Pharmacokinetics/Pharmacodynamics study of Fixtral SB as compared to supra bioavailable itraconazole and conventional itraconazole

BACKGROUND Itraconazole is a broad-spectrum triazole antifungal inhibiting fungal growth by inhibiting ergosterol synthesis and exhibits a nonlinear pharmacokinetic profile.Erratic absorption pattern with wide fluctuations in blood levels causes inconsistent and unpredictable clinical behaviour of this drug despite its low minimum inhibitory concentration(MIC)as compared to other antifungal agents.AIM To compare the oral bioavailability and bioequivalence of Fixtral SB(supra bioavailable itraconazole)with reference product R2(supra bioavailable 2×50 mg itraconazole).METHODS The study population consisted of 54 healthy volunteers,aged between 18-45 years and randomized to receive a single oral dose of either test[T;Fixtral SB(supra bioavailable itraconazole)100 mg]or reference product(R1;Sporanox 100 mg×2 capsules and R2;Lozanoc capsules 50 mg×2 capsules).Blood samples were taken pre-dose and post-dose up to 96 h.The study evaluated bioequivalence by comparing the oral bioavailability of the test product with reference product R2.The pharmacodynamic characteristics of the drug were evaluated by comparing the test product with reference product R1.Pharmacokinetics(PK)-PD comparative analysis[area under the concentration-time curve(AUC)/minimum inhibitory concentration(MIC)>25]was performed for conventional itraconazole 100 mg and supra bioavailable itraconazole 50 mg.Adverse events(AEs)assessments were performed in each study period and post-study evaluation.RESULTS Statistical analysis of primary PK variables revealed bioequivalence,with confidence intervals being completely inside the acceptance criteria of 80%-125%.The peak concentration levels of itraconazole were achieved at 10 h(T)and 8.5 h(R2),respectively.Pharmacodynamic parameter assessment showed that AUC/MIC for R1 are comparable to Fixtral SB 100mg for MIC levels up to 16mcg/mL(P>0.05 and observed P=0.3196).Six AEs were observed that were mild to moderate in severity and resolved.No severe AE was reported.CONCLUSION Test product itraconazole Capsule 100 mg is bioequivalent with the reference product(R2)at 100 mg dose(2 capsules of Lozanoc®50 mg)under fed conditions.Pharmacodynamics activity in terms of AUC/MIC is comparable between the test product at 100 mg dose and marketed itraconazole 200 mg.Fixtral SB is expected to have therapeutically similar efficacy at half the equivalent dose.Tested formulations were found to be safe and well tolerated.

Evaluating the Effects of Crystallinity on Drug Release Behaviour in Itraconazole- or Miconazole-Loaded PLGA Microparticles Prepared Using a Co-Grinding Method

This study aimed to prepare and characterize itraconazole (ITCZ)- or miconazole (MCZ)-loaded poly (lactide-co-glycolide) (PLGA) microparticles (MP) using a co-grinding method with ball milling, which is a solvent-free and convenient procedure. PLGA MP was prepared by grinding for 60 min, and the fixed theoretical drug loading was set at 9.1% and 16.7% for both drugs. The obtained loading efficiency for both drugs was estimated to be approximately 100%. The average diameters of the drug-loaded PLGA MP were approximately 20 - 35 μm. Powder X-ray diffraction (PXRD) or differential scanning calorimetry (DSC) confirmed amorphization of ITCZ and MCZ in ITCZ- or MCZ-loaded PLGA MP in all formulations. The drug release percentage from 9.1%-loaded ITCZ-PLGA7505 MP at 24 h was almost 50%, which was higher than that of ITCZ powder. The drug release percentage from MCZ-loaded PLGA7505 MP at 4 h was over 80%, which was higher than that of MCZ powder. This enhancement of release rate is caused by the amorphization of ITCZ or MCZ in the PLGA matrix. MCZ-loaded PLGA7510 MP showed a sustained release profile up to 24 h, suggesting that MCZ exists in an amorphous form in the PLGA matrix;however, the release rate declined owing to the large molecular weight of PLGA. Therefore, the release enhancement of antifungal drugs loaded on PLGA MP could be achieved by their amorphization using a co-grinding method with ball milling.

