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    28 August 2022, Volume 17 Issue 4
    Original articles
    Influence of CHK1 gene on ultrastrcture and fIuconazole susceptibility of Candida albicans
    HUANG Yue, CAI Liangqi, ZHANG Ziping, CHENG Bo
    2022, 17(4):  265-268,288. 
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    Objective To explore the influence of CHK1 gene on ultrastructure of Candida albicans and the susceptibility with fIuconazole. Methods Ultrastructure of Candida albicans in CHK21 group(chk1/chk1 double mutant) and CAF-2 group were observed under scanning electronmicroscope(SEM) and transmission electron microscope(TEM). We also compare the susceptibility with fluconazole of two strains. Result Under scanning electron microscope, two groups of cells appeared round or ellipse with the CHK21 showed rough and uneven surface while CAF-2 cells appeared smooth with much more budding scars. Under transmission electron microscope,the walls of CHK21 showed the electron dense layers disappeared somewhere. In contrast CAF-2 cells wall were integrity. The MIC of CAF-2 and CHK21 with fluconazole were 1ug/mL、0.125~0.25ug/mL respectly. Conclusion CHK1 gene may regulate the biosynthesis of cell wall in Candida albicans and they may also play a role in the susceptibility of C.albicans with fiuconazole.
    Clinical data and drug susceptibilities of Cryptococcus neoformans infection cases in a hospital in recent 5 years in Chongqing
    ZHANG Chuanming, DAI Wei, NIU Siqiang, XU Xiuyu
    2022, 17(4):  269-272,293. 
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    Objective To investigate the infection type, treatment regimen, prognosis and drug susceptibility of Cryptococcus neoformans infection (CNI) in Chongqing area. Methods The clinical data of patients with CNI and the susceptibility of Cryptococcus neoformans isolates to 6 antifungal agents in our hospital in recent 5 years were analyzed retrospectively. Results A total of 47 cases with CNI were enrolled. Cryptococcal meningitis (72.3%) was the main type of Cryptococcus neoformans infection in our hospital, 78.7% of the patients were male, and most of the patients were non-HIV infection. In addition, 17.1% of the patients were diagnosed with cryptococcal pneumonia. Cryptococcal capsular polysaccharide antigen in serum and/or cerebrospinal fluid was assayed for 37 patients, and the positive rate was 100%. All strains were wild-type to itraconazole and voriconazole, more than 90% of strains were wild-type to 5-flucytosine and posaconazole, and 85.1% of strains were wild-type to fluconazole, but only 53.2% of strains were wild-type to amphotericin B. Good prognosis after antifungal treatment achieved in 78.0% patients. But only 16.7% of the untreated patients had a good prognosis. Conclusion Timely detection of cryptococcal capsular polysaccharide antigen can improve the diagnostic accuracy and positive rate of Cryptococcus neoformans infection. Drug susceptibility testing is also necessary after Cryptococcus neoformans was isolated. According to the Results of drug susceptibility testing, early combination therapy plays an important role in improving the prognosis of patients.
    Analysis of clinical characteristics and risk factors of nosocomial fungal urinary tract infection in ICU
    ZHU Junfeng, ZHOU Ziyang, HU Wangchao, TANG Jianguo
    2022, 17(4):  273-277. 
