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Background and Objectives: Fungal burn wound infections (FBWIs) are one of the most disastrous complications in burn patients. The present study investigated the incidence and the species distribution of fungal agents isolated from burn lesions and reviewed the feautures, underlying conditions, and outcomes of patients. Materials and Methods: The wounds were swabbed and cultured on Sabouraud Dextrose Agar with chloramphenicol medium. Fungal identification was performed using internal transcribed spacer (ITS) and beta-tubulin sequencing. Results: A total of 380 swab specimens were obtained. Of these, 101 patients (26.75 %) were positive in culture. Among the 101 positive cases, most isolates were from males (n= 68, 67.33%) and most of them were over 30 years old. Flame (n=38, 37.63%) was the predominant cause of burns, and previous history of ICU admission (n=35, 34.66%), presence of central venous catheter (n=25, 24.75%), and diabetes mellitus (n=17, 16.83%) were the main underlying conditions. Candida parapsilosis complex (n=36, 35.64%), and Pichia kudriavzevii (C. krusei) (n=8, 7.92%) represent the most commonly isolated species Also, 2 out of 101 patients (2%) died. Conclusion: In the present study, non-albicans Candida species were much higher frequent than C. albicans with most cases associated with Candida parapsilosis complex.

Abstract Yeast species are a group of coexistent microorganisms in the oral cavity that can cause opportunistic infections in vulnerable individuals, including addicts. This study aimed to identify the yeast species profile responsible for oral yeast colonization (OYC) and the associated risk factors in patients with substance use disorder (SUD) in Ahvaz, Iran. Oral samples were collected from drug users hospitalized in 12 addiction treatment centers, and the related clinical information was mined. Oral yeast species were identified using 21-plex PCR and sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). A total of 244 yeast strains were identified from 245 individuals with substance abuse. Candida albicans was the most common species (37.7%) and non-albicans Candida was responsible for 57.7% of OYC, primarily C. dubliniensis (33.2%) and C. glabrata (11.9%). Moreover, uncommon oral yeasts constituted 5.3% of species, including Saccharomyces cerevisiae, Clavispora lusitaniae, Pichia kluyveri, Geotrichum candidum, Magnusiomyces capitatus, Hanseniospora opuntiae, Wickerhamomyces subpelliculosus, Trichosporon asahii, and Aureobasidium pullulans. Importantly, OYC exhibited associations with such factors as duration of drug use, daily drug consumption rate, opioid utilization, oral drug administration, and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) score. The present study is the pioneering investigation revealing the prevalence and diversity of oral yeast species, along with associated risk factors, in individuals with SUD in southwestern Iran. Furthermore, it underscores the importance of developing efficient and cost-effective diagnostic methods tailored for resource-constrained settings.

Coexisting pulmonary aspergillosis and tuberculosis in a post-COVID-19 patient is rare. Here, we are going to report a case of combined pulmonary aspergillosis and tuberculosis in a 51-year-old female who was previously diagnosed with COVID-19 pneumonia. The patient was treated with voriconazole and anti-tuberculosis agents.

Cryptococcal meningitis (CM) is an uncommon and severe infection that tends to affect both immunocompromised and immunocompetent hosts. To gain insights into the clinical and epidemiological characteristics of CM in Iran, this study evaluated patients with subacute or chronic meningitis referred to 15 Iranian hospitals. Relevant clinical and epidemiological characteristics of the patients were analyzed. Diagnosis of CM cases was performed by microscopic examination, culture, latex agglutination assay, lateral flow assay, and multiplex PCR on cerebrospinal fluid (CSF) samples. The isolates were processed and subjected to molecular identification and in vitro susceptibility antifungal profile. Among the 272 evaluated patients, 7 (2.6 %) CM cases were diagnosed. Out of seven CM cases, 6 (86 %) were male with a median age of 36 years. The most common neurological signs were headache (100 %), followed by nausea and vomiting (71.4 %). All CSF samples from CM patients exhibited positive results across all mycological tests conducted. The isolates were identified as Cryptococcus neoformans (86 %) and Cryptococcus gattii (14 %). All isolates were susceptible to voriconazole and fluconazole, while resistance was observed with itraconazole (MIC value of 0.5 μg/mL) and amphotericin B (MIC values of 4 and 1 μg/mL). The highest mortality (6/7, 86 %) was observed among patients. While a comprehensive study on this subject is currently lacking in Iran, the data acquired through this research play a crucial role in enhancing the clinical and epidemiological understanding of this infection, particularly within low-income countries. Moreover, these findings will serve as a cornerstone for future international comparative studies in this field.

Background and Purpose: Wickerhamomyces myanmarensis is a new opportunistic yeast previously named Pichai myanmarensis, which belongs to the order Saccharomycetales. Since its discovery, one environmental isolate of W. myanmarensis has been reported from Myanmar, and one clinical sample from Iran.Case Report:We report a case of bloodstream infection related to an implantable venous access port. W. myanmarensis was isolated from patient's blood after chemotherapy, which was meant to control and heal T-cell lymphoblastic lymphoma. Broth dilution minimum inhibitory concentrations were performed according to the CLSI M27-A3 document. The patient recovered with intravenous voriconazole and was discharged with the recommended prescription of oral voriconazole as a maintenance drug.Conclusion: So far, only one case of W. myanmarensis fungemia has been reported in the world in 2019. This is the second case of bloodstream infection with this yeast from a patient undergoing chemotherapy in Iran.

Candida auris has emerged globally as a multidrug-resistant pathogen causing outbreaks in health care facilities. Whole genome sequencing (WGS) analysis has identified four major clades, while earlier WGS data from a single Iranian isolate suggested the existence of a potential fifth clade. Here, we confirm the existence of this fifth clade by providing WGS data of another four Iranian isolates. These clade V isolates differed less than 100 single-nucleotide polymorphisms (SNPs) between each other, while they were separated from the other clades by more than 200,000 SNPs. Two of these isolates were resistant to fluconazole and were found to harbour mutations in the TAC1b and ERG11 genes.

The admitted patients of intensive care units with coronavirus disease 2019 (COVID-19) meet the challenges of subsequent infections. Opportunistic fungal infections such as Pneumocystis pneumonia (PCP) are among the important factors in the context of COVID-19 patients affecting illness severity and mortality. We reviewed the literature on COVID-19 patients with PCP to identify features of this infection. Although studies confirmed at least the presence of one immunosuppressive condition in half of PCP patients, this disease can also occur in immunocompetent patients who developed the immunosuppressive condition during Covid-19 treatment. The major risk factors associated with COVID-19 patients with PCP can be considered low lymphocyte counts and corticosteroid therapy. Diagnostic and treatment options are complicated by the overlapping clinical and radiologic characteristics of PCP and COVID-19 pneumonia. Therefore, physicians should comprehensively evaluate high-risk patients for PCP prophylaxis.

