scholarly journals Antifungal Resistance among Less Prevalent Candida Non-albicans and Other Yeasts versus Established and under Development Agents: A Literature Review

2021 ◽  
Vol 7 (1) ◽  
pp. 24
Author(s):  
Ana Espinel-Ingroff ◽  
Emilia Cantón ◽  
Javier Pemán
Keyword(s):  
Candida Species ◽  
Resistance Mechanisms ◽  
Fungal Species ◽  
Antifungal Resistance ◽  
Antifungal Drugs ◽  
Candida Spp ◽  
In Vitro Susceptibility ◽  
Susceptibility Data ◽  
Development Agents

Fungal diseases and antifungal resistance continue to increase, including those caused by rare or emerging species. However, the majority of the published in vitro susceptibility data are for the most common fungal species. We reviewed the literature in order to pool reference minimal inhibitory concentration (MIC) data (Clinical and Laboratory Standards Institute—CLSI and European Committee on Antimicrobial Susceptibility—EUCAST) for rare/non-prevalent Candida and other yeast species. MIC results were compared with those for Candida albicans, C. glabrata, and C. krusei. Data were listed for twenty rare and emerging Candida spp., including C. auris, as well as two Cryptococcus spp., two Trichosporon spp., Saccharomyces cerevisiae and five Malassezia spp. The best detectors of antimicrobial resistance are the breakpoints, which are not available for the less common Candida species. However, epidemiological cutoff values (ECVs/ECOFFs) have been calculated using merely in vitro data for both reference methods for various non-prevalent yeasts and recently the CLSI has established ECVs for other Candida species. The ECV could identify the non-wild type (NWT or mutants) isolates with known resistance mechanisms. Utilizing these ECVs, we were able to report additional percentages of NWT, especially for non-prevalent species, by analyzing the MIC distributions in the literature. In addition, since several antifungal drugs are under development, we are listing MIC data for some of these agents.

scholarly journals Antifungal resistance profile and enzymatic activity of Candida species recovered from human and animal samples

Bio-Research ◽  
2019 ◽  
Vol 17 (1) ◽  
pp. 1044A-1055A
Author(s):  
IE Mba ◽  
EI Nweze
Keyword(s):  
Enzymatic Activity ◽  
Candida Species ◽  
Vaginal Swab ◽  
Fungal Species ◽  
Resistance Rate ◽  
Antifungal Resistance ◽  
Candida Spp ◽  
Significant Difference ◽  
The Difference

Candida is currently the most implicated pathogenic fungal species recognized as the major cause of a variety of human infections all over the world. This study investigated species distribution, enzymatic activities, and antifungal resistance profiles of human and animal Candida species. Clinical Candida species (n=220) were isolated from urine, high vaginal swab (HVS) and blood while Candida species (n=128) were isolated from rectal swab, ear swab, blood, feces, and milk in animals: goat, sheep, cattle, pig and chicken. The identification of the species was performed using standard methods. Enzymatic activity was screened using plate methods. Susceptibility testing was carried out using disk diffusion and broth microdilution methods. A statistically significant difference (P=0.031) was observed in the distribution of Candida spp. recovered from humans and animals. The Pz values of human Candida species for proteinase, hemolysin, lipase and phospholipase were 0.65±0.97, 0.61±0.81, 0.59±0.47 and 0.76±0.74 respectively while that of Candida species recovered from animal were 0.67±0.13, 0.61±0.95, 0.62±0.67 and 0.69±0.70 respectively. No statistically significant difference (P>0.05) in the in vitro enzymatic activity was observed between the two groups. High azole-resistance rate was observed. Resistance was higher among human Candida isolates compared to animal isolates although the difference was not considered statistically significant (p = 0.519). Our findings suggest that the enzymatic activity (virulence potential) and resistance patterns are similar in the two groups investigated. This study underscores the importance of animals especially pets and their products as potential sources/reservoirs of pathogenic and multi-azole resistant Candida species in Nigeria.

scholarly journals Antifungal Resistance Regarding Malassezia pachydermatis: Where Are We Now?

