Itraconazole Group Research Articles

Acute effect of Fluconazole, Itraconazole and Voriconazole on blood glucose in normoglyceamic & diabetic rats: an experimental study

Anti-fungal and antimicrobials are frequently co-prescribed either to manage or treat either the secondary complications or other diseases. Among antifungal drugs Fluconazole, Itraconazole & Voriconazole are most commonly used. The present study was undertaken to further confirm the effect of Voriconazole as well as other antifungal drugs on blood Glucose level. Aim & Objectives: 1. To Study the effect of Fluconazole, Itraconazole & Voriaconazole in Normoglycemic & Diabetic Rats on Blood Glucose. 2. To compare the effects between all drugs. Material & Methodology: Grouping: Animals divided into 8 groups in each group 6 animals. Group 1- 4: Normoglycemic rats, Group 5-8 Diabetic rats (alloxan induced) Group 1,5: received vehicle (Normal saline) Group 2,6: received Fluconazole (18mg/kg BW), Group 3,7 received Itraconazole (18mg/kg BW) Group 4,8 received Voriconazole (18mg/kg BW). The glucose levels were estimated by Glucometer method (Accu-check active) at the interval of 0, ½ hr, 1hrs, 2hrs & 4hrs after drug administration. Results: Effect on blood glucose in Normoglycemic Rats: Voriconazole had a significant hypoglycaemic effect which appeared after 1 hr (‘p’ value= 0.0102) of administration & persisted up to 2 hrs (‘p’ value=0.0001). However effect of Voriconzole was found to be declined after 2 hrs. There was no significant change in blood glucose in normoglycemic rats with Fluconazole & Itraconazole. Effect on blood glucose in Diabetic Rats: (Table 2): Voriconazole had a significant hypoglycaemic effect which appeared after 1 hr (‘p’ value=0.013) of administration & persisted up to 2 hrs (‘p’ value=0.001) in acute studies. However effect of Voriconzole was found to be declined after 2 hrs. There was no significant change in blood glucose in diabetic rats with Fluconazole & Itraconazole treated. Conclusion: Itraconazole, Fluconazole can be safely used in diabetic with fungal infections. Voriconazole should be avoided in diabetics to minimise the further hypoglycaemia.

Itraconazole Combined with Daunorubicin Synergistically Inhibit Proliferation and Enhance Apoptosis on KG-1a Cell Line through the Suppression of Hedgehog Pathway

Background:Itraconazole is widely used as antifungal drug. It was recently found to be a potent antagonist of the Hedgehog (Hh) signaling pathway. Due to its inhibition of Hedgehog singling, it may prove beneficial in the treatment of hematological malignancies when combined with chemotherapy.Objective To explore the effect of single itraconazole and in combination with daunorubicin on the growth, apoptosis and expression of shh and Gli1 of acute myeloid leukemia cell line KG1α.Methods Different concentrations of itraconazole (ITC), daunorubicin (DNR) and IC30 concentration of daunorubicin (0.73 μΜ) in combination with different concentrations of itraconazole (2, 6,15μΜ) were added to acute myeloid leukemia cell line KG1α. Cell proliferation activity were detected with CCK8 method after cultivating for 48h. Cell apoptosis rate, mitochondria injury and cell cycle arrest condition were detected 48 hours after the action with single drug or drug combination with flow cytometry. Clone forming experiment was performed to detect the clone forming ability of KG 1α continuously treated with the drug. 46 kinds of apoptosis related protein were detected by protein array. Expression of shh and Gli1 were detected by Western Blot.Results: The detected KG1α cell proliferation inhibition rate increased with the increase of the concentration of daunorubicin and itraconazole. The combination of DNR 0.73μΜ and ITC 6μΜ showed synergistic effect; The apoptosis rate in two drug combination group was of statistical difference compared with that of ADM 0.73μM group and ITC 6μM group (P<0.01). Mitochondria injury showed that the P2/P3 ratio in single ADM and ITC group was significantly lower than that of the combination group (P<0.05). DNR arrested the cells in G2 phase, while ITC arrested cells in G1 phas; the two drugs combination significantly arrested cells in G2 phase, with statistical difference. Protein array showed significantly decrease of apoptosis inhibit factor Xiap and increase of apoptosis induce factor Smac in the combination group. ITC inhibited cell’s clone forming ability, and down-regulated the expression of shh and Gli1.Conclusion: Itraconazole or in combination with daunorubicin may inhibit KG1α cell proliferation, induce mitochondria injury and apoptosis, which might be caused by the suppression of Hedgehog signal pathway related protein. DisclosuresLiu:It was supported by National Natural Science Foundation of China (81270647, 81300445, 81200388); National High Technology Research and Development Program of China (863 Program) (2011AA020105); National Public Health Grand Research Foundation (201202017);: Research Funding; It was supported by Natural Science Foundation of Guangdong Province (S2012010009299); the project of health collaborative innovation of Guangzhou city (201400000003-4, 201400000003-1);: Research Funding; It was supported by the Technology Plan of Guangdong Province of China (2012B031800403); the project of the Zhujiang Science & Technology Star of Guangzhou city (2013027).: Research Funding.

