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Objective To evaluate the cost-effectiveness of posaconazole compared with voriconazole in the empiric or diagnostic-driven treatment of invasive mould diseases (IMD) in immunocompromised patients from the perspective of Chinese health system. Methods A decision tree model was constructed based on a phase Ĕ clinical trial and other publicly available data to evaluate the incremental cost-effectiveness ratio (ICER) of posaconazole versus voriconazole. One-way sensitivity analysis, probability sensitivity analysis, and scenario analysis were conducted. Results The results of base-case analysis indicated that, at a willingness-to-pay (WTP) threshold of 3 times Chinese GDP per capita, posaconazole gained 0.0327 quality-adjusted life years (QALYs) with the cost savings of CNY 1 711.24, demonstrating a clear cost-effectiveness advantage. Sensitivity analysis revealed that the cost of voriconazole and posaconazole significantly influenced the ICER. Under different WTP thresholds, posaconazole consistently maintained its economic advantage over voriconazole. Scenario analysis showed that the incidence of mucormycosis did not impact the results, but a price reduction in voriconazole could change result. Conclusion In the empiric or diagnostic-driven treatment of IMD in immunocompromised patients, posaconazole was both an effective and economically viable choice when compared to voriconazole. [ABSTRACT FROM AUTHOR]

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OBJECTIVE: To validate and evaluate the chemiluminescence immunoassay (CLIA ) for the determination of voriconazole blood concentration. METHODS: (1) The CLIA method was verified in five aspects: detection limit, repeatability, linearity, accuracy and precision. (2) The CLIA method was evaluated. Plasma samples of 113 patients who were monitored for voriconazole blood concentration in the hospital from Jan. to Feb. 2023 were collected and detected by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS / MS) and CLIA method respectively. The correlation and consistency of the two methods were compared by using paired t-test, intragroup correlation coefficient (ICC), Passing-Bablok regression, and Bland-Altman analysis. RESULTS: It was validated that the CLIA method for the determination of voriconazole blood concentration met the requirements of analytical techniques, and the method was stable and reliable. The mean concentration of voriconazole in plasma was (3. 843 ± 2. 056) μg / mL determined by CLIA method, higher than (3. 399 ± 1. 959) μg / mL by UPLC-MS / MS method, with statistically significant differences (P<0. 01). ICC of the two methods was 0. 932 (P<0. 001). The Passing-Bablok regression equation was Y = 0. 083 4+1. 099 X (R = 0. 956, n = 113), the slope of the equation was 1. 099 (95%CI = 1. 030-1. 161), and the intercept was 0. 083 4 (95%CI = -0. 062-0. 251), there was a good linear correlation between the two methods. According to the Bland-Altman analysis, the mean absolute bias between CLIA and UPLC-MS / MS was 0. 442 μg / mL (95% CI = 0. 331-0. 558 μg / mL), the average bias in percentage between CLIA and UPLC-MS / MS was 14. 49% (95%CI = 11. 47%-17. 51%), which was an acceptable consistency between the two methods. CONCLUSIONS: The CLIA method is stable, reliable, easy to operate, and has high detection efficiency, making it more suitable for clinical sample testing. The correlation between the results determined by CLIA method and UPLC-MS / MS method is good and in acceptable consistency, and the CLIA method can be used for the clinical detection of voriconazole as a potential alternative to the UPLC-MS / MS method. [ABSTRACT FROM AUTHOR]

Fusarium is the most common mold in clinical practice, which may cause superficial infection in hosts with normal immune function, such as keratitis and severe disseminated infection (primarily manifested as fungemia) in individuals with poor immune function. Prevention and treatment of fusaridiosis are associated with long-term survival of kidney transplant recipients. To promote the standardization of clinical diagnosis and treatment of invasive fusaridiosis in kidney transplant recipients, Branch of Organ Transplantation of Chinese Medical Association initiated and formulated “Guidelines for Clinical Diagnosis and Treatment of Invasive Fusaridiosis in Kidney Transplant Recipients in China”. In this guideline, the levels of evidence and strengths of recommendation for each clinical problem were classified using Oxford Center for Evidence-based Medicine of 2009. Regarding 13 clinical problems related to clinical diagnosis and treatment of invasive fusaridiosis after kidney transplantation, 14 recommendations were proposed in accordance with clinical diagnosis and treatment practice in China, aiming to promote the standardization of diagnosis and treatment of invasive fusaridiosis after kidney transplantation and improve long-term survival of both recipients and renal allografts after kidney transplantation. [ABSTRACT FROM AUTHOR]

Background Central nervous system aspergillosis is clinically rare. We present one case of central nervous system aspergillosis diagnosed by pathology, analyze its clinical features, review the literature，and summarize key diagnostic and therapeutic points. Methods and Results The patient, a 50- year-old woman, presented clinically with progressive weakness in limbs, epileptic seizures, and cognitive decline. Systemic inflammation - immune markers and cerebrospinal fluid (CSF) analysis showed no significant abnormalities. Head MRI revealed abnormal signals in both frontal and parietal lobes with patchy and ring-enhancing lesions and meningeal enhancement. Neuropathology suggested vasculitis and brain tissue necrosis with hemorrhage. Periodic acid methenamine staining revealed fungal hyphae with apparent septation and branching at 45° angles. The final diagnosis was central nervous system aspergillosis. Following antifungal and other symptomatic treatments, the patient's symptoms improved, and follow-up brain MRI showed reduction in lesion size. Conclusions Patients with central nervous system aspergillosis may not have a clear underlying immunodeficiency, and clinical manifestations are lack of specificity. CSF may show no inflammatory changes, and metagenomic next-generation sequencing (mNGS) may be negative. Brain biopsy is the primary diagnostic method. Early, adequate and full-course antifungal treatment with voriconazole can improve the prognosis.

