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Candida parapsilosis is a non-albicans Candida spp. associated with bloodstream infections in critically ill patients. Failure to treat it effectively due to delay in diagnosis often leads to serio...

A hospital-based cross-sectional study was conducted during 2018-2019 to decipher the prevalence of yeast mastitis. The results indicated a 19.68% prevalence of clinical mastitis in bovines. Among them, 5.51% of samples revealed yeasts constituting 1.09% overall prevalence. Candida albicans was recorded as a significant fungal agent involved in clinical bovine mastitis. We record the association of Kodamaea ohmeri in clinical bovine mastitis. On proteomic and molecular confirmation, K. ohmeri isolates were re-identified from phenotypically identified Candida isolates associated with bovine mastitis. After conventional identification, the yeast isolates were re-identified by MALDI-TOF MS-based proteomic approaches. The D1/D2 domains of 26S-rRNA gene and 5.8S-internal transcribed spacer (ITS) rDNA regions based molecular phylogenetic analysis identified the isolates as K. ohmeri. The isolates were resistant to fluconazole. This study reports the first systemic study of K. ohmeri isolates recovered from bovine clinical mastitis, utilizing conventional, automated, proteomic, and genomic approaches followed by antifungal susceptibility. The findings suggest K. ohmeri as a potent opportunistic emerging pathogen of veterinary and public health concern, need for accurate identification of fungal agents from mycotic mastitis, and use of validated antifungal susceptibility assay because of developing resistance to antimycotic agents. Our findings suggest judicious use of fluconazole and alternative antifungal agents may be considered in case of an outbreak.

This study aimed to assess the effect of voriconazole (VCZ)-loaded nano-liposomes on biological activity and expression of ERG11, CDR1, and CDR2 genes in fluconazole (FCZ)-resistant Candida albican...

Aim: The purpose of this study was to evaluate the antifungal activity of midazolam, alone and in association with azoles, against isolates of clinical Candida spp. in planktonic and biofilm form. Materials & methods: The antifungal activity was observed using the broth microdilution technique. Flow cytometry tests were performed to investigate the probable mechanism of action and the comet test and cytotoxicity test were applied to evaluate DNA damage. Results: Midazolam (MIDAZ) showed antifungal activity against planktonic cells (125–250 μg/ml) and reduced the viability of Candida spp. biofilms (125 a 2500 μg/ml). The interaction of MIDAZ against Candida spp. biofilms was observed through scanning electron microscopy, causing alteration of their appearance. Therefore, MIDAZ has antifungal potential against Candida spp.

Background: Malassezia though known for its cutaneous infections can potentially cause invasion. The skin infections caused by Malassezia have poor patient compliance due to its chronicity and recurrent nature of the disease. There is also a lack of standardised antifungal susceptibility profile for Malassezia due to its complex growth requirement. Objective: This study was performed to understand the epidemiological pattern of disease and to study the antifungal susceptibility testing (AFST) profile so as to choose the appropriate drug/drugs to treat the infections caused by Malassezia. Materials and Methods: Samples were collected and processed, species were identified by conventional method and AFST was done by broth microdilution method. Results: The epidemiological pattern showed adolescent females commonly affected in torso. The most common lesion was pityriasis versicolor. The systemic antifungal of choice was itraconazole with the lowest minimum inhibitory concentration (MIC) of 0.125–1 μg/ml. The best topical drug with the lowest MIC value was clotrimazole 0.03–0.5 μg/ml. Conclusion: AFST is important as it will help the dermatologist to choose the appropriate antifungal agents for the patient and thereby reduce the chronicity of the disease with good patient compliance