2020 ◽  
Vol 6 (2) ◽  
pp. 93
Author(s):  
Andrea Peano ◽  
Elizabeth Johnson ◽  
Elisa Chiavassa ◽  
Paolo Tizzani ◽  
Jacques Guillot ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Antifungal Agents ◽  
Standard Procedure ◽  
Resistance Mechanisms ◽  
Antifungal Resistance ◽  
Antifungal Drugs ◽  
Malassezia Pachydermatis ◽  
Development Of Resistance ◽  
Ear Canals

Malassezia pachydermatis is a yeast inhabiting the skin and ear canals in healthy dogs. In the presence of various predisposing conditions it can cause otitis and dermatitis, which are treated with multiple antifungal agents, mainly azole derivatives. This manuscript aims to review the available evidence regarding the occurrence of resistance phenomena in this organism. Various findings support the capacity of M. pachydermatis for developing resistance. These include some reports of treatment failure in dogs, the reduced antifungal activity found against yeast isolates sampled from dogs with exposure to antifungal drugs and strains exposed to antifungal agents in vitro, and the description of resistance mechanisms. At the same time, the data reviewed may suggest that the development of resistance is a rare eventuality in canine practice. For example, only three publications describe confirmed cases of treatment failure due to antifungal resistance, and most claims of resistance made by past studies are based on interpretive breakpoints that lack sound support from the clinical perspective. However, it is possible that resistant cases are underreported in literature, perhaps due to the difficulty of obtaining a laboratory confirmation given that a standard procedure for susceptibility testing of M. pachydermatis is still unavailable. These considerations highlight the need for maintaining surveillance for the possible emergence of clinically relevant resistance, hopefully through a shared strategy put in place by the scientific community.

scholarly journals In Vitro Activity of Carbosilane Cationic Dendritic Molecules on Prevention and Treatment of Candida Albicans Biofilms

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 918
Author(s):  
Irene Heredero-Bermejo ◽  
Natalia Gómez-Casanova ◽  
Sara Quintana ◽  
Juan Soliveri ◽  
Francisco Javier de la Mata ◽  
...  
Keyword(s):  
Cell Viability ◽  
Biofilm Formation ◽  
Fungal Pathogens ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Candida Spp ◽  
Screening Process

Candida spp. are one of the most common fungal pathogens. Biofilms formed by Candidaalbicans offer resistance mechanisms against most antifungal agents. Therefore, development of new molecules effective against these microorganisms, alone or in combination with antifungal drugs, is extremely necessary. In the present work, we carried out a screening process of different cationic carbosilane dendritic molecules against C. albicans. In vitro activity against biofilm formation and biofilms was tested in both Colección Española de Cultivos Tipo (CECT) 1002 and clinical C. albicans strains. Cytotoxicity was studied in human cell lines, and biofilm alterations were observed by scanning electron microscopy (SEM). Antifungal activity of the carbosilane dendritic molecules was assessed by monitoring cell viability using both established and novel cell viability assays. One out of 14 dendritic molecules tested, named BDSQ024, showed the highest activity with a minimum biofilm inhibitory concentration (MBIC) for biofilm formation and a minimum biofilm damaging concentration (MBDC) for existing biofilm of 16–32 and 16 mg/L, respectively. Synergy with amphotericin (AmB) and caspofungin (CSF) at non-cytotoxic concentrations was found. Therefore, dendritic compounds are exciting new antifungals effective at preventing Candida biofilm formation and represent a potential novel therapeutic agent for treatment of C. albicans infection in combination with existing clinical antifungals.

