ABSTRACT
Abstract In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL-1, and a MFC of 512-1,024 µg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.
Resumo No atual contexto de patógenos fúngicos resistentes emergentes tais como Candida albicans e Candida parapsilosis, a descoberta de novos agentes antifúngicos é uma questão urgente. Esta pesquisa teve como objetivo avaliar o potencial antifúngico da 2-cloro-N-fenilacetamida contra cepas clínicas de C. albicans e C. parapsilosis resistentes a fluconazol. A atividade antifúngica da substância foi avaliada in vitro através da determinação da concentração inibitória mínima (CIM), concentração fungicida mínima (CFM), ruptura e inibição da formação de biofilme, ensaios de sorbitol e ergosterol, e associação entre esta molécula e antifúngicos comuns, anfotericina B e fluconazol. O produto teste inibiu todas as cepas de C. albicans e C. parapsilosis, com uma CIM variando de 128 a 256 µg.mL-1, e uma CFM de 512-1,024 µg.mL-1. Também inibiu até 92% da formação de biofilme e causou a ruptura de até 87% de biofilme pré-formado. A 2-cloro-N-fenilacetamida não promoveu atividade antifúngica pela ligação ao ergosterol da membrana celular fúngica, tampouco danificou a parede celular. Antagonismo foi observado ao combinar esta substância com anfotericina B e fluconazol. A substância exibiu atividade antifúngica significativa ao inibir tanto as células planctônicas quanto o biofilme das cepas resistentes ao fluconazol. Sua combinação com outros antifúngicos deve ser evitada e seu mecanismo de ação deve ser estabelecido.
ABSTRACT
In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL-1, and a MFC of 512-1,024 µg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.
No atual contexto de patógenos fúngicos resistentes emergentes tais como Candida albicans e Candida parapsilosis, a descoberta de novos agentes antifúngicos é uma questão urgente. Esta pesquisa teve como objetivo avaliar o potencial antifúngico da 2-cloro-N-fenilacetamida contra cepas clínicas de C. albicans e C. parapsilosis resistentes a fluconazol. A atividade antifúngica da substância foi avaliada in vitro através da determinação da concentração inibitória mínima (CIM), concentração fungicida mínima (CFM), ruptura e inibição da formação de biofilme, ensaios de sorbitol e ergosterol, e associação entre esta molécula e antifúngicos comuns, anfotericina B e fluconazol. O produto teste inibiu todas as cepas de C. albicans e C. parapsilosis, com uma CIM variando de 128 a 256 µg.mL-1, e uma CFM de 512-1,024 µg.mL-1. Também inibiu até 92% da formação de biofilme e causou a ruptura de até 87% de biofilme pré-formado. A 2-cloro-N-fenilacetamida não promoveu atividade antifúngica pela ligação ao ergosterol da membrana celular fúngica, tampouco danificou a parede celular. Antagonismo foi observado ao combinar esta substância com anfotericina B e fluconazol. A substância exibiu atividade antifúngica significativa ao inibir tanto as células planctônicas quanto o biofilme das cepas resistentes ao fluconazol. Sua combinação com outros antifúngicos deve ser evitada e seu mecanismo de ação deve ser estabelecido.
Subject(s)
In Vitro Techniques , Candida albicans , Fluconazole , Candida parapsilosis , Antifungal AgentsABSTRACT
The global morbidity of invasive fungal diseases (IFD) tends to increase, especially in immunocompromised people.Due to the atypical symptoms, unclear etiological mechanism, and emerging antifungal resistance, IFD challenge current clinical diagnosis and treatment.The World Health Organization (WHO) developed the first WHO fungal priority pathogens list in 2022.The most concerning fungal pathogens were listed and summarized to promote further understanding of the epidemiology of IFD and antifungal drug resistance.It is hoped to provide a basis for the prevention and interventions of IFD.
