scholarly journals Role and Interpretation of Antifungal Susceptibility Testing for the Management of Invasive Fungal Infections

2020 ◽  
Vol 7 (1) ◽  
pp. 17
Author(s):  
Frederic Lamoth ◽  
Russell E. Lewis ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Antifungal Therapy ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Invasive Fungal Infections ◽  
Antifungal Susceptibility Testing ◽  
Candida Auris ◽  
Candida Spp ◽  
Neutropenic Patients

Invasive fungal infections (IFIs) are associated with high mortality rates and timely appropriate antifungal therapy is essential for good outcomes. Emerging antifungal resistance among Candida and Aspergillus spp., the major causes of IFI, is concerning and has led to the increasing incorporation of in vitro antifungal susceptibility testing (AST) to guide clinical decisions. However, the interpretation of AST results and their contribution to management of IFIs remains a matter of debate. Specifically, the utility of AST is limited by the delay in obtaining results and the lack of pharmacodynamic correlation between minimal inhibitory concentration (MIC) values and clinical outcome, particularly for molds. Clinical breakpoints for Candida spp. have been substantially revised over time and appear to be reliable for the detection of azole and echinocandin resistance and for outcome prediction, especially for non-neutropenic patients with candidemia. However, data are lacking for neutropenic patients with invasive candidiasis and some non-albicans Candida spp. (notably emerging Candida auris). For Aspergillus spp., AST is not routinely performed, but may be indicated according to the epidemiological context in the setting of emerging azole resistance among A. fumigatus. For non-Aspergillus molds (e.g., Mucorales, Fusarium or Scedosporium spp.), AST is not routinely recommended as interpretive criteria are lacking and many confounders, mainly host factors, seem to play a predominant role in responses to antifungal therapy. This review provides an overview of the pre-clinical and clinical pharmacodynamic data, which constitute the rationale for the use and interpretation of AST testing of yeasts and molds in clinical practice.

scholarly journals SUSCEPTIBILITY TEST FOR FUNGI: CLINICAL AND LABORATORIAL CORRELATIONS IN MEDICAL MYCOLOGY

2015 ◽  
Vol 57 (suppl 19) ◽  
pp. 57-64 ◽  
Author(s):  
Ana ALASTRUEY-IZQUIERDO ◽  
Marcia S.C. MELHEM ◽  
Lucas X. BONFIETTI ◽  
Juan L. RODRIGUEZ-TUDELA
Keyword(s):  
Susceptibility Testing ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Fungal Species ◽  
Medical Mycology ◽  
Candida Spp ◽  
Disease Epidemiology ◽  
Resistant Strains ◽  
European Standards

SUMMARYDuring recent decades, antifungal susceptibility testing has become standardized and nowadays has the same role of the antibacterial susceptibility testing in microbiology laboratories. American and European standards have been developed, as well as equivalent commercial systems which are more appropriate for clinical laboratories. The detection of resistant strains by means of these systems has allowed the study and understanding of the molecular basis and the mechanisms of resistance of fungal species to antifungal agents. In addition, many studies on the correlation of in vitro results with the outcome of patients have been performed, reaching the conclusion that infections caused by resistant strains have worse outcome than those caused by susceptible fungal isolates. These studies have allowed the development of interpretative breakpoints for Candida spp. and Aspergillus spp., the most frequent agents of fungal infections in the world. In summary, antifungal susceptibility tests have become essential tools to guide the treatment of fungal diseases, to know the local and global disease epidemiology, and to identify resistance to antifungals.

scholarly journals Antifungal Susceptibly Testing by Concentration Gradient Strip Etest Method for Fungal Isolates: A Review

2019 ◽  
Vol 5 (4) ◽  
pp. 108 ◽  
Author(s):  
Eric Dannaoui ◽  
Ana Espinel-Ingroff
Keyword(s):  
Concentration Gradient ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Antifungal Susceptibility Testing ◽  
Epidemiological Surveillance ◽  
Diffusion Method ◽  
Dilution Method ◽  
Strip Method

Antifungal susceptibility testing is an important tool for managing patients with invasive fungal infections, as well as for epidemiological surveillance of emerging resistance. For routine testing in clinical microbiology laboratories, ready-to-use commercial methods are more practical than homemade reference techniques. Among commercially available methods, the concentration gradient Etest strip technique is widely used. It combines an agar-based diffusion method with a dilution method that determinates a minimal inhibitory concentration (MIC) in µg/mL. Many studies have evaluated the agreement between the gradient strip method and the reference methods for both yeasts and filamentous fungi. This agreement has been variable depending on the antifungal, the species, and the incubation time. It has also been shown that the gradient strip method could be a valuable alternative for detection of emerging resistance (non-wild-type isolates) as Etest epidemiological cutoff values have been recently defined for several drug-species combinations. Furthermore, the Etest could be useful for direct antifungal susceptibility testing on blood samples and basic research studies (e.g., the evaluation of the in vitro activity of antifungal combinations). This review summarizes the available data on the performance and potential use of the gradient strip method.