A Randomized, Controlled, Prospective Study for Efficacy of Micafungin Versus Itraconazole As Empirical Antifungal Therapy for Febrile Neutropenic Patients with Acute Leukemia

Background: Micafungin, one of the powerful ecchinocandins, needs to be clarified its efficacy and safety of empirical therapy on febrile neutropenic patients compared with other anti-fungal drugs such as azole compounds.Methods: A randomized, multi-center, prospective study (age-, sex-, diagnosis-, risk-controlled) was conducted for a comparison of efficacy and safety between micafungin and intravenous itraconazole as an empirical therapy on febrile neutropenic patients with acute leukemia. Anti-fungal drugs (study drug, micafungin; control drug, itraconazole) were administrated for sustained high fever following appropriate empirical antibiotic therapy (°Ã 3 days of combination antibiotics). The overall success rate [if the patient meets all of the following criteria: (1) no breakthrough fungal infection; (2) survived for 7 days past the end of the therapy; (3) no premature discontinuation; (4) disappearance of fever during neutropenia; (5) successfully treated base-line fungal infection] and side effects were evaluated. And duration of fever and neutropenic fever were estimated and compared between two groups.Results: A total of 134 patients with acute leukemia were enrolled in the study (86 patients with AML, 41 patients with ALL, 7 patients with secondary leukemia). The overall success rate of micafungin and itraconazole was 63.6% and 53.2%, respectively (p = NS) (Figure 2). However, duration of fever and duration of neutropenic fever were significantly shorter in micafungin group (p = 0.0007, p = 0.0118, respectively) and survival benefit was marginal (OS, median months, 10.93 vs. 4.77, p = NS) (Figure 1). Grade III-IV adverse events including hyperbilirubinemia (2 vs. 7), elevation of transaminase level (2 vs. 4), electrolytes imbalance (1 vs. 2), atrial fibrillation (1 vs. 0), and anaphylaxis (1 vs. 0) occurred at 7 and 13 patients in micafungin (10.4%) and itraconazole (18.8%) group, respectively. All adverse events were manageable however, 4 patients died of progression of infection in each group.Conclusion: This randomized, controlled, prospective study documented that micafungin, when compared with itraconazole, showed significantly superior effect on shortening the duration of fever and neutropenic fever, resulting in marginal survival benefit on acute leukemia patients who are suffering from life-threatening neutropenic period under anti-leukemic therapy. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Evaluation of the protective effect of silibinin in rats with liver damage caused by itraconazole.

Itraconazole (ITZ) belongs to the triazole group of antifungals with potent keratinophilic and lipophilic features. Hepatotoxicity is one of its most remarkable features. Silibinin (SIL) is a plant used worldwide which is used in the treatment of many liver diseases and it is especially very well known for its hepatoprotective-cytoprotective effect. The aim of our study was to research the protective effect of SIL in ITZ-induced hepatotoxicity using biochemical and pathological tests. Liver enzymes and antioxidant enzyme activities were measured spectrophotometrically by using commercial kits. ALT and AST levels in ITZ group were significantly increased compared to the group, while the activities of GSH-Px and SOD had decreased (p<0.05). When ITZ group was compared to ITZ+SIL group, AST, ALT, and levels of NO and MPO were significantly decreased, while the activities of GSH-Px and SOD were increased (p<0.05). Histopathological evaluation showed that SIL significantly decreased periportal inflammation and parenchymal hepatocyte apoptosis in ITZ and ITZ+SIL groups (p<0.05). Eventhough not statistically significant, partial improvement with the use of SIL has been detected (p>0.05) in hepatocyte degeneration and multinuclear giant cell formation. According to the evaluation performed with comet assay method, ITZ leads to DNA damage, and the use of SIL significantly decreases DNA damage (p<0.05). We have detected that the use of ITZ increases oxidative stress (MPO, NO), decreases antioxidant activity (SOD and GSH-Px), and leads to DNA damage and histopathological liver damage, whereas the use of SIL has a cytoprotective effect on the liver by increasing the antioxidant effect (SOD, GSH-Px) and by decreasing the oxidative stress (NO, MPO). ITZ causes the generation of ROS and leads to DNA damage and liver damage. SIL has a cytoprotective effect on the liver by increasing antioxidant enzyme activities, preventing the formation of ROS.