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Abstract Invasive infections caused by Candida species have been strongly associated with poor prognosis and high resistance rates to some antifungals. This study aimed to identify Candida species isolated from different anatomical sites and to describe their susceptibility profile to antifungals. Ninety-four clinical isolates of Candida were obtained from a Medical Laboratory of Santa Catarina/Brazil. Species identification was performed by MALDI-TOF MS. Susceptibility assays were performed as described by Clinical Laboratory Standard Institute (CLSI) microboth method. Among the analyzed samples, C. albicans was the pathogen most incident (59.9%) followed by C. parapsilosis complex (14.9%), C. glabrata complex (8.5%), and C. tropicalis (6.3%). 37 Candida strains were isolated from vaginal content (39.3%), 21 from the nail (22.4%), 8 from tracheal aspirates (8.5%), and 7 from urine (7.4%). Together, the Candida isolates presented decreased susceptibility to azole drugs, mainly to fluconazole and itraconazole. Amphotericin B showed sensibility in 95.7% of samples analyzed. Previous knowledge about etiology and antifungal susceptibility becomes indispensable to conduct an efficient treatment.
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Extracorporeal membrane oxygenation (ECMO), a kind of life support technology that can replace lung and heart function, is widely used in critical respiratory and circulatory exhaustion. Because of the serious diseases and the use of interventional catheters, patients receiving ECMO life support are often administrated with broad-spectrum antimicrobial agents, which increase the risk of fungal infection. Fungal infection during ECMO can increase mortality. How to effectively control fungal infection is a thorny problem faced by clinicians. During the treatment of ECMO, the patient's physiological status, ECMO oxygenation membrane, circulation pipeline and other factors may change the pharmacokinetic profiles of antifungal drugs, thereby affect the clinical efficacy of drugs. This artical reviews the pharmacokinetic characteristics of antifungal drugs during ECMO support, in order to provide references for clinical antifungal treatment.
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Objective: The main purpose of this work was to prepare tolnaftate (TOL) loaded nanostructured lipid carriers (NLCs), Evaluate its characteristics and in vitro release study. Methods: Tolnaftate loaded Nanostructured lipid carriers were prepared by the high shear homogenization method using different liquid lipids types (DERMAROL DCO® and DERMAROL CCT®) and concentrations, different concentration ratios of tween80® to span20® and different homogenization speeds. All the formulated nanoparticles were subjected to particle size (PS), zeta potential (ZP), polydispersity index (PI), drug entrapment efficiency (EE), Differential Scanning Calorimetry (DSC), Transmission Electron microscopy (TEM), release kinetics and in vitro release study was determined. Results: The results revealed that NLC dispersions had spherical shapes with an average size between 154.966±1.85 nm and 1078.4±103.02 nm. High entrapment efficiency was obtained with negatively charged zeta potential with PDI value ranging from 0.291±0.02 to 0.985±0.02. The release profiles of all formulations were characterized by a sustained release behavior over 24 h and the release rates increased as the amount of surfactant decreased. The release rate of TOL is expressed following the theoretical model by Higuchi. Conclusion: From this study, It can be concluded that NLCs are a good carrier for tolnaftate delivery
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Introduction: Incidence of invasive fungal infections is now rising. An estimated 4.7 million HIV-1–infected persons are living in Asia. The aim of the study was to know the anti fungal susceptibility profile of Candida spp. and Aspergillus spp.in northen India region. Material and methods: In this study we took 150 patients attending outpatient department and admitted in the wards of T.B. and Respiratory Diseases, along with those attending antiretroviral treatment clinic and ICTC (Department of Microbiology), in J. N. Medical College, AMU. Results: Amongst Candida isolates, resistance to fluconazole was seen in 6.9% isolates of C. albicans. 50% of C. dubliniensis and 20% of C.glabrata were resistant to fluconazole. Also, resistance to ketoconazole was observed in 25% isolates of C. dubliniensis. Only 1 isolate was resistant to AMB which was of C.glabrata (20%) and no isolate was resistant to Caspofungin. Resistance to Amphotericin B was seen in 11.8% of A. fumigatus, 10% of A. flavus and 33.3% of A. niger. Resistance to Itraconazole was found in 11.8% of A. fumigatus, 20% of A. flavus and 33.3% of A. niger. Resistance to Ketoconazole was seen in 11.1% of A. fumigatus, 14.2% of A. flavus and 100% of A. niger. No resistance was seen against Caspofungin against any species of Aspergillus. Conclusion: There is gradual increase in the antifungal resistance among higher drugs reported from other regions, is a major concern for today.