IntroductionThis study was intended to investigate the clinical features and predisposing factors of fungal keratitis (FK), as well as molecular identification and antifungal susceptibility of causative agents in Tehran, Iran.MethodsThis cross-sectional study was carried out from April 2019 to May 2021. All fungi isolates were identified using conventional methods and were confirmed by DNA-PCR-based molecular assays. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) was used to identify yeast species. Minimum inhibitory concentrations (MIC) of eight antifungal agents were assessed according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) microbroth dilution reference method. ResultsFungal etiology was confirmed in 86 (7.23%) of 1189 corneal ulcers. A significant predisposing factor for FK was ocular trauma caused by plant materials. Therapeutic penetrating keratoplasty (PKP) was required in 60.4% of cases. The predominant fungal species isolated was Fusarium spp. (39.5%) followed by Aspergillus spp. (32.5%) and Candida spp. (16.2%).DiscussionThe MIC results indicate that amphotericin B may be appropriate for treating FK caused by Fusarium species. FK caused by Candida spp. can be treated with flucytosine, voriconazole, posaconazole, miconazole, and caspofungin. In developing countries such as Iran, corneal infection due to filamentous fungi is a common cause of corneal damage. In this region, fungal keratitis is observed primarily within the context of agricultural activity and subsequent ocular trauma. Fungal keratitis can be managed better with understanding the ”local“ etiologies and antifungal susceptibility patterns.

Abstract Background Pseudallescheria keratitis is rare but important type of fungal keratitis because of the inherently resistance of the organism to many existing antifungal agents. Methods Slit-lamp and confocal microscopy were used for clinical examinations. Fungal isolates were identified based on morphological characteristics and DNA sequence of the internal transcribed spacer region (ITS). In vitro antifungal susceptibility testing for fungal isolates was performed according to the Clinical and Laboratory Standards Institute (CLSI, M38-A2). Result All patients had a history of ocular trauma. In clinical examination hypopion were seen in three patients. The main antifungal medications were topical voriconazole. After treatment the visual acuity of all patients improved in 2–3 weeks. Conclusion All four patients of Pseudallescheria keratitis had similar clinical features. Accurate and rapid identification of species should be helpful in treating p. boydii keratitis.

Background and Purpose: Coronavirus disease 2019 (COVID-19) has become a significant clinical challenge in healthcare settings all over the world. Critically ill COVID-19 patients with acute respiratory distress syndrome may be at increased risk of co-infection with pulmonary aspergillosis. This study aimed to describe a clinical case of proven pulmonary aspergillosis caused by Aspergillus tubingensis in a 59-year-old man with a history of hospitalization due to COVID-19 infection.Case report: The Covid-19 infection was confirmed by positive nasopharyngeal polymerase chain reaction. He had a cavitary lesion measured 20 mm in diameter with intracavitary soft tissue density in the left lung in the first chest computerized tomography scan. After 25 days, he showed two cavitary lesions in both lungs which raised suspicion of fungal infection; hence, the patient underwent a trans-thoracic biopsy of the cavitary lesion. The direct examination and culture of the biopsy material revealed Aspergillus species. To confirm the Aspergillus species identification, the beta-tubulin region was sequenced. The patient was treated with oral voriconazole.Conclusion: This report underlined the importance of early diagnosis and management of invasive fungal infections in severe COVID-19 patients

Abstract Nocardia species are an uncommon but important cause of keratitis. The purpose of this review is to discus previous published papers relation to the epidemiology, etiology, diagnosis and management of Nocardia keratitis. Nocardia asteroides is the most frequently reported from Nocardia keratitis. Pain, photophobia, blepharospasm and lid swelling are mainly clinical manifestations. Usual risk factors for Nocardia keratitis are trauma, surgery, corticosteroids, and contact lens wear. Several antibiotics were used for treatment of Nocardia infection but according to studies, topical amikacin is the drug of choice for Nocardia keratitis. Topical steroid should not prescribe in these patients. In conclusion, although Nocardia keratitis is rare, early diagnosis and treatment are essential to prevent any scar formation and preserve a good visual acuity.

Introduction: Candida parapsilosis (C. parapsilosis) is a common non-albicans Candida species ranked as the second common cause of bloodstream infections. Azole resistance and elevated echinocandin MICs have been reported for these fungi. This study was conducted to determine the interactions between azoles and echinocandins against C. parapsilosis species complex. Materials and methods: Fifteen fluconazole-resistant clinical isolates of C. parapsilosis complex were included: C. parapsilosis sensu stricto (n = 7), C. orthopsilosis (n = 5) and C. metapsilosis (n = 3). The activity of azoles (fluconazole, itraconazole) and echinocandins (anidulafungin, micafungin) alone and in combination was determined using checkerboard broth microdilution. The results were determined based on the fractional inhibitory concentration index (FICI). Results: In vitro combination of fluconazole with anidulafungin was found to be synergistic (FICI 0.07–0.37) and decreased the MIC range from 4–64 μg/mL to 0.5–16 μg/mL for fluconazole and from 2–8 μg/mL to 0.125–1 μg/mL for anidulafungin. Similarly, interactions of fluconazole with micafungin (FICI 0.25–0.5), itraconazole with anidulafungin (FICI 0.15–0.37) and itraconazole with micafungin (FICI 0.09–0.37) were synergistic. Conclusion: The combination of fluconazole and itraconazole with either anidulafungin or micafungin demonstrated synergistic interactions against C. parapsilosis species complex, especially against isolates with elevated MIC values. However, the use of these combinations in clinical practice and the clinical relevance of in vitro combination results remain unclear.

