Drug-resistant Candida Species Research Articles

Antifungal activity of Fe3O4@SiO2/Schiff-base/Cu(II) magnetic nanoparticles against pathogenic Candida species

The antifungal efficacy and cytotoxicity of a novel nano-antifungal agent, the Fe3O4@SiO2/Schiff-base complex of Cu(II) magnetic nanoparticles (MNPs), have been assessed for targeting drug-resistant Candida species. Due to the rising issue of fungal infections, especially candidiasis, and resistance to traditional antifungals, there is an urgent need for new therapeutic strategies. Utilizing Schiff-base ligands known for their broad-spectrum antimicrobial activity, the Fe3O4@SiO2/Schiff-base/Cu(II) MNPs have been synthesized. The Fe3O4@SiO2/Schiff-base/Cu(II) MNPs was characterized by Fourier Transform-Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), Energy-dispersive X-ray (EDX), Vibrating Sample Magnetometer (VSM), and Thermogravimetric analysis (TGA), demonstrating successful synthesis. The antifungal potential was evaluated against six Candida species (C. dubliniensis, C. krusei, C. tropicalis, C. parapsilosis, C. glabrata, and C. albicans) using the broth microdilution method. The results indicated strong antifungal activity in the range of 8–64 μg/mL with the lowest MIC (8 μg/mL) observed against C. parapsilosis. The result showed the MIC of 32 μg/mL against C. albicans as the most common infection source. The antifungal mechanism is likely due to the disruption of the fungal cell wall and membrane, along with increased reactive oxygen species (ROS) generation leading to cell death. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay for cytotoxicity on mouse L929 fibroblastic cells suggested low toxicity and even enhanced cell proliferation at certain concentrations. This study demonstrates the promise of Fe3O4@SiO2/Schiff-base/Cu(II) MNPs as a potent antifungal agent with potential applications in the treatment of life-threatening fungal infections, healthcare-associated infections, and beyond.

Manganese(II), copper(II) and silver(I) complexes containing 1,10-phenanthroline/1,10-phenanthroline-5,6-dione against Candida species.

Background: New chemotherapeutics are urgently required to treat Candida infections caused by drug-resistant strains. Methods: The effects of 16 1,10-phenanthroline (phen)/1,10-phenanthroline-5,6-dione/dicarboxylate complexed with Mn(II), Cu(II) and Ag(I) were evaluated against ten different Candida species. Results: Proliferation of Candida albicans, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis and Candida tropicalis was inhibited by three of six Cu(II) (MICs 1.52-21.55μM), three of three Ag(I) (MICs 0.11-12.74μM) and seven of seven Mn(II) (MICs 0.40-38.06μM) complexes. Among these [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O, where oda=octanedioic acid, exhibited effective growth inhibition (MICs 0.4-3.25μM), favorable activity indexes, low toxicity against Vero cells and good/excellent selectivity indexes (46.88-375). Conclusion: [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O represents a promising chemotherapeutic option for emerging, medically relevant and drug-resistant Candida species.

Synthesis of 3-((4-Hydroxyphenyl)amino)propanoic Acid Derivatives as Promising Scaffolds for the Development of Antimicrobial Candidates Targeting Multidrug-Resistant Bacterial and Fungal Pathogens.

Infections caused by multidrug-resistant bacterial and fungal pathogens represent a significant global health concern, contributing to increased morbidity and mortality rates. Therefore, it is crucial to develop novel compounds targeting drug-resistant microbial strains. Herein, we report the synthesis of amino acid derivatives bearing an incorporated 4-hydroxyphenyl moiety with various substitutions. The resultant novel 3-((4-hydroxyphenyl)amino)propanoic acid derivatives 2-37 exhibited structure-dependent antimicrobial activity against both ESKAPE group bacteria and drug-resistant Candida species. Furthermore, these derivatives demonstrated substantial activity against Candida auris, with minimum inhibitory concentrations ranging from 0.5 to 64 µg/mL. Hydrazones 14-16, containing heterocyclic substituents, showed the most potent and broad-spectrum antimicrobial activity. This activity extended to methicillin-resistant Staphylococcus aureus (MRSA) with MIC values ranging from 1 to 8 µg/mL, vancomycin-resistant Enterococcus faecalis (0.5-2 µg/mL), Gram-negative pathogens (MIC 8-64 µg/mL), and drug-resistant Candida species (MIC 8-64 µg/mL), including Candida auris. Collectively, these findings underscore the potential utility of the novel 3-((4-hydroxyphenyl)amino)propanoic acid scaffold for further development as a foundational platform for novel antimicrobial agents targeting emerging and drug-resistant bacterial and fungal pathogens.

