1376. Antifungal Activity of Cerium Nitrate Against Fungal Isolates Associated with Combat-Related Injuries Including Burns

Abstract Background Fungal infections are a critical cause of morbidity and mortality in burn patients. In addition to debridement and systemic antifungal therapy, various topical adjuncts have been used, and topical burn care is a key component of infection prevention and treatment. Cerium nitrate (CN) has been used in combination with silver sulfadiazine (SS) in burn care. Previous studies showed that CN had bacteriostatic activity, and suggested anti-biofilm activity against Candida biofilms. In this study, we evaluated the in vitro activity of CN against fungal isolates associated with combat-related injuries. Methods The efficacy of CN was evaluated against 14 mold (three Aspergillus spp., two Fusarium spp., five different mucormycetes, two Bipolaris spp., one Alternaria spp., one Exophiala spp.) and 21 Candida spp. isolates collected as part of the Trauma Infectious Disease Outcomes Study. Fungicidal activity of various concentrations of CN (2.2%, 1%, 0.5% and 0.2%) was determined using an established time-kill assay. Standard conidia/cell suspensions were prepared according to Clinical and Laboratory Standards Institute guidelines and then exposed to the CN solutions for 24 hours. At different times (0, 5, 15, 30 minutes, 1, 1.5, 3, 6, 12, and 24 hours) aliquots were plated and incubated at 35ºC. Colony forming unit (CFU) counts were determined after 24 hours incubation or after an appropriate time for slow growing molds. Results All mold isolates had persistent growth at 24 hours with most having no significant change in colony counts over the 24-hour period. The only exception was Mucor circinelloides, which appeared to have a time-dependent reduction in CFUs at 24 hours for all CN concentrations. Exophiala did not grow as well in CN solutions compared with the control (mean 65 vs. 28.2 CFUs with a difference of mean 37.4 CFUs, P = 0.0001), but this was not time or concentration dependent. All yeast species showed a time-dependent killing after 6–12 hours. Conclusion CN demonstrated time-dependent killing of the yeasts. However, very little activity was observed against the tested molds. Since CN is often used in combination with SS there might be a synergistic effect against molds. Further research will evaluate higher concentrations of CN and its toxicity for cells and tissue. Disclosures All authors: No reported disclosures.

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2115. Activity of a Long-Acting Echinocandin Rezafungin and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates: SENTRY 2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1795 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S716-S716 ◽

Cited By ~ 1

Author(s):

Michael A Pfaller ◽

Cecilia G Carvalhaes ◽

Shawn A Messer ◽

Paul R Rhomberg ◽

Mariana Castanheira

Keyword(s):

Drug Exposure ◽

Fungal Infections ◽

Hot Spot ◽

Good Activity ◽

Candida Spp ◽

Fluconazole Resistance ◽

Fungal Isolates ◽

Long Acting ◽

In Vitro Data

Abstract Background Echinocandins are the first-line treatment of candidemia. We evaluated the activity of rezafungin (RZF), a novel long-acting echinocandin with front-loaded drug exposure and extensive distribution to sites of infection, and comparators using CLSI broth microdilution methods against 709 invasive fungal isolates collected worldwide during 2018. Methods Susceptibility (S) tests on 663 Candida spp. (6 species), 21 C. neoformans (CNEO), and 25 A. fumigatus (ASF) were conducted for RZF, anidulafungin (ANF), caspofungin (CSF), micafungin (MCF), and azoles. CLSI clinical breakpoint (CBP) and epidemiological cutoff value (ECV) interpretive criteria were applied. Isolates displaying echinocandin MIC>ECV were sequenced for fks hot spot (HS) mutations. Results RZF inhibited 99.7% of C. albicans (CA) isolates (MIC50/90, 0.015/0.06 mg/L), 100.0% of C. tropicalis (CT) (MIC50/90, 0.03/0.06 mg/L), 98.9% of C. glabrata (CG) (MIC50/90, 0.03/0.06 mg/L), 100.0% of C. krusei (CK) (MIC50/90, 0.015/0.12 mg/L), and 100.0% of C. dubliniensis (CD) (MIC50/90, 0.03/0.06 mg/L) at ≤0.12 mg/L. All (104/104 [100.0%]) C. parapsilosis (CP) isolates (MIC50/90,1/2 mg/L) were inhibited by RZF at ≤2 mg/L. Fluconazole resistance was detected among 9.0% of CG, 17.3% of CP, and 1.6% of CT. The activity of RZF against these 6 Candida spp. was similar to that of the other echinocandins, the vast majority of which were susceptible/wild type (WT) using CBP/ECV. A total of 5 isolates (3 CG, 1 CA, and 1 CT) displayed 1 or more non-WT or-resistant MIC values and were sequenced for fks HS mutations. Fluconazole and other azoles displayed good activity against CNEO whereas echinocandins including RZF displayed limited activity against CNEO isolates. Echinocandins displayed good activity against ASF, and RZF activity was similar to that of anidulafungin, caspofungin, and micafungin. All but 1 isolate (non-WT MIC for itraconazole, 2 mg/L) displayed WT MIC values for the mould-active azoles. Conclusion Rezafungin was as active as other echinocandins against common organisms recovered from invasive fungal infections. These in vitro data contribute to accumulating research demonstrating rezafungin potential for prevention and treatment of invasive fungal infection. Disclosures All authors: No reported disclosures.