Invasive Candidiasis and the Utility of Antifungal Susceptibility Testing in the ICU

2010 ◽  
Vol 23 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Elizabeth A. Coyle
Keyword(s):  
Health Care ◽  
Invasive Candidiasis ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Bloodstream Infections ◽  
Antifungal Susceptibility Testing ◽  
Candida Spp ◽  
Candida Infections ◽  
Prompt Diagnosis

Invasive fungal infections are a major cause of health care–associated morbidity and mortality in the ICU. In particular, Candida spp. are among one of the leading causes of bloodstream infections and sepsis. Advances in antifungal therapy in the last decade have led to many more options in the treatment of fungal infections, yet increasing resistance and clinical failures are common, especially in the management of invasive candidiasis in the ICU. Prompt diagnosis of these infections and appropriate antifungal treatment are imperative for improving survival. Although reliable antifungal susceptibility testing is available to aid in the therapy of fungal infections, testing is not always recommended. This review addresses the epidemiology of Candida infections in the ICU, antifungal resistance, therapy, and the usefulness of antifungal susceptibility testing in the ICU setting.

scholarly journals A Statewide Assessment of Antifungal Stewardship Activities in Acute-Care Hospitals in Connecticut

2020 ◽  
Vol 41 (S1) ◽  
pp. s105-s105
Author(s):  
Romina Bromberg ◽  
Vivian Leung ◽  
Meghan Maloney ◽  
Anu Paranandi ◽  
David Banach
Keyword(s):  
Infectious Diseases ◽  
Acute Care ◽  
Antifungal Therapy ◽  
Antibiotic Stewardship ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Acute Care Hospitals ◽  
Antifungal Susceptibility Testing ◽  
Antifungal Stewardship ◽  
Infectious Diseases Consultation

Background: Morbidity and mortality associated with invasive fungal infections and concerns of emerging antifungal resistance have highlighted the importance of optimizing antifungal therapy among hospitalized patients. Little is known about antifungal stewardship (AFS) practices among acute-care hospitals. We sought to assess AFS activities within Connecticut and to identify opportunities for improvement. Methods: An electronic survey assessing AFS practices was distributed to infectious disease physicians or pharmacy antibiotic stewardship program leaders in Connecticut hospitals. Survey questions evaluated AFS activities based on antibiotic stewardship principles, including several CDC Core Elements. Questions assessed antifungal restriction, prospective audit and feedback practices, antifungal utilization measurements, and the perceived utility of a local or statewide antifungal antibiogram. Results: Responses were received from 15 respondents, which represented 20 of 31 hospitals (65%); these hospitals made up the majority of the acute-care hospitals in Connecticut. Furthermore, 18 of these hospitals (58%) include antifungals in their stewardship programs. Also, 16 hospitals (52%) conduct routine review of antifungal ordering and provide feedback to providers for some antifungals, most commonly for amphotericin B, voriconazole, micafungin, isavuconazole, and flucytosine. All hospitals include guidance on intravenous (IV) to oral (PO) conversions, when appropriate. Only 14 of hospitals (45%) require practitioners to document indication(s) for systemic antifungal use. Most hospitals (17, 55%) provide recommendations for de-escalation of therapy in candidemia, though only 4 (13%) have institutional guidelines for candidemia treatment, and only 11 hospital mandates an infectious diseases consultation for candidemia. Assessing outcomes pertaining to antifungal utilization is uncommon; only 8 hospitals (26%) monitor days of therapy and 5 (16%) monitor antifungal expenditures. Antifungal susceptibility testing on Candida bloodstream isolates is performed routinely at 6 of the hospitals (19%). Most respondents (19, 95%) support developing an antibiogram for Candida bloodstream isolates at the statewide level. Conclusions: Although AFS interventions occur in Connecticut hospitals, there are opportunities for enhancement, such as providing institutional guidelines for candidemia treatment and mandating infectious diseases consultation for candidemia. The Connecticut Department of Public Health implemented statewide Candida bloodstream isolate surveillance in 2019, which includes antifungal susceptibility testing. The creation of a statewide antibiogram for Candida bloodstream infections is underway to support empiric antifungal therapy.Funding: NoneDisclosures: None

scholarly journals The Emerging Terbinafine-Resistant Trichophyton Epidemic: What Is the Role of Antifungal Susceptibility Testing?

