The present study was designed to obtain omparative data on in vitro antifungal activities of imidazole derivatives. Minimum inhibitory oncentrations of clotrimazole, miconazole, econazole, ketoconazlole and griseofulvin on 4 strains of Trichophyton mentagrophytes, 3 strains of Trichophyton rubrum, 2 strains of Microsporum canis and ] strain of Sporothriv: schenckii were etermined after 3 week' incubation at room temperature on Sabouraud's dextrose liquid media. In addition, the fungicidal activities of miconazole and econazole were tested against Z'richophyton mentagrophytes and Microsporum canis, using the techniques described by Vanbreuseghern(1967) The results are summarzed as follows: ] In most of the dermatophytes studied, 1 to 10 pg/ml of M1C were detected. Diverse susceptibility pattern was observed among different fungal species, but no or minor variability was noted within the same species. The susceptibility of Z'ri- chophyton rubrum showed at MIC of 0. 01 to 10 pg/ml, T ichophyton mentagro- phyt.es and Mic osporum canis at 0.1 to 10 pg/ml and 0. 1 to 1000 gg/ml respec- tively. The Trichophyton rubrum was the most sensitive. In the susceptibility test of Sporothrix schenckii, the high resistance to clotrimazole and griseofuhin was observed. The fungistatic activities of miconazole, econazole and ketoconazole were observed only at concentrations higher than JpQ pg/ml.
Arthrodermataceae ; Clotrimazole ; Econazole ; Glucose ; Griseofulvin ; Ketoconazole ; Miconazole ; Microsporum ; Sporothrix ; Trichophyton

BACKGROUND: The frequency of nosocomial bloodstream infections by Candida species has risen dramatically in the past two decades, and a noticeable shift in the species of Candida causing bloodstream infection toward non-albicans species has occurred. Also, the isolation frequency of Candida species are influenced by patient type, nation and region, study period, and investigators. The aim of this study is to investigate the isolation rates and antifungal susceptibility of Candida species isolated from blood cultures at Wonju Christian Hospital during the recent four years (1997~2000). METHODS: For one-hundred twenty-seven isolates of Candida species from blood cultures, we analyzed the isolation frequency by year, age/sex, and department. Identification of yeasts was done by germ tube test and ATB ID 32 C kit. Antifungal susceptibilities to flucytosine, amphotericin B, nystatin, miconazole, econazole, and ketoconazole were determined by ATB FUNGUS. RESULTS: The isolation rates of Candida species in decreasing order were C. albicans (44.9%), C. parapsilosis (21.3%), C. glabrata (14.2%), and C. tropicalis (9.5%). The isolation rates of Candida species by year were as follows; C. albicans decreased from 61.5% in 1997 to 33.3% in 2000; C. tropicalis decreased from 23.1% in 1997 to 5.0% in 2000; C. parapsilosis increased from 0% in 1997 to 30.8% in 2000; and C. glabrata increased from 7.7% in 1997 to 18.0% in 2000. Of 127 Candida species, all but one isolates were susceptible to amphotericin B. CONCLUSION: This data showed that the candidemia by C. albicans and C. tropicalis are decreasing trend, and candidemia by C. parapsilosis and C. glabrata are increasing trend in recent four years.
Amphotericin B ; Candida* ; Candidemia ; Econazole ; Flucytosine ; Fungi ; Gangwon-do ; Humans ; Ketoconazole ; Miconazole ; Nystatin ; Research Personnel ; Yeasts

Econazole is one of the new imidazole derivatives displaying antifungal and antibacterial properties in vitro and in vivo. The present study was undertaken to evaluate the therapeutic efficacy of Econazole in patients with dermatomycoses anl to determine the minimal inhibitory concentration in vitro. A total of 48 patients with various forrns of dermatomycoses(25 patienta with T. cruris, 13 with T. pedis, l with T. corporis, 4 with T. versicolor and 5 with candidiasis) entered this study at the Departement of Dermatology, University Hospital, College of Medicine, Seoul National University during 3 months period. from July to September, 1976. Dia,gnosis was established clinically as well as microscopically by direct KOH mount. All patients were instructed to apply 1:o Econazole solution two to three times daily on the affected area for four to seven weeks and weekly examination of the clinical lesions and direct KOH mount were performed. In addition, minimal inhibitory concentration for Trichophyton mentagrophy tes was determined by the modified dilution technique in vitro. The results were as follows. 1. Thirty five patients (72. 9F) were cured clinically and microscopieally and thc remainders showed marked clinical improvement but positive KOH mount at 4 th week of treatment. At 7th week, nine (18.8io) of the remainders were cured clinically and microscopically and the overall cure rate at 7th week was 91. 7%. Five patients with tinea cruris experienced trar.sient irritation derrnatitis on their crural regions. 2. The minimal inhibitory coriceritration of Econazole for Trichophyton mentagrophytes was 25 pg per ml. of medium. The authors concluded that the 1 i Econazole was highly effective in the treatment of superficial rnycoses and the side effects were rninimal and only transient.
Dermatology ; Dermatomycoses* ; Dronabinol ; Econazole* ; Humans ; Indicator Dilution Techniques ; Seoul ; Tinea ; Trichophyton

