No abstract available.
Diabetes Mellitus, Type 2 ; Pyrazines ; Triazoles ; Sitagliptin Phosphate

No abstract available.
Diabetes Mellitus, Type 2 ; Pyrazines ; Triazoles ; Sitagliptin Phosphate

BACKGROUND: There are limited data regarding the antifungal susceptibility of Candida albicans causing recurrent vulvovaginal candidiasis. OBJECTIVE: The aim of the present study was to evaluate the effect of azoles susceptibilities on treatment failure and recurrence of vulvovaginal candidiasis. METHODS: Species identification was performed on 84 vaginal Candida isolates collected from October 2008 to June 2010 from 404 patients with suspected vulvovaginitis. MICs of C. albicans (26 isolates) to fluconazole, itraconazole, and voriconazole were tested by broth microdilution method of the Clinical and Laboratory Standards Institute (CLSI) M27-A2. RESULTS: C. albicans was the most frequently isolated (88.1%). All isolates were susceptible to fluconazole, itraconazole, and voriconazole. Trailing growth was found in treatment success group (10.0%) and treatment failure group (33.3%). CONCLUSIONS: The results of this study suggest the possibility that trailing growth have influence on treatment failure of vulvovaginal candidiasis.
Azoles ; Candida ; Candida albicans ; Candidiasis, Vulvovaginal ; Danazol ; Fluconazole ; Humans ; Itraconazole ; Pyrimidines ; Recurrence ; Treatment Failure ; Triazoles ; Vulvovaginitis

BACKGROUND: Candida species are the fourth leading cause of nosocomial bloodstream infections and have one of the highest mortality rates among nosocomial pathogens. C. tropicalis has been reported to be one of the leading Candida species other than C. albicans to cause Candida infection in patients who have malignancy, diabetes mellitus, and burn. This study was designed to determine whether burn might influence the species distribution and susceptibilities of azoles against clinical isolates of Candida species including C. tropicalis. METHODS: A total 372 Candida isolates from various samples in a tertiary burn center were studied, and the MICs of Candida isolates to fluconazole, itraconazole, and voriconazole were tested by broth microdilution method of the Clinical and Laboratory Standards Institute (CLSI) M27-A2. A comparison was made between Candida isolates from burn patients and non-burn patients. RESULTS: The percentages of C. albicans, C. tropicalis, C. parapsilosis and C. glabrata isolates from burn patients and non-burn patients were 42.3% and 64.2% (P=0.000), 35.7% and 21.6% (P=0.002), 11.9% and 7.8%, and 10.1% and 6.4%, respectively. Decreased susceptibilities to fluconazole, itraconazole, and voriconazole were observed more frequently in burn patients (4.76%, 19.05%, and 0.60%, respectively) than non-burn patients (2.45%, 14.22%, and 0%, respectively). CONCLUSION: The results of this study suggest that burn may lead to influence the species distribution and susceptibilities to azoles of Candida species.
Azoles ; Burn Units ; Burns ; Candida ; Candida tropicalis ; Danazol ; Diabetes Mellitus ; Fluconazole ; Humans ; Itraconazole ; Pyrimidines ; Triazoles

Aantifungal agents were tested against 30 clinical isolates of Cryptococcus neoformans var. neoformans using the NCCLS method (M27-A2). Posaconazole, itraconazole and amphotericin B had lower MIC than the remaining four antifungal agents. The MIC result for posaconazole was over 220-fold lower active than fluconazole. Fluconazole MICs for most isolates fell within the dose-dependant range. The overall MIC ranges and MIC50s were amphotericin B (0.03-0.25; 0.25), fluconazole (0.5-64; 16), itraconazole (0.015-1; 0.125), terbinafine (0.06->2; 1), caspofungin (8-32; 32), voriconazole (0.015-0.5; 0.25), and posaconazole (0.015-0.25; 0.06 microg/ml), respectively. In conclusion, the MIC50s of these drugs did not exhibit any sign of an upward shift with the exception of fluconazole and tendency cross-resistance between the seven drugs was not observed. We conclude that in vitro resistance to antifungal agents has not significantly changed despite the recent wide-spread use of triazoles for long-term treatment of Cryptococcal meningitis.
Amphotericin B* ; Antifungal Agents ; Cryptococcus neoformans* ; Cryptococcus* ; Fluconazole* ; Itraconazole* ; Meningitis, Cryptococcal ; Triazoles