The patient was a 32-year-old woman who presented with “right eye vision loss with floating dark shadow for 10 days”. The patient had a history of anemia, a hemoglobin of 71.0g/L, and no history of other systemic diseases. The best corrected visual acuity was 0.05 and 1.0 in the right (OD) and left eye (OS), respectively. In the right eye, the conjunctival was mildly congested with significant anterior chamber reaction (Tyndall (+++)) and 1mm hypopyon. The vitreous was moderately cloudy and the fundus examination revealed a blurred view of flat retina. Optical coherence tomography (OCT) in the right eye showed a localized proliferative epiretinal membrane in the temporal macula, and the signal below is obscured. Fluorescein fundus angiography showed slight leakage of fluorescence in the late phase from retinal vessels in the right eye. The patient was initially diagnosed with right uveitis, which improved after local glucocorticoid therapy. More than 1 month later, the patient returned to the doctor due to continued and worsening vision loss in both eyes. The visual acuity decreased to FC/BE (OD) and FC/50cm (OS). The fundus was indistinct due to vitreous opacity in the right eye. Tyndall was positive with a 0.5 mm hypopyon and moderately cloudy vitreous body in the left eye. The fundus was blurred and a suspected yellowish-white lesion was observed between the optic disc and macula in this eye. To determine the cause, the patient was treated with vitrectomy combined with epiretinal membrane stripping on right eye. The vitreous obtained during the operation was smeared and cultured for bacteria and fungi. At the same time, the vitreous was sent for metagenomic next-generation sequencing, which showed Candida albicans (+). It was confirmed by further G-test, even though the smear and culture results were negative. The revised diagnosis was bilateral endogenous fungal endophthalmitis (EFE), and examination revealed that the patient had fungal vaginitis. The patient was immediately treated with bilateral intravitreal injection of voriconazole combined with systemic voriconazole. After that, vitrectomy combined with epiretinal membrane peeling was performed in the left eye due to no significant improvement. Thereafter, the patient’s binocular symptoms improved, visual acuity increased, and there has being no recurrence so far. Discussion and experience: Endogenous fungal endophthalmitis is easily misdiagnosed as uveitis in the early stage, especially in patients with no underlying disease. It is necessary to improve the awareness of this disease, carefully inquire about patients’ history, initiate antifungal treatment as soon as possible, and consider vitrectomy if necessary. [ABSTRACT FROM AUTHOR]

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Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

OBJECTIVE: To investigate whether Nematavir tablet / Ritonavir tablet ( co-packaged) ( hereinafter referred to as “ nematavir/ ritonavir ”) in combination with voriconazole would affect voriconazole exposure. METHODS: Patients who were concurrently treated with voriconazole and nirmatrelvir/ ritonavir during the COVID-19 outbreak in Beijing from Dec. 2022 to Jan. 2023 at the National Center for Respiratory Medicine were retrospectively enrolled. Dosage, drug combination, voriconazole concentration and adverse drug reactions were recorded and analyzed. RESULTS: A total of 17 voriconazole concentrations of 14 patients were included. Only 1 patient had low blood drug concentration, 2 patients exceeded 50% of the upper limit of treatment, most patients were within the therapeutic range. Among the 7 patients with baseline voriconazole concentration data, all but 1 patient’ voriconazole concentration was similar to or slightly higher than the baseline concentration. Compared with other data of voriconazole concentration, the proportion of higher voriconazole concentration was slightly increased in the combined one. No adverse drug reactions attributable to the two drugs were found. CONCLUSIONS: Different from the instructions, the combined use of voriconazole and nirmatrelvir/ ritonavir is feasible in Chinese population. Therapeutic drug monitoring is recommended to ensure safety and effectiveness. [ABSTRACT FROM AUTHOR]

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Objective To explore the correlation between dose, blood concentration and efficacy of voriconazole in the treatment of invasive fungal infection in children. Methods 68 children treated with voriconazole during January 2019 to December 2019 were collected. The plasma concentration of voriconazole was assayed by high performance liquid chromatography (HPLC). The correlation between blood concentration and clinical efficacy was statistically analyzed. Results Different drug blood concentrations were obtained with different dosages: <4.0 mg/kg (6 cases) with the trough concentration ranged from 0.4 to 3.31 μg/ml (r=0.613, P=0.195). (4.0 - 7.0) mg/kg (44 cases), ranged from 0.35 to 7.02 μg/ml (r=0.325, P=0.018); >7.0 mg/kg (18 cases), ranged from 1.46 to 12.45 μg/ml (r=0.584，P＜0.023). There was a difference between the three groups (F=7.270, P=0.026). The relationship between the drug blood concentration and the therapeutic effect was obvious. In the <1.0 μg/ml group of 14 cases, 10 cases (71.4%) were effective, and 4 cases were ineffective. In the 1.0 - 5.5 μg/ml group of 48 cases, 44 cases (91.7%) were effective, and 4 cases were ineffective. In the >5.5 μg/ml group of 6 cases, 4 cases (66.7%) were effective and 2 cases ineffective. The difference among the three groups was obvious (χ2=5.360, P=0.039). Among the 68 cases, 58 cases (85.3%) were effective, and 10 cases (14.7%) were ineffective. Adverse reactions occurred in 10 cases (14.7%) with mild liver function injury, which did not affect the treatment and recovered with liver protection treatment. Conclusion This study showed that voriconazole was generally safe and effective in the treatment of invasive fungal infections in children. There was a significant dose-blood concentration and efficacy correlation. Further studies on pharmacokinetics and efficacy should be carried out to optimize the individualized treatment. [ABSTRACT FROM AUTHOR]

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OBJECTIVE: To investigate the distribution characteristics of voriconazole plasma trough concentration in patients with acquired immunodeficiency syndrome ( AIDS ) complicated with fungal infection, analyze the influencing factors of voriconazole trough concentration, and evaluate the medication safety. METHODS : General data, biochemical indicators, renal function, drug combination and adverse events of patients with AIDS complicated with fungal infection treated with voriconazole in this hospital from Jul. 2019 to Apr. 2021 were retrospectively collected. Ultra-high performance liquid chromatography tandem mass spectrometry was used to detect the steady-state trough concentration during drug administration, and statistical analysis was performed by using SPSS 25. 0 software . RESULTS: A total of 112 patients with AIDS complicated with fungal infection were included in this study. The initial median voriconazole trough concentration was 3. 4 µg/mL (from 1. 8 µg/mL to 5. 8 µg/mL), and 43 patients were not within the treatment window ( from 0. 5 µg/mL to 5. 0 µg/mL) . After adjusting the dose for 40 patients whose trough concentration was not within the treatment window ( the remaining 3 patients were discontinued ), the number of patients with appropriate concentration increased from 61. 6% ( 69/112) to 87. 5% ( 35/ 40) . Analysis of influencing factors showed that aspartate aminotransferase ( AST ), aspartate aminotransferase/ alanine aminotransferase ( AST/ ALT), albumin levels and drug combination of proton pump inhibitors had significant effects on voriconazole trough concentration(P

