Azole resistance poses a problem for the management of patients with invasive aspergillosis. Former species are in fact groups of closely related species (or complexes); cryptic species frequently ...show high antifungal resistance. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) EUCAST Definitive Document (E.Def) 9.3.2 includes guidelines for antifungal susceptibility testing on
spp. and clinical breakpoints for amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole against
,
,
,
, and
. New clinical breakpoints were released in February 2020 and one of the most relevant modifications was the definition of the new "susceptible, increased exposure" (formerly "intermediate") category. Another relevant change was the adoption of the concept of area of technical uncertainty (ATU) that refers to problematic areas which involve uncertainty of susceptibility categorisation (e.g., when minimum inhibitory concentrations (MICs) for susceptible and resistant organisms overlap). To accommodate both the new "susceptible, increased exposure" category and the concept of ATU, MICs of azoles and amphotericin B that fall in the former "intermediate" category have been automatically categorized as either R (amphotericin B) or ATU (triazoles). Finally, EUCAST-AFST (Antifungal Susceptibility Testing) decided to adopt new breakpoints for less common species provided that the epidemiological cut-off value (ECOFF) is below or comparable to the breakpoint for the type species (
).
Candida parapsilosis
is a leading cause of invasive candidiasis in southern Europe, Latin America and Asia.
C. parapsilosis
has been mostly considered susceptible to triazoles, but fluconazole ...resistance is on the rise in some countries. The main mechanism related to fluconazole resistance is the presence of ERG11p substitutions, dominated by the Y132F amino acid substitution. Isolates harbouring this substitution mimic
C. auris
given that they may cause hospital outbreaks, become endemic, and emerge simultaneously in distant areas around the world. At the moment, Spain is experiencing a brusque emergence of fluconazole resistance in
C. parapsilosis
; isolates harbouring the Y132F substitution were detected for the first time in 2019. A recent study on
Candida
spp isolates from blood cultures collected in 16 hospitals located in the Madrid metropolitan area (2019 to 2021) reported that fluconazole resistance in
C. parapsilosis
reached as high as 13.6%. Resistance rates rose significantly during those three years: 3.8% in 2019, 5.7% in 2020, and 29.1% in 2021; resistant isolates harboured either the dominant Y132F substitution (a single clone found in four hospitals) or G458S (another clone found in a fifth hospital). The COVID-19 pandemic may have increased the number of candidaemia cases. The reason for such an increase might be a consequence of uncontrolled intra-hospital patient-to-patient transmission in some hospitals, as an increase not only in
C. parapsilosis
candidaemia episodes but also in the spread of clonal fluconazole-resistant isolates might have occurred in other hospitals during the pandemic period. Patients affected with fluconazole-resistant
C. parapsilosis
harbouring the Y132F substitution presented a mortality rate ranging from 9% to 78%, were mainly admitted to intensive care wards but did not have differential risk factors compared to those infected by susceptible isolates. With scarce exceptions, few patients (≤20%) infected with fluconazole-resistant isolates had previously received fluconazole, thus supporting the fact that, although fluconazole might have been a key factor to promote resistance, the main driver promoting the spread of fluconazole-resistant isolates was patient-to-patient transmission.
We studied 19 cases of proven/probable mucormycosis diagnosed from 2007 to 2015 in our hospital and assessed the microbiological characteristics of the isolates. We recorded the incidence of ...mucormycosis and clinical and microbiological data of infected patients. Isolates were identified to molecular level and tested for their antifungal susceptibility to azoles, amphotericin B, and liposomal amphotericin B according to the CLSI M-38 A2 procedure. The incidence of mucormycosis in cases/100,000 hospital admissions during 2007-2015 increased significantly with respect to that reported in 1988-2006 (3.3 vs. 1.2; P<0.05). Patients mainly had hematological malignancies (52.6%) and/or trauma/surgical wounds (52.6%) and had received antifungal agents before the diagnosis of mucormycosis in 68% of cases. Diagnosis was by isolation (n = 17/19) and/or direct staining (n = 17/18) of Mucorales fungi in clinical samples. Identification was by panfungal PCR in patients with negative results in culture and in direct staining. The microorganisms identified were Lichtheimia spp. (42%), Rhizopus spp. (21%), Cunninghamella bertholletiae (16%), and others (21%). Liposomal amphotericin B was always more active than the other drugs against all the microorganisms except C. bertholletiae. All patients received antifungal treatment with 1 or more antifungal agents, mainly liposomal amphotericin B (17/19). Mortality was 47.4%, although this was significantly lower in the 11 patients in whom debridement was performed (18% vs. 87.5%) (P = 0.015). The incidence of mucormycosis has risen in recent years. The proportion of cases with soft tissue involvement was high, and Lichtheimia was the most frequently involved species. The highest antifungal activity was observed with liposomal amphotericin B.