Metabonomic analysis of plasma biochemical changes in pyrexia rats after treatment with Gegenqinlian decoction,aspirin and itraconazole by UHPLC-FT-ICR-MS

A metabonomic approach involving an ultrahigh-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry(UHPLC-FT-ICR-MS)was used to investigate the changes in the endogenous metabolites in the plasma of rats with yeast-induced pyrexia treated with Gegenqinlian decoction(GQLD),aspirin and itraconazole.The differences in the small molecule profiles of treatment using traditional Chinese medicine,etiological treatment and symptomatic treatment were elucidated.Thirty-six plasma metabolites were identified or putatively identified,and the effects of the three medicines on the thirty-six metabolites were studied.Their metabolic pathways indicated that GQLD,aspirin and itraconazole ameliorated the rats with yeast-induced pyrexia predominantly by regulating the metabolisms of phospholipid,sphingolipid,fatty acid oxidation,fatty acid amides,amino acid and glycerolipid in vivo.The pharmacodynamics and metabonomic results showed that the three medicines exhibited the therapeutic effects on pyrexia by regulating the perturbations of multiple metabolisms.The study provided a scientific basis for an in-depth understanding of the therapeutic effects of GQLD,aspirin and itraconazole on rats with yeast-induced pyrexia.

Supersaturation induced by Itraconazole/Soluplus micelles provided high GI absorption in vivo

To investigate the effect of supersaturation induced by micelle formation during dissolution on the bioavailability of itraconazole(ITZ)/Soluplus~? solid dispersion. Solid dispersions prepared by hot melt extrusion (HME) were compressed into tablets directly with other excipients. Dissolution behavior of ITZ tablets was studied by dissolution testing and the morphology of micelles in dissolution media was studied using transmission electron microscopy (TEM). Drug transferring from stomach into intestine was simulated to obtain a supersaturated drug solution. Bioavailability studies were performed on the ITZ tablets and Sporanox~? in beagle dogs. The morphology of micelles in the dissolution media was observed to be spherical in shape, with an average size smaller than 100 nm. The supersaturated solutions formed by Soluplus~? micelles were stable and no precipitation took place over a period of 180 min. Compared with Sporanox~?, ITZ tablets exhibited a 2.50-fold increase in the AUC (0–96) of ITZ and a 1.95-fold increase in its active metabolite hydroxyitraconazole (OHITZ) in the plasma of beagle dogs. The results obtained provided clear evidence that not only the increase in the dissolution rate in the stomach, but also the supersaturation produced by micelles in the small intestine may be of great assistance in the successful development of poorly water-soluble drugs. The micelles formed by Soluplus~? enwrapped the molecular ITZ inside the core which promoted the amount of free drug in the intestinal cavity and carried ITZ through the aqueous boundary layer(ABL), resulting in high absorption by passive transportation across biological membranes. The uptake of intact micelles through pinocytosis together with the inhibition of P-glycoprotein-mediated drug efflux in intestinal epithelia contributed to the absorption of ITZ in the gastrointestinal tract. These results indicate that HME with Soluplus~?, which can induce supersaturation by micelleformation, may be of great assistance to the successful development of poorly watersoluble drugs.

Selective Determination of Itraconazole in the Presence of Its Oxidative Degradation Product by A New Spectrophotometric Method

A simple,specific,accurate and precise spectrophotometric stability indicating method is developed for determination of itraconazole in the presence of its oxidative degradation product and in pharmaceutical formulations.A newly developed spectrophotometric method called ratio difference method by measuring the difference in amplitudes between 230 and 265nm of ratio spectra.The calibration curve is linear over the concentration range of 5~25μg·mL-1 with mean percentage recovery of 99.81±1.002.Selective quantification of itraconazole,singly in bulk form,pharmaceutical formulations and in the presence of its oxidative degradation product is demonstrated.The results have been statistically compared with a pharmacopeial method.

Itraconazole therapy for infant hemangioma:Two case reports

BACKGROUND Infantile hemangiomas(IHs)are the most common childhood benign tumors,showing distinctive progression characteristics and outcomes.Due to the high demand for aesthetics among parents of IH babies,early intervention is critical in some cases.β-Adrenergic blockers and corticosteroids are first-line medications for IHs,while itraconazole,an antifungal medicine,has shown positive results in recent years.CASE SUMMARY In the present study,itraconazole was applied to treat two IH cases.The therapeutic course lasted 80-90 d,during which the visible lesion faded by more than 90%.Moreover,no obvious side effects were reported,and the compliance of the baby and parents was desirable.CONCLUSION Although these outcomes further support itraconazole as an effective therapeutic choice for IHs,large-scale clinical and basic studies are still warranted to improve further treatment.