Objective To investigate the relationship between voriconazole trough concentration and liver injury in elderly patients with lung invasive aspergillosis. Methods The clinical data of patients receiving voriconazole therapeutic drug monitoring matched with the inclusion criteria, who admitted to our hospital from 1 January, 2018 to 30 June, 2019 were retrospectively analyzed. Patients were divided into elderly group (≥60 years) and adult group (≥18~ < 60 years) according to age. The route of administration, daily voriconazole dose, voriconazole trough concentration, and liver injury of patients were compared between the two groups. Results A total of 179 patients with lung invasive aspergillosis were included in, with 329 voriconazole trough concentration. There were 87 patients in elderly group, with 131 voriconazole trough concentration. There were 92 patients in elderly group, with 198 voriconazole trough concentration. Most patients in the elderly group received an intravenous drip, which was higher than that in adult group (P < 0.01). The voriconazole dosing was similar in the two cohorts (P > 0.05). The voriconazole trough concentration in elderly group was 3.86 (2.02, 6.00) μg/mL, which was higher than 2.6 (1.5, 4.0)μg/mL in adult group (P < 0.01). The proportion of voriconazole trough concentrations higher than 5 μg/mL in the elderly group was higher than that in the adult group (P < 0.01). The incidence rate of alanine aminotransferase (ALT) increasing in elderly group was lower than that in the adult group (P < 0.01). The incidence rate of albumin decreasing in elderly group was higher than that in the adult group (P < 0.01). The incidence of increased alkaline phosphatase (ALP), ALT, and gamma-glutamyl transpeptidase (GGT) concentrations and decreased albumin level was higher in the elderly group than that in the adult group when the voriconazole trough concentration was higher than 5 μg/mL (P < 0.05). There were no correlations of voriconazole trough concentration with ALP, ALT, aspartate aminotransferase (AST), GGT, total bilirubin, and albumin in elderly group (r=0.018, 0.154, 0.166, -0.171, -0.138, -0.118, P > 0.05). There were positive correlation of voriconazole trough concentration with AST and total bilirubin in adult group (r=0.267, 0.618, P < 0.01). There was negative correlation between voriconazole trough concentration and albumin in adult group (r=-0.214, P < 0.05). Conclusion The voriconazole trough concentration in elderly patients was higher than that in adult patients; the elderly patients have the high incidence of liver injury when the voriconazole trough concentration was higher than 5 μg/mL; there were no correlations of voriconazole trough concentration and liver function indexes in elderly patients.

Objective To investigate the incidence rates of voriconazole-induced hypokalemia and hyponatremia and their correlations with voriconazole trough concentration in the patients with lung invasive aspergillosis. Methods The clinical data of the patients receiving therapeutic drug monitoring for voriconazole due to lung invasive aspergillosis in our hospital from 8 October, 2017 to 30 April, 2019 were collected and retrospectively analyzed. Sex, age, body weight, baseline diseases, types of fungal infection, route of administration, daily voriconazole dose, voriconazole trough concentration, serum potassium and sodium concentrations, and the times of hypokalemia and hyponatremia after administration were collected in all the patients. The relationships of voriconazole trough concentration with serum potassium and sodium concentrations were analyzed with Pearson's correlation analysis. Results A total of 142 patients with lung invasive aspergillosis were enrolled, with 267 voriconazole trough concentrations. The patients were mainly men (64.1%). Their mainly baseline diseases were majorly leukaemia (26.8%) and hypertension (32.4%), followed by diabetes mellitus, chronic obstructive pulmonary disease, kidney transplantation, and coronary atherosclerotic heart disease. The most common infected fungus was Aspergillus (40.8%). The voriconazole trough concentration was 2.9 (1.6, 4.9) μg/mL, with a range of 0.4~15.5 μg/mL among the patients, 42 patients suffered from hypokalemia, accounting for 29.6%, and 21 patients suffered from hyponatremia, accounting for 14.8%. Hypokalemia and hyponatremia were mainly observed in 1 to 5 d after voriconazole administration, accounting for 57.1% and 42.9%, respectively. Most of the patients with hypokalemia and hyponatremia received the agent through intravenous injection. The duration of hypokalemia after oral administration was long, while the time with intravenous injection was short. There were no correlations of voriconazole trough concentration with serum potassium and sodium (r=0.001, P=0.989; r=0.150, P=0.052). Conclusion Under routine dose, the incidences of hypokalemia and hyponatremia are quite high after intravenous injection of voriconazole, and they mainly occur in the early time after administration. Special attention should be paid to the adverse effects in clinical practice.

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Objective To investigate the effects of JAK2 rs10119004 gene polymorphism on voriconzole blood concentration (Cmin) and therapeutic efficiency, and provide a reference for the individualized treatment of intensive care unit (ICU) patients who were diagnosed with invasive fungal infection. Methods The genotypes of JAK2 rs10119004 were detected by PCR and Sanger sequencing methods. The steady-state trough plasma concentration of voriconazole was detected by LC-MS/MS. The characteristics of Cmin, curative effects and adverse reactions in patients with different genotypes were analyzed. Results The trough blood concentration of voriconazole in 70 patients ranged from 0.12 to 12.23 mg/L, with an average of 3.07 (1.92, 5.48) mg/L. JAK2 genotypes were distributed as follows, 25 cases of wild unmutated G/G, 32 cases of heterozygous mutant G/A and 13 cases of homozygous mutant A/A. There were no significant differences in the effective rate of treatment and the incidence of adverse reactions between patients with different blood drug concentrations and different genotypes. There were significant differences in the plasma concentration of voriconazole between patients with different ages, plasma albumin (ALB) levels and JAK2 rs10119004 genotypes. The statistically significant influencing factors were included in the multiple regression model to obtain the final regression model C1=7.479+0.048×Age-0.233×ALB+1.405×X1 and C2=7.479+0.048×Age-0.233×ALB+1.208×X2 (X1: G/A=1, non G/A=0; X2: A/A=1, non A/A=0). Conclusion The genotypes of JAK2 rs10119004 can affect the Cmin of voriconazole in patients with invasive fungal infection in ICU. [ABSTRACT FROM AUTHOR]

