Advancements in nanoparticle-based therapies for multidrug-resistant candidiasis infections: a comprehensive review.

Candida auris, a rapidly emerging multidrug-resistant fungal pathogen, poses a global health threat, with cases reported in over 47 countries. Conventional detection methods struggle, and the increasing resistance ofC. auristo antifungal agents has limited treatment options. Nanoparticle-based therapies, utilizing materials like silver, carbon, zinc oxide, titanium dioxide, polymer, and gold, show promise in effectively treating cutaneous candidiasis. This review explores recent advancements in nanoparticle-based therapies, emphasizing their potential to revolutionize antifungal therapy, particularly in combatingC. aurisinfections. The discussion delves into mechanisms of action, combinations of nanomaterials, and their application against multidrug-resistant fungal pathogens, offering exciting prospects for improved clinical outcomes and reduced mortality rates. The aim is to inspire further research, ushering in a new era in the fight against multidrug-resistant fungal infections, paving the way for more effective and targeted therapeutic interventions.

Advances of liposomal mediated nanocarriers for the treatment of dermatophyte infections.

Due to the adverse effects associated with long-term administration of antifungal drugs used for treating dermatophytic lesions like tinea unguium, there is a critical need for novel antifungal therapies that exhibit improved absorption and minimal adverse effects. Nanoformulations offer a promising solution in this regard. Topical formulations may penetrate the upper layers of the skin, such as the stratum corneum, and release an appropriate amount of drugs in therapeutic quantities. Liposomes, particularly nanosized ones, used as topical medication delivery systems for the skin, may have various roles depending on their size, lipid and cholesterol content, ingredient percentage, lamellarity, and surface charge. Liposomes can enhance permeability through the stratum corneum, minimize systemic effects due to their localizing properties, and overcome various challenges in cutaneous drug delivery. Antifungal medications encapsulated in liposomes, including fluconazole, ketoconazole, croconazole, econazole, terbinafine hydrochloride, tolnaftate, and miconazole, have demonstrated improved skin penetration and localization. This review discusses the traditional treatment of dermatophytes and liposomal formulations. Additionally, promising liposomal formulations that may soon be available in the market are introduced. The objective of this review is to provide a comprehensive understanding of dermatophyte infections and the role of liposomes in enhancing treatment.

Clinical Features, Risk Factors, and Management of Candida Keratitis.

BACKGROUND/AIMS: To determine the clinical features, predisposing factors, and management of infectious keratitis caused by Candida spp. METHODS: Retrospective chart review. RESULTS: The medical records of 52 patients (54 eyes) with Candida keratitis were available for statistical analysis. Thinning of the corneal stroma was identified in 34 eyes (63.0%), and corneal perforation occurred in 16 eyes (29.6%). Corneal thinning and perforation were more common in Candida albicans compared with non-albicans (P-val < .001, P = .09, respectively). The most common predisposing factors for Candida keratitis were topical steroid use (21 patients, 40.4%), previous corneal transplantation (17 patients, 32.7%), and preexisting ocular surface disease (15 patients, 28.8%). Fourteen eyes (25.9%) required cyanoacrylate glue application and 10 eyes (18.5%) underwent therapeutic penetrating keratoplasty (TPK). CONCLUSION: Local immunosuppression and ocular surface disease play an important role in Candida keratitis. C. albicans appears to be more invasive compared with non-albicans spp.

Fungal keratitis in Iran: Risk factors, clinical features, and mycological profile.

