Phenotypes characterization and ABC genotypes distribution of clinical Candida albicans isolates.

BACKGROUND: Candidemia and vaginitis are the most common types of candidiasis mostly caused by Candida albicans species. C. albicans has several genotypes and the potential ability to form different phenotype colonies on specific media. This study aimed to evaluate the genotype distribution of blood and vaginal C. albicans isolates and phenotype characteristics on Spider and yeast peptone dextrose agar medium. METHODS: A total of 40 clinical Candida albicans isolates comprising vagina (20) and blood (20) were used. ABC typing using CA-INT-R and CA-INT-L primers was performed to span the transposable group I intron of the 25S rDNA gene. For colony phenotypic characteristics, the Spider and YPDA media were used. RESULTS: Among the blood and vaginal isolates, genotype A (12/60%) and genotype C (10/50%) were the most common types, respectively. The highest phenotype shape frequency of the colonies in blood and vaginal samples was the ring and the lowest was the hat/ring. The dominant color phenotype in blood and vaginal samples was gray. There was a significant relationship between genotype and phenotype forms in the blood sample on YPDA medium (p = 0.02). In the Spider medium, there were no significant differences between genotypes and phenotypes. CONCLUSION: In this study, genotype A and genotype C were predominant in blood and vaginal samples, respectively. In both groups, YPD agar medium demonstrated the most variety of phenotypes that was related to genotypes A and C. The variety of phenotypes in both groups was the same in genotypes A and C on the Spider medium.

Magnetic chitosan nanoparticles loaded with Amphotericin B: Synthesis, properties and potentiation of antifungal activity against common human pathogenic fungal strains.

Amphotericin B has long been regarded as the gold standard for treating invasive fungal infections despite its toxic potential. The main objective of this research was to develop a novel IONPs@CS-AmB formulation in a cost-effective manner in order to enhance AmB delivery performance, with lowering the drug's dose and adverse effects. The chitosan-coated iron oxide nanoparticles (IONPs@CS) were synthesized afterward, AmB-loaded IONPs@CS (IONPs@CS-AmB) prepared and characterized by AFM, FT-IR, SEM, EDX, and XRD. Biological activity of the synthesized NPs determined and the cytotoxicity of IONPs@CS-AmB evaluated using the MTT and in vitro hemolysis tests. The IONPs@CS-AmB was synthesized using the coprecipitation method with core-shell structure in size range of 27.70 to ∼70 nm. The FT-IR, XRD and EDX pattern confirmed the successful synthesis of IONPs @CS-AmB. The IONPs@CS-AmB exhibited significant antifungal activity and inhibited the metabolic activity of Candida albicans biofilms. The hemolysis and MTT assays showed that IONPs@CS-AmB is biocompatible with high cell viability when compared to plain AmB and fungizone. The IONPs@CS-AmB is more effective, less toxic and may be a suitable alternative to conventional drug delivery. IONPs@CS-AmB may be a viable candidate for use as a microbial-resistant coating on the surfaces of biomedical devices.

Molecular characterization and antifungal activity against non-dermatophyte molds causing onychomycosis.

Onychomycosis is a fungal disease that caused by different types of fungi. Non-dermatophyte molds are a large saprophytic fungi group that live in nature and could affect traumatic nails. The aim of this study was to identify non-dermatophyte molds causing onychomycosis and evaluation of several antifungal activities against the isolates. The samples consisted of 50 non-dermatophyte molds isolated from patients with onychomycosis confirmed by direct and culture examination fungal. DNA was extracted, amplified, and sequenced. Disk diffusion method was used to evaluate itraconazole, fluconazole, ketoconazole, terbinafine, posaconazole, and econazole activity against the isolates. The species identified as: Aspergillus flavus 22 (44%), A. niger 12 (24%), A. fumigates, 3 (6%), A. sydowii 3 (6%), A. terreus 1 (2%), Penicillium commune 2 (4%), P. glabrum 2 (4%), P. chrysogenum, 1 (2%), Fusarium solani 3 (6%) and F. thapsinum 1 (2%). Most of the samples were sensitive to terbinafine, itraconazole, and econazole and 94% of the isolates were resistant to fluconazole. This study showed that Aspergillus species were the most common cause of non-dermatophyte mold onychomycosis and fluconazole was the most resistant antifungals. Care must be taken to choose the appropriate antifungal drug for a better cure.