To investigate the distribution of pathogenic bacteria and drug sensitivity results in lower respiratory tract infection in Suzhou First People' s Hospital( hereinafter referred to as "our hospital" ), so as to guide the rational and effective selection of clinical antibiotics. METHODS: From Jan. 2015 to Jan. 2020, 1 636 qualified sputum samples from patients with lower respiratory tract infection in our hospital were examined for etiology. RESULTS: Totally 853 pathogenic bacteria were isolated from 1 636 sputum samples, including 703 Gram-negative bacteria ( 82. 42%), 112 Gram-positive bacteria ( 13. 13%) and 38 fungi (4. 45%). The drug sensitivity results showed that Pseudomonas aeruginosa had the highest resistance rate to cefazolin ( 100. 00%) and the lowest resistance rate to imipenem(4. 65%) and meropenem ( 4. 65%). Klebsiella pneumoniae had the highest resistance rate to ampicillin (100. 00%) and the lowest resistance rate to meropenem( 5. 00%) and imipenem( 5. 00%). Escherichia coli had the highest resistance rate to ampicillin (57. 30%), and the lowest resistance rate to meropenem ( 1. 12%) and imipenem ( 1. 12% ). Acinetobacter baumannii had the highest resistance rates to ampicillin ( 100.00%) and cefazolin ( 100.00%), and the lowest resistance rate to meropenem(54. 69%). Staphylococcus aureus had the highest resistance rate to penicillin ( 100.00%), and the lowest resistance rate to nitrofurantoin ( 0%), tigecycline ( 0%), linezolid (0%), vancomycin ( 0%) and levofloxacin ( 0%). Streptococcus pneumoniae had the highest resistance rate to erythromycin( 100. 00%), clindamycin ( 100.00%) and tetracycline ( 100.00%), and the lowest resistance rate to oxacillin ( 0%), amoxicillin ( 0%), cefoxitin ( 0%), tobramycin ( 0%), rifampicin ( 0%), gentamicin ( 0%), ciprofloxacin( 0%), teicoplanin(0%), vancomycin(0%), nitrofurantoin (0%), tigecycline (0%), linezolid (0%) and levofloxacin ( 0%). Candida albicans had the highest resistance rate to fluconazole ( 20. 00%), and the lowest resistance rate to voriconazole ( 6. 67%). Candida glabrata had the highest resistance rate to fluconazole ( 60. 00%) and itraconazole ( 60.00%), and the lowest resistance rate to amphotericin B (0%) and voriconazole(0%). Candida tropicalis had the highest resistance rate to itraconazole ( 66. 67%) and the lowest resistance rate to amphotericin B (0%) and voriconazole ( 0%). CONCLUSIONS; The lower respiratory tract infections in our hospital in the past 5 years were dominated by Gram-negative bacteria with high resistance to broad-spectrum penicillins and low resistance to carbapenems and compound preparations containing f3-lactamase inhibitors. Clinical selection of antibiotics should be based on bacterial culture results and resistance rates, and individualized treatment protocols should be developed to improve the efficacy and curb the emergence of multi-drug resistant bacteria. [ABSTRACT FROM AUTHOR]

Objective To develop liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the content determination of voriconazole (VRCZ) and its N-oxide (VNO) in human plasma, and to apply it to clinical samples. Methods Ketoconazole was used as the internal standard (IS). The plasma samples were treated with methanol to precipitate protein and analyzed by HPLC-MS/MS. The detection was accomplished with electrospray ionization (ESI) operated in positive ionization mode, and ion reaction pairs were selected to be m/z350.1→m/z127.0 (VRCZ), m/z366.1→m/z224.0 (VNO) and m/z531.0→m/z82.1 (Ketoconazole). Chromatographic separation had been achieved on Inertsil ODS-3 (50/2.1) with methanol-10 mmol/L ammonium acetate (90:10) as the mobile phase. Plasma concentrations of VRCZ and VNO in 23 patients were determined. Results Both VRCZ and VNO were linear (r>0.999) over the concentration ranges of 0.4~10.0 μg/mL, inter- and intra-batch relative standard deviations (RSDs) and matrix effect were all less than 15%. The 2 compounds remained stable during sample storage and handling progress. Plasma concentrations of VRCZ in 23 patients ranged from 0.4 to 14.3 μg/mL, and those of VNO ranged from 0.5 to 7.2 μg/mL. Significant variance was found among these patients. Conclusion LC-MS/MS is simple, quick and sensitive for detection of VRCZ and VNO, and can be used for drug monitoring in clinical practice.

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Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To establish an UPLC-MS/MS method of voriconazole assay in human plasma for clinical therapeutic drug monitoring. Methods The plasma samples were treated with methanol to precipitate protein and the supernatants were assayed by UPLC-MS/MS. The chromatographic column was InertSustain C18 HP (3.0 mm×100 mm, 3 μm) with the mobile phase of water and acetonitrile solution (15:85) at 35 ℃ and 0.3 ml/min flow rate. ESI was used for Mass Spectrum in positive ion MRM mode with target ions m/z: 350.9/282.2(voriconazole) and m/z: 307.0/238.0(fluconazole). Results The linear range of voriconazole was 0.1–20 μg/ml (r=0.999 5）. The lower limit of quantitation was 0.1 μg/ml. The extraction recovery was higher than 90%. RSDs of inter-day and intra-day were all lower than 10%. The plasma concentrations measured by this method were in the range of 0.97 to 18.7 μg/ml from 10 patients with hepatic insufficiency who were treated with voriconazole. Conclusion The established method was fast, accurate and sensitive。It can be applied for the therapeutic drug monitoring of voriconazole， and provided a good base for rationalized medication treatment in patients with hepatic insufficiency. [ABSTRACT FROM AUTHOR]

Objective: To explore the application value of simultaneous monitoring of voriconazole (VRCZ) and voriconazole N-oxide (VNO) in efficacy and safety of VRCZ in the prevention and treatment of fungal infections in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients before engraftment (i.e., days +1 to +30 after transplantation)., Methods: The influencing factors of VRCZ, VNO concentration and MR (C VNO /C VRCZ ) and the difference of VRCZ in the prevention and treatment of fungal infection and liver and kidney injury were analyzed. The receiver operating characteristic curve (ROC) was used to analyze the differences (the corresponding to the maximum of the Youden index on the curve was set as the cut-off value) to confirm the critical value., Results: The factors affecting VRCZ concentration (C VRCZ ), VNO concentration (C VNO ) and MR were patient weight, VRCZ daily dose, and transplantation type (all P < 0.05). C VRCZ and C VNO in the effective group were higher than those in the ineffective group ( P < 0.001), the opposite of MR ( P < 0.001); the liver and renal injury group had lower MR than the normal group ( P < 0.05). ROC showed that C VRCZ , C VNO and MR had important value in predicting VRCZ in the prevention and treatment of invasive fungal infections in allo-HSCT patients before engraftment, and their cutoff of concentrations were 0.95 μg/ml, 1.35 μg/ml and 1.645, respectively (AUC: 0.9677, 0.7634, 0.9564). C VRCZ and MR can assist in indicating liver ［cutoff values: 0.65 μg/ml, 1.96 (AUC: 0.5971, 0.6663)］ and renal injury ［cutoff values: 0.95 μg/ml, 1.705 (AUC: 0.6039, 0.6164)］., Conclusion: The great value of simultaneous monitoring of VRCZ, VNO and MR can predict in the efficacy and safety of VRCZ in allo-HSCT patients before engraftment. The prediction accuracy of C VRCZ was higher than that of MR, followed by that of C VNO . Increased C VRCZ and decreased MR increase the risk of liver and kidney injury.

