OBJECTIVE: To monitor the changes of voriconazole minimum concentration(C_min) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole. METHODS: 136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole C_min were analyzed, and the changes of voriconazole C_min after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole. RESULTS: Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole C_min and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole C_min was negatively correlated with albumin level (r=-2.673). Voriconazole C_min in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole C_min showed that compared with voriconazole C_min 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole C_min> 5.0 mg/L group was increased (χ²=4.318, P=0.038). CONCLUSION The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole C_min, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole C_min of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.
Humans ; Male ; Female ; Voriconazole/therapeutic use* ; Antifungal Agents/therapeutic use* ; C-Reactive Protein ; Creatinine ; Glucocorticoids ; Retrospective Studies ; Drug Monitoring ; Hematologic Diseases

OBJECTIVE: To explore the value of the diagnostic-driven therapy with voriconazole in patients with hematological disorders complicated by invasive fungal disease (IFD). METHODS: A total of 111 patients with hematological disorders complicated by IFD, treated with voriconazole in the hematology department of the General Hospital of South Theatre Command from July 2019 to July 2020, were retrospectively analyzed to compare the differences between the empirical therapy and the diagnostic-driven therapy on the treatment time of voriconazole, hospitalization days and antifungal efficacy. SPSS 23.0 was used for statistical analysis of data. RESULTS: Compared with the diagnostic-driven therapy group, the empirical therapy group had more IFD high-risk patients, including a higher proportion of agranulocytosis patients (95.2% vs 69.5%, P=0.003). However, there were no significant differences on the treatment time of voriconazole, hospitalization days and antifungal efficacy of voriconazole between the two groups. CONCLUSION Using diagnostic-driven therapy in relatively IFD low-risk patients can obtain similar therapeutic outcomes and prognosis as empirical therapy in high-risk patients. Either of two strategies can be used in clinical practice according to the individual conditions of patients.
Antifungal Agents/therapeutic use* ; Hematologic Diseases/drug therapy* ; Humans ; Invasive Fungal Infections/drug therapy* ; Retrospective Studies ; Voriconazole/therapeutic use*

Objective: To investigate the clinical manifestations, treatments, and prognosis of pediatric patients with Talaromyces marneffei infection. Methods: In this retrospective study, 7 children diagnosed with Talaromyces marneffei infection in Shenzhen Children's Hospital from July 2017 to October 2021 were recruited. The clinical features, radiology, pathogen detection, immunological evaluation, treatments, and prognosis were analyzed. Results: In 7 cases, 5 were male, 2 were females. The age was from 0.75 to 8.75 years. The main clinical manifestations were fever in 7 cases, cough in 6 cases, malnutrition in 4 cases, papules in 2 cases and medical history of recurrent infection in 3 cases. Physical examination showed that all 7 patients had hepatosplenomegaly, 4 had superficial lymphadenopathy. Laboratory examination showed that 6 cases had decreased hemoglobin and 3 cases had decreased platelet. Chest CT showed that 4 cases had patchy shadows, pleural effusion, mediastinal or axillary lymph node enlargement, 3 had nodular shadows and 2 had cavities. The positive ratio of Talaromyces marneffei culture was 2/2 with tissue samples, 4/5 with bone marrow. The positive ratio was 3/4 by metagenomic next generation sequencing. The fungus was detected in 3 cases by smear microscopy of bone marrow and (or) peripheral blood. All patients were negative for human immunodeficiency virus by the immune function assay. However, 5 cases were confirmed as primary immunodeficiency disease, including 2 cases with high IgM syndrome, 2 with STAT1 gene variation, and the last with severe combined immunodeficiency (IL2RG gene variation). Exclude 1 case which gave up treatment due to acute intracranial infection, and the other patients received effective treatments along with amphotericin B, voriconazole, and itraconazole alone or in combination. Two cases relapsed after medication withdrawal, but 1 case got complete rehabilitation after hematopoietic stem cell transplantation. Conclusions: The clinical manifestations involve multisystem, the common charateristics are fever and cough. The chest CT imaging manifestations are diverse, it should be considered in differentiating tuberculosis. The amphotericin B, voriconazole and itraconazole are effective, but it will easily relapse when withdrawing those antifungal agents.
Amphotericin B/therapeutic use* ; Antifungal Agents/therapeutic use* ; Child ; Child, Preschool ; Cough ; Female ; Fever ; Humans ; Infant ; Itraconazole/therapeutic use* ; Male ; Mycoses ; Retrospective Studies ; Talaromyces ; Voriconazole

