Objective: This study aimed to evaluate the epidemiological, clinical and mycological characteristics of invasive candidiasis (IC) in China. Methods: A ten-year retrospective study including 183 IC episodes was conducted in a tertiary hospital in Beijing, China. Results: The overall incidence of IC from 2010-2019 was 0.261 episodes per 1,000 discharges. Candidemia (71.0%) was the major infective pattern; 70.3% of the patients tested positive for Conclusion The incidence of IC has declined in the recent five years.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antifungal Agents/pharmacology* ; Candidiasis, Invasive/microbiology* ; Child ; Child, Preschool ; China/epidemiology* ; Drug Resistance, Fungal ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Retrospective Studies ; Tertiary Care Centers/statistics & numerical data* ; Young Adult

OBJECTIVE: To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid (BDSF) and fluconazole (FLU) or itraconazole (ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo. METHODS: Minimum inhibitory concentrations (MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS: BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ⪕ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qRT-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mRNA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis. CONCLUSION The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.
Antifungal Agents ; pharmacology ; Burkholderia cenocepacia ; chemistry ; Candida albicans ; drug effects ; physiology ; Candidiasis ; drug therapy ; Drug Resistance, Fungal ; Fatty Acids, Monounsaturated ; adverse effects ; Fluconazole ; pharmacology ; Humans ; Microbial Sensitivity Tests ; Triazoles ; metabolism

Antifungal drug resistance is a significant clinical problem, and antifungal agents that can evade resistance are urgently needed. In infective niches, resistant organisms often co-existed with sensitive ones, or a subpopulation of antibiotic-susceptible organisms may evolve into resistant ones during antibiotic treatment and eventually dominate the whole population. In this study, we established a co-culture assay in which an azole-resistant Candida albicans strain was mixed with a susceptible strain labeled with green fluorescent protein to mimic in vivo conditions and screen for antifungal drugs. Fluconazole was used as a positive control to verify the validity of this co-culture assay. Five natural molecules exhibited antifungal activity against both susceptible and resistant C. albicans. Two of these compounds, retigeric acid B (RAB) and riccardin D (RD), preferentially inhibited C. albicans strains in which the efflux pump MDR1 was activated. This selectivity was attributed to greater intracellular accumulation of the drugs in the resistant strains. Changes in sterol and lipid compositions were observed in the resistant strains compared to the susceptible strain, and might increase cell permeability to RAB and RD. In addition, RAB and RD interfered with the sterol pathway, further aggregating the decrease in ergosterol in the sterol synthesis pathway in the MDR1-activated strains. Our findings here provide an alternative for combating resistant pathogenic fungi.
ATP-Binding Cassette Transporters ; genetics ; metabolism ; Antifungal Agents ; chemistry ; metabolism ; pharmacology ; Azoles ; pharmacology ; Biosynthetic Pathways ; drug effects ; genetics ; Candida albicans ; chemistry ; drug effects ; metabolism ; Cell Membrane ; chemistry ; metabolism ; Coculture Techniques ; Drug Resistance, Fungal ; drug effects ; Ergosterol ; metabolism ; Fungal Proteins ; genetics ; metabolism ; Lipids ; chemistry ; Molecular Structure ; Permeability ; Phenyl Ethers ; chemistry ; metabolism ; pharmacology ; Sterols ; chemistry ; metabolism ; Stilbenes ; chemistry ; metabolism ; pharmacology ; Triterpenes ; chemistry ; metabolism ; pharmacology

Cross Infection ; microbiology ; therapy ; Drug Resistance, Multiple, Fungal ; Fungi ; classification ; drug effects ; isolation & purification ; Humans ; Mycoses ; microbiology ; therapy ; Patient Care Management ; methods ; Singapore

Adult ; Aged ; Antifungal Agents ; administration & dosage ; adverse effects ; classification ; Candida ; drug effects ; isolation & purification ; Carcinoma ; pathology ; therapy ; Cross Infection ; microbiology ; therapy ; Drug Resistance, Multiple, Fungal ; Female ; Fractures, Bone ; surgery ; Humans ; Male ; Middle Aged ; Mycoses ; microbiology ; therapy ; Patient Care Management ; methods ; Pulmonary Disease, Chronic Obstructive ; complications ; therapy ; Surgical Wound Infection ; microbiology ; therapy ; Symptom Flare Up ; Treatment Outcome