Effect of the addition of antimicrobial agents on Shore A hardness and roughness of soft lining materials.

While the incorporation of antimicrobial agents into soft denture liners has been suggested as a reliable alternative treatment for denture stomatitis, it may affect the liner's properties. The effect of addition of antimicrobial agents for the treatment of denture stomatitis on the surface roughness and Shore A hardness of soft lining materials was evaluated. The test groups comprised specimens (36 × 7 × 6 mm(3) ) of soft materials (Softone and Trusoft) without (control) or with incorporation of drugs (nystatin, miconazole, ketoconazole, chlorhexidine diacetate, and itraconazole). Hardness (Shore A) and roughness (Ra) were evaluated after immersion of specimens (n = 10) in distilled water at 37°C for 24 hours, 7 and 14 days. Data were analyzed by 3-way ANOVA/Tukey's test (α = 0.05). After 14 days, an increase (p < 0.05) was observed in the hardness of soft materials with time for the modified specimens, except for itraconazole. Addition of drugs increased the Softone roughness only for the addition of miconazole and chlorhexidine (p < 0.05), and did not increase the roughness of Trusoft with time. Only chlorhexidine and itraconazole altered the roughness compared to the control for each material (p < 0.05). The smallest changes of hardness and roughness with time in the modified groups compared to controls were observed for itraconazole groups for both materials.

English

AIMS: To compare the efficacy of itraconazole 200mg twice for one day and fluconazole 150mg single dose in the treatment of acute vulvovaginal candidiasis. METHODS: The study was carried out at the Department of Obstetrics & Gynaecology, K.P.C. Medical College & Hospital, Jadavpur, Kolkata, from August 2011 to July 2012 on 80 women with clinical and mycological diagnosis of vulvovaginal candidiasis. Diagnosis was based on history, clinical examination and relevant investigations. The women were divided into two equal groups. After initial assessment, Group 1 was treated with capsule itraconazole 200mg twice for one day, and Group 2 with capsule fluconazole 150mg single dose. They were assessed clinically for cure and relapse on day 7 and 21 respectively. RESULTS: The overall clinical evaluation showed 70% (n=28) cure rate with itraconazole and 50% (n=20) with fluconazole. In Group-1, 9 (22.5%) and in Group-2, 10 (25%) showed some improvement, while 3 (7.5%) in Group 1, and 10 (25%) in Group 2 failed to respond. At the 7th day follow up, Clinical success rates (cure and improvement) were 92.5% in the itraconazole group and 75% in the fluconazole group (P <0.05). Relapse was observed in 5 (18%) and 8 (40%) of the cured cases in Group 1 and Group 2 respectively on day 21. CONCLUSION: Itraconazole was found to be more effective in the treatment of vulvovaginal candidiasis compared to fluconazole with high cure and low relapse rate.

Micafungin Versus Fluconazole Or Itraconazole For Prophylaxis Against Invasive Fungal Infections During Neutropenia In Patients Undergoing Haplo-Identical Hematopoietic Stem Cell Transplantation

