OBJECTIVE: To investigate the effect of arsenic disulfide (AS METHODS: The human DLBCL cell OCI-LY3 was treated with different concentrations of AS RESULTS: The DLBCL cell viability was decreased significantly at 24, 48 or 72 h as cultured with itraconazole. Along with the increasing of itraconazole concentration, the DLBCL cell viability was significantly reduced as compared with that in control group, and the results showed statistically significant(r=-0.690，r=-0.639, r=-0.833, r=-0.808, r=-0.578). The inhibitory and apoptosis rates of the cells were significantly increased as compared with those of the single drug-treated group after treated by the combination of itraconazole and AS CONCLUSION Itraconazole can inhibit proliferation of DLBCL cells in a concentration-and time-dependent manner. In addition, the combination of AS
Apoptosis ; Arsenicals ; Hedgehog Proteins ; Humans ; Itraconazole/pharmacology* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Sulfides

BACKGROUNDThe prevalence of dermatophytoses and the development of new antifungal agents has focused interest on susceptibility tests of dermatophytes. The method used universally for susceptibility tests of dermatophytes was published as document (M38-A) in 2002 by the Clinical and Laboratory Standards Institute (CLSI), dealing with the standardization of susceptibility tests in filamentous fungi, though not including dermatophytes especially. However, it is not a very practical method for the clinical laboratory in routine susceptibility testing. In this test, we developed a novel rapid susceptibility assay-glucose consumption method (GCM) for dermatophytes.

METHODSIn this study, we investigated the antifungal susceptibilities of dermatophytes to itraconazole (ITC), voriconazole (VOC), econazole nitrate (ECN) and terbinafine (TBF) by glucose consumption method (GCM), in comparison to the Clinical and Laboratory Standards Institute (CLSI) M38-A method. Twenty-eight dermatophyte isolates, including Trichophyton rubrum (T. rubrum) (n = 14) and Trichophyton mentagrophytes (T. mentagrophytes) (n = 14), were tested. In the GCM, the minimum inhibitory concentrations (MICs) were determined spectrophotometrically at 490 nm after addition of enzyme substrate color mix. For the CLSI method, the MICs were determined visually.

RESULTSComparison revealed best agreement for TBF against T. mentagrophytes and T. rubrum, since MIC range, MIC50, and MIC90 were identical from two methods. However, for ITC and VOC, GCM showed wider MIC ranges and higher MICs than CLSI methods in most isolates. For ECN against T. rubrum, high MICs were tested by GCM (0.125-16 microg/ml) but not M38-A method (0.5-1 microg/ml). The overall agreements for all isolates between the two methods within one dilution and two dilutions for ITC, VOC, ECN and TBF was 53.6% and 75.0%, 57.1% and 75.0%, 82.1% and 89.3%, and 85.7 and 85.7%, respectively.

CONCLUSIONMeasurement of glucose uptake can predict the susceptibility of T. rubrum and T. mentagrophytes to ECN and TBF.

Antifungal Agents ; pharmacology ; Econazole ; pharmacology ; Glucose ; metabolism ; Itraconazole ; pharmacology ; Microbial Sensitivity Tests ; Naphthalenes ; pharmacology ; Pyrimidines ; pharmacology ; Triazoles ; pharmacology ; Trichophyton ; drug effects ; metabolism ; Voriconazole

BACKGROUNDDuring recent years, the incidence of serious infections caused by opportunistic fungi has increased dramatically due to alterations of the immune status of patients with hematological diseases, malignant tumors, transplantations and so forth. Unfortunately, the wide use of triazole antifungal agents to treat these infections has lead to the emergence of Aspergillus spp. resistant to triazoles. The present study was to assess the in vitro activities of five antifungal agents (voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin) against different kinds of Aspergillus spp. that are commonly encountered in the clinical setting.

METHODSThe agar-based Etest MIC method was employed. One hundred and seven strains of Aspergillus spp. (5 species) were collected and prepared according to Etest Technique Manuel. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 hours at 35°C. MIC(50), MIC(90) and MIC range were acquired by Whonet 5.4 software.

