Iranian National Survey on Tinea Capitis: Antifungal Susceptibility Profile, Epidemiological Characteristics, and Report of Two Strains with a Novel Mutation in SQLE Gene with Homology Modeling.

BACKGROUND: The data on the epidemiological and antifungal susceptibility profile of tinea capitis (TC) in Iran has not been updated in recent decades. This report presents the Iranian epidemiological and drug susceptibility data regarding the distribution of dermatophytes species isolated by six national mycology centers for a period of one year (2020-2021). MATERIAL AND METHODS: A total of 2100 clinical samples from individuals suspeted to TC were subjected to mycological analysis of direct microscopy and culture. For definite species identification, the culture isolates were additionally subjected to PCR-RFLP and PCR-sequencing of the ITS ribosomal DNA (ITS-rDNA) region. Antifungal susceptibility profiles for eight common antifungal drugs were determined by CLSI M38-A3 guidelines. The SQLE gene was partially amplified and sequenced in two terbinafine-resistant and two susceptible T. mentagrophytes isolates to elucidate probable substitutions involved in resistance. RESULTS: TC (n = 94) was diagnosed in 75 children (79.8%) and 19 adults (20.2%) by direct microscopy and culture. Frequency of TC was significantly more among males (66 males = 70.2% vs 28 females = 29.8%). The prevalent age group affected was 5-9 years (39.36%). Thirty-two (34.04%) T. mentagrophytes, 27 (28.7%) T. tonsurans, 14 (14.9%) M. canis, 13 (13.8%) T. violaceum, 5 (5.32%) T. indotineae, 2 (2.1%) T. benhamiae, and 1 (1.1%) T. schoenleinii were identified as the causative agents. MIC values of isolates showed susceptibility to all antifungal agents, except for fluconazole and griseofulvin with GM MIC of 11.91 µg/ml and 2.01 µg/ml, respectively. Terbinafine exhibited more activity against isolates, with GM MIC 0.084 µg/ml followed by ketoconazole (0.100 µg/ml), econazole (0.107 µg/ml), itraconazole (0.133 µg/ml), butenafine (0.142 µg/ml), and miconazole (0.325 µg/ml). Two resistant T. mentagrophytes isolates harbored missense mutations in SQLE gene, corresponding to amino acid substitution F397L. Remarkably, one unique mutation, C1255T, in the SQLE sequence of two terbinafine-susceptible T. mentagrophytes strains leading to a change of leucine at the 419th position to phenylalanine (L419F) was detected. CONCLUSIONS: T. mentagrophytes, T. tonsurans, and M. canis remained the main agents of TC in Iran, however less known species such as T. indotinea and T. benhamiae are emerging as new ones. Terbinafine could still be the appropriate choice for the treatment of diverse forms of TC.

New update on molecular diversity of clinical Staphylococcus aureus isolates in Iran: antimicrobial resistance, adhesion and virulence factors, biofilm formation and SCCmec typing.

BACKGROUND: Staphylococcus aureus is often considered as a potential pathogen and resistant to a wide range of antibiotics. The pathogenicity of this bacterium is due to the presence of multiple virulence factors and the ability to form biofilm. SCCmec types I, II and III are mainly attributed to HA-MRSA, while SCCmec types IV and V have usually been reported in CA-MRSA infections. METHODS AND RESULTS: In this study, we performed a cross-sectional study to determine the antimicrobial resistance, adhesion and virulence factors, biofilm formation and SCCmec typing of clinical S. aureus isolates in Iran. S. aureus isolates were identified using microbiological standard methods and antibiotic susceptibility tests were performed as described by the Clinical and Laboratory Standards Institute (CLSI) guidelines. Inducible resistance phenotype and biofilm formation were determined using D-test and tissue culture plate methods, respectively. Multiplex-PCRs were performed to detect adhesion and virulence factors, antibiotic resistance genes, biofilm formation and SCCmec typing by specific primers. Among 143 clinical samples, 67.8% were identified as MRSA. All isolates were susceptible to vancomycin. The prevalence of cMLSB, iMLSB and MS phenotypes were 61.1%, 22.2% and 14.8%, respectively. The TCP method revealed that 71.3% of isolates were able to form biofilm. The predominant virulence and inducible resistance genes in both MRSA and MSSA isolates were related to sea and ermC respectively. SCCmec type III was the predominant type. CONCLUSIONS: Data show the high prevalence rates of virulence elements among S. aureus isolates, especially MRSA strains. This result might be attributed to antibiotic pressure, facilitating clonal selection.