Objective To observe and compare the plasma concentration of voriconazole and its efficacy in patients who were diagnosed with severe invasive fungal infection ( IFI) with different CYP2C19 * 3 genotypes. Methods A total of 70 IFI patients treated with voriconazole were enrolled. Cubital venous blood was collected and was put into the ethylene diamine tetraacetic acid (EDTA) anticoagulant tubes on the early morning of the third day before giving next dosage. Ge-nomic DNA was extracted from whole blood. Polymerase chain reaction ( PCR) and Sanger sequencing were used to detect human CYP2C19 * 3 genotypes. According to their genotypes of CYP2C19 * 3, patients were classified into three groups: GG, GA, and AA groups. Ultra Performance Liquid Chromatography and Xevo TQS triple quadrupole tandem mass spectrometer were used to detect blood concentration of voriconazole. All 70 patients were given conventional dosage administration for at least one week. The therapeutic effects and adverse reaction were evaluated, and the therapeutic efficiency rate and incidence of adverse reaction were calculated. Results Among 70 IFI patients, there were 60 patients with CYP2C19 * 3 GG genotype and 10 patients with CYP2C19 * 3 GA genotype but there was no CYP2C19 * 3 AA genotype. The plasma concentration of voriconazole for patients with GA genotype [ ( 5. 80 ± 2. 16) mg/L J was higher than for those with GG genotype [ ( 3.58 ± 2.84) mg/L]. There was significant difference in the plasma concentration of voriconazole between the groups with GG genotype and GA genotype ( P < 0. 05). For patients with GG genotype, the rate of therapeutic efficiency was 55% ( 33/60), and the incidence of adverse reaction was 26.67% ( 16/60). For patients with GA genotype, the rate of therapeutic efficiency was 90% ( 9/10), and the incidence of adverse reaction was 40% ( 4/10). There was significant difference in the rate of therapeutic efficiency between the two groups ( P < 0.05), but there was no significant difference between the two groups in the incidence of adverse reaction ( P > 0.05). Conclusion Plasma concentration of voriconazole and therapeutic efficiency rate are higher in patients with CYP2C19 * 3 GA genetype than in patients with CYP2C19 * 3 GG genotype. [ABSTRACT FROM AUTHOR]

Objective ： To explore the characteristics of voriconazole-induced adverse drug reactions (ADRs ) in the nervous system，so as to provide reference for rational drug use clinically .Methods : Clinical manifestations and high risk factors in a case of voriconazole-induced epilepsy seizure and mental disorders were analyzed，and pathogenic mechanism as well as prevention and treatment measures were also analyzed in combination with relevant literature .Results： Epilepsy seizure was rarely seen in neurological ADRs induced by voriconazole .High blood concentration of voriconazole in the patient was the main cause of nervous system ADRs . Conclusion ： Blood concentration monitoring of voriconazole was mandatory clinically，and individualized medication should be implemented，so that ADRs in the nervous system could be avoided due to high blood concentration of voriconazole. [ABSTRACT FROM AUTHOR]

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Objective: To establish a method for the determination of voriconazole in plasma of Wistar rats by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and also to study the pharmacokinetics and distribution of the metabolites voriconazole nitrogen oxides in the tissues of 2 kinds of voriconazole injections in rats. Methods: The rats were randomly divided into 2 groups. Domestic and imported voriconazole injections were respectively injected in tail veins, and then blood and tissue samples were collected at different time points. The drug concentrations were detected by HPLC -MS/MS method. The mobile phase was acetonitrile-0.2% glacial acetic acid aqueous solution (containing 20 mmol/L ammonium acetate) 80 : 20 (V/V), and flow rate was 0.5 ml /min. The multiple reaction monitoring (M RM) was used to detect the levels of voriconazole and voriconazole nitrogen oxides. The detected ion pairs were m/z 350.2→281.0 (voriconazole), m/z 366.1→224.0 (vorconazole nitrogen oxides) and m/z 307.1 →220.1 (fluconazole). The pharmacokinetic parameters of the 2 injections were determined by non-compartment model (statistical moment method) using Phoenix WinNolin 64 data processing software. The distributions of voriconazole and voriconazole nitrogen oxides in the tissues of the heart, liver, brain, lung, spleen and kidney were analyzed statistically. Results: Voriconazole and voriconazole nitrogen oxides were in good linearity with peak area. The precision, reproducibility and stability were good. AUCq-24 h of voriconazole for the domestic and imported voriconazole injec tions was (244. 4 ± 25.1) and (207.1 ± 19.1) µg ⋅ h ⋅ ml-1. AUCq-24 of Voriconazole nitrogen oxides were respectively (60.5 ± 8.6) and (61.3 ± 5.8) µg ⋅ h ⋅ ml-1. Conclusion: This method is simple, rapid and sensitive, and could be used to study in vivo pharmacokinetics of voriconazole. After giving single dose of domestic and imported voriconazole injections in the veins of the rats, no significant differences could be seen in the main pharmacokinetic parameters and overall exposure in the tissues. [ABSTRACT FROM AUTHOR]

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Objective To analyze the clinical characteristics of the recipients infected with cryptococcus neoformans after renal transplantation. Methods Clinical data of 9 patients infected with cryptococcus neoformans after renal transplantation were retrospectively analyzed, including the infection site, clinical manifestations, mycological, histopathological, imaging examination results, treatment process and clinical prognosis. Results Nine recipients were treated with routine triple immunosuppressive therapy of tacrolimus (FK506) + mycophenolate mofetil (MMF)+ prednisone. The median time of onset was 6 years (1-13 years) after operation. Among them, 1 case was diagnosed with cryptococcal meningitis, 5 cases of cryptococcal meningitis complicated with cryptococcal pneumonia, 2 cases of cryptococcal pneumonia and 1 case of cutaneous cryptococcal infection. Cryptococcal pneumonia was clinically manifested as fever, cough, expectoration, shortness of breath and chest pain, etc. Chest CT demonstrated the signs of nodules and pleural effusion, etc. The diagnosis was mainly confirmed by lung biopsy and negative ink staining of the alveolar lavage fluid. Clinical manifestations of cryptococcal meningitis primarily included fever and paroxysmal headache accompanied by vomiting, which was mainly confirmed by blood culture and negative ink staining of the cerebrospinal fluid. Cutaneous cryptococcal infection was characterized by a mass in the right shoulder, which was confirmed by skin biopsy. All patients were given with standard antifungal therapy including amphotericin B and fluconazole, and immunosuppressive therapy at a reduced dosage. Among 9 recipients, 1 recipient died, and the other recipients obtained excellent clinical prognosis. Conclusions Cryptococcus neoformans infection dominantly occurs in the middle and late stage after renal transplantation presenting with non-specific clinical symptoms. Blood culture, lung biopsy and cerebrospinal fluid examination should be timely performed to validate the diagnosis of this disease. Standard anti-fungal therapy can reduce the mortality rate. [ABSTRACT FROM AUTHOR]