Susceptibility of uncommon Candida species to systemic antifungals by the EUCAST methodology

2019 ◽  
Vol 58 (6) ◽  
pp. 848-851 ◽  
Author(s):  
Judith Díaz-García ◽  
Luis Alcalá ◽  
Pablo Martín-Rabadán ◽  
Aina Mesquida ◽  
Carlos Sánchez-Carrillo ◽  
...  
Keyword(s):  
Point Mutation ◽  
Candida Species ◽  
Antifungal Agents ◽  
Wild Type ◽  
In Vitro Susceptibility ◽  
Susceptibility Data ◽  
Fluconazole Resistant ◽  
Type C

Abstract The incidence of infections by uncommon Candida species has increased in recent years, however, in vitro susceptibility data are scarce. Here we assess the susceptibility of C. krusei, C. dubliniensis, C. lusitaniae, and C. guilliermondii complex isolates (n = 120) to antifungal agents by the EUCAST methodology. C. dubliniensis proved to be the most susceptible species, similar to that of C. albicans (P < .05), whereas C. guilliermondii was the least susceptible. Two C. krusei isolates were echinocandin-resistant and harbored a point mutation (L701M) in the FKS1. Some isolates were either fluconazole-resistant (C. lusitaniae, n = 2) or fluconazole non-wild type (C. guilliermondii, n = 3).

scholarly journals In vitro susceptibility testing of Candida species isolated from blood stream infections to five conventional antifungal drugs

2019 ◽  
pp. 124-129
Author(s):  
Mahdis Hosein Khezri ◽  
Farideh Zaini ◽  
Parivash Kordbache ◽  
Mohammad Ghahri ◽  
Pegah Ardi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Candida Species ◽  
Bloodstream Infections ◽  
Blood Stream ◽  
Candida Guilliermondii ◽  
Antifungal Drugs ◽  
In Vitro Susceptibility ◽  
Dose Dependent

Candida is an opportunistic fungal pathogen which can cause fatal bloodstream infections (BSIs) in immunocompromised and immunodeficient persons. In this study, the susceptibility of 196 Candida species isolated from bloodstream infections (BSI) to 5 antifungal drugs were conducted from October 2014 through October 2017. The antifungal drugs used in this study were including fluconazole, itraconazole, voriconazole, Amphotericin B and Caspofungin. From 196 studied isolates, Candida albicans comprised 63.3% of the isolates, followed by C.parapsilosis (18.9 %), C. glabrata (8.7%), C. tropicalis (6.1%), C.krusei (2%) and C.gillermundii (1%). In this study, all isolates of Candida albicans and Candida non-albicans species were completely resistant to voriconazole and itraconazole. Of the 196 Candida isolates, 80 isolates with MIC of 32-16 μg/ml had a dose dependent susceptibility to fluconazole and 111 isolates showed resistance (MIC=64 μg / ml) and only 5 isolates were sensitive (MIC=8 μg / ml) to fluconazole. In this study, out of 196 isolates, 37 isolates were sensitive to amphotericin (MIC=1 μg/ml) and 159 isolates were resistant to amphotericin B (MIC>1 μg/ml). Caspofungin was effective on 104 isolates (MIC<2 μg/ml) and 92 isolates were non-susceptible (MIC>2 μg / ml) to this drug. Out of 124 isolates of Candida albicans, 3 were susceptible, 61 susceptible dose dependent and 60 were resistant to fluconazole. Only 24 isolates were susceptible to amphotericin B and 100 isolates showed resistance to this antifungal drug. Eighty-eight isolates were sensitive to caspofungin and 36 isolates were insensitive. With respect to susceptibility to fluconazole, among 37 isolates of Candida parapsilosis, one was identified as susceptible, 13 isolates were susceptible dose dependent and 13 were resistant. Of these isolates, five were susceptible and 32 isolates were resistant to amphotericin B and caspofungin. Of 12 isolates of Candida tropicalis, 11 showed resistance and 1 was susceptible dose dependent to fluconazole. Of these isolates, 11 were resistant to amphotericin B and 1 isolate was sensitive. Ultimately, only 2 isolates showed susceptibility to caspofungin. Out of 17 isolates of Candida glabrata, 13 isolates were resistant, and 4 isolates had a dose-dependent sensitivity to fluconazole. Eight isolates were susceptible and 9 isolates were resistant to caspofungin. Seven isolates were susceptible and 10 isolates were resistant to amphotericin B. All four Candida krusei isolates showed resistance to the five drugs used in the study. Of the two Candida guilliermondii isolates, both were resistant to amphotericin B, but 1 was sensitive to fluconazole and 1 was identified to be dose-dependent susceptible. One isolate was resistant to and the other one was susceptible to caspofungin. Our findings shows the prevalence of resistant candida species to conventional treatments and indicate that candidemia caused by Candida resistant species is incrasing. Keywords: Candidiasis; Antifungal drugs; Candidemia; Iran

