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

Objective: To determine the in-vitro activity of voriconazole and compare it with amphotericin B, fluconazole, itraconazole, ketoconazole, and caspofungin against local yeast and mold clinical isolates Candida albicans, Candida sp., Aspergillus terreus, Aspergillus niger, and Fusarium cylindrocarpone. Methods: Review of the Institute of Ophthalmology microbiology records were done and was the basis for the local isolates included in the study. Mean inhibitory concentration (MIC) was determined using YeastOne Sensititre Microtitre Colorimery method (TREK Diagnostic Systems, England). Two-way ANOVA, Duncan, and Pearson chi-squared tests were used to analyze the data. Results: All isolates tested were sensitive to voriconazole. Eighty percent (80%) of the isolates were sensitive to amphotericin B and 25% showed resistance to itraconazole. Yeast pathogens were all sensitive to amphotericin B and voriconazole. More than 50% of the yeast pathogens were resistant to ketoconazole. Molds or filamentous fungi showed higher susceptibility to voriconazole than amphotericin B and the other antifungals. Conclusion Voriconazole exhibited good in-vitro activity against the isolates tested. It has the same efficacy on yeast pathogens (Candida albicans and Candida sp.) when compared with amphotericin B. It has superior efficacy on filamentous fungi (Aspergillus and Fusarium). There is a role for voriconazole in the treatment of ocular infections, especially in the setting of poor antifungal drug availability.
Voriconazole ; Amphotericin B ; Candida ; Fusarium ; Aspergillus

Invasive aspergillosis is one of rare causes of mortality for the immune-compromised patients. We present a case of invasive aspergillosis complicated by the occlusion of the internal carotid artery and cerebral infarction in a patient with diabetes mellitus. Although initial biopsy did not find the pathogen, the repeated attempts of sampling showed aspergillosis. Combination of surgical removal of necrotic tissue and voriconazole medication improved symptoms and reduced the burden of infection.
Aspergillosis* ; Biopsy ; Carotid Arteries ; Carotid Artery, Internal* ; Cerebral Infarction* ; Diabetes Mellitus ; Humans ; Mortality ; Voriconazole

We developed a simple, sensitive, and effective ultra-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method with an electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) and positive ion modes to determine diazepam concentrations in human plasma using voriconazole as an internal standard (IS). Diazepam and IS were detected at transition 285.2→193.1 and 350.2→127.1, respectively. After liquid-liquid extraction (LLE) using 1.2 ml of ethyl acetate:n-hexane (80:20, v/v), diazepam and IS were eluted on a Phenomenex Cadenza CD-C18 column (150 × 3.0 mm, 3 µm) with an isocratic mobile phase (10 mM ammonium acetate in water:methanol [5:95, v/v]) at a flow rate of 0.4 mL/min. The peak retention time was 2.32 min for diazepam and 2.01 min for IS, respectively. The lower limit of quantitation (LLOQ) was 0.5 ng/mL (S/N > 10) using 50 µL of plasma, and no interferences were observed in chromatograms. Our analytical method was fully validated and successfully applied to a bioequivalence study of two formulations of diazepam in healthy Korean volunteers.
Ammonium Compounds ; Diazepam* ; Humans* ; Liquid-Liquid Extraction ; Mass Spectrometry ; Methods* ; Plasma* ; Therapeutic Equivalency* ; Volunteers ; 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

OBJECTIVE: This study was performed to compare the changes in the blood concentrations of tacrolimus when either itraconazole or voriconazole is together with tacrolimus to prevent or treat invasive aspergillus pneumonia (IAP) in patients with lung transplants. Therefore we can compare the degree of drug-drug interactions between tacrolimus and itraconazole against tacrolimus and voriconazole. METHODS: Patients who were admitted and had lung transplants in a territory referral hospital from September 2012 to May 2015 were analyzed retrospectively. The effects of itraconazole and voriconazole on the plasma concentrations of tacrolimus were analyzed. RESULTS: Mean tacrolimus concentrations was 10.49±2.35 ng/mL vs. 10.95±2.98 ng/mL (p=0.722), and mean concentration of tacrolimus over the dose of tacrolimus per day was 8.510±5.890 (ng/mL)/(mg/d) vs. 15.45±28.47 (ng/mL)/(mg/d) (p=0.947) in itraconazole vs. voriconazole group each. The ratio of the number of the results out of target tacrolimus concentrations to the total number of tacrolimus concentration results was 18.0±13.3% vs. 24.4±18.5% (p=0.185). CONCLUSION: There were no significant differences between itraconzaole and voriconazole to have influences on mean concentrations of tacrolimus over tacrolimus dose per weight per day. However voriconazole tended to raise tacrolimus plasma concentrations more than itraconazole. Safer and more effective drug management to prevent and treat fungal infections should be done by therapeutic drug monitoring not only of tacrolimus but of itraconazole and voriconazole in lung transplant patients.
Aspergillus ; Drug Interactions ; Drug Monitoring ; Humans ; Itraconazole* ; Lung* ; Plasma* ; Pneumonia ; Referral and Consultation ; Retrospective Studies ; Tacrolimus* ; Transplant Recipients* ; Voriconazole*

