An overview of COVID-19 related to fungal infections: what do we know after the first year of pandemic?

In 2019, severe acute respiratory syndrome caused by CoV-2 virus became a pandemic worldwide, being the fast spread of the disease due to the movement of infected people from one country to another, from one continent to another, or within the same country. Associated comorbidities are important factors that predispose to any fungal coinfections. Because of the importance of fungal infections in COVID-19 patients, the aim of this work was to collect data of the more encountered mycoses related to patients undergoing this disease. Aspergillosis was the first COVID-19-related fungal infection reported, being A. fumigatus the most frequent species for CAPA. Other fungal infections related include mainly candidiasis and mucormycosis, being Rhizopus spp. the more prevalent species found. Influenza-associated pulmonary aspergillosis is well documented; thus, similar complications are expected in severe forms of COVID-19 pneumonia. Therefore, in patients with COVID-19, it is important to take special attention to the surveillance and suspicion of fungal coinfections that might worsen the patient's prognosis.

Combination of Amphotericin B and Terbinafine against Melanized Fungi Associated with Chromoblastomycosis.

Our in vitro studies showed that a combination of amphotericin B and terbinafine had synergistic effects against the majority of melanized fungi associated with chromoblastomycosis (CBM) and similar infections, including those with Cladophialophora carrionii, Cladophialophora arxii, Exophialadermatitidis, Exophialaspinifera, Fonsecaea monophora, Fonsecaea nubica, Fonsecaea pedrosoi, and Phialophora verrucosa. This drug combination could provide an option for the treatment of severe or unresponsive cases of CBM, particularly in cases due to species of Fonsecaea and Cladophialophora.

Combination of Amphotericin B and Flucytosine against Neurotropic Species of Melanized Fungi Causing Primary Cerebral Phaeohyphomycosis.

Primary central nervous system phaeohyphomycosis is a fatal fungal infection due mainly to the neurotropic melanized fungiCladophialophora bantiana,Rhinocladiella mackenziei, andExophiala dermatitidis.Despite the combination of surgery with antifungal treatment, the prognosis continues to be poor, with mortality rates ranging from 50 to 70%. Therefore, a search for a more-appropriate therapeutic approach is urgently needed. Ourin vitrostudies showed that with the combination of amphotericin B and flucytosine against these species, the median fractional inhibitory concentration (FIC) indices for strains ranged from 0.25 to 0.38, indicating synergy. By use of Bliss independence analysis, a significant degree of synergy was confirmed for all strains, with the sum ΔE ranging from 90.2 to 698.61%. No antagonism was observed. These results indicate that amphotericin B, in combination with flucytosine, may have a role in the treatment of primary cerebral infections caused by melanized fungi belonging to the orderChaetothyriales Furtherin vivostudies and clinical investigations to elucidate and confirm these observations are warranted.

In vitro activity of antifungal drugs against Cladophialophora species associated with human chromoblastomycosis.

The antifungal activity of six drugs was evaluated against 41 clinical and environmental isolates of Cladophialophora carrionii and its sister species C. yegresii. Drugs tested, including their ranges, were: 16-0.016 microg/ml for amphotericin B (AMB), itraconazole (ITZ) and voriconazole (VCZ), 8-0.008 microg/ml for terbinafine (TBF), and 64-0.063 microg/ml for flucytosin (5-FC) and fluconazole (FCZ). Strains were tested according to the CLSI guidelines (M38A). The MIC Gmeans for clinical strains in microg/ml were; 0.02 for TBF and ITZ, 0.07 microg/ml for VCZ, 0.49 for 5FC, 6.14 for FCZ and 9.42 for AMB. The MFC Gmeans in microg/ml were; 0.04 for TBF, 0.13 for ITZ, 0.72 for VCZ, 18.83 for 5FC, 36.16 for FCZ and 31.35 for AMB. The most active drugs against the fungi were TBF, ITZ, VCZ and 5FC. However, for all drugs more than two dilution steps were noted between the MIC and the MFC, indicating fungistatic activity. Despite in vitro susceptibility of C. carrionii to antifungal agents, the efficacy of therapy was shown to be not optimal.

