EUCAST has revised the definition of the susceptibility category I from ‘Intermediate’ to ‘Susceptible, Increased exposure’. This implies that I can be used where the drug concentration at the site ...of infection is high, either because of dose escalation or through other means to ensure efficacy. Consequently, I is no longer used as a buffer zone to prevent technical factors from causing misclassifications and discrepancies in interpretations. Instead, an Area of Technical Uncertainty (ATU) has been introduced for MICs that cannot be categorized without additional information as a warning to the laboratory that decision on how to act has to be made. To implement these changes, the EUCAST-AFST (Subcommittee on Antifungal Susceptibility Testing) reviewed all, and revised some, clinical antifungal breakpoints.
The aim was to present an overview of the current antifungal breakpoints and supporting evidence behind the changes.
This document is based on the ten recently updated EUCAST rationale documents, clinical breakpoint and breakpoint ECOFF documents.
The following breakpoints (in mg/L) have been revised or established for Candida species: micafungin against C. albicans (ATU = 0.03); amphotericin B (S ≤/> R = 1/1), fluconazole (S ≤/> R = 2/4), itraconazole (S ≤/> R = 0.06/0.06), posaconazole (S ≤/> R = 0.06/0.06) and voriconazole (S ≤/> R = 0.06/0.25) against C. dubliniensis; fluconazole against C. glabrata (S ≤/> R = 0.001/16); and anidulafungin (S ≤/> R = 4/4) and micafungin (S ≤/> R = 2/2) against C. parapsilosis. For Aspergillus, new or revised breakpoints include itraconazole (ATU = 2) and isavuconazole against A. flavus (S ≤/> R = 1/2, ATU = 2); amphotericin B (S ≤/> R = 1/1), isavuconazole (S ≤ /> R = 1/2, ATU = 2), itraconazole (S ≤/> R = 1/1, ATU = 2), posaconazole (ATU = 0.25) and voriconazole (S ≤/> R = 1/1, ATU = 2) against A. fumigatus; itraconazole (S ≤/> R = 1/1, ATU = 2) and voriconazole (S ≤/> R = 1/1, ATU = 2) against A. nidulans; amphotericin B against A. niger (S ≤/> R = 1/1); and itraconazole (S ≤/> R = 1/1, ATU = 2) and posaconazole (ATU = 0.25) against A. terreus.
EUCAST-AFST has released ten new documents summarizing existing and new breakpoints and MIC ranges for control strains. A failure to adopt the breakpoint changes may lead to misclassifications and suboptimal or inappropriate therapy of patients with fungal infections.
The emergence of azole-resistant Aspergillus fumigatus isolates is a matter of significant concern in Europe, with countries reporting resistance rates (which can be as high as 30%) in hospitalized ...patients. Consequently, the treatment guidelines in The Netherlands, the country with the highest documented prevalence of azole-resistant A. fumigatus, has just been revised to now recommend initial therapy with combination therapy until the susceptibility pattern is known. Therefore, susceptibility testing of clinically relevant isolates has been strongly recommended in the ESCMID-EFISG aspergillosis guidelines. Furthermore, mixed azole-susceptible and azole-resistant (isogenic as well as non-isogenic) infections have been reported to occur, which implies that colonies of clinical cultures may harbour various phenotypes of azole susceptibility.
The EUCAST-AFST (European Committee on Antimicrobial Susceptibility Testing Subcommittee on Antifungal Susceptibility Testing) has released a new screening method document (E.Def 10.1) for the detection of azole-resistant A. fumigatus isolates and updated the QC tables for antifungal susceptibility testing with associated QC endpoints. This review described in detail how to perform the screening test.
This “How to document” is based on the EUCAST azole agar screening method document E.Def 10.1 and the QC tables for antifungal susceptibility testing document, v 2.0 (available at http://www.eucast.org/ast_of_fungi/qcafsttables/)
The method is based on the inoculation of azole-containing and azole-free agars and visual determination of fungal growth after one and two days of incubation. It can easily be implemented in routine laboratories of clinical microbiology and has been validated for simultaneous testing of up to five A. fumigatus colonies using itraconazole and voriconazole (mandatory), and posaconazole (optional).
This easy-to-use screening procedure for the detection of azole resistance in clinical A. fumigatus isolates will allow rapid testing in the daily routine of the microbiology laboratory and thus facilitate earlier appropriate therapy.