Investigation of in vitro antifungal susceptibility testing and genetic diversity of clinical isolates of Trichophyton benhamiae and Trichophyton eriotrephon in Iran.

BACKGROUND: Trichophyton benhamiae is a zoophilic dermatophyte, known as one of the causative agents of dermatophytosis. OBJECTIVES: The purpose of this study was to explore the genotypes of T. benhamiae strains isolated from geographically different areas of Iran and also to evaluate in vitro antifungal susceptibility profile of these strains against seven antifungal drugs. METHODS: Twenty-two strains of T. benhamiae and two strains of T. eriotrephon were isolated from patients with distinct types of dermatophytosis. DNA extraction and amplification of rDNA regions using ITS1 and ITS4 primers were conducted on the isolates. The in vitro antifungal susceptibility of posaconazole (PSC), voriconazole (VRC), itraconazole (ITC), ketoconazole (KET), caspofungin (CAS), terbinafine (TRB) and griseofulvin (GRZ) was evaluated according to CLSI M38-A2 protocol. RESULTS: The multiple alignment of the ITS-rDNA sequences of T. benhamiae indicated a mean similarity of 99.5%, with 0-3 interspecies nucleotide difference. The geometric mean (GM) values of minimum inhibitory concentrations (MICs) and minimum effective concentrations (MECs) across the all isolates were respectively: TRB: 0.025 mg/L, PSC: 0.032 mg/L, ITC: 0.050 mg/L and VRC: 0.059 mg/L with lower values and CAS: 0.31 mg/L, KTZ: 0.56 mg/L and GRZ: 0.76 mg/L with higher values. CONCLUSION: Diverse ITS sequence types of T. benhamiae were shown in different geographical regions of Iran. The TRB, PSC and ITC were the most effective drugs against T. benhamiae strains, respectively. Furthermore, in our study, two strains of T. eriotrephon as a scarce dermatophyte species were described.

Familial Cases of Trichophyton benhamiae Infection Transmitted from a Guinea Pig in Iran.

Trichophyton benhamiae is a zoophilic dermatophyte mainly transmitted to humans from guinea pigs. This zoophilic species can also cause dermatophytosis as reported by human contact with other animals, such as rabbit, cat, and fox. Here, we report the tinea faciei and tinea corporis cases: a 12-year-old girl and her 53-year-old father, with no history of immunodeficiency and underlying disease, caused by T. benhamiae transmitted from a guinea pig in Iran. Dermatological examination revealed several erythematous, round, scaly, and approximately 1-4-cm-diameter lesions in both patients. The girl had seven skin lesions, and her father presented two skin lesions on the front side of his neck. The girl's lesions had started 3 weeks before and her father's lesions appeared 7 days after the first clinical appearance of the lesions in the daughter. The girl had daily close contact with a guinea pig, while her father did not have any direct exposure to the pet. Examination of the lesions scraping with 10% potassium hydroxide (KOH 10%) revealed hyaline septate hyphae and arthroconidia. The dermatophyte isolated in culture was identified as T. benhamiae using molecular analysis. The patients were successfully treated using topical sertaconazole nitrate 2% cream twice a day for 4 weeks.

Molecular Identification and Antifungal Susceptibility of Yeasts and Molds Isolated from Patients with Otomycosis.