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Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.
Subject(s)
Humans , Anti-Infective Agents , Betaine , Cell Membrane , Cryptococcus , Cryptococcus neoformans , Dandruff , Ergosterol , Fungi , Gene Deletion , Genetic Testing , Genomics , Malassezia , Methods , Skin , TranscriptomeABSTRACT
BACKGROUND Sporothrix brasiliensis is the most virulent sporotrichosis agent. This species usually responds to antifungal drugs, but therapeutic failure can occur in some patients. Antifungal susceptibility tests have been performed on this species, but no clinical breakpoints (CBPs) are available. In this situation, minimal inhibitory concentration (MIC) distributions and epidemiological cutoff values (ECVs) support the detection of identification of resistant strains. OBJECTIVES To study the MIC distributions of five antifungal drugs against S. brasiliensis and to propose tentative ECVs. METHODS MICs of amphotericin B (AMB), itraconazole (ITR), ketoconazole (KET), posaconazole (POS), and terbinafine (TRB) against 335 S. brasiliensis strains were determined by the Clinical and Laboratory Standards Institute broth microdilution method. FINDINGS The proposed ECV, in µg/mL, for AMB, ITR, KET, POS, and TRB were 4.0, 2.0, 1.0, 2.0, and 0.25, respectively. Percentages of wild-type strains in our population for the above antifungal drugs were 98.48, 95.22, 95.33, 100, and 97.67%, respectively. MAIN CONCLUSIONS These ECVs will be useful to detect strains with resistance, to define CBPs, and to elaborate specific therapeutic guidelines for S. brasiliensis. Rational use of antifungals is strongly recommended to avoid the emergence of resistant strains and ensure the therapeutic effectiveness of sporotrichosis.
Subject(s)
Humans , Animals , Cats , Sporothrix/drug effects , Triazoles/pharmacology , Amphotericin B/pharmacology , Itraconazole/pharmacology , Ketoconazole/pharmacology , Antifungal Agents/pharmacology , Naphthalenes/pharmacology , Drug Resistance , Cats , Anti-Infective AgentsABSTRACT
BACKGROUND: Candidemia has increased with an increasing number of people in the high risk group and so has become more important. This study was conducted to investigate the isolation rate of Candida species from candidemia patients and the change in rate of antifungal resistance. METHODS: At a single tertiary care hospital, 1,120 blood cultures positive for Candida species from 1997 to 2016 were investigated according to date of culture, gender, age, and hospital department. RESULTS: During the investigation period, the number of candidemia patients increased from 14 in 1997 to 84 in 2016. The most common organism identified during the two decades was Candida albicans (40.8%), followed by Candida parapsilosis (24.1%), Candida tropicalis (13.2%), and Candida glabrata (12.8%). C. glabrata was relatively common in females (45.5%) compared to males. The age group 40-89 years was more frequently infected than other age groups, and the most frequent isolates according to age group were C. albicans in neonate (66.7%), C. parapsilosis in 1-9-year-olds (41.7%), and C. glabrata in those aged ≥60 years (range; 13.3%–20.0%). According to the visited departments, C. albicans, C. glabrata, and Candida haemulonii were more common in medical departments, while C. parapsilosis was more common in surgical departments. In the antifungal susceptibility test, a rising trend of azole resistance among C. albicans and C. glabrata was observed in recent years. CONCLUSION: In this study, it was confirmed that the isolation rate of Candida species in blood is different by age, gender, and hospital department, and the distribution of isolated Candida species changed over time. The resistance patterns of antifungal agents are also changing, and continuous monitoring and proper selection of antifungal agents are necessary.