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In vitro pharmacokinetics/pharmacodynamics modeling and efficacy against systemic candidiasis in Drosophila melanogaster of a bisaryloxypropanamine derivative

Medical Mycology ◽

10.1093/mmy/myaa030 ◽

2020 ◽

Vol 59 (1) ◽

pp. 58-66

Author(s):

Daiane Flores Dalla Lana ◽

Taís Fernanda Andrzejewski Kaminski ◽

Stefânia Neiva Lavorato ◽

Simone Merkel ◽

Régis Adriel Zanette ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Fungal Infections ◽

Pathogenic Fungi ◽

Maximum Effect ◽

Systemic Candidiasis ◽

Candida Spp ◽

Synthetic Compound ◽

Starting Point ◽

Time Kill

Abstract The number of deaths due to systemic fungal infections is increasing alarmingly, which is aggravated by the limitations of traditional treatments and multidrug resistance. Therefore, the research and development of new therapeutic options against pathogenic fungi is an urgent need. To evaluate the fungicidal activity of a synthetic compound, 1,3-bis-(3,4-dichlorophenoxy)propan-2-aminium chloride (2j), through time-kill studies and pharmacokinetics/pharmacodynamics (PK/PD) modeling. The protective effect of the compound was also evaluated using the Drosophila melanogaster minihost model of candidiasis. Mathematical modeling of time-kill data of compound 2j was performed to obtain PD characteristics. Additionally, Toll-deficient D. melanogaster flies were infected with a Candida albicans strain and treated with 2j. We observed that compound 2j demonstrated a time- and dose-dependent fungicidal effect against Candida spp. and dermatophytes, even at low concentrations, and rapidly achieved kill rates reaching the maximum effect in less than one hour. The efficacy of the compound against systemic candidiasis in D. melanogaster flies was comparable to that achieved by fluconazole. These results support the potential of compound 2j as a systemic antifungal agent candidate and serve as a starting point for further studies involving mammalian animal models.

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1260. Activity of Manogepix (APX001A) against 2,669 Fungal Isolates from the SENTRY Surveillance Program (2018-2019) Stratified by Infection Type

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1444 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S646-S647

Author(s):

Michael D Huband ◽

Michael A Pfaller ◽

Robert K Flamm ◽

Shawn A Messer ◽

Beth A Schaefer ◽

...

Keyword(s):