Antifungal Agents ; therapeutic use ; Female ; Humans ; Lung ; microbiology ; pathology ; Lung Diseases, Fungal ; drug therapy ; etiology ; Middle Aged ; Schizophyllum ; drug effects ; pathogenicity ; Voriconazole ; therapeutic use

Aged ; Antifungal Agents ; therapeutic use ; Bronchiectasis ; diagnosis ; drug therapy ; Female ; Humans ; Pulmonary Aspergillosis ; diagnosis ; drug therapy ; Tomography, X-Ray Computed ; Voriconazole ; therapeutic use

Invasive aspergillosis (IA), generally considered an opportunistic infection in immunocompromised hosts, is associated with high morbidity and mortality. IA commonly occurs in the respiratory tract with isolated reports of aspergillosis infection in the nasal sinuses, central nervous system, skin, liver, and urinary tract. Extra-pulmonary aspergillosis is usually observed in disseminated disease. To date, there are a few studies regarding primary and disseminated gastrointestinal (GI) aspergillosis in immunocompromised hosts. Only a few cases of primary GI aspergillosis in non-immunocompromised hosts have been reported; of these, almost all of them involved the upper GI tract. We describe a very rare case of IA involving the lower GI tract in the patient without classical risk factors that presented as multiple colon perforations and was successfully treated by surgery and antifungal treatment. We also review related literature and discuss the characteristics and risk factors of IA in the immunocompetent hosts without classical risk factors. This case that shows IA should be considered in critically ill patients, and that primary lower GI aspergillosis may also occur in the immunocompetent hosts without classical risk factors.
Amphotericin B/administration & dosage/therapeutic use ; Antifungal Agents/administration & dosage/*therapeutic use ; Aspergillosis/*diagnosis/drug therapy/microbiology/surgery ; Aspergillus/*isolation & purification ; Colon/microbiology/radiography/*surgery ; Colonic Diseases/diagnosis/therapy ; Combined Modality Therapy ; Humans ; *Immunocompetence ; Laparotomy ; Male ; Middle Aged ; Treatment Outcome ; Voriconazole/administration & dosage/therapeutic use

Drug Therapy, Combination ; Echinocandins ; administration & dosage ; therapeutic use ; Humans ; Invasive Pulmonary Aspergillosis ; complications ; drug therapy ; Lipopeptides ; Liver Failure ; complications ; drug therapy ; microbiology ; Male ; Middle Aged ; Voriconazole ; administration & dosage ; therapeutic use

OBJECTIVETo investigate the efficacy and tolerability of intravenous voriconazole on primary prevention in invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSAt the time of conditioning regimen, patients without IFD was intravenously administered with voriconazole at a dose of 100 mg two times per day until neutrophils greater than 0.5×10⁹/L. Patients treated with oral fluconazole, 200 mg per day, were control group. The incidence and risk factors of IFD and side effects of medicines were evaluated.

RESULTSOf the total 227 patients, 33 (14.54%) had IFD within 3 months after allo-HSCT. There was significant difference on overall survival between patients with or without IFD by Kaplan-Meier survival curve (P=0.029). Of the 83 cases with intravenous voriconazole, 7 cases occurred IFD (8.43%). In contrast, the incidence of IFD in control group was 18.06% (26 out of 144). There was remarkable difference between the two groups (P=0.048). But there was no significant difference on risk factors of IFD between the two groups. In addition, the incidence of liver function abnormalities between the two groups was no difference. The ratio of auditory hallucination and visual impairment induced by voriconazole was not high.