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    Objective To investigate the clinical characteristics and risk factors of nosocomial fungal urinary tract infection in ICU. Methods The clinical data of patients with fungal urinary tract infection in the ICU of Shanghai Fifth People's Hospital affiliated to Fudan University from January 2016 to December 2020 were retrospectively analyzed, and the clinical characteristics and risk factors of the patients were described. Results ①From 2016 to 2020, a total of 2557 patients were enrolled in the intensive care unit of Shanghai Fifth People's Hospital Affiliated to Fudan University, and 130 patients met the research conditions. The incidence of fungal urinary tract infection was 5.1%. ②The clinical manifestations of nosocomial fungal urinary tract infection in ICU were atypical, and its occurrence was related to gender, age, and catheter indwelling time, but not to the year.③In the urine culture, Candida albicans was the main pathogen, accounting for 42.5%, followed by Candida glabra (31.3%), Candida tropicalis (19.4), Candida parapsilosis (4.5%), and other Candida (2.2%).④The risk factors of nosocomial fungal urinary tract infection in ICU were analyzed. Univariate analysis showed that diabetes, primary disease stroke, antibiotics, preinfection white blood cell count and preinfection enema had statistical significance (P<0.05).The significant indicators from univariate analysis were incorporated into the multivariate analysis. The Results showed that diabetes mellitus (P<0.001,OR=5.488), primary disease stroke (P=0.009,OR=2.782), preinfection white blood cell count (P=0.014,OR=3.515) and preinfection enema (P=0.001,OR=3.567) were independent risk factors for nosocomial fungal urinary tract infection in ICU. Conclusion For the nosocomial fungal urinary tract infection in ICU, we should take active measures to treat the primary disease and the basic disease, and at the same time, we should be alert to the enterogenous pollution caused by enema.
    Amphotericin B in the treatment of AIDS with cryptococcal meningitis clinical features, diagnosis and treatment of 40 cases
    HUO Qin, LIU Min, YANG Honghong, LIU Qian, WU Yushan, LI Mingjun, SHI Feng, HE Kun
    2022, 17(4):  278-282. 
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    Objective To analyze the clinical characteristics and adverse events of amphotericin B in the treatment of AIDS patients with cryptococcal meningitis, and to find out the factors risk adverse events, so as to provide reference for clinical practice. Methods The basic data of hospitalized AIDS patients with cryptococcal meningitis diagnosed in our hospital from January 2017 to December 2018 were retrospectively analyzed. The Results of laboratory examination, drug treatment plan and adverse events were collected and analyzed. Results The average age of 40 AIDS patients with cryptococcal meningitis was (40.54±15.42) years, the length of stay was (32.67±12.22) d, 30 cases (75%) were elevated intracranial pressure, 37 cases (92.5%) were positive for Cryptococcal neoformans antigen, 92.5% cases were positive for CSF culture, 31 cases (77.5%) were positive for CSF culture, and 92.5% cases were positive for ink smear in cerebrospinal fluid, respectively. Amphotericin B combined with fluorocytosine was selected as the treatment regimen in the induction period. During the treatment, the most adverse events were anemia in 22 cases (55.0%), followed by hypokalemia in 17 cases (42.5%); HGB and blood potassium indexes were significantly abnormal in the second week of drug use, and creatinine, total bilirubin and alanine aminotransferase indexes were significantly abnormal in the first week of drug use. The cumulative dose of amphotericin B > 500mg and HGB < 110 g/L before treatment were the influencing factors leading to the treatment course <14 d, and the difference was statistically significant (P=0.001, P=0.006). Conclusion There are different adverse events in the treatment of AIDS and cryptococcal meningitis at different time points during the treatment of amphotericin B. The main influence factors are cumulative dosage and HGB level before treatment.
    Drug susceptibility and clinical analysis of Cryptococcus neoformans from patients with acquired immunodeficiency syndrome in Yunnan province
    GAO Li, ZHAO Ziyi, FAN Hongli, ZHANG Guixian, LI Zhenglun
    2022, 17(4):  283-288. 