Fungal Infections ◽

Infection Type ◽

Chemical Diversity ◽

Candida Spp ◽

Services Research ◽

Fungal Isolates ◽

Infection Types ◽

Center Research ◽

Research Grant

Abstract Background Existing antifungal agents are active against many common fungal pathogens; however, breakthrough fungal infections occur and often involve less frequently encountered yeast and mould isolates. These rarer isolates tend to exhibit diminished susceptibility to current agents. Manogepix (MGX, APX001A) is a novel inhibitor of the fungal Gwt1 enzyme. The prodrug (fosmanogepix), is being evaluated in Phase 2 clinical trials for invasive candidiasis/candidemia, Candida auris infections, and invasive aspergillosis. In this study, we evaluated the in vitro activity of MGX and comparators against 2,669 clinical fungal isolates collected worldwide (2018-2019) and stratified by infection type. Methods Fungal isolates were collected from medical centers located in North America (34 sites; 42.3%), Europe (30 sites; 37.9%), Asia-Pacific (11 sites; 12.3%), and Latin America (7 sites; 7.6%). Isolates were collected from bloodstream infections (BSI; 51.7%), pneumonia in hospitalized patients (PIHP; 21.1%), skin and skin structure infections (SSSI; 5.5%), urinary tract infections (UTI; 2.3%), intraabdominal infections (IAI; 1.9%), and other infection types (17.5%). Results MGX demonstrated potent in vitro activity against 1,887 Candida spp. isolates from BSI, PIHP, SSSI, and all infection types (MIC50/90, 0.008/0.03-0.06 mg/L) outperforming all comparator agents (Table). Similarly, MGX was equally active against 578 Aspergillus spp. isolates (MEC50/90, 0.015/0.03 mg/L), regardless of infection type. MGX was active against Cryptococcus neoformans var. grubii isolates from BSI and ALL infection types with MIC50/90 values of 0.5/2 mg/L. Scedosporium spp. isolates from PIHP and all infection types were inhibited by low concentrations of MGX (MEC50/90, 0.03/0.03 mg/L). Table 1 Conclusion MGX demonstrated potent antifungal activity against Candida spp., Aspergillus spp., C. neoformans var. grubii, and non-Aspergillus moulds, including Scedosporium spp. isolates. Notable activity was seen against C. auris, echinocandin-resistant Candida spp., azole-resistant Aspergillus, and Scedosporium spp. isolates. Further clinical development of fosmanogepix in difficult-to-treat resistant fungal infections is warranted. Disclosures Michael A. Pfaller, MD, Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support) Shawn A. Messer, PhD, Amplyx Pharmaceuticals (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support) Beth A. Schaefer, n/a, Amplyx Pharmaceuticals (Research Grant or Support) Paul Bien, MS, Amplyx Pharmaceuticals (Employee) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)

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Techniques for the Assessment of In Vitro and In Vivo Antifungal Combinations

Journal of Fungi ◽

10.3390/jof7020113 ◽

2021 ◽

Vol 7 (2) ◽

pp. 113

Author(s):

Anne-Laure Bidaud ◽

Patrick Schwarz ◽

Guillaume Herbreteau ◽

Eric Dannaoui

Keyword(s):

Animal Models ◽

Fungal Infections ◽

Acquired Resistance ◽

Adequate Treatment ◽

Combination Treatments ◽

Target Organs ◽

Fungal Load ◽

Time Kill

Systemic fungal infections are associated with high mortality rates despite adequate treatment. Moreover, acquired resistance to antifungals is increasing, which further complicates the therapeutic management. One strategy to overcome antifungal resistance is to use antifungal combinations. In vitro, several techniques are used to assess drug interactions, such as the broth microdilution checkerboard, agar-diffusion methods, and time-kill curves. Currently, the most widely used technique is the checkerboard method. The aim of all these techniques is to determine if the interaction between antifungal agents is synergistic, indifferent, or antagonistic. However, the interpretation of the results remains difficult. Several methods of analysis can be used, based on different theories. The most commonly used method is the calculation of the fractional inhibitory concentration index. Determination of the usefulness of combination treatments in patients needs well-conducted clinical trials, which are difficult. It is therefore important to study antifungal combinations in vivo, in experimental animal models of fungal infections. Although mammalian models have mostly been used, new alternative animal models in invertebrates look promising. To evaluate the antifungal efficacy, the most commonly used criteria are the mortality rate and the fungal load in the target organs.

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In VitroandIn VivoActivities of the Novel Ketolide RBx 14255 against Clostridium difficile

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00015-12 ◽

2012 ◽

Vol 56 (11) ◽

pp. 5986-5989 ◽

Cited By ~ 5

Author(s):

Manoj Kumar ◽

Tarun Mathur ◽

Tarani K. Barman ◽

G. Ramkumar ◽

Ashish Bhati ◽

...

Keyword(s):

Clostridium Difficile ◽

Time Dependent ◽

Kinetics Study ◽

The Novel ◽

Promising Candidate ◽

Hamster Model ◽

Bacterial Killing ◽

Content Type ◽

Time Kill

ABSTRACTThe MIC90of RBx 14255, a novel ketolide, againstClostridium difficilewas 4 μg/ml (MIC range, 0.125 to 8 μg/ml), and this drug was found to be more potent than comparator drugs. Anin vitrotime-kill kinetics study of RBx 14255 showed time-dependent bacterial killing forC. difficile. Furthermore, in the hamster model ofC. difficileinfection, RBx 14255 demonstrated greater efficacy than metronidazole and vancomycin, making it a promising candidate forC. difficiletreatment.