BackgroundInvasive fungal infections (IFIs) are complications that lead to mortality and morbidity in hematologic malignancies. The time of starting antifungal therapy is vital. Preemptive antifungal therapy has appeared recently as a new policy for the management of IFIs based on noninvasive ways in neutropenic patients.MethodsWe enrolled leukemia patients with neutropenia after chemotherapy in Imam Khomeini Hospital Complex, Tehran, Iran. Patients who entered the neutropenic phase were divided into two categories (empirical and preemptive) for receiving antifungal agents. The patients were clinically examined in the preemptive group every day to find IFIs. As soon as clinical evidence of IFIs was observed, antifungal was prescribed. The empirical group patients received antifungals based on the ward protocol. Based on the data in each group, the diagnostic and therapeutic results of cases are followed-up to 3 months. To compare percentages between the two groups, the chi-squared test was used. And to compare two means between the two groups, the independent t-test was used. All the statistical analyses were done in the Statistical Package for the Social Sciences (SPSS) version 24 software (IBM Corporation, Armonk, New York, USA).ResultsWe assessed 132 leukemic patients with inclusion and exclusion criteria. Eventually, 80 patients were enrolled. The mean age was 35.52 years. Demographics data and distribution of leukemia type show no significant differences between the two groups. Despite a higher percentage of IFIs discovered in the preemptive group than the empirical group (25 vs. 18.75%, respectively), but data show no significant differences. The average days of IFIs diagnosis since the beginning of neutropenia in the empirical group were 9.5 days while in the preemptive group, the average days were 5.4 days (p < 0.05). Totally, there were 15 patients with a proven IFI in each group (40% in the empirical group and 60% in the preemptive group). Results significantly show an increase in surgical sinus debridement in the empirical groups (83.3%) vs. the preemptive groups (55.5%), (p < 0.05). The mortality rate differed significantly among the two groups; it was 7.5% in the preemptive group and 25% in the empirical group (p < 0.05).ConclusionDaily oral and nasal cavities examination to find the symptoms of IFIs and then start preemptive antifungal agents may be able to lead to accurate diagnosis, earlier treatment, and decreasing sinus surgery debridement in leukemia patients with neutropenia.

Background: Candida albicans remains the main cause of candidiasis in most clinical settings. Available drugs for candidiasis treatment have many side effects. In this work, novel nitroglycerin derivatives were synthesized and their cytotoxic and antifungal effects evaluated against fluconazole susceptible and resistant clinical C. albicans isolates. Methods: This experimental study was performed in Tehran University of Medical Sciences and Baqiatallah University of Medical Sciences, Tehran, Iran between Feb to Dec 2019. The in vitro activities of two novel nitroglycerin derivatives (1b and 2b) against 25 clinical fluconazole-susceptible and resistant C. albicans isolates and four standard C. albicans strains were determined according to CLSI reference M27-A3 documents. The cytotoxicity of chemical compounds was investigated near the SNL76/7 cells by colorimetric assay. Real-time PCRs were performed to evaluate the alterations in the regulation of ERG11 and CDR1 genes under nitroglycerin derivatives-treated and untreated conditions. Results: The derivatives 1b and 2b exhibited potent antifungal activity against C. albicans isolates; MICs and MFCs varied from 18 μg/ml to 72 μg/ml and 36 μg/ml to 144 μg/ml, respectively. The cell viability evaluation demonstrated that both chemical compounds are safe within 24h. The nitroglycerin derivatives were able to reduce the transcription level of CDR1 and ERG11 genes in all susceptible and resistant C. albicans isolates. Conclusion: Considering the potential and efficacy of these compounds against clinical C. albicans isolates, the complementary in vivo and clinical trials should be investigated.

BackgroundOnychomycosis is one of the most common and recurrent dermatological diseases worldwide. The antimycotic activity of prescribed medications varies according to the causative agents, and treatment failure rates exceeding 30%. This study aimed to assess the epidemiological profile of onychomycosis in Iran. Also, the susceptibilities to conventional and new antifungals were investigated.MethodsIn this descriptive cross-sectional study, during the period of 18 months starting from September 2019 until March 2020, 594 nail specimens were obtained from patients who presented nail changes compatible with a clinical diagnosis of onychomycosis. The patients were referred from different cities, including Tehran, Kermanshah, Arak, Kashan, Rasht, Qom, Urmia, Zahedan, Hamadan, Zanjan, Borujerd, Bushehr, and Yazd. All the samples were subjected to microscopic examination and fungal culture. Fungi identified were confirmed through the PCR-sequencing method. The susceptibility to itraconazole, fluconazole, terbinafine, griseofulvin, posaconazole, ravuconazole, efinaconazole, luliconazole, and tavaborole was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, document M38-A2 for filamentous fungi, and document M27-A3 for yeasts.Results594 patients were included. Of these, in 179 cases (30.1%) (95% CI:0.3 ± 0.037) onychomycosis was confirmed. The majority of patients were ≥ 60 years of age (n=58, 32.6%) and female (n=113, 63.1%). Saprophytic fungi accounted for the vast majority of the nail isolates (n=92, 51.4%) (95% CI:0.051 ± 0.0.073), followed by dermatophytes (n=45, 25.1%) (95% CI:0.25 ± 0.063), and yeasts (n=42, 23.5%) (95% CI:0.23 ± 0.061). Diabetes mellitus (77.3%), hypothyroidism (18.2%), and solid tumors (4.5%) were documented as the most prevalent underlying conditions. Antifungal susceptibility testing was performed against 60 fungal isolates (20 each of Candida species, saprophytic fungi, and dermatophytes). Efinaconazole, ravuconazole, and luliconazole were the most active agents against Candida species. Also, luliconazole, posaconazole, and efinaconazole were most potent against dermatophytes. Luliconazole had the greatest antifungal activity against saprophytic fungi.ConclusionsThe prevalence of onychomycosis in Iranian patients was relatively high. LUL exhibited potent antifungal activity against the three groups of fungi tested, determining its broad-spectrum antimycotic activity and its probable use as the first-line therapy for onychomycosis.

Background and Purpose: Candida parapsilosis complex isolates are mainly responsible for nosocomial catheter-related infection in immunocompromised patients. Biofilm formation is regarded as one of the most pertinent key virulence factors in the development of these emerging infections. The present study aimed to compare in vitro antifungal susceptibility patterns and biofilm-related genes expression ratio in planktonic and biofilm’s cells of clinically C. parapsilosis complex isolates. Materials and Methods: The current study was conducted on a number of 17 clinical C. parapsilosis complex (10 C. parapsilosis sensu stricto, 5 C. orthopsilosis, and 2 C. metapsilosis). The antifungal susceptibility patterns of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and caspofungin in planktonic and biofilm forms were closely examined using CLSI M27-A3 broth microdilution method. The expression levels of biofilm-related genes (BCR1, EFG1, and FKS1) were evaluated in planktonic and biofilm’s cells using Real-time polymerase chain reaction (PCR) technique. Results: The obtained results indicated that all C. parapsilosis complex isolates were able to produce high and moderate amounts of biofilm forms. In addition, the sessile minimum inhibitory concentrations were reported to be high for fluconazole (≥ 64 μg/ml), itraconazole, voriconazole, and posaconazole (≥ 16 μg/ml), as compared to planktonic minimum inhibitory concentrations. Moreover, a significant difference was observed between antifungal susceptibility patterns for all azole antifungal agents (P Conclusion: C. parapsilosis complex isolates were found susceptible to most of the tested antifungal drugs, while biofilms demonstrated a noticeable resistant to azoles. The marked discrepancy noted in antifungal susceptibility patterns among these species should be highlighted to achieve effective therapeutic treatment.