Fungal otitis externa, an infection of the external auditory canal caused by molds and yeasts, accounts for approximately 10-20% of ear canal infections accompanying high recurrence. The purpose of the current study was to assess the pattern of etiological agents of otomycosis and resistance profile as well as the rate of tympanic membrane perforation. A total of 1040 patients with symptoms of fungal otitis externa, in a period of two years, were investigated. The mycological tests revealed the presence of different fungi in 237 ears (22.8%). Fungal otitis was more related to filamentous fungi of the species Aspergillus flavus (54.43%), A. tubingensis (10.97%), and A. niger (8.86%), followed by yeasts, Candida orthopsilosis (7.59%), C. albicans (6.75%), and C. parapsilosis (5.06%). Tympanic membrane perforation rate was found to be 6.75% and was more common with otomycosis caused by A. flavus, A. tubingensis and C. albicans. In antifungal susceptibility tests, all tested drugs showed generally good activity against most isolates of molds and yeasts, while tolnaftate, clotrimazole, nystatin, and terbinafine had lowest effects. We found that among Aspergillus isolates, one A. niger isolate was resistant to voriconazole, and one A. flavus isolate was resistant to amphotericin B. Furthermore, among Candida species, three isolates of C. orthopsilosis showed high MIC values to fluconazole, two C. albicans isolates were considered fluconazole resistant and one isolate of C. parapsilosis was resistant to caspofungin and 3 isolates were resistant to fluconazole. Regarding the existence of the cases with perforated tympanic membrane and emerging species causing fungal otitis in the current report, the importance of the early physical examination, precise molecular identification, and the antifungal susceptibility evaluation is highlighted.

Disseminated phaeohyphomycosis caused by Cyphellophora ludoviensis: A novel case report from Iran.

Disseminated phaeohyphomycosis is a rare and unusual infection that can be caused by dematiaceous fungi. Cyphellophora is an uncommon aetiological agent of cutaneous and systemic fungal infections. This study describes a case of disseminated phaeohyphomycosis caused by C. ludoviensis in Iran. The molecular identification of the isolates was established by DNA sequencing of the internal transcribed spacer (ITS) region of rDNA. The patient was successfully treated with an 8-month course of systemic voriconazole.

In-vitro antifungal susceptibility testing of lanoconazole and luliconazole against Aspergillus flavus as an important agent of invasive aspergillosis.

INTRODUCTION: The incidence of Aspergillus infections has recently increased remarkably in certain tropical and sub-tropical countries, with Aspergillus flavus being identified as the leading cause of infections after A. fumigatus. Lanoconazole (LAN) and luliconazole (LUL) are currently approved for topical treatment of cutaneous fungal infections. We aimed the in-vitro antifungal susceptibility testing of two imidazole, LAN and LUL against A. flavus. METHODS: One hundred and eighty-seven clinical and environmental A. flavus were tested originating from different climate zones of Iran between 2008 and 2015. The identification of all isolates was confirmed by using PCR-sequencing of ß-tubuline ribosomal DNA gene. In-vitro antifungal susceptibility test was performed using CLSI guidelines against LAN, LUL, itraconazole (ITC), voriconazole (VRC), posaconazole (POS), Isavuconazole (ISA), amphotericin B (AMB), 5-flucytosine (5FC), caspofungin (CAS) and anidulafungin (AFG). The minimum inhibitory concentration (MIC) and minimum effect concentration (MEC) values were evaluated according to CLSI M38-A2 guidelines. RESULTS: The geometric mean MICs for tested antifungals, in increasing order, were: 0.009 µg/mL for LUL (ranging from 0.004 to 0.062), 0.02 µg/mL for LAN (ranging from 0.004 to 0.125), POS (0.10), ISA (0.16), ITC (0.24), VRC (0.27), AMB (1.8) and 5FC (63.06) µg/mL. The mean value of MECs for AFG and CAS were 0.06 and 0.07, respectively. CONCLUSION: Overall, LUL and LAN showed the lowest MIC against all isolates of A. flavus. Further studies are required to evaluate the in-vivo efficacy of these agents, and the possibility of using these agents in systemic infections.

