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    28 December 2022, Volume 17 Issue 6
    Original articles
    Study on the activity and mechanism of linalool against Trichophyton rubrum in vitro
    CHENG Fu, ZHANG Qiuhan, TANG Xiaolian, WANG Wanneng
    2022, 17(6):  441-447. 
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    Objective The purpose of the research is to explore the effect and mechanism of linalool against Trichophyton rubrum. Methods The modified CLSI M38-A2 method was used to determine the minimum inhibitory concentration of linalool against Trichophyton rubrum. The effect of alcohol on the cell membrane of Trichophyton rubrum, and the effect of linalool on the synthesis of ergosterol in Trichophyton rubrum was analyzed by UV spectrophotometry. The change of microstructure of Trichophyton rubrum after linalool was observed by transmission electron microscope. To evaluate the therapeutic effect of linalool on dermatophytosis by constructing a guinea pig model infected with Trichophyton rubrum. Results The minimum inhibitory concentration of linalool against Trichophyton rubrum was 320 μg·mL-1; linalool could inhibit the spore germination and the radial growth of hyphae of Trichophyton rubrum, increase the cell membrane permeability and inhibit the synthesis of ergosterol in cell membranes. Microscopic observations revealed that the cell wall was degraded, the surface was blurred, the inner cell membrane shrunken, and the cell contents leaked. Animal experiments showed that linalool could significantly control the process of dermatophytosis and improve the degree of tissue damage in guinea pigs. Conclusion Linalool has the activity of inhibiting Trichophyton rubrum. It inhibits the growth of Trichophyton rubrum by inhibiting its spore germination, mycelial growth, degrading the cell wall, destroying the integrity of the cell membrane and inhibiting the synthesis of ergosterol.
    Analysis of clinical features of pseudohyperaldosteronism induced by posaconazole
    WANG Chunjiang, SUN Wei, WU Cuifang, LIU Shikun, LI Zuojun
    2022, 17(6):  448-453,466. 
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    Objective To understand the clinical features of posaconazole-induced pseudoaldosteronism (PIPH). Methods We searched Chinese and English databases (as of 2021.6), collected case reports of PIPH, extracted patient-related information, and performed descriptive statistical analysis. Results A total of 12 case reports of posaconazole-induced pseudoaldosteronism were retrieved, involving 32 patients (18 males and 14 females), with a median age of 58 years (6-87). Nine patients used posaconazole mainly for the prevention of invasive fungal diseases, and 23 patients were mainly used for the treatment of invasive fungal diseases (12 cases of coccidioidomycosis, 4 cases of mucor, 3 cases of histoplasmosis, 1 case of aspergillus, 1 case of sporotrichosis). The median time of occurrence of pseudo-aldosteronism was 14 weeks (1.4-225). Only 4 patients developed clinical symptoms (flushing, headache, gynecomastia, fatigue, polyuria, edema). The median plasma concentration of posaconazole was 3.80 μg/mL (0.03-6.4). Nineteen patients had systolic blood pressure >140 mmHg, 15 patients had serum potassium <3.5 mmol/L, and 26 patients had elevated 11-deoxycortisol, 2 patients were normal; 30 patients had reduced or undetectable aldosterone levels; 19 patients had reduced or undetectable renin, 11 patients had renin at the lower limit of normal. After the occurrence of pseudo-aldosteronism, 15 patients discontinued posaconazole or reduced the dose in 14 patients, and continued treatment in 3 patients. Three patients were added with spironolactone, and 7 patients were replaced with other antifungal drugs. After discontinuing posaconazole or reducing the dose, the patient's blood pressure and serum potassium were improved compared with before, and the laboratory indicators gradually returned to normal. Conclusion PIPH can be manifested as hypertension and hypokalemia, 11-deoxycortisol is increased, aldosterone and renin are decreased or undetectable, and the serum concentration of posaconazole is increased. Patients receiving posaconazole treatment should be screened for hypertension and hypokalemia. If abnormalities are found, further endocrine evaluation should be performed.
    The real-time PCR of fungal pathogens in bronchoalveolar lavage fluid for the diagnosis of pulmonary fungal diseases in non-neutropenic elderly patients
    MENG Xingye, LIU Xiao, WAN Zhe, CHEN Wei, QUE Chengli, LIN Lianjun, YU Jin, SONG Yinggai, LI Ruoyu
    2022, 17(6):  454-460. 