Cell-free supernatants of probiotic consortia impede hyphal formation and disperse biofilms of vulvovaginal candidiasis causing Candida in an ex-vivo model.

Vulvovaginal candidiasis is the second most common vaginal infection caused by drug-resistant Candida species that affects about 70-75% of reproductive age group women across the globe. As current-day antifungal drugs are ineffective against the biofilms formed by the drug-resistant Candida strains, several natural compounds and antagonistic microbes are being explored as alternative antifungal agents. In the present study, we investigated the anti-biofilm activity of Cell-Free Supernatant (CFS) extracted from the commercially available probiotics VSL-3 against the biofilms of Candida species and also evaluated their efficacy in curbing the yeast-to-hyphal transition. Various methodologies like crystal violet staining and scanning electron microscopy were used to study the effect of CFS against the biofilms formed by the species. The ability of CFS to interfere with yeast to hyphal transition in Candida was studied by colony morphology assay and visually confirmed with phase contrast microscopy. The potential of the CFS of the probiotics was also evaluated using goat buccal tissue, a novel ex-vivo model that mimics the vaginal environment. Moreover, the supernatant extracted from VSL-3 had the ability to down-regulate the expression of virulence genes of Candida from the biofilm formed over the ex-vivo model. These results emphasize the anti-fungal and anti-infective properties of the CFS of VSL-3 against drug-resistant Candida strains causing vulvovaginal candidiasis.

Antifungal potential of the new copper(II)-theophylline/1,10-phenanthroline complex against drug-resistant Candida species.

Candida spp. are the commonest fungal pathogens worldwide. Antifungal resistance is a problem that has prompted the discovery of novel anti-Candida drugs. Herein, 25 compounds, some of them containing copper(II), cobalt(II) and manganese(II) ions, were initially evaluated for inhibiting the growth of reference strains of Candida albicans and Candida tropicalis. Eight (32%) of the compounds inhibited the proliferation of these yeasts, displaying minimum inhibitory concentrations (MICs) ranging from 31.25 to 250μg/mL and minimum fungicidal concentration (MFCs) from 62.5 to 250μg/mL. Drug-likeness/pharmacokinetic calculated by SwissADME indicated that the 8 selected compounds were suitable for use as topical drugs. The complex CTP, Cu(theo)2phen(H2O).5H2O (theo = theophylline; phen = 1,10-phenanthroline), was chosen for further testing against 10 medically relevant Candida species that were resistant to fluconazole/amphotericin B. CTP demonstrated a broad spectrum of action, inhibiting the growth of all 20 clinical fungal isolates, with MICs from 7.81 to 62.5μg/mL and MFCs from 15.62 to 62.5μg/mL. Conversely, CTP did not cause lysis in erythrocytes. The toxicity of CTP was evaluated in vivo using Galleria mellonella and Tenebrio molitor. CTP had no or low levels of toxicity at doses ranging from 31.25 to 250μg/mL for 5days. After 24h of treatment, G. mellonella larvae exhibited high survival rates even when exposed to high doses of CTP (600μg/mL), with the 50% cytotoxic concentration calculated as 776.2μg/mL, generating selectivity indexes varying from 12.4 to 99.4 depending on each Candida species. These findings suggest that CTP could serve as a potential drug to treat infections caused by Candida species resistant to clinically available antifungals.

Potent Antifungal Activity of Penta-O-galloyl-β-d-Glucose against Drug-Resistant Candida albicans, Candida auris, and Other Non-albicans Candida Species.

