Search Results (9)

Antifungal therapy, especially with the azoles, could promote the incidence of less susceptible isolates of Cryptococcus neoformans and C. gattii species complexes (SC), mostly in developing countries. Given that these species affect mostly the immunocompromised host, the infections are severe and difficult to treat. This review encompasses the following topics: 1. infecting species and their virulence, 2. treatment, 3. antifungal susceptibility methods and available categorical endpoints, 4. genetic mechanisms of resistance, 5. clinical resistance, 6. fluconazole minimal inhibitory concentrations (MICs), clinical outcome, 7. environmental influences, and 8. the relevance of host factors, including pharmacokinetic/pharmacodynamic (PK/PD) parameters, in predicting the clinical outcome to therapy. As of now, epidemiologic cutoff endpoints (ECVs/ECOFFs) are the most reliable antifungal resistance detectors for these species, as only one clinical breakpoint (amphotericin B and C. neoformans VNI) is available. Full article

Streptococcus agalactiae is a major health concern in tilapia farming worldwide. In contrast to the availability of susceptibility profile results, interpretative criteria for disk diffusion assays and the influence of serotypes on resistance profiles are not available. To address this, sixty isolates (thirty of each serotype, Ib and III) were evaluated using the disk diffusion assay against six antibiotics, and the epidemiological cut-off value (ECV) was calculated. All the isolates were classified as non-wild type (NWT) for sulfamethoxazole (SUT) and norfloxacin (NOR). The inhibition zones for oxytetracycline (OXY) and doxycycline (DOX) were largely distinct; all serotype Ib and III isolates were classified as wild-type (WT) and NWT, respectively. The results for serotype III of fish group B Streptococcus (GBS) were comparable to the NWT tetracycline profile of human GBS available in EUCAST, suggesting the presence of resistance mechanisms in these fish isolates. The calculation of the cut-off wild type (CO_WT) values for OXY and DOX was appropriate for both serotypes. Differences between the distribution of florfenicol (FLO) and amoxicillin (AMO) were found, and we attribute this to the faster growth rate of serotype III, which promotes smaller inhibition zones. Therefore, using separate CO_WT for each serotype is necessary. In conclusion, the serotype of fish GBS affects its susceptibility profile, and it is recommended to use serotype-specific CO_WT values as interpretative criteria for disk diffusion assays against FLO and AMO. Full article

When method-dependent categorical endpoints are available, namely either BPs or ECVs, MICs could aid in selecting the best treatment agent(s). BPs can categorize an isolate as either susceptible or resistant while the ECVs/ECOFFs can distinguish the wild type (WT, no known resistance mechanisms) from the Non-WT (NWT, harboring resistant mechanisms). Our literature review focused on the Cryptococcus species complex (SC) and the available methods and categorization endpoints. We also covered the incidence of these infections as well as the numerous Cryptococcus neoformans SC and C. gattii SC genotypes. The most important agents to treat cryptococcal infections are fluconazole (widely used), amphotericin B, and flucytosine. We provide data from the collaborative study that defined CLSI fluconazole ECVs for the most common cryptococcal species or genotypes and modes. EUCAST ECVs/ECOFFs are not yet available for fluconazole. We have summarized the incidence of cryptococccal infections (2000–2015) where fluconazole MICs were obtained by reference and commercial antifungal susceptibility tests. This occurrence is documented all over the world and those fluconazole MICs are mostly categorized by available CLSI ECVs/BPs as “resistant” instead of non-susceptible strains, including those by the commercial methods. As expected, the agreement between the CLSI and commercial methods is variable because SYO and Etest data could yield low/variable agreement (<90%) versus the CLSI method. Therefore, since BPs/ECVs are species and method dependent, why not gather sufficient MICs by commercial methods and define the required ECVs for these species? Full article

Providing timely antifungal treatment to patients suffering from life-threatening invasive fungal infections (IFIs) is essential. Due to the changing epidemiology and the emergence of antifungal resistance in Aspergillus, the most commonly responsible mold of IFIs, antifungal susceptibility testing (AFST) has become increasingly important to guide clinical decisions. This study assessed the essential agreement (EA) between broth microdilution methods (the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST)) and the Etest of amphotericin B (AmB), liposomal amphotericin B (L-AmB), and isavuconazole (ISA) against 112 Aspergillus section Terrei. An EA within ±2 dilutions of ≥90% between the two methods was considered acceptable. Excellent EA was found between EUCAST and CLSI of AmB and ISA (98.2% and 95.5%, respectively). The correlation of Etest results and EUCAST/CLSI was not acceptable (<90%) for any tested antifungal; however, Etest and CLSI for AmB (79.6%) and ISA (77.6%) showed a higher EA than Etest and EUCAST for AmB (49.5%) and ISA (46.4%). It was concluded that the Etest method requires its own clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs), and interpreting Etest results using EUCAST and CLSI-adapted CBPs and ECVs could result in misinterpretation as Etest shows lower minimum inhibitory concentrations (MICs). Full article