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    Objective To evaluate the diagnostic accuracy of an in-house real-time PCR assay of fungal pathogens performed in bronchoalveolar lavage fluid (BALF) for diagnosing pulmonary fungal diseases in non-neutropenic elderly patients. Methods This one-year (2020-2021) retrospective study included 294 elderly patients suspected pulmonary infection who underwent bronchoscopy (BALF n=325) at Peking University First Hospital. All BALF samples tested with the real-time PCR of fungal pathogens, which covered the Aspergillus, Mucorales, Cryptococcus and Pneumocystis jirovecii and five species of Aspergillus (A. fumigatus, A. flavus, A.terreus, A. niger and A.nidulans). Twenty-seven patients had proven/probable invasive pulmonary fungal diseases, among which 7(25.9%) patients had more than one fungal pathogen. Six patients had chronic pulmonary aspergillosis. Results The area under the receiver operating characteristic curve of Aspergillus PCR cycle threshold (Ct) value was 0.936 (95% confidence interval 0.865-1.000), and the optimal cut-off value was 34.8 which yielded 95.7% sensitivity and 92.1% specificity for aspergillosis. Pneumocystis jirovecii PCR yielded 94.7% sensitivity and 99.7% specificity at the cut-off Ct value of 37.1. With cut-off Ct value 35.0, the positive rates of Cryptococcus and Mucorales PCR were 50%(2/4) and 100%(1/1) in pulmonary cryptococcosis and mucormycosis respectively. Collectively, when positive results defined by the pathogens detected by real-time PCR were consistent with the final diagnosis, the sensitivity specificity, positive and negative predictive value of PCR was 86.5%(32/37), 91.0%(253/278), 56.1%(32/57) and 98.1%(253/258), and the agreement rate was 91.4%. Conclusions The real-time PCR of fungal pathogens covers the most common pathogens of pulmonary fungal infection and is highly specific and sensitive for the diagnosis of pulmonary fungal diseases in non-neutropenic elderly patients with the cut-off value preliminarily explored in our study.
    Clinical characteristics and prognosis of 44 patients with Talaromyces marneffei infection
    QIU Fulan, QIU Shusheng, LIN Yanqing, LIU Hui, ZHONG Rongrong
    2022, 17(6):  461-466. 
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    Objective To understand the clinical features and prognosis of patients with Talaromyces marneffei infection in Longyan, Fujian Province, and provide evidence for early identification and effective treatment of the disease. Methods The data of 44 patients with Talaromyces marneffei infection treated in Longyan first hospital and Longyan Second Hospital Affiliated to Fujian Medical University from January 2017 to November 2021 were collected. It includes general data, clinical manifestations, laboratory examination results, imaging changes, strain identification, drug sensitivity test, treatment and prognosis. Comparison between the two groups by χ2 test or Mann Whitney U test was made. Results Among the 44 patients, 22 were HIV positive and 22 were HIV negative. The significant differences were existed in onset age, clinical symptoms, WBC, CD4+T lymphocytes, HB, PLT, AST, ALT, ALB and PCT between the two groups. The CD4+T lymphocytes of 95.4% AIDS combined with TSM patients was less than 50/μL. The HIV positive group was dominated by disseminated TSM, while the HIV negative group was localized TSM. The positive rates of serum G test and GM test to HIV positive TSM were 81.8% and 70.7%, while they were 18.2% and 9.1% in HIV negative TSM. The MIC values of posaconazole, itraconazole, voriconazole and amphotericin B were lower, and MICs of echinocandins and fluconazole were higher in 12 TM strains. The mortality of Talaromycesis marneffii infection was 45.5%. Conclusion There is no specificity in clinical symptoms and imaging results of TSM patients, so relevant etiological examination should be carried out as soon as possible. G and GM tests have early diagnostic values for AIDS patients with TSM. Timely use of antifungal therapy is of great significance in reducing mortality.
    Clinical characteristics and drug resistance analysis of candidemia in children
    ZHANG Lingling, LIU Quanbo
    2022, 17(6):  467-471,481. 
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    Objective To investigate the clinical characteristics of children with candidemia, and provide clinical experience for the diagnosis and treatment of candidemia. Methods A retrospective analysis was carried out to analysis the Candida isolates from blood from the Children's Hospital of Chongqing Medical University from January 2014 to December 2020,and they were divided into Candida albicans and non-albicans Candida, the differences in clinical characteristics between the two groups were compared. Results A total of 124 cases were enrolled, these patients mainly came from the department of neonatology, the department of hematologic oncology and the department of ICU. Candida albicans (61cases, 49.2%) had the highest detection rate, followed by Candida parapsilosis (26 cases, 21.0%) and Candida tropicalis (14 cases, 11.3%). The resistance rates of Candida to itraconazole, voriconazole and fluconazole were 16.5%, 12.6% and 11.6% respectively. Compared with Candida albicans, the non-albicansCandida had higher infection rate in tumorous diseases and bone marrow suppression after chemotherapy(P<0.05). Those who used β-lactams and enzyme inhibitors, intravenous catheters, and intravenous nutrition were susceptible to Candida albicans, and those who used immunosuppressive agents and neutropenia were susceptible to non-albicans Candida (P<0.05). The incidence of C-reactive protein >8mg/L,white blood cell ≥ 10×109/L and neutrophilic granulocyte percent > 80% in Candida albicans was higher than that in non-albicans Candida,and the rate of sepsis and resistance to amphotericin B in non-albicans Candida was higher than that in Candida albicans (P<0.05). Conclusion Candidemia had serious underlying diseases, complex risk factors, atypical clinical manifestations, which was not conducive to early diagnosis, and was easy to missed diagnose and misdiagnose. Therefore, for children with high-risk factors and when the clinical anti-infection treatment is not effective, it is necessary to be alert to the possibility of candidemia, and relevant examinations should be improved in time for early diagnosis.