Objectives Over the past decade, invasive fungal infections (IFI) have remained an important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. Patients and Methods we conducted a retrospective, bi-institutional comparative clinical study, (Institut Paoli-Calmettes at Marseille France and Humanitas cancer center at Rozzano, Italy), and we compared the efficacy and safety of Micafungin 50mg/day (iv) with those of fluconazole (400mg/day) or itraconazole 200mg/day (iv) as prophylaxis for adult patients with various haematological diseases receiving haplo-identical allogeneic stem cell transplantation (haplo-SCT). Patients received prophylaxis with the beginning of the transplant conditioning regimen until the hospital discharge, or until occurrence of an IFI. We compared the incidence of proven or probable IFI (the primary end point) between the micafungin and fluconazole or itraconazole groups; death from any cause and time to death was secondary end points. Patients were followed for 100 days after haplo-SCT and for 30 days after the last dose of the prophylaxis drug administrated. Results From January 2009 to May 2013, a total of 99 patients were identified; 30 patients received micafungin, and 69 patients received fluconazole or itraconazole. 81 patients (82%) received a non myeloabaltive conditioning regimen (NMA), with Fludarabine, Cyclophosphamide and Total body irradiation (TBI) 2 Gy based , or Fludarabine, Busulfan, and Cyclophosphamide based (3%) or other (9%), while five patients (5%) received a thiotepa-based conditioning regimen. The patients and transplant details are shown in the table 1. Proven or probable invasive fungal infections were reported in 2 patients (7%) in the micafungin group and 8 patients (12%) in the fluconazole or itraconazole group (absolute reduction in the micafungin group, −5%; 95% confidence interval, 0.0565-3.1395, P=0.72). Fewer patients in the micafungin group had invasive aspergillosis (1 [3%] vs. 5 [7%], P=0.6). A total of 4 (13%) patients in the micafungin group and 23 (33%) patients in the fluconazole or itraconazole group received empirical antifungal therapy (P = 0.14). No serious adverse events related to treatment were reported by patients and there was no treatment discontinuation because of drug related adverse event in both groups. Overall Survival and disease free survival were similar among the two groups (P = 0.97). 6 patients (20%) in the micafungin group died within 100 days, as did 10 patients (14%) in the fluconazole or itraconazole group (P = 0.57). Interestingly the transplant related mortality (TRM) at 100 days was 0% in the micafungin group vs 13% in the second group [CI 95% (0-22)] (p=0,06), whereas the relapse or progression rate at 100 days was 27% vs. 8% respectively [CI 95% (14-44)] (p=0,14). Conclusions In patients undergoing to haplo-SCT, antifungal prophylaxis with micafungin is well tolerated and effective to prevent IFI. Furthermore, the incidence of IFI and invasive aspergillosis seems lower even if this did not attend statistical power, probably due to low number of patients. Disclosures: No relevant conflicts of interest to declare.

Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in pediatric patients following allogeneic hematopoietic stem cell transplantation

Oral antifungal prophylaxis with extended-spectra azoles is widely used in pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT), while controlled studies for oral antifungal prophylaxis after bone marrow transplantation in children are not available. This survey analyzed patients who had received either itraconazole, voriconazole, or posaconazole. We focused on the safety, feasibility, and initial data of efficacy in a cohort of pediatric patients and adolescents after high-dose chemotherapy and HSCT. Fifty consecutive pediatric patients received itraconazole, 50 received voriconazole, and 50 pediatric patients received posaconazole after HSCT as oral antifungal prophylaxis. The observation period lasted from the start of oral prophylactic treatment with itraconazole, voriconazole, or posaconazole until two weeks after terminating the oral antifungal prophylaxis. No incidences of proven or probable invasive mycosis were observed during itraconazole, voriconazole, or posaconazole treatment. A total of five possible invasive fungal infections occurred, two in the itraconazole group (4 %) and three in the voriconazole group (6 %). The percentage of patients with adverse events potentially related to clinical drugs were 14 % in the voriconazole group, 12 % in the itraconazole group, and 8 % in the posaconazole group. Itraconazole, voriconazole, and posaconazole showed comparable efficacy as antifungal prophylaxis in pediatric patients after allogeneic HSCT.

Itraconazole in chronic cavitary pulmonary aspergillosis: a randomised controlled trial and systematic review of literature

Patients with aspergilloma can be safely managed with supportive therapy in absence of massive haemoptysis. We hypothesised that chronic cavitary pulmonary aspergillosis (CCPA) could also be managed on similar grounds. The aim of this prospective, randomised controlled trial was to evaluate the efficacy and safety of itraconazole in CCPA. Consecutive patients of CCPA with presence of chronic pulmonary/systemic symptoms; and pulmonary cavities; and presence of Aspergillus (immunological or microbiological) were randomised to receive either supportive treatment alone or itraconazole 400mg daily for 6months plus supportive therapy. Response was assessed clinically, radiologically and overall after 6months therapy. A total of 31 patients (mean age, 37years) were randomised to itraconazole (n=17) or the control (n=14) group. The number of patients showing overall response was significantly higher in the itraconazole group (76.5%) vs. the control (35.7%) group (P=0.02). The numbers of patients demonstrating clinical or radiological response were also significantly higher in the itraconazole group (P=0.016 and 0.01 respectively). Adverse events were noted in eight patients in the itraconazole group, however, none was serious or led to discontinuation of the study drug. Itraconazole was found to be superior to standard supportive treatment alone in stabilising cases of CCPA. (clinicaltrials.gov; NCT01259336).