Characterization of recrystallized itraconazole prepared by cooling and anti-solvent crystallization

The objective of the present study was to alter the crystal habit of itraconazole(ITZ)by cooling and anti-solvent crystallization and characterize its properties.ITZ was recrystallized in different solvents and the effects of each solvent on morphology of crystals,dissolution behavior and solid state of recrystallized drug particles were investigated.The results revealed that ITZ crystals recrystallized by cooling and anti-solvent crystallization showed the different crystal habits from the untreated ITZ.Using cooling crystallization tended to provide needle-shaped crystals while the crystals obtained from anti-solvent crystallization showed more flaky,plate shape.This indicated the importance of preparation method on nucleation and crystal growth.No change in drug polymorphism was observed,according to determination of thermal property and crystalline state by differential scanning calorimetry and powder X-ray diffractometry,respectively.The recrystallized ITZ showed higher drug dissolution than untreated ITZ and the highest drug dissolution was observed from the samples recrystallized in the presence of PEG 200,which provided the small plate-shaped crystals with tremendously increased in surface area.However,the increasing of drug dissolution is relatively small,therefore,further development may be required.

A New In-Situ Gel Formulation of Itraconazole for Vaginal Administration

In this paper, mucoadhesive in-situ gel with poloxamer and hydroxypropylmethylcellulose formulations of itraconazole were prepared for vaginal application. In addition, rheological, mechanical and mucoadhesive properties and syringeability of the formulations were characterized. The mixtures of Poloxamer 407 and 188 with two different types of hydroxypropylmethylcellulose were used as polymers for gel formulations. Flow rheometry studies and oscillatory analysis of each formulation were performed at 20℃ ± 0.1℃ and 37℃ ± 0.1℃. All formulations exhibited pseudo-plastic flow and typical gel-type mechanical spectra (G′ > G″) after the determined frequency value at 37℃. Texture profile analysis presented that F3 formulation containing 20% poloxamer 407, 10% poloxamer 188 and 0.5% hydroxypropylmethylcellulose appeared to offer more suitable mechanical and mucoadhesive performance. Using different hydroxypropylmethylcellulose type in formulations didn’t significantly change syringeability values. The evaluation of the entire candidate formulations indicated that vaginal formulation of itraconazole will be an alternative for the treatment of vaginal candidiasis with suitable textural and rheological properties. Our results showed that the developed formulations were found worthy of further studies.

Preparation and physical properties of itraconazole-loaded nanoemulsions using pineapple starch as co-emulsifier

Pineapple plant(Ananascomosus L.Merr.)is a leading edible member of the Bromeliaceae family[1].Nanoemulsions containing itraconazole,a poorly water-soluble drug using pectin as a polymeric emulsifier,are currently under investigation[2].The physicochemical and rheological properties as well as structural characterizations of cassava and mungbean starches have been reported[3].However,the application of pineapple starch as co-emulsifier of pharmaceutical excipients for pharmaceutical industry has not been investigated.

Development of Liposome containing sodium deoxycholate to enhance oral bioavailability of itraconazole

The aim of this study was to enhance oral bioavailability of itraconazole(ITZ) by developing Liposome containing sodium deoxycholate(ITZ-Lip-NaDC). The liposome, consisting of egg yolk lecithin and sodium deoxycholate, was prepared by thin-film dispersion method.Differential Scanning Calorimetry(DSC) results indicated an amorphous state in the liposome. The physicochemical characteristics including particle size, morphology, entrapment efficiency, dissolution properties were also investigated. The performance of single-pass intestinal infusion exhibited that the transport order of intestinal segment was jejunum,duodenum, colon and ileum, and that all the segments participated in the absorption of ITZ in intestinal tract. The bioavailability study in rats showed that the AUC0-72 of the liposome was nearly 1.67-fold higher than that of commercial capsules(SPORANOX) in terms of oral administration, and the RSD of AUC0-72 of ITZ-Lip-NaD C was also decreased. Our results indicated that ITZ-Lip-NaDC liposome was facilitated to improve dissolution efficiency,augment transmembrane absorption, and then enhance the oral bioavailability of ITZ,successfully.