Background and Purpose: Aspergillus fumigatus is one of the most common opportunistic fungus, which causes infection in immunocompromised and neutropenic patients. The current guidelines recommend voriconazole as the initial therapeutic and prophylactic agent for almost all cases, especially in patients with organ transplants, which leads to increased medication resistance in A. fumigatus. The aim of the present study was to evaluate the antifungal activity and effect of kombucha as a natural compound on A. fumigatus growth, as well as on the expression of cgrA and cyp51A genes. Materials and Methods: A panel of 15 A. fumigatus strains with two quality controls of CM237 and CM2627 as susceptible and resistant strains were obtained from Tehran Medical Mycology Laboratory, Tehran,Iran(TMML).Antifungal susceptibility testing assay was performed according to the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. Moreover, the mycelial dry weight of the fungus was calculated before and after being treated with kombucha. In addition, the quantitative changes in the expression of cgrA and cyp51A genes were analyzed by real-time polymerase chain reaction (real-time PCR) technique. Results: In the present study, the minimum inhibitory concentration ranges of kombucha were measured at 6,170 and 12,300 μg/mL for ten A. fumigatus azole-susceptible strains and 24,700 μg/mL for five A. fumigatus resistant strains. Moreover, changes in mycelial dry weight under kombucha treatment conditions underwent a significant reduction (P≤0.05). A coordinate down-regulation of expression in cgrA and cyp51A genes was observed in all azole-susceptible and -resistant A. fumigatus strains, after treating the fungus with different concentrations of kombucha (P≤0.05). Conclusion: According to the obtained results, kombucha as a natural antioxidant , can exert inhibitory effects against the growth and expression of some genes in A. fumigatusstrains.

Background and Purpose: Emergence and development of antifungal drug resistance in Candida species constitute a serious concern. Candida auris as an emerging multidrug-resistant fungus is the most important public health threat with high levels of mortality and morbidity. Almost all C. auris isolates are resistant to fluconazole, and there have been reports of elevated minimum inhibitory concentrations (MICs) to amphotericin B and echinocandins. To overcome the growing challenge of antifungal resistance, a valuable alternative option would be the use of drug combination. Materials and Methods: The present study evaluated the in vitro combination of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac and aspirin with fluconazole against fluconazole-resistant C. auris in comparison to other fluconazole-resistant Candida species, including C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei originating from patients with candidiasis. Results: The MIC ranges of fluconazole-ibuprofen and fluconazole-diclofenac decreased from 32-256 to 32-128 and 16-256 μg/ml, respectively and remained the same for fluconazole-aspirin against C. auris. However, the combination of fluconazole with ibuprofen resulted in a synergistic effect for 5 strains, including C. albicans (n=2), C. tropicalis (n=1), C. glabrata (n=1), and C. krusei (n=1), by decreasing the MIC of fluconazole by 2-3 log2 dilutions. Conclusion: Although the interaction of NSAIDs with fluconazole was not synergistic against fluconazole-resistant C. auris isolates, no antagonism was observed for any combinations. Therefore, combination with newer azole agents needs to be conducted.

The emerging pathogen “Candida auris” is attracting considerable international attention due to its rising reports, transmission through health professionals, high rate of treatment failure and resistance to multiple antifungal agents, particularly fluconazole. In spite of the global emergence of C. auris, epidemiological data and true prevalence of infections due to this organism are not clearly determined due to incapability of conventional and biochemical identification methods. Consequently, this species is erroneously identified as C. haemulonii or Rhodotorula glutinis because of their close phenotypical and biochemical resemblance. Therefore, awareness of serious menace posed by C. auris is of great importance for physicians and health laboratory personnel. This awareness could play a beneficial role in prevention of healthcare-associated outbreaks, timely and definite diagnosis, prompt initiation of C. auris-targeted therapy, and subsequently improving treatment outcomes. This review aimed to discuss the epidemiology, drug resistance, diagnostic challenges, the mode of transmission, and the strategies for prevention of C. auris-related infections.

Fusarium species are filamentous fungi that cause a variety of infections in humans. Because they are commonly resistant to many antifungal drugs currently available in clinical settings, research into alternative targets in fungal cells and therapeutic approaches is required. The antifungal activity of miltefosine and four comparators, amphotericin B, voriconazole, itraconazole, and caspofungin, were tested in vitro against a collection of susceptible and resistant clinical (n = 68) and environmental (n = 42) Fusarium isolates. Amphotericin B (0.8 μg/mL) had the lowest geometric mean (GM) MICs/MECs values followed by miltefosine (1.44 μg/mL), voriconazole (2.15 μg/mL), caspofungin (7.23 μg/mL), and itraconazole (14.19 μg/mL). Miltefosine was the most effective agent against Fusarium isolates after amphotericin B indicating that miltefosine has the potential to be studied as a novel treatment for Fusarium infections.

Clonal expansion of fluconazole resistant (FLZ-R) Candida parapsilosis isolates is increasingly being identified in many countries, while there is no study exploring the antifungal susceptibility pattern, genetic diversity, and clinical information for Iranian C. parapsilosis blood isolates. Candida parapsilosis species complex blood isolates (n = 98) were recovered from nine hospitals located in three major cities, identified by MALDI-TOF MS, and their genetic relatedness was examined by AFLP fingerprinting. Antifungal susceptibility testing followed CLSI-M27-A3 and ERG11, MRR1 and hotspots 1/2 (HS1/2) of FKS1 were sequenced to assess the azole and echinocandin resistance mechanisms, respectively. Ninety-four C. parapsilosis and four Candida orthopsilosis isolates were identified from 90 patients. Only 43 patients received systemic antifungal drugs with fluconazole as the main antifungal used. The overall mortality rate was 46.6% (42/90) and death mostly occurred for those receiving systemic antifungals (25/43) relative to those not treated (17/47). Although, antifungal-resistance was rare, one isolate was multidrug-resistant (FLZ = 16 μg/ml and micafungin = 8 μg/ml) and the infected patient showed therapeutic failure to FLZ prophylaxis. Mutations causing azole and echinocandin resistance were not found in the genes studied. AFLP revealed five genotypes (G) and G1 was the main one (59/94; 62.7%). Clinical outcome was significantly associated with city (P = 0.02, α

