Effect of chlorogenic and gallic acids combined with azoles on antifungal susceptibility and virulence of multidrug-resistant Candida spp. and Malassezia furfur isolates

2020 ◽  
Vol 58 (8) ◽  
pp. 1091-1101
Author(s):  
Wafa Rhimi ◽  
Chioma Inyang Aneke ◽  
Giada Annoscia ◽  
Domenico Otranto ◽  
Teun Boekhout ◽  
...  
Keyword(s):  
Extracellular Enzymes ◽  
Antifungal Susceptibility ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
High Morbidity ◽  
Candida Spp ◽  
Pichia Kudriavzevii ◽  
Malassezia Spp ◽  
Time Kill

Abstract Chlorogenic acid (CHA) and gallic acid (GA) are safe natural phenolic compounds that are used as enhancers of some drugs in influencing antioxidant, anticancer, and antibacterial activities. Among fungi, Candida spp. and Malassezia spp. are characterized by an increasing prevalence of multidrug resistance phenomena and by a high morbidity and mortality of their infections. No data are available about the efficacy of CHA and GA combined with azoles on the antifungal susceptibility and on the virulence of both fungi. Therefore, their antifungal and antivirulence effects have been tested in combination with fluconazole (FLZ) or ketoconazole (KTZ) on 23 Candida spp. and 8 M. furfur isolates. Broth microdilution chequerboard, time-kill studies, and extracellular enzymes (phospholipase and hemolytic) activities were evaluated, displaying a synergistic antifungal action between CHA or GA and FLZ or KTZ on C. albicans, C. bovina, and C. parapsilosis, and antagonistic antifungal effects on M. furfur and Pichia kudriavzevii (Candida krusei) isolates. The time-kill studies confirmed the chequerboard findings, showing fungicidal inhibitory effect only when the GA was combined with azoles on Candida strains. However, the combination of phenolics with azoles had no effect on the virulence of the tested isolates. Our study indicates that the combination between natural products and conventional drugs could be an efficient strategy for combating azole resistance and for controlling fungistatic effects of azole drugs.

scholarly journals Antimicrobial Effects of Minocycline, Tigecycline, Ciprofloxacin, and Levofloxacin against Elizabethkingia anophelis using In Vitro Time-Kill Assays and In Vivo Zebrafish Animal Models

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 285
Author(s):  
Jiun-Nong Lin ◽  
Chung-Hsu Lai ◽  
Yi-Han Huang ◽  
Chih-Hui Yang
Keyword(s):  
Animal Models ◽  
Antibacterial Activities ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Time Kill

Elizabethkingia anophelis is a multidrug-resistant pathogen. This study evaluated the antimicrobial activity of minocycline, tigecycline, ciprofloxacin, and levofloxacin using in vitro time-kill assays and in vivo zebrafish animal models. The E. anophelis strain ED853-49 was arbitrarily selected from a bacterial collection which was concomitantly susceptible to minocycline, tigecycline, ciprofloxacin, and levofloxacin. The antibacterial activities of single agents at 0.5–4 × minimum inhibitory concentration (MIC) and dual-agent combinations at 2 × MIC using time-kill assays were investigated. The therapeutic effects of antibiotics in E. anophelis-infected zebrafish were examined. Both minocycline and tigecycline demonstrated bacteriostatic effects but no bactericidal effect. Minocycline at concentrations ≥2 × MIC and tigecycline at concentrations ≥3 × MIC exhibited a long-standing inhibitory effect for 48 h. Bactericidal effects were observed at ciprofloxacin and levofloxacin concentrations of ≥3 × MIC within 24 h of initial inoculation. Rapid regrowth of E. anophelis occurred after the initial killing phase when ciprofloxacin was used, regardless of the concentration. Levofloxacin treatment at the concentration of ≥2 × MIC consistently resulted in the long-lasting and sustainable inhibition of bacterial growth for 48 h. The addition of minocycline or tigecycline weakened the killing effect of fluoroquinolones during the first 10 h. The minocycline-ciprofloxacin or minocycline–levofloxacin combinations achieved the lowest colony-forming unit counts at 48 h. Zebrafish treated with minocycline or a combination of minocycline and levofloxacin had the highest survival rate (70%). The results of these in vitro and in vivo studies suggest that the combination of minocycline and levofloxacin is the most effective therapy approach for E. anophelis infection.