BACKGROUND: To evaluate the clinical efficacy of sitagliptin for reducing plasma glucose levels in Korean subjects with type 2 diabetes mellitus during a 14-week treatment period. METHODS: Our study design involved the addition of 100 mg sitagliptin once-daily to three ongoing combination therapy regimens and changing from glimepiride and metformin to sitagliptin and metformin. RESULTS: The addition of sitagliptin 100 mg/day produced a statistically significant reduction in mean HbA1c level (mean HbA1c reduction of 0.99+/-0.85%, P<0.01). In the group taking a combination of sitagliptin and metformin (n=143, initial mean HbA1c level=7.48%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 0.72+/-0.76% (P<0.01), 47+/-65 mg/dL (P<0.01), and 15+/-44 mg/dL (P<0.01), respectively. In the group taking a combination of sitagliptin, glimepiride, and metformin (n=125, initial mean HbA1c level=8.42%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 1.09+/-0.86% (P<0.01), 62+/-64 mg/dL (P<0.01), and 31+/-45 mg/dL (P<0.01), respectively. In the group taking a combination of sitagliptin, glimepiride, metformin, and alpha-glucosidase inhibitor (n=63, initial mean HbA1c level=9.19%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 1.27+/-0.70% (P<0.01), 72+/-65 mg/dL (P<0.01), and 35+/-51 mg/dL (P<0.01), respectively. In the group that had previous hypoglycemic events and that changed from glimepiride to sitagliptin, HbA1c level did not change but fasting glucose increased significantly (14+/-29 mg/dL, P<0.01). CONCLUSION: Sitagliptin combination therapy for 14 weeks significantly improved glycemic control and was well-tolerated in Korean subjects with type 2 diabetes mellitus.
alpha-Glucosidases ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Metformin ; Plasma ; Pyrazines ; Sulfonylurea Compounds ; Triazoles ; Sitagliptin Phosphate

BACKGROUND: Sitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects. METHODS: We obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (DeltaHbA1c) and fasting plasma glucose (DeltaFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in DeltaHbA1c or >20% in DeltaFPG levels at 24 weeks. RESULTS: We classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70+/-2.40 vs. 26.00+/-2.26, P< or =0.01) and were younger (58.83+/-11.57 years vs. 62.87+/-12.09 years, P=0.03) than the non-responder group. CONCLUSION: In Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders.
Body Mass Index ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Insulin ; Metformin ; Plasma ; Pyrazines ; Triazoles ; Sitagliptin Phosphate

BACKGROUNDDuring recent years, the incidence of serious infections caused by opportunistic fungi has increased dramatically due to alterations of the immune status of patients with hematological diseases, malignant tumors, transplantations and so forth. Unfortunately, the wide use of triazole antifungal agents to treat these infections has lead to the emergence of Aspergillus spp. resistant to triazoles. The present study was to assess the in vitro activities of five antifungal agents (voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin) against different kinds of Aspergillus spp. that are commonly encountered in the clinical setting.

METHODSThe agar-based Etest MIC method was employed. One hundred and seven strains of Aspergillus spp. (5 species) were collected and prepared according to Etest Technique Manuel. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 hours at 35°C. MIC(50), MIC(90) and MIC range were acquired by Whonet 5.4 software.

RESULTSThe MIC(90) of caspofungin against A. fumigatus, A. flavus and A. nidulans was 0.094 µg/ml whereas the MIC(90) against A. niger was 0.19 µg/ml. For these four species, the MIC(90) of caspofungin was the lowest among the five antifungal agents. For A. terrus, the MIC(90) of posaconazole was the lowest. For A. fumigatus and A. flavus, the MIC(90) in order of increasing was caspofungin, posaconazole, voriconazole, itraconazole, and amphotericin B. The MIC of amphotericin B against A. terrus was higher than 32 µg/ml in all 7 strains tested.