INTRODUCTION The prevalence of azole resistance in C parapsilosis is very low in most parts of the world. However, South Africa has reported an exceptionally high prevalence of azole resistance in C parapsilosis strains isolated from candidaemia cases. We aimed to determine the possible molecular mechanisms of fluconazole resistance in C parapsilosis isolates obtained through surveillance at a large neonatal unit at a South African academic hospital. METHODS We sequenced the ERG11 and MRR1 genes of C parapsilosis isolates recovered from cases of neonatal candidemia, followed by microsatellite genotyping. A total of 73 isolates with antifungal susceptibility results were analysed. RESULTS Of these, 57 (78%) were resistant, 11 (15%) susceptible dose-dependent and 5 (7%) susceptible. The most commonly identified amino acid substitution within the ERG11 gene was Y132F in 68% (39/57) of fluconazole-resistant isolates and none in susceptible isolates. Three amino acid substitutions (R405K, G583R and A619V) and 1 nucleotide deletion at position 1331 were identified within MRR1 gene in 19 (26%) isolates. Microsatellite genotyping grouped isolates into four clusters (50 isolates). Cluster 1 accounted for 23% (17/73) of all cases, cluster 2 for 22% (16/73), cluster 3 for 14% (10/73) and cluster 4 for 10% (7/73). We found an association between cluster type and fluconazole resistance (P-value = .004). Isolates harbouring the Y132F substitution were more likely to belong to a cluster than non-Y132F isolates. CONCLUSION Fluconazole resistance in C parapsilosis strains from a single South African neonatal unit was associated with cluster type and predominantly driven by Y123F amino acid substitutions in the ERG11 gene.

Objective The aim of the study was to review recent clinic cases with mixed vaginitis due to bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) with reference to demographics, clinical presentation, diagnosis, and treatment. Materials and methods This is a retrospective chart review of patients defined with mixed vaginitis due to BV and VVC in academic vaginitis clinic over 3 years (2018-2021). Results Thirty-eight women, mean age 32.6 years, met mixed vaginitis definition criteria. Diagnosis was invariably suspected clinically and rapidly confirmed using standard point of care diagnostic tests. Most patients (>90%) had a history of long-standing recurrent vaginitis both BV and VVC. Condom use was infrequent at 30% and 100% of yeast isolates were Candida albicans. Dual antimicrobial therapy achieved short term therapeutic success in 66.7% with failure in part due to fluconazole resistant C. albicans strains. Conclusions Mixed vaginitis is not uncommon and serves as a significant therapeutic challenge requiring initial dual antimicrobial therapy and additional consideration for long-term antimicrobial therapy.

BACKGROUND: Since the first report of Candida auris in 2016, the Colombian Instituto Nacional de Salud (INS) has implemented a national surveillance of the emerging multidrug-resistant fungus. OBJECTIVES: This report summarizes the findings of this laboratory-based surveillance from March 2016 to December 2020. RESULTS: A total of 1,720 C. auris cases were identified, including 393 (23%) colonization cases and 1,327 (77%) clinical cases. Cases were reported in 20 of 32 (62%) Departments of Colombia and involved hospitals from 33 cities. The median age of patients was 34 years; 317 (18%) cases were in children under 16 years, 54% were male. The peak number of cases was observed in 2019 (n=541). In 2020, 379 (94%) of 404 cases reported were clinical cases, including 225 bloodstream infections (BSI) and 154 non-BSI. Among the 404 cases reported in 2020, severe COVID-19 was reported in 122 (30%). Antifungal susceptibility was tested in 379 isolates. Using CDC tentative breakpoints for resistance, 35% of isolates were fluconazole resistant, 33% were amphotericin B resistant, and 0.3% isolate were anidulafungin resistant, 12% were multidrug resistant, and no pan-resistant isolates were identified. CONCLUSION: For five years of surveillance, we observed an increase in the number and geographic spread of clinical cases and an increase in fluconazole resistance. These observations emphasize the need for improved measures to mitigate spread.

Background and Purpose: Encapsulation can lead to improved efficacy and safety of antifungal compounds. The attention of scientists has recently turned to biocompatible lipids as the carriers for the delivery of antifungal drugs, such as fluconazole. Although several research reports have already been published on fluconazole loaded solid lipid nanoparticles (FLZ-SLNs) and fluconazole loaded nanostructured lipid carriers (FLZ-NLCs), the possible advantages of NLCs over SLNs have not yet been fully established. Studies performed so far have given several contradictory results. Materials and Methods: Both formulations of fluconazole were synthesized using probe ultrasonication method and the characteristics were analyzed. Antifungal susceptibility testing (AFST) was performed with FLZ, FLZ-SLNs, and FLZ-NLCs using CLSI document M60 against some common fluconazole-resistant Candida species. Results: A significant decrease was observed in minimum inhibitory concentration values when both formulations were applied. Nonetheless, FLZ-NLCs were significantly more effective (P Conclusion: Based on the obtained results, FLZ-NLCs could reverse the azole-resistance phenomenon in the most common Candida species more effectively, as compared to FLZ-SLNs.