Emerging of Fatal Colitis with Multidrug-Resistant Candida glabrata after Small Bowel Transplantation.

BACKGROUND: Small bowel transplantation is a potential option for patients with intestinal-failure, and the incidences of infections caused by Candida species that are more resistant to antifungal drugs are increasing in these patients. In this manuscript, we reported a case of fatal colitis after small bowel transplantation induces by multidrug-resistant (MDR) Candida glabrata. Case Presentation. A 52-year-old man has undergone an extensive small bowel resection with the length of the remaining bowel which was less than 40 cm who became a candidate for transplantation. Four months after transplantation, the patient experienced severe bloody diarrhea with abdominal distension. Ileoscopy and colonoscopy did not show neither pathological change and rejection nor cytomegalovirus (CMV) infection posttransplantation. Abdomen computed tomography showed diffuse moderate small bowel wall thickening. After detection of budding yeast in the stool samples, stool culture was positive for Candida, DNA was extracted, and ITS1-5.8s-ITS2 region of the fungal agent was amplified. Sequencing analysis of PCR and antifungal susceptibility testing revealed that this isolate was multidrug-resistant C. glabrata. Besides, there was no evidence for other pathogens known to cause infection in various laboratory tests. Immediate antifungal treatments with caspofungin remained unsuccessful, and on the eighteenth day of admission, the patient expires with septic shock. CONCLUSION: These findings highlight the challenging management of candidiasis in patients with small bowel transplantation. Infectious diseases due to MDR organisms have emerged as a vital clinical problem in this patient population.

Evaluation of fungal contamination and ochratoxin A detection in different types of coffee by HPLC-based method.

BACKGROUND: Mycotoxins are secondary fungal metabolites that are produced by some toxigenic fungi on foodstuffs which are poisoning and potentiate for human's health hazards. In coffee samples, ochratoxin A and fungal contamination were examined. METHODS: Immunoaffinity columns were used for treating of all 50 samples from four types of coffee, after that high-performance liquid chromatography was used for determining the amount of ochratoxin. For the identification of fungi, all coffee samples were cultured in appropriated media. RESULTS: The results showed that all samples were contaminated by ochratoxin A but only up to 50% of them had toxins higher than acceptable level as detected in black beans (47%), green beans (33.3%), torch (33.3%), and espresso (25%). Black coffee had a higher mean concentration of ochratoxin A than green coffee. CONCLUSION: Predominant fungi isolated from coffee samples were Aspergillus species. Finally, careful monitoring of mycotoxins in coffee samples is essential to improve the quality of this favorable beverage in future.

Potential Pathogenicity of Candida Species Isolated from Oral Cavity of Patients with Diabetes Mellitus.

INTRODUCTION: In the recent decade, the increased immunocompromised population such as diabetic patients makes a high incidence of invasive Candida infections. Diabetes mellitus is the most common endocrine metabolic disorder, and diabetic patients are more susceptible to oral candidiasis infection. Candidiasis is an opportunistic fungal infection caused by many species of Candida. Secretion of exoenzymes plays an important role in the virulence and pathogenesis of Candida species. The aim of this study was to evaluate the potential role of phospholipase, esterase, and hemolytic activity of Candida species isolated from oral cavity lesions of diabetic patients. METHODS: A total of 108 Candida species including 75 Candida albicans and 33 non-Candida albicans species were recovered from the oral cavity of diabetic patients included in our study. Egg yolk agar, Tween 80 opacity medium, and blood agar plate assays were used for determining phospholipase, esterase, and hemolytic activities, respectively. RESULTS: Candida albicans species had the most exoenzyme activity in comparison to non-albicans isolates. Candida albicans isolates showed 97.3%, 100%, and 77.3% phospholipase, hemolysin, and esterase activities, respectively. The difference between Candida albicans and non-Candida albicans was significant in phospholipase (P < 0.001) and hemolytic activity (P = 0.027), but not significant in esterase activity (P = 0.076). CONCLUSION: This study showed that most of the isolates had different enzymatic patterns, and Candida albicans isolates had the most exoenzyme activity. So due to the potential effects of these enzymes in pathogenesis and virulence effects of Candida species, we can conclude that the severity of extracellular enzymes may play a role in the severity of signs and symptoms of Candida oral cavity infections in diabetic patients.