We assessed the performance of Abbott's SARS-CoV-2 IgG assay and the Panbio
COVID-19 IgG/IgM rapid test device for the diagnosis of either active or cured COVID-19. Three cohorts of patients were ...chosen. Cohort 1, patients (n = 65) who attended the emergency department on March 30, 2020 with clinical suspicion of active COVID-19 (n = 56 with proven/probable COVID-19). Cohort 2, hospital workers (n = 92) who had either been (n = 40) or not (n = 52) diagnosed with proven/probable COVID-19 and were asymptomatic at the time of the sampling. Cohort 3, patients (n = 38) cared at the hospital before the start of the COVID-19 pandemic. Detection of serum antibodies was done using Abbott´s SARS-CoV-2 IgG assay and the Panbio
COVID-19 IgG/IgM device. Both methods showed 98% agreement for IgG detection. No antibodies were detected in the 38 samples from hospitalized pre-COVID subjects. The diagnostic performance of IgGs detected by Abbott´s SARS-CoV-2 assay in Cohorts 1/2 was: sensitivity (60.7%/75%) and specificity (100%/84.6%). The diagnostic performance of IgM by Panbio
COVID-19 in Cohorts 1/2 was: sensitivity (16%/17.5%) and specificity (100%/98.1%). We show that IgG detection alone is insufficient for the diagnosis of active or cured COVID-19. IgM detection has a limited diagnostic value.
Invasive candidiasis is a hospital-acquired infection with a high associated mortality.1 The antifungal drug armamentarium to manage patients with invasive candida infections is quite small and ...restricted to three drug families: the polyenes, the azoles, and the echinocandins. The Infectious Diseases Society of America and European Society for Clinical Microbiology Diseases international guidelines both support the use of echinocandins as first-line drugs for the treatment of invasive candida infections.2,3 Caspofungin, the first-in-class echinocandin, was approved in 2001 and preceded the marketing of micafungin (launched in 2005) and anidulafungin (launched in 2006). These echinocandins show similar in-vitro activity, pharmacokinetic parameters, and clinical efficacy, and are administered intravenously once a day.4 Rezafungin (formerly SP3025 and CD101) is a next-generation echinocandin derived from anidulafungin. It has echinocandin-expected in-vitro activity against Candida spp and has a chemical modification that confers high stability, a longer half-life, and allows for a once-a-week dosing regimen.5 Rezafungin showed safety and a low potential for drug–drug interactions in a phase 1 study,6 and safety and clinical efficacy in the randomised, controlled, phase 2 STRIVE trial.7
We report here for the first time the presence of Candida parapsilosis isolates harbouring the Y132F ERG11 gene substitution in patients admitted to a Spanish hospital.
We studied the available ...(n = 104) C parapsilosis isolates from patients admitted to the Son Espases reference hospital in the Balearic Islands from 1 April 2019 to 30 November 2020. Isolates were sourced from 70 patients: catheter (n = 41), blood cultures (n = 37), lower respiratory tract (n = 15), intra-abdominal (n = 8), and other samples (n = 3). Isolates were genotyped and tested for antifungal susceptibilities to amphotericin B, triazoles, anidulafungin, and micafungin using EUCAST E.Def 7.3.2. The ERG11 gene was sequenced in fluconazole-resistant isolates.
Among the 104 isolates, fluconazole and voriconazole resistance was found in 87 (84%) and 30 (29%) isolates, respectively; all isolates were fully susceptible to echinocandins and amphotericin B. All fluconazole-resistant isolates harboured the Y132F substitution in the ERG11 gene and were grouped into 11 clonally related genotypes. A genotype accounted for 70% (61/87) of fluconazole-resistant isolates. Genotypes involving the fluconazole-resistant isolates were different from those found in the remaining fluconazole-susceptible genotypes. Fifty-six patients harboured fluconazole-resistant genotypes, and 35 of the 56 had candidaemia (48%), abdominal candidiasis (17%), or other forms of candidiasis (35%). Only 20% of the study patients infected by fluconazole-resistant genotypes had a history of azole use.
Fluconazole resistance in C parapsilosis isolates from patients admitted to this reference hospital is not attributable to prior azole use, but rather to the presence of a group of fluconazole-resistant C parapsilosis genotypes that have become endemic.
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The diagnosis of invasive aspergillosis is challenging because no sufficiently sensitive or specific tests have been developed to date. Infection can only be confirmed using histology, although this ...approach is unavailable in many patients. Therefore, diagnosis of invasive aspergillosis is based on a combination of the presence of host factors, radiological and clinical findings, and mycological criteria. In clinical practice, lack of optimal diagnostics often leads to empirical therapy and great cost and toxicity. Mycological criteria include the isolation of
Aspergillus
from clinical samples or the detection of biomarkers in fluids. Culture is cheap and easy and enables the identification of fungi and performance of antifungal susceptibility testing; however, it has low sensitivity and specificity. Non-culture-based diagnosis is based on the detection of fungal biomarkers such as galactomannan or (1 → 3)-β-
d
-glucan in normally sterile body fluids. These procedures enable faster and more sensitive and specific detection of
Aspergillus
; however, diagnostic accuracy is affected by the patient’s underlying condition. Finally, while detection of
Aspergillus
DNA is promising, the lack of standardization limits its inclusion as a mycological criterion for the definition of probable invasive aspergillosis. New diagnostic procedures based on lateral flow technology are also promising but need further evaluation. In the present review, we discuss current culture-based and non
-
culture-based procedures for the microbiological diagnosis of invasive aspergillosis.
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