Aim: This work studied the impact of the quorum-sensing molecule, farnesol (FAR), on fluconazole (FLC)-resistant Candida albicans isolate CY 1123 compared with the susceptible standard strain C. al...

Resistance to azole antifungal agents is a challenging limitation in Candida glabrata treatment. It is associated with decreased intracellular concentrations of antifungal agents as a result of overexpression of efflux pumps on the cellular plasma membranes. This work evaluates the potential of silver nanoparticles to reverse resistance of fungal cells to fluconazole. Silver nanoparticles were prepared using wet chemical method and characterized by UV-Vis spectrophotometry, dynamic light scattering, and zeta potential. Broth microdilution and pour plates methods were used to study the anticandidal activity using two C. glabrata fluconazole-resistant strains (DSY565 and CBS138) known to overexpress active efflux pumps, and a standard fluconazole sensitive strain ATCC22553. Silver nanoparticles -fluconazole combinations decreased concentrations of fluconazole substantially without compromising the activity. These findings suggest that silver nanoparticles enhance the efficacy of fluconazole and offer a promising application in therapy of C. glabrata infections.

Candida species are fungal pathogens known to cause a wide spectrum of diseases, and Candida albicans and Candida glabrata are the most common associated with invasive infections. A concerning aspect of invasive candidiasis is the emergence of resistant isolates, especially those highly resistant to fluconazole, the first choice of treatment for these infections. Fungal sphingolipids have been considered a potential target for new therapeutic approaches and some inhibitors have already been tested against pathogenic fungi. The present study therefore aimed to evaluate the action of two sphingolipid synthesis inhibitors, aureobasidin A and myriocin, against different C. albicans and C. glabrata strains, including clinical isolates resistant to fluconazole. Susceptibility tests of aureobasidin A and myriocin were performed using CLSI protocols, and their interaction with fluconazole was evaluated by a checkerboard protocol. All Candida strains tested were sensitive to both inhibitors. Regarding the evaluation of drug interaction, both aureobasidin A and myriocin were synergic with fluconazole, demonstrating that sphingolipid synthesis inhibition could enhance the effect of fluconazole. Thus, these results suggest that sphingolipid inhibitors in conjunction with fluconazole could be useful for treating candidiasis cases, especially those caused by fluconazole resistant isolates.

A series of 5-phenylthiophene derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible and drug-resistant fungal infections. The antifungal activity of the synthesized compounds was assessed against seven susceptible strains and six fluconazole-resistant strains. It is especially encouraging that compounds 17b and 17f displayed significant antifungal activities against all tested strains. Furthermore, the potent compounds 17b and 17f could prevent the formation of fungi biofilms and 17f displayed satisfactory fungicidal activity. Preliminary mechanistic studies showed that the potent antifungal activity of compound 17f stemmed from inhibition of C. albicans CYP51. In addition, Compounds 17b and 17f were almost nontoxic to mammalian A549, MCF-7, and THLE-2 cells. These results strongly suggested that compounds 17b and 17f are promising as novel antifungal drugs.

Nearly all isolates harbored Pdr1p mutations and were associated with a high mortality rate., We investigated the clinical outcomes and molecular mechanisms of fluconazole-resistant (FR) Candida glabrata bloodstream infections. Among 1,158 isolates collected during multicenter studies in South Korea during 2008–2018, 5.7% were FR. For 64 patients with FR bloodstream infection isolates, the 30-day mortality rate was 60.9% and the 90-day mortality rate 78.2%; these rates were significantly higher than in patients with fluconazole-susceptible dose-dependent isolates (30-day mortality rate 36.4%, 90-day mortality rate 43.8%; p

Background: Oral Candidiasis (OC) still mainly oportunistic infection problem in HIV/AIDS Patients.Due to increasing report of fluconazole resistant as common antifungal drugs nowadays, there have beenmany studies focusing on natural substances and its antifungal properties. In this study, a form of green teaextract, named Epigallocathechingallate (EGCG) 1,25% were examined for their in vitro antifungal activity against Candida sp in comparison to fluconazole (2 mg/ml) as standard antifungal agents.Objective:To evaluate the antifungal activity of EGCG in compare with fluconazole against Candida isolates takenfrom HIV / AIDS patients with OC. Methods: Fourty Candida sp. isolates taken from HIV / AIDS patientswith OC in the Outpatient Unit and Inpatient Installation of the Infectious Disease Intermediate Care Unit(UPIPI) Dr. Soetomo, Surabaya. Antifungal activity were evaluated by using microdilution tests. Results:The microdilution test revealed the MIC of EGCG for all Candida sp. was 0.625%, while the MIC offluconazole was 100% for all Candida sp. There was significant difference (p