Introduction: This study was intended to investigate the clinical features and predisposing factors of fungal keratitis (FK), as well as molecular identification and antifungal susceptibility of causative agents in Tehran, Iran. Methods: This cross-sectional study was carried out from April 2019 to May 2021. All fungi isolates were identified using conventional methods and were confirmed by DNA-PCR-based molecular assays. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) was used to identify yeast species. Minimum inhibitory concentrations (MIC) of eight antifungal agents were assessed according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) microbroth dilution reference method. Results: Fungal etiology was confirmed in 86 (7.23%) of 1189 corneal ulcers. A significant predisposing factor for FK was ocular trauma caused by plant materials. Therapeutic penetrating keratoplasty (PKP) was required in 60.4% of cases. The predominant fungal species isolated was Fusarium spp. (39.5%) followed by Aspergillus spp. (32.5%) and Candida spp. (16.2%). Discussion: The MIC results indicate that amphotericin B may be appropriate for treating FK caused by Fusarium species. FK caused by Candida spp. can be treated with flucytosine, voriconazole, posaconazole, miconazole, and caspofungin. In developing countries such as Iran, corneal infection due to filamentous fungi is a common cause of corneal damage. In this region, fungal keratitis is observed primarily within the context of agricultural activity and subsequent ocular trauma. Fungal keratitis can be managed better with understanding the "local" etiologies and antifungal susceptibility patterns.

COVID-19-associated fungal infections in Iran: A systematic review.

OBJECTIVES: This systematic review aims to summarize the mycological and clinical features of COVID-19-associated fungal infections (CAFIs) in Iran. METHODS: PubMed, Web of Science, Scopus, Cochrane Library, SID, Magiran, IranDoc, and Google Scholar were searched for Persian and English articles published from January 1, 2020, to November 5, 2021, using a systematic search strategy. Studies on Iranian patients suffering from CAFIs were included in the review. RESULTS: Twenty-two studies comprising 169 patients were retrieved. Reported CAFIs included candidiasis (85, 50.30%), mucormycosis (35, 20.71%), aspergillosis (29, 17.16%), fusariosis (6, 3.55%), three cases caused by rare pathogens (Rhodotorula mucilaginosa, Diaporthe foeniculina, and Sarocladium kiliense) and 11 (6.51%) uncharacterized mold infections. The most common underlying diseases were diabetes (67/168, 39.88%), cardiovascular diseases (55/168, 32.74%), and hypertension (43/168, 25.59%). The use of antibiotics (111/124, 89.52%), corticosteroids (93/132, 70.44%), and mechanical ventilation (66, 51.16%) were the most common predisposing factors. Totally, 72 (50.35%) of 143 patients with CAFIs died (data were not available for 26 patients). CONCLUSION: Fungal infections are evident to be a complication of COVID-19 in Iran; thus, clinicians should consider them as a differential diagnosis, especially in patients with comorbidities and previous antibiotic or corticosteroid use.

Drug repurposing against Candida auris: A systematic review.

Candida auris is a drug-resistant pathogen with several reported outbreaks. The treatment of C. auris infections is difficult due to a limited number of available antifungal drugs. Thus, finding alternative drugs through repurposing approaches would be clinically beneficial. A systematic search in PubMed, Scopus and Web of Science databases, as well as Google Scholar up to 1 November 2021, was conducted to find all articles with data regarding the antifungal activity of non-antifungal drugs against the planktonic and biofilm forms of C. auris. During database and hand searching, 290 articles were found, of which 13 were eligible for inclusion in the present study. Planktonic and biofilm forms have been studied in 11 and 8 articles (with both forms examined in 6 articles), respectively. In total, 22 and 12 drugs/compounds have been reported as repositionable against planktonic and biofilm forms of C. auris, respectively. Antiparasitic drugs, with the dominance of miltefosine, were the most common repurposed drugs against both forms of C. auris, followed by anticancer drugs (e.g. alexidine dihydrochloride) against the planktonic form and anti-inflammatory drugs (e.g. ebselen) against the biofilm form of the fungus. A collection of other drugs from various classes have also shown promising activity against C. auris. Following drug repurposing approaches, a number of drugs/compounds from various classes have been found to inhibit the planktonic and biofilm forms of C. auris. Accordingly, drug repurposing is an encouraging approach for discovering potential alternatives to conventional antifungal agents to combat drug resistance in fungi, especially C. auris.