CONCLUSIONIntravenous voriconazole on primary prevention for IFD after allo-HSCT is much better than oral fluconazole with well tolerability and satisfactory efficacy.

Administration, Intravenous ; Adolescent ; Adult ; Antifungal Agents ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Female ; Fluconazole ; administration & dosage ; therapeutic use ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Mycoses ; etiology ; prevention & control ; Postoperative Complications ; prevention & control ; Treatment Outcome ; Voriconazole ; administration & dosage ; therapeutic use ; Young Adult

Antifungal Agents ; administration & dosage ; therapeutic use ; Candidiasis ; complications ; diagnosis ; drug therapy ; Child ; Echinocandins ; administration & dosage ; therapeutic use ; Hematologic Diseases ; complications ; Humans ; Lipopeptides ; Mycoses ; complications ; diagnosis ; drug therapy ; Neoplasms ; complications ; Pediatrics ; Practice Guidelines as Topic ; Voriconazole ; administration & dosage ; therapeutic use

BACKGROUNDIn our clinical practice we have been attracted by a group of patients with airway aspergillosis who have airway obstruction; we termed the condition as pseudomembranous necrotizing tracheobronchial aspergillosis (PNTA). In this study we analyzed the clinical data from patients with PNTA, so as to guide the diagnosis and treatment of the disease.

METHODSA total of 16 PNTA patients were treated in Changhai Hospital from January 2000 to January 2009. Their clinical data, including the demographic information, clinical symptoms, imaging findings, bronchoscopy findings, treatment strategies and efficacy, and prognosis, were retrospectively analyzed.

RESULTSAll 16 patients were found to have primary systemic immunodeficiency diseases and/or damage of the focal airways. Nine patients (9/16, 56.3%) had pulmonary and tracheobronchial tumors, 5/16 (31.3%) had tracheobronchial involvement secondary to non-pulmonary tumors, and 2/16 (12.5%) had lung transplantation. The most common causes of PNTA included local radiotherapy (10/16, 62.5%), repeated chemotherapy (7/16, 43.8%) and recurrent intervention therapy by bronchoscope (4/16, 25.0%). Aspergillus fumigatus was the most frequent pathogen (62.5%, 10/16). The main clinical manifestations included progressive dyspnea (14/16, 87.5%) and irritable cough (12/16, 75.0%). The trachea was involved in 9/16 patients (56.3%), right main bronchus in 10/16 (62.5%). All 16 patients were treated with systemic anti-aspergillosis agents, local anti-aspergillosis agents with amphotericin B inhalation and direct perfusion of amphotericin B by bronchoscope, and interventional treatment by bronchoscope to ensure an unobstructed airway. The total efficiency was 31.3%.

CONCLUSIONSPNTA is an infectious disease caused by aspergillus and it mainly involves the trachea, primary bronchus and segmental bronchus. A. fumigatus is the most common pathogen. PNTA can pose a severe clinical threat and often occurs after systemic immunodeficiency and/or local airway damage, with the main symptoms including dyspnea and irritable cough. Bronchoscopic findings supply the main evidence for diagnosis of PNTA. Treatment of PNTA is difficult and requires a long course. Systemic and local anti-aspergillosis agents plus bronchoscopy debridement can improve the prognosis of the disease.

Adult ; Aged ; Amphotericin B ; therapeutic use ; Antifungal Agents ; therapeutic use ; Aspergillosis ; diagnosis ; drug therapy ; Bronchoscopy ; Echinocandins ; therapeutic use ; Female ; Humans ; Itraconazole ; therapeutic use ; Lipopeptides ; Lung Diseases, Fungal ; diagnosis ; drug therapy ; Male ; Middle Aged ; Pyrimidines ; therapeutic use ; Triazoles ; therapeutic use ; Voriconazole