Table of Content

28 April 2023, Volume 18 Issue 2

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Original articles

Analysis of susceptibility factors forinfection with Talaromyces marneffei in non-HIV individuals

LI Tiantian, LI Bingkun, HUANG Xiaolu, LIAO Liuwei, JIANG Zhiwen, HE Xiaojuan, MO Nanfang, LI Xiuying, JIANG Li, PAN Kaisu, CAO Cunwei

2023, 18(2):  97-103,110. 

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Objective To analyze the immune-related susceptibility factors of Talaromyces marneffei infection (TSM) in non-HIV patients, so as to improve the understanding and management of this disease among clinicians. Methods The clinical characteristics of HIV-negative patients diagnosed with TSM from 2012 to 2021 in Guangxi and other provinces and cities in China collected by our group were prospectively studied to analyse their immune-related susceptibility factors. Results 154 patients were included, and immunodeficiency was detected in 132 cases. Primary immunodeficiency diseases predominated in pediatric patients; immunodeficiency syndrome associated with anti-interferon-gamma autoantibodies predominated in adult patients, and the remainder included co-morbid malignancies and underlying diseases such as connective tissue disease. Conclusion TSM can occur in non-HIV patients with different forms of immunodeficiency and a complete immune status assessment strategy based on susceptibility factors should be established to improve patient prognosis.

Analysis of clinical distribution and drug resistance of Candida in a hospital in Inner Mongolia from 2012 to 2021

LI Min, ZHAO Jianping, FENG Jiangtao

2023, 18(2):  104-110. 

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Objective To analyze the distribution and drug resistance of Candida in a hospital in Inner Mongolia from 2012 to 2021, so as to provide evidence for clinical management of Candida infection. Methods The distribution and drug susceptibility test results of Candida strains in a hospital from January 2012 to December 2021 were retrospectively analyzed. Results A total of 5472 strains of Candida were isolated. The samples were mainly from urine, sputum and secretions, accounting for 41.28%, 31.69% and 11.22%, respectively. The distribution of clinical departments was mainly from health ward, respiratory and critical care ward and ICU, accounting for 27.54%, 18.29% and 17.71%, respectively. The drug resistance rates of Candida albicans, C. tropicalis, C. paracalbicans, C. glabrata, C. nameless, C. krondo and C. Portugal to 5-flucytosine, amphotericin B, voriconazole, fluconazole and itraconazole were 0.14%-3.53%, 0.39%-22.41%, 0-2.82%, 0-12.5%, 0%, 0.53%-5.88%, 1.05%-57.895% and 0-12.22% respectively. The change of drug resistance of C. albicans was not obvious. Conclusions C. albicans had been the most common candida in our hospital from 2012 to 2021, but the proportion of C. albicans isolated in 2020 and 2021 showed a downward trend, while non-Candida albicans showed an upward trend. Among C. tropicalis isolated in our hospital, the resistance rate to triazole antifungal drugs was high in C.tropicalis, and the resistance rates to 5-flucytosine and itraconazole were the highest in C. kronoris except for the natural resistance to fluconazole, while the resistance rates of other Candida strains were low.

Clinical analysis of 3 casesof very preterm/extremely preterm infant with bloodstream infection caused by multi-drug resistant Candida haemulonii

ZHONG Meizhen, GUO Shaoqing, LI Xiaozhong, ZHU Bo

2023, 18(2):  111-116,134. 

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Objective To explore the clinical characteristics,treatment and prognosis of bloodstream infection caused by multi-drug resistant Candida haemulonii in premature infants. Methods The clinical data of premature infants with candidemia caused by multi-drug resistance Candida haemulonii in October 2017 were retrospectively analyzed, and the relevant literatures were reviewed. Results The gestational age of these three very preterm/extremely preterm infants was 25 weeks^{+ 1}, 30 weeks and 30 weeks, respectively. And the birth weight was 725 g, 1 000 g and 1 070 g, respectively. The time of infection was 45, 24, 28 days after hospitalization, respectively. All 3 cases had peripheral central venous catheterization(PICC). Broad-spectrum antibiotics were administered and low doses fluconazole was used to prevent fungal infection in all cases before candidemia occurred, The total of 4 strains of Candida haemulonii isolated from the blood cultures and 2 strains from the catheter were all resistant to fluconazole, amphotericin B, itraconazole, voriconazole and 5-fluorocytosine,but were sensitive to micafengin. Fluconazole and/or voriconazole did not improve the clinical condition of 3 patients, and finally they were treated with micafengin and recovered, without obvious side-effects about liver, kidney and blood. Conclusion It should be concerned vigilantly the occurrence of multi-drug resistant non-albicans candidemia in very preterm/extremely preterm infants with fluconazole for prevention of fungal infection. Micafungin is effective and tolerated in the treatment of multidrug-resistant Candida haemulonii bloodstream infection in premature infants.