Candida auris otomycosis in Iran and review of recent literature.

Candida auris is a multidrug-resistant yeast emerging in immunocompromised and in otherwise healthy individuals. Due to difficulties in microbiological identification of C. auris because of the lack of available laboratory technology in developing countries, the number of patients affected is most likely underestimated. We report the first case of C. auris otitis which now adds Iran as the fifth country around the Persian Gulf, in addition to Kuwait, Oman, United Arab Emirates and Saudi Arabia. Candida auris is an unknown pathogen in routine laboratories in Iran because most Candida isolates are probably misdiagnosed. Otomycosis seems to be a different clinical presentation of C. auris mainly involving isolates from the East-Asian clade. We compared the mycological and clinical details of the Iranian patient with other cases of otitis reported since the last review of C. auris otomycosis in 2017.

Discrimination of Aspergillus flavus from Aspergillus oryzae by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry.

BACKGROUND: Aspergillus flavus is a major cause of severe non-invasive fungal infections in the Middle Eastern countries. However, it is difficult to distinguish A flavus from A oryzae. OBJECTIVES: To assess the potential of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) in discriminating between A flavus and A oryzae and compare it with ß-tubulin gene sequencing. METHODS: We used the Bruker Daltonik MALDI-TOF MS system to analyse 200 clinical and environmental A flavus isolates and one A pseudonomius and one A alliaceus (Aspergillus section Flavi) isolate a priori identified as such by sequencing of the ß-tubulin gene. RESULTS: All 200 A flavus isolates were identified at the genus level and 176 (88%) at the species levels by MALDI-TOF MS based on the spectral log-scores (≥2.0 and 1.7-1.99, respectively); among them, only 18 (10.2%) were confirmed as A flavus, whereas 35 (19.9%) were identified as A oryzae and 123 (69.9%) as A flavus/A oryzae. Aspergillus pseudonomius and A alliaceus were misidentified as A flavus and A parasiticus with log-score values of 1.39 and 1.09, respectively. CONCLUSIONS: The results indicate that the commercially available Bruker Daltonik MALDI-TOF MS score database cannot separate A flavus and A oryzae species. We also showed that establishment of an in-house library is a useful tool to discriminate closely related Aspergillus species, including A flavus and A oryzae.

In Vitro Antifungal Susceptibility Profiles of 12 Antifungal Drugs against 55 Trichophyton schoenleinii Isolates from Tinea Capitis Favosa Patients in Iran, Turkey, and China.

Trichophyton schoenleinii is an anthropophilic dermatophyte mainly causing tinea favosa of the scalp in certain regions of the world, especially Africa and Asia. We investigated the in vitro susceptibilities of 55 T. schoenleinii isolates collected over the last 30 years from Iran, Turkey, and China to 12 antifungals using the CLSI broth microdilution method. Our results revealed that terbinafine and ketoconazole were the most potent antifungal agents among those tested, independently of the geographic regions where strains were isolated.

Genetic Diversity and In Vitro Antifungal Susceptibility of 200 Clinical and Environmental Aspergillus flavus Isolates.

