Analysis of health care professionals' incident reports on medical devices in Croatia.

AIM: To assess the quantity and quality of incident reports on medical devices by health care professionals from 2012 to 2021 and evaluate the effect of reporting on manufacturers' post-market surveillance. METHODS: Eighty-five incident reports were scored according to a self-developed evaluation system, and categorized as excellent, good, medium, qualified, and unqualified. The completeness of data in critical fields was assessed. For each report, the type and city of the reporter, and medical device risk class were extracted to calculate the frequency of report occurrence per risk class and outcomes for reportable reports. RESULTS: The number of reports received from health care professionals was low; the highest number of reports in a year was 17. The majority of reports were deemed as unqualified (61.18%) and only 4.71% as excellent. Still, 67.65% of incident reports importantly affected the manufacturer's post-market surveillance, either as added information that contributes to risk monitoring or directly triggering a field safety corrective action. CONCLUSION: The number of total reports and reports per year shows extensive underreporting in Croatia, and the quality of the provided reports is insufficient.

The readiness of the spontaneous reporting system for COVID-19 vaccines safety monitoring in Croatia.

We aimed to identify whether a spontaneous reporting system (SRS) in Croatia could timely identify and confirm signals for COVID-19 vaccines. Post-marketing spontaneous reports of adverse drug reactions (ADRs) following COVID-19 immunisation reported to the Agency for Medicinal Products and Medical Devices of Croatia (HALMED) were extracted and analysed. 6624 cases reporting 30 655 ADRs following COVID-19 immunisation were received from 27th December 2020 to 31st December 2021. Available data in those cases were compared with data available to the EU network at the time when signals were confirmed and minimisation measures were implemented. 5032 cases, reporting 22 524 ADRs, were assessed as non-serious, and 1,592 cases, reporting 8,131 ADRs as serious. The most reported serious ADRs, which were listed in the MedDRA Important medical events terms list, were syncope (n = 58), arrhythmia (n = 48), pulmonary embolism (n = 45), loss of consciousness (n = 43), and deep vein thrombosis (n = 36). The highest reporting rate had Vaxzevria (0.003), followed by Spikevax and Jcovden (0.002), and Comirnaty (0.001). Potential signals were identified, however, they couldn't be timely confirmed solely on cases retrieved by SRS. In order to overcome the limitations of SRS, active surveillance and post-authorisation safety studies of vaccines should be implemented in Croatia.

Quality analysis of manufacturer's incident reports regarding medical devices.

BACKGROUND: Medical devices provide a great number of medical treatments and have an important role in patients' healthcare; however, there are certain risks, sometimes even serious incidents, associated with their usage. To ensure that benefits of medical device usage always outweigh associated risks, it is necessary to closely monitor known risks post-market and detect new ones as early as possible. Among others, valuable instrument of post-market surveillance is manufacturer incident report. Yet to accomplish its intended use, such report must be sufficiently populated and supplied with correct information. Aim of this paper is to assess the quality of manufacturer's incident reports received in HALMED since 2012 to May 2021. METHODS: The study included 578 initial reports and 566 final reports that were scored according to the evaluating system we designed and categorized as Excellent, Good, Medium, Qualified and Unqualified. For each report medical device risk class was also extracted to calculate the frequency of report occurrence per risk class and time that passed between the initial and final report. Difference in quality of the reports between manufacturers based on EU countries and countries outside the EU was determined by Mann Whitney U test. RESULTS: Most of initial and final reports fall into two highest quality category level, which means that a sufficient amount of reports are of good/excellent quality and quality of reports prevails. However, the study's results indicate the need for higher scores, especially in critical fields of the form. CONCLUSIONS: Data obtained from the manufacturer can be scarce and insufficient, causing negative influence on Competent Authority's investigation procedure. Another issue we recognized is extensive underreporting in Croatia, which can seriously undermine the established system.

Medical devices as a source of phthalate exposure: a review of current knowledge and alternative solutions.

Phthalates are a group of phthalic acid esters used as plasticisers in a large number of products to improve their flexibility, softness, and extensibility. Their wide use in medical devices, however, raises a lot of concern, as they can enter the organism and have toxic effects on human liver, thyroid, kidneys, lungs, reproductive, endocrine, nervous, and respiratory system and are associated with asthma, obesity, autism, and diabetes. The aim of this review is to summarise current knowledge about phthalate migration from medical devices during different medical procedures and possible impact on patient health. It also looks at alternative plasticisers with supposedly lower migration rates and safer profile. Not enough is known about which and how many phthalates make part of medical devices or about the health impacts of alternative plasticisers or their migration rates.