Among fungal pathogens, infections by drug-resistant Candida species continue to pose a major challenge to healthcare. This study aimed to evaluate the activity of the bioactive natural product, penta-O-galloyl-β-d-glucose (PGG) against multidrug-resistant (MDR) Candida albicans, MDR Candida auris, and other MDR non-albicans Candida species. Here, we show that PGG has a minimum inhibitory concentration (MIC) of 0.25-8 μg mL-1 (0.265-8.5 μM) against three clinical strains of C. auris and a MIC of 0.25-4 μg mL-1 (0.265-4.25 μM) against a panel of other MDR Candida species. Our cytotoxicity studies found that PGG was well tolerated by human kidney, liver, and epithelial cells with an IC50 > 256 μg mL-1 (>272 μM). We also show that PGG is a high-capacity iron chelator and that deletion of key iron homeostasis genes in C. albicans rendered strains hypersensitive to PGG. In conclusion, PGG displayed potent anti-Candida activity with minimal cytotoxicity for human cells. We also found that the antifungal activity of PGG is mediated through an iron-chelating mechanism, suggesting that the compound could prove useful as a topical treatment for superficial Candida infections.

Vitamin D3: A promising antifungal and antibiofilm agent against Candida species.

Candida species are opportunistic fungal pathogens that cause mild to life-threatening infections in both immunocompetent and immunocompromised populations. The increasing prevalence of drug-resistant Candida species has posed a significant challenge to the management of infections in clinical settings. Therefore, this study aimed to investigate the direct antifungal and antibiofilm effect of vitamin D3 against Candida species. The antifungal activity of vitamin D3 was evaluated by broth microdilution method based on the Clinical and Laboratory Standard Institute. Prevention of biofilm formation by Candida albicans was measured using the XTT assay following exposure to different concentrations of vitamin D3. Moreover, expression of Agglutinin-like sequence gene 1 (ALS1), hyphal wall protein gene (HWP1), secreted aspartyl proteinase 6 gene (SAP6), and morphogenesis pathway regulatory gene (EFG1) were analyzed by real-time polymerase chain reaction using the comparative Ct method (ΔΔ Ct) after exposure to vitamin D3. Vitamin D3 showed antifungal activity against Candida species ranging from 1-128 μg/mL. Furthermore, vitamin D3 inhibited biofilm formation in a dose-dependent manner, with IC50 of 7.5 μg/mL. Treatment with vitamin D3 resulted in significant upregulation of the EFG1, ALS1, and SAP6 genes under hypha-inducing conditions to overcome environmental challenges. Results of the current study demonstrated that vitamin D3 has a significant inhibitory effect on Candida growth and biofilm formation. Considering its demonstrated antifungal and antibiofilm properties, vitamin D3 holds promise as a potential agent for medical applications.

Azobenzene derivatives with activity against drug-resistant Candida albicans and Candida auris.

Increasing resistance against antimycotic drugs challenges anti-infective therapies today and contributes to the mortality of infections by drug-resistant Candida species and strains. Therefore, novel antifungal agents are needed. A promising approach in developing new drugs is using naturally occurring molecules as lead structures. In this work, 4,4'-dihydroxyazobenzene, a compound structurally related to antifungal stilbene derivatives and present in Agaricus xanthodermus (yellow stainer), served as a starting point for the synthesis of five azobenzene derivatives. These compounds prevented the growth of both fluconazole-susceptible and fluconazole-resistant Candida albicans and Candida auris strains. Further in vivo studies are required to confirm the potential therapeutic value of these compounds.

Distribution, trends, and antifungal susceptibility of Candida species causing candidemia in Japan, 2010-2019: A retrospective observational study based on national surveillance data.

The increasing incidence of candidemia and the emergence of drug-resistant Candida species are major concerns worldwide. Therefore, long-term surveillance studies are required. Here, we provide one of the largest longitudinal overviews of the trends in the prevalence of Candida species using national data of 57 001 candidemia isolates obtained from > 2000 hospitals for the 2010–2019 period in the Japan Nosocomial Infections Surveillance database. The proportion of Candida species, except Candida krusei and Candida guilliermondii, was almost the same during the study period. The proportion of C. guilliermondii surpassed that of C. krusei in 2014. The incidence of candidemia due to C. albicans (P < 0.0001), C. parapsilosis (P = 0.0002), and C. tropicalis (P < 0.0001) have decreased significantly over this period. Azole susceptibility of C. tropicalis was low, with 17.8% of isolates resistant to fluconazole and 13.5% resistant to voriconazole. The micafungin susceptibility of C. glabrata was low, with 8.0% of isolates showing resistance. The resistance rate of C. krusei toward amphotericin B fluctuated considerably (between 3.2% and 35.7%) over this period. The incidence rate of candidemia caused by C. parapsilosis and C. guilliermondii in hospitals responsible for bone marrow transplantation was significantly higher than that in other hospitals. Overall, our study suggests that in Japan, the species distribution of Candida was almost the same in this period and similar to that reported in North America and Europe. A relatively high resistance to azoles and micafungin was observed in C. glabrata, C. tropicalis, and C. krusei isolates, which require continued surveillance.