Abstract Background Opportunistic infections due to Candida species occur frequently in cancer patients because of their inherent immunosuppression. The aim of the present study was to investigate the epidemiology of yeast species from the oral cavity of patients during treatment for oncological and haematological malignancies. Methods MALDI-TOF was performed to identify yeasts isolated from the oral cavity of 350 cancer patients. Moreover, antifungal susceptibility testing was performed in according to CLSI guidelines (M27-A3). Results Among 162 yeasts and yeast-like fungi isolated from the oral cavity of cancer patients, Candida albicans was the most common species (50.6%), followed by Candida glabrata (24.7%), Pichia kudriavzevii (Candida krusei (9.9%)), Candida tropicalis (4.3%), Candida dubliniensis (3.7%), Kluyveromyces marxianus (Candida kefyr (3.7%)) and Candida parapsilosis (1%). In addition, uncommon yeast species i.e., Saprochaete capitata, Saccharomyces cerevisiae, Clavispora lusitaniae (C. lusitaniae) and Pichia kluyveri (C. eremophila) were recovered from oral lesions. Oral colonization by C. albicans, non-albicans Candida species and uncommon yeasts were as follow; 55%, 44% and 1%, whereas oral infection due to C. albicans was 33.3%, non-albicans Candida species 60.6%, and uncommon yeasts 6.1%. Poor oral hygiene and xerostomia were identified as independent risk factors associated with oral yeast colonization. The overall resistance to fluconazole was 11.7% (19/162). Low MIC values were observed for anidulafungin for all Candida and uncommon yeast species. Conclusions This current study provides insight into the prevalence and susceptibility profiles of Candida species, including emerging Candida species and uncommon yeasts, isolated from the oral cavity of Iranian cancer patients. The incidence of oral candidiasis was higher amongst patients with hematological malignancies. The majority of oral infections were caused by non-albicans Candida species which were often more resistant to anti-fungal agents. Our findings suggest that anidulafungin should be used as antifungal of choice for prophylaxis in clinically high-risk patients with documented oral colonization or infection.

Mycetoma is a chronic-granulomatous disease characterized by the inflammation, swollen organ, draining sinuses containing blood, pus, and grains. We present a case of madura foot with novel etiologic agent Madurella pseudomycetomatis. Diagnosis was based on morphologic, physiologic, histipathologic and molecular methods. In vitro antifungal susceptibility tests revealed that MIC values for itraconazole, amphotericin B, and posaconazole were 0.0313 μg/ml, 0.0313 μg/ml, and 0.004 μg/ml, respectively. The patient was treated and recovered by itraconazole(400 mg/day) after prolonged course. Keywords: Mycetoma, Madura foot, Madurella pseudomycetomatis, Itraconazole

Background and Purpose: Candida parapsilosis is a predominant species found in nosocomial infection, particularly in hospitalized patients. The molecular epidemiology of the clinical strains of this species has not been well studied. The present study was performed with the aim of investigating the microsatellite genotyping of Candida parapsilosis among the Iranian clinical isolates. Materials and Methods: This study was conducted on 81 independent clinical C. parapsilosis isolates that were genotyped by using a panel of six microsatellite markers. Results: The short tandem repeat (STR) typing of clinical C. parapsilosis isolates demonstrated 68 separate genotypes, among which 57 genotypes were observed once and the remaining 11 cases were identified for multiple times. The Simpson’s diversity index for the panel of combined six markers yielded a diversity index of 0.9951. The heterogeneity was observed among the Iranian and the Netherlands clinical C. parapsilosis isolates. Conclusion: As the findings indicated, the clinical C. parapsilosis isolates from Iran showed a high genetic diversity. It can be concluded that molecular epidemiology could be useful for screening during outbreak investigation where C. parapsilosis is involved.

Background and Purpose: Aspergillosis is one of the most common opportunistic fungal infections in immunocompromised and neutropenic patients. Aspergillus fumigatus (A. fumigatus) is the most common causative agent of this infection. Due to variable CO2 concentrations that pathogens are exposed to during the infection process and to understand the role of CO2, we examined the effects of various CO2 concentrations as one of the environmental factors on morphological changes and induction of antifungal resistance in A. fumigatus. Materials and Methods: A. fumigatus strains were cultured and incubated under 1%, 3%, 5%, and 12% CO2 atmospheres, each time for one, two, and four weeks. The control culture was maintained for one week without CO2 atmosphere. Morphological changes were investigated and antifungal susceptibility test was performed according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The results of different CO2 atmospheres were compared with that of the control sample. Results: We found that 1%, 3%, 5%, and 12% CO2 atmospheres were associated with morphological colony changes. Macroscopically, the colonies were shallow dark green, smooth, crisp to powdery with reduced growth; microscopic examination revealed the absence of conidiation. The induction of antifungal resistance in the susceptible strains to itraconazole, voriconazole, and amphotericin B increased after exposure to 12% CO2 atmosphere and four weeks of incubation. The MIC values for itraconazole, voriconazole, and amphotericin B were 16 g/ml, 1 g/ml, and 16 g/ml, respectively. These values for the control group were 0.125 g/ml, 0.125 g/ml, and 2 g/ml, respectively. Conclusion: Exposure to different CO2 atmospheres induced morphological changes in A. fumigatus, it seems to increase the MIC values, as well. In parallel, resistance to both itraconazole and voriconazole was also observed.

Background and Purpose: Candida albicans is the most common Candida species (spp.) isolated from fungal infections. Azole resistance in Candida species has been considerably increased in the last decades. Given the toxicity of the antimicrobial drugs, resistance to antifungal agents, and drug interactions, the identification of new antifungal agents seems essential. In this study, we assessed the antifungal effects of biogenic selenium nanoparticles on C. albicans and determined the expression of ERG11 and CDR1 genes. Materials and Methods: Selenium nanoparticles were synthesized with Bacillus sp. MSH-1. The ultrastructure of selenium nanoparticles was evaluated with a transmission electron microscope. The antifungal susceptibility test was performed according to the modified Clinical and Laboratory Standards Institute M27-A3 standard protocol. The expression levels of the CDR1 and ERG11 genes were analyzed using the quantitative real-time polymerase chain reaction (PCR) assay. Results: The azole-resistant C. albicans and wild type C. albicans strains were inhibited by 100 and 70 µg/mL of selenium nanoparticle concentrations, respectively. The expression of CDR1 and ERG11 genes was significantly down-regulated in these selenium nanoparticle concentrations. Conclusion: As the findings indicated, selenium nanoparticles had an appropriate antifungal activity against fluconazole-resistant and -susceptible C. albicans strains. Accordingly, these nanoparticles reduced the expression of CDR1 and ERG11 genes associated with azole resistance. Further studies are needed to investigate the synergistic effects of selenium nanoparticles using other antifungal drugs.

