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

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

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

OBJECTIVETo summarize the clinical features, imaging characteristics, diagnosis and treatment of a case with central nervous system infection caused by Exophiala dermatitidis, as well as to review the related literature.

METHODAssociated literature and clinical data of an 8-year-old boy who was diagnosed as central nervous system infection caused by Exophiala dermatitidis in Beijing Children's Hospital Affiliated to Capital Medical University and hospitalized twice from 2012 to 2014 were analyzed retrospectively.

RESULTThe boy was 8 years old with the chief complaint of dizziness for 2 months, intermittent fever for 1 month accompanied with spasm twice. He was diagnosed as bile ducts space-occupying lesions 2 years ago, when the pathological diagnosis was fungal infection. The boy was treated with irregular anti-fungal therapy. Then the boy developed nervous symptoms, impaired consciousness and abnormal physical activity that developed gradually. After hospitalization the cerebral MRI of the boy showed space-occupying lesions accompanied with edema of surrounding area. Filamentous fungi was found by brain biopsy, which was culture positive for Exophiala dermatitidis. After diagnosis the boy was treated with amphotericin B (AMB), voriconazole and 5-Fu, as well as symptomatic treatment. The state of the boy was improved gradually. Two months later, the boy could communicate with others normally and move personally. The lesions and edema seen on the MRI was decreased moderately. Accordingly, the boy was treated with oral voriconazole maintenance treatment for about 1 year and 4 months after discharge. During this period, the state of him was stable without symptoms. The lesions shown by MRI did not disappear but decreased on regular examination. However, recently the disease of the boy progressed again, with dizziness, neck pain, headache and progressive nervous symptoms (intermittent spasm, inability to cough, and impaired consciousness). The boy died at last, even with the active treatment at the second hospitalization. Exophiala dermatitidis was culture-positive again in his CSF, and was confirmed by PCR successfully.

CONCLUSIONThe central nervous system infection caused by Exophiala dermatitidis is rare. Clinical features of this disease were similar to those of other fungal CNS infection, cerebral MRI of which could show the similar lumpy lesions. Diagnosis of the disease should be based on pathology and culture.

Amphotericin B ; administration & dosage ; Antifungal Agents ; administration & dosage ; Brain ; diagnostic imaging ; microbiology ; pathology ; Central Nervous System Infections ; diagnosis ; drug therapy ; microbiology ; Cerebrospinal Fluid ; microbiology ; Child ; Drug Therapy, Combination ; Exophiala ; isolation & purification ; Fatal Outcome ; Fluorouracil ; administration & dosage ; Humans ; Magnetic Resonance Imaging ; Male ; Mycoses ; diagnosis ; drug therapy ; microbiology ; Radiography ; Voriconazole ; administration & dosage

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

Adolescent ; Adult ; Aged ; Antifungal Agents ; therapeutic use ; Drug Therapy, Combination ; Echinocandins ; administration & dosage ; therapeutic use ; Female ; Hematologic Neoplasms ; drug therapy ; microbiology ; Humans ; Lipopeptides ; Male ; Middle Aged ; Mycoses ; drug therapy ; Pyrimidines ; administration & dosage ; therapeutic use ; Treatment Outcome ; Triazoles ; administration & dosage ; therapeutic use ; Voriconazole ; Young Adult

The therapeutic effect of sustained intravitreal injectable voriconazole microspheres (VCZ-MS) on an experimental endophthalmitis of Aspergillus fumigatus was investigated. VCZ-MS was prepared successfully and its physico-chemical property was also evaluated. Right eyes of albino rabbits were infected with an intravitreal injection of 1 000 CFU x mL(-1) of susceptible Aspergillus fumigatus. All fungal endophthalmitis models were randomly divided into five groups 48 hours later: Group A is control group with no treatment; in group B, vitrectomy was performed combined with intravitreal 3 times injections of 100 microg x 0.1 mL(-1) voriconazole every other day. In group C, D and E, vitrectomy was performed combined with intravitreal injection of 0.5 mg, 1.0 mg and 1.5 mg VCZ-MS respectively. The treatment effect was assessed by slit lamp and indirect ophthalmoscope funduscopy examination, using clinical grading system of inflammation in the anterior chamber and the vitreous opacity. The optical microscopy revealed that microspheres obtained from the experiment design were opaque, discrete and spherical particles with smooth surfaces. The drug content and encapsulation efficiency of microspheres were 29.94% and 73.5%, respectively. Endophthalmitis occurred in all eyes of group A, and rapidly developed to panophthalmitis. The inflammation grade of group B, C, D or E was lower than that of group A (P < 0.05). The grade of vitreous opacity in group C, D, E is lower than group B (P < 0.05). Two eyes in group C developed to panophthalmitis. But in group D and E, all eyes whose inflammation was controlled had no recurrence with vitreous clear. Histopathological examination showed normal structures in the cured eyes, while most uncured eyes were atrophic and with eyeball destroyed. So, it can be safely concluded that the curative effect of intravitreal VCZ-MS is significantly better than that of routine intraocular injection of voriconazole. The optimal dose is the one containing 1.0 mg voriconazole.
Animals ; Antifungal Agents ; administration & dosage ; therapeutic use ; Aspergillosis ; drug therapy ; pathology ; Aspergillus fumigatus ; Delayed-Action Preparations ; Endophthalmitis ; drug therapy ; microbiology ; pathology ; Eye ; microbiology ; pathology ; Female ; Intravitreal Injections ; Lactic Acid ; Male ; Microspheres ; Polyglycolic Acid ; Pyrimidines ; administration & dosage ; therapeutic use ; Rabbits ; Random Allocation ; Triazoles ; administration & dosage ; therapeutic use ; Voriconazole