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Objective: To explore pharmaceutical care by clinical pharmacists in the individualized treatment with voriconazole, so as to provide reference for rational use of drugs. Methods: Through analysis of the treatment of 3 cases by voriconazole, the clinical thinking of clinical pharmacists involved in drug treatment was clearly elucidated, and the entry point of pharmaceutical care was analyzed. Results; Based on the results of therapeutic drug monitoring (TDM ), clinical pharmacists proposed proper adjustment in the voriconazole treatment profile, and as a result, clinical efficacy was improved, the rate of adverse drug reactions (ADRs) was reduced, and more importantly medication safety was well ensured. Conclusion; TDM is a powerful tool for active involvement of clinical pharmacists in the individualized treatment with voriconazole, and its proper application could improve clinical efficacy and drug safety. [ABSTRACT FROM AUTHOR]

Objective To establish a HPLC method for the determination of the voriconazole concentration in human plasma, which can be used for voriconazole monitoring clinically. Methods High performance liquid chromatography (HPLC-UV) detection method was used with papaverine as internal standard. Acetonitrile protein precipitation method was employed to treat plasma samples. The chromatographic column was ACE5C18-AR150 mm×4.6 mm with the mobile phase 0.025 mol/L sodium dihydrogen phosphate (containing triethylamine 400 μl/L, pH=7.0 adjusted by 0.25 mol/L sodium hydroxide) - acetonitrile (67:33). The flow rate was l ml/min, the column temperature at 40 °C, the detection wavelength at 255, 276 nm (double wavelength detection) and sampling amount 20 μl. Results The retention time of voriconazole nitrogen oxide, voriconazole and papaverine were 4.5, 11.3 and 13.7 min respectively. The linear ranges of voriconazole and voriconazole nitrogen oxides in plasma were 0.5-20.0 μg/ml (r=0.999 5). The quantitative lower limits were 0.5 μg/ml with RSD< 11%. The recovery rates of extraction were between 90.3% and 109.9%. Conclusion This simple and accurate method is suitable for clinical monitoring of voriconazole. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT. Methods: Nineteen patients with IFR after allo-HSCT at Peking University People's Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) . Results: Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10-59) years. The median IFR onset time was 68 (9-880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation ( P =0.021) , hemorrhagic cystitis after transplantation ( P =0.012) , delayed platelet engraftment ( P =0.008) , and lower transplant mononuclear cell count ( P =0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively ( P <0.01) . Conclusion: Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.

OBJECTIVE: To investigate the clinical application of oral dosage form and intravenous drip dosage form of voriconazole in the Second Xiangya Hospital of Central South University(hereinafter referred to as "our hospital"), and to probe into the application characteristics and tendency of voriconazole, so as to provide references for the clinical reasonable medication and scientific management of voriconazole. METHODS: The clinical application of voriconazole in inpatients from our hospital during 2012-2016 was retrospectively analyzed. Excel software was used to calculate the application departments of voriconazole, the application rate of each department, the frequency of medication and the consumption amount; and the statistical results were analyzed. RESULTS: During 2012-2016, the application rate of oral voriconazole and voriconazole for injection increased continuously, and the frequency of medication showed a trend of increasing year by year; departments with the highest frequency of voriconazole administration were respectively department of urology, hematology, ICU and emergency. The application departments of voriconazole and the consumption amount of the voriconazole were in an increasing tendency. CONCLUSIONS: The clinical application of voriconazole has been increasing gradually and its range of application has been expanding. Therefore, voriconazole plays an important role in the application of antifungal drugs in our hospital. [ABSTRACT FROM AUTHOR]

OBJECTIVE: By participating in pharmaceutical practice for individualized medication for patients after lung transplantation, the clinical pharmacists discusses the application of therapeutic drug monitoring during treatment of immunosuppressive therapy after lung transplantation. METHODS: The clinical pharmacists went into the clinic, performed routine tacrolimus blood concentration monitoring on one patient after lung transplantation, adjusted the medication regimen according to patient’s clinical manifestations, drug combination and auxiliary examination results, and then analyzed the causes of large fluctuation of tacrolimus concentration in the patient, so as to provided individualized treatment for the patient. RESULTS: Due to the drug interactions between tacrolimus and voriconazole, the instability of blood concentration of tacrolimus in patients increased the risk of rejection and adverse drug reactions in patients. The clinical pharmacists monitored the blood drug concentration of tacrolimus closely, adjusted the dose, and finally maintained it within the effective therapeutic ranges. There was no significant renal toxicity. CONCLUSIONS:Although the application of therapeutic drug monitoring in organ transplant patients has certain limitations, it is still the best way to ensure the effectiveness and safety of immunosuppressive therapy after organ transplantation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the effects of voriconazole combined with imatinib on drug valley concentration and steady-state pharmacokinetics in inpatients. METHODS ： HPLC method was adopted to determine the drug valley concentration and steady-state pharmacokinetics in inpatients before and after application of voriconazole combined with imatinib, DAS 3. 2. 8 was used to calculate the pharmacokinetic parameters, SAS 9. 0 software was adopted to statistically analyze the drug valley concentration and main pharmacokinetics parameters. RESULTS： After drug combination, the drug valley concentration of imatinib increased significantly compared with before drug combination, with statistically significant difference ( P < 0. 05 ) . The drug valley concentration of voriconazole was higher than the effective concentration. Yet there was no statistical significance between two groups in the pharmacokinetic parameters of imatinib before and after drug combination(P > 0. 05 ) . CONCLUSIONS： Voriconazole combined with imatinib can increase the drug valley concentration of imatinib, yet has few influence on the pharmacokinetic. And the blood concentration of voriconazole should be monitored during drug combination. [ABSTRACT FROM AUTHOR]