Aspergillus osteomyelitis is a rare infection. We reviewed 310 individual cases reported in the literature from 1936 to 2013. The median age of patients was 43 years (range, 0–86 years), and 59% were ...males. Comorbidities associated with this infection included chronic granulomatous disease (19%), haematological malignancies (11%), transplantation (11%), diabetes (6%), pulmonary disease (4%), steroid therapy (4%), and human immunodeficiency virus infection (4%). Sites of infection included the spine (49%), base of the skull, paranasal sinuses and jaw (18%), ribs (9%), long bones (9%), sternum (5%), and chest wall (4%). The most common infecting species were Aspergillus fumigatus (55%), Aspergillus flavus (12%), and Aspergillus nidulans (7%). Sixty-two percent of the individual cases were treated with a combination of an antifungal regimen and surgery. Amphotericin B was the antifungal drug most commonly used, followed by itraconazole and voriconazole. Several combination or sequential therapies were also used experimentally. The overall crude mortality rate was 25%.
Purpose
We compared the risk factors, the diagnostic tools and the outcome of filamentous fungal infections (FFIs) in hematological patients (HAEs) and non-hematological patients (non-HAEs).
Methods
...Prospective surveillance (2009–2011) of
proven
and
probable
FFIs was implemented in 23 Italian hospitals.
Results
Out of 232 FFIs, 113 occurred in HAEs and 119 in non-HAEs. The most frequent infection was invasive aspergillosis (76.1 % for HAEs, 56.3 % for non-HAEs), and the localization was principally pulmonary (83.2 % for HAEs, 74.8 % for non-HAEs). Neutropenia was a risk factor for 89.4 % HAEs; the main underlying condition was corticosteroid treatment (52.9 %) for non-HAEs. The distribution of
proven
and
probable
FFIs was different in the two groups:
proven
FFIs occurred more frequently in non-HAEs, whereas
probable
FFIs were correlated with the HAEs. The sensitivity of the galactomannan assay was higher for HAEs than for non-HAEs (95.3 vs. 48.1 %). The overall mortality rate was 44.2 % among the HAEs and 35.3 % among the non-HAEs. The etiology influenced the patient outcomes: mucormycosis was associated with a high mortality rate (57.1 % for HAEs, 77.8 % for non-HAEs).
Conclusions
The epidemiological and clinical data for FFIs were not identical in the HAEs and non-HAEs. The differences should be considered to improve the management of FFIs according to the patients’ setting.
A case of systemic infection due to
Saprochaete capitata
in a patient with chronic lymphocytic leukemia is described. A review of the literature was conducted to identify all reported cases of this ...infection described between 1977 and August 2013. One hundred and four cases (included the present one) were identified. The median age of the patients was 56 years and 56 % were males. Comorbidities included acute myeloid leukemia (52 %), acute lymphoid leukemia (22 %), other hematological malignancies (13 %) and non-hematological diseases (9 %). At the time of the infection, 82 % of the patients were neutropenic. In 75 % of the cases, the yeast was isolated from blood culture, in 25 % from other sterile sites. Empirical treatment was done in 36 % of the cases. Fifty-eight percent of the individual cases were treated with a combination or a sequential antifungal therapy. Amphotericin B was the antifungal drug most commonly used, followed by voriconazole and itraconazole. The overall crude mortality was 60 %.
Saprochaete capitata
causes life-threatening infections in neutropenic patients. This comprehensive literature review may help the clinician to optimize the management of this rare infection.
Nineteen Cryptococcus neoformans AD-hybrid isolates were investigated to assess whether hybrid genomic background could affect virulence in a mouse model. The level of heterozygosity of each strain ...was analyzed using primers specific for allele A and D of 15 polymorphic genes. Virulence was tested in a mouse model of systemic infection by measuring time of survival. In addition, the putative virulence attributes, melanin, phospholipase, and capsule production, as well as growth at 39°C and UV sensitivity were investigated. Eight strains showed to be heterozygous in up to 70% of loci, other eight strains were heterozygous in less than 60% of loci, while the remaining three strains were homozygous at all tested loci. Mice infected with hybrids with a high percentage of heterozygosis showed significantly (P < 0.01) shorter survival than mice infected with the other hybrids. Mortality was not correlated with the mating-type locus pattern, as well as it was not correlated with the level of expression of the different virulence attributes investigated. The present study confirms that hybridization in C. neoformans could represent an important evolutionary driving force in increasing the fitness of this yeast in the environment and in the host.
Aspergillus spp. invasive external otitis (IEO) is a rare infection. We performed a seven-year, single-centre retrospective study from 2007 to 2014 including all patients with proven Aspergillus spp. ...IEO. Twelve patients were identified. All patients had a poorly controlled diabetes mellitus and one underwent solid organ transplant. The most frequently isolated species was Aspergillus flavus (n = 10) and voriconazole was the first-line therapy in all cases, with a median length of treatment of 338.5 days (158–804 days). None of the patients underwent extensive surgery. The clinical outcome was excellent. However, otological sequelae were reported, including hearing impairment (n = 7) and facial palsy (n = 3).
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