BACKGROUND: Invasive fungal infections (IFIs) are a life-threatening problem in immunocompromised patients. Despite timely diagnosis and appropriate antifungal therapy, clinical outcomes of IFIs remain unsatisfactory, necessitating treatment with a combination of antifungal agents. Therefore, childhood leukemic patients treated with voriconazole plus caspofungin were evaluated for the safety and efficacy of the combination antifungal therapy to treat IFIs. METHODS: In this retrospective study, medical records were retrieved for patients admitted to the Pediatric Department of Yeungnam University Hospital, Daegu, South Korea, between April 2009 and May 2013. Medical records of 22 patients were analyzed. RESULTS: Of the 22 patients studied, nine (41%) had been diagnosed with probable IFI, and 13 (59%) with possible IFI. All patients, except one, were already receiving antifungal monotherapy for the treatment of neutropenic fever. After a diagnosis of IFI was confirmed, antifungal monotherapy was replaced with combination therapy. The study's overall response rate was 90.9%, with complete responses in 86.3% of the patients. Two patients experienced a side effect of a small increase in liver enzyme levels. CONCLUSION: Voriconazole plus caspofungin combination therapy is an effective and safe treatment for serious IFI in pediatric patients with acute leukemia.
Antifungal Agents ; Aspergillosis ; Child* ; Daegu ; Diagnosis ; Echinocandins ; Fever ; Humans ; Immunocompromised Host ; Korea ; Leukemia* ; Liver ; Medical Records ; Retrospective Studies ; Voriconazole*

Dermatophytes usually infect keratinized epithelial structures such as hair and nails. However, they can also cause deep and extensive fungal infections, especially in immunocompromised patients. We report a case with multiple dermal abscesses, which is a rare manifestation of Trichophyton rubrum infection. A 54-year-old man presented with multiple subcutaneous nodules in both inguinal areas with associated tinea cruris. Histopathological findings showed abscesses with fungal hyphae highlighted using Periodic acid-Schiff diastase (PAS-D) staining. Trichophyton rubrum was isolated on a fungal culture of the biopsy specimen obtained from a subcutaneous nodule in the inguinal area. The lesions were resistant to treatment with itraconazole (100 mg twice a day for 6 months); thus, we changed the drug to voriconazole (200 mg twice a day for 3 months). In addition, we extracted the remaining big lesions by incision and drainage. The patient was successfully treated with voriconazole and surgical method.
Abscess* ; Amylases ; Arthrodermataceae ; Biopsy ; Drainage ; Hair ; Humans ; Hyphae ; Immunocompromised Host ; Itraconazole ; Methods ; Middle Aged ; Tinea ; Trichophyton* ; Voriconazole

Dermatophytes usually infect keratinized epithelial structures such as hair and nails. However, they can also cause deep and extensive fungal infections, especially in immunocompromised patients. We report a case with multiple dermal abscesses, which is a rare manifestation of Trichophyton rubrum infection. A 54-year-old man presented with multiple subcutaneous nodules in both inguinal areas with associated tinea cruris. Histopathological findings showed abscesses with fungal hyphae highlighted using Periodic acid-Schiff diastase (PAS-D) staining. Trichophyton rubrum was isolated on a fungal culture of the biopsy specimen obtained from a subcutaneous nodule in the inguinal area. The lesions were resistant to treatment with itraconazole (100 mg twice a day for 6 months); thus, we changed the drug to voriconazole (200 mg twice a day for 3 months). In addition, we extracted the remaining big lesions by incision and drainage. The patient was successfully treated with voriconazole and surgical method.
Abscess* ; Amylases ; Arthrodermataceae ; Biopsy ; Drainage ; Hair ; Humans ; Hyphae ; Immunocompromised Host ; Itraconazole ; Methods ; Middle Aged ; Tinea ; Trichophyton* ; Voriconazole

OBJECTIVETo investigate the diagnosis and treatment of invasive pulmonary aspergillosis (IPA) in children.

METHODThe clinical data of 16 cases of proven or probable IPA who had been in our Hospital from January 2006 to June 2014 were retrospectively analyzed.

RESULTAmong the 16 patients, 11 were males and 5 were females. One child had proven IPA and 15 children had probable IPA. Host risk included long duration use of multiple broad-spectrum antibiotics in 16 cases, neutropenia in 9 cases, invasive mechanical ventilation in 3 cases, primary immunodeficiency disease in 2 cases, long-term use of glucocorticoids in 2 cases, measles in 2 cases, and congenital pulmonary hypoplasia in 1 case. Fever, cough and expectoration were present in all the children with IPA. At the time of diagnosis, the halo sign and subpleural wedge consolidation shadows were more common in neutropenia group (5/9, 7/9) than those in non-neutropenia group(0/7, 1/7)(P<0.05). The cavities and"air-crescent sign"were more common after 15 days to 1 month when the children had been treated with anti-aspergillosis drugs than that at the onset of diagnosis of IPA (P<0.05). The positive rate of serum galactomannan (GM) test was higher than that of sputum culture and serum G test (P<0.05). Thirteen children received voriconazole, in 7 of the children the treatment was effective.

CONCLUSIONNeutropenia were the common host risk factors in children with IPA. Subpleural wedge consolidation shadows, the halo sign and the"air-crescent"sign were highly suggestive of the diagnosis of IPA in children. Subpleural wedge consolidation shadows and the halo sign were more common in neutropenia group than in non-neutropenia group in the early stage of the course. Serum GM test played an important role in the diagnosis of IPA in children. Voriconazole was effective in majority of the children with IPA.

Anti-Bacterial Agents ; Aspergillosis ; Child ; Cough ; Female ; Fever ; Glucocorticoids ; Humans ; Male ; Mannans ; Measles ; Neutropenia ; Retrospective Studies ; Risk Factors ; Sputum ; Voriconazole