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

Chronic pulmonary aspergillosis (CPA) is a rare disease. It is usually diagnosed in immunocompromised patients with other chronic respiratory disorders. Diagnosis can be challenging due to non-specific symptoms. It is based on clinical, radiological, and microbiological criteria and excludes other causes of the symptoms. The outcomes of antifungal treatment may be unpredictable as optimal treatment duration has not yet been standardized. This is the case of a 74-year-old male who presented via teleconsultation with hemoptysis. GeneXpert for pulmonary tuberculosis was negative. Chest radiograph showed a cavitary lesion with an aspergilloma within. This led to a longstanding treatment effort with voriconazole, as he was a poor candidate for surgical resection due to the risk of post-operative complications. Three months into the treatment, the patient unexpectedly suffered from a severe episode of dyspnea, culminating in cardiac arrest. While the patient has been resuscitated with no residuals, it is only one of the many steps on his road to recovery and his second lease on life, this time coming to terms with his own preferences and values regarding his medical care. The patient showed clinical improvement and the promise of a cure in his fifth month of treatment. Learning points include the role of family physicians in a patient’s well-being even in specialized cases, the value of individualized care and the application of technology in hybrid consultation and monitoring.
Aspergillosis ; hemoptysis ; voriconazole

Humans ; Child ; Voriconazole/adverse effects* ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy* ; Renal Dialysis ; Seizures ; Antibodies, Antineutrophil Cytoplasmic

Objective: To explore the epidemiological characteristics of sample distribution and antifungal susceptibilities of clinically invasive C. tropicalis isolates from 2017 to 2021 in East China. Methods: Using a retrospective analysis, the East China Invasive Fungal Infection Group (ECIFIG) collected C. tropicalis clinically isolated from 32 hospitals in East China between January 2017 and December 2021. The identification results of the strains were reviewed using mass spectrometry by the central laboratory of the Shanghai East Hospital. The minimum inhibitory concentrations (MICs) of the strains against fluconazole (FLU), voriconazole (VOR), itraconazole (ITR), Posaconazole (POS), isavuconazole (ISA), anidulafungin (ANI), caspofungin (CAS), micafungin (MICA) and 5-fluorocytosine (FCT) were tested by the ThermoFisher CMC1JHY colorimetric microdilution method. The MIC of amphotericin B (AMB) was tested by the broth microdilution method. The MIC results were analyzed based on the clinical breakpoints and epidemiological cutoff values (ECV) published by the Clinical and Laboratory Standards Institute (CLSI) M27 Ed3 and M57 Ed4 documents. Data analysis was conducted using the Kruskal-Wallis test and paired t-test. Results: In total, 305 C. tropicalis isolates were collected. There were 38.0% (116/305) strains isolated from blood, 11.5% (35/305) ascites, 8.9% (27/305) catheter and 8.9% (27/305) drainage fluid. The resistance rate of C. tropicalis to FLU was 32.5%, to VOR was 28.5%, and the cross-resistance rate to FLU and VOR was 28.5%. The wild-type proportions for ITR and POS were 79.3% and 29.2% respectively. There was no significant difference in resistance rates, MIC₅₀, and MIC₉₀ of FLU and VOR, or in the wild-type rates of ITR and POS over five years. More than 95.0% of the isolates were susceptible to echinocandins. However, one strain was identified as being multi-drug resistant. In azole antifungals, voriconazole, itraconazole, posaconazole, and isavuconazole have similar GM MIC values. The GM MIC of fluconazole is significantly higher than that of itraconazole (t=9.95, P<0.05), posaconazole (t=9.99, P<0.05), and voriconazole (t=10.01, P<0.05), Meanwhile, among echinocandins, the GM MIC of ANI was comparable to that of CAS (t=1.17, P>0.05), both of which were significantly higher than MICA (t=11.56, P<0.05; t=4.15, P<0.05). Conclusion: The clinical isolates of C. tropicalis in East China from 2017 to 2021 were relatively susceptible to echinocandins. However, there was consistently high resistance to fluconazole and voriconazole. More intensive efforts should be made on the monitoring of drug resistance in C. tropicalis.
Humans ; Antifungal Agents/pharmacology* ; Fluconazole/pharmacology* ; Candida tropicalis ; Voriconazole/pharmacology* ; Itraconazole/pharmacology* ; Retrospective Studies ; Candida ; China/epidemiology* ; Echinocandins/pharmacology* ; Microbial Sensitivity Tests