Aspergillus flavus has been frequently reported as the leading cause of invasive aspergillosis in certain tropical and subtropical countries. Two hundred A. flavus strains originating from clinical and environmental sources and collected between 2008 and 2015 were phylogenetically identified at the species level by analyzing partial ß-tubulin and calmodulin genes. In vitro antifungal susceptibility testing was performed against antifungals using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. In addition, genotyping was performed using a short-tandem-repeat (STR) assay of a panel of six microsatellite markers (A. flavus 2A, 2B, 2C, 3A, 3B, and 3C), in order to determine the genetic variation and the potential relationship between clinical and environmental isolates. The geometric means of the minimum inhibitory concentrations/minimum effective concentrations (MICs/MECs) of the antifungals across all isolates were (in increasing order): posaconazole, 0.13 mg/liter; anidulafungin, 0.16 mg/liter; itraconazole, 0.29 mg/liter; caspofungin, 0.42 mg/liter; voriconazole, 0.64 mg/liter; isavuconazole, 1.10 mg/liter; amphotericin B, 3.35 mg/liter; and flucytosine, 62.97 mg/liter. All of the clinical isolates were genetically different. However, an identical microsatellite genotype was found between a clinical isolate and two environmental strains. In conclusion, posaconazole and anidulafungin showed the greatest in vitro activity among systemic azoles and echinocandins, respectively. However, the majority of the A. flavus isolates showed reduced susceptibility to amphotericin B. Antifungal susceptibility of A. flavus was not linked with the clinical or environmental source of isolation. Microsatellite genotyping may suggest an association between clinical and environmental strains, although this requires further investigation.

Candida glabrata oropharyngeal infection in a patient with oral squamous cell carcinoma after COVID-19 infection.

Background and Purpose: The COVID-19 pandemic may be an aggravating risk factor for the delay of the diagnoses of serious illnesses, such as oral squamous cell carcinoma, as well as poor management of patients with underlying morbidities, the onset of oral lesions, and antifungal susceptibility to opportunistic fungal infections. Oral candidiasis is one of the most common oral features of COVID-19. Case Report: This study aimed to report an 83-year-old female diagnosed with oral carcinoma who developed oropharyngeal candidiasis after falling ill with COVID-19. In late 2020, this patient was hospitalized for COVID-19 pneumonia. A fissured tongue with white scars appeared after the COVID-19 recovery that caused pain, dysphasia, and dysarthria. The sequencing result based on the internal transcribed spacer rDNA region confirmed Candida glabrata. Its antifungal susceptibility showed susceptibility to nystatin, fluconazole, and caspofungin, but resistance to the other azoles and amphotericin B. Conclusion: Risk of fungal infections, such as Candida seems to be high in patients with severe COVID-19, mainly affecting the oral mucosa. However, whether they are directly attributed to COVID-19 or other surrounding factors is unknown.

Antifungal Resistance of Clinical Candida albicans Isolates in Iran: A Systematic Review and Meta-Analysis.

Background: The present systematic review aimed to investigate the drug susceptibility patterns of Iranian clinical Candida albicans isolates to antifungal drugs (azoles, polyenes, and echinocandins). Methods: Six electronic databases including "PubMed," "Scopus," "Web of Science," "IranDoc", "SID", and "Magiran" were searched from May 2000 to June 2021. The susceptibility of 6322 C. albicans strains from 19967 patients against 14 antifungal drugs was evaluated according to CLSI method. Results: The pooled prevalence of antifungal resistance ranged from 0% to 26%. The lowest resistance levels among azoles were observed in luliconazole with a frequency of 0% and voriconazole of 3.94%. Conclusion: Due to the emergence of multi-drug resistant C. albicans, rational drug prescription based on the anti-fungal stewardship strategy and therapeutic drug monitoring is warranted.

Confirmation of fifth Candida auris clade by whole genome sequencing.

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.

First report of rhino-orbital mucormycosis caused by Syncephalastrum racemosum in a diabetic patient with COVID-19 in Iran and review of recent literature.

