scholarly journals Changing scenario of superficial fungal infection: Emerging resistance, recurrence and remedy in Bangladesh

2020 ◽  
Vol 8 (2) ◽  
pp. 108-111
Author(s):  
Mohammad Kamrul Ahsan ◽  
Mir Nazrul Islam
Keyword(s):  
Drug Resistance ◽  
Fungal Infection ◽  
Antifungal Therapy ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Genetic Alterations ◽  
Antifungal Drug ◽  
Fungal Resistance ◽  
Related Factors ◽  
Clinical Resistance

Superficial fungal infections (dermatophytes) affecting skin, nail and hair are the most common infective dermatosis seen in dermatology outpatient clinics. There is a rising prevalence of dermatophytosis, especially in tropical countries like Bangladesh, with a concomitant increase in the number of difficult to treat cases. The reason for this phenomenon is not yet clear, but may be related to inadequate treatment regimen or discontinuation of medication, difficulties in eliminating predisposing factors and sources of re-infection. The pathogenesis and severity of fungal infection depend on various immunological and nonimmunological factors. The rampant use of antifungal therapy in immunocompromised individuals marked the onset of antifungal drug resistance. Fungal resistance can be microbiological or clinical. Genetic alterations in the fungi cause microbiological resistance. Clinical resistance is due to host or drug related factors. All these factors may cause fungal resistance individually or in tandem. Appropriate drug dosing along with antifungal drug susceptibility testing, especially for the dermatophytes isolated from chronic, recurrent cases or those with atypical presentation should be encouraged. Other ways to avoid resistance is the use of combination antifungal therapy. Combination therapy offers advantages in increased synergistic action with enhanced spectrum activity. Finally, newer insights into molecular mechanisms of drug resistance will help in the development of appropriate antifungal therapy. Till then experience based treatment of dermatophytosis is more effective than the standard guideline. Bangladesh Crit Care J September 2020; 8(2): 108-111

Antimycotic drugs and their mechanisms of resistance to Candida species

2021 ◽  
Vol 22 ◽  
Author(s):  
Sweety Dahiya ◽  
Namita Sharma ◽  
Aruna Punia ◽  
Pooja Choudhary ◽  
Prity Gulia ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Candida Species ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Treatment Strategies ◽  
Distinct Species ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Success Rates ◽  
Antifungal Drug Resistance

: Fungal infections have shown an upsurge in recent decades, mainly because of the increasing number of immunocompromised patients, and the occurrence of invasive candidiasis is found to be 7-15 folds greater than that of invasive aspergillosis. The genus Candida comprises of more than 150 distinct species; however, only a few of them are found to be pathogenic to humans. Mortality rates of Candida species are found to be around 45%, and the reasons for this intensified mortality are inefficient diagnostic techniques and unfitting initial treatment strategies. There are only a few antifungal drug classes that are employed for the remedy of invasive fungal infections, including azoles, polyenes, echinocandins, and pyrimidine analogs. During the last 2-3 decades, the usage of antifungal drugs has increased several folds, due to which the reports of escalating antifungal drug resistance have also been recorded. The resistance is mostly to the triazole-based compounds. Due to antifungal drug resistance, the success rates of treatment have been reduced and major changes have been observed in the frequency of fungal infections. In this review, we have summarized the major molecular mechanisms for the development of antifungal drug resistance.

scholarly journals Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance

1998 ◽  
Vol 11 (2) ◽  
pp. 382-402 ◽  
Author(s):  
Theodore C. White ◽  
Kieren A. Marr ◽  
Raleigh A. Bowden
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Cellular Level ◽  
Antifungal Drug ◽  
Clinical Factors ◽  
Antifungal Drug Resistance ◽  
Aids Epidemic ◽  
Immunosuppressed Patients ◽  
Target Enzyme

