Antifungal Agents in the Treatment of Candidosis and Susceptibility Tests

The high mortality rates associated with candidemia episodes and the emergence of resistance to antifungal agents necessitate the monitoring of the susceptibility of fungal isolates to antifungal treatments. The new, recently approved, species-specific clinical breakpoints (SS-CBPs)(M27-S4) for evaluating susceptibility require careful interpretation and comparison with the former proposals made using the M27-A3 breakpoints, both from CLSI. This study evaluated the susceptibility of the different species of Candida that were isolated from candidemias based on these two clinical breakpoints. Four hundred and twenty-two isolates were identified and, among them, C. parapsilosis comprised 46.68%, followed by C. albicans (35.78%), C. tropicalis (9.71%), C. glabrata (3.55%), C. lusitaniae (1.65%), C. guilliermondii (1.65%) and C. krusei (0.94%). In accordance with the M27-A3 criteria, 33 (7.81%) non-susceptible isolates were identified, of which 16 (3.79%) were resistant to antifungal agents. According to SS-CBPs, 80 (18.95%) isolates were non-susceptible, and 10 (2.36%) of these were drug resistant. When the total number of non-susceptible isolates was considered, the new SS-CBPs detected 2.4 times the number of isolates that were detected using the M27-A3 interpretative criteria. In conclusion, the detection of an elevated number of non-susceptible species has highlighted the relevance of evaluating susceptibility tests using new, species-specific clinical breakpoints (SS-CBPs), which could impact the profile of non-susceptible Candida spp. to antifungal agents that require continuous susceptibility monitoring.

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Comparison of Two Commercial Colorimetric Broth Microdilution Tests for Candida Susceptibility Testing: Sensititre YeastOne versus MICRONAUT-AM

Journal of Fungi ◽

10.3390/jof7050356 ◽

2021 ◽

Vol 7 (5) ◽

pp. 356

Author(s):

Sophie Philips ◽

Frederik Van Van Hoecke ◽

Emmanuel De De Laere ◽

Steven Vervaeke ◽

Roos De De Smedt ◽

...

Keyword(s):

Amphotericin B ◽

Antifungal Agents ◽

Susceptibility Testing ◽

Antifungal Susceptibility ◽

Reference Method ◽

Daily Practice ◽

Broth Microdilution ◽

Minimal Inhibitory Concentrations ◽

Clinical Breakpoints ◽

Susceptibility Tests

Two colorimetric broth microdilution antifungal susceptibility tests were compared, Sensititre YeastOne and MICRONAUT-AM for nine antifungal agents. One hundred clinical Candida isolates were tested, representing a realistic population for susceptibility testing in daily practice. The reproducibility characteristics were comparable. Only for fluconazole, caspofungin, 5-flucytosine and amphotericin B, an essential agreement of ≥90% could be demonstrated. Sensititre minimal inhibitory concentrations (MICs) were systematically higher than MICRONAUT MICs for all antifungals, except for itraconazole. CLSI clinical breakpoints (CBPs) and epidemiological cut-off values (ECVs) were used for Sensititre MICs while for MICRONAUT the EUCAST CBPs and ECVs were used. Only fluconazole, micafungin, and amphotericin B had a categorical agreement of ≥90%. For fluconazole, micafungin, and amphotericin B the susceptibility proportions were comparable. Susceptibility proportion of posaconazole and voriconazole was higher using the MICRONAUT system. For itraconazole and anidulafungin, the susceptibility proportion was higher using Sensititre. It was not possible to determine the true MIC values or the correctness of a S/I/R result since both commercial systems were validated against a different reference method. These findings show that there is a significant variability in susceptibility pattern and consequently on use of antifungals in daily practice, depending on the choice of commercial system.

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Quality Control Limits for Broth Microdilution Susceptibility Tests of Ten Antifungal Agents

Journal of Clinical Microbiology ◽

10.1128/jcm.38.9.3457-3459.2000 ◽

2000 ◽

Vol 38 (9) ◽

pp. 3457-3459 ◽

Cited By ~ 110

Author(s):

A. L. Barry ◽

M. A. Pfaller ◽

S. D. Brown ◽

A. Espinel-Ingroff ◽

M. A. Ghannoum ◽

...

Keyword(s):

Quality Control ◽

Antifungal Agents ◽

Candida Parapsilosis ◽

Clinical Laboratory ◽

Collaborative Study ◽

Candida Krusei ◽

National Committee ◽

Broth Microdilution ◽

Susceptibility Tests ◽

Control Limits

Broth microdilution susceptibility tests of Candidaspecies have now been standardized by the National Committee for Clinical Laboratory Standards (NCCLS). An eight-laboratory collaborative study was carried out in order to document reproducibility of tests of Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258 by the NCCLS method. Replicate broth microdilution tests were used to define control limits for 24- and 48-h MICs of amphotericin B, flucytosine, fluconazole, voriconazole, ketoconazole, itraconazole, caspofungin (MK 0991), ravuconazole (BMS 207147), posaconazole (SCH 56592), and LY 303366.