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2106. Evaluation of Isavuconazole for the Prophylaxis and Treatment of Invasive Fungal Infections at a Large Academic Medical Center

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1786 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S712-S713

Author(s):

Christine Vu ◽

Meenakshi Rana ◽

Patricia Saunders-Hao

Keyword(s):

Fungal Infections ◽

Medical Center ◽

Academic Medical Center ◽

Retrospective Chart Review ◽

Invasive Fungal Infections ◽

Prescribing Practices ◽

Candida Spp ◽

Antifungal Stewardship ◽

Hospital Formulary

Abstract Background Isavuconazole is an azole antifungal with in vitro activity against various fungi, including Candida spp, Aspergillus, and Mucormycetes. Currently, isavuconazole is FDA approved for the treatment of invasive aspergillosis and mucormycosis; however, there remains limited data to support prophylaxis use. Compared with other first-line azoles, isavuconazole’s broad spectrum of activity, favorable safety profile, and oral bioavailability makes it an attractive antifungal option. In July 2017, isavuconazole was added to our hospital formulary as a restricted antimicrobial. Since then, we have seen increased use for both prophylaxis and treatment of invasive fungal infections. Methods A single-center, retrospective chart review was conducted on adult patients who received at least 1 dose of isavuconazole at The Mount Sinai Hospital between July 1, 2017 and December 31, 2018. The electronic medical record was utilized to collect information on therapeutic indication, dosing, formulation, duration, reasons for switching to isavuconazole, prior antifungals, and proven or probable breakthrough invasive fungal infections (bIFIs) based on EORTG/MTG definitions. Results 54 patients received 61 courses of isavuconazole. Reasons for switching to isavuconazole are described in Table 1. Eleven patients received inappropriate intravenous formulations and 14% of orders were prescribed isavuconazole without a loading dose (Table 2). We identified 4 proven/probable bIFIs, representing 7.4% of patients and 6.6% of courses (Table 3). All patients died within 60 days of bIFI onset. Conclusion Since its addition to hospital formulary, we have observed varying isavuconazole prescribing practices, highlighting the need for improved antifungal stewardship. Rates of bIFIs on isavuconazole were lower than previously reported studies. Additional studies are needed to provide guidance on isavuconazole use and determine its role as prophylaxis therapy. Disclosures All authors: No reported disclosures.

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Antibiofilm Potential of Medicinal Plants against Candida spp. Oral Biofilms: A Review

Antibiotics ◽

10.3390/antibiotics10091142 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1142

Author(s):

Rafaela Guimarães ◽

Catarina Milho ◽

Ângela Liberal ◽

Jani Silva ◽

Carmélia Fonseca ◽

...

Keyword(s):

Natural Products ◽

Medicinal Plants ◽

Oral Cavity ◽

Plant Extracts ◽

Fungal Infections ◽

High Capacity ◽

Biologically Active ◽

Antibiofilm Activity ◽

Candida Spp

The use of natural products to promote health is as old as human civilization. In recent years, the perception of natural products derived from plants as abundant sources of biologically active compounds has driven their exploitation towards the search for new chemical products that can lead to further pharmaceutical formulations. Candida fungi, being opportunistic pathogens, increase their virulence by acquiring resistance to conventional antimicrobials, triggering diseases, especially in immunosuppressed hosts. They are also pointed to as the main pathogens responsible for most fungal infections of the oral cavity. This increased resistance to conventional synthetic antimicrobials has driven the search for new molecules present in plant extracts, which have been widely explored as alternative agents in the prevention and treatment of infections. This review aims to provide a critical view and scope of the in vitro antimicrobial and antibiofilm activity of several medicinal plants, revealing species with inhibition/reduction effects on the biofilm formed by Candida spp. in the oral cavity. The most promising plant extracts in fighting oral biofilm, given their high capacity to reduce it to low concentrations were the essential oils extracted from Allium sativum L., Cinnamomum zeylanicum Blume. and Cymbopogon citratus (DC) Stapf.