SUMMARY In the past decade, the frequency of diagnosed fungal infections has risen sharply due to several factors, including the increase in the number of immunosuppressed patients resulting from the AIDS epidemic and treatments during and after organ and bone marrow transplants. Linked with the increase in fungal infections is a recent increase in the frequency with which these infections are recalcitrant to standard antifungal therapy. This review summarizes the factors that contribute to antifungal drug resistance on three levels: (i) clinical factors that result in the inability to successfully treat refractory disease; (ii) cellular factors associated with a resistant fungal strain; and (iii) molecular factors that are ultimately responsible for the resistance phenotype in the cell. Many of the clinical factors that contribute to resistance are associated with the immune status of the patient, with the pharmacology of the drugs, or with the degree or type of fungal infection present. At a cellular level, antifungal drug resistance can be the result of replacement of a susceptible strain with a more resistant strain or species or the alteration of an endogenous strain (by mutation or gene expression) to a resistant phenotype. The molecular mechanisms of resistance that have been identified to date in Candida albicans include overexpression of two types of efflux pumps, overexpression or mutation of the target enzyme, and alteration of other enzymes in the same biosynthetic pathway as the target enzyme. Since the study of antifungal drug resistance is relatively new, other factors that may also contribute to resistance are discussed.

scholarly journals Molecular Mechanisms of 5-Fluorocytosine Resistance in Yeasts and Filamentous Fungi

2021 ◽  
Vol 7 (11) ◽  
pp. 909
Author(s):  
Fatima Zohra Delma ◽  
Abdullah M. S. Al-Hatmi ◽  
Roger J. M. Brüggemann ◽  
Willem J. G. Melchers ◽  
Sybren de Hoog ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Filamentous Fungi ◽  
Antifungal Therapy ◽  
Molecular Mechanisms ◽  
Molecular Level ◽  
Fungal Diseases ◽  
Antifungal Drug ◽  
Effective Management ◽  
Antifungal Drug Resistance

Effective management and treatment of fungal diseases is hampered by poor diagnosis, limited options for antifungal therapy, and the emergence of antifungal drug resistance. An understanding of molecular mechanisms contributing to resistance is essential to optimize the efficacy of currently available antifungals. In this perspective, one of the oldest antifungals, 5-fluorocytosine (5-FC), has been the focus of recent studies applying advanced genomic and transcriptomic techniques to decipher the order of events at the molecular level that lead to resistance. These studies have highlighted the complexity of resistance and provided new insights that are reviewed in the present paper.

scholarly journals Exploiting evolutionary trade-offs for posttreatment management of drug-resistant populations

2020 ◽  
Vol 117 (30) ◽  
pp. 17924-17931
Author(s):  
Sergey V. Melnikov ◽  
David L. Stevens ◽  
Xian Fu ◽  
Hui Si Kwok ◽  
Jin-Tao Zhang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Genetic Alterations ◽  
Trna Synthetase ◽  
Molecular Defect ◽  
Antibiotic Resistant ◽  
Resistance Evolution ◽  
Growth Defects ◽  
Trade Offs ◽  
Resistant Cells

Antibiotic resistance frequently evolves through fitness trade-offs in which the genetic alterations that confer resistance to a drug can also cause growth defects in resistant cells. Here, through experimental evolution in a microfluidics-based turbidostat, we demonstrate that antibiotic-resistant cells can be efficiently inhibited by amplifying the fitness costs associated with drug-resistance evolution. Using tavaborole-resistantEscherichia colias a model, we show that genetic mutations in leucyl-tRNA synthetase (that underlie tavaborole resistance) make resistant cells intolerant to norvaline, a chemical analog of leucine that is mistakenly used by tavaborole-resistant cells for protein synthesis. We then show that tavaborole-sensitive cells quickly outcompete tavaborole-resistant cells in the presence of norvaline due to the amplified cost of the molecular defect of tavaborole resistance. This finding illustrates that understanding molecular mechanisms of drug resistance allows us to effectively amplify even small evolutionary vulnerabilities of resistant cells to potentially enhance or enable adaptive therapies by accelerating posttreatment competition between resistant and susceptible cells.

scholarly journals Multiple Molecular Mechanisms Contribute to a Stepwise Development of Fluconazole Resistance in Clinical Candida albicans Strains

1998 ◽  
Vol 42 (12) ◽  
pp. 3065-3072 ◽  
Author(s):  
Renate Franz ◽  
Steven L. Kelly ◽  
David C. Lamb ◽  
Diane E. Kelly ◽  
Markus Ruhnke ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Molecular Mechanisms ◽  
Multiple Drug Resistance ◽  
Genetic Alterations ◽  
Mutant Form ◽  
Mrna Levels ◽  
Fluconazole Resistance ◽  
Stepwise Development ◽  
Target Enzyme