Subject(s)
Female , Humans , Infant, Newborn , Male , Antifungal Agents , Candida albicans , Candida glabrata , Candida tropicalis , Candida , Candidemia , Danazol , Drug Resistance, Fungal , Hospital Departments , Prevalence , Tertiary HealthcareABSTRACT
A droplet microfluidic chip system was developed for drug screening against Candida albicans. The microfluidic chip was designed and prepared for the formation of droplets. Alamar blue was selected as an indicator for its characteristic of fluorescence mission in live cells. Four antifungal drugs (amphotericin B, caspofungin, 5-fluorocytosine, terbinafine) and a new drug (iodiconazole) were selected as model drugs to test the microfluidic chip approach. At the same time, 96-well microplate method was performed to verify the applicability of the chip method. The results showed that the developed droplet microfluidic chip platform was able to complete the antifungal susceptibility test within 2 h. In comparison with the 96-well microplate method, the microfluidic chip method showed a consistence of 100% with regard to the minimum inhibition concentrations and less reagent consumption. The new droplet microfluidic chip method is simple, rapid and suitable for rapid screening of antifungal drugs.
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In recent years,the epidemiology of Candida infection has changed.Although Candida albicans is still the main pathogens causing invasive candidiasis,non-albicans Candida species are increasingly encountered.Different Candida species show distinct sensitivity of different drugs.The emergence of drug resistance has become the main problem of Candida in-fection treatment.Antifungal resistance of clinical Candida infections often lead to treatment failure.The review of resistance mechanisms and the effect on clinical treatment is very significant to improve the prognosis of patients and strengthen the control of infection.This text reviews the present state of the detection of mechanisms of resistance in Candida spp .
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Objective To analyze the constitute and antifungal susceptibility of Candida spp . causing bloodstream infection in a hospital,so as to provide evidence for the prevention and treatment of bloodstream infection caused by Candida spp .Methods Candida spp . isolated from blood specimens of clinical patients in a hospital between 2009 and 2013 were analyzed retrospectively,the high risk factors for Candida bloodstream infection were analyzed. Results A total of 42 isolates of Candida spp . were isolated from blood specimens of 42 patients between 2009 and 2013,the major was Candida parapsilosis (C.parapsilosis ,n =20,47.62%),followed by C.albicans (n =16, 38.10%),C.tropicalis (n=4,9.52%),and C.glabrata(n=2,4.76%).Candida spp .were mainly distributed in emergency intensive care unit(n=11),departments of urologic surgery (n=9)and cardiothoracic surgery(n=8). The venous catheters of 37 patients(88.10%)were isolated the same Candida spp . as blood culture,the average time from indwelling venous catheters to positive culture of blood and catheters were 31 .47 and 33.18 days respec-tively;the percentage of positive culture for blood and catheters both increased with the prolongation of catheteriza-tion (both P < 0.001 ).Susceptibility rates of Candida spp . to fluconazole and voriconazole were 75.00% -100.00%,to amphotericin B were all 100.00%,to itraconazole varied significantly with different species (0 -87.50%).Conclusion The major Candida strains causing bloodstream infection in this hospital is C.parapsilosis , and is related to the use of intravenous catheters,susceptibility rates to fluconazole,amphotericin B,and voricon-azole are all high.
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OBJECTIVE: Candidaemia is the fourth most common cause of nosocomial bloodstream infections. The objective of this paper was to evaluate the risk factors associated with mortality in patients with candidaemia with respect to Candida species and their susceptibilities, retrospectively. METHODS: All consecutive patients who developed candidaemia at an 800-bed training and research hospital were enrolled in this retrospective, observational, single centre study during the period June 2006 to December 2011. RESULTS: A total of 97 candidaemia episodes were identified in 97 patients during the study period with an overall incidence of four episodes/10 000 admissions in adults. Crude 30-day mortality rates among patients with candidaemia were 56% (55 of 97 cases). Urinary catheterization, immunosuppressive therapy, acute physiology and chronic health evaluation (APACHE) II score (>16) and hypoal-buminaemia were found to be independent risk factors for fatal candidaemia. CONCLUSIONS: Adult cases with candidaemia who have risk factors associated with mortality are more likely to have poor prognosis despite appropriate and timely initiated antifungal drug treatment. Empiric antifungal drug should be tailored according to the severity of the patients ' conditions and local antifungal susceptibility.