Pharmacokinetic changes and influencing factors of amphotericin B in patients with severe invasive fungal infection

WANG Haofei, WANG Jinlong, HU Wenhan, SONG Qianwen, WU Changde, HE Jie, HU Linlin, XU Jingyuan, LI Qing, PAN Chun, XIE Jianfeng, HUANG Yingzi

2023, 18(2):  117-122. 

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Objective To investigate the PK characteristics and target value of deoxycholate amphotericin B in patients with severe invasive fungal infection and analyze the influencing factors of PK changes. Methods Patients with severe invasive fungal disease who were admitted to the Department of Critical Care Medicine of Zhongda Hospital Affiliated to Southeast University from November 2018 to November 2022 and received deoxycholate amphotericin B infusion therapy were selected. Amphotericin B was gradually accumulated from 1 mg/d to 50 mg/d, and was continuously pumped intravenously for 6 h. On the 7th and 14th day of administration, 2 mL of peripheral blood was collected every time before administration and at 1, 3,6,9 and 12 h after administration. The concentration of amphotericin B in plasma was determined by LC-MS/MS method. The PK characteristics of amphotericin B were observed and the influencing factors of PK changes were analyzed by linear regression method. Results A total of 12 patients with severe invasive fungal disease were included. Compared with the pharmacokinetic parameters of deoxycholate amphotericin B obtained in normal subjects, the trough concentration, CL, half-life (t_1/2), and AUC of amphotericin B in severe IFI patients were higher than those in healthy subjects (all P＜0.05 ), and its Cmax and Vd were higher. Univariate analysis showed that real-time APACHE II score may be the influencing factor of amphotericin B peak concentration (P=0.008). Conclusion The trough concentration, CL, half-life (t_1/2) and AUC of amphotericin B in patients with severe IFI were higher than those in healthy subjects, but there was no significant difference in Cmax between the two groups. Real-time APACHE II score might be the influencing factor of amphotericin B peak concentration. The faster cumulative acceleration of amphotericin B did not show a significant increase in the incidence of immediate adverse reactions, and there was a higher pharmacodynamic concentration.

Retrospective analysis of Kodamaea ohmeri infection in Asia from 2002 to 2022

ZHU Xinlin, LI Chen, HU Dongying, CHEN Xianzhen, JIANG Weiwei, LIU Yinuo, CHEN Tianyang, CHEN Tiancheng, LIAO Wanqing, LIU Xiaogang, PAN Weihua

2023, 18(2):  123-129. 

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Objective To analyze epidemiological trends and clinical characteristics of cases caused by Kodamaea ohmeri in Asia, and to provide a scientific basis for improving the clinical diagnosis and treatment of K. ohmeri infections. Methods Using the methods of literature review and meta-analysis to analyze retrospectively the information of patient’s nationality, sex and aged composition, risk factors, onset organs, clinical manifestations, therapeutic methods and prognosis of K. ohmeri. Results K. ohmeri infections could occur in both immunocompetent and immunocompromised person. The gender ratio of the infection host was 1.59:1, predominantly in premature neonate and middle aged people, and the blood system was the most commonly affected site. More than half of the patients had immunodeficiency diseases or other risk factors, and there were no early specific symptom with chief complaints of fever. Diagnosis of K. ohmeri infections mainly relied on culture. The patients had a poor prognosis, with high mortality. Conclusion The incidence of K. ohmeri infections has increased recently and the diagnosis mainly depends on culture. Strengthening the in vitro antifungal susceptibility monitoring and the studying of epidemiology for K. ohmeri are significant to improve the diagnosis and prognosis of K. ohmeri infections.

