scholarly journals Can We Improve Antifungal Susceptibility Testing?

2021 ◽  
Vol 11 ◽  
Author(s):  
Charlotte Durand ◽  
Danièle Maubon ◽  
Muriel Cornet ◽  
Yan Wang ◽  
Delphine Aldebert ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Imaging Techniques ◽  
Low Cost ◽  
Antifungal Susceptibility ◽  
Turnaround Time ◽  
Antifungal Susceptibility Testing ◽  
Antifungal Stewardship ◽  
Minimal Inhibitory Concentrations

Systemic antifungal agents are increasingly used for prevention or treatment of invasive fungal infections, whose prognosis remains poor. At the same time, emergence of resistant or even multi-resistant strains is of concern as the antifungal arsenal is limited. Antifungal susceptibility testing (AFST) is therefore of key importance for patient management and antifungal stewardship. Current AFST methods, including reference and commercial types, are based on growth inhibition in the presence of an antifungal, in liquid or solid media. They usually enable Minimal Inhibitory Concentrations (MIC) to be determined with direct clinical application. However, they are limited by a high turnaround time (TAT). Several innovative methods are currently under development to improve AFST. Techniques based on MALDI-TOF are promising with short TAT, but still need extensive clinical validation. Flow cytometry and computed imaging techniques detecting cellular responses to antifungal stress other than growth inhibition are also of interest. Finally, molecular detection of mutations associated with antifungal resistance is an intriguing alternative to standard AFST, already used in routine microbiology labs for detection of azole resistance in Aspergillus and even directly from samples. It is still restricted to known mutations. The development of Next Generation Sequencing (NGS) and whole-genome approaches may overcome this limitation in the near future. While promising approaches are under development, they are not perfect and the ideal AFST technique (user-friendly, reproducible, low-cost, fast and accurate) still needs to be set up routinely in clinical laboratories.

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 Antifungal susceptibility testing of Aspergillus niger on silicon microwells by intensity-based reflectometric interference spectroscopy

2019 ◽  
Author(s):  
Christopher Heuer ◽  
Heidi Leonard ◽  
Nadav Nitzan ◽  
Ariella Lavy-Alperovitch ◽  
Naama Massad-Ivanir ◽  
...  
Keyword(s):  
Aspergillus Niger ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Fungal Growth ◽  
Antifungal Susceptibility Testing ◽  
Label Free ◽  
Broth Microdilution ◽  
Silicon Phase ◽  
Reflectometric Interference Spectroscopy

AbstractThe increasing number of invasive fungal infections among immunocompromised patients and the emergence of antifungal resistant pathogens has resulted in the need for rapid and reliable antifungal susceptibility testing (AFST). Accelerating antifungal susceptibility testing allows for advanced treatment decisions and the reduction in future instances of antifungal resistance. In this work, we demonstrate the application of a silicon phase grating as sensor for the detection of growth of Aspergillus niger (A. niger) by intensity-based reflectometric interference spectroscopy and its use as an antifungal susceptibility test. The silicon gratings provide a solid-liquid interface to capture micron-sized Aspergillus conidia within microwell arrays. Fungal growth is optically tracked and detected by the reduction in the intensity of reflected light from the silicon grating. The growth of A. niger in the presence of various concentrations of the antifungal agents voriconazole and amphotericin B is investigated by intensity-based reflectometric interference spectroscopy and used for the determination of the minimal inhibitory concentrations (MIC), which are compared to standard broth microdilution testing. This assay allows for expedited detection of fungal growth and provides a label-free alternative to standard antifungal susceptibility testing methods, such as broth microdilution and agar diffusion methods.

scholarly journals Antifungal susceptibility testing of candida – Methods and issues in current practice

2019 ◽  
Vol 10 (3) ◽  
pp. 1778-1784
Author(s):  
Lakshmi Krishnasamy ◽  
Priya Santharam ◽  
Chitralekha Saikumar
Keyword(s):  
Current Practice ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Antifungal Susceptibility Testing ◽  
Antifungal Drugs ◽  
Testing Methods ◽  
Antifungal Drug Resistance ◽  
Resistant Strains

Despite the availability of many antifungal drugs in clinical practice, the occurrence of antifungal drug resistance is on the rise. Since the antifungal susceptibility testing (AFST) is not done routinely in many of the microbiology laboratories, it is very difficult to determine which antifungal agent is very effective for a particular infection. There is a real need for precise, reproducible and extrapolative antifungal susceptibility testing methods to aid the therapeutic management. The practice of empirical treatment for fungal infections further promotes the emergence of resistant strains. The AFST practice would essentially help the clinicians in appropriate decision making. Although conventional AFST methods are somewhat cumbersome, many novel AFST methods are currently available in many laboratory settings which would provide a quicker result many times. In essence, the application of AFST along with identification of the fungus up to species level would definitely be very helpful in selecting the primary antifungal agents for treatment especially in difficult to manage and invasive fungal infections. This review will throw light on the various AFST methods available and their issues in the current practice.

scholarly journals Antifungal Susceptibility Testing: A Primer for Clinicians

2021 ◽  
Author(s):  
Nathan P Wiederhold
Keyword(s):  
Susceptibility Testing ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Fungal Species ◽  
Antifungal Susceptibility Testing ◽  
Clinical Laboratories ◽  
Invasive Infections ◽  
Clinical Breakpoints

Abstract Clinicians treating patients with fungal infections may turn to susceptibility testing to obtain information regarding the activity of different antifungals against a specific fungus that has been cultured. These results may then be used to make decisions regarding a patient’s therapy. However, for many fungal species that are capable of causing invasive infections, clinical breakpoints have not been established. Thus, interpretations of susceptible or resistant cannot be provided by clinical laboratories, and this is especially true for many molds capable of causing severe mycoses. The purpose of this review is to provide an overview of susceptibility testing for clinicians, including the methods used to perform these assays, their limitations, how clinical breakpoints are established, and how the results may be put into context in the absence of interpretive criteria. Examples of when susceptibility testing is not warranted are also provided.

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 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.

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