Many reports represent that angiotensin II (ANG II) caused a dose dependent biphasic effects on fluid transport in the proximal tubule. However, respective roles of different signaling pathways in mediating these effects remain unsettled. The aim of the present study was to examine signaling pathways at high doses of ANG II on the Na+ uptake of primary cultured rabbit renal proximal tubule cells(PTCs) in hormonally defined serum-free medium. High concentrations of ANG II (> 10(-9) M) inhibited Na+ uptake and increased (Ca2+)i level in the PTCs. However, low concentrations of (< 10(-11) ANG II) stimulated Na+ uptake and did not affect (Ca2+)i level. 8-(N, N-diethylamino)-octyl-3,3,5- trimethoxybenzoate (TMB-8), ethylene glycol-bis(beta-amino ethyl ether)-N,N,N', N'-tetra acetic acid (EGTA), and nifedifine partially blocked the inhibitory effects of ANG II on Na+ uptake. When ANG II and bradykinin (BK) were treated together, Na+ uptake was further reduced (88.47 +/- 1.98% of that of ANG II, 81.85 +/- 1.84% of that of BK). In addition, W-7 and KN-62 blocked the ANG II-induced inhibition of Na+ uptake. Arachidonic acid reduced Na+ uptake in a dose-dependent manner. When ANG II and arachidonic acid were treated together, inhibitory effects on Na+ uptake significantly exhibited greater reduction than that of each group, respectively. When PTCs were treated by mepacrine (10(-6) M) and AACOCF, (10-5 M) for 1 hr before the addition of 10(-9) M ANG II, the inhibitory effect of ANG II was reversed. In addition, econazole (10(-6) M) blocked ANG II-induced inhibition of Na+ uptake. In conclusion, the (Ca2+)i (calcium-calmodulin-dependent kinase) and phospholipase A2 (PLA2) metabolites are involved in the inhibitory effects of ANG II on Na+ uptake in the PTCs.
Acetic Acid ; Angiotensin II* ; Angiotensins* ; Arachidonic Acid ; Bradykinin ; Econazole ; Ion Transport* ; Kidney ; Negotiating ; Phospholipases A2 ; Quinacrine

Ear Canal ; drug effects ; Econazole ; therapeutic use ; Endoscopy ; Humans ; Otomycosis ; drug therapy ; Triamcinolone Acetonide ; therapeutic use

BACKGROUND: The epidemiology of Candida species isolated from nonsterile as well as normally sterile sites is important because colonization of the former may precede invasive Candida infections. METHODS: We investigated the epidemiology and antifungal susceptibility of Candida species recovered in Busan Paik Hospital during the past 6 years and compared these results according to the type of specimens. RESULTS: Among the 2364 strains, C. albicans (53.8%) was the most frequently isolated, followed by C. tropicalis (17.5%), and C. guilliermondii (10.0%). Non-albicans Candida species were more prevalent in normally sterile sites (P<0.001); the prevalence of C. tropicalis and C. parapsilosis was significantly higher in normally sterile than in nonsterile sites (P<0.001). The prevalence of C. parapsilosis was higher in blood, intravenous catheter tips, and ear discharge, whereas C. tropicalis was more frequently isolated from urine. C. guilliermondii was the most frequently isolated from bronchial washings. The susceptibilities of Candida species to 5-flucytosine, amphotericin B, nystatin, miconazole, econazole, and ketoconazole were 98.3, 99.3, 99.7, 94.9, 86.3, and 94.5%, respectively. The susceptibilities of the organisms from normally sterile sites were lower than those from nonsterile sites. CONCLUSION: The distribution of Candida species differed among various types of specimens, especially those from normally sterile versus nonsterile sites. We assume that the frequency of infections of exogenous origin is high. We presume that the candidemia of C. parapsilosis is associated with the use of central venous catheter and that C. parapsilosis is acquired from exogenous sources.
Amphotericin B ; Busan ; Candida* ; Candidemia ; Catheters ; Central Venous Catheters ; Colon ; Ear ; Econazole ; Epidemiology ; Ketoconazole ; Miconazole ; Nystatin ; Prevalence

The development of selective and safe antifungal agents are relatively delayed, compared to that of other antibiotics. The reasons are the relatively lesser interest of pharmaceutical companies because of the fewer occurrence of fungal disease and the apparent lack of a highly selective fungal target, not present in other eukaryotic (including mammalian) cells. Until the 1940s, fungal skin infection was treated by keratinolytics, antiseptics, and antibacterial chemicals. The first selective antifungal agent was polylene compounds in the early 1950s, which were topical nystatin and fungizone (amphotericin-B). In 1958, the first oral fungal agents, 'griseofulvin', as developed and have been used effectively to tinea capitis and other dermatophytes. Between the late 1960s and early 1970s, the azole compound, 'the real broad spectrum antifungal agents' was introduced, and clotrimazole was the first topical azole compound followed, by miconazole and econazole. Ketoconazole was released in early 1980s and it was the first real oral antifungal agent for systemic and superficial fungal infections. However, because of serious side effects of symptomatic hepatic injury, its use was replaced by triazole antifungal agents such as itraconazole and fluconazole. Triazole was more safe and effective, and caused advancement in the treatment of onychomycosis. In addition, terbinafine 'belonging to the allylamine compounds and developed in 1984', has been approved as a very potent antifungal agent for dermatophytes and also is being used widely to cutaneous infection by candidia species and some molds.
Allylamine ; Amphotericin B ; Anti-Bacterial Agents ; Anti-Infective Agents, Local ; Antifungal Agents* ; Arthrodermataceae ; Clotrimazole ; Danazol ; Dermatomycoses* ; Econazole ; Fluconazole ; Fungi ; Itraconazole ; Ketoconazole ; Miconazole ; Nystatin ; Onychomycosis ; Skin ; Tinea Capitis