Objective To clarify the necessity of therapeutic drug monitoring (TDM) of voriconazole, and give relevant clinical tips, by comparing the plasma concentration of different clinical specialties before and after adjustment of dose. Methods This is a retrospective study of voriconazole TDM data. It involves 435 cases voriconazole plasma trough concentration measurement results of 154 inpatients to make a preliminary assessment. Results 4.3% plasma concentration were higher than 5.5 μg/ml, 26.5% plasma concentration were less than 1.0 μg/ml in renal transplantation department; while 52.3% plasma concentration were higher than 5.5 μg/ml, no less than 1.0 μg/ml in infectious disease department. Conclusions Therapeutic drug monitoring is necessary for rational use of voriconazole. The majority of plasma concentrations in renal transplantation patients were <1.0 μg/ml, lower than recommended treatment concentration range; while most infectious disease patients have > 5.5 μg/ml, higher than recommended treatment concentration range. Clinical pharmacists can be more closely involved in the clinical use of voriconazole based on the results of the therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

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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 (χ 2 =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.

Objective To evaluate the in vitro antifungal activity of Cinnamaldehyde in combination with Voriconazole（VRC） against clinically isolated Aspergillus fumigatus strains. Methods According to the Clinical and Laboratory Standards Institute（CLSI） M38-A2 document,the minimal inhibitory concentrations（MIC） of Cinnamaldehyde and VRC alone or in combination against 42 clinical Aspergillus fumigatus isolates were determined by both microdillution method and check-board method respectively. The MIC50, MIC90, MICG and MICs distribution were compared between single drug and both incombination. The concentration-accumulative curve was drawn and fractional inhibitory concentration index（FICI） was calculated to evaluate the interaction between two test agents. Results The values of MIC50, MIC90 and MICG were significantly decreased（P<0.001） when combination of the two drugs than those of their single use, with their MIC distribution concentration-accumulative curves shifted to the left. The value of FICI of Cinnamaldehye-VRC combination ranged from 0.187 5to 1.5. Sixteen strains（38.10%） of them showed the synergistic effect, 19 strains（45.23%） showed additive effect, and 7strains（16.67%） showed an unrelated effect, and no antagonist effect on tested Aspergillus fumigatus strains in vitro. Conclusion Cinnamaldehye in combination with VRC mainly shows a combined synergic and additive inhibitory effect on Aspergillus fumigatus isolates, and this combination appears to be more active against the test strains, which are less susceptible to voriconazole. [ABSTRACT FROM AUTHOR]

Objective ：To analyze drug therapy in a patient with invasive pulmonary aspergillosis and explore methods for the delivery of pharmaceutical care. Methods ：Clinical pharmacists were actively involved in the whole process of drug therapy for one case of severe invasive pulmonary aspergillus infection, assisted physicians to develop individualized therapeutic regimen and deliver special pharmaceutical care in main drug therapy. Results ：Once the diagnosis of pulmonary aspergillosis was ascertained, clinical pharmacists should advise that voriconazole and other drugs be used without delay. After rational and active treatment, body temperature, blood routine, Creactive protein and other indicators were improved markedly. Inflammatory foci of the lungs were obviously absorbed, as compared with those before treatment. Sputum culture of A spergillus fumigatus turned negative following treatment, and the patient was transferred to local hospital for further treatment. During the whole process of treatment, clinical pharmacists provided good pharmaceutical care and there were no obvious voriconazole-induced adverse drug reactions. Conclusion：Active involvement of clinical pharmacists in the development of antifungal individualized therapeutic regimen and delivery of pharmaceutical care could help to ensure safety and efficacy of treatment. [ABSTRACT FROM AUTHOR]

Objective: To investigate the concentrations of voriconazole (VCZ) in the central nervous system (CNS) of patients with cryptococcal meningitis and the relationship thereof., Methods: We retrospectively analyzed the trough concentration of VCZ in the cerebrospinal fluid (CSF) and the blood of 25 adult patients who had cryptococcal meningitis, and who were not infected with HIV. We also examined patient-level characteristics that could contribute to the differences in CSF/plasma VCZ concentration ratio., Results: The trough concentration of VCZ in plasma ranged from 0.38 to 8.56 mg/L, and the median (P 25 , P 75 ) was 1.81 (1.40, 3.84) mg/L. The trough concentration of VCZ in CSF ranged from 0.17 to 3.92 mg/L, and the median (P 25 , P 75 ) was 1.02 (0.54, 1.84) mg/L. The CSF VCZ trough concentration showed a slight negative correlation with the nucleated cell counts in CSF, but the correlation was not statistically significant ( r =-0.377, P =0.063). There was a positive correlation between VCZ concentrations in CSF and that in the plasma ( r =0.736, P <0.001), and the median (P 25 , P 75 ) CSF/plasma ratio was 0.43 (0.34, 0.68). The CSF/plasma ratio did not statistically correlate with age, body surface area (BSA), radiology changes (hydrocephalus), or intracranial pressure., Conclusion: There is a positive correlation between VCZ concentration in CSF and VCZ concentration in the plasma, and no influencing factors of CSF/plasma ratio were found., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

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.

Fonsecaea species are major etiologic agents of Chromoblastomycosis (CBM). By genetic analysis, the genus Fonsecaea has recently been revised and classified into F. pedorosoi. F. monophora and F. nubica. Here we report a severe chronic case of CBM caused by F. monophora. A 55-year-old Filipino male developed progressive skin lesions on the left lateral ankle in 1973, when he worked at a coconut plantation in the Philippines. In 1999, he received medical treatments for enlarged, multiple lesions on the left lower limb. When he moved to Japan in 2005, the lesions were remarkably improved and he discontinued taking the medicine. On our first examination in October 2008, a large, reddish, cicatricial plaque was observed on the left lower aspect of his leg. Several tumorous lesions surrounded the plaque, indicating that the therapies performed before had been insufficient. In addition, there were many patchy scars scattered on the thigh and the upper part of the lower leg. The diagnosis of CBM was made by the presence of muriform cells. Black, pulverulent colonies were yielded in culture of skin scrapings and tissues. Although the fungus could not be identified by microscopic morphology. r-RNA ITS sequence analysis enabled identification of Fonsecaea monophora. The patient responded well to oral voriconazole combined with local thermotherapy using pocket warmers. The tumoral masses subsided in 6 months, leaving pink scars with negative fungal culture. Voriconazole treatment was continued for 18 months. It seems that drugs are insufficiently delivered in the cicatricial lesions because of the paucity of blood flow, suggesting that a long-term follow-up is necessary for such a case. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the clinical efficacy of caspofungin and voriconazole in treatment of patients with severe invasive fungal infections. METHODS: 100 cases of invasive fungal infections were selected to be divided into observation group and control group via random number table, with 50 cases in each. The observation group were treated with caspofungin (70 mg loading dose, 50 mg maintenance dose) intravenous infusion, while the control group were given voriconazole (400 mg loading dose, 200 mg maintenance dose) intravenous infusion;the clinical efficacy were compared between two groups. RESULTS: The recovery rate of observation group was 44.00% (22/50) , the total effective rate was 86.00% (43/50), higher than those of control group 32.00% (16/50) and 74.00% (37/50), with statistically significant difference (P <0.05). The average hospitalization time, average hospitalization cost of observation group were significantly lower than those of control group, yet the rate of bacteria clearance was higher than that of control group, with statistically significant difference (P<0.05). After treatment of 4 days, the decrease of numeration of leukocyte, C reactive protein and procalcitonin in observation group was more significant than that of before group, and significantly higher than that of control group, with statistically significant difference (P<0.05). There were few changes in liver and kidney function in two groups. CONCLUSIONS: The efficacy of caspofungin in treatment of patients with severe invasive fungal infections is significant, with few adverse drug reactions, which can be used for patients with severe anti-fungal therapy. [ABSTRACT FROM AUTHOR]