Etest ECVs/ECOFFs for detection of resistance in prevalent and three non-prevalent Candida spp. to triazoles and amphotericin B and Aspergillus spp. to caspofungin: Further assessment of modal variability

2021 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
M. Sasso ◽  
J. Turnidge ◽  
M. Arendrup ◽  
F. Botterel ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Point Mutations ◽  
Fungal Species ◽  
Candida Spp ◽  
Pichia Kudriavzevii ◽  
Routine Testing ◽  
Data Points

Susceptibility testing is an important tool in the clinical setting; its utility is based on the availability of categorical endpoints, breakpoints (BPs) or epidemiological cutoff values (ECVs/ECOFFs). CLSI and EUCAST have developed antifungal susceptibility testing, BPs and ECVs for some fungal species. Although the Concentration Gradient Strip BioMerieux Etest is useful for routine testing in the clinical laboratory, ECVs are not available for all agent/species; the lack of clinical data precludes development of BPs. We re-evaluated and consolidated Etest data points from three previous studies, and included new data. We defined ECOFFinder Etest ECVs for three sets of species/agent combinations: fluconazole, posaconazole and voriconazole and 8 Candida spp.; amphotericin B and 3 non-prevalent Candida spp.; and caspofungin and 5 Aspergillus spp. The total of Etest MICs from 23 laboratories (Europe, the Americas, South Africa) included (antifungal agent/dependent): 17,242 Candida albicans , 244 C. dubliniensis , 5,129 C. glabrata species complex (SC), 275 C. guilliermondii ( Meyerozyma guilliermondii ), 1,133 C. krusei ( Pichia kudriavzevii ), 933 C. kefyr ( Kluyveromyces marxianus ), 519 C. lusitaniae ( Clavispora lusitaniae ), 2,947 C. parapsilosis SC, 2,214 C. tropicalis , 3,212 Aspergillus fumigatus , 232 A. flavus , 181 A. niger , and 267 A. terreus SC isolates. Triazole MICs for 66 confirmed non-wild-type (non-WT) Candida isolates were available ( ERG11 point mutations). Distributions fulfilling CLSI ECV criteria were pooled and ECOFFinder Etest ECVs were established for triazoles (9 Candida spp.); amphotericin B (3 less-prevalent Candida spp.) and caspofungin (4 Aspergillus spp.). Etest fluconazole ECVs could be good detectors of Candida non-WT isolates (59/61 Non-WT: 4 of 6 species).

scholarly journals Thermogenic Characterization and Antifungal Susceptibility of Candida auris by Microcalorimetry

2019 ◽  
Vol 5 (4) ◽  
pp. 103 ◽  
Author(s):  
Mariagrazia Di Luca ◽  
Anna Koliszak ◽  
Svetlana Karbysheva ◽  
Anuradha Chowdhary ◽  
Jacques Meis ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Heat Production ◽  
Therapeutic Option ◽  
Antifungal Susceptibility ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Candida Spp ◽  
Heat Curve ◽  
Candida Lusitaniae ◽  
Minimum Heat