scholarly journals In Vitro Activities of Various Antifungal Drugs against Aspergillus terreus: Global Assessment Using the Methodology of the European Committee on Antimicrobial Susceptibility Testing

2008 ◽  
Vol 53 (2) ◽  
pp. 794-795 ◽  
Author(s):  
Cornelia Lass-Flörl ◽  
Ana Alastruey-Izquierdo ◽  
Manuel Cuenca-Estrella ◽  
Susanne Perkhofer ◽  
Juan Luis Rodriguez-Tudela
Keyword(s):  
Antimicrobial Susceptibility ◽  
Aspergillus Terreus ◽  
Susceptibility Testing ◽  
Antimicrobial Susceptibility Testing ◽  
Antifungal Drugs ◽  
In Vitro Susceptibility ◽  
Susceptibility Data ◽  
European Committee ◽  
Susceptibility Patterns

ABSTRACT This study presents in vitro susceptibility data for clinical (n = 48) and environmental (n = 31) isolates of Aspergillus terreus against nine antifungal agents. The methodology of the European Committee on Antimicrobial Susceptibility Testing was applied. Posaconazole and anidulafungin had the lowest and amphotericin B the highest MICs. No differences in susceptibility patterns were observed between environmental and clinical isolates.

scholarly journals 146. antifungal Susceptibility Patterns of candida Parapsilosis Bloodstream Isolates in the US, 2008–2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S203-S203
Author(s):  
Brenda L Tesini ◽  
Meghan Lyman ◽  
Brendan R Jackson ◽  
Anita Gellert ◽  
William Schaffner ◽  
...  
Keyword(s):  
Candida Species ◽  
Regional Variation ◽  
Antifungal Susceptibility ◽  
Bloodstream Infections ◽  
Emerging Infections ◽  
In Vitro Susceptibility ◽  
Fluconazole Resistance ◽  
The Us ◽  
Susceptibility Patterns

Abstract Background Multidrug resistant Candida is an increasing concern. C. parapsilosis in particular has decreased in vitro susceptibility to echinocandins. As a result, fluconazole had been favored for C. parapsilosis treatment. However, there is growing concern about increasing azole resistance among Candida species. We report on antifungal susceptibility patterns of C. parapsilosis in the US from 2008 through 2018. Methods Active, population-based surveillance for candidemia through the Centers for Disease Control and Prevention’s (CDC) Emerging Infections Program was conducted between 2008–2018, eventually encompassing 9 states (GA, MD,OR, TN, NY, CA, CO, MN, NM). Each incident isolate was sent to the CDC for species confirmation and antifungal susceptibility testing (AFST). Frequency of resistance was calculated and stratified by year and state using SAS 9.4 Results Of the 8,704 incident candidemia isolates identified, 1,471 (15%) were C. parapsilosis; the third most common species after C. albicans and C. glabrata. AFST results were available for 1,340 C. parapsilosis isolates. No resistance was detected to caspofungin (MIC50 0.25) or micafungin (MIC50 1.00) with only one (&lt; 1%) isolate resistant to anidulafungin (MIC50 1.00). In contrast, 84 (6.3%) isolates were resistant to fluconazole and another 44 (3.3%) isolates had dose-dependent susceptibility to fluconazole (MIC50 1.00). Fluconazole resistance increased sharply from an average of 4% during 2008–2014 to a peak of 14% in 2016 with a subsequent decline to 6% in 2018 (see figure). Regional variation is also observed with fluconazole resistance ranging from 0% (CO, MN, NM) to 42% (NY) of isolates by site. Conclusion The recent marked increase in fluconazole resistance among C. parapsilosis highlights this pathogen as an emerging drug resistant pathogen of concern and the need for ongoing antifungal resistance surveillance among Candida species. Our data support the empiric use of echinocandins for C. parapsilosis bloodstream infections and underscore the need to obtain AFST prior to fluconazole treatment. Furthermore, regional variation in fluconazole resistance emphasizes the importance of understanding local Candida susceptibility patterns. Disclosures Lee Harrison, MD, GSK (Consultant)Merck (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant)