Background and Purpose: Candida auris, as a new characterized pathogenic yeast,has attracted remarkable attention in the recent decade due to its rapid global emergence and multidrug resistance traits. This unique species is able to cause nosocomial outbreaks and tolerate adverse conditions; however, it has been mostly misidentified by conventional methods. Case report: This report aimed to describe the first fluconazole-resistant case of C.auris otitis in an immunocompetent patient in Iran. The isolate showed minimum inhibitory concentration of ≥ 32 μg/ml for fluconazole; however, the patient was treated with topical clotrimazole and miconazole with no recurrence. Conclusion: This was the second strain of C. auris isolated from otitis in Iran which was fluconazole-resistant, unlike the first Iranian isolate.

Despite the advent of echinocandins and newer triazoles (voriconazole, posaconazole, and isavuconazole) (1), fluconazole (FLZ) remains an important component of today’s antifungal arsenal, particularly for treatment of Candida infections (2, 3).…

Clonal outbreaks of fluconazole-resistant (FLZR) Candida parapsilosis isolates have been reported in several countries. Despite its being the second leading cause of candidemia, the azole resistance mechanisms and the clonal expansion of FLZR C. parapsilosis blood isolates have not been reported in Turkey. In this study, we consecutively collected C. parapsilosis blood isolates (n = 225) from the fifth largest hospital in Turkey (2007 to 2019), assessed their azole susceptibility pattern using CLSI M27-A3/S4, and sequenced ERG11 for all and MRR1, TAC1, and UPC2 for a selected number of C. parapsilosis isolates. The typing resolution of two widely used techniques, amplified fragment length polymorphism typing (AFLP) and microsatellite typing (MST), and the biofilm production of FLZR isolates with and without Y132F were compared. Approximately 27% of isolates were FLZR (60/225), among which 90% (54/60) harbored known mutations in Erg11, including Y132F (24/60) and Y132F+K143R (19/60). Several mutations specific to FLZR isolates were found in MRR1, TAC1, and UPC2. AFLP grouped isolates into two clusters, while MST revealed several clusters. The majority of Y132F/Y132F+K143R isolates grouped in clonal clusters, which significantly expanded throughout 2007 to 2019 in neonatal wards. Candida parapsilosis isolates carrying Y132F were associated with significantly higher mortality and less biofilm production than other FLZR isolates. Collectively, we documented the first outbreak of FLZR C. parapsilosis blood isolates in Turkey. The MRR1, TAC1, and UPC2 mutations exclusively found in FLZR isolates establishes a basis for future studies, which will potentially broaden our knowledge of FLZR mechanisms in C. parapsilosis. MST should be a preferred method for clonal analysis of C. parapsilosis isolates in outbreak scenarios. Copyright © 2020 American Society for Microbiology. All Rights Reserved., Shanghai Municipal Health and Family Planning Commission 2018ZX10101003 Science and Technology Commission of Shanghai Municipality, STCSM: 17DZ2272900, 14495800500 National Natural Science Foundation of China, NSFC: 31770161, This work was supported by the Major National R&D Projects of the National Health Department (2018ZX10101003), National Natural Science Foundation of China (31770161), Shanghai Science and Technology Committee (17DZ2272900 and 14495800500), Shanghai Municipal Commission of Health and Family Planning

We describe the microbiological characterization and clinical presentation of two fungemia cases caused by fluconazole-resistant Candida auris in neonatal intensive care unit of a hospital in Beijing, China. We advocate for the need of guidelines or recommendations to improve identification, surveillance, and implementation of infection control measures in Chinese hospitals.