Prevalence of superficial-cutaneous fungal infections in Shiraz, Iran: A five-year retrospective study (2015-2019).

BACKGROUND: Superficial and cutaneous fungal infections are common in tropical areas. The aim of this study was to provide a basic database of superficial and cutaneous mycoses and the most common etiological agents among patients. METHODS: Between 2015 and 2019, a total of 1807 patients suspected of superficial and cutaneous mycosis referring to the mycology laboratory of Shiraz medical school, Fars, Iran were evaluated. Specimens were taken from the patients' affected area, and clinical samples were examined by direct microscopy and culture. The epidemiological profile of the patients was collected. RESULTS: A total of 750 patients were confirmed with mycoses. Positive samples totaled 750 cases consisting of the nail (373/49.7%), skin (323/43%), head (47/6.26%), and mucosal membrane (4/0.5%). The yeasts group included 304 Candida spp. (70.3%), 123 Malassezia spp. (28.47%), and 5 Rhodotorula spp. (1.1%). The filamentous fungi were distributed as 34.8% dermatophytes and 7.5% non-dermatophyte. The clinical types of dermatophytosis were tinea unguium (110/261), tinea capitis (50/261), tinea pedis (48/261), tinea corporis (37/261), and tinea cruris (16/261). Non-dermatophyte molds included A. flavus 17, A. niger 4, Aspergillus spp. 15, Penicillium. 10, Fusarium 6, Mucor 2, Stemphylium 1, and Alternaria 1. CONCLUSION: This study provides useful data for the study trends of superficial and cutaneous fungal infections in a specific area. The mycological data confirmed higher incidence of candidiasis (mainly onychomycosis) and dermatophytosis in patients affected by fungal pathogens, which helped to better understand the epidemiological aspects of these mycoses.

Survey of aflatoxins and ochratoxin A contamination in spices by HPLC-based method in Shiraz, Southern of Iran.

Among food and agricultural products, spices play important roles in the diets of millions of people worldwide. These products may be colonized by fungi genus and subsequently mycotoxin production. Due to the large demand and supply of spice for cooking, preservative effects, or medicine purpose, it is essential that further investigation is designed to examine mycotoxins in spice. In the present study, the possible contamination of spices by aflatoxins (AFTs) and ochratoxin A (OTA) were analyzed. A total of 80 spice samples (curry, sumac, ginger, and saffron) were purchased and cultured on appropriate medium. Simultaneously mycotoxins from spices were extracted with immunoaffinity columns (IAC), and the occurrence of AFTs (B1 + B2 + G1 + G2) and OTA was then determined using high-performance liquid chromatography (HPLC) with a fluorescence detector (FD). The results depicted that 62 (77.5%) and 58 (72.5%) spice samples were contaminated with AFTs and OTA, respectively. Out of the 80 analyzed spices samples, the mean concentration of AFTs and OTA was higher in the curry samples. Among spices that contaminated with mycotoxins, 5 (6.25%) and 2 (10%) of the samples were above the acceptable limit of AFTs (≥ 10 µg/kg) and OTA (≥ 15 µg/kg), respectively. Aspergillus species were the predominant species isolated, followed by Penicillium, and finally Mucor species.Among the examined samples, only few curry samples were contaminated with mycotoxins above acceptable limit. Despite this low level of contamination, this spice is used daily in the cuisine of this region of the world, and consequently, even the small amount of these heat stable toxins for a long time may cause many adverse effects. Hence, it is recommended to monitor the toxicogenous fungi contamination and level of mycotoxins in the spices.