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.

Objective: To analyze the etiological changes of children with infectious keratitis. Methods: Retrospective study. Data of patients diagnosed as bacterial, fungal, and amoebic keratitis from 2007 to 2016, aged no more than 14 years old, were collected in the Department of Ophthalmology, Beijing Tongren Hospital. A total of 649 samples were obtained for routine laboratory culture identification and drug sensitivity tests. There were 361 males and 278 females, aged (5.6±4.4) years. The data were analyzed according to age ≤3 years, 4 to 7 years and>7 years. The qualitative data were analyzed by the Chi-square test. Results: Among 649 samples, 140 were culture positive, and the positive rate was 21.6%. Bacteria were the main pathogens, accounting for 81.4%. The positive rate was 31.0% among bacterial samples (114/368), and the bacterial flora was mainly Gram-positive cocci, followed by Gram-negative bacilli. Streptococcus (34.2%) ranked first, followed by Staphylococcus (27.2%) and Pseudomonas (7.9%). For children no more than 7 years old, Streptococcus pneumoniae was the most common bacterial species, while Staphylococcus epidermidis was most common in those aged 8-14 years. Gram-positive cocci were sensitive to vancomycin. Most bacteria were more sensitive to fluoroquinolones and less sensitive to cephalosporins and aminoguanidine. The detection rate of methicillin-resistant Staphylococcus was 68% (17/25). Gatifloxacin had the highest sensitivity, while the difference between gatifloxacin and moxifloxacin, levofloxacin, ofloxacin were not statistically significant ( χ ²=0.836,0.358, 1.490; P =0.361,0.550,0.222). A total of 254 specimens were cultured for fungi, of which 22 were positive, and the positive rate was 8.7%. The isolated fungi included Fusarium (34.8%, 8/22), Aspergillus (26.1%, 6/22) and Candida (13.0%, 3/22). The positive rate of fungal culture was 9.2% (11/119) from 2007 to 2011, and 8.1% (11/135) from 2012 to 2016, no significant difference was found between two period ( χ ²=0.096, P =0.757). Fusarium showed a relatively high sensitivity to terbinafine, but it was not sensitive to fluconazole and itraconazole. The sensitivities of Aspergillus to terbinafine and voriconazole were high, followed by amphotericin. Candida had high sensitivities to amphotericin, fluconazole, itraconazole and voriconazole. In 27 specimens for Acanthamoeba culture, 4 specimens were positive, and the positive rate was 14.8%. Risk factors of Acanthamoeba infection included wearing orthokeratology lenses and trauma. Conclusions: Bacteria are the main pathogenic agent of infectious keratitis in children. Streptococcus pneumoniae is the most common in children aged 7 and below, and Staphylococcus epidermidis is the most common in children aged 8-14. Fungal infection was significantly lower than that of bacteria, mainly Fusarium , Aspergillus and Candida.

Objective ：To evaluate clinical application of voriconazole in the Second Hospital Affiliated to Xi ’an Jiaotong University in ２０１４ ．Methods ：The evaluation criteria for clinical application of voriconazole were established ．The use of voriconazole in １００ inpatients of the hospital in ２０１４ was analyzed retrospectively ．Results ：The rates of indication ，drug selection ，dosage regimen ，drug interaction and rationality of detected indicators were ９２％ ，９５ ．６５％ ，５５ ．４３％ ，７８％ and ７４％ ，respectively ．Conclusion ：There was much misunderstanding in the clinical application of voriconazole in the hospital ．For this reason ， it was absolutely necessary to evaluate rational application of drugs in the hospital. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical characteristics, treatment and prognosis of congenital pulmonary airway malformation (CPAM) complicated with chronic pulmonary aspergillosis (CPA) in children. Methods: The clinical manifestation, laboratory test, radiological feature, treatment and prognosis of 4 pediatric patients diagnosis of CPAM with CPA ascertained between March 2016 and April 2020 at the Department of No.2 Respiratory Medicine and Thoracic Surgery of Beijing Children's Hospital were retrospectively analyzed. Results: The 4 children included 2 males and 2 females, their age ranged from 9.9 to 13.6 years. Cough presented in 3 cases, hemoptysis in 2 cases, whereas in 1 case, pneumothorax was the first manifestation of the condition. Past history revealed multiple hospital admissions for pneumonia in 2 children and 1 with more than 2 episodes of wheezing. Aspergillus IgG was positive in 3 patients. Significantly elevated total IgE and fumigatus-specific IgE levels were noted in 2 children. CT demonstrated multiple cystic lesions, and fungal balls were seen in 2 children. They all underwent lobectomy and the lung tissue from the 4 children all demonstrated CPAM with Aspergillus infection. Aspergillus fumigatus was isolated from the abscess collected during operation in 1 patient. Postoperative, voriconazole was given in 3 children for 8 weeks, recurrence was observed in 2 children with characteristics of allergic bronchopulmonary aspergillosis. Voriconazole was given in one patient for 12 weeks with no recurrence. Conclusions: CPAM might be complicated with CPA,if there are hemoptysis, and fungal ball in chest CT, cautious preoperative examinations for microorganism are necessary. The necessity and duration of postoperative antifungal therapy need to be determined on individual basis.