ANTIFUNGAL DRUG RESISTANCE PATTERN AMONG BIOFILM PRODUCING STRAINS OF CANDIDA SPECIES ISOLATED FROM BLOODSTREAM INFECTIONS

Background &amp; objectives: The emergence of drug resistant Candida species has become an important cause of health care associated infections. Antimicrobial resistance is very high in biolm-producing Candida strains. This study was carried out with an aim to study species distribution of Candida isolates among candidemia patients, biolm formation as a virulence factor and their antifungal susceptibility pattern. A total ofMethods: 100 consecutive Candida isolates obtained from blood culture samples were included in the study. Identication of the isolates were done by conventional method and VITEK 2. The antifungal susceptibility were done by VITEK 2 and E test method. Biolm formation was detected using Congo red agar medium, Test tube method and Microtitre plate method. Of the total 100 Candida isolates evaluated, Candida albicansResults: (n=34 isolates) was most common followed by C. tropicalis (n=20 isolates). A larger number of Candida spp. (71%) produced biolm. Biolm production by NAC was signicantly more frequent (75.75%) than that by C. albicans (61.76%). Antifungal resistance rates for Fluconazole (30.98%), Amphotericin B (15.49%) and Flucytosine (11.26%) were higher among the biolm producing strains. All the strains of C. krusei were resistant to Fluconazole and Flucytosine and all strains of C. auris were found resistant to uconazole. Interpretation &amp; Conclusion: Speciation of Candida becomes important as the prevalence of NAC is increasing. Biolm formation exhibits increased resistance to commonly available antifungal therapies. These data has become necessary to reduce the net effect of the increasing severity of Candida infections, drug resistance, and economic burden.

Study of Colonisation Pattern and Antifungal Sensitivity Profile of Candida Species in Diabetic Patients

Introduction: In recent times, various studies have pointed out the rise in prevalence of Candida species causing Urinary Tract Infections (UTIs). Candiduria appears to be underdiagnosed entity and thus has been the source of morbidity and mortality. Emergence of drug resistant Candida species has further complicated the patient management. Aim: To understand the colonisation pattern and antifungal sensitivity profile of Candida species in diabetic patients. Materials and Methods: This cross-sectional study was conducted for a period of six months (July 2019 to December 2019) at a tertiary care teaching centre of southern Haryana, India. A total of 360 urine samples were collected from patients admitted both outpatient and in-patient. Glycated Haemoglobin (HbA1c) ≥6.5% was taken as having diabetes. The urine samples were collected as per standard guidelines. Urine wet mount examination was performed. Confirmation of identification and antifungal susceptibility testing was done for all the Candida isolates. Data was analysed using statistical software. Results: The prevalence of candiduria was 65 (18.1%) among study subjects. Out of significant candiduria patients 19 (29.23%) were having Candida albicans, 30 (46.16%) were Candida tropicalis, 10 (15.38%) were Candida krusei, 6 (9.23%) Candida glabrata. Candida albicans was found to be sensitive to amphotericin-B in 100% of cases. Sensitivity to flucytosine, voriconazole and fluconazole was found to be 89.47%, 89.47% and 84.21% respectively in case of Candida albicans. Conclusion: The prevalence of candiduria is definitely high in this region. Non albicans Candida species are more resistant to antifungal drugs compared to Candida albicans.

Drug Resistance and Novel Therapeutic Approaches in Invasive Candidiasis.

Candida species are the leading cause of invasive fungal infections worldwide and are associated with acute mortality rates of ~50%. Mortality rates are further augmented in the context of host immunosuppression and infection with drug-resistant Candida species. In this review, we outline antifungal drugs already in clinical use for invasive candidiasis and candidaemia, their targets and mechanisms of resistance in clinically relevant Candida species, encompassing not only classical resistance, but also heteroresistance and tolerance. We describe novel antifungal agents and targets in pre-clinical and clinical development, including their spectrum of activity, antifungal target, clinical trial data and potential in treatment of drug-resistant Candida. Lastly, we discuss the use of combination therapy between conventional and repurposed agents as a potential strategy to combat the threat of emerging resistance in Candida.