Candida auris has emerged globally as a multidrug-resistant fungal pathogen. Isolates of C. auris are reported to be misidentified as Candida haemulonii. The aim of the study was to compare the heat production profiles of C. auris strains and other Candida spp. and evaluate their antifungal susceptibility using isothermal microcalorimetry. The minimum heat inhibitory concentrations (MHIC) and the minimum biofilm fungicidal concentration (MBFC) were defined as the lowest antimicrobial concentration leading to the lack of heat flow production after 24 h for planktonic cells and 48 h for biofilm-embedded cells. C. auris exhibited a peculiar heat production profile. Thermogenic parameters of C. auris suggested a slower growth rate compared to Candida lusitaniae and a different distinct heat profile compared to that of C. haemulonii species complex strains, although they all belong to the Metschnikowiaceae clade. Amphotericin B MHIC and MBFC were 0.5 µg/mL and ≥8 µg/mL, respectively. C. auris strains were non-susceptible to fluconazole at tested concentrations (MHIC > 128 µg/mL, MBFC > 256 µg/mL). The heat curve represents a fingerprint of C. auris, which distinguished it from other species. Treatment based on amphotericin B represents a potential therapeutic option for C. auris infection.

scholarly journals Beta vulgaris Assisted Fabrication of Novel Ag-Cu Bimetallic Nanoparticles for Growth Inhibition and Virulence in Candida albicans

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1957
Author(s):  
Majid Rasool Kamli ◽  
Maqsood Ahmad Malik ◽  
Shabir Ahmad Lone ◽  
Jamal S. M. Sabir ◽  
Ehab H. Mattar ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Beta Vulgaris ◽  
Extracellular Enzymes ◽  
Bimetallic Nanoparticles ◽  
Antifungal Susceptibility ◽  
Extracellular Enzyme ◽  
Inhibitory Effect ◽  
Water Soluble ◽  
Haemolytic Assay

Beta vulgaris extract contains water-soluble red pigment betanin and is used as a food colorant. In this study, the biogenic Ag-Cu bimetallic nanoparticles were synthesized and characterized by different spectroscopic and microscopic techniques, including UV–Visible, FTIR, TEM. SEM-EDX, XRD, and TGA. Further, Ag-Cu bimetallic nanoparticles capped with Beta vulgaris biomolecules were evaluated for their antifungal activity against Candida albicans via targeting its major virulence factors, including adherence, yeast to hyphae transition, extracellular enzyme secretion, biofilm formation, and the expression of genes related to these pathogenic traits by using standard methods. C. albicans is an opportunistic human fungal pathogen that causes significant morbidity and mortality, mainly in immunocompromised patients. The current antifungal therapy is limited with various shortcomings such as host toxicity and developing multidrug resistance. Therefore, the development of novel antifungal agents is urgently required. Furthermore, NPs were screened for cell viability and cytotoxicity effect. Antifungal susceptibility testing showed potent antifungal activity of the Ag-Cu bimetallic NPs with a significant inhibitory effect on adherence, yeast to hyphae transition, extracellular enzymes secretion, and formation of biofilms in C. albicans at sub-inhibitory and inhibitory concentrations. The RT-qPCR results at an MIC value of the NPs exhibited a varying degree of downregulation in expression levels of virulence genes. Results also revealed the dose-dependent effect of NPs on cellular viability (up to 100%) using MUSE cell analyzer. Moreover, the low cytotoxicity effect of bimetallic NPs has been observed using haemolytic assay. The overall results indicated that the newly synthesized Ag-Cu bimetallic NPs capped with Beta vulgaris are proven to possess a potent anticandidal activity, by affecting the vital pathogenic factors of C. albicans.

scholarly journals Setting a Protocol for Identification and Detecting the Prevalence of Candida auris in Tertiary Egyptian Hospitals Using the CDC Steps

2021 ◽  
Vol 9 (A) ◽  
pp. 397-402
Author(s):  
Sahar Mohammed Khairat ◽  
Mervat Gaber Anany ◽  
Maryam Mostafa Ashmawy ◽  
Amira Farouk Ahmed Hussein
Keyword(s):  
Opportunistic Infections ◽  
Antifungal Susceptibility ◽  
Multidrug Resistant ◽  
University Hospitals ◽  
Candida Auris ◽  
Candida Spp ◽  
Maldi Tof ◽  
The World ◽  
Cdc Guidelines ◽  
Resistance Patterns