Presence of nitrosamine impurities in medicinal products.

In 2018, some sartan medicinal products were reported to be contaminated with nitrosamine compounds, which are potent mutagenic carcinogens. Two nitrosamines received particular attention: N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA). These have since been confirmed in different types of medicinal products, including ranitidine and metformin. Consequently, the European Medicines Agency (EMA) started an investigation into the cause of contamination and an assessment of the risk to patients taking contaminated medicinal products. The main source of contamination were changes in production, which involves combinations of amines and nitrogen compounds and the use of specific catalysts and reagents. Withdrawals of medicinal products that took place in Croatia did not lead to a shortage of sartan- or metformin-containing medicines. Moreover, ranitidine had been preventively withdrawn all over the EU, including Croatia, creating shortages at the time, but was subsequently replaced with therapeutic alternatives.

Community pharmacists' use, perception and knowledge on dietary supplements: a cross sectional study.

BACKGROUND: Pharmacists are commonly tasked with recommending the appropriate dietary supplement and advising the patients of their correct and safe use. Previous research, conducted on pharmacy students, showed that they did not always use the evidence based sources of information, with personal use identified as a significant predictor influencing the decision to recommend a supplement. OBJECTIVES: To compare use, perceptions and knowledge of dietary supplements of pharmacists with different years of work experience and to explore factors that could influence their recommendation of supplements. METHODS: A questionnaire based cross-sectional study was conducted on Croatian community pharmacists in September 2017. The questionnaire explored pharmacists' demographic characteristics, use, perceptions and knowledge of dietary supplements. Pharmacists (N=102) were divided in two groups based on their work experience: P0 (<10 years) and P1 (≥10 years). RESULTS: All included pharmacists had high knowledge scores without differences between groups (P0=10, IQR 9-12 vs P1=11, IQR 9-12, expressed as median and interquartile range (IQR), p=0.275). Less experienced pharmacists perceived there was less research conducted on the dietary supplements compared to their more experienced counterparts (P0=1, IQR 1-2 vs P1=2, IQR 2-3, expressed as median and interquartile range, p<0.001). Groups differed in sources used when choosing the appropriate supplement with P0 using higher quality sources such as systematic reviews in comparison to P1 (32.1% vs 8.7%, p=0.004). Pharmacists' decision to recommend a dietary supplement was influenced by their personal use (odds ratio 0.216, 95%CI 0.068:0.689, p=0.01) and work experience (odds ratio 0.154, 95%CI 0.045:0.530, p=0.003). CONCLUSIONS: Pharmacists did not use the high quality sources when recommending dietary supplements and their decision to recommend the supplement was not based on objective evaluation of evidence. Further education about the practice of evidence-based pharmacy is necessary, with special emphasis on senior pharmacists who might have missed that aspect during their formal education.

Community pharmacists' use, perception and knowledge on dietary supplements: a cross sectional study

BACKGROUND: Pharmacists are commonly tasked with recommending the appropriate dietary supplement and advising the patients of their correct and safe use. Previous research, conducted on pharmacy students, showed that they did not always use the evidence based sources of information, with personal use identified as a significant predictor influencing the decision to recommend a supplement. OBJECTIVES: To compare use, perceptions and knowledge of dietary supplements of pharmacists with different years of work experience and to explore factors that could influence their recommendation of supplements. METHODS: A questionnaire based cross-sectional study was conducted on Croatian community pharmacists in September 2017. The questionnaire explored pharmacists' demographic characteristics, use, perceptions and knowledge of dietary supplements. Pharmacists (N=102) were divided in two groups based on their work experience: P0 (<10 years) and P1 (≥10 years). RESULTS: All included pharmacists had high knowledge scores without differences between groups (P0=10, IQR 9-12 vs P1=11, IQR 9-12, expressed as median and interquartile range (IQR), p = 0.275). Less experienced pharmacists perceived there was less research conducted on the dietary supplements compared to their more experienced counterparts (P0=1, IQR 1-2 vs P1=2, IQR 2-3, expressed as median and interquartile range, p < 0.001). Groups differed in sources used when choosing the appropriate supplement with P0 using higher quality sources such as systematic reviews in comparison to P1 (32.1% vs 8.7%, p = 0.004). Pharmacists' decision to recommend a dietary supplement was influenced by their personal use (odds ratio 0.216, 95%CI 0.068:0.689, p = 0.01) and work experience (odds ratio 0.154, 95%CI 0.045:0.530, p = 0.003). CONCLUSIONS: Pharmacists did not use the high quality sources when recommending dietary supplements and their decision to recommend the supplement was not based on objective evaluation of evidence. Further education about the practice of evidence-based pharmacy is necessary, with special emphasis on senior pharmacists who might have missed that aspect during their formal education