RESULTSThe MIC(90) of caspofungin against A. fumigatus, A. flavus and A. nidulans was 0.094 µg/ml whereas the MIC(90) against A. niger was 0.19 µg/ml. For these four species, the MIC(90) of caspofungin was the lowest among the five antifungal agents. For A. terrus, the MIC(90) of posaconazole was the lowest. For A. fumigatus and A. flavus, the MIC(90) in order of increasing was caspofungin, posaconazole, voriconazole, itraconazole, and amphotericin B. The MIC of amphotericin B against A. terrus was higher than 32 µg/ml in all 7 strains tested.

CONCLUSIONSThe in vitro antifungal susceptibility test shows the new drug caspofungin, which is a kind of echinocandins, has good activity against the five species of Aspergillus spp. and all the triazoles tested have better in vitro activity than traditional amphotericin B.

Amphotericin B ; pharmacology ; Antifungal Agents ; pharmacology ; Aspergillus ; drug effects ; Echinocandins ; pharmacology ; Itraconazole ; pharmacology ; Lipopeptides ; Microbial Sensitivity Tests ; Pyrimidines ; pharmacology ; Triazoles ; pharmacology ; Voriconazole

BACKGROUNDVulvovaginal candidiasis (VVC) was a common infection associated with lifelong harassment of woman's social and sexual life. The purpose of this study was to describe the species distribution and in vitroCandidaCandida spp.) isolated from patients with VVC over 8 years.

METHODSSpecies which isolated from patients with VVC in Peking University First Hospital were identified using chromogenic culture media. Susceptibility to common antifungal agents was determined using agar diffusion method based on CLSI M44-A2 document. SPSS software (version 14.0, Inc., Chicago, IL, USA) was used for statistical analysis, involving statistical description and Chi-square test.

RESULTSThe most common strains were Candida (C.) albicans, 80.5% (n = 1775) followed by C. glabrata, 18.1% (n = 400). Nystatin exhibited excellent activity against all species (<4% resistant [R]). Resistance to azole drugs varied among different species. C. albicans: clotrimazole (3.1% R) < fluconazole (16.6% R) < itraconazole (51.5% R) < miconazole (54.0% R); C. glabrata: miconazole (25.6% R) < clotrimazole (50.5% R) < itraconazole (61.9% R) < fluconazole (73.3% R); Candida krusei: clotrimazole (0 R) < fluconazole (57.7% R) < miconazole (73.1% R) < itraconazole (83.3% R). The susceptibility of fluconazole was noticeably decreasing among all species in the study period.

CONCLUSIONSNystatin was the optimal choice for the treatment of VVC at present. The species distribution and in vitroCandida spp. isolated from patients with VVC had changed over time.

Antifungal Agents ; pharmacology ; Candida ; drug effects ; pathogenicity ; Candidiasis, Vulvovaginal ; microbiology ; China ; Clotrimazole ; pharmacology ; Drug Resistance, Fungal ; Female ; Fluconazole ; pharmacology ; Humans ; Itraconazole ; pharmacology ; Miconazole ; pharmacology ; Microbial Sensitivity Tests