Comparable Efficacy of Terbinafine and Itraconazole in the Treatment of Tinea Pedis

Background: Tinea pedis (athlet’s foot) is the most common fungal infection. Relapse is common in tinea pedis and may be result of recurrence following inadequate treatment or reinfection. Objective: To evaluate the comparable efficacy of terbinafine and itraconazole in the treatment of tinea pedis. Methods: 120 patients of tinea pedis confirmed by KOH microscopy were included in the study. The study was carried out in three different Hospitals and Private Chambers for a period of 3 years from July 2006 to June 2009. Mean age of the patients was 40.28±10.23. The patients were devided into 2 equal group:A &amp; B. Group- A was given terbinafine 250 mg/day and group-B was given intraconazole 200 mg/day for 2 weeks. Results: Follow up 2 weeks after cessation of therapy revealed clinical and mycological cure of 93.3% in terbinafine group and 86.6% in itraconazole group. Conclusion: Efficacy analysis revealed that terbinafine is superior than itraconazole in the treatment of tinea pedis (P value 0.224). DOI: http://dx.doi.org/10.3329/bjmed.v21i2.13615 Bangladesh J Medicine 2010; 21: 74-79

Effects of 5-HT4 selective receptor agonist, mosapride citrate on electrocardiogram in dogs

Mosapride stimulated dietary motility was introduced because of the arrhythmogenic effect of cisapride. Cisapride, 5-HT receptor agonist, induces prolongation of QT interval. Additionally, this condition can raise the possibility of acute, “malignant” arrhythmias such as torsade de pointes. It is hard to find any reports about effects of mosapride on cardiac parameters in dogs. By confirming electrocardiogram (ECG) parameters, the surface extremity leads ECG that was obtained from the four-limb electrodes and which was recorded by an ECG recorder after administration of mosapride 3 mg/kg PO b.i.d, and mosapride 3 mg/kg with itraconazole 5 mg/kg PO b.i.d, respectively. QT interval was shortened on the days of 3, 5, and post-day 1 in both mosapride 3 mg/kg administrated group and mosapride with itraconazole group. Heart rate increased significantly. QTc was slightly prolonged in mosapride administration group and mosapride with itraconazole group. However, all dogs of QTc were in normal variation (150~250 msec). Besides, the dogs showed no side effects reported in human medicine during the administration with these drugs. Although mosapride can increase the heart rate, this study suggest that mosapride may be useful for the dogs with disorders of gastrointestinal motility because of no fatal arrhythmogenic effect inspite of administration with itraconazole in dogs.

Phase behavior of itraconazole–phenol mixtures and its pharmaceutical applications

The aims of this study were to examine the phase behavior of itraconazole-phenol mixtures and assess the feasibility of topical formulations of itraconazole using eutectic mixture systems. Itraconazole-phenol eutectic mixtures were characterized using differential scanning calorimetry, Fourier transform infrared spectroscopy, (1)H-nuclear magnetic resonance, and powder X-ray diffractometry. The skin permeation rates of itraconazole-phenol eutectic formulations were determined using Franz diffusion cells fitted with excised hairless mouse skins. Itraconazole can form eutectic compounds with phenol, and the hydrogen-bonding interactions between the carbonyl group in the itraconazole and hydroxyl group in phenol play a major role in itraconazole-phenol eutectic formation. Despite its high molecular weight and hydrophobicity, the drug (i.e., itraconazole) can be permeated through excised hairless mouse skins from itraconazole-phenol eutectic formulations. The findings of this study emphasize the capabilities of the topical application of itraconazole via external preparations.

Retrospective Analysis of Itraconacole, Voriconazole and Posaconazole As Oral Antifungal Prophylaxis in Pediatric Patients Following Allogeneic Stem Cell Transplantation