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    Objective To investigate the distribution,drug resistance and clinical treatment effect of Cryptococcus neoformans(C. neoformans) isolated from patients with acquired immunodeficiency syndrom(AIDS) in Yunnan province. Methods A total of 424 strains of C. neoformans isolated from AIDS patients in Yunnan Infectious Diseases Hospital from January 2010 to December 2020 were identified by VITEK Compact automatic microorganism analyzer,and the sensitivity of 5 antifungal drugs was detected by ATB FUNGUS 3.The clinical data were alalyzed. Results The highest proportion of 424 strains of C. neoformans was detected in cerebrospinal fluid, 62.50%(265/424).Blood was the second,accounting for 30.90%(131/424).The third was sputum,accounting for 2.83%(12/424).The MIC for azole(except fluconazole) to C. neoformans was ≤ 2 μg/mL, the MIC for amphotericin B of polyene was ≤ 4 μg/mL, and the MIC for fluconazole and 5-fluorocytosine was ≤ 64 μg/mL. The sensitivity rate to amphotericin B, fluconazole and 5-fluorocytosine was 95.28%(404/424), 80.66%(342/424) and 75.71%(321/424),respectively.The epidemiologic cutoff value of 5-fluorocytosine and fluconazole was 16 μg/mL, and the ECV of amphotericin B itraconazole and voriconazole was 0.5 μg/mL. Conclusion Cryptococcus neoformances is more sensitive to amphotericin B, while fluconazole and 5-flucytosine have gradually emerged as non-sensitive strains in the clinical medication process for so many years, and the MIC range of itraconazole and voriconazole is ≤ 2 μg/mL. The Results of drug sensitivity test of C. neoformans provide reference for clinicians to select drugs.Combined amphotericin B with 5-fluorocytosine was the first choice of treatment of C. neoformans. Cryptococcus, as an important pathogenic fungus in clinic, should be valued highly by laboratory and clinic.
    Study on the antifungal activity of small G protein inhibitor CASIN in vitro
    CHAO Wen, DENG Zhongyu, GUO Shijin, GUO Yifan, YAN Lan, QIU Lijuan, LV Quanzhen
    2022, 17(4):  289-293. 
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    Objective In order to find antifungal compounds with new structure, the antifungal activity of small G protein inhibitors were tested in vitro. Methods Micro-dilution method was used to investigate the minimum inhibitory concentration (MIC) of different small G protein inhibitors against Candida. After that, the more active compounds were selected for the further antifungal spectrum determination. Time-growth curves and time-kill curves were used to investigate the effect of CASIN on the growth and proliferation of Candida albicans. Hyphae formation experiment was used to investigate the inhibitory effect of compound CASIN on the formation of Candida albicans hyphae. XTT was used to investigate the inhibitory effect of compound CASIN on the formation of Candida albicans biofilms. Results Among the investigated small G protein inhibitors, CASIN had the strongest in vitro antifungal activity. It also had a good inhibitory effect on Candida parapsilosis, Candida krusei, Candida tropicalis, and Candida glabrata with the MIC of 8-16 μg/mL. 16 μg/mL of CASIN could effectively inhibit the growth and proliferation of Candida albicans in YPD medium, and also exhibited fungicidal activity against Candida albicans in RPMI1640 medium. The hyphae formation of Candida albicans was significantly inhibited by 8 μg/mL of CASIN. 8 μg/mL of CASIN had an inhibition rate of more than 80% for the biofilms formation of Candida albicans. Conclusion CASIN, a small G protein inhibitor, has strong antifungal activity in vitro.
    Case reports
    Three cases of Trichophyton mentagrophytes infection among two girls and their mother
    YANG Sixuan, SHAN Baihui, LI Fuqiu
    2022, 17(4):  297-299,303. 
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    Case-1 was a 9-year-old girl with erythema, papules, scales and abscesses at the head for 1 month, having accepted a traditional incisional drainage 1 day ago. Case-2 was a 9-year-old girl with erythema for 2 weeks and pustules for 3 days at her nasal dorsum. Case-3 was a 38-year-old woman with erythema, scales and pruritus at her face for 1 week.Case-1 and Case-2 are twins and Case-3 is their mother. The pathogenic strains of them were identified as Trichophyton mentagrophytes. Case one had close contact with an ill stray cat. The lesion of Case-1 was improved by oral methylprednisolone tablets, oral administration of itraconazole, and external application of ketoconazole lotion. Case-2 and Case-3 were cured after external application of luliconazole without cicatrization. The three patients are still being followed-up.
    A case report: treatment of pulmonary Rhizopus infection by bronchoscopic local infusion of amphotericin B combined with argon knife
    YANG Zhipeng, LIU Chun, LIU Caihong, LIU Jianming, XIE Lihua
    2022, 17(4):  300-303. 