Objective: To explore the epidemiological characteristics of sample distribution and antifungal susceptibilities of clinically invasive C. tropicalis isolates from 2017 to 2021 in East China. Methods: Using a retrospective analysis, the East China Invasive Fungal Infection Group (ECIFIG) collected C. tropicalis clinically isolated from 32 hospitals in East China between January 2017 and December 2021. The identification results of the strains were reviewed using mass spectrometry by the central laboratory of the Shanghai East Hospital. The minimum inhibitory concentrations (MICs) of the strains against fluconazole (FLU), voriconazole (VOR), itraconazole (ITR), Posaconazole (POS), isavuconazole (ISA), anidulafungin (ANI), caspofungin (CAS), micafungin (MICA) and 5-fluorocytosine (FCT) were tested by the ThermoFisher CMC1JHY colorimetric microdilution method. The MIC of amphotericin B (AMB) was tested by the broth microdilution method. The MIC results were analyzed based on the clinical breakpoints and epidemiological cutoff values (ECV) published by the Clinical and Laboratory Standards Institute (CLSI) M27 Ed3 and M57 Ed4 documents. Data analysis was conducted using the Kruskal-Wallis test and paired t-test. Results: In total, 305 C. tropicalis isolates were collected. There were 38.0% (116/305) strains isolated from blood, 11.5% (35/305) ascites, 8.9% (27/305) catheter and 8.9% (27/305) drainage fluid. The resistance rate of C. tropicalis to FLU was 32.5%, to VOR was 28.5%, and the cross-resistance rate to FLU and VOR was 28.5%. The wild-type proportions for ITR and POS were 79.3% and 29.2% respectively. There was no significant difference in resistance rates, MIC₅₀, and MIC₉₀ of FLU and VOR, or in the wild-type rates of ITR and POS over five years. More than 95.0% of the isolates were susceptible to echinocandins. However, one strain was identified as being multi-drug resistant. In azole antifungals, voriconazole, itraconazole, posaconazole, and isavuconazole have similar GM MIC values. The GM MIC of fluconazole is significantly higher than that of itraconazole (t=9.95, P<0.05), posaconazole (t=9.99, P<0.05), and voriconazole (t=10.01, P<0.05), Meanwhile, among echinocandins, the GM MIC of ANI was comparable to that of CAS (t=1.17, P>0.05), both of which were significantly higher than MICA (t=11.56, P<0.05; t=4.15, P<0.05). Conclusion: The clinical isolates of C. tropicalis in East China from 2017 to 2021 were relatively susceptible to echinocandins. However, there was consistently high resistance to fluconazole and voriconazole. More intensive efforts should be made on the monitoring of drug resistance in C. tropicalis.
Humans ; Antifungal Agents/pharmacology* ; Fluconazole/pharmacology* ; Candida tropicalis ; Voriconazole/pharmacology* ; Itraconazole/pharmacology* ; Retrospective Studies ; Candida ; China/epidemiology* ; Echinocandins/pharmacology* ; Microbial Sensitivity Tests

Objective: To explore the epidemiological characteristics of sample distribution and antifungal susceptibilities of clinically invasive C. tropicalis isolates from 2017 to 2021 in East China. Methods: Using a retrospective analysis, the East China Invasive Fungal Infection Group (ECIFIG) collected C. tropicalis clinically isolated from 32 hospitals in East China between January 2017 and December 2021. The identification results of the strains were reviewed using mass spectrometry by the central laboratory of the Shanghai East Hospital. The minimum inhibitory concentrations (MICs) of the strains against fluconazole (FLU), voriconazole (VOR), itraconazole (ITR), Posaconazole (POS), isavuconazole (ISA), anidulafungin (ANI), caspofungin (CAS), micafungin (MICA) and 5-fluorocytosine (FCT) were tested by the ThermoFisher CMC1JHY colorimetric microdilution method. The MIC of amphotericin B (AMB) was tested by the broth microdilution method. The MIC results were analyzed based on the clinical breakpoints and epidemiological cutoff values (ECV) published by the Clinical and Laboratory Standards Institute (CLSI) M27 Ed3 and M57 Ed4 documents. Data analysis was conducted using the Kruskal-Wallis test and paired t-test. Results: In total, 305 C. tropicalis isolates were collected. There were 38.0% (116/305) strains isolated from blood, 11.5% (35/305) ascites, 8.9% (27/305) catheter and 8.9% (27/305) drainage fluid. The resistance rate of C. tropicalis to FLU was 32.5%, to VOR was 28.5%, and the cross-resistance rate to FLU and VOR was 28.5%. The wild-type proportions for ITR and POS were 79.3% and 29.2% respectively. There was no significant difference in resistance rates, MIC₅₀, and MIC₉₀ of FLU and VOR, or in the wild-type rates of ITR and POS over five years. More than 95.0% of the isolates were susceptible to echinocandins. However, one strain was identified as being multi-drug resistant. In azole antifungals, voriconazole, itraconazole, posaconazole, and isavuconazole have similar GM MIC values. The GM MIC of fluconazole is significantly higher than that of itraconazole (t=9.95, P<0.05), posaconazole (t=9.99, P<0.05), and voriconazole (t=10.01, P<0.05), Meanwhile, among echinocandins, the GM MIC of ANI was comparable to that of CAS (t=1.17, P>0.05), both of which were significantly higher than MICA (t=11.56, P<0.05; t=4.15, P<0.05). Conclusion: The clinical isolates of C. tropicalis in East China from 2017 to 2021 were relatively susceptible to echinocandins. However, there was consistently high resistance to fluconazole and voriconazole. More intensive efforts should be made on the monitoring of drug resistance in C. tropicalis.
Humans ; Antifungal Agents/pharmacology* ; Fluconazole/pharmacology* ; Candida tropicalis ; Voriconazole/pharmacology* ; Itraconazole/pharmacology* ; Retrospective Studies ; Candida ; China/epidemiology* ; Echinocandins/pharmacology* ; Microbial Sensitivity Tests

