Current Medical Mycology
Volume:5 Issue: 3, Sept 2019

Azoles are preferred antifungal agents given their inexpensiveness, limited toxicity, and potentiality of oral administration. However, the extensive use of prophylactic azole therapy for chronic infections, especially in immunocompromised patients, has led to an increase in azole resistance, thereby rising health care costs. Fluconazole resistance is associated with poor clinical outcomes and the emergence of new infections. The present study aimed to investigate the mutations of ERG11 gene in fluconazole-resistant Candida albicans isolates.

This study was conducted on 80 clinical samples collected from HIV-infected patients with suspected candidiasis in Tagore Medical College Hospital and Government Hospital of Thoracic Medicine, Chennai, India, for a period of 18 months (May 2016-December 2017). The antifungal susceptibility pattern was determined by agar diffusion and broth dilution techniques as per the Clinical and Laboratory Standards Institute guidelines. The ERG11 gene of the known fluconazole-resistant strains of C. albicans was amplified by polymerase chain reaction (PCR). In addition, the samples were subjected to sequencing and mutation analysis.

A total of 60 Candida species were isolated from HIV patients and were speciated using standard, conventional, and molecular methods. Candida albicans comprised 28.3% (n=17) of the Candida isolates, 59% (n=10) of which were resistant to fluconazole. Sequencing of the amplified product of ERG11 C. albicans gene isolates showed that they were highly mutated and included many nonsense mutations which were not reported earlier.

The molecular characterization of ERG11 gene showed many missense and nonsense mutations. Such mutations, which were unique to the geographical area under investigation, could be concluded to account for the development of resistance to fluconazole.

Sporotrichosis is a subcutaneous and chronic fungal infection that is caused by a dimorphic fungus, namely Sporothrix schenckii sensu lato. Lymphocutaneous sporotrichosis is the most clinical form, which accounts for nearly 80% of the cases of cutaneous sporotrichosis. Platelets contain several substances with antimicrobial properties. Regarding this, the present study was performed to investigate the effect of blood-based biomaterials, especially platelets in the treatment of lymphocutaneous sporotrichosis.

This study was performed on 12 golden hamsters, divided into three groups of control, platelet-rich plasma, and platelet lysate. For the purpose of the study, Sporothrix conidia suspension was injected subcutaneously on the back of the animals. After the induction of subcutaneous lesions, the Gomori methenamine silver method was applied to verify lymphocutaneous sporotrichosis. Subsequently, plasma-rich platelet and platelet lysate were injected into the created lesions in the animals in 3-day intervals (due to the short lifetime of platelets). In the final sage, skin tissue samples were examined to check for the presence of yeast cells and their quantification.

The data were indicative of the presence of yeast cells with/without bud in the tissue of lymphocutaneous sporotrichosis lesions in the infected animals. Histological investigation revealed that each of the two biomaterials under study (i.e., plasma-rich platelet and platelet lysate) played a positive role in the removal of the yeast cells of sporotrichosis.

The results of this study showed that both plasma-rich platelet and platelet lysate were able to effectively prevent from the progression of cutaneous sporotrichosis. Accordingly, much attention has been given to new therapies, including treatment with blood-derived biomaterials.

Pneumocystis pneumonia (PCP) is one of the most common and life-threatening fungal diseases in patients with human immunodeficiency, treated with immunosuppressive medications. Immunocompetent people can also be a spreading agent for PCP. Regarding this, the aim of the present study was to diagnose and identify Pneumocystis jirovecii in bronchoalveolar lavage (BAL) samples obtained from patients with pulmonary disorder using a molecular method.

For the purpose of the study, BAL samples (n=138) were collected from patients, undergoing bronchoscopy at the different departments of university hospitals affiliated to Mashhad University of Medical Sciences, Mashhad, Iran, during a period of one year (i.e., April 2014 until May 2015). Giemsa staining and molecular identification were carried out for each sample. The samples were also subjected to nested polymerase chain reaction (PCR), sequencing, and genotyping based on mitochondrial ribosomal large subunit (mtLSU rRNA) of P. jirovecii. The phylogenic tree was constructed by MEGA6 software.

The results of direct microscopic examination revealed the presence of P. jirovecii in 3 (2.2%) out of 138 samples; in addition, nested PCR and sequencing led to the detection of species in 17 (12.3%) samples. Out of patients with positive results, 10 (25%) and 7 (7.1%) cases were immunosuppressed and immunocompetent, respectively. The most common clinical symptoms among patients with pneumocystis were fever, dyspnea, and dry cough. In addition, genotypes III and II were the dominant genotypes in our dataset.

Nested PCR and sequencing methods showed higher sensitivity and specificity as compared with a direct staining technique. Genotype III was identified as the most dominant type in patients with pulmonary disorder in Mashhad.

Pneumocystis jirovecii colonization plays a key role in the progression of pulmonary infection. However, there are limited data regarding the colonization of these fungi in the patients residing in different regions of Iran. Regarding this, the present study was conducted to evaluate the prevalence of P. jirovecii colonization in non-HIV-infected patients with respiratory failure introduced by physicians using nested polymerase chain reaction (PCR).

This study was conducted on 136 samples obtained from 136 patients with respiratory disorders referring to different hospitals in the capital and north of Iran during 2013-2015. The samples were collected using bronchoalveolar lavage (BAL; n=121) and sputum induction (n=15). Nested PCR method targeting mtLSU rRNA gene was used for the detection of P. jirovecii DNA in the specimens.