Many uncommon Candida spp. (species other than C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and C. krusei) have been shown to emerge in tertiary care facilities. We aimed to investigate these uncommon candidemia in children. Forty-six cases of candidemia caused by uncommon Candida spp. were identified during 2003–2015 from a medical center in Taiwan. The most common specie was C. guilliermondii (31.2%), followed by C. lusitaniae (18.8%) and C. metapsilosis (18.8%). These cases were analyzed and compared with 148 episodes of C. albicans candidemia. The incidence density of uncommon Candida spp. candidemia and the proportion to all candidemia episodes increased substantively during the study period. Prior exposure to azoles was uncommon in the 30 days prior to infection, but fluconazole resistant strains were significantly more common (n = 19, 41.3%). The increased incidence density of uncommon Candida spp. candidemia was associated with increasing use of antifungal agents. No differences in demographics, underlying comorbidities, risk factors, clinical features, dissemination, and 30-day mortality were found between uncommon Candida spp. and C. albicans candidemia. Patients with uncommon Candida spp. candidemia were more likely to require modifications in antifungal treatment and receive echinocandin drugs (43.5% vs 21.6%, p = 0.007). Candidemia caused by uncommon Candida spp. had poorer response to antifungal treatment, led to longer duration of candidemia (median 4.0 versus 2.5 days, p = 0.008), and had a higher treatment failure rate (56.5% vs 38.5%, p = 0.040).

Increasing resistance Candida spp. In HIV-infected patients, often receiving long-term antifungal preparations, both for preventive and therapeutic purposes. It is necessary to develop effective treatment regimens based on the study of the resistance of Candida spp. to antifungal drugs, at species and genetic levels.

Clinicians are increasingly challenged by patients with refractory vulvovaginal candidiasis (VVC) caused by azole-resistant Candida species. Fluconazole resistant C.albicans is a growing and perplexing problem following years of indiscriminate drug prescription and unnecessary drug exposure and for which there are few therapeutic alternatives. Regrettably, although the azole class of drugs has expanded, new classes of antifungal drugs have not been forthcoming, limiting effective treatment options in patients with azole resistant Candida vaginitis.This review covers published data on epidemiology, pathophysiology and treatment options for women with azole-resistant refractory VVC.Fluconazole resistant C.albicans adds to the challenge of azole resistant non-albicans Candida spp. Both issues follow years of indiscriminate drug prescription and unnecessary fluconazole exposure. Although an understanding of azole resistance in yeast has been established, this knowledge has not translated into useful therapeutic advantage. Treatment options for such women with refractory symptoms are extremely limited. New therapeutic options and strategies are urgently needed to meet this challenge of azole drug resistance.

The newly recognised and emerging fungal species,Candida auris, has caused worldwide invasive infections and has been implicated in difficult to control hospital outbreaks. Challenges are encountered in the correct identification of this fungus as commonly used phenotypic and biochemical methods fail to differentiateC. aurisfrom otherCandidaspecies. Its resistance profile, over 90% of isolates are fluconazole resistant and 35% are resistant to amphotericin, confronts clinicians with the restricted arsenal of antifungals and concerns about optimal treatment. The very firstC. aurisisolate was recovered from a paediatric patient in retrospect. Although infections with the more antifungal-resistantCandidaspecies are less frequently observed in paediatric patients, this seems to be different forC. aurisinfections.

Background The incidence of azole-resistant Candida infections is increasing. Consequently, guidelines for treating systemic Candida infection (SCI) recommend a "de-escalation" strategy: initial broad-spectrum antifungal agents (e.g., echinocandins), followed by switching to fluconazole if isolates are fluconazole sensitive, rather than "escalation" with initial fluconazole treatment and then switching to echinocandins if isolates are fluconazole resistant. However, fluconazole may continue to be used as first-line treatment in view of its low acquisition costs. The aim of this study was, therefore, to evaluate the budget impact of the de-escalation strategy using micafungin compared with the escalation strategy in France and Germany. Methods A budget impact model was used to compare de-escalation to escalation strategies. As well as survival, clinical success (resolution/reduction of symptoms and radiographic abnormalities associated with fungal infection), was considered, as was mycological success (eradication of Candida from the bloodstream). Health economic outcomes included cost per health state according to clinical success and mycological success, and budget impact. A 42-day time horizon was used. Results For all patients with SCI, the budget impact of using de-escalation rather than escalation was greater, but improved rates of survival, clinical success and mycological success were apparent with de-escalation. In patients with fluconazole-resistant isolates, clinical success rates and survival were improved by ~72% with de-escalation versus escalation, producing cost savings of €6,374 and €356 per patient in France and Germany, respectively; improvements of ~72% in mycological success rates with de-escalation versus escalation did not translate into cost savings. Conclusion Modeling provides evidence that when treating SCI in individuals at risk of azole-resistant infections, de-escalation from micafungin has potential cost savings associated with improved clinical success rates.

