First azole-resistant Aspergillus fumigatus isolates with the environmental TR46 /Y121F/T289A mutation in Iran.

BACKGROUND: Azole resistance in Aspergillus fumigatus is an emerging problem and reported from all continents. As triazole antifungals are the mainstay of therapy in the management of invasive aspergillosis, azole-resistant A fumigatus has become a major medical concern and with complicated clinical management. OBJECTIVE: Screening of environmental presence of azole-resistant A fumigatus in Iran. METHODS: Compost from Northern Iran, collected between 2017 and 2018, was screened for the presence of azole-resistant A fumigatus with azole-containing agar. Phenotypic MICs were obtained from selected, molecularly confirmed isolates. cyp51A gene sequencing and genotyping of azole-resistant isolates were done. RESULTS: Among 300 compost samples, three A fumigatus isolates had high voriconazole MICs (≥16 mg/L) and harboured the TR46 /Y121F/T289A mutation in the cyp51A gene. Microsatellite typing of these isolates showed that two strains had the same allele across all nine examined microsatellite loci and were genotypically related to Indian azole-resistant strains. The other isolate had a different genotype. CONCLUSION: This is the first report of A fumigatus with TR46 /Y121F/T289A mutation from the region. Monitoring and surveillance of antifungal susceptibility of clinical A fumigatus is warranted in Iran and elsewhere in the region.

Expression Patterns of ABC Transporter Genes in Fluconazole-Resistant Candida glabrata.

Clinical management of fungal diseases is compromised by the emergence of antifungal drug resistance in fungi, which leads to elimination of available drug classes as treatment options. An understanding of antifungal resistance at molecular level is, therefore, essential for the development of strategies to combat the resistance. This study presents the assessment of molecular mechanisms associated with fluconazole resistance in clinical Candida glabrata isolates originated from Iran. Taking seven distinct fluconazole-resistant C. glabrata isolates, real-time PCRs were performed to evaluate the alternations in the regulation of the genes involved in drug efflux including CgCDR1, CgCDR2, CgSNQ2, and CgERG11. Gain-of-function (GOF) mutations in CgPDR1 alleles were determined by DNA sequencing. Cross-resistance to fluconazole, itraconazole, and voriconazole was observed in 2.5 % of the isolates. In the present study, six amino acid substitutions were identified in CgPdr1, among which W297R, T588A, and F575L were previously reported, whereas D243N, H576Y, and P915R are novel. CgCDR1 overexpression was observed in 57.1 % of resistant isolates. However, CgCDR2 was not co-expressed with CgCDR1. CgSNQ2 was upregulated in 71.4 % of the cases. CgERG11 overexpression does not seem to be associated with azole resistance, except for isolates that exhibited azole cross-resistance. The pattern of efflux pump gene upregulation was associated with GOF mutations observed in CgPDR1. These results showed that drug efflux mediated by adenosine-5-triphosphate (ATP)-binding cassette transporters, especially CgSNQ2 and CgCDR1, is the predominant mechanism of fluconazole resistance in Iranian isolates of C. glabrata. Since some novel GOF mutations were found here, this study also calls for research aimed at investigating other new GOF mutations to reveal the comprehensive understanding about efflux-mediated resistance to azole antifungal agents.

Potent Activities of Novel Imidazoles Lanoconazole and Luliconazole against a Collection of Azole-Resistant and -Susceptible Aspergillus fumigatus Strains.

A collection of azole-susceptible (n = 141) and azole-resistant (n = 27) Aspergillus fumigatus isolates was tested against seven antifungal drugs, including the new imidazoles lanoconazole and luliconazole. The luliconazole and lanoconazole MIC90 values for the azole-susceptible strains were 0.001 µg/ml and 0.008 µg/ml, and those for the azole-resistant strains were 0.016 µg/ml and 0.032 µg/ml.

Genotyping of clinical and environmental Aspergillus flavus isolates from Iran using microsatellites.

Aspergillus flavus is the second most important Aspergillus species causing human infections in tropical countries. Despite an increasing number of infections of A. flavus in Iran, the molecular epidemiology of clinical and environmental strains has not been well studied. We used a panel of nine microsatellite markers to analyse the genetic relatedness of A. flavus. Microsatellite typing of 143 (n = 119 clinical and n = 24 environmental) isolates demonstrated 118 different genotypes. A possible outbreak at a pulmonary ward was discovered. The discriminatory power for the individual markers ranged from 0.4812 to 0.9457 and the panel of all nine markers combined yielded a diversity index of 0.9948. This high-resolution typing method assists in better understanding of the molecular epidemiology of A. flavus.