The Epidemiological, Clinical, Mycological, and Pathological Features of Rhino-cerebral Mucormycosis: A Systematic Review.

Cerebral mucormycosis (CM) is a life-threatening manifestation of mucormycosis, an angioinvasive fungal infection caused by Mucorales. We sought to systematically review all available case reports to describe epidemiologic features, clinical manifestations, predisposing factors, and diagnostic and treatment strategies of CM. A systematic search was conducted using a combination of the following keywords: "Mucor", "Zygomycetes", "mucormycosis", "cereb*", "brain", "central nervous system", and "intracranial", separately and in combination until December 31st 2018. Data sources included PubMed, Scopus, EMBASE, Web of Science, Science Direct, and Proquest without limiting the time of publication. We included 287 articles corresponding to 345 cases of CM. Out of the 345 cases, 206 (60%) were male with a median age of 44 years; 130 (38%) were reported from North America; 87 (25%) from Asia; and 84 (24%) from Europe. The median time from onset of symptoms to presentation was 3-7 days (65/345, 65%). The highest mortality was observed among patients with diabetes mellitus (P=0.003). Debridement of infected brain tissue was associated with improved survival in CM cases (OR 1.5; 95% CI 01.3-1.8; P<0.0001). The use of liposomal amphotericin B (L-AMB) was significantly associated with patients' recovery (OR 2.09; 95% CI 1.2-3.4; P=0.003). The combination of L-AMB and posaconazole (12.5%) was more effective than the monotherapy treatment of CM cases (P=0.009). Clinicians should consider DM as an important risk factor for CM. Moreover, surgical debridement and antifungal combination therapy could be an effective approach in the management of CM patients.

Inhibitory effects of different fractions separated from standardized extract of Myrtus communis L. against nystatin-susceptible and nystatin-resistant Candida albicans isolated from HIV positive patients.

Background: and Purpose: Myrtle (Myrtus communis L.) is a medicinal herb that plays an essential role in treating fungal infections. The present study investigated the antifungal properties of different fractions of the M. communis L. leaf extract against Candida albicans (susceptible and resistant to nystatin). Materials and methods: Total extract (TE) and petroleum ether (PE), chloroform (CH), ethyl acetate (EA), and methanol (ME) fractions were prepared using the sonication method. The study used the standard strain sample (ATCC 76645) and nystatin-resistant C. albicans from oral samples of HIV-infected individuals. The identification of resistant isolate was performed using phenotypic and molecular methods. Minimum inhibitory concentration (MIC) and Minimum fungicidal concentration (MFC) of the fractions along total extract were determined by microdilution method on nystatin-resistant and susceptible Candida albicans. The Folin-Ciocalteu method was used to determine the total phenolic content of the extract. Results: The extraction yield (w/w) was 13.50 for TE, 2.10 for PE, 2.23 for Ch, 2.14 for EA, and 10.03 for ME fractions. Chloroform extract showed good anti-candida activity against nystatin susceptible and resistant C. albicans (62.5 â€‹µg/mL). Ethyl acetate fraction exhibited the greatest MIC against nystatin susceptible and resistant C. albicans (250 â€‹µg/mL). The MIC value of fluconazole was >64 µg/mL for both susceptible and -resistant strains. The amount of phenolic compounds of the total extract was reported to be equal to 5.4%, equivalent to gallic acid. Conclusion: Results revealed that the PE and CH fractions showed greater antifungal effects than the total extract against both susceptible and resistant strains of Candida albicans. It can conclude that active antifungal compounds of the plant belong to a specific group of metabolites, which according to the type of solvent, probably have non-polar nature. Further separation is carrying out.

First molecular report of causative agent of otomycosis due to Aspergillus luchuensis.