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    This paper reports a case of pulmonary Rhizopus microsporus infection after haematopoietic stem cell transplantation treated by transbronchoscopic local instillation of amphotericin B combined with argon knife technique. The patient was diagnosed with hepatitis-associated severe aplastic anaemia and presented with high fever, cough, sputum and shortness of breath after peripheral blood stem cell transplantation. Imaging showed infectious lesions and partial solidity in both lungs with bilateral pleural effusion and partial swelling of both lower lungs. The pathology and second-generation gene sequencing confirmed the infection as Rhizopus microsporus, which was successfully cured by bronchoscopic treatment with a total of 16 precise instillations of amphotericin B in the right main bronchus and right lower basal segment.
    A case of hyalohyphomycosis caused by Penicillium citrinum and review of the literature
    SHI Haiyan, CHEN Mei, ZHANG Li, SUN Yi, ZENG Tongxiang, LIU Bing, ZHANG Qiuqiu
    2022, 17(4):  304-307. 
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    To report a case of hyalohyphomycosis caused by Penicillium citrinum, and to carry on the review to the related literature. A 55-year-old female was admitted to the hospital due to plaque and nodules on her left forearm for more than 4 months. Fungal fluorescence microscopy of the scrapings from the surface of the lesions was performed, little hyphae were visible by direct fluoroscopic ophthalmoscopy. The biopsies were surgically removed along with pathological examination, bacterial culture, and fungal culture. Histopathological results indicated that there were hyphae and spores in the infected granuloma after PAS staining. Fungal DNA derived from biopsy tissue and DNA derived from formalin fixed paraffin embedded tissues were both amplified and identified as P. citrinum by sequencing alignment analysis, which was consistent with morphological identification. A checkerboard microdilution assay was performed to measure the MIC value of itraconazole as a single agent was 0.5μg/mL.It was diagnosed as hyalohyphomycosis caused by P. citrinum, which was significantly improved by giving itraconazole 200 mg/d orally for 1 month.
    Atrophic cutaneous sporotrichosis: a case report
    LI Xiangjun, MU Yueming, CHUI Yan, TIAN Yaping
    2022, 17(4):  308-310,323. 
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    A male of 50 years old presented cluster-distributed atrophic patches and papules in the left anterior chest for one and a half years. Herpes zoster was previously diagnosed in the local hospital, but the condition did not improve after intermittent treatment. Dermatological examination of the left anterior chest showed atrophic dark red spots, dark red papules with the size of rice grains to soybeans. Histopathological examination of skin lesions showed that acanthal thickening, dermal lymphocyte and plasma cell infiltration,suggesting inflammatory granuloma changes. Periodic Acid-Schiff stain showed round spores. Dark brown villous colonies of skin lesions were cultured in Schaefer's medium. The mycelia and conidia of elongated segregated branches were observed by agar culture and lactic acid phenol-cotton stain. According to its phenotypic characteristics, it was identified as Sporothrix schenckii sensu lato, which is identifitied as sporothrix globosa by DNA sequencing. The diagnosis was sporotrichosis. Treatment:Oral itraconazole 200 mg/d treatment for 4 months, medication continued until the rash symptoms disappeared for 2 to 4 weeks, there was no recurrence after 6 months follow-up".
    A case of diabetic ketoacidosis complicated with acute explosive rhino-orbital-cerebral Aspergillus infection
    Li Bozhi, Cao Xia, Guo Hongwei, Hu Huaiqiang, Cao Bingzhen
    2022, 17(4):  311-314. 
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    A 24-year-old male patient was admitted with headache, runny nose for 3 days and abdominal pain for 1 day. During this period, the symptoms were acutely aggravated, including hemiplegia of the left limb and blindness of the right eye. After physical examination, imaging and pathology, it was definitely diagnosed as acute explosive rhino-orbital-cerebral Aspergillus infection. After treatment with minocycline hydrochloride combined with caspofungin, the symptoms were controlled and craniotomy was performed at a later time. One year follow-up after the onset of the disease, the patient was lying in bed with hemiplegia, and the right eye vision had light perception, and the overall condition was stable.
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