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Antimicrobial resistance among fungi from patients with urinary tract infections in Ojo, Lagos, Nigeria

GSC Biological and Pharmaceutical Sciences ◽

10.30574/gscbps.2021.14.3.0082 ◽

2021 ◽

Vol 14 (03) ◽

pp. 254-264

Author(s):

Dauphin Dighitoghi Moro ◽

Oluwole Moses David

Keyword(s):

Urinary Tract ◽

Amphotericin B ◽

Urinary Tract Infections ◽

Fungal Pathogens ◽

Fungal Infections ◽

Antifungal Susceptibility ◽

Candida Spp ◽

Fungal Isolates ◽

Vaginal Swabs ◽

Tract Infections

The incidence of fungal urinary tract infections has risen gradually and has thus constituted a public health challenge. The aim of this study was to determine the prevalence of urinary tract infections by fungi in two health centres in Ojo, Lagos. A total of 200 patients attending the health centers constituting 160 males’ urines and 40 females’ vaginal swabs were recruited for this study. Midstream urine samples and vaginal swabs were aseptically collected and processed using standard mycological techniques. Fungal isolates were identified based on cultural characteristics, lactophenol blue stain, chlamydospore formation, colony colour on CHROM agar Candida medium and API yeast identification. Antifungal susceptibility testing of the isolates was performed by using the Broth dilution and Kirby-Bauer disk diffusion methods using two of the most commonly used antifungal agents. A total of 122 fungal isolates, of which 68 (55.7%) were Candida spp. and 54(44.3%) Aspergillus spp. were recovered. The Candida spp. included 64 (52.5%) C. albicans and 4(3.3%) C. glabrata while Aspergillus spp. included A. flavus, 20(16.4%), A. fumigatus, 24 (19.8%) and A niger, 10(8.2%). The most common fungal pathogens in the urinary tracts of the subjects were Candida albicans and Aspergillus fumigatus. Both C. albicans and A. fumigatus were highly susceptible to both fluconazole and amphotericin B in dimethyl sulphoxide and water (90-100%). Similarly, all Aspergillus spp. were susceptible to both antifungals except A. flavus which showed a slight resistance (10-15%), which appears to be emerging. Both fluconazole and amphotericin B still show high chances of therapeutic efficacy against fungal infections of the urinary tracts.

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QSAR Study of Some 1,3-Oxazolylphosphonium Derivatives as New Potent Anti-Candida Agents and Their Toxicity Evaluation

Current Drug Discovery Technologies ◽

10.2174/1570163815666180418145422 ◽

2019 ◽

Vol 16 (2) ◽

pp. 204-209

Author(s):

Maria M. Trush ◽

Vasyl Kovalishyn ◽

Alla D. Ocheretniuk ◽

Oleksandr L. Kobzar ◽

Maryna V. Kachaeva ◽

...

Keyword(s):

Fungal Infections ◽

Electric Organ ◽

Biological Marker ◽

Diffusion Method ◽

Phosphonium Salts ◽

Candida Spp ◽

Qsar Study ◽

Disk Diffusion Method ◽

Qsar Models

Background: The incidence of invasive fungal infections caused by Candida spp. has increased continuously in recent decades, especially in populations of immunocompromised patients or individuals hospitalized with serious underlying diseases. Therefore, the goal of our study was the search for new potent Candida albicans inhibitors via the development of QSAR models that could speed up this search process. A number of the most promising 1,3-oxazol-4-yltriphenylphosphonium derivatives with predicted activities were synthesized and experimentally tested. Furthermore, the toxicity of the studied compounds was determined in vitro using acetylcholinesterase enzyme as a biological marker. Methods: The classification QSAR models were created using Random Forests (WEKA-RF), k-Nearest Neighbors and Associative Neural Networks methods and different combinations of descriptors on the Online Chemical Modeling Environment (OCHEM) platform. Аntifungal properties of the investigated compounds were performed using standard disk diffusion method. The enzyme inhibitory action of the compounds was determined by modified Ellman's method using acetylcholinesterase from the electric organ of Electrophorus electricus. Results: Three classification QSAR models were developed by the WEKA-RF, k-NN and ASNN methods using the ALogPS, E-State indices and Dragon v.7 descriptors. The predictive ability of the models was tested through cross-validation, giving a balanced accuracy BA = 80-91%. All compounds demonstrated good antifungal properties against Candida spp. and slight inhibition of the acetylcholinesterase activity. Conclusion: The high percentage of coincidence between the QSAR predictions and the experimental results confirmed the high predictive power of the developed QSAR models that can be applied as tools for finding new potential inhibitors against Candida spp. Furthermore, 1,3-oxazol-4- yl(triphenyl)phosphonium salts could be considered as promising candidates for the treatment of candidiasis and the disinfection of medical equipment.

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

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652015000700011 ◽

2015 ◽

Vol 57 (suppl 19) ◽

pp. 57-64 ◽

Cited By ~ 57

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.

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