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Antimicrobial Resistance: Physicians' and Pharmacists' Perspective.

Aims: The aim of this study was to evaluate pharmacists' and physicians' attitudes and knowledge about antimicrobial treatment and resistance and based on the results to identify possible gaps and suggest opportunities for collaboration between the two professions. Methods: The physician's questionnaire consisted of 47 items and the pharmacists' questionnaire consisted of 50 items. Participants were asked to identify situations in which they were more likely to prescribe/dispense an antimicrobial without a firm indication, to identify the greatest contributors to antimicrobial resistance (AMR) among health care workers, to rate statements related to AMR, how frequently they used different sources of information and to rate the possible causes of AMR. Furthermore, preparedness for specific actions in practice was self-rated and knowledge was evaluated. The questionnaires were anonymous and participation in the study was voluntary. Results: This research included 180 community pharmacists and 181 physicians. As many as 76 (42.0%) physicians stated they would prescribe an antimicrobial when unsure whether the infection was of viral or bacterial etiology. More than half of the participants considered family medicine doctors the greatest contributors to AMR (N = 216, 59.8%), followed by patients (N = 175, 48.5%). In questions focusing on knowledge, physicians scored significantly higher compared with pharmacists (4.06 ± 1.01 vs. 3.71 ± 1.08, p = 0.001). Conclusion: This research revealed practices among pharmacists and physicians that should be improved and it highlighted gaps in knowledge by both professions. More attention should be given to patient consultation when dispensing and prescribing an antimicrobial as this may reduce their contribution to AMR.

Protective effects of olive oil phenolics oleuropein and hydroxytyrosol against hydrogen peroxide-induced DNA damage in human peripheral lymphocytes.

This study investigates antioxidant capacity and protective effects of phenolic compounds oleuropein (OLP) and hydroxytyrosol (HT), present in olive oil and olive leaves, against H2O2-induced DNA damage in human peripheral lymphocytes. Antioxidant potency was determined using the measurement of radical-scavenging activity (ABTS∙+ assay), ferric reducing power (FRAP assay) and cupric reducing antioxidant capacity (CUPRAC assay). Both substances were found to be potent antioxidant agents due to their free radical-scavenging activities. Antigenotoxic effects of oleuropein and hydroxytyrosol against H2O2-induced damage in human lymphocytes were evaluated in vitro by alkaline comet assay. At tested concentrations (1, 5, 10 µmol L-1), oleuropein and hydroxytyrosol did not induce a significant increase of primary DNA damage in comparison with the negative control. Pretreatment of human lymphocytes with each of the substances for 120 min produced a dose-dependent reduction of primary DNA damage in the tested cell type. Hydroxytyrosol showed a better protective effect against H2O2-induced DNA breaks than oleuropein which could be associated with their free radical-scavenging efficacy.

Analysis of spontaneous reporting of suspected adverse drug reactions for non-analgesic over-the-counter drugs from 2008 to 2017.