Objective: To explore the epidemiological characteristics of sample distribution and antifungal susceptibilities of clinically invasive C. tropicalis isolates from 2017 to 2021 in East China. Methods: Using a retrospective analysis, the East China Invasive Fungal Infection Group (ECIFIG) collected C. tropicalis clinically isolated from 32 hospitals in East China between January 2017 and December 2021. The identification results of the strains were reviewed using mass spectrometry by the central laboratory of the Shanghai East Hospital. The minimum inhibitory concentrations (MICs) of the strains against fluconazole (FLU), voriconazole (VOR), itraconazole (ITR), Posaconazole (POS), isavuconazole (ISA), anidulafungin (ANI), caspofungin (CAS), micafungin (MICA) and 5-fluorocytosine (FCT) were tested by the ThermoFisher CMC1JHY colorimetric microdilution method. The MIC of amphotericin B (AMB) was tested by the broth microdilution method. The MIC results were analyzed based on the clinical breakpoints and epidemiological cutoff values (ECV) published by the Clinical and Laboratory Standards Institute (CLSI) M27 Ed3 and M57 Ed4 documents. Data analysis was conducted using the Kruskal-Wallis test and paired t-test. Results: In total, 305 C. tropicalis isolates were collected. There were 38.0% (116/305) strains isolated from blood, 11.5% (35/305) ascites, 8.9% (27/305) catheter and 8.9% (27/305) drainage fluid. The resistance rate of C. tropicalis to FLU was 32.5%, to VOR was 28.5%, and the cross-resistance rate to FLU and VOR was 28.5%. The wild-type proportions for ITR and POS were 79.3% and 29.2% respectively. There was no significant difference in resistance rates, MIC₅₀, and MIC₉₀ of FLU and VOR, or in the wild-type rates of ITR and POS over five years. More than 95.0% of the isolates were susceptible to echinocandins. However, one strain was identified as being multi-drug resistant. In azole antifungals, voriconazole, itraconazole, posaconazole, and isavuconazole have similar GM MIC values. The GM MIC of fluconazole is significantly higher than that of itraconazole (t=9.95, P<0.05), posaconazole (t=9.99, P<0.05), and voriconazole (t=10.01, P<0.05), Meanwhile, among echinocandins, the GM MIC of ANI was comparable to that of CAS (t=1.17, P>0.05), both of which were significantly higher than MICA (t=11.56, P<0.05; t=4.15, P<0.05). Conclusion: The clinical isolates of C. tropicalis in East China from 2017 to 2021 were relatively susceptible to echinocandins. However, there was consistently high resistance to fluconazole and voriconazole. More intensive efforts should be made on the monitoring of drug resistance in C. tropicalis.
Humans ; Antifungal Agents/pharmacology* ; Fluconazole/pharmacology* ; Candida tropicalis ; Voriconazole/pharmacology* ; Itraconazole/pharmacology* ; Retrospective Studies ; Candida ; China/epidemiology* ; Echinocandins/pharmacology* ; Microbial Sensitivity Tests

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

OBJECTIVE: To develop a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of atorvastatin and voriconazole in rat plasma and investigate the pharmacokinetics of atorvastatin and the changes in voriconazole concentration in rats after administration. METHODS: Plasma samples were collected from rats after intragastric administration of atorvastatin alone or in combination with voriconazole. The samples were treated with sodium acetate acidification, and atorvastatin and voriconazole in the plasma were extracted using a liquidliquid extraction method with methyl tert-butyl ether as the extractant. The extracts were then separated on a Thermo Hypersil Gold C18 (2.1×100 mm, 1.9 μm) column within 6 min with gradient elution using acetonitrile and water (containing 0.1% formic acid) as the mobile phase; mass spectrometry detection was achieved in selective reaction monitoring (SRM) mode under the positive ion scanning mode of heated electrospray ion source (H-ESI) and using transition mass of m/z 559.2→440.2 for atorvastatin and m/z 350→280 for voriconazole, with m/z370.2→252 for lansoprazole (the internal standard) as the quantitative ion. RESULTS: The calibration curves were linear within the concentration range of 0.01-100 ng/mL (=0.9957) for atorvastatin and 0.025-100 ng/mL (=0.9966) for voriconazole. The intra-day and inter-day precisions were all less than 13%, and the recovery was between 66.50% and 82.67%; the stability of the plasma samples met the requirements of testing. The AUC of atorvastatin in rat plasma after single and combined administration was 438.78±139.61 and 927.43±204.12 h·μg·L, CLz/F was 23.89±8.14 and 10.43±2.58 L·h·kg, C was 149.62±131.10 and 159.37±36.83 μg/L, t was 5.08±1.63 and (5.58±2.11 h, and T was 0.37±0.14 and 3.60±1.52 h, respectively; AUC, CLZ/F and T of atorvastatin in rat plasma differed significantly between single and combined administration. The HPLC-MS/MS system also allowed simultaneous determination of voriconazole concentration in rat plasma after combined administration. CONCLUSIONS The HPLC-MS/MS system we established in this study is simple, rapid and sensitive and allows simultaneous determination of atorvastatin and voriconazole in rat plasma. Some pharmacokinetic parameters of atorvastatin are changed in the presence of voriconazole, and their clinical significance needs further investigation.
Administration, Oral ; Animals ; Atorvastatin ; Chromatography, High Pressure Liquid ; Rats ; Tandem Mass Spectrometry ; Voriconazole