BACKGROUND: Candida is considered the most common cause of opportunistic infections in the world. Increased use of antifungal agents may have led to increasing resistance of Candida for antifungals and may be related to therapeutic failures. Recently, a multidrug-resistant Candida auris has immerged causing outbreaks in several countries all over the world. This discovered superbug is widely spread causing a broad range of health care-associated infections. AIM: This study aims to set a protocol for the identification and detection of the prevalence of C. auris in tertiary Egyptian hospitals following the center of disease and control (CDC) methodology. METHODOS: Over almost 2 years, 400 Candida isolates were collected from different wards of Cairo University Hospitals. Identification of species of all isolates was done by germ tube test followed by sub-culturing on chromogenic agar media for confirmation. Candida non-albicans isolates were further subjected to thermotolerance. Isolates that grew in 42°C were further identified by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry for definite species identification. Antifungal susceptibility using E-test was done for isolates identified by MALDI to detect resistance patterns. RESULTS: Among the 400 isolates, 227 (56.75%) were Candida albicans while 180 (43.25%) were non-albicans Candida. Candida non-albicans was classified by Chromagar as following; 25 (13.8%) were Candida tropicalis, 43 (23.8%) were Candida krusei, and 112 (62.2%) were other Candida spp. (Candida glabrata, Candida kefyr, Candida parapsilosis, and Candida lusitaniae). Using thermotolerance, 10 isolates grew at 42°C suspecting C. auris. MALDI-TOF was used for definite and final identification; five isolates were identified as C. glabrata, four as C. krusei, and one C. kefyr. Antifungal susceptibility testing of the 10 identified isolates revealed total resistance to fluconazole. CONCLUSION: Following the set protocol for identification based on CDC guidelines, C. auris is not prevalent in Egyptian hospitals. Fluconazole resistance is on the surge among candida isolates. Further studies on a bigger scale including larger number of hospitals are recommended.

Synergistic Effect of Tazobactam on Amikacin MIC in Acinetobacter baumannii Isolated from Burn Patients in Tehran, Iran

2020 ◽  
Vol 21 (10) ◽  
pp. 997-1004
Author(s):  
Leila Azimi ◽  
Sahel V. Tahbaz ◽  
Reza Alaghehbandan ◽  
Farank Alinejad ◽  
Abdolaziz R. Lari
Keyword(s):  
Acinetobacter Baumannii ◽  
Inhibitory Concentration ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Resistant Bacteria ◽  
High Morbidity ◽  
Burn Patients ◽  
Global Public Health ◽  
Before And After

Background: Burn is still an important global public health challenge. Wound colonization of antibiotic resistant bacteria such as Acinetobacter baumannii can lead to high morbidity and mortality in burn patients. The aim of this study was to evaluate the inhibitory effect of tazobactam on efflux pump, which can cause aminoglycoside resistant in A. baumannii isolated from burn patients. Methods: In this study, 47 aminoglycoside resistant A. baumannii spp. were obtained from burn patients, admitted to the Shahid Motahari Burns Hospital in Tehran, Iran, during June-August 2018. The inhibitory effect of tazobactam against adeB such as efflux pump was evaluated by Minimum Inhibitory Concentration (MIC) determination of amikacin alone and in combination with tazobactam. Fractional Inhibitory Concentration index (FIC) was used to determine the efficacy of tazobactam/ amikacin combination. Further, semi-quantitative Real- Time PCR was performed to quantify the expression rates of the adeB gene before and after addition of tazobactam/amikacin. Results: The MIC values were significantly reduced when a combined amikacin and tazobactam was utilized. The most common interaction observed was synergistic (78.2%), followed by additive effects (21.8%), as per FIC results. The adeB mRNA expression levels were found to be downregulated in 60.7% of isolates treated with tazobactam. Conclusions: Tazobactam can have impact on resistance to aminoglycoside by inhibiting efflux pump. Thus, the combination of tazobactam with amikacin can be used as an alternative treatment approach in multidrug resistant A. baumannii infections.