BACKGROUND: Adverse drug reaction (ADR) reporting practices by health care professionals remain poor. Over-the-counter (OTC) drugs are perceived as safe; however, they can also cause ADRs. The objective of this study was to analyze ADR reporting for OTC drugs in a 10-year period, in order to evaluate frequency of ADRs, population that ADRs most affect and reporters of ADRs of OTC drugs in Croatia. METHODS: Spontaneously reported ADRs of non-analgesic OTC drugs, collected from January 2008 to December 2017 were analyzed. Data was obtained from Agency for Medicinal Products and Medical Devices of Croatia (HALMED). RESULTS: There were 547 ADRs of OTC drugs reported in total and an increase in number of reports through the years was observed. Pharmacists reported 45.4% of all ADRs, and were most frequent reporters (p < 0.001). In 2017 majority of reports, 62 (49.2%), were obtained from consumers. ADRs were most frequently observed in patients aged 70 years and older (15% of ADRs). Five percent of all reports were accidental exposures among children. CONCLUSIONS: Pharmacists most frequently reported ADRs of OTC drugs and consumers' awareness of ADR reporting has risen. Other health care professionals (e.g., nurses and dentists) must be offered proper education in order to improve reporting practice of ADRs. Health care professionals should address concerns about OTC drug safety in elderly and children.

Screening of flavonoid aglycons' metabolism mediated by the human liver cytochromes P450.

Biological effects of flavonoids have been extensively studied in the last 80 years. As flavonoids represent a rather large group of compounds, data on metabolic biotransformations of these compounds is relatively limited to those well studied. The objective of this study was to screen the metabolism of 30 selected flavonoid aglycons mediated by the most relevant metabolic enzymes, human liver cytochromes P450. For this purpose, in vitro experiments with human liver microsomes and recombinant enzymes were conducted. To evaluate flavonoid's metabolism and structure of the products, high-performance liquid chromatography coupled with high-resolution mass spectrometry was used. Out of 30 flavonoids, 15 were susceptible to oxidative metabolism mediated by cytochromes P450. Dominant reactions were aromatic hydroxylation and O-demethylation, or a combination of these reactions. The dominant enzyme responsible for the observed metabolic reactions is CYP1A2, whereas other human liver cytochromes P450, namely, CYP2C19, CYP2D6, CYP2E1 and CYP3A4, contribute to flavonoid metabolism to a lesser degree. These results, to some extent, contribute to the understanding of the metabolism of constituents found in antioxidant dietary supplements and their possible interactions with other xenobiotics, i.e., medicinal products.

Mutual recognition in the European system: A blueprint for increasing access to medicines?

The European regulatory system for approval of medicinal products is globally recognised as a unique platform for regulatory work-sharing and mutual recognition. As such, it potentially serves as a role model for regulatory capacity building worldwide. While focusing on mutual recognition and decentralised procedures, this paper illustrates key success factors and structures allowing for the reliance-based authorisation of medicines in the European Economic Area from the perspective of a national regulatory authority (NRA). This paper presents major challenges in fulfilling the requirements for joining the European Medicines Regulatory Network (EMRN) and the strategies regarding how those challenges could be successfully addressed based on the example of the Agency for Medicinal Products and Medical Devices of Croatia, the most recent NRA in the EMRN. It also discusses the hallmarks of successful implementation of the European system of reliance as a blueprint for increasing access to safe and efficacious medicines from the perspective of a NRA.

Evaluation of accordance of antibiotics package size with recommended treatment duration of guidelines for sore throat and urinary tract infections.

Background: The aim of this study was to investigate whether marketed antibiotics package sizes are in accordance with treatment durations recommended in guidelines for prescribing antibiotics in sore throat and urinary tract infections. Methods: National drug database was searched with limitation to Antibacterials for systemic use. Formulations which did not have pre-specified dosage unit by the manufacturer were excluded (e.g. powders for oral solutions). The final list contained 94 drugs with 23 different active substances. This list was then cross-referenced with selected antimicrobial prescribing guidelines provided by Intersectoral Society for Antibiotic Resistance Control (ISKRA), National Institute for Health and Care Excellence (NICE) and The Infectious Diseases Society of America (IDSA). Results: Seven packages matched ISKRA guidelines on sore throat while 16 were mismatched. Considering drug packages under reimbursement, 3 matched ISKRA guidelines and 8 were mismatched. Only 3 packages matched IDSA guidelines for comparable indications, and 18 were mismatched. When considering NICE guidelines there were 5 mismatched and only one package that was in accordance with the guidelines. ISKRA guidelines for urinary tract infections matched 23 packages and mismatched 58 packages. IDSA guidelines for urinary tract infections matched one package and were mismatched in 15 cases. Conclusions: One of the causes of leftover antibiotics is poor accordance of antibiotic package size with treatment recommendation duration. This should be identified as a potential target for reduction of excess antibiotics in the community. Measures that promote patient adherence to therapy and patient education should be considered essential to manage proper handling of leftover antibiotics.