Trends of the Epidemiology of Candidemia in Switzerland: A 15-Year FUNGINOS Survey.

BackgroundThe increasing incidence of candidemia and emergence of drug-resistant Candida species are major concerns worldwide. Long-term surveillance studies are needed.MethodsThe Fungal Infection Network of Switzerland (FUNGINOS) conducted a 15-year (2004–2018), nationwide, epidemiological study of candidemia. Hospital-based incidence of candidemia, Candida species distribution, antifungal susceptibility, and consumption were stratified in 3 periods (2004–2008, 2009–2013, 2014–2018). Population-based incidence over the period 2009–2018 derived from the Swiss Antibiotic Resistance Surveillance System (ANRESIS).ResultsA total of 2273 Candida blood isolates were studied. Population and hospital-based annual incidence of candidemia increased from 2.96 to 4.20/100 000 inhabitants (P = .022) and 0.86 to 0.99/10 000 patient-days (P = .124), respectively. The proportion of Candida albicans decreased significantly from 60% to 53% (P = .0023), whereas Candida glabrata increased from 18% to 27% (P < .0001). Other non-albicans Candida species remained stable. Candida glabrata bloodstream infections occurred predominantly in the age group 18–40 and above 65 years. A higher proportional increase of C glabrata was recorded in wards (18% to 29%, P < .0001) versus intensive care units (19% to 24%, P = .22). According to Clinical and Laboratory Standards Institute, nonsusceptibility to fluconazole in C albicans was observed in 1% of isolates, and anidulafungin and micafungin nonsusceptibility was observed in 2% of C albicans and C glabrata. Fluconazole consumption, the most frequently used antifungal, remained stable, whereas use of mold-active triazoles and echinocandins increased significantly in the last decade (P < .0001).ConclusionsOver the 15-year period, the incidence of candidemia increased. A species shift toward C glabrata was recently observed, concurring with increased consumption of mold-active triazoles.

Factors influencing the presence of Candida dubliniensis and other non-albicans species in patients with oral lichen planus: a retrospective observational study

ObjectivesThe epidemiologic distribution of non-albicans species in the oral cavity of oral lichen planus (OLP) patients remains uncertain. Therefore, the aim of this study was to identify factors associated with the presence of C. dubliniensis and other non-albicans species. Furthermore, independent risk factors for Candida superinfection in OLP should be identified.Material and methodsEpidemiologic data and microbiological findings from 268 symptomatic OLP patients who underwent continuous oral swab culture over a 5-year period (2015–2019) were retrospectively reviewed. Candida species identification and semi-quantification were obtained by culture on CHROMagar Candida, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).ResultsC. albicans was the most frequently isolated species (72.3%), followed by C. glabrata (7.3%), C. dubliniensis (5.8%), C. krusei and C. parapsilosis (both 2.6%). The presence of C. dubliniensis was significantly associated with tobacco smoking. Other non-albicans spp. were significantly more often detected in patients using removable dentures. Increasing age and the intake of psychotropic drugs were identified as independent risk factors of Candida superinfection in OLP.ConclusionIn OLP patients, certain local and systemic factors increase the risk of carrying potentially drug-resistant Candida species and the development of Candida superinfection of OLP lesions.Clinical relevanceDue to the frequent detection of non-albicans species in OLP, resistance or at least reduced sensitivity to azole antifungals should be expected, especially in smokers and patients using removable dentures. In the case of oral complaints, a superinfection with Candida should be considered, whereby older patients and patients taking psychotropic drugs have an increased risk for oral infection with Candida.

Flow Cytometric Measurement of Efflux in Candida Species.

A technique to assess the ability of distinct Candida strains to efflux substrates, as well as to compare the effectiveness of efflux inhibitors, is important for analysis of antifungal drug resistance mechanisms and the mode of action of antifungals. We describe a method that measures the ability of Candida species to extrude the fluorescent dye Nile red as an output for efflux activity. This involves exposing cells to Nile red and using flow cytometry to quantify cellular fluorescence, enabling numerous samples to be processed in a limited time frame. This protocol provides a simple, yet effective method for quantifying efflux in drug-resistant Candida species. © 2020 Wiley Periodicals LLC Basic Protocol 1: Growth and sample preparation of stained Candida Basic Protocol 2: Quantitative measurement of fluorescence by flow cytometry Alternate Protocol: Qualitative determination of fluorescence using microscopy.