In Vitro Activities of Five Antifungal Drugs Against Opportunistic Agents of Aspergillus Nigri Complex.

Black aspergilli, particularly Aspergillus niger and A. tubingensis, are the most common etiological agents of otomycosis followed by onychomycosis, pulmonary aspergillosis and aspergilloma. However, so far there is no systematic study on their antifungal susceptibility profiles. A collection of 124 clinical and environmental species of black aspergilli consisted of A. niger, A. tubingensis, A. uvarum. A. acidus and A. sydowii were verified by DNA sequencing of the partial ß-tubulin gene. MICs of amphotericin B, itraconazole, voriconazole, posaconazole, and MECs of caspofungin were performed based on CLSI M38-A2. Posaconazole and caspofungin had the lowest MIC range (0.016-0.125 µg/ml and 0.008-0.031 µg/ml, respectively), followed by amphotericin B (0.25-4 µg/ml), voriconazole (0.125-16 µg/ml) and itraconazole (0.25 to >16) in an increasing order. Some strains of A. niger showed high MIC value for itraconazole and voriconazole (>16 µg/ml), in contrast only environmental isolates of A. tubingensis had high itraconazole MICs (>16 µg/ml). These results confirm that posaconazole and caspofungin are potential drugs for treatment of aspergillosis due to opportunistic agents of Aspergillus Nigri complex. However, in vivo efficacy remains to be determined.

Coinfection of Pulmonary Hydatid Cyst and Aspergilloma: Case Report and Systematic Review.

Aspergilloma infection consists of a mass of fungal hyphae, inflammatory cells, fibrin, mucus, and tissue debris and can colonize lung cavities due to underlying diseases such as tuberculosis, sarcoidosis, bronchiectasis, cavitary lung cancer, neoplasms, ankylosing spondylitis, bronchial cysts, and pulmonary infarction. Here we report coinfection of pulmonary hydatid cyst and aspergilloma in a 34-year-old female who had had history of minor thalassemia and suffered from chest pain, dyspnea, non-productive cough for at least five months, and hemoptysis for 20 days. Radiographic sign showed a large cavitary lesion (5 × 6 × 6 cm) involving left lower lobe (LLL). Dichotomous septate hyphae were observed in bronchoalveolar lavage and biopsy specimens from LLL. The patient subsequently improved after combined anti-helminth therapies with albendazole (400 mg/bd) and lobectomy. According to morphological and molecular characterization, Aspergillus niger was confirmed. In vitro antifungal susceptibility tests revealed that the MIC values for the antifungals used in this case in increasing order were posaconazole (0.125 µg/ml), itraconazole and voriconazole (0.5 µg/ml), and amphotericin B (1 µg/ml). The minimum effective concentration for caspofungin was 0.125 µg/ml. Subsequently, we systematically reviewed 22 confirmed cases of pulmonary hydatid cyst and aspergilloma during a period of 19 years (1995-2014) and discussed the epidemiology, clinical features, and treatment of this disease.

Molecular Characterization of Highly Susceptible Candida africana from Vulvovaginal Candidiasis.

Phylogenetic studies highlight Candida africana as an atypical variant within Candida albicans species complex which is dominantly recovered from vaginal specimens. This study aimed to characterize C. africana isolates from patients with vulvovaginal candidiasis (VVC) by molecular methods and in vitro susceptibilities. One hundred and fifty-six (48.44%) Candida strains were collected from 322 patients diagnosed with VVC. Of these, 114 (73.07%) were germ tube positive and presented green color on the chromogenic medium, thus classified as C. albicans species complex. One hundred and nine (95.61%) out of 114 isolates were identified as C. albicans, while five (4.38%) isolates were identical with C. africana based on hwp1 PCR. C. africana appeared to be highly susceptible to the tested antifungals. For all strains of C. africana, fluconazole MIC was 2-log2-dilution steps less active than amphotericin B, which in turn was 2-log2-dilution steps and 3-log2-dilution steps less active than other azoles and echinocandin agents, respectively. In conclusion, among the C. albicans species complex, C. albicans predominantly and C. africana rarely occur in vaginal mucosa. Due to limited information on molecular epidemiology of this novel yeast, more studies using molecular methods are needed to elucidate the inter- and intraspecific genomic variations of C. africana isolates.

