In-vivo efficiency of the novel azole compounds (ATTAF-1 and ATTAF-2) against systemic candidiasis in a murine model.

BACKGROUND: Antifungal resistance is the main health concern in the control of invasive fungal infections. This research was designed to further assess the antifungal activity of aryl-1,2,4-triazole-3-ylthio analogs of fluconazole (ATTAFs) against Candida albicans systemic candidiasis in the murine model. MATERIALS & METHODS: The murine model of systemic candidiasis was designed via the inoculation of 1 × 106 CFU of Candida albicans. The treatment dosages of 3.5 and 35 mg/kg per day were selected for ATTAFs and fluconazole, respectively. The median survival time (MST) was assayed for 30 days post-infection. The quantitative and qualitative (via histopathology staining) fungal burden was also assessed. Furthermore, immunohistochemistry and biochemistry assays were performed to monitor anti-inflammatory activity using the Cyclooxygenase-2 (Cox-2) marker and changes in serum protein levels. RESULTS: ATTAFs considerably improved the survival of the murine model (P < 0.003). Compared with fluconazole, the antifungal activity of ATTAFs and their MST showed no difference (P > 0.05). However, these compounds decreased the fungal burden in the kidneys, spleen, and liver. CONCLUSION: Our research indicates that ATTAF-1 and ATTAF-2 are effective therapeutic agents due to their fungal clearing and increasing the MST in the murine model of systemic candidiasis. Although we concluded that these components are novel and promising candidates for the management of invasive candidiasis, further studies are warranted to correlate these findings with clinical outcomes.

Fatal pulmonary Scedosporium aurantiacum infection in a patient after near-drowning: A case report.

Background and Purpose: Scedosporium spp. is a saprophytic fungus that may cause invasive pulmonary infection due to the aspiration of contaminated water in both immunosuppressed and immunocompetent hosts. Case report: Herein, we report a fatal case of pulmonary infection caused by Scedosporium species associated with a car crash and near-drowning in a sewage canal. Scedosporium aurantiacum isolated from bronchoalveolar lavage was identified by PCR-sequencing of ß-tubulin genes. The minimum inhibitory concentration values for amphotericin B, itraconazole, posaconazole, isavuconazole were >16 µg/ml, and >8 µg/ml for anidulafungin, micafungin, and caspofungin. Voriconazole was found to be the most active agent with a MIC of 1 µg/ml. Conclusion: This report, as the first case of pulmonary scedosporiosis after near-drowning in Iran, highlights the importance of high suspicion in near-drowning victims, prompt identification of Scedosporium spp., and early initiation of appropriate antifungal therapy.

In Vitro Susceptibility and Trailing Growth Effect of Clinical Isolates of Candida Species to Azole Drugs.

BACKGROUND: Emergence of resistance to respective antifungal drugs is a primary concern for the treatment of candidiasis. Hence, determining antifungal susceptibility of the isolated yeasts is of special importance for effective therapy. For this purpose, the clinical laboratory standard institute (CLSI) has introduced a broth microdilution method to determine minimum inhibitory concentration (MIC). However, the so-called "Trailing effect" phenomenon might sometimes pose ambiguity in the interpretation of the results. OBJECTIVES: The present study aimed to determine the in vitro susceptibility of clinical isolates of Candida against azoles and the frequency of the Trailing effect. MATERIALS AND METHODS: A total of 193 Candida isolates were prospectively collected and identified through the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Using a broth microdilution test, according to the guidelines of CLSI M27-A3, antifungal susceptibilities of the isolated yeasts against Fluconazole (FLU), Itraconazole (ITR), Ketoconazole (KET) and Voriconazole (VOR) were assessed. Moreover, trailing growth was determined when a susceptible MIC was incubated for 24 hours, and turned into a resistant one after 48 hours of incubation. RESULTS: Among the tested antifungal drugs in this study, the highest rate of resistance was observed against ITR (28.5%) followed by VOR (26.4%), FLU (20.8%) and KET (1.5%). The trailing effect was induced in 27 isolates (14.0%) by VOR, in 26 isolates (13.5%) by ITR, in 24 isolates (12.4%) by FLU, and in 19 isolates (9.8%) by KET. CONCLUSIONS: The monitoring of antifungal susceptibilities of Candida species isolated from clinical sources is highly recommended for the efficient management of patients. Moreover, the trailing effect should be taken into consideration once the interpretation of the results is intended.