Molecular identification and antifungal susceptibility among clinical isolates of dermatophytes in Shiraz, Iran (2017-2019).

Dermatophytosis is a common superficial mycotic infection affecting individual's quality of life worldwide. The present study aimed to perform species-level identification and evaluate the antifungal susceptibility patterns of dermatophytes isolated in Shiraz, Iran. This cross-sectional study was conducted on clinical samples collected during 2017-2019 from 307 patients suspected of having dermatophytosis. The isolates were identified by direct microscopy, culture and internal transcribed spacer ribosomal DNA sequencing, and their antifungal susceptibility patterns were determined by the microdilution method. Among 307 patients, dermatophytosis was diagnosed by microscopy in 190 (61.8%) subjects and confirmed in 130 (42.3%) cases by both microscopy and culture. It was found out tinea pedis was the most common clinical manifestation, and Trichophyton mentagrophytes was the most prevalent species (28.4%), followed by T tonsurans (23.8%), Microsporum canis (11.5%), T interdigitale (10%), T verrucosum (6.9%), T rubrum (6.9%), T benhamiae (4.6%), T violaceum (3%), T simii (3%), Epidermophyton floccosum (0.7%) and M ferrugineum (0.7%). Moreover, it was revealed that luliconazole with a geometric mean (GM) minimum inhibitory concentration (MIC) of 0.03 µg ml-1 was the most effective agent against all tested isolates. Regardless of species, 30% of isolates responded to high MICs of griseofulvin (MIC90  > 2 µg ml-1 ). The increasing prevalence of nonindigenous species of T simii, T benhamiae and M ferrugineum in Shiraz, Iran, was a notable finding. In addition, infections due to zoophilic species showed an increasing trend. These epidemiological data, along with antifungal susceptibility patterns, may have implications for clinical decision-making and successful treatment.

High detection of virulence factors by Candida species isolated from bloodstream of patients with candidemia.

OBJECTIVE: Candida species are the normal inhabitants of the skin and mucosa that cause a wide range of debilitating diseases in immunocompromised patients and other susceptible individuals. The present study aimed to evaluate the production of exoenzymes and the biofilm formation capacity of Candida species isolated from candidemia. MATERIALS AND METHODS: In this study, a total of 100 stock Candida species isolates consist of 50 Candida albicans and 50 non-Candida albicans Candida species (24 C. glabrata, 15 C. parapsilosis, 5 C. dubliniensis, 3 C. tropicalis, 2 C. krusei and 1 C. fabianii) which previously were recovered from patients with candidemia were used. The enzymatic activity tests for hemolysin, proteinase, and phospholipase were performed by using blood Sabouraud dextrose agar, bovine serum albumin medium and egg yolk agar, respectively. Biofilm formation was determined by microplate assay method. RESULT: All of the Candida albicans species could produce hemolysin. The predominant enzyme activity of species included strong and very strong levels of phospholipase, proteinase and hemolysin activity were belonged to Candida albicans isolates. There were statistically significant differences in hemolysin (P < 0.001), proteinase (P = 0.003) and phospholipase (P < 0.001) activity between two groups of albicans and non-albicans species. The biofilm formation was seen in 30 (60%) of C. albicans and 49 (98%) of non-C. albicans species. There was significant statistical differences between the two groups of isolates in biofilm formation (P < 0.001). CONCLUSION: It is clear that Candida species have ability to produce several enzymes as virulence factors to contribute its pathogenicity. There were significant differences in virulence factors between the two C. albicans and non- C. albicans group. The ability for biofilm formation and producing exo-enzyme were an important virulence factors in Candida species isolates. This differences found in this report might have role in severity of disease caused by different species.

Comparative Analysis of Virulence Factors of Homozygous and Heterozygous Strains of Candida albicans Vaginal Isolates.