    Clinical characteristics and drug resistance analysis of 232 cases of Candida tropicalis infections
    ZHAO Xuchu, HU Ailing, WANG Dong, HENG Yuan, WANG Na
    2022, 17(6):  472-475,489. 
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    Objective To study and analyze the clinical distribution and drug resistance characteristics of Candida tropicalis in our hospital,and to provide reference for clinical prevention and treatment of C. tropicalis infection. Methods The clinical data of patients with C.tropicalis infection in the first hospital of Qinhuangdao from January 2018 to December 2021 were analyzed retrospectively. Results A total of 232 strains of C.tropicalis were collected, and the samples were mainly urine samples (134 strains, accounting for 57.8%),including 156 males and 76 females, with an average age of 68.5±16.5 years; The main sources of departments were intensive care units(102 strains), respiratory department(39 strains)and nephrology department (14 strains). And the Candida tropicalis infection in the top three departments accounted for 66.8%; The results of drug sensitivity test showed that the isolated Candida tropicalis strains were completely sensitive to 5-fluorocytosine and amphotericin B. The resistance rates to fluconazole, itraconazole and voriconazole were 41.3%, 44.9% and 42.7% respectively, and the sensitivity rate to itraconazole was the lowest, 30.7%.And resistance to voriconazole was most pronounced in surgical wards and intensive care units. According to the statistics on the change trend of drug resistance of commonly used antibiotics in clinic, the drug resistance rates of C.tropicalis to fluconazole, itraconazole and voriconazole had been very high from 2018 to 2020, and the drug resistance rate decreased significantly in 2021. Conclusion The drug resistance of C.tropicalis in our hospital has improved significantly from 2021, which is closely related to the strengthening of the control of antibiotic use in clinical departments. Therefore, in order to reduce or delay the emergence of drug-resistant strains and prevent the outbreak of drug-resistant fungal infection.We should continue to strengthen the control.
    Clinical value of (1,3)-β-D-glucan levels in diagnosis and prognosis of AIDS patients complicated with Pneumocystis pneumonia
    LAN Huihui, CHEN Tao, JIANG Zhongsheng, LI Minji, QIN Jinyu, MO Shenglin, MENG Dali, TANG Gui
    2022, 17(6):  476-481. 
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    Objective To evaluate the clinical value of level of the plasma(1,3)-β-D-glucan in diagnosis and prognosis of the acquired immune deficiency syndrome(AIDS) patients complicated with Pneumocystis pneumonia(PCP).Methods A retrospective analysis of 110 AIDS patients who were hospitalized to Liuzhou People's Hospital from January 2012 to January 2021, 55 patients who were clinically diagnosed with PCP were assigned as the observationg, while 55 patients with non-opportunistic infections were set as the control group. The observation group was further divided into improvement group (31 cases) and death group (24 cases). The plasma levels of (1,3)-β-D-glucan were compared. The clinical diagnosis and prognosis values of (1,3)-β-D-glucan for PCP AIDS patients with PCP were evaluated by ROC curve.Results (1,3)-β-D-glucan level in control group was lower than that in observation group[9.00(4.00,56.95) pg/mL vs. 182.50(100.60,355.00) pg/mL], improvement group(baseline) was lower than death group(baseline)[115.20(92.40,198.20) pg/mL vs. 360.70(253.50,523.20) pg/mL], improvement group(baseline) was higher than post-treatment (4 weeks) group[115.20(92.40,198.20) pg/mL vs. 34.39(10.00,81.45) pg/mL], death group(baseline) was lower than post-treatment (at death) group[360.70(253.50,523.20) pg/mL vs. 550.90(369.48,631.30) pg/mL]. The positive rate of (1,3)-β-D-glucan in control group was lower than that in observation group[21.82%% vs. 92.73%], the positive rate of (1,3)-β-D-glucan in improvement group(baseline) was higher than that in post-treatment (4 weeks) group[87.10% vs. 25.81%]. When (1,3)-β-D-glucan ≥ 77.65pg/mL,the sensitivity、specificity、positive predictive value and negative value for diagnosis of PCP were 89.09%、87.27%、87.50% and 88.89% respectively. When (1,3)-β-D-glucan ≥ 247.95 pg/mL,the sensitivity、specificity、positive predictive value and negative value for predicting the prognosis of PCP were 79.17%、93.55%、90.48% and 85.29% respectively.Conclusion Plasma (1,3)-β-D-glucan levels can be used as an early diagnostic marker of PCP and to predict the clinical outcome of patients.