Susceptibility testing can yield variable results because it is method (commercial or reference), agent, and species dependent. Therefore, in order for results to be clinically relevant, MICs (minimal inhibitory concentrations) or MECs (minimal effective concentrations) should help in selecting the best treatment agent in the clinical setting. This is accomplished by categorical endpoints, ideally, breakpoints (BPs) and/or ECVs/ECOFFs (epidemiological cutoff values). BPs and ECVs are available by the reference methods (CLSI [Clinical and Laboratory Standards Institute] and EUCAST [European Committee on Antifungal Susceptibility Testing]) for a variety of species/agent combinations. The lack of clinical data precludes establishment of BPs for susceptibility testing by the commercial methods and ECVs have only been calculated for the Etest and SYO assays. The goal of this review is to summarize the variety of commercial methods for antifungal susceptibility testing and the potential value of Etest and SYO ECVs for detecting mutants/non-wild type (NWT) Candida isolates. Therefore, the literature search focused on publications where the commercial method, meaning MICs and ECVs, were reported for specific NWT isolates; genetic mutations have also been listed. For the Etest, the best performers recognizing the NWT were anidulafungin ECVs: 92% for the common species; 97% for C. glabrata and fluconazole ECVs, mostly for C. parapsilosis (45 NWT isolates). By the SYO, posaconazole ECVs recognized 93% of the C. albicans and 96% of the C. parapsilosis NWT isolates and micafungin ECVs 94% (mostly C. albicans and C. glabrata). Smaller sets, some with clinical data, were also listed. These are promising results for the use of both commercial methods to identify antifungal resistance (NWT isolates). However, ECVs for other species and methods need to be defined, including the C. neoformans complex and emerging species. Full article

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. Full article

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. Full article

Local antimicrobial susceptibility surveys are crucial for optimal empirical therapy guidelines and for aiding in antibiotic stewardship and treatment decisions. For many laboratories, a comprehensive overview of local antimicrobial susceptibility patterns of anaerobic bacteria is still lacking due to the long incubation time and effort involved. The present study investigates the antimicrobial susceptibility patterns and related clinical and demographic data of 2856 clinical isolates of anaerobic bacteria that were submitted for analysis to the Institute for Medical Microbiology and Hygiene of the Freiburg University Medical Center (a tertiary university medical center in Southern Germany) between 2015 and 2019. Antimicrobial susceptibility testing has been carried out according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. Minimum inhibitory concentration (MIC)₅₀ and MIC₉₀ for penicillin, metronidazole, moxifloxacin, and clindamycin were established for Gram-positive anaerobes and for ampicillin-sulbactam, meropenem, metronidazole, moxifloxacin, and clindamycin for Gram-negative anaerobes. The distribution of MIC-values for various antibiotics against anaerobic bacteria was also established, especially for those having no specific breakpoints according to EUCAST guidelines. Most clinically relevant anaerobic bacteria originated from general surgery, neurological, and orthopedic wards. A high proportion of isolates were resistant to moxifloxacin and clindamycin indicating the importance of their susceptibility testing before administration. Based on our study metronidazole and other β-lactam/β-lactamase inhibitor combinations such as ampicillin-sulbactam remain suitable for empirical treatment of infections with anaerobic bacteria. Full article

In vitro susceptibility testing of Fusarium is becoming increasingly important because of frequency and diversity of infections and because resistance profiles are species-specific. Reference methods for antifungal susceptibility testing (AFST) are those of Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility (EUCAST), but breakpoints (BPs) have not yet been established. One of the problems is that phylogenetic distances between Fusarium species are much smaller than between species of, e.g., Candida. Epidemiological cutoff values (ECVs) for some Fusarium species have been determined in order to differentiate wild-type from non-wild-type isolates. In clinical routine, commercially available assays such as Etest, Sensititre or others provide essential agreement with reference methods. Our objective is to summarize antifungal susceptibility testing of Fusarium genus in the clinical laboratory: how to do it, when to do it, and how to interpret it. Full article