OBJETIVO: La candidemia es la cuarta causa más común de infecciones nosocomiales del flujo sanguíneo. El objetivo del presente trabajo fue evaluar los factores de riesgo asociados con la mortalidad en pacientes con candidemia con respecto a las especies de Candida y sus susceptibilidades, de manera retrospectiva. MÉTODOS: Todos los pacientes consecutivos que desarrollaron candidemia en un hospital de capacitación e investigación de 800 camas, fueron inscritos en este estudio retrospectivo, observacional, monocéntrico, durante el período de junio de 2006 a diciembre de 2011. RESULTADOS: Se identificaron un total de 97 episodios de candidemia en 97 pacientes durante el período de estudio con una incidencia general de cuatro episodios/10 000 ingresos en adultos. Las tasas brutas de mortalidad de 30 días entre los pacientes con candidemia fueron 56% (55 de 97 casos). Se halló que la cateterización urinaria, la terapia inmunosupresiva, y la puntuación (> 16) de la escala de Evaluación de la fisiología aguda y salud crónica (APACHE II) así como la hipoalbuminemia, constituyen factores de riesgo para una candidemia fatal. CONCLUSIONES: Los casos adultos con candidemia que tienen factores de riesgo asociados con mortalidad son más propensos a tener un pronóstico pobre a pesar del tratamiento apropiado y oportuno con medicamentos antimicóticos. Los antimicóticos empírico se deben adaptar según la severidad de las condiciones de los pacientes y la susceptibilidad antifúngica local.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Candida/classification , Drug Resistance, Multiple, Fungal , Candidemia/microbiology , Candidemia/mortality , Candida/drug effects , Incidence , Retrospective Studies , Risk FactorsABSTRACT
Background: The purpose of this study was to isolate the Candida spp. & examine their susceptibility to antifungal drugs from various clinical specimens. One hundred fifty isolates of Candida spp. were included in this study. Clinical history revealed that all patients were on systemic broad spectrum antibacterial drugs. Materials and Methods: Candida spp. was differentiated by germ tube test, culture characteristics on special media for fungus, sugar fermentation, sugar assimilation and growth on corn meal agar. Antifungal drug susceptibility testing against Fluconazole, Ketoconazole, Itraconazole, Voriconazole, Nystatin and Amphotericin B were done on basis of CLSI guidelines on Methylene blue containing Mueller Hinton Agar by disk diffusion method. Result: We found 52% and 48%, C.albicans & Non albicans candida spp., respectively. There were no resistance to Nystatin and Amphotericin B. C.albicans was more susceptible than Non albicans candida. Nystatin & Amphotericin B were susceptible to all isolated Candida spp. In present scenario, Fluconazole is most commonly used empirical antifungal drug, which is more effective to C.albicans than Non albicans Candida. Conclusion: Due to emergence of resistance in Azole group of antifungal among Non albicans candida, it should be mandatory to use antifungal drugs as per the susceptibility testing.
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The extensive use of azole antifungal agents has promoted the resistance of Candida spp to these drugs. Candida glabrata is a problematic yeast because it presents a high degree of primary or secondary resistance to fluconazole. In Brazil, C. glabrata has been less studied than other species. In this paper, we compared the activity of three major classes of antifungal agents (azoles, echinocandins and polyenes) against fluconazole-susceptible (FS) and fluconazole-resistant (FR) C. glabrata strains. Cross-resistance between fluconazole and voriconazole was remarkable. Among the antifungal agents, the echinocandins were the most effective against FS and FR C. glabrata and micafungin showed the lowest minimal inhibitory concentrations.