BACKGROUND: Candida auris was first isolated from the ears of Japanese and Korean patients. However, the prevalence of yeast isolates from ear cultures and their antifungal susceptibility profiles in these nations remain unclear.METHODS: We assessed yeast isolates recovered from ear cultures from a university hospital in Korea over a 4-year period from January 2014 to December 2017. Species identification was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and/or sequence analysis. Antifungal minimal inhibitory concentrations (MICs) were determined using the broth microdilution method of the Clinical and Laboratory Standards Institute.RESULTS: Among 81 non-duplicate isolates from ear cultures, Cadida parapsilosis was the most frequently detected yeast species (34.6%), followed by C. auris (28.4%), Candida metapsilosis (9.9%), Candida orthopsilosis (8.6%), Candida albicans (7.4%), and others (11.1%). The MICs of the isolates were 0.125 to > 64 µg/mL, ≤0.03 to 4 µg/mL, 0.25 to 1 µg/mL, 0.125 to 1 µg/mL, and ≤0.03 to 2 µg/mL for fluconazole, voriconazole, amphotericin B, caspofungin, and micafungin, respectively. Of the 81 isolates, 44.4% (36/81) showed decreased susceptibility to fluconazole (MIC ≥4 µg/mL). Of the 23 C. auris isolates, 19 (82.6%) had a fluconazole MIC of ≥32 µg/mL. None of the isolates showed resistance to amphotericin B or echinocandins. Most of these patients suffered from chronic otitis media (84%).CONCLUSION: Candida parapsilosis complex and C. auris were the yeast species identified most frequently from ear cultures and they exhibited a high rate of fluconazole non-susceptibility, particularly C. auris.
Amphotericin B ; Asian Continental Ancestry Group ; Candida ; Candida albicans ; Ear ; Echinocandins ; Fluconazole ; Humans ; Korea ; Mass Spectrometry ; Methods ; Otitis Media ; Prevalence ; Sequence Analysis ; Voriconazole ; Yeasts

PURPOSE: To report polymicrobial keratitis involving Pseudomonas aeruginosa, Acinetobacter baumannii, and Ochrobactrum anthropi. CASE SUMMARY: A 53-year-old female complained of pain and secretion in her right eye, which started 6 weeks before her visit. She applied steroid ointment, which was received from the dermatologist, to her eyelid 7 days prior to her visit but this treatment worsened her symptoms. At the initial visit, the visual acuity of the right eye was light perception, and purulent secretions were observed. Using a slit lamp, severe conjunctival hyperemia, hypopyon, and a ring-shaped central corneal ulcer were observed. The anterior chamber and fundus were not observed due to corneal lesions but ultrasonography showed no intraocular inflammation. Infectious keratitis was suspected and cultured by corneal scraping. During the incubation period, 0.5% moxifloxacin, 2% voriconazole, and 1% cyclopentolate were administered. A total of 400 mg of moxifloxacin and 100 mg of doxycycline were given orally. In the primary culture, Pseudomonas aeruginosa and Acinetobacter baumannii were identified so 5% ceftazidime, which was sensitive for the antibiotic susceptibility results was further instilled. Thereafter, the keratitis improved but the keratitis again worsened while maintaining the topical treatment. A secondary culture was positive for Ochrobactrum anthropi. Treatment with 1.4% gentamicin, which was sensitive for the antibiotic susceptibility test was added and the keratitis improved. A conjunctival flap was performed because of the increased risk of perforation. CONCLUSIONS: We report polymicrobial keratitis involving Pseudomonas aeruginosa, Acinetobacter baumannii, and Ochrobactrum anthropi for the first time in the Republic of Korea.
Acinetobacter baumannii ; Acinetobacter ; Anterior Chamber ; Ceftazidime ; Corneal Ulcer ; Cyclopentolate ; Doxycycline ; Eyelids ; Female ; Gentamicins ; Humans ; Hyperemia ; Inflammation ; Keratitis ; Middle Aged ; Ochrobactrum anthropi ; Ochrobactrum ; Pseudomonas aeruginosa ; Pseudomonas ; Republic of Korea ; Slit Lamp ; Ultrasonography ; Visual Acuity ; Voriconazole