Multi-drug resistance Trichophyton indotineae in a stray dog.

A 2.5-year-old stray dog showed signs of hair loss, mild skin crusting, and redness on extremities and trunk. The etiologic agent was confirmed as Trichophyton indotineae by sequencing of ITS region. Using the Clinical and Laboratory Standards Institute (CLSI M38-A3) guideline, antifungal susceptibility testing showed multidrug resistance phenotype against terbinafine (16 µg/mL-1), itraconazole, and some other tested antifungals (minimum inhibitory concentration, MIC≥16 µg/mL-1). However, luliconazole was found to be active in- vitro (0.016 µg/mL-1). Upon further studies, sequencing of SQLE gene showed an amino acids substitution of Phe397Leu and Ala448Thr, which is potentially linked to terbinafine resistance in Trichophyton species.

Asymptomatic colonization of stray dogs and domestic cats with Trichophyton mentagrophytes II in Northern Iran.

BACKGROUND: Despite changes in the epidemiology of dermatophyte infections, the incidence of fungal infections associated with Trichophyton species still remains high among dogs and cats. The objective of the present study was to isolate and characterize dermatophytes from dogs and cats in Iran. METHOD: From December 2022 to May 2023, skin and hair samples were collected from symptomatic and asymptomatic cats and dogs in Mazandaran, a northern province of Iran. The samples were then inoculated into Mycosel™ Agar. Dermatophyte isolates were identified by sequencing the internal transcribed spacer region. Antifungal susceptibility tests were conducted using the Clinical and Laboratory Standards Institute (CLSI-M38-A3). RESULT: Of the 250 samples collected (from 200 dogs and 50 cats), 20 (from 19 dogs and one cat) (8.0 %) were positive for dermatophyte growth. Based on sequence and phylogenetic analysis, all isolates belonged to T. mentagrophytes II*. Of these positive samples, 14 (70.0 %), 3 (15.0 %), 2 (10.0 %), and 1 (2.0 %) were isolated from asymptomatic stray dogs, symptomatic stray dogs, symptomatic domestic dogs, and symptomatic cats, respectively. Luliconazole and terbinafine displayed potent activity against all T. mentagrophytes isolates, with Minimum inhibitory concentration (MIC) values of 0.016 µg/ml. Miconazole and griseofulvin demonstrated higher MIC (1 and 8 µg/ml). CONCLUSION: The present study indicated that T. mentagrophytes II* asymptomatic carriage is frequent in stray dogs in Iran. The potential risk to public health needs to be evaluated However, T. mentagrophytes genotype VIII, considered as an endemic and emerging human pathogenic clone in several countries, was not detected during the present survey.

Role of nanostructured lipid carriers in the expression alterations of ATP-binding cassette transporter genes in fluconazole-resistant Candida glabrata.

Introduction: This study was proposed to assess the potential role of efflux transporters in reversing fluconazole resistance in Candida glabrata isolates treated with fluconazole loaded nanostructured lipid carriers (FLZ-NLCs). Methods: The ultrasound technique was used to synthesize the FLZ-NLCs. Four fluconazole-resistant, as well as one susceptible standard C. glabrata isolates, were applied and exposed to FLZ/ FLZ-NLCs for 20 h at 37°C. Real-time PCRs were done to estimate the likely changes in ATP-binding cassette transporter genes. Results: Similar to the FLZ-exposed-susceptible standard strain which showed no alteration, the genes were not up-regulated significantly under the FLZ-NLCs treated condition. While they were over-expressed when the yeasts were treated with fluconazole. Conclusion: It is highly suggested that due to the nature of the NLCs which shields the whole conformation of the drug, FLZ is not recognized by the efflux transporter subunits and consequently the translocation would not happen.

Caspian Sea Mycosands: The Variety and Abundance of Medically Important Fungi in Beach Sand and Water.