Despite the increasing occurrence of Candida orthopsilosis and Candida metapsilosis in clinical settings, little is known about their microbiological and clinical properties. Herein, we conducted a national retrospective study (2014–2019) from multiple centers in Iran. Among the 1,770 Candida isolates collected, we identified 600 Candida parapsilosis species complex isolates. Isolate identification was performed by 9-plex PCR, matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF MS), and rDNA sequencing, and antifungal susceptibility testing (AFST) followed CLSI M27-A3/S4; genotyping was performed by amplified fragment length polymorphism (AFLP) analysis; and clinical information was mined. Thirty-one isolates of C. orthopsilosis from various clinical sources, one mixed sample (blood) concurrently containing C. orthopsilosis and C. parapsilosis and one isolate of C. metapsilosis from a nail sample were identified. Although both 9-plex PCR and MALDI-TOF successfully identified all isolates, only 9-plex PCR could identify the agents in a mixed sample. For the C. orthopsilosis isolates, resistance (non-wild type) was noted only for itraconazole (n = 4; 12.5%). Anidulafungin and fluconazole showed the highest and voriconazole had the lowest geometric mean values. AFLP analysis showed three main and four minor genotypes. Interestingly, 90% of nail isolates clustered with 80% of the blood isolates within two clusters, and four blood isolates recovered from four patients admitted to a hospital clustered into two genotypes and showed a high degree of similarity (>99.2%), which suggests that C. orthopsilosis disseminates horizontally. Supported by our data and published case studies, C. orthopsilosis and C. metapsilosis can be linked to challenging clinical failures, and successful outcomes are not always mirrored by in vitro susceptibility. Accordingly, conducting nationwide studies may provide more comprehensive data, which is required for a better prognosis and clinical management of patients.

Occurrence of non-Candida albicans Candida (NCAC) species that are associated with elevated MIC values and therapeutic failures are increasing. As a result, timely and accurate means of identification to the species level is becoming an essential part of diagnostic practices in clinical settings. In this study, 301 clinically isolated yeast strains recovered from various anatomical sites [Blood (n = 145), other sites (n = 156)] were used to assess the accuracy and practicality of API 20C AUX and 21-plex PCR compared to MALDI-TOF MS and large subunit rDNA (LSU rDNA). MALDI-TOF MS correctly identified 98.33% of yeast isolates, 100% of top five Candida species, 95.7% of rare yeast species, while 1.3% of isolates were misidentified. API 20C AUX correctly identified 83.7% of yeast isolates, 97.2% of top five Candida species, 61.8% of rare yeast species, while 16.2% of yeast isolates were misidentified. The 21-plex PCR, accurately identified 87.3% of yeast isolates, 100% of top five Candida species, 72% of rare yeast species, but it misidentified 1.3% of rare yeast species while 9.9% of whole yeast isolates were not identified. The combination of rapidity of 21-plex PCR and comprehensiveness of API 20C AUX, led to correct identification of 92% of included yeast isolates. Due to expensiveness of MALDI-TOF MS and sequencing, this combination strategy could be the most accurate and inexpensive alternative identification strategy for developing countries. Moreover, by the advent and development of cost-effective, reliable, and rapid PCR machines that cost 130 US dollars, 21-plex could be integrated in routine laboratories of developing and resource-limited countries to specifically identify 95% causative agents of yeast-related infections in human. Databases of MALDI-TOF MS, API 20C AUX, and the number of target species identified by 21-plex require further improvement to keep up with the diverse spectrum of yeast species.

Background and Purpose: Formation of pseudohyphae is considered a virulence factor in Candida species. Generally, Candida glabrata grows as budding yeast cells; however, reports illustrated that C. glabrata could form pseudohyphal cells in response to some stimuli. In this study, we provided insight into the ability of C. glabrata in forming pseudohyphal cells under different levels of carbon dioxide (CO2). Materials and Methods: Candida glabrata reference strain (ATCC 90030) was used in this study. Yeast samples were cultured on Sabouraud dextrose broth (SDB) medium and incubated under 3%, 5%, and 10% CO2 levels for 24, 48 and72 h. Control cultures were prepared without CO2 pressure for three days. The possibility of pseudohyphae and mycelium formation in C. glabrata was investigated. Results: The results of this study revealed that the most branching filament-like cells were obtained at high CO2 pressure (10%) after 72 h. After three days of low CO2 pressure (3%), only yeast and budding cells were observed without any pseudohyphae formation. Conclusion: CO2 could act as a stimulus and induced formation of pseudohyphae in Candida glabrata yeast cells.

Invasive candidiasis remains one of the most prevalent systemic mycoses, and several studies have documented the presence of mixed yeast (MY) infections. Here, we describe the epidemiology, clinical, and microbiological characteristics of MY infections causing invasive candidiasis in a multicenter prospective study. Thirty-four centers from 14 countries participated. Samples were collected in each center between April to September 2018, and they were sent to a reference center to confirm identification by sequencing methods and to perform antifungal susceptibility testing, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A total of 6895 yeast cultures were identified and MY occurred in 150 cases (2.2%). Europe accounted for the highest number of centers, with an overall MY rate of 4.2% (118 out of 2840 yeast cultures). Of 122 MY cases, the most frequent combinations were Candida albicans/C. glabrata (42, 34.4%), C. albicans/C. parapsilosis (17, 14%), and C. glabrata/C. tropicalis (8, 6.5%). All Candida isolates were susceptible to amphotericin B, 6.4% were fluconazole-resistant, and two isolates (1.6%) were echinocandin-resistant. Accurate identification of the species involved in MY infections is essential to guide treatment decisions.

Azole-resistance in Aspergillus fumigatus is a worldwide medical concern complicating the management of aspergillosis (IA). Herein, we report the clonal spread of environmental triazole resistant A. fumigatus isolates in Iran. In this study, 63 A. fumigatus isolates were collected from 300 compost samples plated on Sabouraud dextrose agar supplemented with itraconazole (ITR) and voriconazole (VOR). Forty-four isolates had the TR34/L98H mutation and three isolates a TR46/Y121F/T289A resistance mechanism, while two isolates harbored a M172V substitution in cyp51A. Fourteen azole resistant isolates had no mutations in cyp51A. We found that 41 out of 44 A. fumigatus strains with the TR34/L98H mutation, isolated from compost in 13 different Iranian cities, shared the same allele across all nine examined microsatellite loci. Clonal expansion of triazole resistant A. fumigatus in this study emphasizes the importance of establishing antifungal resistance surveillance studies to monitor clinical Aspergillus isolates in Iran, as well as screening for azole resistance in environmental A. fumigatus isolates.