Although the epidemiology of pathogenic Candida species is changing due to invasive diseases, Candida albicans has become the common cause of human infections worldwide. Candida albicans is a diploid yeast with a mostly clonal mode of reproduction and without known complete sexual cycle. This species has two heterozygous and homozygous strains at hyphal wall protein 1 gene locus (hwp1). Little is known about virulence factors of these strains. The aim of this study was to evaluate the exoenzyme activity of heterozygous and homozygous C. albicans strains. A total of 60 stock Candida albicans species isolates, which consisted of 30 homozygous and 30 heterozygous strains, were used for exoenzyme activities. We used egg yolk agar, Sabouraud blood agar, and bovine serum albumin agar for evaluation of phospholipase, hemolysin, and proteinase activity, respectively. Homozygous strains of Candida albicans had more phospholipase and proteinase activity than heterozygous strains. However, there were no significant statistical differences between the two strains in the severity of exoenzymes production. Beta hemolysin activity was seen in 100% and 96.7% of the homozygous and heterozygous strains, respectively. The results of this study indicated that both of the strains exhibited exoenzyme activities in different ranges. There were no significant statistical differences in virulence factors between the homozygous and heterozygous strains.

Identification and Antifungal Activity Profile of Candida Species Isolated from Patients with Pemphigus Vulgaris with Oral Lesions.

Pemphigus vulgaris is an autoimmune disease that mostly affects the mucosa and oral cavity. Candida species can invade the mucosal lesions of these patients and cause diseases. The aim of this study was to identify the fungal agents isolated from mucosal lesions and evaluate antifungal activity profile against the isolates. A total of 25 patients with pemphigus vulgaris with active oral lesions and 25 healthy people serving as a control group were included in this study. Identification of the fungal isolates was performed based on conventional methods and DNA sequence analysis of the internal transcribed spacer (ITS) rDNA gene region. The sequence results were deposited in the NCBI database using the Basic Local Alignment Search Tool. Antifungal activity of fluconazole, itraconazole, ketoconazole, posaconazole, econazole, and amphotericin B against the isolates were evaluated based on the CLSI M-44 A protocol. Oral candidiasis was detected in 20% of the patients. Candida species isolated from oral lesions of patients with pemphigus were identified as Candida albicans 22/25, Candida glabrata 2/25, and Candida dubliniensis 1/25. All of the isolates were sensitive to amphotericin and econazole, 96% to fluconazole and posaconazole, and 92% to ketoconazole and itraconazole. One patient showed a profile resistant to fluconazole, posaconazole, and ketoconazole, simultaneously. Ninety six percent of control group isolates were sensitive to six antifungals. Candida albicans was the most prevalent species isolated from oral lesions of patients with pemphigus vulgaris and the control group. Amphotericin B and econazole were the most effective antifungals against the isolates.

Evaluation of biofilm formation in the homozygous and heterozygous strains of vaginal Candida albicans isolates.

BACKGROUND AND PURPOSE: Candida albicans is one of the most opportunistic yeasts around the world. This species has two heterozygous and homozygous strains at hyphal wall protein 1 (hwp1) gene locus. A simple method for the discrimination of these two strains is the amplification of HWP1 gene. Regarding this, the aim of this study was to discriminate C. albicans heterozygous and homozygous strains via the amplification of hwp1 gene and evaluation of biofilm formation between the strains. MATERIALS AND METHODS: A total of 60 homozygous (n=30) and heterozygous (n=30) strains were discriminated among 126 C. albicans vaginal isolates by the amplification of HWP1 gene, using specific primers. The evaluation of biofilm formation was accomplished using the visual method. RESULTS: According to the results, the homozygous and heterozygous strains produced one and two DNA fragments, respectively. The frequency of homozygous strains among the C. albicans vaginal isolates was 76.2%. Biofilm formation activity in the heterozygous strains was more than that in the homozygous strains. However, statistical analysis showed no significant difference between the strains in terms of biofilm formation. CONCLUSION: As the findings indicated, the frequency of the heterozygous strains in C. albicans was lower than that of the homozygous strains. Both of the strains could form biofilm in the different ranges of severity. High activity of biofilm formation in heterozygous strains may set the ground for its pathogenicity.