Samples from a total of 67 stations, distributed amongst 32 cities along the Caspian Sea coastline, were collected during the summer of 2021 on sunny days. The samples were collected from each station, including both dry/wet sand and shoreline water. The grown samples were primarily analyzed for the macro/microscopic morphologic features of the fungi. Moreover, identification by PCR-RFLP was performed for yeasts, dermatophytes, and Aspergillus sp. strains. Antifungal susceptibility tests were performed for probable-isolated Aspergillus and Candida sp. A total of 268 samples were collected, from which 181 (67.54%) isolates were recovered. Yeast-like fungi and potential pathogenic black fungi were detected in 12 (6.6%) and 20 (11%) of the sand (dry/wet) samples. Potential pathogenic hyaline fungi were identified in 136 (75.1%) samples, in which Aspergillus sp. was the predominant genus and was detected in 76/136 (47.8%) samples as follows: A. section Flavi n = 44/76 (57.9%), A. section Nigri n = 19/76 (25%), A. section Nidulantes n = 9/76 (11.8%), and A. section Fumigati n = 4/76 (5.3%). The most effective azole antifungal agent was different per section: in A. section Fumigati, PSZ; in Aspergillus section Nigri, ITZ and ISZ; in A. section Flavi, EFZ; and in A. section Nidulantes, ISZ. Candida isolates were susceptible to the antifungals tested.

Evaluation of Candida colonization index, molecular identification, and antifungal susceptibility pattern of Candida species isolated from critically ill pediatric patients: A single-center study in Iran.

Background and Purpose: Given the high mortality rate of invasive candidiasis in hospitalized pediatric patients, it is crucial to establish a predictive system to achieve early diagnosis and treatment of patients who are likely to benefit from early antifungal treatment. This study aimed to assess the Candida colonization index, species distribution, and antifungal susceptibility pattern of Candida strains isolated from pediatric patients with high Candida colonization index (CI). Materials and Methods: This study was carried out at the Children's Medical Center in Tehran-Iran. In total, 661 samples were collected from 83 patients. The Candida CI was calculated according to the descriptions of previous studies. The isolates were identified using polymerase chain reaction-based techniques. The Clinical and Laboratory Standard Institute protocol M60 was used to conduct the antifungal susceptibility test. Results: A colonization index greater than 0.5 was confirmed in 29 cases (58% of positive samples) with two children developing candidemia. Candida albicans (n=53, 49.5%) was the most common Candida species in patients with CI > 0.5. Except for acute lymphoblastic leukemia, no risk factors were linked to a high index in colonized children (P > 0.05). Twelve isolates (7.01%) were multi-azole resistant with high MICs against both isavuconazole and ravuconazole and seven strains (4.09%) were echinocandins resistant. Conclusion: In pediatric intensive care units, patients are at risk of fungal infection, particularly candidemia. In this study, more than half of the children with positive yeast cultures had CI > 0.5, and 6.8% developed candidemia.

Molecular typing of clinical and environmental Aspergillus fumigatus isolates from Iran using microsatellites.

BACKGROUND AND PURPOSE: Because of the growing incidence of Aspergillus infection, typing methods of Aspergillus species are increasingly being used. Accordingly, studying the spread and population dynamics of strains isolating from clinical and environment, from a single host to large-scale ecosystems is definitely needed. In the current study, we carried out a genetic analysis of nine microsatellite loci in isolates from different regions of Iran to compare and explore the genetic diversity between environmental and clinical A. fumigatus strains. MATERIALS AND METHODS: Sixty-six clinical (n=43) and environmental (n= 23) isolates of A. fumigatus, have collected from six cities of Iran. All A. fumigatus isolates identified based on macroscopic and microscopic characters, the ability to grow at above 45°C, and confirmed using DNA sequencing of the partial b-tubulin gene. Sixty-six A. fumigatus isolates were subjected by microsatellite typing using three separate multiplex PCRs with a panel of nine short tandem repeats (STR) to evaluate the genetic relatedness. RESULTS: The STR typing of 66 A. fumigatus isolates revealed 38 distinct genotypes distributed among environmental and clinical isolates. We identified 12 clones including 40 different isolates representing 60% of all isolates tested, which each clone included 2-7 isolates. CONCLUSION: The STR typing is considered as a valuable tool with excellent discriminatory power to study the molecular epidemiology and genotypic diversity of A. fumigatus isolates. These findings show that the high genetic diversity observed of Iranian A. fumigatus isolates with those outside Iran and formed a separate cluster.

In vitro interaction between glabridin and voriconazole against Aspergillus fumigatus isolates.