The nested PCR analysis resulted in the detection of P. jirovecii DNA in 32 (23.5%) patients. The mean age of the participants was 49.04±11.94 years (age range: 14-90 years). The results revealed no correlation between Pneumocystis colonization and gender. The studied patients were divided into two groups of immunocompromised and immunocompetent patients. In the regard, 25.4% of the patients with detectable P. jirovecii DNA were immunocompromised and had cancer, organ transplantation, asthma, sarcoidosis, dermatomyositis, chronic obstructive pulmonary disease, bronchiectasis, and pulmonary vasculitis. On the other hand, Pneumocystis DNA was detected in 21.8% of the immunocompetent patients. Frequencies of P. jirovecii DNA detection in the patients with tuberculosis, hydatid cyst, and unknown underlying diseases were obtained as 20.8%, 25%, and 22%, respectively. The prevalence of Pneumocystis colonization varied based on age. In this regard, P. jirovecii colonization was more prevalent in patients aged above 70 years.

As the findings indicated, non-HIV-infected patients, especially the elderly, had a high prevalence of P. jirovecii colonization. Therefore, these patients are probably a potential source of infection for others. Regarding this, it is of paramount importance to adopt monitoring and prophylactic measures to reduce this infection.

Emergence and development of antifungal drug resistance in Candida species constitute a serious concern. Candida auris as an emerging multidrug-resistant fungus is the most important public health threat with high levels of mortality and morbidity. Almost all C. auris isolates are resistant to fluconazole, and there have been reports of elevated minimum inhibitory concentrations (MICs) to amphotericin B and echinocandins. To overcome the growing challenge of antifungal resistance, a valuable alternative option would be the use of drug combination.

The present study evaluated the in vitro combination of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac and aspirin with fluconazole against fluconazole-resistant C. auris in comparison to other fluconazole-resistant Candida species, including C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei originating from patients with candidiasis.

The MIC ranges of fluconazole-ibuprofen and fluconazole-diclofenac decreased from 32-256 to 32-128 and 16-256 μg/ml, respectively and remained the same for fluconazole-aspirin against C. auris. However, the combination of fluconazole with ibuprofen resulted in a synergistic effect for 5 strains, including C. albicans (n=2), C. tropicalis (n=1), C. glabrata (n=1), and C. krusei (n=1), by decreasing the MIC of fluconazole by 2-3 log2 dilutions.

Although the interaction of NSAIDs with fluconazole was not synergistic against fluconazole-resistant C. auris isolates, no antagonism was observed for any combinations. Therefore, combination with newer azole agents needs to be conducted.

Candida species are opportunistic fungi, capable of causing acute and chronic infections in the gastrointestinal tract, vagina, and oral mucosa, among which Candida albicans is the most important species. The Securigera securidaca L. is used as an antiseptic to treat some diseases in traditional Iranian medicine. The aim of this study was to evaluate the antimicrobial activity of S. securidaca extracts and vaginal gel against different Candida species.

Antifungal effects of different extracts and vaginal gel of S. securidaca were investigated against Candida species. By using well diffusion test, different concentrations of the collected S. securidaca extracts and vaginal gel were examined to test their antifungal activity against C. albicans, C. parapsilosis, and C. krusei.

The ethanol extract and vaginal gel with the ethanol extract of S. securidaca showed the most anti-fungal activity against all three strains.

The S. securidaca extract had a significant inhibitory effect on the different species of Candida; however, the highest inhibitory effect was found against C. albicans. In order to treat candidiasis, more research is required to check the efficacy of this plant in this domain.

Aspergillus fumigatus is one of the most common opportunistic fungus, which causes infection in immunocompromised and neutropenic patients. The current guidelines recommend voriconazole as the initial therapeutic and prophylactic agent for almost all cases, especially in patients with organ transplants, which leads to increased medication resistance in A. fumigatus. The aim of the present study was to evaluate the antifungal activity and effect of kombucha as a natural compound on A. fumigatus growth, as well as on the expression of cgrA and cyp51A genes.

A panel of 15 A. fumigatus strains with two quality controls of CM237 and CM2627 as susceptible and resistant strains were obtained from Tehran Medical Mycology Laboratory, Tehran,Iran(TMML).Antifungal susceptibility testing assay was performed according to the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. Moreover, the mycelial dry weight of the fungus was calculated before and after being treated with kombucha. In addition, the quantitative changes in the expression of cgrA and cyp51A genes were analyzed by real-time polymerase chain reaction (real-time PCR) technique.

In the present study, the minimum inhibitory concentration ranges of kombucha were measured at 6,170 and 12,300 μg/mL for ten A. fumigatus azole-susceptible strains and 24,700 μg/mL for five A. fumigatus resistant strains. Moreover, changes in mycelial dry weight under kombucha treatment conditions underwent a significant reduction (P≤0.05). A coordinate down-regulation of expression in cgrA and cyp51A genes was observed in all azole-susceptible and -resistant A. fumigatus strains, after treating the fungus with different concentrations of kombucha (P≤0.05).

According to the obtained results, kombucha as a natural antioxidant , can exert inhibitory effects against the growth and expression of some genes in A. fumigatusstrains.

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.

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.

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.

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.