Genetic Variant of Glucocorticoid Receptor Gene at rs41423247 and Its Association with Major Depressive Disorder: A Case-Control Study.

BACKGROUND: Extensive distribution of glucocorticoid receptors (GCRs) in different brain areas along with disruption of hypothalamic-pituitary-adrenal (HPA) axis in major depressive disorder (MDD) and the cross talk between GCRs and HPA proposes genetic variants of GC receptor genes as potential contributors in MDD. Among the GCR polymorphisms, rs41423247, rs6195 and rs6189/rs6190 are suggested to be involved in MDD. MATERIALS AND METHODS: We investigated the association between rs41423247, rs6195 and rs6189/rs6190 and MDD in a case-control study. One hundred MDD patients along with 100 healthy individuals were enrolled in this study. genetic variants of rs41423247, rs6195 and rs6189/rs6190 were determined in extracted DNAs using PCR-RFLP. RESULT: The prevalence of heterozygote and mutant carriers of rs41423247 were significantly and by 1.9 fold greater in cases versus controls (P=0.033; OR; 95%CI=1.9; 1.1-3.3). Moreover, carriers of the mutant (G) allele were by 1.8 fold more prevalent in MDD group (P=0.013; OR;95%CI=1.8; 1.1-2.8). CONCLUSION: Specific carriers of rs41423247 might be more susceptible to developing MDD. This supports the hypothesis of the involvement of GCRs in pathophysiology of MDD.

Glucocorticoid Receptor Genetic Variants and Response to Fluoxetine in Major Depressive Disorder.

Hyperactivity of the hypothalamic pituitary adrenocortical (HPA) axis is one of the main clinical findings in depression. The HPA axis is interrelated with glucocorticoid signaling via glucocorticoid receptors (GCRs). Thus, functional genetic variants on GCRs might influence therapeutic outcomes in depression. The aim of the present study was to investigate the association between three functional polymorphisms (rs41423247, rs6195, and rs6189/rs6190) on GCR and response to fluoxetine in a group of depressed patients. One hundred newly diagnosed patients completed 6 weeks of fluoxetine treatment. Response to treatment was defined as a 50% decrease in the Hamilton Depression Rating Scale score. Variants of rs41423247, rs6195, and rs6189/rs6190 polymorphisms were determined in extracted DNAs using PCR-RFLP method. Regarding rs41423247 polymorphism, carriers of the CG and GG genotype responded significantly better to fluoxetine compared with CC carriers (p=0.008, OR=3.3, 95% CI=1.35-8.07). Moreover, the G allele of rs41423247 polymorphism was strongly associated with response to fluoxetine (p=0.032, OR=2.2, 95% CI=1.09-4.44). There was no significant association between different genotypes and alleles of rs6195, rs6189/rs6190 variants, and response to fluoxetine (p=0.213 and 0.99, respectively). In conclusion, rs41423247 polymorphism might be a predictor for better response to fluoxetine. These findings support the idea that some variants of the GCR might contribute to interindividual variability of response to antidepressants.

Patulin contamination in apple products marketed in Shiraz, Southern Iran.

BACKGROUND AND PURPOSE: Patulin is one of the important mycotoxins, produced by a wide range of molds, including Penicillium, Aspergillus, and Bysochlamys. Patulin is mainly found in the rotten parts of fruits and vegetables, such as apples, pears, peach, apricots, and grapes. Currently, the Codex Alimentarius and Food and Drug Administration have recommended a maximum level of 50 µg/L patulin for apple products. The purpose of this study was to investigate patulin contamination of apple juice and cans in 75 samples collected from 15 manufacturers in Shiraz, southern Iran. MATERIALS AND METHODS: The detection of patulin was accomplished using a high-performance liquid chromatography with an ultraviolet detector. RESULTS: A total of 38 apple juice samples (53%) and 17 apple cans (45%) were contaminated with patulin. Overall 50% and 3% of the apple juice and apple cans samples had a patulin level of > 3 µg/L. CONCLUSION: Although the maximum level of patulin in our samples was considerably lower than the permitted level established by the European Union (i.e., 50 µg/L), the high incidence of this mycotoxin in our samples should be lessen by improving their good manufacturing practice.