To investigate apoptosis of mouse leukemia cell (WEHI-3) induced by econazole and its mechanism, apoptosis induced by econazole was examined by flow cytometry, while free calcium ([Ca(2+)]i) was determined by Fura-2 fluorescein load technique. The protein was isolated from endoplasmic reticulum of WEHI-3 cells, and then the expression of caspase-12 and caspase-7 was evaluated by Western blot. The results showed that WEHI-3 exhibited typical change of apoptosis when it was treated by econazole, [Ca(2+)]i was significantly higher in comparison with the control. The expression of caspase-12 and caspase-7 enhanced as the econazole concentration increased. In conclusion, econazole can induce WEHI-3 cell apoptosis and the caspase-12 plays a key role in this process.
Animals ; Apoptosis ; drug effects ; Blotting, Western ; Calcium ; metabolism ; Caspase 12 ; metabolism ; Caspase 7 ; metabolism ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Econazole ; pharmacology ; Flow Cytometry ; Leukemia ; metabolism ; pathology

BACKGROUND: We thought that nitroimidazoles including metronidazole had been overused empirically for treatment of trichomoniasis in Korea. But there were not any reports about in vitro-drug susceptibility and distribution of resistant strains of Trichomonas vaginalis up to date. Therefore, we made an experiment in order to observe the susceptibility of clinical isolates of T. vaginalis to a variety of antiprotozoal agents. METHODS: Twenty-six strains of T. vaginalis isolated from 217 patients afflicted with the increased vaginal discharge were tested by Meingassner's microtiter plate method in newly devised anaerobic box, in which anaerobic and microaerobic conditions were more easily manipulated. The agents used in this study for testing the minimal lethal concentration (MLC) to the clinical isolates were as follows; nitroimidazoles, doxycycline, Zinc sulfate and gentian violet as chemotherapeutic agents and povidone-iodine as vaginal cleansing agents were studied. RESULTS: In anaerobic culture, according to anaerobic resistance cut-point (minimal lethal concentration >3.1 microgram/mL) proposed by M ller etc., metronidazole (MTZ)-, tinidazole (TNZ)-and ornidazole (ONZ)-resistant strains were four (4/26, 15.4%), two (2/26, 7.7 %) and two (2/26, 7.7%) strains, respectively. Among these resistant strains, two strains (G7 and G16) were resistant to two drugs and one strain (G20) resistant to three drugs concomitantly. Their resistance range was narrow as 6.25~12.5 microgram/mL. MLC of clotrimazole was > or = 2,000 microgram/mL in all strains, econazole was as high as 62.5~250 microgram/mL and miconazole was also high as 62.5~> or = 2,000 microgram/mL. In microaerobic culture (O2 concentration <5%), all strains showed lower MLC to MTZ, TNZ and ONZ than >100 microgram/ mL (aerobic resistance cut-point proposed by M ller etc.). MLC of doxycycline ranged 62.5 to 250 microgram/mL both in microaerobic and anaerobic conditions. All strains of T. vaginalis growed well in 3,000 microgram/mL of povidone-iodine. 22 strains (84.6%) among 26 T. vaginalis strains showed MLCs of 3.5 mM~7.0 mM to zinc sulfate. Gentian violet showed 15.6~62.5 microgram/mL of MLC. CONCLUSION: In absolute anaerobic culture, 4 strains (15.4%) among 26 T. vaginalis strains were resistant to metronidazole. But these 4 strains were not resistant in microaerobic culture depending on Miler's aerobic resistance cut-point (>50~100 microgram/mL), the value decided in normal O2 pressure. Vaginal PO2 is 0~28mm Hg (median 1 mmHg) at healthy or trichomonas-infected women. Therefore, we think that his aerobic resistance cut-point value is hard to be available in microaerobic condition and microaerobic resistance guide-line is to be established newly.
Anti-Infective Agents ; Antiprotozoal Agents* ; Clotrimazole ; Detergents ; Doxycycline ; Econazole ; Female ; Gentian Violet ; Humans ; Korea ; Metronidazole ; Miconazole ; Nitroimidazoles ; Ornidazole ; Povidone-Iodine ; Tinidazole ; Trichomonas vaginalis* ; Trichomonas* ; Vaginal Discharge ; Zinc Sulfate

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