High frequency of Candida krusei colonization in critically ill pediatrics: A cross-sectional study in children's medical center, Tehran, Iran.

Background and Purpose: This study aimed to evaluate the species distribution and susceptibility pattern of the strains isolated from Candida colonization in pediatric patients staying at pediatric intensive care unit (ICU) and infant ICU of Children's Medical Center in Tehran, Iran. Materials and Methods: This study was conducted in the Children's Medical Center in Tehran, Iran. In total, 440 samples from 56 patients with oral cavity, skin surrounded catheters, and ear, throat, nasal, and urine cultures were collected. All patients were evaluated in terms of Candida colonization on the admission day as well as the days 7, 14, and 28 according to the previous studies. CHROMagar Candida medium was applied for primary/multiple species identification and the isolates were identified by using polymerase chain reaction-based methods to the species-specific complex level. The antifungal susceptibility test was performed according to the Clinical and Laboratory Standards protocol published as M27-A3 and M60 documents. Results: In total, 136 yeast samples from 26 individuals (30.9%) out of 440 samples were considered colonization. The most prevalent species in IICU was C. albicans (27%, n=20) followed by C. krusei (24 %, n=18) and C. parapsilosis (16%, n=12). In PICU, the predominant species was C. krusei (40%, n=24) followed by C. parapsilosis (18%, n=11) and C. dubliniensis (16%, n=10). Among the 40 tested isolates from both units, fluconazole-resistant isolates (n=11, 8.15%) were determined according to the new breakpoints. In the case of echinocandins, 2 isolates, including C. albicans (n=1) and C. krusei (n=1) were resistant against both caspofungin and anidulafungin (totally 1.48%). Conclusion: In the present study, since C. krusei is intrinsically-resistance against fluconazole, emphasizing the importance of species-level identification of Candida isolates is outstanding. However, according to the antifungal susceptibility testing results, only 7.2% of the strains were resistant to fluconazole. It would be beneficial to monitor the ICU patients who are at high risk of invasive Candida infection.

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.

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.

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.

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.