Attitudes and Knowledge Regarding Antimicrobial Use and Resistance Among Pharmacy and Medical Students at the University of Split, Croatia.

Purpose: Future physicians and pharmacists have to be educated and prepared to rationally manage the use of antimicrobials. The aim of this study was to evaluate attitudes and knowledge regarding the use of antimicrobials and antimicrobial resistance of medical and pharmacy students. Methods: We conducted a survey-based cross-sectional study at the University of Split School of Medicine (USSM). The survey consisted of 50 items. A total of 161 students participated in the study across 3 study programs as follows: Medicine (N = 78), Medical Studies in English (MSE; N = 37), and Pharmacy (N = 46). Results: Majority of students believe that antimicrobials are overused (90.7%). Keeping a stock of antibiotics at home is a practice more commonly seen among students who have a family member working in a health related field (58.5% vs. 25.0%, p < 0.001). There was no difference in average knowledge score among medical, MSE, or pharmacy students (p = 0.416). Students who achieved higher knowledge score were more likely to rate their education about antimicrobial use and resistance as very useful (p < 0.001). Conclusion: This study reveals that medical and pharmacy students at the USSM have a relatively good understanding of antibiotic resistance. However, more education on the appropriate use of antimicrobials is needed.

Membrane of Candida albicans as a target of berberine.

BACKGROUND: We investigated the mechanisms of anti-Candida action of isoquinoline alkaloid berberine, active constituent of medically important plants of Barberry species. METHODS: The effects on membrane, morphological transition, synthesis of ergosterol and the consequent changes in membrane permeability have been studied. Polarization and lipid peroxidation level of the membrane following berberine treatment have been addressed. RESULTS: Minimal inhibitory concentration (MIC) of berberine against C. albicans was 17.75 µg/mL. Cytotoxic effect of berberine was concentration dependent, and in sub-MIC concentrations inhibit morphological transition of C. albicans cells to its filamentous form. Results showed that berberine affects synthesis of membrane ergosterol dose-dependently and induces increased membrane permeability causing loss of intracellular material to the outer space (DNA/protein leakage). Berberine also caused membrane depolarization and lipid peroxidation of membrane constituents indicating its direct effect on the membrane. Moreover, ROS levels were also increased following berberine treatment indicating further the possibility of membrane damage. CONCLUSION: Based on the obtained results it seems that berberine achieves its anti-Candida activity by affecting the cell membrane.

Antifungal Activity of Oleuropein against Candida albicans-The In Vitro Study.

In the present study we investigated activity of oleuropein, a complex phenol present in large quantities in olive tree products, against opportunistic fungal pathogen Candida albicans. Oleuropein was found to have in vitro antifungal activity with a minimal inhibitory concentration (MIC) value of 12.5 mg·mL-1. Morphological changes in the nuclei after staining with fluorescent DNA-binding dyes revealed that apoptosis was a primary mode of cell death in the analyzed samples treated with subinhibitory concentrations of oleuropein. Our results suggest that this antifungal agent targets virulence factors essential for establishment of the fungal infection. We noticed that oleuropein modulates morphogenetic conversion and inhibits filamentation of C. albicans. The hydrophobicity assay showed that oleuropein in sub-MIC values has significantly decreased, in both aerobic and anaerobic conditions, the cellular surface hydrophobicity (CSH) of C. albicans, a factor associated with adhesion to epithelial cells. It was also demonstrated that the tested compound inhibits the activity of SAPs, cellular enzymes secreted by C. albicans, which are reported to be related to the pathogenicity of the fungi. Additionally, we detected that oleuropein causes a reduction in total sterol content in the membrane of C. albicans cells, which might be involved in the mechanism of its antifungal activity.

Olive leaf extract activity against Candida albicans and C. dubliniensis - the in vitro viability study.