Abstract 3011▪FN2▪This icon denotes a clinically relevant abstract Background:Pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at high risk of acquiring fungal infections. Post-transplant immune deficiency, additional immunosuppression, viral infection, persistent fever during neutropenia, and GvHD are known risk factors for fungal infections. Antifungal prophylaxis early after allogeneic stem cell transplantation is therefore indicated. Oral antifungal prophylaxis with extended-spectra azoles, e.g. voriconazole or itraconazole, is preferentially used in pediatric patients after allogeneic HSCT, although only few studies have been published on the matter. Due to the absence of controlled studies for oral antimycotic prophylaxis in children after BMT, we retrospectively analyzed patients who received posaconazole based on data in adult patients. Cornely and colleagues published that posaconazole was more effective than fluconazole or itraconazole in the prevention of invasive fungal infections in adult patients undergoing chemotherapy for myelodysplastic syndrome or acute myeloid leukemia. Retrospectively, we assessed the safety, feasibility and initial data of efficacy for itraconazole, voriconazole and posaconazole with regard to pediatric patients and adolescents after high-dose chemotherapy and HSCT. Patients and Methods:The study is a single centre, retrospective survey on antimycotic prophylaxis in pediatric patients under eighteen years of age undergoing allogeneic HSCT between January 2004 and June 2011 at the University Children’s Hospital Tübingen, Germany. 50 pediatric patients received posaconazole, 50 pediatric patients received voriconazole and 50 pediatric patients received itraconazole after HSCT as oral antifungal prophylaxis. The observation period was defined as the time from the start of oral prophylactic treatment with itraconazole, voriconazole or posaconazole until the end of oral antimycotic prophylaxis, a maximum of 200 days post transplant. Results:The median observation period in the itraconazole group (median age 8.5 years) was 109 days (range 20 – 200 days), 105 days (range 18 – 200 days) in the voriconazole group (median age 7.5 years) and 117 days (range 16 – 200 days) in the posaconazole group (median age of 8.5 years), respectively. No incidences of proven or probable invasive mycosis according to EORTC definitions (De Pauw et al., 2008) occurred under itraconazole, voriconazole, and posaconazole during the observation period. Cases of possible fungal infections according to EORTC definitions in the voriconazole group (10%) and itraconazole group (5%) were higher, but still not significantly different from those in the posaconazole group (0%). The percentage of patients with adverse events potentially related to clinical drugs was higher in the voriconazole (17.5%) and itraconazole (15.0%) group than posaconazole (9.8%) group, but not statistically significant. Laboratory investigations were comparable during itraconazole, voriconazole, and posaconazole treatment. Statistical analysis by the Wilcoxon Matched-Pairs Signed Rank Test showed a significant increase beyond the upper normal limit of ALT between baseline before conditioning and maximum during oral antimycotic prophylaxis in all three groups, itraconazole (P = 0.000015), voriconazole (P = 0.0033), posaconazole (P = 0.000013), and a significant increase of AST during itraconazole (P = 0.00023), voriconazole (P = 0.0004), and posaconazole (P = 0.00026) treatment. Significant decreases of potassium (P = 0.000000024) and bicarbonate (P = 0.0026) below the lower limit of the normal range were observed during voriconazole treatment. Moderate elevation of CsA levels were observed during voriconazole and posaconazole treatment, but were also not statistically significant. Conclusion:Taken together, itraconazole, voriconazole and posaconazole showed comparable efficacy as antifungal prophylaxis in pediatric patients after allogeneic HSCT. With regard to the clinical tolerability, posaconazole was superior to itraconazole and voriconazole. Disclosures:No relevant conflicts of interest to declare.

Role of Itraconazole in Sinonasal Polyposis

Objective: 1) Diagnose fungal disease in sinonasal polyposis. 2) Compare the clinical outcome of patients with sinonasal polyposis treated with and without itraconazole. Method: Two-year, randomized case controlled study in university hospital. Thirty patients with sinonasal polyposis. Random allocation to study and control group. All underwent nasal endoscopy, CT PNS, Nasal swab for fungal smear and culture. Study group received itraconazole, per oral for 2 and 4 weeks pre- and postoperative period. Results: A total of 60% of preoperative nasal swab were KOH positive for fungal hyphae. Both groups presented with headache and nasal obstruction. Wormald classification was used to grade polyps, edema, and discharge. Fungus was isolated in 46% of study and 34% of control group; the predominant fungus grown was Aspergillus flavus. Histopathology showed 66% inflammatory polyps and 44% allergic polyps. Statistical analysis and comparison of control and study group showed significantly lower clinical scores in study (itraconazole) group ( P &lt; .002) at 6 months posttreatment. The Lund Mackay score for CT scan did not show significant difference. Conclusion: Fungal disease co-exists in a majority of patients with sinonasal polyposis. It is not known if it is a causative factor. Itraconazole was found to improve the clinical outcome in patients treated for sinonasal polyposis. No untoward side effects of the drug was identified in our study.