Otomycosis is a fungal infection of the external auditory canal caused mainly by the genus Aspergillus. Aspergillus luchuensis, an industrially important fungus, is a member of Aspergillus section Nigri. In this report, we present a case of otomycosis due to Aspergillus luchuensis in a 43-year-old female patient. We performed a partial PCR-sequencing of ß-tubulin and calmodulin genes to identify the isolate to the species level. Further, we determined the in vitro susceptibility of the isolate to nystatin, clotrimazole and itraconazole according to the Clinical & Laboratory Standards Institute (CLSI) M38-A2 protocol. Accordingly, the minimum inhibitory concentrations of clotrimazole, nystatin and itraconazole were 0.25µg/mL, 0.5µg/mL and 1µg/mL, respectively. This is the first report of clinically relevant isolation of Aspergillus luchuensis identified by a molecular technique as a causative agent of otomycosis.

Fungal keratitis caused by Pseudallescheria boydii: clinical and mycological characteristics.

BACKGROUND: Pseudallescheria keratitis is rare but important type of fungal keratitis because of the inherently resistance of the organism to many existing antifungal agents. METHODS: Slit-lamp and confocal microscopy were used for clinical examinations. Fungal isolates were identified based on morphological characteristics and DNA sequence of the internal transcribed spacer region (ITS). In vitro antifungal susceptibility testing for fungal isolates was performed according to the Clinical and Laboratory Standards Institute (CLSI, M38-A2). RESULT: All patients had a history of ocular trauma. In clinical examination hypopion were seen in three patients. The main antifungal medications were topical voriconazole. After treatment the visual acuity of all patients improved in 2-3 weeks. CONCLUSION: All four patients of Pseudallescheria keratitis had similar clinical features. Accurate and rapid identification of species should be helpful in treating p. boydii keratitis.

Clinical and mycological characteristics of keratitis caused by Colletotrichum gloeosporioides: A case report and review of literature.

INTRODUCTION: Colletotrichum species are well-known plant pathogens, which have been increasingly reported as the cause of keratitis or subcutaneous lesions in humans. In this study we reported a rare case of fungal keratitis from Iran and reviewed the literature. CASE PRESENTATION: A 69-year-old man whose right eye was injured by herbal material was examined by slit-lamp biomicroscopy and mycology investigation of corneal scrapings was done. The grown filamentous fungal was identified as Colletotrichum gloeosporioides based on morphological characteristics and DNA sequence of the internal transcribed spacer region. The isolated strain was sensitive to amphotericin B, caspofungin, anidolafungin, micafungin, voriconazole, and relatively resistant to fluconazole, and itraconazole. Patient was successfully treated with voriconazole. CONCLUSIONS: This report highlights that the early and accurate identification and therapy can helpful to management keratitis caused by C. gloeosporioides.

New weapons to fight a new enemy: A systematic review of drug combinations against the drug-resistant fungus Candida auris.

Candida auris is an emerging and drug-resistant pathogen. Drug combination is a promising approach against such pathogens. This study was conducted to provide an overview of all the studied drug combinations against C. auris. Relevant articles reporting results of any drug/non-drug combinations against C. auris were found by a systematic search in PubMed, Scopus and Web of Science (ISI), and in Google Scholar up to 1 October 2020. From 187 articles retrieved in the primary search, 23 met the inclusion criteria. In total, 124 different combinations including antifungal with antifungal (45), antifungal with other antimicrobials (11), antifungal with non-antimicrobials (32), antifungal with natural compounds (25) and between natural compounds (11) have been reported. Complete or partial synergistic effects have been reported for 3 out of 45 (6.67%) combinations of two antifungal agents, 8 out of 11 (72.73%) combinations involving antifungal agents and antimicrobials, 15 out of 32 (46.88%) of combinations between antifungal agents with non-antimicrobials, 16 out of 25 (64%) of combinations involving antifungal agents and natural compounds, and 3 out of 11 (22.27%) of combinations involving multiple natural compounds. Antagonistic interactions have been reported for 1 out of 32 (3.13%) and 8 out of 25 (32%) of combinations between antifungal drugs with non-antimicrobials and with natural compounds, respectively. Different drugs/compounds could potentiate the activity of antifungal drugs using this approach. However, despite the availability of this promising initial data, many more studies will be required to elucidate whether favourable interactions observed in vitro might translate into tangible clinical benefits.

Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers. Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated. Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%. Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.

Proven pulmonary aspergillosis in a COVID-19 patient: A case report.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) has become a significant clinical challenge in healthcare settings all over the world. Critically ill COVID-19 patients with acute respiratory distress syndrome may be at increased risk of co-infection with pulmonary aspergillosis. This study aimed to describe a clinical case of proven pulmonary aspergillosis caused by Aspergillus tubingensis in a 59-year-old man with a history of hospitalization due to COVID-19 infection. CASE REPORT: The Covid-19 infection was confirmed by positive nasopharyngeal polymerase chain reaction. He had a cavitary lesion measured 20 mm in diameter with intracavitary soft tissue density in the left lung in the first chest computerized tomography scan. After 25 days, he showed two cavitary lesions in both lungs which raised suspicion of fungal infection; hence, the patient underwent a trans-thoracic biopsy of the cavitary lesion. The direct examination and culture of the biopsy material revealed Aspergillus species. To confirm the Aspergillus species identification, the beta-tubulin region was sequenced. The patient was treated with oral voriconazole. CONCLUSION: This report underlined the importance of early diagnosis and management of invasive fungal infections in severe COVID-19 patients.

In Vitro Antifungal Activity of Green Synthesized Silver Nanoparticles in Comparison to Conventional Antifungal Drugs Against Trichophyton Interdigitale, Trichophyton Rubrum and Epidermophyton Floccosum.

BACKGROUND: Dermatophytosis is a globally distributed fungal infection. Treatment failure and relapse is common in this disease. Silver nanoparticles are known for their promising antimicrobial activity. The aim of this study was to determine the antifungal activity of these nanoparticles against common dermatophyte species. METHODS: A set of 30 molecularly identified dermatophytes including Trichophyton interdigitale (n=10), Trichophyton rubrum (n=10), and Epidermophyton floccosum (n=10) were used in this study. Green synthesized silver nanoparticles using chicory (Cichorium intybus) were tested for their antifungal activity in comparison to fluconazole, itraconazole and terbinafine. Interspecies differences in minimum inhibitory concentrations of antifungal drugs and silver nanoparticles were tested using Kruskal-Wallis test in SPSS software version 21. RESULTS: The highest minimum inhibitory concentrations (MICs) among antifungal drugs were observed for fluconazole [range: 4-64 µg/mL, geometric mean (GM) =17.959 µg/mL], followed by itraconazole (range: 0.008-0.5, GM= 0.066) and terbinafine (range: 0.004-0.25 µg/mL, GM=0.027 µg/mL). Silver nanoparticles showed potent antifungal activity against all dermatophyte isolates with MICs (range: 0.25-32 µg/mL, GM=4.812 µg/mL) higher than those of itraconazole and terbinafine, but lower than fluconazole. MIC values of silver nanoparticles demonstrated significant differences between species (P=0.044), with E. floccosum having the highest MICs (GM=9.849 µg/mL) compared to T. interdigitale (GM=3.732 µg/mL) and T. rubrum (GM=3.031 µg/mL). CONCLUSION: Silver nanoparticles demonstrated promising anti-dermatophyte activity against the studied dermatophytes. Due to their wide-spectrum activity against other fungal and bacterial pathogens, they could be a potential choice, at least in the case of cutaneous and superficial infections.

Current diagnostic tools and management modalities of Nocardia keratitis.