Effect of itraconazole on the cornea in a murine suture model and penetrating keratoplasty model

AIM: To investigate the anti-(lymph)angiogenic and/or anti-inflammatory effect of itraconazole in a corneal suture model and penetrating keratoplasty(PK) model. METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among itraconazole, amphotericin B, dexamethasone, phosphate buffered saline(PBS) and surgery-only groups following subconjunctival injection in mice that underwent PK and corneal suture. Immunohistochemical staining and analysis were performed in each group. Real-time polymerase chain reaction(RT-PCR) was performed to quantify the expression of inflammatory cytokines(TNF-alpha, IL-6) and vascular endothelial growth factor(VEGF)-A, VEGF-C, VEGFR-2, and VEGFR-3.RESULTS: In the suture model, the itraconazole group showed less angiogenesis, less lymphangiogenesis, and less inflammatory infiltration than the PBS group(all P<0.05). The itraconazole group showed reduced expression of VEGF-A, VEGFR-2, TNF-alpha, IL-6 than the PBS group(all P<0.05). In PK model, the two-month graft survival rate was 28.57% in itraconazole group, 62.50% in dexamethasone group, 12.50% in PBS group, 0 in amphotericin B group and 0 in surgery-only group. Graft survival in the itraconazole group was higher than that in the amphotericin, PBS and surgery-only group(P=0.057, 0.096, 0.012, respectively). The itraconazole group showed less total angiogenesis and lymphangiogenesis than PBS group(all P<0.05).CONCLUSION: Itraconazole decrease neovascularization, lymphangiogenesis, and inflammation in both a corneal suture model and PK model. Itraconazole has anti-(lymph)-angiogenic and anti-inflammatory effects in addition to its intrinsic antifungal effect and is therefore an alternative treatment option in cases where steroids cannot be used.

Microemulsion-based hydrogels of itraconazole:Evaluation of characteristics and stability

Itraconazole (ITZ) is a broad spectrum triazole antifungal drug and commercially available as oral forms. However, effective topical forms are interesting to avoid systemic adverse effects,to directly deliver antifungal drugs to the target sites and to enhance patient compliance (1)Microemulsion-based hydrogel (MBH), a semisolid form of microemulsion (ME), is one of novel formulations practically used as topical drug carriers [2].

Itraconazole and Nail Scraping in the Treatment of Onychomycosis( A open trial of175 cases)

Objective Itraconazole pulse therapy is at lest as efficient as itraconazole continuous treatment for onychomyocsis, but the long term oral antimycotic therapy has potential hepatotoxicity.Methods\ 40% urea paste was thickly applied to each affected nail which was dressed by three cloth adhesive tapes. The urea paste was changed every day or every other day for 5 to 7 days. The sick softened nails were scraped off thoroughly with razer blade. After sick nails were removed, all patients received 200 mg of itraconazole twice a day for seven consecutive days. Results\ Fingernail onychomycosis were cured in 93% (130/140), markedly improved in 6.4% (9/140). Toenail onychomycosis were cured in 82% (29/35), markedly improved in 17.1(6/35). And in a 18 month follow up period, 16(10 2%) of 147 patients had relapses. Conclusion\ The treatment of onychomycosis with oral itraconazole plus nail scraping is as effective as that of itraconazole pulse therapy but has less side effect and lower cost.\;

Intravenous-oral itraconazole versus oral posaconazole in preventing invasive fungal diseases for acute leukemia patients

Invasive fungal diseases(IFDs)are major and lethal infectious complications for patients with neutropenia after chemotherapy.Prophylaxis with intravenous and oral suspended itraconazole(200 mg Q12h intravenously×2 days followed by 5 mg/kg·d orally in twice)or oral suspension of posaconazole(200 mg Q8h)was administered for preventing IFDs.The only 2 episodes of proven IFDs were not included after propensity-score matching(PSM),while the incidence of possible IFDs was 8.2%(9/110)in itraconazole group and 1.8%(2/110)in posaconazole group,respectively(P=.030).In clinical failure analysis,the failure rate of posaconazole group was lower as compared to the itraconazole group(2.7%vs 10.9%,P=.016).Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs,while posaconazole suspension seems more tolerable.

Efficacy and safety of itraconazole use in infants

Background:Itraconazole has been used to treat fungal infections,in particular invasive fungal infections in infants or neonates in many countries.Data sources:Literature search was conducted through Ovid EMBASE,PubMed,ISI Web of Science,CNKI and Google scholarship using the following key words:“pediatric”or“infant”or“neonate”and“fungal infection”in combination with“itraconazole”.Based on the literature and our clinical experience,we outline the administration of itraconazole in infants in order to develop evidence-based pharmacotherapy.Results:Of 45 articles on the use of itraconazole in infancy,13 are related to superficial fungal infections including tinea capitis,sporotrichosis,mucosal fungal infections and opportunistic infections.The other 32 articles are related to systemic fungal infections including candidiasis,aspergillosis,histoplasmosis,zygomycosis,trichosporonosis and opportunistic infections as caused by Myceliophthora thermophila.Conclusion:Itraconazole is safe and effective at a dose of 5 mg/kg per day in a short duration of therapy for superficial fungal infections and 10 mg/kg per day for systemic fungal infections in infants.With a good compliance,it is cost-effective in treating infantile fungal infections.The profiles of adverse events induced by itraconazole in infants are similar to those in adults and children.