Subject(s)
Humans , Amphotericin B/pharmacology , Antifungal Agents/pharmacology , Candida glabrata/drug effects , Echinocandins/pharmacology , Fluconazole/pharmacology , Pyrimidines/pharmacology , Triazoles/pharmacology , Candida glabrata/isolation & purification , Drug Resistance, Fungal/drug effects , Lipopeptides/pharmacology , Microbial Sensitivity TestsABSTRACT
ObjectiveTo investigate the flora distribution and drug resistance status of nosocomial fungal infection in cancer hospitals for providing the scientific basis for clinical prevention and control.Methods The related clinical data and results of drug sensitivity tests of fungal infection in hospitalized patients from April 2006 to November 2010 were analyzed retrospectively.ResultsA total of 1011 strains of candida were isolated in five years, in which, Candida albicans (41.6％ on average) were the highest detection rate strains.The proportion of Candida albicans declined from 53.8％ in 2006 to 31.7％ in 2010, while the other non-Candida albicans increased from 46.2％ in 2006 to 68.3％ in 2010.In the General surgery, the Internal medicine,the Hepatobiliary surgery, and the Chinese and Western medicine, the number of candida were more than the other departments.The specimens were mainly isolated from sputum and swab, followed by blood specimens.In vitro susceptibility test results showed that: voriconazole, amphotericin B and 5-fluorocytosine showed high sensitivity and itraconazole, fluconazole showed high drug resistance to albicans.Conclusion Distribution of pathogens causing nosocomial fungal infection has changed, and the rates of fungal resistance were rising,so this situation should arouse the clinician's attention.
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The correlated proteome of Penicillium marneffei resistant to fluconazole was investigated in the present study, in which 11 strains of P. marneffei of both the mycelial and yeast forms sensitive to fluconazole were cultivated in Sabouraud's liquid medium containing 8 g fluconazole and the MICs of fluoconazile to P.marneffei before and after inducing cultures were tested by E-test method. The strains of the mycelial and yeast forms showing the most significant increase in MIC value were selected and the protein clip CM10 was used to detect the proteome differences before and after inducing cultures. It was found that 11 strains of the mycelial forms and 2 strains of the yeast forms could tolerate the action of fluconazole and could grow at a drug concentration of 8 μg/mL. Furthermore, the MICs of fluoconazole to the mycelial forms were significantly increased after 7 days of inducing culture and the geometric means of MICs were increased from 1.22 μg /mL to 55.56 μg/mL. After the mycelial forms had been induced to be resistant, 16 proteins were highly expressed with specific expression of the 4581.1 Da and 6109.7 Da proteins; whereas 22 resistant yeast form were highly expressed with specific expression of the 3575.2 Da, 8507.0 Da and 8563.3 Da proteins. These results suggest that the mycelial form of P.narneffei seems to be more tolerant to the action of fluconazole than the yeast form. The resistance of these organisms to fluconazole may be associated to some specific proteins.
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OBJECTIVE To approach the flora distribution and drug-resistance status in deep fungal nosocomial infection in tumor patients and offer scientific evidence of prevention and controlling of it.METHODS Retrospective reviews were performed to analyze the 153 cases of deep fungal nosocomial infections in tumor department.Fungal cultivation,identification and susceptibility tests were performed strictly according to Rules of Operation in Clincal Laboratory of Nationwide.RESULTS The lower respiratory tract was the main site in deep fungal nosocomial infection in tumor patients,accounting for 61.4%.The digestive tract infection rated the second,accounting for 13.1%.Pathogenic bacteria mainly included Candida albicans(60.1%)and C.tropicalis(20.9%).The susceptibility test showed that the drug-resistance rate to amphotericin B and nystatin were all 0 and that to itraconazole and clotrimazole was 0-7.6%.The resistance rate(17.4-30.0%) to fluconazole showed upgrading tendency.CONCLUSIONS We should think highly of etiological detection and monitoring of drug-resistance in deep fungal nosocomial infections in tumor patients in order to control the infections effectively.
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The incidence of invasive fungal infection has increased worldwide along with the increasing population of high risk patients. Recently developed antifungal agents, such as second-generation triazoles and echinocandins, provide the potential to improve therapeutic options against invasive fungal infections. However, treatment of invasive fungal infections has been hampered by both intrinsic and acquired resistance to antifungal agents among many fungal pathogens. A better understanding of the clinical impact of antifungal resistance is important for selecting the proper antifungal agent in patients with systemic fungal infections. This article reviews the current situation with regard to intrinsic and acquired resistance of clinically significant yeasts and filamentous fungi against currently available antifungal agents.