Tinea nigra palmaris: presentación de un caso clínico en la República Argentina

Se presenta el caso clínico de una paciente que consultó por una mancha oscura en la palma izquierda. El examen micológico permitió determinar que la infección había sido producida por un hongo pigmentado, Hortaea werneckii, agente etiológico de la tinea nigra palmaris. Esta es una infección benigna que puede ser rápidamente diagnosticada y tiene tratamiento eficaz. La paciente fue tratada con econazol durante un mes, con remisión completa de las lesiones. Frente a la sospecha de una infección fúngica por la presencia de manchas de color pardo es muy importante practicar el estudio micológico, ya que mediante una técnica no invasora es posible establecer un diagnóstico diferencial y descartar fácilmente otras patologías más graves con las que puede confundirse en el examen clínico.

A clinical case of a female patient with a black spot on the palm of her left hand is presented. The infection was due to a black fungus identified as Hortaea werneckii, the aetiological agent of tinea nigra palmaris. This infection can be easily diagnosed and it is important to establish the differential diagnosis from other skin pathologies. Normally, the treatment has a successful outcome. In this case, the patient was treated with econazole locally applied during one month, with complete remission of the lesions. In conclusion, the early diagnosis of this disease is very important since the mycology procedures are fast and non-invasive and cure is obtained with local treatment.

[Tinea nigra palmaris: a clinical case in Argentina]. / Tinea nigra palmaris: presentacion de un caso clínico en la República Argentina.

A clinical case of a female patient with a black spot on the palm of her left hand is presented. The infection was due to a black fungus identified as Hortaea werneckii, the aetiological agent of tinea nigra palmaris. This infection can be easily diagnosed and it is important to establish the differential diagnosis from other skin pathologies. Normally, the treatment has a successful outcome. In this case, the patient was treated with econazole locally applied during one month, with complete remission of the lesions. In conclusion, the early diagnosis of this disease is very important since the mycology procedures are fast and non-invasive and cure is obtained with local treatment.

In vitro activity of amphotericin B, itraconazole, terbinafine and 5-fluocytosine against Exophiala spinifera and evaluation of post-antifungal effects.

Antifungal susceptibility profiles were determined for 16 strains of the black yeast Exophiala spinifera applying different temperature regimens. Fluconazole was the least effective in vitro. Lowest minimal inhibitory concentration (MIC) values were found with itraconazole. The activities of antifungal agents against environmental and clinical strains were similar. Post-antifungal effect (PAFE) of four drugs was determined for 11 clinical strains. PAFE was observed only for amphotericin B, with extended inhibition times seen at high drug concentrations.

In vitro activity of amphotericin B and itraconazole in combination with flucytosine, sulfadiazine and quinolones against Exophiala spinifera.

The combined effects of antifungal and antibiotic drugs against Exophiala spinifera were evaluated in vitro by the chequer-board method, calculated as a fractional inhibitory concentration (FIC) index. Amphotericin B was combined with flucytosine and ciprofloxacin, whereas itraconazole was combined with ciprofloxacin, levofloxacin, lomefloxacin and sulfadiazine. Synergic effects were observed for the combinations of itraconazole with ciprofloxacin and levofloxacin, and amphotericin B with ciprofloxacin and flucytosine. No antagonism was observed for any combination tested.

Molecular diversity, new species and antifungal susceptibilities in the Exophiala spinifera clade.

Black yeasts morphologically identified as Exophiala cf. spinifera were re-analyzed on the basis of morphology, nutritional physiology and ITS rDNA sequencing data. Ribosomal small subunit (SSU) DNA sequence data confirmed that strains belonged to a clade containing the ex-type strain of E. spinifera. Variation in the Internal Transcribed Spacer (ITS) region of the rDNA was studied within this group. Five infraspecific groups were delineated. Phylogenetic analysis of the SSU rDNA data revealed that several of the strains analyzed were located at considerable evolutionary distance from the E. spinifera clade. ITS rDNA sequencing showed that the deviating strains could not be identified with any existing species. Two new species, E. attenuata and E. nishimurae, were therefore proposed. Antimycotic susceptibility data of the new species were compared with those obtained with members of the E spinifera clade.