CONCLUSIONSThe in vitro antifungal susceptibility test shows the new drug caspofungin, which is a kind of echinocandins, has good activity against the five species of Aspergillus spp. and all the triazoles tested have better in vitro activity than traditional amphotericin B.

Amphotericin B ; pharmacology ; Antifungal Agents ; pharmacology ; Aspergillus ; drug effects ; Echinocandins ; pharmacology ; Itraconazole ; pharmacology ; Lipopeptides ; Microbial Sensitivity Tests ; Pyrimidines ; pharmacology ; Triazoles ; pharmacology ; Voriconazole

BACKGROUNDThe prevalence of dermatophytoses and the development of new antifungal agents has focused interest on susceptibility tests of dermatophytes. The method used universally for susceptibility tests of dermatophytes was published as document (M38-A) in 2002 by the Clinical and Laboratory Standards Institute (CLSI), dealing with the standardization of susceptibility tests in filamentous fungi, though not including dermatophytes especially. However, it is not a very practical method for the clinical laboratory in routine susceptibility testing. In this test, we developed a novel rapid susceptibility assay-glucose consumption method (GCM) for dermatophytes.

METHODSIn this study, we investigated the antifungal susceptibilities of dermatophytes to itraconazole (ITC), voriconazole (VOC), econazole nitrate (ECN) and terbinafine (TBF) by glucose consumption method (GCM), in comparison to the Clinical and Laboratory Standards Institute (CLSI) M38-A method. Twenty-eight dermatophyte isolates, including Trichophyton rubrum (T. rubrum) (n = 14) and Trichophyton mentagrophytes (T. mentagrophytes) (n = 14), were tested. In the GCM, the minimum inhibitory concentrations (MICs) were determined spectrophotometrically at 490 nm after addition of enzyme substrate color mix. For the CLSI method, the MICs were determined visually.

RESULTSComparison revealed best agreement for TBF against T. mentagrophytes and T. rubrum, since MIC range, MIC50, and MIC90 were identical from two methods. However, for ITC and VOC, GCM showed wider MIC ranges and higher MICs than CLSI methods in most isolates. For ECN against T. rubrum, high MICs were tested by GCM (0.125-16 microg/ml) but not M38-A method (0.5-1 microg/ml). The overall agreements for all isolates between the two methods within one dilution and two dilutions for ITC, VOC, ECN and TBF was 53.6% and 75.0%, 57.1% and 75.0%, 82.1% and 89.3%, and 85.7 and 85.7%, respectively.

CONCLUSIONMeasurement of glucose uptake can predict the susceptibility of T. rubrum and T. mentagrophytes to ECN and TBF.

Antifungal Agents ; pharmacology ; Econazole ; pharmacology ; Glucose ; metabolism ; Itraconazole ; pharmacology ; Microbial Sensitivity Tests ; Naphthalenes ; pharmacology ; Pyrimidines ; pharmacology ; Triazoles ; pharmacology ; Trichophyton ; drug effects ; metabolism ; Voriconazole

BACKGROUND/AIMS: The gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the 13C-acetic acid breath test. METHODS: Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted for overnight and were randomly assigned to receive 50 mg sitagliptin 2 hours before ingestion of the liquid test meal (200 kcal per 200 mL, containing 100 mg 13C-acetate) or the test meal alone. Under both conditions, breath samples were collected for 150 minutes following the meal. Liquid gastric emptying was estimated by the values of the following parameters: the time required for 50% emptying of the labeled meal (T1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (Tlag), the gastric emptying coefficient and the regression-estimated constants (beta and kappa), calculated by using the 13CO2 breath excretion curve using the conventional formulae. The parameters between the 2 test conditions were compared statistically. RESULTS: No significant differences in the calculated parameters, including T1/2, Tlag, gastric emptying coefficient or beta and kappa, were observed between the 2 test conditions. CONCLUSIONS: The present study revealed that single-dose sitagliptin intake had no significant influence on the rate of liquid gastric emptying in asymptomatic volunteers.
Breath Tests ; Cross-Over Studies ; Eating ; Gastric Emptying ; Gastrointestinal Motility ; Humans ; Incretins ; Male ; Meals ; Pyrazines ; Triazoles ; Sitagliptin Phosphate