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Thirteen-Year Evolution of Azole Resistance in Yeast Isolates and Prevalence of Resistant Strains Carried by Cancer Patients at a Large Medical Center

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.4.734 ◽

1998 ◽

Vol 42 (4) ◽

pp. 734-738 ◽

Cited By ~ 41

Author(s):

Cynthia R. Boschman ◽

Ulana R. Bodnar ◽

Michelle A. Tornatore ◽

Arlene A. Obias ◽

Gary A. Noskin ◽

...

Keyword(s):

Antifungal Agents ◽

Hematologic Malignancy ◽

Medical Center ◽

High Risk Patient ◽

Clinical Isolates ◽

Microbial Pathogens ◽

Resistant Isolate ◽

Transplant Patients ◽

Susceptibility Tests ◽

Therapeutic Decision Making

ABSTRACT Drug resistance is emerging in many important microbial pathogens, including Candida albicans. We performed fungal susceptibility tests with archived isolates obtained from 1984 through 1993 and fresh clinical isolates obtained from 1994 through 1997 by testing their susceptibilities to fluconazole, ketoconazole, and miconazole and compared the results to the rate of fluconazole use. All isolates recovered prior to 1993 were susceptible to fluconazole. Within 3 years of widespread azole use, we detected resistance to all agents in this class. In order to assess the current prevalence of resistant isolates in our hematologic malignancy and transplant patients, we obtained rectal swabs from hospitalized, non-AIDS, immunocompromised patients between June 1995 and January 1996. The swabs were inoculated onto sheep’s blood agar plates containing 10 μg of vancomycin and 20 μg of gentamicin/ml of agar. One hundred one yeasts were recovered from 97 patients and were tested for their susceptibilities to amphotericin B, fluconazole, flucytosine, ketoconazole, and miconazole. The susceptibility pattern was then compared to those for all clinical isolates obtained throughout the medical center. The antifungal drug histories for each patient were also assessed. The yeasts from this surveillance study were at least as susceptible as the overall hospital strains. There did not appear to be a direct linkage between prior receipt of antifungal agent therapy and carriage of a new, drug-resistant isolate. Increased resistance to newer antifungal agents has occurred at our medical center, but it is not focal to any high-risk patient population that we studied. Monitoring of susceptibility to antifungal agents appears to be necessary for optimizing clinical therapeutic decision making.

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Pyrogallol and Fluconazole Interact Synergistically In Vitro Against Candida glabrata Through an Efflux-Associated Mechanism

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00100-21 ◽

2021 ◽

Author(s):

Dongting Yao ◽

Guanyi Zhang ◽

Weiqin Chen ◽

Jia Chen ◽

Zhen Li ◽

...

Keyword(s):

Candida Glabrata ◽

Antifungal Agents ◽

Inhibitory Concentration ◽

Rhodamine 6G ◽

Pcr Analysis ◽

Potential Mechanism ◽

Combination Therapies ◽

Qrt Pcr ◽

Susceptibility Tests

Candida glabrata is currently the first or second most commonly encountered non-albicans Candida species worldwide. The potential severity of Candida resistance mandates the discovery of novel antifungal agents, including those that can be used in combination therapies. In this study, we evaluated the in vitro interactions of pyrogallol (PG) and azole drugs against 22 clinical C. glabrata isolates. The potential mechanism underlying the synergism between PG and fluconazole (FLC) was investigated by the rhodamine 6G efflux method and quantitative reverse transcription (qRT)-PCR analysis. In susceptibility tests, PG showed strong synergism with FLC, itraconazole (ITC), and voriconazole (VRC), with fractional inhibitory concentration index values of 0.188–0.375 for PG+FLC, 0.250–0.750 for PG+ITC, and 0.141–0.750 for PG+VRC. Cells grown in the presence of PG+FLC exhibited reduced rhodamine 6G extrusion and significantly downregulated expression of the efflux-related genes CgCDR1, CgCDR2, and CgPDR1 when compared with cells grown in the presence of PG or FLC alone. PG did not potentiate FLC when tested against a ΔCgpdr1 strain. Restoration of a functional CgPDR1 allele also restored the synergism. These results indicate that PG is an antifungal agent that synergistically potentiates the activity of azoles. Further, PG appears to exert its effects by inhibiting efflux pumps and by downregulating CgCDR1, CgCDR2, and CgPDR1, with CgPDR1 probably playing a crucial role in this process.

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Trends in Antifungal Susceptibility of Candida Species – One Year Observation

Polish Journal of Microbiology ◽

10.33073/pjm-2014-028 ◽

2014 ◽

Vol 63 (2) ◽

pp. 217-222 ◽

Cited By ~ 4

Author(s):

M. GOŁAŚ ◽

I. NETSVYETAYEVA ◽

M. SIKORA ◽

K. PISKORSKA ◽

B. SULIK-TYSZKA ◽

...