Background and Purpose: Invasive mucormycosis is a rare mycosis that affects most cases of uncontrolled diabetes and has a high mortality rate. Patients with COVID-19 are at high risk of developing invasive mucormycosis due to the consumption of anti-inflammatory drugs such as corticosteroids and dexamethasone. Rhizopus species followed by Rhizomucor spp. and Mucor spp. are the main common etiological agents of rhino-orbital mucormycosis. Therefore, this study aimed to present a case of mucormycosis due to Syncephalastrum racemosum in a diabetic patient with COVID-19 for the first time in Iran. Case report: A 73-year-old diabetic female was referred to Ayatollah Rouhani Hospital in Babol, Iran, with a confirmed COVID-19 diagnosis, based on positive RT-PCR and computed tomography of the lungs. She has received methylprednisolone due to severe lung complications. Nasal involvement and left orbital swelling were observed 20 days after the hospitalization. By sinus endoscopic surgery, debridement was done and histopathology indicated wide hyphae (without septa). The sequenced PCR products displayed Syncephalastrum racemosum. In the antifungal susceptibility test, amphotericin B showed good activity against S. racemosum and the patient survived with timely treatment. Conclusion: This is the first case report of rhino-orbital mucormycosis due to S. racemosum in COVID-19 patient; therefore, S. racemosum can be considered one of the etiological factors of rhino-orbital mucormycosis in COVID-19 cases.

First fluconazole-resistant Candida auris isolated from fungal otitis in Iran.

BACKGROUND AND PURPOSE: Candida auris, as a new characterized pathogenic yeast, has attracted remarkable attention in the recent decade due to its rapid global emergence and multidrug resistance traits. This unique species is able to cause nosocomial outbreaks and tolerate adverse conditions; however, it has been mostly misidentified by conventional methods. CASE REPORT: This report aimed to describe the first fluconazole-resistant case of C. auris otitis in an immunocompetent patient in Iran. The isolate showed minimum inhibitory concentration of ≥ 32 µg/ml for fluconazole; however, the patient was treated with topical clotrimazole and miconazole with no recurrence. CONCLUSION: This was the second strain of C. auris isolated from otitis in Iran which was fluconazole-resistant, unlike the first Iranian isolate.

Role of Clotrimazole in Prevention of Recurrent Otomycosis.

Otomycosis is one of the relatively common diseases in the world which is caused by different fungi especially saprophytes. Concerning the relapse of this disease in a number of individuals, the present study was performed to evaluate the inhibitory effect of clotrimazole drop in the relapse of otomycosis. Clinical samples were taken by an ENT specialist from patients suspicious of having otomycosis. A part of these samples were stained, and others were cultured. The diagnosis of otomycosis was made on the basis of the recognizable and characteristic appearance of fungal hyphae or mycelium and fruiting bodies and/or conidiophores under microscopic examination. Patients with suspected otomycosis are not at risk of recurrence after treatment with clotrimazole drops. Out of the 161 individuals in whom definite diagnosis of otomycosis was made, the most affected individuals were, in the age range of 40-49 years, women, urban citizens, and housewives. Pruritus and diminished hearing were the main complaints of the patients. Aspergillus niger and A. flavus as well as Candida albicans were the main causes of the disease. The relapse of disease was observed in only five patients (3.1%), where A. niger was the main fungus. Most relapses were observed in women and in those with diminished hearing, manipulating the ears, ulcers in the canal, and tympanum. Our results suggested that usage of clotrimazole can be effective in reducing the relapse of otomycosis, and concerning the high cost of treating otomycosis while the low cost of using clotrimazole, usage of this drop is recommended to reduce the relapse of otomycosis.

Identification of clinical dermatophyte isolates obtained from Iran by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND AND PURPOSE: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is widely used to discriminate among pathogenic microorganisms in clinical laboratories. The aim of this study was to assess the utility of MALDI-TOF MS in the routine identification of clinical dermatophyte isolates obtained from various geographical regions of Iran. MATERIALS AND METHODS: A total of 94 isolates, including Trichophyton interdigitale (n=44), T. rubrum (n=40), T. tonsurans (n=4), Microsporum canis (n=4), and Epidermophyton floccosum (n=1), were analyzed in this study. The identity of each isolate was determined by polymerase chani reaction amplification and sequencing of the internal transcribed spacer (ITS) region of nuclear-encoded ribosomal DNA and also MALDI-TOF MS. The obtained data by molecular approach were compared with MALDI-TOF MS. RESULTS: The MALDI-TOF MS led to the identification of 44 (47%) isolates at the species level by generating the spectral score values of ≥ 2.0. However, there was not sufficient agreement between the results of the molecular-based ITS identification methods and MALDI-TOF MS in the species identification of 16 (17%) isolates. The Bruker Daltonics database was also not able to identify protein spectra related to 12 isolates (13%), including T. interdigitale (n=5), T. rubrum (n=4), M. canis (n=2), and T. tonsurans (n=1). CONCLUSION: According to the results, the utility of MALDI-TOF MS as a routine diagnostic tool for the accurate and reliable identification of dermatophytes can be justified whenever the protein spectra of a large set of worldwide clinical isolates are included in the commercial libraries. In addition, MALDI-TOF MS can be alternatively used to construct an in-house reference database.