OBJECTIVETo establish a model of Candida biofilm and to explore its characteristics, ultrastructure, influences by saliva and serum, and sensitivity to antifungal agents.

METHODSEvaluations of the in vitro growth kinetics, influences by saliva and serum, and sensitivity to antifungal agents of Candida biofilm were performed with the abated tetrazolium salt XTT method on a 96-well microtire petri dish. The ultrastructure of Candida biofilm was observed under Confocal Laser Scanning Microscope (CLSM).

RESULTSThe bioactivity of Candida biofilm increased with culturing time and serum could obviously increase the action of biofilm. The Candida biofilm was significantly resistant to routine antifungal agents.

CONCLUSIONThe Candida cells adhered in biofilms are significantly different in morphology from those in suspension and are resistant to routine antifungal agents such as Amphotericine B, Fluconazole and Itraconazole.

Amphotericin B ; pharmacology ; Antifungal Agents ; pharmacology ; Biofilms ; drug effects ; Candida ; drug effects ; ultrastructure ; Drug Resistance, Fungal ; Fluconazole ; pharmacology ; Itraconazole ; pharmacology ; Microbial Sensitivity Tests ; Microscopy, Confocal

PURPOSE: The incidence of Candida bloodstream infections (BSI) has increased over the past two decades. The rank order of occurrence and the susceptibility to antifungals of the various Candida species causing BSI are important factors driving the establishment of empirical treatment protocols; however, very limited multi-institutional data are available on Candida bloodstream isolates in Korea. MATERIALS AND METHODS: We investigated the susceptibility to azole antifungals and species distribution of 143 Candida bloodstream isolates recovered from eight university hospitals over a six-month period. Minimal inhibitory concentrations (MICs) of fluconazole, itraconazole, and voriconazole for each isolate were determined by the broth microdilution method of the Clinical and Laboratory Standards Institute (CLSI). RESULTS: The Candida species recovered most frequently from the blood cultures was C. albicans (49%), followed by C. parapsilosis (22%), C. tropicalis (14%), and C. glabrata (11%). The MIC ranges for the Candida isolates were 0.125 to 64microgram/mL for fluconazole, 0.03 to 2microgram/mL for itraconazole, and 0.03 to 1microgram/mL for voriconazole. Overall, resistance to fluconazole was found in only 2% of the Candida isolates (3/143), while the dose-dependent susceptibility was found in 6% (8/143). The resistance and dose-dependent susceptibility of itraconazole were found in 4% (6/143) and 14% (20/143) of the isolates, respectively. All bloodstream isolates were susceptible to voriconazole (MIC, < or = 1microgram/mL). CONCLUSION: Our findings show that C. albicans is the most common cause of Candida-related BSI, followed by C. parapsilosis, and that the rates of resistance to azole antifungals are still low among bloodstream isolates in Korea.
Antifungal Agents/*pharmacology ; Azoles/*pharmacology ; Bacteremia/*microbiology ; Candida/classification/*drug effects/isolation & purification ; Candidiasis/*microbiology ; Drug Resistance, Fungal ; Fluconazole/pharmacology ; Hospitals, University ; Humans ; Itraconazole/pharmacology ; Microbial Sensitivity Tests ; Population Surveillance ; Pyrimidines/pharmacology ; Triazoles/pharmacology