Olive leaf extract is characterized by a high content of polyphenols (oleuropein, hydroxytyrosol and their derivatives), which is associated with its therapeutic properties. The objective of the present research was to evaluate the antifungal activity of olive leaf extract against Candida albicans ATCC 10231 and C. dubliniensis CBS 7987 strains. Minimum inhibitory concentrations (MIC) of the extract were determined by several in vitro assays. The extract showed a concentration depended effect on the viability of C. albicans with MIC value of 46.875 mg mL-1 and C. dubliniensis with MIC value 62.5 mg mL-1. Most sensitive methods for testing the antifungal effect of the extracts were the trypan blue exclusion method and fluorescent dye exclusion method while MIC could not be determined by the method according to the EUCAST recommendation suggesting that herbal preparations contain compounds that may interfere with this susceptibility testing. The fluorescent dye exclusion method was also used for the assessment of morphological changes in the nuclei of treated cells. According to the obtained results, olive leaf extract is less effective against the tested strains than hydroxytyrosol, an olive plant constituent tested in our previous study.

Generic Medicines in Croatia--Regulatory Aspects and Statistics.

A generic medicine is an equivalent of an originator pharmaceutical product. It contains the same active substance as, is "essentially similar" to, and is therefore interchangeable with, the originator product. The objective of this study was to determine the share of generic medicines of the total received marketing authorization applications in Croatia, and the specificities in the approval of generic medicines with regard to assessments of their quality documentation. We collected the information from the Agency's medicinal products databases. Absolute numbers are shown for the applications for the authorizations of medicines in total and generics in particular in the period from 2005-2009. Data were analyzed using descriptive statistics. The annual number of marketing authorization applications for generic medicines received in Croatia increased from 148 applications in 2005 to 276 applications in 2009. In the period from 2005-2009, the number of applications for the approval of generic medicines accounted for 55% of all submitted applications. More than five generic medicines were approved for the following active compounds: amlodipine, lisinopril, atorvastatin, tamsulosin and omeprazole. In the following years, the number of applications from international manufacturers stagnated, while the number of applications by local manufacturers is on a steady climb, with the exception of 2008. From 2005-2009, an almost continual increase in the number of applications for the approval of generic medicines is evident. The largest number of generic medicines was approved for generic medicines intended for the treatment of cardiovascular disease (amlodipine, lisinopril, atorvastatin). A continual increase of applications from local manufacturers has been recorded. In the approval of these medicines, it is very important to develop a uniform approach to assessing the quality of each medicine, in order to guarantee a high quality product for the patient.

Analysis of purity profiles of generic lisinopril tablets marketed in Croatia.

In view of an increasing number of generic drugs emerging, a comparative study was performed including the approved lisinopril preparations in the form of tablets marketed in Croatia, to compare purity profiles of generic drugs versus the original medicinal product. Several batches of each individual medicinal product at different stages of their shelf life were analyzed. Impurities were determined by means of high performance liquid chromatography (HPLC). Impurity profiles were demonstrated to be specific for each individual drug. Original drug, as compared to its generic copies, had the lowest values and also the lowest variability of all the tested parameters--type, total number and content of impurities--suggesting that its manufacturing process is to certain degree better controlled compared to other manufacturers. A characteristic impurity C appearing in all the assessed preparations has the lowest levels in the original drug, whereas the amount of the highest unknown impurity does not exceed 0.10% in any of the analyzed preparations. Although the original drug stands out from all the generic preparations with its purity, it can be generally concluded that, as regarding impurities levels, all the analyzed medicinal products are within the ranges of specification limits; accordingly, it is therefore not expected that, in case of lisinopril tablets, administration of the original drug as compared to any of its generic drugs, will be safer for the patient.

Hydroxytyrosol expresses antifungal activity in vitro.

Hydroxytyrosol (HT) is a potent antioxidant found in olive oil and leaves. Using several in vitro approaches, we tested antifungal activity of HT. HT showed broad spectrum of antifungal activity against medically important yeasts and dermatophyte strains with MIC values ranging between 97.6 µgml⁻¹ and 6.25 mgml⁻¹. The antimicrobial activity of HT was also tested using the time-kill methodology. Below the MIC value, HT showed potent damage of cell wall of Candida albicans ATCC 10231 using fluorescent dye-exclusion method. At the subinhibitory concentration, HT also influenced dimorphic transition of Candida indicating that HT is inhibitor of germ-tube formation as one of the most important virulence factor of C. albicans. Furthermore, HT showed disturbances in cell surface hydrophobicity (CSH) of C. albicans. The in vitro results indicate that HT caused a significant cell wall damage and changes in CSH as well as inhibition of germ-tube formation as virulence factor of C. albicans. The study indicates that HT has a considerable in vitro antifungal activity against medically important yeasts.