Clinical characteristics and risk factors for mortality of 94 patients with Candida bloodstream infection

ZHOU Tingting, QIN Renli, XU Qiuhong, LUO Liuchun

2023, 18(2):  130-134. 

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Objective To investigate the clinical distribution of 94 patients with blood flow infection of Candida and the related risk factors of death. Methods The clinical characteristics and death risk factors of patients with blood flow infection of Candida diagnosed in Liuzhou People's Hospital from January 2019 to December 2021 were analyzed retrospectively. Results From 2019 to 2021, 94 cases of Candida were detected in blood flow infection patients, mainly distributed in ICU and surgery, accounting for 58.5%; The top three Candida species were C. albicans, C. tropicalis and C. parapsilosis, accounting for 48.9%, 16.0% and 13.8% respectively;33 of 94 patients with blood flow infection of Candida died, the mortality rate was 35.1%. C. albicans (57.6%, 19/33) was most frequently detected in the dead patients, mainly distributed in ICU (57.6%, 19/33). The sensitivity rate of C. parapsilosis to azoles was 100%, the resistance rate of C. albicans to triazoles was less than 7% and the resistance rate of C. glabrata and C. tropicalis was 20%~26.7%. Univariate analysis showed that age ≥60 years, ≥2 basic diseases, mechanical ventilation and endotracheal intubation were associated with mortality (P<0.05). Logistic binary regression analysis showed that mechanical ventilation was an independent risk factor associated with mortality in patients with Candidal blood flow infection. Conclusion The detection rate of C. albicans in Candidal blood flow infection was the highest. Mechanical ventilation was an independent risk factor for death in patients with blood flow infection of Candida.

Clinical dosage regimens of fluconazole evaluated by Monte Carlo simulation in candidal urinary tract infection

ZHANG Mengxiang, XU Yuewei, YANG Manqin

2023, 18(2):  135-139. 

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Objective To provide reference for clinical individual medication of fluconazole by combining PK/PD and Monte Carlo simulation. Methods Candida albicans and Candida glabrata strains isolated from urine samples of patients with urinary tract infection in our hospital from January 2020 to December 2021 were collected. The distributions of MICs(minimum inhibitory concentrations,MICs) of fluconazole to Candida albicans and Candida glabrata were summarized as well as the pharmacokinetic parameters of fluconazole. Using probability of target attainment (probability of target attainment,PTA) and cumulative fraction of response(cumulative fraction of response,CFR)as indexes,crystal ball software 11.1.2.4 was used for Monte Carlo simulation of different dosage regimens. Results A total of 73 strains of Candida albicans and 108 strains of Candida glabrata were isolated (181 strains in total). The resistance rates to fluconazole were 12.3% and 57.4% respectively. The CFRs of 200 mg/d fluconazole for Candida albicans and Candida glabrata were both less than 90%(85.85% and 38.08% respectively). The CFR of 400 mg/d fluconazole for Candida albicans was more than 90%(90.15%), and that for Candida glabrata was less than 90%(45.54%). When the MICs of Candida albicans and Candida glabrata were ≤4 mg / L, the PTAs of 200 mg/d were greater than 90%; and when the MICs of Candida albicans and Candida glabrata were ≤8 mg / L, the PTAs of 400 mg/d were greater than 90%. Conclusions 400 mg/d fluconazole can be up to standard for urinary tract infection caused by Candida albicans infection,conversely, both 2 of dosage regimens can not be up to standard in Candida glabrata urinary tract infection. It is recommended to use other drugs recommended by relevant guidelines, such as amphotericin B.

Soluble expression and purification of caspase recruitment domain-containing protein 9

PENG Min, ZHANG Chen, WANG Jue, CHEN Hao, KONG Qingtao, SANG Hong

2023, 18(2):  140-145. 