BACKGROUND: Voriconazole (VRC) is widely recommended as the first-line therapy for invasive aspergillosis. However, surveillance studies have demonstrated that there is an increase in the frequency of azole resistance among Aspergillus fumigates isolates. In recent years, more studies on effective synergisms between natural agents and antifungal drugs have been published. AIMS: To evaluate the synergistic antifungal effect of glabridin (Gla) and VRC against A. fumigatus isolates. METHODS: Potential interactions between Gla and VRC were studied by using a microdilution checkerboard method based on the CLSI reference technique. To assess the interaction of drugs the fractional inhibitory concentration index (FICI) was calculated based on the Loewe Additivity model. RESULTS: The minimum inhibitory concentrations (MIC) obtained with Gla alone were relatively high (MIC50 16µg/ml). However, our results showed synergistic interaction between Gla and VRC against A. fumigatus strains, with FICI range values between 0.15 and 0.5. CONCLUSIONS: Synergistic activity of Gla and VRC against both VRC-sensitive and -resistant A. fumigatus isolates may lead to design new antifungal agents, especially for inhibiting those azole-resistant strains.

Overexpression of Efflux Pump Genes is an Alternative Mechanism in Voriconazole Resistant Aspergillus fumigatus isolates Without Relative Mutations in CYP5A.

BACKGROUND: The overexpression of the efflux transporter genes is one of the important mechanisms of resistance in fungal pathogens such as Candida and Aspergillus species. OBJECTIVE: Here, the expression alterations of drug efflux transporter genes were evaluated in non- Cyp51A voriconazole-resistant Aspergillus fumigatus isolates. METHODS: Six A. fumigatus isolates including four voriconazole-resistant isolates with and without azole-resistance-related mutations in addition to two susceptible A. fumigatus isolates were selected from 300 previously characterized A. fumigatus clinical and environmental isolates, received during 2013-2015. In order to extract RNA, the minimum inhibitory concentrations (MICs) for the isolates were determined according to the broth microdilution protocol regarding the Clinical and Laboratory Standards Institute document M38-A2 (CLSI, 2008). Alteration in the expression of AfuMDR1, AfuMDR2, AfuMDR3, AfuMDR4, Cyp51A, and atrF was studied using the real-time polymerase chain reaction assay. RESULTS: Based on REST® output, significant overexpression of atrF, AfuMDR1, AfuMDR3, and AfuMDR4/Cyp51A, atrF, AfuMDR2, AfuMDR4 genes was observed in the isolates without azoleresistance- related mutations, respectively. No significant overexpression was seen in the isolates with T34/L98H except for the AfuMDR3 and AfuMDR4(P<0.05). CONCLUSION: Our results support the hypothesis that efflux pump transporters can contribute to voriconazole resistance in A. fumigatus.

Clonal Expansion of Environmental Triazole Resistant Aspergillus fumigatus in Iran.

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.

Hazard of agricultural triazole fungicide: Does cyproconazole induce voriconazole resistance in Aspergillus fumigatus isolates?

BACKGROUND AND PURPOSE: The present study aimed to evaluate the effect of cyproconazole, the most used fungicide in Iranian wheat farms, on the induction of voriconazole resistance in Aspergillus fumigatus isolates. MATERIALS AND METHODS: A collection of 20 clinical and environmental isolates were selected for investigation of the in vitro activity of fungicides. The minimum inhibitory concentrations (MICs) were determined by the documented broth microdilution method M38-A2 (CLSI, 2008). Induction experiments were performed and the possibly induced isolate(s) were subjected to antifungal susceptibility testing, sequencing of the CYP51A promoter, and full coding gene. Furthermore, CYP51-protein homology modeling and docking modes were evaluated using SWISS-MODEL (https://swissmodel.expasy.org/) and SEESAR software (version 9.1). RESULTS: Among 10 susceptible isolates, only one strain showed a high MIC value against voriconazole (MIC=4µg/ml) after 25 passages. Nevertheless, sequencing of the CYP51A promoter and full coding gene did not reveal any mutations. Cyproconazole, which has three nitrogen atoms in the aromatic ring, coordinated to the iron atom of heme through a hydrogen bond contact to residue Lys147 present in the active site of the A. fumigates Cyp51 homology model. CONCLUSION: Cyproconazole is being applied extensively in wheat farms in Iran. According to the results, cyproconazole may not play a key role in the induction of azole resistance in the isolates through the environmental route. However, the potential ability of the fungicide to induce medically triazole-resistant strains over a long period of application should not be neglected.

Echinocandin resistance in Candida parapsilosis sensu stricto: Role of alterations in CHS3, FKS1 and Rho gene expression.