Nocardia species are an uncommon but important cause of keratitis. The purpose of this review is to discus previous published papers relation to the epidemiology, etiology, diagnosis and management of Nocardia keratitis. Nocardia asteroides is the most frequently reported from Nocardia keratitis. Pain, photophobia, blepharospasm and lid swelling are mainly clinical manifestations. Usual risk factors for Nocardia keratitis are trauma, surgery, corticosteroids, and contact lens wear. Several antibiotics were used for treatment of Nocardia infection but according to studies, topical amikacin is the drug of choice for Nocardia keratitis. Topical steroid should not prescribe in these patients. In conclusion, although Nocardia keratitis is rare, early diagnosis and treatment are essential to prevent any scar formation and preserve a good visual acuity.

Effect of photo core, LuxaCore, and core max II core building materials on fracture resistance of endodontically-treated teeth restored with fiber-reinforced composite posts and ParaPosts.

BACKGROUND: Post and core treatment is commonly performed for endodontically treated teeth to replace the lost tooth structure and reinforce and protect the remaining dental tissue. This study aimed to compare the effect of three-core building materials on fracture resistance of endodontically-treated teeth restored with fiber-reinforced composite (FRC) posts and ParaPosts. MATERIALS AND METHODS: This in vitro, experimental study evaluated 108 sound, single-rooted mandibular first premolars extracted for orthodontic purposes. The teeth were randomly divided into nine groups (n = 12) of control (no endodontic or restorative treatment), FRC + Photo Core (Group 2), FRC + LuxaCore (Group 3), FRC + Core Max II with bonding agent (Group 4), FRC + Core Max II without bonding agent (Group 5), ParaPost + Photo Core (Group 6), ParaPost + LuxaCore (Group 7), ParaPost + Core Max II with bonding agent (Group 8), and ParaPost + Core Max II without bonding agent (Group 9). The fracture resistance was measured by applying the load at 45° angle relative to the longitudinal axis of the tooth with a crosshead speed of 1 mm/min using a universal testing machine. Data were through descriptive statistics, Tukey's test, and one-way analysis of variance (α = 0.05). RESULTS: The mean fracture resistance was 454.0 ± 62.7, 410.8 ± 48.3, 365.1 ± 42.1, 423.7 ± 111.7, 392.4 ± 90.0, 292.3 ± 83.9, 242.3 ± 73.4, 278.2 ± 67.9, and 247.3 ± 49.6 N in Groups 1-9, respectively. Group 4 showed the highest fracture resistance, which was significantly higher than this study the value in all ParaPost and control groups (P < 0.05) but had no significant difference with the fracture resistance of other groups (P > 0.05). CONCLUSION: Fracture resistance is independent of the type of core building material used, and the tested products had no superiority over each other. The mean fracture resistance of FRC post groups were significantly higher than that of ParaPost groups. Furthermore, Core Max II + bonding agent yielded insignificantly higher fracture resistance than Core Max II without bonding agent.

Distribution, antifungal susceptibility pattern and intra-Candida albicans species complex prevalence of Candida africana: A systematic review and meta-analysis.

Candida africana is a pathogenic species within the Candida albicans species complex. Due to the limited knowledge concerning its prevalence and antifungal susceptibility profiles, a comprehensive study is overdue. Accordingly, we performed a search of the electronic databases for literature published in the English language between 1 January 2001 and 21 March 2020. Citations were screened, relevant articles were identified, and data were extracted to determine overall intra-C. albicans complex prevalence, geographical distribution, and antifungal susceptibility profiles for C. africana. From a total of 366 articles, 41 were eligible for inclusion in this study. Our results showed that C. africana has a worldwide distribution. The pooled intra-C. albicans complex prevalence of C. africana was 1.67% (95% CI 0.98-2.49). Prevalence data were available for 11 countries from 4 continents. Iran (3.02%, 95%CI 1.51-4.92) and Honduras (3.03%, 95% CI 0.83-10.39) had the highest values and Malaysia (0%) had the lowest prevalence. Vaginal specimens were the most common source of C. africana (92.81%; 155 out of 167 isolates with available data). However, this species has also been isolated from cases of balanitis, from patients with oral lesions, and from respiratory, urine, and cutaneous samples. Data concerning the susceptibility of C. africana to 16 antifungal drugs were available in the literature. Generally, the minimum inhibitory concentrations of antifungal drugs against this species were low. In conclusion, C. africana demonstrates geographical variation in prevalence and high susceptibility to antifungal drugs. However, due to the relative scarcity of existing data concerning this species, further studies will be required to establish more firm conclusions.