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Objective The caspase recruitment domain-containing protein 9 (CARD9) mediates intracellular signaling by Toll-like and C-type lectin receptors, and plays a critical role in the regulation of fungal infection. Since it is insoluble, the in vitro expression of the complete sequence of CARD9 is currently not feasible; hence, its structure and function remain unclear. In this study, we constructed a prokaryotic systemic expression plasmid using molecular cloning techniques to produce the TrxA-CARD9 protein and its clinical mutant phenotype in vitro. Methods Screening with different isopropyl β-d-1-thiogalactopyranoside concentrations and temperatures led to the successful expression of soluble full-length CARD9. To increase the solubility of the target protein, arginine was used to assist its non-denaturing solubilization. After the removal of nucleic acids and partial heteroprotein using polyethyleneimine and ammonium sulfate precipitation, respectively, the fusion protein was purified using an anion-exchange and heparin affinity chromatography column. Results We successfully achieved highly soluble expression of full-length CARD9 sequence in a prokaryotic system and provided an optimized purification protocol. Conclusion This study provides a basis for future in vitro experiments studying the biological structure and function of CARD9 protein. It proposes a new research idea to find potential targets for the treatment of fungal infections and the treatment of critical fungal infections.

Case reports

Pulmonary infection and encephalopyosis induced by Scedosporium apiospermum:a case report and literatures review

CAO Ya, TAN Qingche, ZHANG Jiatang, ZHAO Hong, SU Min, MA Yubao, HE Mianwang, YANG Fei, YU Shengyuan

2023, 18(2):  146-150. 

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To reported one case of pulmonary infection and encephalopyosis caused by Scedosporium apiospermum, and to discuss the clinical features and the treatment. The patient’s broncholveolr lvge fluid, cerebrospinal fluid and intracranial drainage specimens were taken for fungal culture and morphological identification, and next generation sequencing. Surgical drainage and voriconazole antifungal therapy were used. According to the morphological characteristics of the strain and the results of gene sequencing, it was identified as Scedosporium apiospermum. Pulmonary and central nervous system fungal infections caused by Scedosporium apiospermum are less common and their identification relies primarily on morphological features and genetic analysis. Surgical drainage and voriconazole have a good therapeutic effect on this. However, a further follow-up is requied.

Pulmonary infection caused by Schizophyllum commune complicated with atelectasis: a case report and review of the literature

YE Jinghuan, CHEN Zhuni, LIU Yu, LI Yaqing, XIE Wei

2023, 18(2):  151-155. 

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Filamentous fungus Schizophyllum commune(S. commune) is a conditional pathogen. There were rare reports of S. commune caused deep invasive infection in human. A patient with pulmonary infection of S.commune with normal immune function was treated in our hospital, who came from Guangdong and presented recurrent non-irritating cough and yellowish-white mucus sputum. Computed tomography of the patient’s chest showed atelectasis with mucus thrombus in the upper lobe of the right lung. Fiberoptic bronchoscopy revealed that there was a mucinous embolus in the upper lobe of the right lung with massive yellow purulent discharge. Alveolar lavage fluid culture were positive for S. commune. His clinical status was improved and discharged after a week of itraconazole treatment. After being discharged from the hospital, the patient was maintained on itraconazole treatment for 3 months,computed tomography of the patient’s chest showed that the lesion was absorbed and the upper lobe of the right lung was completely dilated at his final follow-up, which suggested that the antifungal treatment was effective.

A case of eyelid abscess caused by Talaromyces marneffei in non-HIV patient

HU Qin, WU Qiong, OUYANG Yi

2023, 18(2):  156-159. 

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A 43-year-old woman was found to have multiple swollen lymph nodes in the neck with a 11-month history. After taking a lymph node biopsy, she was diagnosed as "lymphatic tuberculosis." During anti-tuberculosis treatment, the patient experienced swelling of the upper left eyelid. She received "mass removal (anterior opening of the orbit) + pedicle flap transplantation", postoperative pus culture showed: Talaromyces marneffei. Treatment with intravenous amphotericin B was initiated, and later changed to itraconazole 200 mg twice-daily orally due to increased creatinine. The patient was discharged after totally 7 weeks treatment. Oral itraconazole 200 mg twice-daily was continued for 6 months followed by 200mg qd for 8 months, and there was no recurrence during a two-year follow-up.

A case report of disseminated cryptococcosis in a child and literature review

TANG Lujing, LOU Jingan, ZHAO Hong, FU Linchen, HAN Yan

2023, 18(2):  160-162,177. 

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A case who complained with jaundice more than 1 month and fever 8 days was diagnosed as disseminated cryptococcosis (involving the liver, spleen, bile duct and brain) via liver biopsy, cerebrospinal fluid culture and detection of the Cryptococcus neoformans antigen. Disseminated cryptococcosis with jaundice as the first symptom was rare in clinic.