Evaluation of CAMP-Like Effect, Biofilm Formation, and Discrimination of Candida africana from Vaginal Candida albicans Species.

Candida africana as a species recovered from female genital specimens is highly close to C. albicans. The present study was conducted to discriminate C. africana from presumptive vaginal C. albicans strains by molecular assay and evaluate their hemolysin activity, biofilm formation, and cohemolytic effect (CAMP) with vaginal bacterial flora. A total of 110 stock vaginal C. albicans isolates were examined by HWP1 gene amplification. Hemolysin activity and the ability of biofilm formation were evaluated by blood plate assay and visual detection methods, respectively. Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus agalactiae were used to evaluate the CAMP-like effects in Sabouraud blood agar media. Based on the size of the amplicons (941 bp), all isolates were identified as C. albicans. All samples were able to produce beta-hemolysin. Moreover, 69 out of 110 of the isolates (62.7%) were biofilm-positive, 54 out of 110 Candida isolates (49%) demonstrated cohemolytic effects with S. agalactiae, and 48 out of 110 showed this effect with S. aureus (43.6%). All isolates were CAMP-negative with S. epidermidis. We detected all isolates as Candida albicans and almost half of the isolates were CAMP-positive with S. aureus and S. agalactiae, suggesting that these bacteria increase the pathogenicity of Candida in vaginal candidiasis.

Knowledge, attitude and practice of General Practitioners towards adverse drug reaction reporting in South of Iran, Shiraz (Pharmacoepidemiology report).

BACKGROUND: An adverse drug reaction (ADRs) is linked with the use of medications and unpredictable negative consequences. The Iranian Pharmacovigilance center (IPC) has reported that the rate of ADR is very low. OBJECTIVE: Thus, this study was performed to find the reasons for this under-reporting, and investigate the level of knowledge, attitude and practice (KAP) of General Practitioners (GPs) about spontaneous reporting system in Shiraz. METHODS: The present cross-sectional study was conducted on 350 general practitioners (GPs) working in Shiraz, Iran from Oct 2014 to March 2015. A semi-structured questionnaire was used which included demographic features, and evaluated KAPs of GPs regarding ADRs, Pharmacovigilance, and yellow card reporting. Statistical analysis was done by descriptive and analytical statistics (frequency, Mean±SD, Student t-test, Chi-square) using SPSS version 16. RESULTS: Of 350 (95.1%) GPs, 333 completed the questionnaire. The respondents aged from 26 to76 years, of whom 176 (52.9%) were males with mean age 39.6±8.8 SD years. In regard to work place, 85 (25.5%) had their own office, and 112 (33.7%), 101 (30.9%), and 35 (10.5%) worked in private hospitals, in governmental hospitals, and in more than one place, respectively. Work experience mean was 13.3±8.2SD years and median was 12 years (range 1-50 years). Although, less than half of the participants (n = 151; 45.3%) described ADR correctly, 215 (64.6%) respondents claimed that they were not familiar with physician's responsibility regarding ADR reporting. Overall, few of the participants were aware of the steps in either ADR reporting or using Yellow Card System. On the whole, 100 (30%) respondents achieved acceptable knowledge score, while the median score was 9 out of 14 and minimum and maximum being 5 and 14, respectively. CONCLUSIONS: The physicians in Shiraz have poor knowledge of the pharmacovigilance system; however self-education leads to a better knowledge and positive attitude regarding ADRs reporting system. National Pharmacovigilance center should play a more active role in improving physicians' adherence to the ADRs reporting systems and the comprehensive educational pack can be used in local and national meetings. The main factor for low ADR reporting rates is lack of information about ADRs and how to report an ADR. Otherwise, obligatory education and training courses should be designed for general practitioners on reporting ADRs during and after graduation.