    Case reports
    A case of Aspergillus fumigatus endocarditis
    ZHOU Chen, LU Jiajie
    2022, 17(6):  486-489. 
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    Aspergillus fumigatus infective endocarditis was characterized as difficult in diagnosis and with high mortality and poor prognosis. We reported a case of infective endocarditis, identified by next-generation metagenomic sequencing (mNGS) as Aspergillus fumigatus. The patient was treated with voriconazole and therapeutic drug monitoring (TDM) was performed to ensure efficacy and safety. Being conbined with surgical treatment, the patient got better and was discharged. Therefore, mNGS played an important role in the diagnosis of endocarditis caused by Aspergillus infection. Adjusting the dose of voriconazole by TDM can not only ensure the curative effect, but also reduce the occurrence of adverse reactions, providing a safe and effective treatment choice of Aspergillus fumigatus infective endocarditis.
    Neonatal leukemic reaction caused by umbilical phlebitisof Candida albicans in premature infants: two case reports
    HAO Dongjie, QIAN Yaqi, LI Aiyun
    2022, 17(6):  490-494. 
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    Candida albicans was the most common pathogenic fungus in obstetrics and gynecology. This paper retrospectively analyzed two pregnancy women with vaginal Candida albicans infection. Then C.albicans caused infection of the placenta and umbilical, and lead to fetal preterm delivery and neonatal leukemic reaction in premature infants. This article analyzed the causes and coping strategies, so as to provide reference for clinical prevention and treatment.
    Tinea capitis in a child and tinea corporis in the mother caused by Microsporum canis
    GAO Qiaoli, XIONG Mei, LUO Zhicheng
    2022, 17(6):  495-497. 
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    A 2-year-old girl presented with scalp erythema, papules, scales and alopecia for 4 months. The child's mother was 29 years old and had scaly erythema with itching on the back for 2 weeks. Microscopic examination and culture of broken hair of the child and the mother's back sample were positive. Molecular biological identification showed that both strains were Microsporum canis with 100% homology. Oral itraconazole capsule 0.06g/d, external application of luiconazole and compound ketoconazole cream, and ketoconazole lotion were selected for the treatment of the child. After a total course of 2 months, the child's skin lesions subsided, and the broken hair regrew. Microscopy and culture were negative. The mother was treated with external use of luiconazole and compound ketoconazole cream. The skin lesions on the back subsided after 3 weeks, and the microscopic examination of fungi was negative. There was no recurrence of skin lesions in the child and her mother during a year follow-up.
    Stephanoascus ciferrii isolated from ear secretion in one patient with middle ear cholesteatoma
    CHENG Zhi, YANG Ming, CHEN Jingwen, DONG Ke
    2022, 17(6):  498-499,507. 
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    A 38-year-old female patient had left ear abscess 10 years ago without obvious cause. She felt hearing loss in the left ear for one month, and was admitted to hospital for diagnosis of "middle ear cholesteatoma (double)". Then Stephanoascus ciferrii isolated from her left ear secretion. A combined approach typanoplasty was performed on her left ear on April 22, 2021,the operation was successful and fluconazole was given,postoperative recovery was well.
    Positive Malassezia hyphae in lesions in one patient with lichen planopilaris
    LI Juanjuan, SHI Dongmei
    2022, 17(6):  500-502. 
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    A 14-year-old male presented with erythema and irregular hair loss lesions on the scalp for over 2 years, aggravated for 6 months. A large number of sausages-like Malassezia hyphae were found under fungal fluorescence microscope. The isolate was identified as Malasseziaglobosa by ITS sequencing. Histopathological examination showed reticular keratosis of epidermis; the melanophagocytes were observed in the superficial dermis; the follicular units disappeared and sebaceous glands reduced in superficial and deep dermis; lymphocytes infiltrated around remaining subcutaneous appendages; collagen hyperplasia could be seen in the deep dermis. The diagnosis of lichen planopilaris was made based on the clinical and pathological feature. The patient was given oral itraconazole capsule combined with topical ketoconazole lotion. The hair loss stopped accompanied with the disappear of fungal hyphae after two weeks of treatment.
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