ABSTRACT From each of two AIDS patients with oropharyngeal candidiasis, fiveCandida albicans isolates from recurrent episodes of infection which became gradually resistant against fluconazole during antimycotic treatment were analyzed for molecular changes responsible for drug resistance. In both patients, a single C. albicans strain was responsible for the recurrent infections, but the CARE-2 fingerprint pattern of the isolates exhibited minor genetic alterations, indicating that microevolution of the strains took place during fluconazole therapy. In the isolates from patient 1, enhanced mRNA levels of theMDR1 gene, encoding a multiple drug resistance protein from the superfamily of major facilitators, and constitutive high expression of the ERG11 gene, coding for the drug target enzyme sterol 14α-demethylase, correlated with a stepwise development of fluconazole resistance. The resistant strains exhibited reduced accumulation of fluconazole and, for the last in the series, a slight increase in drug needed to inhibit sterol 14α-demethylation in vitro. In the isolates from patient 2, increasedMDR1 mRNA levels and the change from heterozygosity to homozygosity for a mutant form of the ERG11 gene correlated with continuously decreased drug susceptibility. In this series, reduced drug accumulation and increased resistance in the target enzyme activity, sterol 14α-demethylase, were observed. These results demonstrate that different molecular mechanisms contribute to a gradual development of fluconazole resistance in C. albicans.

scholarly journals Mini Review on Dermatomycosis

2019 ◽  
Vol 8 (1) ◽  
pp. 6-15
Author(s):  
P. M. Ridzuan ◽  
C. M. Nazira ◽  
Manuel Ruth ◽  
C. N. Abdul Rassip ◽  
M. H Nur Raihan ◽  
...  
Keyword(s):  
Drug Treatment ◽  
Fungal Infection ◽  
Human Body ◽  
Molecular Mechanisms ◽  
Review Paper ◽  
Fungal Infections ◽  
Diagnostic Methods ◽  
Molecular Diagnostic ◽  
Development Of Resistance

Dermatomycosis is a fungal infection of the skin, hair and nail caused by Trichophyton, Microsporum and Epidermophyton. These organisms are found in the environment, humans and animals in forms of yeast or mold. There are many factors that contribute to the growth of fungal infections in human body. But still majority of virulent factors and mechanisms of the diseases of fungi are not clear. This review paper describes types of fungal infections, their classification, epidemiology and new insights into pathogenesis with the focus on molecular mechanisms of the diseases. Furthermore, traditional and novel molecular diagnostic methods and the variety of drug treatment and the development of resistance against these drugs are discussed.

Efficacy and Safety of Micafungin as An Empirical Antifungal Therapy for Suspected Fungal Infection in Patients with Hematological Disorders.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1939-1939
Author(s):  
Minoru Yoshida ◽  
Kazuo Tamura ◽  
Masahiro Imamura ◽  
Yoshiro Niitsu ◽  
Takeshi Sasaki ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Antifungal Therapy ◽  
Clinical Symptoms ◽  
Fungal Infections ◽  
Efficacy And Safety ◽  
Hematopoietic Stem ◽  
Persistent Fever ◽  
Hematological Disorders ◽  
Study Results ◽  
Empirical Antifungal Therapy