The Role of Antifungal Therapy in the Prevention of Recurrent Allergic Fungal Rhinosinusitis after Functional Endoscopic Sinus Surgery: A Randomized, Controlled Study

Allergic fungal rhinosinusitis (AFRS) is the most common form of fungal sinus disease. Its recurrence rate is high despite numerous strategies to prevent it. We conducted a study to assess the effect of systemic and topical antifungal agents-both separately and in combination-in preventing recurrence of AFRS following functional endoscopic sinus surgery (FESS). Our initial study population was made up of 50 adults who were diagnosed with AFRS by clinical, radiologic, histopathologic, and laboratory workup and who subsequently underwent FESS. Postoperatively, these patients were randomized into 5 different treatment groups matched for sex, age, and socioeconomic status. Four of the groups received a different antifungal regimen in addition to convenient medical treatment (CMT), while a fifth group served as a control. The antifungal regimens included oral itraconazole (group A), fluconazole nasal spray (group B), combined oral itraconazole and nasal fluconazole (group C), and irrigation with a fluconazole solution through the nasal fossa (group D); the group of 10 controls (group E) received CMT only. A total of 41 patients were available for follow-up (9 mo maximum). Recurrence rates in the 5 groups were 66.7, 10.0, 14.3, 28.6, and 75.0%, respectively. Based on our findings, we conclude that treatment with topical fluconazole as either a nasal spray or an irrigation solution can significantly reduce the rate of recurrence of AFRS after FESS.

Itraconazole vs Fluconazole as a Primary Prophylaxis for Fungal Infections in HIV-Infected Patients in Thailand

Disseminated fungal infections are common presenting opportunistic infections among AIDS patients in developing countries. Primary prophylaxis with itraconazole has been shown to be effective in northern Thailand. This study aimed to compare the efficacy of fluconazole vs itraconazole as primary prophylaxis for fungal infections in HIV-infected patients. A retrospective cohort study was conducted among HIV-infected patients who received primary prophylaxis with fluconazole 400 mg once weekly or itraconazole 200 mg once daily at Chiang Mai University Hospital. We compared the incidence of systemic fungal infections and the probability of disease-free survival between groups. From January 2000 to June 2010, 308 HIV-infected patients who received primary fungal prophylaxis were enrolled; 148 were male (48.1%) and the mean age was 38.2 ± 8.0 years. 276 patients received fluconazole and 32 received itraconazole. Baseline CD4+ cell count was 35 (IQR 15, 70) and 50 (IQR 21,75) cells/mm(3) in fluconazole and itraconazole groups, respectively (p=0.159). The median follow-up time was 12 months (IQR 7, 19) in fluconazole group and 15.5 months (IQR 9, 21.5) in itraconazole group. Seven patients (2.5%) who received fluconazole and 2 patients (6.3%) who received itraconazole developed systemic fungal infections, giving the incidence of 17.0 and 34.8/10000 person-months, respectively (p=0.261). The probability of developing any systemic fungal infections or death did not differ between groups. Although P. marneffei has a reduced susceptibility in in vitro to fluconazole, our study has demonstrated that once-weekly fluconazole is at least as effective as once-daily itraconazole as primary prophylaxis for systemic fungal infections in AIDS patients in northern Thailand.

Comparative Study of 250 mg/day Terbinafine and 100 mg/day Itraconazole for the Treatment of Cutaneous Sporotrichosis

Itraconazole is currently used for the treatment of cutaneous sporotrichosis. Terbinafine at a daily dose of 250mg has been successfully applied to the treatment of cutaneous sporotrichosis. To compare the efficacy of 250mg/day terbinafine and 100mg/day itraconazole for the treatment of cutaneous sporotrichosis. A bidirectional cohort study was conducted on 55 patients receiving 250mg/day terbinafine and 249 patients receiving 100mg/day itraconazole. The latter patients were matched for age and clinical form to the terbinafine group at a ratio of 5:1. Sporothrix schenckii was isolated by culture from all patients (age range: 18-70years), who were submitted to the standard care protocol consisting of clinical and laboratory evaluation and periodic visits. Cure was observed in 51 (92.7%) patients of the terbinafine group and 229 (92%) of the itraconazole group within a similar mean period of time (11.5 and 11.8weeks, respectively). An increase in the terbinafine dose to 500mg was necessary in two patients due to the lack of a response, and one patient presented recurrence. In the itraconazole group, two patients required a dose increase and three presented recurrence. Adverse events were equally frequent among patients receiving terbinafine (n=4, 7.3%) and itraconazole (n=19, 7.6%) and were generally mild without the need for drug discontinuation, except for two patients of the itraconazole group. Terbinafine administered at a daily dose of 250mg is an effective and well-tolerated option for the treatment of cutaneous sporotrichosis.