scholarly journals 1593. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against OXA-48 β-lactamase–Producing Enterobacterales Collected in International Medical Centers, Including the United States, in 2017–2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S793-S793
Author(s):  
Lynn-Yao Lin ◽  
Dmitri Debabov ◽  
William Chang
Keyword(s):  
Antimicrobial Agents ◽  
The United States ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Multiple Resistance ◽  
In Vitro Susceptibility ◽  
Medical Centers ◽  
Custom Made

Abstract Background OXA-48 is a carbapenemase with low-level hydrolytic activity toward cephalosporins. This study evaluated in vitro activities of ceftazidime-avibactam (CAZ-AVI), meropenem (MEM), meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T), and other antimicrobial agents against 113 OXA-48-producing Enterobacterales with multiple resistance mechanisms collected in a 2017–2018 global surveillance program. Methods Nonduplicate clinical isolates of 113 Enterobacterales were collected from medical centers in 25 countries in 2017–2018. In vitro susceptibility tests were performed by broth microdilution with a custom-made panel consisting of CAZ-AVI, ceftazidime (CAZ), MEM, MVB, C/T, colistin (COL), gentamicin (GEN), levofloxacin (LEV), and amikacin (AMK). Whole genome sequencing or quantitative PCR data were used to analyze resistance mechanisms, such as OXA-48, extended-spectrum β-lactamase (ESBL), original-spectrum β-lactamase (OSBL), and AmpC β-lactamase. Clinical and Laboratory Standards Institute breakpoints were applied for susceptibility interpretations. Results Of 113 OXA-48–producing clinical isolates, 20 carried OXA-48 alone. The remaining 93 isolates carried additional β-lactamases, including 63 with ESBL (CTX-M-15) + OSBL (SHV, TEM), 15 with AmpC (DHA, AAC, CMY) + ESBL (CTX-M-15), and 15 with OSBL (SHV, TEM). 99.1% (all but 1) of all isolates tested were susceptible to CAZ-AVI, whereas 71.7%, 17.7%, and 14.2% were susceptible to MVB, MEM, and C/T, respectively. Among isolates harboring multiple resistance mechanisms (OXA-48 + ESBL + OSBL; n=63), 98.4%, 69.8%, 11.1%, and 7.9% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively. Among isolates carrying OXA-48 + AmpC + ESBL + OSBL (n=15), 100%, 66.7%, 13.3%, and 13.3% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively (Table). Aminoglycosides (AMK and GEN) and other β-lactams (eg, CAZ) were 20%–90% active against these isolates. COL was the second most effective comparator, inhibiting 83.2% of these isolates. Table Conclusion CAZ-AVI was the most effective agent in this study compared with other antibiotics, including β-lactams, β-lactam–β-lactamase inhibitor combinations, aminoglycosides, and COL, against OXA-48-producing Enterobacterales carrying multiple β-lactamases. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee)

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