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.
Antifungal Agents ; Candida albicans ; Candida glabrata ; Candida tropicalis ; Candida* ; Candidemia* ; Danazol ; Drug Resistance, Fungal* ; Female ; Hospital Departments ; Humans ; Infant, Newborn ; Male ; Prevalence* ; Tertiary Healthcare*

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

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

Purpureocillium(P) lilacinum is a ubiquitous, saprophytic filamentous fungus that is infrequently reported in keratitis and cutaneous infections. However, the microbiological characterization of the culture isolates is limited in Korea. A 56-year-old male who suffered a pine needlestick to his right eye 10 days previously presented with ocular opacity and pain. A microscopic examination of a corneal scraping by Gram staining and calcofluor white staining was negative for bacteria and fungi. Fungal culture yielded pure white cottony molds on Sabouraud's dextrose agar after a 3-day incubation. Microscopic examination further revealed a mixture of a verticillate arrangement of phialides resembling the Penicillium structure and sparsely branched conidiophores bearing single to small clusters of conidia. This was initially presumed to be a species of Penicillium but the colonies never turned green with further incubation. It was subsequently identified as P. lilacinum by 28S rDNA sequencing and MALDI-TOF mass spectrometry. Antifungal susceptibility test revealed that this organism was resistant to flucytosine, amphotericin B, fluconazole, itraconazole, voriconazole, and caspofungin. After treatment with topical 5% voriconazole and oral itrazonazole combined with multiple debridements for 2 weeks, the patient was discharged with improved visual acuity. We thus report the first case of P. lilacinum infection that required molecular identification due to mixed conidiogenesis features and that showed laboratory-confirmed antifungal resistance in Korea.
Agar ; Amphotericin B ; Bacteria ; Debridement ; DNA, Ribosomal ; Drug Resistance ; Fluconazole ; Flucytosine ; Fungi ; Glucose ; Humans ; Itraconazole ; Keratitis* ; Korea ; Male ; Mass Spectrometry ; Middle Aged ; Needlestick Injuries ; Penicillium ; Sequence Analysis, DNA ; Spores, Fungal ; Visual Acuity ; Voriconazole

OBJECTIVETo investigate the effects of ethyl acetate extract of Huanglian Jiedu decoction (EAHD) , alone and in combination with fluconazole (FLZ) on FLZ-resistant Candida albicans.

METHODThe minimum inhibitory concentrations (MIC) and sessile MIC80 (SMIC80) of EAHD and FLZ to FLZ-resistant C. albicans were determined by CLSI M27-A3 microdilution method, and the synergy of EAHD combined with FLZ were examined by the checkerboard microdilution assay. Agar plate-method was adopted to observe the rate of antifungal activity according to time-kill curve. HPLC and qRT-PCR were utilized to evaluate the changes of ergosterol content and expressions of related genes, respectively.

RESULTMICs of EAHD ranged from 156 to 1,250 mg · L(-1), those of FLZ from 256 to above 2,048 mg · L(-1) with FICI approximate 0.066 in combination; SMIC80 of EAHD were higher than 1,250 mg · L(-1), SMIC80 of FLZ were higher than 512 mg · L(-1) and up to above 2,048 mg · L(-1). Combination group also showed synergy effect except one group showing addition effect. The results of T-K experiment also confirmed obviously fungicidal effect when treated for 12 h. When compared with control groups, the ergosterol was reduced 85% and 50% in the treatments of combination and EAHD alone by HPLC, respective- ly. The expressions of ERG1, ERG2, ERG6, ERG7 and ERG11 were upregulated, and ACS1, ACS2, MET6 were downregulated when exposed to FLZ. The expressions of the above genes were downregulated by treatment of EAHD. The expressions of ERG2, ERG6, ERG11 were upregulated, while ERG1, ERG7, ACS1, ACS2, MET6 were downregulated in combination group.

CONCLUSIONThe combination of EAHD and FLZ exhibited synergy against FLZ-resistant C. albicans through decreasing the synthesis of ergosterol, and resulting in the breakage of cell membrane.

Antifungal Agents ; pharmacology ; Candida albicans ; drug effects ; growth & development ; metabolism ; Drug Resistance, Fungal ; drug effects ; Drug Synergism ; Drugs, Chinese Herbal ; pharmacology ; Ergosterol ; biosynthesis ; Fluconazole ; pharmacology ; Microbial Sensitivity Tests