Quantitative analysis of the effects of antimycotic agents on the hyphal growth of Trichophyton rubrum: a preliminary study

The thallus diameter is commonly used as a quantitative parameter to evaluate hyphal growth. However, a different parameter is required to evaluate hyphal growth more precisely. The hyphal growth of Trichophyton rubrum in the presence of antimycotic agents was evaluated using the number of hyphal crossings as a quantitative parameter. Continuous video images of hyphal growth were taken for 48 h. Culture medium contained 0.4 μg ml(-1) of terbinafine (TBF) and itraconazole (ITCZ). Image analyses were performed every 6 h using a 50 μm square grid. The mean density of the hyphal crossings in each sampling frame was used as a parameter of hyphal growth. The mean ratio of hyphal crossings on distressed hyphae to total hyphal crossings was used as a parameter representing the antimycotic effects of TBF and ITCZ. The mean density of total hyphal crossings in the TBF group was significantly lower than in the control and ITCZ groups. The ratio of distressed hyphae significantly increased during the 48-h time course in the TBF group, but not in the ITCZ group. Counting the number of hyphal crossings provides a new method for assessing hyphal growth and antimycotic activity quantitatively.

The effects of caspofungin and voriconazole in an experimental fungal infection of the ear due to Aspergillus

The purpose of the study was to evaluate the effectiveness of caspofungin and voriconazole in the treatment of experimental Aspergillus otitis media in an experimental rabbit model. A total of 30 New Zealand white rabbits were divided into four treatment groups and one control group. The rabbits were immunosuppressed by cyclophosphamide and triamcinolone acetonide. The right ear of each rabbit was infected by an injection of the inoculum of 0.1 ml (8.6 x 103 CFU/0.1 ml) of Aspergillus fumigatus into the middle ear cavity. At 72 h after the inoculation, amphotericin B 1 mg/kg per day (n = 6), itraconazole 10 mg/kg per day (n = 6), voriconazole 10 mg/kg per day (n = 6) and caspofungin 5 mg/kg per day (n = 6) were injected to each treatment group. No antifungal drug was administered to the control group (n = 6). Clinical and histopathological examination scores and microbiological analysis of middle ear mucosa were compared.There was statistically significant difference in the clinical scores, histopathological scores, and mean CFU/g between the treatment and control groups (P < 0.05). There was no statistically significant difference among the treatment groups in the clinical and histopathological scores, whereas there was statistically significant difference in the mean CFU/g (P < 0.05). The mean CFU/g of amphotericin B and caspofungin groups were similar and both were lower than the itraconazole and voriconazole groups. Also, the mean CFU/g of voriconazole group was lower than the itraconazole group (P < 0.05). Caspofungin and voriconazole were demonstrated at least as effective as amphotericin B and itraconazole. We suggest that caspofungin and voriconazole may be considered for the treatment of fungal infection of the ear.

In Vitro Evaluation of Combination Antifungal Activity against Fusarium Species Isolated from Ocular Tissues of Keratomycosis Patients

To determine the minimum inhibitory concentrations (MICs) of five antifungal agents against Fusarium species isolated from ocular tissues and to evaluate anti-Fusarium species activities of eight combination treatments in vitro. Experimental research. Thirty-eight isolates of Fusarium species were collected from patients' ocular tissues and were cultured in vitro. The MICs of natamycin, terbinafine, itraconazole fluconazole, and amphotericin B, either used alone or combined with other compounds, were evaluated by checkerboard microdilution technique based on the Clinical Laboratory Standards Institute proposed standard. The interactions were assessed using the Fractional Inhibitory Concentration Index model. In the MIC study, the MIC(90) of each drug used alone were: natamycin, 16 microg/ml; terbinafine, 8 microg/ml; itraconazole, >16 microg/ml; fluconazole, >64 microg/ml; and amphotericin B, 4 microg/ml. Synergism was obtained in the amphotericin B plus terbinafine (81.6%) group and in the amphotericin B plus itraconazole (84.2%) group, with an obviously decreased MIC value of amphotericin B. Antagonism was shown in the natamycin plus azoles and in the natamycin plus terbinafine groups in 52.6% to 60.5% of Fusarium species strains. Amphotericin B plus terbinafine or itraconazole demonstrated more effective anti-Fusarium species activity than single-use in vitro treatment, which implies that these combinations may be helpful in treating fungal keratitis. The combinations of natamycin plus azoles or natamycin plus terbinafine were not satisfactory and can be avoided. Further in vivo studies are needed to elucidate the potential usefulness of these combination therapies.