Dermatology ◽  
2021 ◽  
pp. 1-20
Author(s):  
Julia J. Shen ◽  
Maiken C. Arendrup ◽  
Shyam Verma ◽  
Ditte Marie L. Saunte
Keyword(s):  
Gene Mutation ◽  
Susceptibility Testing ◽  
Geometric Mean ◽  
Antifungal Susceptibility ◽  
Antifungal Susceptibility Testing ◽  
Squalene Epoxidase ◽  
Exclusion Criteria ◽  
Huge Variation

<b><i>Background:</i></b> Dermatophytosis is commonly encountered in the dermatological clinics. The main aetiological agents in dermatophytosis of skin and nails in humans are <i>Trichophyton</i> (<i>T</i>.) <i>rubrum</i>, <i>T. mentagrophytes</i> and <i>T. interdigitale</i> (former <i>T. mentagrophytes-</i>complex). Terbinafine therapy is usually effective in eradicating infections due to these species by inhibiting their squalene epoxidase (SQLE) enzyme, but increasing numbers of clinically resistant cases and mutations in the SQLE gene have been documented recently. Resistance to antimycotics is phenotypically determined by antifungal susceptibility testing (AFST). However, AFST is not routinely performed for dermatophytes and no breakpoints classifying isolates as susceptible or resistant are available, making it difficult to interpret the clinical impact of a minimal inhibitory concentration (MIC). <b><i>Summary:</i></b> PubMed was systematically searched for terbinafine susceptibility testing of dermatophytes on October 20, 2020, by two individual researchers. The inclusion criteria were <i>in vitro</i> terbinafine susceptibility testing of <i>Trichophyton (T.) rubrum</i>, <i>T. mentagrophytes</i> and <i>T. interdigitale</i> with the broth microdilution technique. The exclusion criteria were non-English written papers. Outcomes were reported as MIC range, geometric mean, modal MIC and MIC<sub>50</sub> and MIC<sub>90</sub> in which 50 or 90% of isolates were inhibited, respectively. The reported MICs ranged from &#x3c;0.001 to &#x3e;64 mg/L. The huge variation in MIC is partly explained by the heterogeneity of the <i>Trichophyton</i> isolates, where some originated from routine specimens (wild types) whereas others came from non-responding patients with a known SQLE gene mutation. Another reason for the great variation in MIC is the use of different AFST methods where MIC values are not directly comparable. High MICs were reported particularly in isolates with SQLE gene mutation. The following SQLE alterations were reported: F397L, L393F, L393S, H440Y, F393I, F393V, F415I, F415S, F415V, S443P, A448T, L335F/A448T, S395P/A448T, L393S/A448T, Q408L/A448T, F397L/A448T, I121M/V237I and H440Y/F484Y in terbinafine-resistant isolates.

Use of spectrophotometric reading for in vitro antifungal susceptibility testing ofAspergillusspp.

1999 ◽  
Vol 45 (10) ◽  
pp. 871-874 ◽  
Author(s):  
Eric Dannaoui ◽  
Florence Persat ◽  
Marie-France Monier ◽  
Elisabeth Borel ◽  
Marie-Antoinette Piens ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Antifungal Susceptibility Testing ◽  
Aspergillus Species ◽  
National Committee ◽  
Broth Microdilution Method

A comparative study of visual and spectrophotometric MIC endpoint determinations for antifungal susceptibility testing of Aspergillus species was performed. A broth microdilution method adapted from the National Committee for Clinical Laboratory Standards (NCCLS) was used for susceptibility testing of 180 clinical isolates of Aspergillus species against amphotericin B and itraconazole. MICs were determined visually and spectrophotometrically at 490 nm after 24, 48, and 72h of incubation, and MIC pairs were compared. The agreement between the two methods was 99% for amphotericin B and ranged from 95 to 98% for itraconazole. It is concluded that spectrophotometric MIC endpoint determination is a valuable alternative to the visual reference method for susceptibility testing of Aspergillus species.Key words: antifungal, susceptibility testing, Aspergillus, spectrophotometric reading.

Vaginitis Due To Pichia fermentans in a Patient Affected by Endometrial Cancer: A Novel Case Report

2021 ◽  
Vol 17 ◽  
Author(s):  
Zarifeh Adampour ◽  
Malihe Hasanzadeh ◽  
Hossein Zarrinfar ◽  
Maryam Nakhaei ◽  
Monika Novak Babič
Keyword(s):  
Endometrial Cancer ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Female Genital Tract ◽  
Antifungal Susceptibility Testing ◽  
Vein Thrombosis ◽  
Microbial Infections ◽  
Life Threatening ◽  
In Vitro Antifungal Susceptibility

Introduction: Endometrial cancer is one of the most common malignancies of the female genital tract, which can be serious or life-threatening. Microbial infections can be one of the underlying causes of this type of cancer. Case Presentation: The present study describes the isolation of Pichia fermentans (Candida firmentaria var. firmentaria) from the vaginal secretions of a 61-year-old woman affected by endometrial cancer. She reported abdominal pain and vaginal discharge for 3 months, and had a history of diabetes, hypertension, Deep Vein Thrombosis (DVT), and Acute Myeloid Leukemia (AML). The isolated yeast was identified based on nuclear ribosomal internal transcribed spacer (ITS1-ITS2 rDNA) sequence analysis. The in vitro antifungal susceptibility testing showed a higher effect for ketoconazole against P. fermentans than fluconazole, itraconazole and voriconazole. Conclusion: Correct differentiation between P. fermentans and other yeast should be considered. The in vitro antifungal susceptibility testing is recommended for rare yeast, and will help the physicians in providing the best treatment.

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