Effect of combination therapy with ceftizoxime and clotrimazole in the treatment of otomycosis.

BACKGROUND AND PURPOSE: There are controversial findings regarding the efficacy of antifungal drugs in the treatment of a ruptured eardrum following fungal infections. Regarding this, the aim of the present study was to evaluate the therapeutic effect of the co-administration of antifungal and antibacterial agents in the treatment of otomycosis with tympanic membrane perforation. MATERIALS AND METHODS: This analytical, clinical trial was conducted on 87 patients with otomycosis showing no bacterial elements in the direct observation and culture. The study population was assigned into two groups of intervention (n=45) and control (n=42). The demographic and clinical data, as well as the data related to the direct observation and culture of the ear samples were recorded in a checklist. All statistical analysis was performed in SPSS (version 24). RESULTS: The most prevalent symptoms in both groups were hearing loss and itching, and the most common finding was secretion. Aspergillus and Candida were the most frequent fungi isolated from the samples. After the implementation of combination therapy, the intervention group demonstrated a significant decrease in symptoms and signs, compared to the control group (P=0.005). CONCLUSION: The findings of the present study indicated that the use combination therapy with ceftizoxime powder and clotrimazole ointment was effective the in treatment of the patients with tympanic membrane rupture showing no bacterial effects in direct examination and culture.

In Vitro Antifungal Susceptibility of Candida Species Isolated from Iranian Patients with Denture Stomatitis.

BACKGROUND: Candida-associated denture stomatitis (CADS) is a common fungal infection in people who wear dentures. The main objective of this study was to make molecular identification of causative agents of CADS and in vitro antifungal susceptibility testing (AFST) in the Iranian patients with denture stomatitis. METHODS: A total of 134 Candida spp. were obtained from patients with denture stomatitis. The Candida spp. were identified using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) involving the universal internal transcribed spacer (ITS1 and ITS4) primers, which were subjected to digestion with MspI and BlnI restriction enzymes. The in vitro antifungal susceptibility of Candida spp. to fluconazole (FLC), terbinafine (TRB), itraconazole (ITC), voriconazole (VRC), posaconazole (POS), ketoconazole (KET), amphotericin B (AMB), and caspofungin (CAS) was evaluated using the Clinical and Laboratory Standards Institute M27-A3 and M27-S4 guidelines. RESULTS: Overall, C. albicans was the most commonly isolated species (n = 84; 62.6%), followed by C. glabrata (n = 23; 17.2%), C. tropicalis (n = 16; 12%), and C. parapsilosis (n = 11; 8.2%). Posaconazole had the lowest geometric mean minimum inhibitory concentration (MIC) (0.03 µg/ml), followed by AMB (0.05 µg/ml), ITC (0.08 µg/ml), VRC (0.11 µg/ml), CAS (0.12 µg/ml), KET (0.15 µg/ml), and FLC (0.26 µg/ml). DISCUSSION: Our study showed that C. albicans was most prevalent in Iranian patients with CADS and was susceptible to both azoles and amphotericin B. In addition, POS could be an appropriate alternative to the current antifungal agents used for the treatment of CADS, as well as in the treatment of recurrent candidiasis.