Keyword(s):

Invasive Candidiasis ◽

Lower Respiratory Tract ◽

Antifungal Agents ◽

Fungal Infections ◽

Antifungal Susceptibility ◽

Test Method ◽

Predominant Species ◽

The Past ◽

One Year ◽

Susceptibility Tests

In the past years opportunistic fungal infections have seriously increased, mainly in immunocompromised patients. The aim of the study was to determine the prevalence of yeast-like fungi in invasive candidiasis and to estimate its susceptibility to chosen antifungal agents. One hundred and sixty strains of yeast-like fungi were cultured from various clinical material: samples from lower respiratory tract, blood, the peritoneal cavity and others. The susceptibility tests were established according to the quantitative E-test method. The Candida genus represented the main etiological factor of invasive candidiasis. The predominant species were: C. glabrata (71/160), C. albicans (34/160), C. krusei (17/160), C. tropicalis (14/160). All tested strains were the most resistant to itraconazole. Candida glabrata presented the 100% susceptibility to amphotericin B and caspofungin and was the least susceptible to itraconazole, posaconazole and voriconazole. Candida albicans was the most susceptible species to all antymicotics.

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Sporothrix schenckii associated with armadillo hunting in Southern Brazil: epidemiological and antifungal susceptibility profiles

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822010000500010 ◽

2010 ◽

Vol 43 (5) ◽

pp. 523-525 ◽

Cited By ~ 22

Author(s):

Sydney Hartz Alves ◽

Cecília Schubert Boettcher ◽

Daniele Carvalho de Oliveira ◽

Giordano Rafael Tronco-Alves ◽

Maria Aparecida Sgaria ◽

...

Keyword(s):

Antifungal Agents ◽

Antifungal Susceptibility ◽

Sporothrix Schenckii ◽

Rio Grande ◽

Wild Animal ◽

Southern Brazil ◽

Rio Grande Do Sul ◽

Cultural Aspects ◽

Susceptibility Tests ◽

Susceptibility Profiles

INTRODUCTION: Sporotrichosis is the most common subcutaneous mycosis observed in Brazil and it is generally consequent to a little trauma caused by vegetal particles or spines which inoculate the fungi in the subcutaneous area. Although sporotrichosis had been frequently mentioned with armadillo hunting this form has not been widely reported in Brazil until now. In this study we report ten cases of sporotrichosis evolving the armadillo's hunting diagnosed in some towns located in the central and west regions of Rio Grande do Sul State. METHODS: The cases were established based on clinical and classic mycological laboratorial techniques. The susceptibility tests were conducted by microdilution technique according to M38-A2 CLSI documents. RESULTS: Ten cases of sporotrichosis associated with armadillo hunting detected in the State of Rio Grande do Sul were diagnosed by mycological methods. The susceptibility tests of Sporothrix schenckii isolates to antifungal agents itraconazole, ketoconazole and terbinafine showed that all the isolates were susceptible. CONCLUSIONS: The paper discusses some cultural aspects related to hunting of this wild animal as well as possible causes of this unexpected occurrence in southern Brazil.

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Invasive Pulmonary Aspergillosis Due to Aspergillus Lentulus in a Liver Transplant Recipient: a Case Report and Literature Review

10.21203/rs.3.rs-1020737/v1 ◽

2021 ◽

Author(s):

Yao Sun ◽

Yuyi Zhang ◽

Jing Xu ◽

Ting Wang ◽

Xiaoping Shi

Keyword(s):

Amphotericin B ◽

Antifungal Agents ◽

Invasive Pulmonary Aspergillosis ◽

Drug Susceptibility ◽

Drug Susceptibility Test ◽

Case Presentation ◽

Minimal Inhibitory Concentrations ◽

Aspergillus Lentulus ◽

Susceptibility Tests ◽

A New Species

Abstract Background: Aspergillus lentulus, a new species discovered in 2005, is a rare fungal pathogen with reduced sensitivity to antifungal agents. Case presentation: Here we reported a 58-year-old male who underwent a liver transplantation on January 2020 and followed by maintenance immunosuppressive therapy. Then A.lentulus was cultured from his sputum twice and identified by using the MALDI-TOF-MS and confirmed by the reference of RUO database. In the susceptibility tests of the isolate, minimal inhibitory concentrations for amphotericin B, voriconazole, posaconazole, and caspofungin were found to be 0.5 mg/L, 1.0 mg/L, 0.5 mg/L and 8 mg/L, respectively. The patient was improved after treatment with a voriconazole 0.2g q12h orally plus caspofungin 50mg qd intravenously. Conclusion: A. lentulus is easily confused with A. fumigatus and its susceptibility to amphotericin B and azoles antifungal agents is reduced. Therefore, the identification of strain and drug susceptibility test are very important for clinical treatment.

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