Select health care–associated infections are declining

Central line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), and Clostridioides difficile infections all declined between 2017 and 2018 across four health care settings, according to CDC’s National and State Healthcare-Associated Infections Progress Report, released in November 2019. Health care–associated infections can result in increased morbidity and mortality, length of hospital stay, and health care–associated costs. The report compiles data from more than 22,000 active hospitals and other health care facilities: acute care hospitals, critical access hospitals, inpatient rehabilitation facilities, and long-term acute care hospitals. The results suggest that interventions targeted at reducing these types of infections appear to be working, with antibiotic stewardship efforts a main factor in the declining rates. Overall, CLABSIs decreased 9% between 2017 and 2018, with the largest decrease in the ICU (11%). One intervention that has led to reduced CLABSI rates is bundle implementation with use of chlorhexidine dressings, said Amy Hanson, PharmD, BCPS AQ-ID, an antimicrobial stewardship and infectious disease pharmacist at the Chicago Department of Public Health, in an interview with Pharmacy Today. “In a study conducted during my time at Rush [University Medical Center in Chicago], we published data showing that moving from peripheral draw to phlebotomist draw via central lines had a reduction in CLABSI rates over time, by reducing the contamination risk (false-positive CLABSIs),” said Hanson. “This was particularly true in certain patient populations, such as our hematology/oncology patients. We were also able to show a reduction in vancomycin use over time.” For CAUTIs, there was about an 8% decrease between 2017 and 2018, with the largest decrease also observed in the ICU for this infection (10%). Hanson noted that a number of basic interventions could have contributed to the reduction in CAUTI rates, such as the many interventions focused primarily on education and training. Others include local adoption of guidelines or protocols, use of an opinion leader, audit and feedback, multidisciplinary team involvement, and reminders and stop orders. Hospital-onset C. difficile infections saw about a 12% decrease between 2017 and 2018. Antibiotic stewardship intervention efforts aimed at lowering C. difficile rates, such as those recommended in the C. difficile guidelines of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America, have surely contributed to this decline, noted Hanson. These include implementation of restrictions on the use of certain antibiotics (primarily fluoroquinolones) and the potentially broader use of prophylactic oral vancomycin in high-risk patients receiving broad-spectrum systemic antibiotics. Another CDC report, Antibiotic Resistance Threats in the U.S. 2019, revealed improvements in select areas, with 18% fewer deaths from antibiotic resistance and 28% fewer deaths from antibiotic resistance in hospitals. When individual pathogens were assessed, infections caused by vancomycin-resistant Enterococcus decreased by 41%, multidrug-resistant Pseudomonas aeruginosa by 29%, methicillin-resistant Staphylococcus aureus (MRSA) by 21%, carbapenem-resistant Acinetobacter baumannii by 33%, and drug-resistant Candida species by 25%. Rates of carbapenem-resistant Enterobacteriaceae and drug-resistant tuberculosis disease cases remained stable. CDC attributed some of these findings to interventions that focus on preventing device- and procedure-related infections, such as urinary catheters or central lines; stopping the spread of resistant germs within and between health care facilities; containing emerging threats through early detection and aggressive response; tracking and improving appropriate antibiotic use; and infection prevention and control in nonhospital settings, such as long-term-care facilities. Although rates of CLABIs, CAUTIs, and C. difficile appear to be declining, other infections saw no change in their rates between 2017 and 2018, including ventilator-associated pneumonia, skin and soft tissue infections, and hospital-onset MRSA bacteremia. In addition, in CDC’s report on antibiotic resistance, the agency reported that more than 2.8 million antibiotic-resistant infections—and more than 35,000 deaths from antibiotic resistance—occur each year. These data suggest that more work needs to be done to help reduce the rates of these infections. Pharmacists working in acute and long-term health care settings can play an active role in helping implement interventions aimed at improving the rates of these infections, with a focus on antibiotic stewardship efforts.

A budding case of infectious endocarditis: Candida lusitaniae.

This is a case of recurrent Candida lusitaniae prosthetic valve endocarditis with budding yeast and pseudohyphae on the histopathology. This case illustrates the importance of keeping vigilant in recognizing some of the emerging drug resistant Candida species in our practice.