Invasive Candidiasis

2020 ◽  
Vol 41 (01) ◽  
pp. 003-012 ◽  
Author(s):  
María F. Gonzalez-Lara ◽  
Luis Ostrosky-Zeichner
Keyword(s):  
Invasive Candidiasis ◽  
Antifungal Agents ◽  
Multiorgan Failure ◽  
Antifungal Susceptibility ◽  
Multidrug Resistant ◽  
Etiologic Agent ◽  
Failure Diagnosis ◽  
High Morbidity ◽  
Candida Auris ◽  
Resistant Species

AbstractInvasive candidiasis (IC) is the most frequent health care associated invasive fungal infection. It is also associated with high morbidity, mortality, and cost. The most frequent etiologic agent is Candida albicans, but non-albicans species are increasing and associated with reduced antifungal susceptibility and outbreaks. Candida auris is an emerging multidrug-resistant species recently described. IC presents as a spectrum of disease, going from fungemia to deep-seated candidiasis, and to septic shock with multiorgan failure. Diagnosis of IC is challenging. Several biomarkers and molecular methods are available for improving diagnosis. Early initial treatment with echinocandins is the treatment of choice. Step-down therapy when antifungal susceptibility is available is possible. Several new antifungal agents for the treatment of IC are in clinical development.

scholarly journals Espécies se Candida Spp. em Isolados Clínicos e Suscetibilidade a Antifúngicos de uso Hospitalar

2015 ◽  
Vol 8 (1) ◽  
pp. 7 ◽  
Author(s):  
Vanusa Aparecida Althaus ◽  
Alissara Regginato ◽  
Vanessa Bossetti ◽  
Juliana Cristina Schmidt
Keyword(s):  
Antifungal Susceptibility ◽  
Common Species ◽  
Urine Samples ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
High Morbidity ◽  
Candida Spp ◽  
Santa Catarina ◽  
Antifungal Susceptibility Test ◽  
Susceptibility Profiles

A levedura Candida spp., pertencente à microbiota normal, pode causar graves infecções, principalmente em pacientes no ambiente hospitalar. Os variados graus de patogenicidade e sensibilidade a antifúngicos apresentados pelas diversas espécies, combinados ao aumento da frequência de infecções por Candida spp. e às altas taxas de morbimortalidade, apontam a importância da identificação das espécies, assim como a realização de testes de suscetibilidade para o sucesso do tratamento de candidíases. Neste estudo foram identificadas espécies de Candida em isolados clínicos de pacientes atendidos em um hospital da região oeste de Santa Catarina, Brasil, utilizando o método CHROMagar Candida, bem como avaliados seus respectivos perfis de suscetibilidade a antifúngicos usados no âmbito hospitalar utilizando o método de disco-difusão em ágar. Das 43 amostras analisadas, a maior prevalência da candidíase foi encontrada em pacientes com idade entre 51 e 70 anos e do gênero masculino. A maioria do isolados foi obtida de amostras de urina (n=25) e da Unidade de Terapia Intensiva (n=22). As espécies mais frequentes foram C. albicans (n=24) e C. glabrata (n=13). A maioria dos isolados foi sensível à anfotericina B (86,05%) e a minoria (13,95%) sensível ao fluconazol. O setor de UTI, as amostras de urina e as culturas identificadas como C. albicans apresentaram vários isolados resistentes a todos os antifúngicos testados. O elevado número de isolados resistentes aos antifúngicos azólicos, provenientes principalmente de pacientes de UTI, indicam a importância do antifungigrama para a escolha do antifúngico e da dose mais adequados no tratamento de candidíases em pacientes críticos. Species of Candida Spp. in Clinical Isolates and Susceptibility for Antifungals used at Hospital Level ABSTRACT: The Candida yeast belongs to normal microbiota and can cause serious infections especially in the hospital environment. The various degrees of pathogenicity and sensitivity to antifungal presented by several species, combined with the increased frequency of infections caused by Candida spp. and the high morbidity and mortality rates indicate the importance of species identification as well as performing susceptibility testing for the successful treatment of candidiasis. In this study Candida species were identified in clinical isolates of patients treated in a hospital in the western region of Santa Catarina, Brasil, using CHROMagar Candida method and evaluated their susceptibility profiles to antifungal agents used in hospitals by disk diffusion agar method. Of the 43 samples analyzed, the highest prevalence of candidiasis was found in patients aged between 51 and 70 years old and male. Most of the isolates were obtained from urine samples (n = 25) and the Intensive Care Unit (ICU) (n = 22). The most common species were C. albicans (n = 24) and C. glabrata (n = 13). Most isolates were sensitive to amphotericin B (86.05%) and the minority (13.95%) sensitive to fluconazole. The ICU sector, urine samples and cultures identified as C. albicans showed several isolates resistant to all tested antifungals. The high number of isolates resistant to azole antifungal mainly from ICU patients indicate the importance of antifungal susceptibility test to select the most appropriate antifungal and dose in the treatment of candidiasis in critically ill patients.