Abstract Background: Invasive fungal infections (IFIs) are of serious concern in the management of immunocompromised patients (pts) with hematological disorders. Empiric antifungal therapy is recommended for neutropenic pts with persistent fever, because treatment after confirmation of fungal infection often produces poor outcomes. Micafungin (MCFG), one of the echinocandin families, was launched first in Japan in 2002, and has now been approved in more than 11 countries and areas including the USA and the EU. Although the efficacy and safety of MCFG against both Candida and Aspergillus infections has been shown in many clinical trials, there are few clinical study reports on the empiric therapy of a suspected fungal infection. Here, we report the multi-center study results of MCFG for the empiric antifungal therapy, which were conducted from April 2005 to September 2006 in Japan. Objective: This prospective study was performed to clarify the efficacy and safety of MCFG for the empirical antifungal therapy on suspected fungal infection in pts with hematological disorders and neutropenia. Methods: Study design: A multiple-center, open, uncontrolled study. The investigator registered pts with neutropenia (< 1,000/μl) who met the following criteria to the Subject Registration Center. Suspected fungal infections were divided into two categories: possible fungal infection defined by positive clinical symptoms/findings and serological testing (beta-D-glucan or galactomannan) or diagnostic imaging (chest X-ray or CT scan), refractory fever defined by unexplained persistent fever (an axillary temperature higher than 37.5 °C) after the antibacterial treatment over 2 days and by positive clinical symptoms/findings. IFIs categorized as proven or probable were not included in this study. Efficacy evaluation was performed using an algorithm based on each of the evaluation of clinical symptoms/findings, imaging study findings, and serological tests. Results: 388 pts (M:234, F:154, mean age:57.8 years old) were registered. The mean dosage and duration of treatment with MCFG were 154.6±55.3 mg/day and 14.0±6.9 days, respectively. The main underlying hematological disorders were acute leukemia (61.3%), non-Hodgkin’s lymphoma (18.3%) and myelodysplastic syndrome (10.8%). The number of pts with hematopoietic stem cell transplantation (HSCT) was 76 (19.6%). The clinical response rate (CRR), excluding 4 non-evaluable pts was 63.3% (243/384): 60.1% (89/148) for pts with possible fungal infection and 65.3% (154/236) for pts with refractory fever, respectively. Even in persistent neutropenic pts whose neutrophil counts were < 500/μL throughout the treatment with MCFG, the CRR was high enough: 46.9% (61/130). No difference was observed in the CRR among the main underlying hematological disorders. The CRR in pts with HSCT and other conditions were 63.2% (48/76) and 63.3% (195/308), respectively. Drug-related adverse events (DAEs) were observed in 16.8% (65/388). Serious DAEs such as elevation of serum bilirubin and renal dysfunction was observed in 0.52% (2/388). Conclusion: MCFG was confirmed to have high clinical efficacy and be safe for the treatment of suspected fungal infection in pts with hematological disorders and neutropenia.

scholarly journals Molecular Mechanisms of Antifungal Drug Resistance in Candida Species

2018 ◽  
Author(s):  
Lakshmi Krishnasamy ◽  
Sharanya Krishnakumar ◽  
Govindasamy Kumaramanickavel ◽  
Chitralekha Saikumar
Keyword(s):  
Drug Resistance ◽  
Candida Species ◽  
Molecular Mechanisms ◽  
Antifungal Drug ◽  
Antifungal Drug Resistance

scholarly journals Management of dermatophytosis with a novel itraconazole formulation: a research survey

2020 ◽  
Vol 7 (1) ◽  
pp. 33
Author(s):  
Susmit Haldar
Keyword(s):  
Antifungal Therapy ◽  
Fungal Infections ◽  
Real Life ◽  
Pharmacokinetic Profile ◽  
Antifungal Drug ◽  
The Novel ◽  
Research Survey ◽  
Oral Itraconazole ◽  
Orally Active ◽  
Global Population

<p class="abstract"><strong>Background:</strong> Dermatophytic infections are the most prevalent fungal infections, which affect majority of the global population. Indian climate, especially the hot and humid conditions contribute majorly to dermatophytosis. Itraconazole is an orally active triazole antifungal drug, which has demonstrated a broad spectrum of activity and a favourable pharmacokinetic profile. Itraconazole at an appropriate dosage and duration schedule has been reported to be an effective antifungal drug and has achieved optimal results.</p><p class="abstract"><strong>Methods:</strong> The present survey aimed at evaluating the efficacy of the novel itraconazole formulation,</p><p class="abstract">I-Tyza 100 [itraconazole 100 mg (Abbott health care pvt ltd)] with multi-particulate in solid dispersion (MPSD) technology in patients with tinea infections. The data collection was based on the proportion of patients presenting in the clinics for tinea infections, the choice and duration of therapy, real life efficacy of the drug, and for understanding the overall antifungal therapy in dermatomycosis.<strong></strong></p><p class="abstract"><strong>Results:</strong> The responses obtained from 177 doctors were evaluated, and statistical analyses were carried out. The results suggested that clinical presentation of patients with tinea infections per week ranged between 30% and 60%. For the management of tinea infections, oral itraconazole was preferred by maximum doctors, followed by terbinafine, griseofulvin and fluconazole. Also, majority of the doctors (83%) opined that MPSD technology could improve therapeutic efficacy of the novel itraconazole formulation.</p><p class="abstract"><strong>Conclusions:</strong> The survey findings indicated that the novel itraconazole formulation is a preferred oral antifungal therapy for the management of tinea infections.</p>

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