Isolation and Identification of Actinomycetes with Anticandida Activity from Mangrove Soil

Candida albicans, a common human commensal, is the leading cause of nosocomial infections due to the emergence of drug resistance. The present study reports the isolation and identification of actinomycetes from mangrove soil and characterization of its antagonistic activity against drug resistant Candida species. Mangrove soils from Khargar, Navi Mumbai were screened for actinomycetes with anti-candida activity. In total, 20 actinomycetes culture were isolated from mangrove soil sample, amongst the culture designated as MB was found to inhibit all tested pathogenic Candida cultures. The isolate MB was identified using biochemical tests and 16S rRNA sequencing as Streptomyces viridocromogenes. MB culture showed maximum activity after incubation period of 48 to 72 h, pH of 6.2 and temperature of 30℃. Partially purified active molecule was found to be inactivated by heat treatment but resisted proteinase K, indicating the compound can be an antibiotic in nature. The study highlights the isolation of Streptomyces viridocromogenes with antagonistic activity against multidrug resistant Candida from mangrove soil. This culture is an ideal candidate for further characterization studies for anti-candida molecules.

Proteomic analysis uncovers the modulation of ergosterol, sphingolipid and oxidative stress pathway by myristic acid impeding biofilm and virulence in Candida albicans

Candida albicans, a dimorphic opportunistic fungus is known to form robust biofilm and commonly associated with superficial and life threatening systemic infections. The repertoire of C. albicans infection is comprehensive due to its biofilm mediated virulence and occurrence of resistance against conventional antifungal drugs. Natural bioactive compounds are known for their antivirulence potency against fungi circumventing their resistance. In the present study, antibiofilm and antihyphal efficacies of myristic acid (MA), a major component of Myristica fragrans against C. albicans was assessed. Results of biofilm assays, optical microscopic analyses showed the potent inhibition of biofilm and hyphal formation by MA at 125 μg mL−1. Proteomic analysis revealed the ability of MA to target proteins involved in various virulence pathways such as ergosterol synthesis, sphingolipid metabolism, multidrug resistance and the oxidative stress. The results of gene expression analysis and biochemical assays validated the outcomes of proteomic analysis. This investigation emphasized the potent antibiofilm and virulence inhibitory potentials of MA. Hence, MA could be clinically utilized to control infections caused by C. albicans. Biological significanceThe conventional antifungal drugs acquire single target pattern by regulating either sterol synthesis or drug efflux pump in C. albicans that ushers drug-resistance. But Myristic acid attenuates C. albicans virulence by negative regulation of proteins involved in sterol synthesis & uptake, sphingolipids and antioxidant activity. In the current study, the multi-target efficacy and the ability to inhibit biofilm and hyphae mediated virulence factors without affecting the cellular metabolism of C. albicans marks myristic acid as a potent anti-candida agent against drug resistant Candida species.

Anethumgraveolens and Apiumgraveolens leaf-extract and their antifungal effects on pathogenic Candida species: In vitro study

Background and objective: The constant increase of Candida infection and unstopping emergence of drug resistant Candida species is a major concern. Natural medicinal products particularly those of edible plant could be a safe and effective alternative to synthetic substances. Considering their anti-microbial contents, the leave extracts of Anethemgraveolens and Apiumgraveolens have been investigated for their effects against Candida species. Methods: Fresh leaves of Anethem and Apium were collected from Erbil province in Iraq. The leaves were dried then after grinding the ethanol extract was prepared. The radical scavenging activity of extracts was measured via DPPH inhibition activity method. Anti-Candida effect was assessed against C. albicans, C. glabrata, C. krusei, C. tropicalis, C. tamatta, C. parapsiosis, and C. guilliermondii. Standard antifungal drugs were used as control including Nystatin, Clotrimazole, Fluconazole, Ketoconazole, and Miconazole. Results: The highest radical scavenging activity of both extracts was found at 0.2 mg/mL. Both extracts did not affect the growth inhibition of C. krusei, C. tropicalis, and C. tamatta. However, they were significantly effective to the extent of other antifungal drugs against the growth of other Candida species including C. albicans, C. glabrata, C. guillermondii, and C. parapsiosis. Conclusion: The findings of this study suggest that both Apium and Anethem which are widespread vegetable and could have similar anti-Candia effects which can be a great alternative to the commonly used antifungal drugs.