scholarly journals High frequency of azole resistant Candida spp. colonization among presumptive multidrug resistant tuberculosis (MDR-TB) patients

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242542
Author(s):  
Surya Darma ◽  
Angga Ambara ◽  
Abu Tholib Aman ◽  
Luthvia Annisa ◽  
Nurrokhman ◽  
...  
Keyword(s):  
Candida Albicans ◽  
High Frequency ◽  
Antifungal Susceptibility ◽  
Multidrug Resistant ◽  
Dependent Manner ◽  
Candida Spp ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Tuberculosis Therapy

Background Tuberculosis is one of the major causes of death globally. The problems become even more complicated with the rise in prevalence of multidrug resistant tuberculosis (MDR-TB). Many diseases have been reported to occur with tuberculosis making it more difficult to manage. Candida spp., which are yeast-like fungi and a constituent of normal flora in humans, are notoriously reported to be one of the most common opportunistic nosocomial infections. This study aimed to measure the proportion of presumptive MDR-TB patients colonized with Candida spp. and to characterize its susceptibility against azole group antifungal agents. Methods Sputum from presumptive MDR-TB patients were collected and examined for the presence of Mycobacterium tuberculosis and its rifampicin resistant status using GeneXpert. It was further cultured on Sabouroud’s Dextrose Agar (SDA) to isolate the Candida spp. The Candida species were determined using HiCrome™ Candidal Differential Agar. Antifungal susceptibility was tested using microbroth dilution methods. Checkerboard microdilution assays were performed to measure the interaction between rifampicin and fluconazole to C. albicans. Results There were 355 presumptive MDR-TB patients enrolled. A total of 101 (28.4%) patients were confirmed to have M. tuberculosis. There were 113 (31.8%) sputum positive for Candida spp., which corresponded to 149 Candida spp. isolates. Candida albicans was the most frequent (53.7%) species isolated from all patients. The susceptibility of Candida spp. against fluconazole, itraconazole, and ketoconazole were 38.3%, 1.3%, and 10.7% respectively. There was significant association between rifampicin exposure history and susceptibility of Candida albicans against fluconazole (Odds Ratio: 9.96; 95% CI: 1.83–54.19; p <0.01), but not for ketoconazole and itraconazole. The checkerboard microdilution assays showed that rifampicin decreased the fungicidal activity of fluconazole to C. albicans in a dose-dependent manner. Conclusion There was high frequency of azole resistant Candida spp. isolates colonizing the respiratory tract of presumptive MDR-TB patients. This presence might indicate the association of chronic exposure to rifampicin, the main drug for tuberculosis therapy, with the induction of azole resistance.

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