Itraconazole Promotes Macrophage M1 Polarization and Phagocytic Capacity of Macrophage to Candida Albicans

Objective: The present study was designed to evaluate whether and how itraconazole affects the macrophage polarization and its reactivity to Candida albicans. Methods: Cell toxicity of itraconazole was measured using cell counting kit-8 assay in RAW264.7 cells. The cell models were induced by lipopolysaccharide (LPS), interleukin (IL)-4, or Candida albicans. Levels of cytokines secreted by RAW246.7 treated with itraconazole were detected by Luminex or Cytometric Bead Array compared to the controls without itraconazole treatment, and the expressions of inducible nitric oxide synthase and arginase (Arg) were determined by Western blot. Phagocytosis ability was measured by both flow cytometry and fluorescence microscope. The Student's t test and one-way analysis of variance were used to calculate the differences between groups. Results: In comparison to the control, itraconazole inhibited the growth of the cells in both a time- and a dosedependent manner. Increased secretion of IL-6 (0.25μmol/L ITZ [538.03±60.23pg/mL, P<0.05], 0.5μmol/L [550.32 ±47.87 pg/mL, P<0.05] and 1 μmol/L [626.95±75.24pg/mL, P<0.01] vs. control [370.43±33.98pg/mL]) and tumor necrosis factor-alpha (TNF-α) (1μmol/L ITZ vs. control: 2521.51±444.06pg/mL vs. 1617.85±94.57 pg/mL, P<0.05) were detected in the LPS-induced cell model with itraconazole treatment. In the cells induced by IL-4, itraconazole increased the secretion of IL-6 (1μmol/L ITZ vs. control: 528.33±11.60pg/mL vs. 466.99±28.32 pg/mL, P<0.05), TNF-α (1μmol/L ITZ vs. control: 4.85±0.32pg/mL vs. 4.30±0.19 pg/mL, P<0.05), and IL-1β (0.25μmol/L [325.95±13.97pg/mL, P<0.05], 0.5μmol/L [332.38±11.97pg/mL, P<0.05] and 1μmol/L [334.35±16.23 pg/mL, P<0.05] vs. control [291.62±17.03pg/mL]), and reduced the secretion of IL-10 (1μmol/L ITZ vs. control: 7.21±0.68 pg/mL vs. 9.11±0.14pg/mL, P<0.05). The secretion of IL-6 (1μmol/L ITZ vs. control: 38.34±1.36pg/mL vs. 32.32± 0.84pg/mL, P<0.05) and TNF-α (1μmol/L ITZ vs. control: 1060.17±80.16pg/mL vs. 890.84±52.82 pg/mL, P<0.01) was improved in Candida albicans-stimulated RAW264.7 cells under the treatment of itraconazole, while the secretion of IL-4 (0.5μmol/L [2.86±0.20 pg/mL, P<0.05] and 1μmol/L [2.24±0.33 pg/mL, P<0.001] vs. control [3.91±0.23 pg/mL]) and IL-10 (1μmol/L ITZ vs. control: 19.46±2.05pg/mL vs. 25.67±1.95pg/mL, P<0.05) decreased. In all three activated patterns, itraconazole enhanced the expression of inducible nitric oxide synthase (P<0.01) and slightly inhibited the Arg-1 expression (P<0.05). Phagocytosis ability of RAW264.7 cells at 1μmol/L ITZ treatment was increased by 7.53%±2.21% (P<0.01) and 9.73%±2.03% (P<0.01) at the ratio of cells: yeast of 1:4 and 1:8, respectively, in comparison to the control group.Itraconazole improved M1 polarization of RAW264.7 cells and enhanced the phagocytic capacity of RAW264.7 to Candida albicans, indicating a significant immunological enhancement. The study improves the understanding of undergoing mechanisms related to the anti-tumor and anti-infection effects of itraconazole.