Candidiasis is a fungal infection caused by yeasts that belong to the genus Candida. There are over twenty species of Candida yeasts that can cause infection in humans, the most common of which is Candida albicans. Candida yeasts normally reside in the intestinal tract and can be found on mucous membranes and skin without causing infection; however, overgrowth of these organisms can cause symptoms to develop. Presence of other diseases that compromises the patient's immunity makes it more difficult to treat. Candidiasis is majorly divided into superficial infections (oral or vaginal) and systemic infections, also known as invasive candidiasis. The conventional therapeutic modalities used to treat candidiasis are associated with several side effects that limits the dose and dosing frequency. Development of novel drug delivery systems for reduction in dose and alleviation of side effects is an important strategy to improve the clinical efficacy and patient acceptability. This review gives a bird's eye view of the classification and current therapeutic regime of candidiasis. It presents the varied types of drug delivery systems that have been exploited for delivery of antifungal agents with measurable benefits. It also touches upon echinocandins a relatively new class of drugs that are amenable for translation into novel dosage forms with application against biofilm producing and fluconazole resistant strains contributing to a better therapeutic management of candidiasis.

Summary Objective Honey is well known to possess a broad spectrum of activity against medically important organisms. The purpose of this study was to assess the antifungal activity of different honeys against 40 fluconazole (FLU) resistant Candida species, including Candida albicans ( C . albicans ), Candida glabrata , Candida krusei and Candida tropicalis . Materials and methods Three honey samples were collected from northern (Mazandaran, A), southern (Hormozgan, B) and central (Lorestan, C) regions of Iran. A microdilution technique based on the CLSI, M27-A2 protocol was employed to compare the susceptibility of honeys “A”, “B” and “C” against different pathogenic Candida isolates. Results The results showed that different Candida isolates were resistant to FLU, ranging from 64 μg/mL to 512 μg/mL. All of the honeys tested had antifungal activities against FLU-resistant Candida species, ranging from 20% to 56.25% (v/v) and 25% to 56.25% (v/v) for minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs), respectively. Honey “A” (MIC: 31.59%, v/v) showed higher anti- Candida activity than honey “B” (MIC: 35.99%, v/v) and honey “C” (MIC: 39.2%, v/v). No statistically significant differences were observed among the mean MIC values of the honey samples ( P > 0.05). The order of overall susceptibility of Candida species to honey samples were; C . krusei > C . glabrata > C . tropicalis > C . albicans ( P > 0.05). In addition, the mean MICs of Candida strains isolated from the nail, vagina and oral cavity were 33.68%, 36.44% and 39.89%, respectively, and were not significantly different ( P > 0.05). Conclusion Overall, varying susceptibilities to the anti- Candida properties of different honeys were observed with four FLU-resistant species of Candida. Further research is needed to assess the efficacy of honey as an inhibitor of candidal growth in clinical trials.

Almost 75% of women experience vulvovaginal Candida infection at least once during their lifetime and 90% of these infections are due to Candida albicans (Marchaim et al. 2012). Both diagnosis and ...

BackgroundCockroaches are common pests in homes and hospitals. They are known to cause allergic reactions in certain individuals and have found to be potential vectors for various bacterial and parasitic pathogens. This study assessed the potential of hospital cockroaches to act as vectors of medically important fungal pathogens on their external surfaces.MethodsCockroaches were captured from the main Intensive care unit (ICU), burn unit, adult surgical wards , pediatric oncology wards, intern hostel kitchen and the central kitchen of a national referral teaching hospital in Tanzania. Normal saline washings from the external surface of cockroaches were cultured on standard mycological media to facilitate isolation and identification of medically important molds and yeasts. Susceptibility of Candida sp isolates to fluconazole was tested using the CLSI M27-A3 microdilution method.ResultsAt total of 72 cockroaches were captured from various sites of the hospital between February and March 2015. All cockroaches captured were shown to carry medically importance fungi. A total of 956 medically important fungi were isolated, 57.9 % were Candida sp., 23.2%, Aspergillus sp. , 3.1% Cladosporium sp., 1.8% Rhizopus sp., 1.2 % Geotrichum sp., 0.9 % Pencillum sp. , 0.7% Alternaria sp, 0.6 % Fusarium sp , 0.3% Mucor sp and 10.1% others. Aspergillus fumigatus (50.0%) was the most commonly isolated followed by Aspergillus niger ( 15.8%) among the Aspergillus isolates.Over 16.3 % of the Candida isolates not intrinsically resistant to fluconazole showed resistance to this drug.mResistance was most frequently found in Candidapseudotropicalis (23.8%) and Candida glabarata (20.0%) and least in isolates of Candida albicans ( 6.3%). ConclusionThe external surfaces of cockroaches from this hospital may act as reservoirs of medically important opportunistic fungi exhibiting resistance to fluconazole.