BACKGROUNDDuring the past decades, the incidence of invasive aspergillosis (IA) caused by Aspergillus fumigatus has increased dramatically. The aims of this study were to investigate the susceptibility of clinical isolates of A. fumigatus to triazole and the underlying cyp51A mutations in triazole-resistant A. fumigatus.

METHODSA total of 126 A. fumigatus clinical isolates from 126 patients with proven or probable IA were obtained from four large tertiary hospitals in Nanjing, China, between August 2012 and July 2015. The determination of minimal inhibitory concentrations (MICs) for itraconazole, voriconazole, and posaconazole was performed by broth microdilution according to the European Committee on Antimicrobial Susceptibility Testing reference method.

RESULTSA total of 4 A. fumigatus isolates (3.17%) were confirmed to be itraconazole resistant, with MICs of ≥8 mg/L, and one isolate (0.8%) was confirmed to be voriconazole resistant and posaconazole resistant, with MICs of 4 mg/L and 0.5 mg/L, respectively. We found that two of the 4 isolates of triazole-resistant A. fumigatus had the L98H amino acid substitution in combination with a 34-base pair tandem repeat in the promoter region, one isolate had an M220I mutation, and another itraconazole-resistant isolate did not have a substitution in the cyp51A gene.

CONCLUSIONSThis study shows that triazole-resistant A. fumigatus clinical isolates are present in Nanjing, China, which is a new challenge to the clinical management of IA.

Antifungal Agents ; pharmacology ; Aspergillus fumigatus ; drug effects ; genetics ; China ; Drug Resistance, Fungal ; Itraconazole ; pharmacology ; Microbial Sensitivity Tests ; Promoter Regions, Genetic ; genetics ; Tandem Repeat Sequences ; genetics ; Triazoles ; pharmacology ; Voriconazole ; pharmacology

Candidaemia associated with intravascular catheter-associated infections is of great concern due to the resulting high morbidity and mortality. The antibiotic lock technique (ALT) was previously introduced to treat catheter-associated bacterial infections without removal of catheter. So far, the efficacy of ALT against Candida infections has not been rigorously evaluated. We investigated in vitro activity of ALT against Candida biofilms formed by C. albicans, C. glabrata, and C. tropicalis using five antifungal agents (caspofungin, amphotericin B, itraconazole, fluconazole, and voriconazole). The effectiveness of antifungal treatment was assayed by monitoring viable cell counts after exposure to 1 mg/mL solutions of each antibiotic. Fluconazole, itraconazole, and voriconazole eliminated detectable viability in the biofilms of all Candida species within 7, 10, and 14 days, respectively, while caspofungin and amphotericin B did not completely kill fungi in C. albicans and C. glabrata biofilms within 14 days. For C. tropicalis biofilm, caspofungin lock achieved eradication more rapidly than amphotericin B and three azoles. Our study suggests that azoles may be useful ALT agents in the treatment of catheter-related candidemia.
Amphotericin B/administration & dosage/pharmacology ; Antifungal Agents/*administration & dosage/pharmacology/therapeutic use ; Biofilms/*drug effects ; Candida albicans/*drug effects/physiology ; Candida glabrata/*drug effects/physiology ; Candida tropicalis/*drug effects/physiology ; Candidiasis/drug therapy ; Catheter-Related Infections/drug therapy ; Catheterization, Central Venous ; Drug Administration Routes ; Echinocandins/administration & dosage/pharmacology ; Fluconazole/administration & dosage/pharmacology ; Humans ; Itraconazole/administration & dosage/pharmacology ; Microbial Sensitivity Tests ; Pyrimidines/administration & dosage/pharmacology ; Triazoles/administration & dosage/pharmacology