Central nervous system Aspergillus quadrilineatus infection in a COVID-19 patient, a case report and literature review.

BACKGROUND: Viral pneumonia such as COVID-19-associated aspergillosis could increase susceptibility to fungal super-infections in critically ill patients. METHODS: Here we report a pediatric case of Aspergillus quadrilineatus cerebral infection in a recently diagnosed COVID-19-positive patient underlying acute lymphocytic leukemia. Morphological, molecular methods, and sequencing were used to identify this emerging species. RESULTS: Histopathological examination showed a granulomatous necrotic area containing dichotomously branching septate hyphae indicating a presumptive Aspergillus structure. The species-level identity of isolate growing on brain biopsy culture was confirmed by PCR sequencing of the ß-tubulin gene as A. quadrilineatus. Using the CLSI M38-A3 broth microdilution methodology, the in vitro antifungal susceptibility testing demonstrated 0.032 µg/mL MIC for posaconazole, caspofungin, and anidulafungin and 8 µg/mL against amphotericin B. A combination of intravenous liposomal amphotericin B and caspofungin therapy for 8 days did not improve the patient's condition. The patient gradually continued to deteriorate and expired. CONCLUSIONS: This is the first COVID-19-associated cerebral aspergillosis due to A. quadrilineatus in a pediatric patient with acute lymphocytic leukemia. However, comprehensive screening studies are highly recommended to evaluate its frequency and antifungal susceptibility profiles. Before being recommended as first-line therapy in high-risk patients, more antifungal susceptibility data are needed.

Potential Inhibitory Effect of Miltefosine against Terbinafine-Resistant Trichophyton indotineae.

Several prolonged and significant outbreaks of dermatophytosis caused by Trichophyton indotineae, a new emerging terbinafine-resistant species, have been ongoing in India in recent years, and have since spread to various countries outside Asia. Miltefosine, an alkylphosphocholine, is the most recently approved drug for the treatment of both visceral and cutaneous leishmaniasis. Miltefosine in vitro activity against terbinafine-resistant and susceptible T. mentagrophytes/T. interdigitale species complex, including T. indotineae, is limited. The current study aimed to assess miltefosine's in vitro activity against dermatophyte isolates, which are the most common causes of dermatophytosis. Miltefosine, terbinafine, butenafine, tolnaftate, and itraconazole susceptibility testing was performed using Clinical and Laboratory Standards Institute broth microdilution methods (CLSI M38-A3) against 40 terbinafine-resistant T. indotineae isolates and 40 terbinafine-susceptible T. mentagrophytes/T. interdigitale species complex isolates. Miltefosine had MIC ranges of 0.063-0.5 µg/mL and 0.125-0.25 µg/mL against both terbinafine-resistant and susceptible isolates. In terbinafine-resistant isolates, the MIC50 and MIC90 were 0.125 µg/mL and 0.25 µg/mL, respectively, and 0.25 µg/mL in susceptible isolates. Miltefosine had statistically significant differences in MIC results when compared to other antifungal agents (p-value 0.05) in terbinafine-resistant strains. Accordingly, the findings suggest that miltefosine has a potential activity for treating infections caused by terbinafine-resistant T. indotineae. However, further studies are needed to determine how well this in vitro activity translates into in vivo efficacy.

In Vitro Combination of Terbinafine with Ketoconazole Against Aspergillus Species with Terbinafine High MIC Values Isolated From Otomycosis.

Otomycosis is a common mycotic infection of the external auditory canal, and Aspergillus species are one of the most frequent causative agents worldwide. The limited antifungal arsenal, the high toxicity and side effects of antifungal agents, and the growing resistance to the currently available antifungals underscore the need for new therapeutic strategies. The present study aimed to evaluate the combined in vitro efficacy of terbinafine and ketoconazole against Aspergillus species with terbinafine high MIC values isolated from patients with otomycosis.84 Aspergillus species with high MIC values to terbinafine (≥ 4 µg/ml), consisting of A. flavus, A. tubingensis, A. niger, and A. terreus, were included in this study. The checkerboard microdilution method evaluated the in vitro interactions using the CLSI reference technique. Synergistic effects were observed for 66.67% (56/84) of all isolates (FICI ranging from 0.19 to 0.5). However, the interactions of terbinafine and ketoconazole exhibited indifference in 33.33% (28/84) of the isolates, and no antagonism was observed for any combination. The interaction of terbinafine and ketoconazole showed synergistic activity against Aspergillus species with high MIC values, suggesting that this is an alternative and promising approach for treating otomycosis.