OBJECTIVES: The rate of resistance of Candida parapsilosis to echinocandins remains unexplored in Iran. The main aims of this study were to investigate the susceptibility patterns and possible mechanisms of echinocandin resistance in echinocandin-resistant clinical C. parapsilosis isolates in Iran. METHODS: A total of 105 isolates of C. parapsilosis sensu stricto underwent antifungal susceptibility testing to echinocandins by the broth microdilution reference method. Sequences of the CpERG3 and CpFKS1 genes were analysed using MEGA6 software, and alterations in CHS3, FKS1 and Rho gene expression were evaluated by quantitative reverse transcription (RT-qPCR). REST® software was used to analyse the results. RESULTS: The rate of echinocandin cross-resistance was 2.9% (3/105). No substitutions were detected in Fks1p except for the naturally occurring P660A amino acid substitution observed in isolates both with high and low minimum inhibitory concentrations (MICs). Moreover, the G111R amino acid substitution was not found in Erg3p. Following echinocandin exposure, expression of Rho and FKS1 genes was significantly increased in resistant isolates, whilst the CHS3 gene showed no change. CONCLUSION: Alterations in the expression of some key genes may be responsible for echinocandin resistance among C. parapsilosis isolates. Understanding the mechanisms responsible for drug resistance in C. parapsilosis is not only crucial for the development of new antifungals but is also important in choosing appropriate antifungals for patient treatment at the earliest stage.

An update on the application of nano-scaled carriers against fluconazole-resistant Candida species: nanostructured lipid carriers or solid lipid nanoparticles?

BACKGROUND AND PURPOSE: Encapsulation can lead to improved efficacy and safety of antifungal compounds. The attention of scientists has recently turned to biocompatible lipids as the carriers for the delivery of antifungal drugs, such as fluconazole. Although several research reports have already been published on fluconazole loaded solid lipid nanoparticles (FLZ-SLNs) and fluconazole loaded nanostructured lipid carriers (FLZ-NLCs), the possible advantages of NLCs over SLNs have not yet been fully established. Studies performed so far have given several contradictory results. MATERIALS AND METHODS: Both formulations of fluconazole were synthesized using probe ultrasonication method and the characteristics were analyzed. Antifungal susceptibility testing (AFST) was performed with FLZ, FLZ-SLNs, and FLZ-NLCs using CLSI document M60 against some common fluconazole-resistant Candida species. RESULTS: A significant decrease was observed in minimum inhibitory concentration values when both formulations were applied. Nonetheless, FLZ-NLCs were significantly more effective (P<0.05). However, three species groups were not statistically different in terms of the activity of FLZ-NLCs. CONCLUSION: Based on the obtained results, FLZ-NLCs could reverse the azole-resistance phenomenon in the most common Candida species more effectively, as compared to FLZ-SLNs.

High prevalence of itraconazole resistance among Candida parapsilosis isolated from Iran.

BACKGROUND AND PURPOSE: Candida parapsilosis isolates usually have a low minimum inhibitory concentration (MIC) against azoles. Although Candida parapsilosis isolates usually have low MICs against azoles, recent studies candida invasive infections due to azole resistant-C. parapsilosis isolates . Regarding this, the main aim of this study was to determine the susceptibility pattern of Iranian clinical C. parapsilosis against available azole antifungal drugs. MATERIALS AND METHODS: This study was conducted on 105 previously-identified isolates of C. parapsilosis sensu stricto. For the purpose of the study, the isolates were subjected to antifungal susceptibility testing against fluconazole (FLZ), itraconazole (ITZ), voriconazole (VRZ), and two new azole drugs, namely luliconazole (LUZU) and lanoconazole (LZN). The broth microdilution reference method adopted in this study was according to the Clinical & Laboratory Standards Institute M27-A3 and M27-S4 documents. RESULTS: According to the results, 89% (n=94) of C. parapsilosis isolates showed a MIC of ≥ 1 µg/ml, indicating resistance against ITZ. Multi-azole resistance was observed in 3.8% of the isolates. In addition, LUZU and LZN demonstrated the highest efficacy with the MIC50 values of 0.5 and 1 µg/ml, respectively. CONCLUSION: The majority of the isolates showed high MIC values against ITZ. This may have been associated with the long-term ITZ prophylaxis/therapy in patients infected with candidiasis. Hence, the adoption of an appropriate antifungal agent is a crucial step for starting the treatment.