Microbial biofilms act as reservoirs for pathogenic sessile microbes which reside inside the three dimensional matrix of the biofilm, and are thus protected against anti-microbial drugs. Most of the anti-microbial drugs fail to completely abolish the biofilm associated infections. In the present study, we provide evidence of Hibiscus sabdariffa (Hs) extract having possible anti-microbial activity, with emphasis on Candida albicans biofilm. The Hs extract was shown to be effective against C. albicans pre-formed biofilm at 3.125 mg/ml and was able to inhibit the hyphae initiation and adherence of cells. Furthermore, Hs extract was able to reduce the C. albicans load in C. elegans by effectively killing the Candida cells thereby reducing the viable colony count and effectively increasing the lifespan of worms. The percentage of viable hatched progeny of worms exposed to Hs extract (both at conc. 1.5 mg/ml and 6.25 mg/ml), was also comparable to that of the control untreated eggs. The Hs extract was also found to be significantly effective against fluconazole resistant C. albicans isolated from patients. Thus, we, for the first time, propose Hs extract as a prospective drug candidate and substitute for eradicating pre-formed biofilm and inhibiting the growth of C. albicans.

AIM During the last decade a continuous increase in non-albicans species isolation has been observed with Candida parapsilosis being one of the leading species. Aim of this study was to describe the epidemiology of candidemia, particularly of C parapsilosis, its predictors and clinical outcome. MATERIALS AND METHODS Incidences of candidemia was evaluated analyzing data from both a prospective collection (2012-2016) and a retrospective one (2008-2011). Predictors and outcome were based only on the prospective phase. C parapsilosis potential clusters were analysed by randomly amplified polymorphic DNA (RAPD) technique. RESULTS 1240 episodes were identified. Incidences of candidemia increased from 1.97 episodes/10 000 patient-days in 2008 to 4.59/10 000 patient-days in 2016 (P

A series of β-azole-phenylacetone derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible fungal infections and drug-resistant fungal infections. The antifungal activity of the synthesized compounds was assessed against five susceptible strains and five fluconazole-resistant strains. Antifungal activity tests showed that most of the compounds exhibited excellent antifungal activities against five pathogenic strains with MIC values in the range of 0.03–1 μg/mL. Compounds with R1 = 3-F substituted and 15o and 15ae exhibited moderate antifungal activities against fluconazole-resistant strains 17# and CaR with MIC values in the range of 1–8 μg/mL. Compounds with R1 = H or 2-F (such as 15a, 15o, 15p) displayed moderate to good antifungal activity against fluconazole-resistant strains 632, 901 and 904 with MIC values in the range of 0.125–4 μg/mL. Notably, 15o and 15ae exhibited antifungal activity against five susceptible strains and five fluconazole-resistant strains. Preliminary mechanistic studies showed that the potent antifungal activity of compound 15ae stemmed from inhibition of C. albicans CYP51. Compounds 15o, 15z and 15ae were nearly nontoxic to mammalian A549 cells.

SummaryBackground The use of photodynamic antimicrobial chemotherapy (PACT) to treat localized Candida infections is an emerging and promising therapeutic approach. Aim To assess the photodynamic inactivation (PDI) efficacy of haematoporphyrin monomethyl ether (HMME) on the biofilms produced by standard (ATCC 10231) and fluconazole-resistant Candida albicans strains. Methods The PDI efficacy was evaluated by incubating C. albicans biofilms with 0.01–10 μmol/L HMME for 30 min in the dark, followed by irradiation with 400–800 nm light for 30 min. Results HMME inactivated the biofilms in a concentration-dependent manner in the presence of light, but it exhibited no significant toxicity without light. After treatment with 10 μmol/L HMME and irradiation for 30 min, 2.47 and 3.26 log10 reductions in survival were achieved for C. albicans ATCC 10231 and fluconazole-resistant C. albicans, respectively. Conclusions Biofilms formed by the two strains were sensitive to HMME-mediated PDI.

