate of 10% to echinocandin.
Above [14-16]
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The results of a recent study on rare Candida species showed that compared with Candida albicans, Amphotericin B has a lower MIC value for most rare Candida species (except Candida auris), while triazole drugs and echinocandin The MIC value of the class of drugs is mostly elevated [17]
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2.
Cryptococcus: previous HIV infection and organ transplantation are important risk factors for cryptococcosis [31,33]; more data in recent years have confirmed that cryptococcosis can occur in patients with no significant recognizable immunodeficiency; Studies have found that 70% of cryptococcosis patients are non-HIV non-transplant populations, such as diabetes, chronic liver disease, chronic kidney disease, chronic lung disease, etc.
[30,33]
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A wonderful review of the diagnosis, treatment and new drug developments of invasive fungal diseases in the past! Rare fungi and drug-resistant fungi should not be underestimated! | ECCMID will quickly send you the latest literature, guidelines and cutting-edge information in the field of hepatitis, AIDS, and antifungal.
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