Oropharyngeal candidiasis in hospitalised COVID-19 patients from Iran: Species identification and antifungal susceptibility pattern.

BACKGROUND: Emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. Apparently, the novel coronavirus (SARS-CoV-2) is armed by special abilities to spread and dysregulate the immune mechanisms. The likelihood of oropharyngeal candidiasis (OPC) development in COVID-19 patients with a list of attributable risk factors for oral infections has not yet been investigated. OBJECTIVES: We here aim to investigate the prevalence, causative agents and antifungal susceptibility pattern of OPC in Iranian COVID-19 patients. PATIENTS AND METHODS: A total of 53 hospitalised COVID-19 patients with OPC were studied. Relevant clinical data were mined. Strain identification was performed by 21-plex PCR and sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, amphotericin B, caspofungin, micafungin and anidulafungin was performed according to the CLSI broth dilution method. RESULTS: In 53 COVID-19 patients with OPC, cardiovascular diseases (52.83%) and diabetes (37.7%) were the principal underlying conditions. The most common risk factor was lymphopaenia (71%). In total, 65 Candida isolates causing OPC were recovered. C albicans (70.7%) was the most common, followed by C glabrata (10.7%), C dubliniensis (9.2%), C parapsilosis sensu stricto (4.6%), C tropicalis (3%) and Pichia kudriavzevii (=C krusei, 1.5%). Majority of the Candida isolates were susceptible to all three classes of antifungal drugs. CONCLUSION: Our data clarified some concerns regarding the occurrence of OPC in Iranian COVID-19 patients. Further studies should be conducted to design an appropriate prophylaxis programme and improve management of OPC in critically ill COVID-19 patients.

In vitro synergy of echinocandins with triazoles against fluconazole-resistant Candida parapsilosis complex isolates.

INTRODUCTION: Candida parapsilosis (C. parapsilosis) is a common non-albicans Candida species ranked as the second common cause of bloodstream infections. Azole resistance and elevated echinocandin MICs have been reported for these fungi. This study was conducted to determine the interactions between azoles and echinocandins against C. parapsilosis species complex. MATERIALS AND METHODS: Fifteen fluconazole-resistant clinical isolates of C. parapsilosis complex were included: C. parapsilosis sensu stricto (n = 7), C. orthopsilosis (n = 5) and C. metapsilosis (n = 3). The activity of azoles (fluconazole, itraconazole) and echinocandins (anidulafungin, micafungin) alone and in combination was determined using checkerboard broth microdilution. The results were determined based on the fractional inhibitory concentration index (FICI). RESULTS: In vitro combination of fluconazole with anidulafungin was found to be synergistic (FICI 0.07-0.37) and decreased the MIC range from 4-64 µg/mL to 0.5-16 µg/mL for fluconazole and from 2-8 µg/mL to 0.125-1 µg/mL for anidulafungin. Similarly, interactions of fluconazole with micafungin (FICI 0.25-0.5), itraconazole with anidulafungin (FICI 0.15-0.37) and itraconazole with micafungin (FICI 0.09-0.37) were synergistic. CONCLUSION: The combination of fluconazole and itraconazole with either anidulafungin or micafungin demonstrated synergistic interactions against C. parapsilosis species complex, especially against isolates with elevated MIC values. However, the use of these combinations in clinical practice and the clinical relevance of in vitro combination results remain unclear.