Autosomal recessive deficiency in the caspase recruitment domain containing protein 9 (CARD9) results in susceptibility to fungal infections. In the last decade, infections associated with CARD9 deficiency are more reported due to the advent of genome sequencing. The aim of this study was to evaluate the frequency, geographic distribution and nature of mutations in patients with CARD9 deficiency. We identified 60 patients with 24 mutations and different fungal infections. The presence of the homozygous (HMZ) p.Q295X (c.883C > T) and HMZ p.Q289X (c.865C > T) mutations were associated with an elevated risk of candidiasis (OR: 1.6; 95% CI: 1.18–2.15; p = 0.004) and dermatophytosis (OR: 1.85; 95% CI: 1.47–2.37; p < 0.001), respectively. The geographical distribution differed, showing that the main mutations in African patients were different Asian patients; HMZ p.Q289X (c.865C > T) and HMZ p.Q295X (c.865C > T) accounted for 75% and 37.9% of the African and Asian cases, respectively. The spectrum of CARD9 mutations in Asian patients was higher than in African. Asia is the most populous continent in the world and may have a greater genetic burden resulting in more patients with severe fungal infections. The presence of a high diversity of mutations revealing 24 distinct variations among 60 patients emphasize that the unique genetic alteration in CARD9 gene may be associated with certain geographical areas.

Background and Purpose: Chronic obstructive pulmonary disease (COPD) has been recognized as a risk factor for invasive aspergillosis. Airway colonization by Aspergillus species is a common feature of chronic pulmonary diseases. Nowadays, the incidence of COPD has increased in critically ill patients. The aim of the present study was to isolate and identify Aspergillus colonies in the respiratory tract of COPD patients. Materials and Methods: This study was performed on 50 COPD patients, who were aged above 18 years, and were in intensive care units of three hospitals in Sari, Iran, for at least six days. All the samples obtained from sputum, bronchoalveolar lavage, and tracheal aspirates were cultured for fungi each week. According to the conventional techniques, Aspergillus isolates were initially based on growth and standard morphological characteristics. To confirm the identification of grown Aspergillus, the partial beta-tubulin gene was sequenced using specific primers. Results: A total of 50 patients, who met our inclusion criteria, were enrolled in the study during 2012-14. The results showed that 27 (54%) and 23 (46%) of the participants were male and female, respectively. The majority of the patients developed dyspnea followed by hemoptysis, chest pain, and high fever. Corticosteroids and broad-spectrum antibacterial agents were administered to 75% and 80% of the patients, respectively. Based on the conventional and molecular approaches, A. fumigatus (seven cases 43.7%), A. flavus (five cases 31.2%), A. niger (one case 6.2%), A. terreus (one case 6.2%), A. orezea (one case 6.2%), and A. tubingensis (one case 6.2%) were recovered. Conclusion: Recovery of Aspergillus species from the respiratory tract of COPD patients with pneumonia indicates two possibilities: either colonization or invasive aspergillosis

Chronic obstructive pulmonary disease (COPD) is associated with a chronic inflammatory response in airways and lung parenchyma that results in significant morbidity and mortality worldwide. Cigarette smoking considered as an important risk factor plays a role in pathogenesis of disease. Pneumocystis jirovecii is an atypical opportunistic fungus that causes pneumonia in immunosuppressed host, although the low levels of its DNA in patients without signs and symptoms of pneumonia, which likely represents colonization. The increased prevalence of P. jirovecii colonization in COPD patients has led to an interest in understanding its role in the disease. P. jirovecii colonization in these patients could represent a problem for public health since colonized patients could act as a major reservoir and source of infection for susceptible subjects. Using sensitive molecular techniques, low levels of P. jirovecii DNA have been detected in the respiratory tract of certain individuals. It is necessary to elucidate the role of P. jirovecii colonization in the natural history of COPD patients in order to improve the clinical management of this disease. In the current review paper, we discuss P. jirovecii colonization in COPD patients.

Background: Due to the predisposing conditions in patients with cystic fibrosis (CF) caused by defective mucociliary clearance facilitating colonization and invasion with Candida species has dramatically increased. Traditional methods for identifying problems are imminent and time-consuming. Therefore, molecular techniques utilizing amplification of target DNA provide quick and precise methods for the diagnosis and identification of Candida species. Therefore, the aim of the current study was to identify the most medically common isolated Candida species from the air way of CF patients by PCR-RFLP and amplification of HWP1 gene. Materials and Methods: A total of 42 CF patients presenting symptoms who referred to pediatric respiratory diseases research center were screened for the presence of Candida spp. The isolates initially were phenotypically identified and confirmed by molecular approaches based on restriction fragment length polymorphism ( PCR -RFLP) for the discrimination of C. albicans of non-albicans and the amplification of HWP1 gene for the discrimination of C. albicans from C. dubliniensis and C. africana was conducted. Results: The results show that C. albicans was the most frequently isolated species (83.8%) followed by non-albicans included C. parapsilosis (7.1%), C. glabrata (3.2%), and C. tropicalis (3.2%). The restriction patterns of each Candida species were perfectly specific. Since MspI could not discriminate between the three morphological related species, C. albicans, C. dubliniensis and C. africana, we used PCR amplification of HWP1 gene, which (7.1%) species from C. albicans identified as C. dubliniensis, however C. africana strains were not found. Conclusion: The present study found that C. albicans as predominant species wereisolated from the CF patients. It could be concluded that molecular diagnostic methods are reliable and would be useful for the identification of medically important Candida species in clinical samples . Therefore, considerable attention has been paid to the prevention and treatment of microbial growth, which has resulted in the improvement of patient management.

We assessed the intensive care unit (ICU) patients for Invasive aspergillosis (IA) with culture and non-culture based diagnostic methods from Iran. Thirty-six ICU patients with underlying predisposing conditions for IA were enrolled in the study. Sixty eight Bronchoalveolar lavage (BAL) samples were collected by bronchoscope twice a weekly. BAL samples were analyzed by microscopic examination, fungal culture and galactomannan (GM) detection. The Platelia Aspergillus GM EIA was used to quantify GM indices. Samples with a BAL GM index ≥1 were considered as positive for GM. Patients were classified as having probable or possible IA. Out of 36 suspected patients to IA, 36.1% of cases showed IA which were categorized as: 4 cases of possible IA and 9 of probable IA. 76.2% of BAL samples were positive for GM. From 13 patients with IA, 11 (84.6%) had at least one positive BAL GM index. Of these patients, 9 (81.8%) showed probable IA. The main underlying predisposing conditions were neutropenia (53.8%) and COPD (30.8%). Our study has indicated that COPD must be considered as one of the main predisposing condition for occurrence of aspergillosis in ICU patients. Our data have also revealed that GM detection in BAL samples play a significant role to IA diagnosis.