BACKGROUND Over the last two decades, Candida blood stream infections (BSIs) have been increasingly reported from various parts of the world. Recent studies on invasive candidiasis have documented the emergence of non albicans Candida (NAC) species as major pathogens. Candida spp. belonging to NAC group often demonstrate intrinsic or acquired or both resistance to fluconazole which is the most readily available and prescribed cost effective antifungal agent. Echinocandins are recent addition to antifungal armamentarium and are now increasingly used as first line drugs for treatment and management of candidemia. OBJECTIVE The aim of this study was to determine echinocandin susceptibility profile of fluconazole resistant Candida Spp. isolated from BSIs. RESULTS Predominance of NAC spp was noted. C. glabrata followed by C. krusei and C. parapsilosis demonstrated high resistance to fluconazole. Echinocandins demonstrated good activity against all Candida spp. CONCLUSION As species distribution of Candida isolates varies greatly by country and by different health care setups within the country, species identification and antifungal susceptibility results are often useful to guide the selection of empiric treatment and design of local therapeutic guidelines. On the basis of antifungal susceptibility profile of the isolates, caspofungin can be suggested as a useful antifungal drug for the treatment of candidemia due to fluconazole resistant species.

We present the case of an HIV-seropositive individual with cryptococcal meningitis who was found to have a fluconazole resistant strain of Cryptococcus neoformans. The individual required multiple rounds of amphotericin and fluconazole 800–1200 mg after several episodes of clinical relapse. Cerebrospinal fluid sterilization was achieved and maintained with high doses of fluconazole. This case demonstrates the emerging dilemma of increasing rates of fluconazole resistance in Cryptococcus and the clinical difficulties in meningitis management.

Stephanoascus ciferrii is an ascomycetous yeast-like fungus, rarely causing human infections. It is also a teleomorph of Candida ciferrii. This species has a strong tendency to become resistant especially in patients on fluconazole prophylaxis. We report a case of post-mastoidectomy with continuous aural discharge not responding to topical and systemic treatment. Further characterisation showed ascospore formation and fluconazole resistance. Therefore, in vitro susceptibility testing is mandatory for the selection of appropriate antifungal drugs. This case report will alert the clinicians to look for fluconazole resistant yeast causing highly resistant aural infections.

Curtachalasins C–E (1–3), which have an unprecedent bridged 6/6/6/6 ring system, were identified from the endophytic fungus Xylaria cf. curta. Residual dipolar coupling analyses associating with density functional theory calculations were utilized to determine the relative configuration of noncrystallizable compound 2. The absolute configurations of 1–3 were determined by X-ray diffraction and electronic circular dichroism calculations. Remarkably, curtachalasin C (1) showed significant resistance reversal activity against fluconazole-resistant Candida albicans.

OBJECTIVES The emergence of fluconazole resistance in Candida parapsilosis healthcare-associated infections has recently been increasingly reported. Antifungal susceptibility profiles and mechanisms of fluconazole resistance in C. parapsilosis (n = 199) from nine hospitals in India collected over a period of 3 years were studied. Further, clonal transmission of fluconazole-resistant isolates in different hospitals was investigated. METHODS Antifungal susceptibility testing of five azoles, amphotericin B and 5-flucytosine was performed by the CLSI microbroth dilution method. The azole target ERG11 gene was sequenced, and the significance of a novel ERG11 mutation in C. parapsilosis was determined using a gap-repair cloning approach in Saccharomyces cerevisiae. In addition, microsatellite analysis was performed to determine the clonal lineage of C. parapsilosis-resistant strains circulating among different hospitals. RESULTS A total of 64 (32%) C. parapsilosis isolates were non-susceptible to fluconazole, which included resistant (n = 55; MIC >4 mg/L) and susceptible dose-dependent (n = 9) isolates. Of these 64 non-susceptible isolates, a novel K143R amino acid substitution was noted in 92%, and the remaining five isolates had the Y132F substitution. Elevated azole MICs (≥16-fold) were detected in S. cerevisiae upon expression of C. parapsilosis ERG11 alleles carrying Y132F or K143R substitutions. Two major clusters of non-susceptible isolates were circulating in seven Indian hospitals. CONCLUSIONS We report a novel K143R amino acid substitution in ERG11p causing fluconazole resistance in C. parapsilosis. Fluconazole-non-susceptible C. parapsilosis isolates carrying the novel K143R amino acid substitution should be identified in clinical microbiology laboratories to prevent further clonal transmission.