Cardiac Toxicity of Azole Antifungals

Cardiac toxicity is an uncommon side effect of anti-fungal therapy. Until the recent reports of itraconazole (ITZ) associated cardiac failure, amphotericin was the antifungal most frequently reported with arrhythmias. We evaluated the cardiac effect of azole antifungals, specifically ITZ, and possible mechanisms of toxicity. Ex vivo live-heart studies were performed utilizing Sprague Dawley rats. Short exposure (<5 minutes), random crossover, dose ranging studies were performed with each pharmacologic agent. ITZ focused trials also included dose ranging utilizing a non-crossover design. The only azole found to have significant toxicity was ITZ. At ITZ ~ ED25 (2 - 2.5 ug/mL) exposures, contractility decreased by 22.2% ± 15.7% and amplitude of left ventricular pressure decreased by 11% ± 0.17%. Electron micrograph and alterations in mitochondrial respiration suggest mitochondrial toxicity as an underlying mechanism. In conclusion, ITZ was associated with reductions in contractility, possibly secondary to mitochondrial dysfunction and dilated cardiomyopathy.

Physicochemical evaluation and in vitro release studies on itraconazolium sulfate salt

To counter the poor aqueous solubility of itraconazole(ITC),its sulfate salt(ITCSUL)was synthesized and characterized by 1 H NMR,MS,FTIR,DSC,XRPD,DLS and SEM.Antifungal properties of ITCSUL were confirmed against different fungal pathogens by broth microdilution method.Enhanced solubility of the salt in various pharmaceutical solvents was observed.Approximately 5.5 fold increase in percentage drug release from ITCSUL than that of ITC in 3 h was observed.Further,the physical mixtures of ITCSUL with two cyclodextrins;b-cyclodextrin(b-CD)and HP-b-cyclodextrin(HP-b-CD)were prepared in 3 M ratios.The in vitro release studies of CD mixtures of ITC and ITCSUL exhibited markedly enhanced dissolution in comparison to ITC and ITCSUL respectively.The promising in vitro performance of ITCSUL and ITCSUL CD mixtures along with advantage of expedient preparation suggest their potential applications in designing a better oral drug delivery system.

<i>Rhizopus oryzae</i>Retro-Orbital Abscess: Comparison of Spores and Hyphae Antifungal Susceptibility and Clinical Outcome

Rhizopus is fungus of the order Mucorales, responsible for invasive diseases called mucormycosis. The correct identification of these fungi is one of the main questions raised in the literature since the diagnosis is not simple, being the necessary detection in biopsies of infected tissues and isolation of the microorganism for identification by morphological and molecular methods. In vitro susceptibility testing results are not fully clear since there are reports showing that in vitro resistance does not always mean therapeutic failure. This paper describes a case of rhino-orbito-cerebral mucormycosis in a patient with alcoholic chronic pancreatitis and secondary mellitus diabetes involving microbiological diagnostic, antifungal susceptibility tests for conidia and hypha and clinical correlation. The causative agent was identified by morphological characteristics and DNA sequencing. Minimal Inhibitory Concentration (MIC) for amphotericin B (AMB), itraconazole (ITZ) and terbinafine (TERB) was determined by broth microdilution method. Standardization of the dynamic growth evaluation patterns using the automated system BCT (BioCell-Tracer?) was obtained allowing to determining hyphae growth control and evaluating the effect of different concentrations of amphotericin B, itraconazole and terbinafine directly on growing hyphae. The fractional inhibitory concentration (FIC) for the combination of the two antifungals that the patient received at the same time, terbinafine and itraconazole, was also determined trying to correlate with clinical outcome. Strains isolated of retro-orbital abscess were identified as Rhizopus oryzae. MIC results (MIC) testing conidia showed high sensibility to amphotericin B and itraconazole in comparison to the obtained for terbinafine. The tests in the automated system BCT using hyphae showed sensibility to all tested antifungal agents and the FIC results for combination in vitro between terbinafine and itraconazole showed synergism consistent with the therapeutic success obtained for the patient who received initial treatment with amphotericin B followed for maintenance treatment with the combination itraconazole and

Atypical Cutaneous Leishmaniasis by Leishmania Mexicana: A Case Report with Dermoscopic, Histopathological and Molecular Study

Cutaneous leishmaniasis is a neglected tropical skin endemic disease, with worldwide distribution. By 2020 in the Americas, Mexico was in 12th place with 11 states reporting new cases. Molecular biology with different targets for diagnosis and species identification has been used for decades, also dermoscopy, a non-invasive diagnostic tool has shown its usefulness. We present the first case of cutaneous leishmaniasis in non-endemic place (Guerrero, Mexico) identifying Leishmania mexicana with molecular biology, and treated with itraconazole.