Aims. Biofilms formed by Candida species which associated with drastically enhanced resistance against most antimicrobial agents. The aim of this study was to identify and determine the antifungal susceptibility pattern of Candida species isolated from endotracheal tubes from ICU patients. Methods. One hundred forty ICU patients with tracheal tubes who were intubated and mechanically ventilated were surveyed for endotracheal tube biofilms. Samples were processed for quantitative microbial culture. Yeast isolates were identified to the species level based on morphological characteristics and their identity was confirmed by PCR-RFLP. Antifungal susceptibility testing was determined according to CLSI document (M27-A3). Results. Ninety-five strains of Candida were obtained from endotracheal tubes of which C. albicans (n=34; 35.7%) was the most frequently isolated species followed by other species which included C. glabrata (n=24; 25.2%), C. parapsilosis (n=16; 16.8%), C. tropicalis (n=12; 12.6%), and C. krusei (n=9; 9.4%). The resulting MIC90 for all Candida species were in increasing order as follows: caspofungin (0.5 μg/mL); amphotericin B (2 μg/mL); voriconazole (8.8 μg/mL); itraconazole (16 μg/mL); and fluconazole (64 μg/mL). Conclusion. Candida species recovered from endotracheal tube are the most susceptible to caspofungin.

(Received 16 Jan, 2010 ; Accepted 11 May, 2010)AbstractThe genus Aspergillus is ubiquitous filamentous fungi with a wide distribution in nature. The species of Aspergillus are associated with a varied spectrum of diseases including allergy, superficial colonization and invasive infection in humans. Invasive aspergillosis (IA) is a serious and fulminate mycosis in immuno-deficient individuals. Over the last decade, IA has also been reported as a fungal infection in critically ill patients, admitted to ICU with high morbidity and mortality rate. However, long term admission in ICU, treatment with immuno-suppressive agents caused by increasing incidence of IA in the ICU. It is expressed that delay in proper diagnosis, no timely treatment and the presence of different underlying diseases and neutropenia are the important reasons of high mortality in these patients.In spite of advances in diagnosis and treatment of IA, it appears that the occurrence of IA in ICU patients is due to lack of estimation and proper diagnosis of disease. In addition to traditional methods, using the specialized methods such as PCR, evaluation of serological markers including Galactomanan and β-D Glucan in different types of specimens, is necessary to show the true rate of IA risk in ICU patients and also to have a proper program for hygienic and preventive actions.Along with the increase in the number of ICU units comes a surge in admission of patients in these centers, but because there was no such study in Iran, we reviewed the papers in this field to consider different aspects of IA with emphasis on diagnostic methods.Key words: Invasive Aspergillosis, intensive Care Units, galactomannan, PCRJ Mazand Univ Med Sci 2009; 20(74): 99-112 (Persian).

Cutaneous anthrax has a mortality rate of 20% if no antibacterial treatment is applied. The clinical manifestations of cutaneous anthrax are obviously striking, but coinfection may produce atypical lesions and mask the clinical manifestations and proper laboratory diagnosis. Anthrax is known to be more common in the Middle East and Iran is one of the countries in which the zoonotic form of anthrax may still be encountered. We report a case of a 19-years-old male who used to apply Venetian ceruse on his skin. Venetian ceruse (also known as Spirits of Saturn) is an old cosmetic product used for skin whitening traditionally made from sheep’s spinal cord. The patient referred to the Referral Laboratory, Mazandaran University of Medical Sciences, Sari, Iran, with atypical dermatosis, pronounced pain, and oedema of the affected tissue. It was confirmed by both conventional and molecular analysis that culture was a mixture of Bacillus anthracis and Trichophyton interdigitale. The patient was initially treated with ceftriaxone (1000 mg/day for two weeks), gentamicin (1.5–2 mg/kg/day), terbinafine (200 mg/week for one month), and 1% clotrimazole cream (5 weeks) two times per day which resulted in gradual improvement. No relapse could be detected after one-year follow-up. Anthrax infection might present a broader spectrum of symptoms than expected by clinicians. These unfamiliar characteristics may lead to delayed diagnosis, inadequate treatment, and higher mortality rate. Clinicians need to be aware of this issue in order to have successful management over this infection.

Actinomycosis is an indolent, slowly progressive infection caused by anaerobic or microaerophilic bacteria, primarily of genus Actinomyces, which colonize the mouth, colon and vagina. Mucosal disruption may lead to infection virtually at any sites in the body. The aim of this study was to underline different features of actinomycosis and to represent total data about etiologic agents, clinical, diagnostic and therapeutic approaches these infections. From a total of 38 case reports or series, ninety one cases were obtained by using of relevant articles reported as recorded cases in Iran (1972 to 2012). Analyzed data represented 21 cases of oral-servicofacial (23.1%), 7 cases of thoracic (7.7%), 17 cases of abdominal (18.7%), 21 cases of disseminated forms (23.1%) and 25 cases of others (27.5%). Findings indicated more common of these infections in men (61.5%). Actinomyces naeslundii (21 cases) was found as the most common causative agents in comparison with A. Israeli (15 cases), A. viscosus (3 cases) and A. bovis (1 case). The most patients had been successfully treated with penicillin although some cases needed surgery along with antibiotic therapy. Since some clinical features of actinomycosis are similar to malignancies, so the differential diagnosis of invasive forms must be considered. This report emphasizes on the importance of differential diagnosis of actinomycosis from similar diseases by clinicians.

Background and Objectives: Onychomycosis is a common fungal infection which has been conducted in many parts of the world. The aim of this study was to evaluate the epidemiology and to identify the aetiological factors of onychomycosis in Mazandaran province, Iran. Materials and Methods: During the period of 10 years (2003–2012) 1100 patients suspected with onychomycosis, referred to the Mycology Laboratory of the Referral Laboratory and Boali Sina Hospital of Mazanadaran University of Medical Sciences, Sari, Iran, were assessed for the presence of onychomycosis with mycological examination based on conventional techniques. Results: Among 1100 subjects (398 males and 702 females, aged 1-88 years) onychomycosis was diagnosed in 625(56.8%) cases. Among cases of onychomycosis, laboratorial confirmation was reached through direct examination with positive cultures in 464 samples (74.3%), while only by positive direct exam in 114 cases (18.2 %) or just positive culture in 47 cases (7.5%). The results of fungal culture revealed Candida spp. isolated in (61.9%) of the cases as the most common agents of onychomycosis while among dermatophytes, Trichophyton mentagrophytes was found in 17.7% followed by T. rubrum (1.7%), Epidermophyton floccosum (0.7%), T. violaceum (0.2%), T. verrucosum (0.2%), T. tonsurans (0.2%) and Microsporum gypseum (0.2%). Among the non-dermatophyte moulds, Aspergillus spp. was the most prevalent species (14.2%). Conclusion: The results demonstrated that onychomycosis was diagnosed in 625(56.8%) cases and the most common isolates were Candida spp., followed by dermatophytes and moulds. This epidemiological data collected may be useful in the development of preventive and educational strategies.