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Microbiology Spectrum Sep 2023Members of the species complex are able to cause superficial and life-threatening systemic infections with low susceptibility to azoles and echinocandins. We tested 130...
Members of the species complex are able to cause superficial and life-threatening systemic infections with low susceptibility to azoles and echinocandins. We tested 130 bloodstream complex isolates collected from eight Latin American medical centers over 18 years (period 1 = 2000-2008 and period 2 = 2009-2018) to investigate trends in species distribution and antifungal resistance. The isolates were identified by rDNA ITS region sequencing, and antifungal susceptibility tests were performed against fluconazole, voriconazole, anidulafungin, and amphotericin B using the CLSI microbroth method. (s.s.; = 116) was the most prevalent species, followed by ( = 12) and ( = 2). Based on rDNA ITS identification, three clades within were characterized (clade 1 = 94; clade 2 = 19; and clade 3 = 3). In the second period of study, we found a substantial increment in the isolation of (3.4% versus 13.8%; = 0.06) and clade 2 s.s. exhibiting lower susceptibility to one or more triazoles. IMPORTANCE Yeast-invasive infections play a relevant role in human health, and there is a concern with the emergence of non- pathogens causing disease worldwide. There is a lack of studies addressing the prevalence and antifungal susceptibility of different species within the complex that cause invasive infections. We evaluated 130 episodes of species complex candidemia documented in eight medical centers over 18 years. We detected the emergence of less common species within the complex causing candidemia and described a new clade of with limited susceptibility to triazoles. These results support the relevance of continued global surveillance efforts to early detect, characterize, and report emergent fungal pathogens exhibiting limited susceptibility to antifungals.
PubMed: 37698428
DOI: 10.1128/spectrum.05115-22 -
Journal de Mycologie Medicale Nov 2023Invasive fungal infection (IFI) accounts for substantial morbidity during the treatment of acute myeloid leukemia (AML) in adults. Antifungal prophylaxis (AP) is needed...
INTRODUCTION
Invasive fungal infection (IFI) accounts for substantial morbidity during the treatment of acute myeloid leukemia (AML) in adults. Antifungal prophylaxis (AP) is needed during intensive chemotherapy, and posaconazole is not widely available. In this study, we aimed to examine the impact of prophylactic anidulafungin during intensive AML remission induction.
METHODS
This is a retrospective cohort encompassing newly diagnosed AML adult patients. All subjects received intensive chemotherapy and were divided into three groups: patients who did not receive any AP and patients who received fluconazole (150-400 mg/day) or anidulafungin (100 mg/day).
RESULTS
During AML induction, 82 patients did not receive AP, 108 and 14 patients received anidulafungin and fluconazole, respectively. IFI incidence was 27%, classified as possible, probable, and proven in 65, 2 and 33%, respectively. Multivariable analysis showed that lower neutrophil counts are associated with IFI (OR = 2.8), whereas age, genetic classification, and lymphocyte counts were not. To examine the impact of anidulafungin in comparison with 'no AP', a propensity score matching analysis was performed. Use of anidulafungin was not related to less IFI during induction, while neutrophil counts remained significant. Patients under prophylactic anidulafungin received less amphotericin B (p < 0.001) but not voriconazole (p = 0.49).
DISCUSSION
To our knowledge, this is the first study addressing the role of anidulafungin during AML induction. Here, the incidence of mold infections did not decrease with AP, suggesting that in a setting with a high incidence of IFI, broad spectrum AP might be more suitable.
Topics: Adult; Humans; Antifungal Agents; Fluconazole; Anidulafungin; Retrospective Studies; Propensity Score; Remission Induction; Leukemia, Myeloid, Acute
PubMed: 37683564
DOI: 10.1016/j.mycmed.2023.101434 -
Medizinische Klinik, Intensivmedizin... Sep 2023Invasive fungal infections caused by Candida or Aspergillus are associated with a high mortality. Knowledge about the risk factors, diagnosis and treatment management... (Review)
Review
BACKGROUND
Invasive fungal infections caused by Candida or Aspergillus are associated with a high mortality. Knowledge about the risk factors, diagnosis and treatment management is crucial for improving the survival of those affected.
OBJECTIVE
To give a practical overview about risk factors and treatment management of Candida and Aspergillus infections as well as providing an outlook on new antifungal agents.
MATERIAL AND METHODS
Summary of the relevant literature and recommendations on candidemia and invasive candidiasis as well as invasive and chronic pulmonary aspergillosis.
RESULTS
The first line treatment of candidemia and invasive candidiasis are echinocandins including caspofungin, anidulafungin and micafungin. Regular blood cultures have to be taken to determine the duration of treatment. After the first negative control blood culture treatment should be continued for another 14 days. The first line treatment of invasive pulmonary aspergillosis is azoles including voriconazole and isavuconazole. The duration of treatment depends on disease severity and is recommended for 6-12 weeks. The duration of treatment for chronic pulmonary aspergillosis is 6-12 months. Therapeutic drug monitoring is recommended for voriconazole and for posaconazole. New antifungal agents including olorofim, fosmanogepix, opelconazole, rezafungin or ibrexafungerp will broaden the therapeutic spectrum in the foreseeable future.
CONCLUSION
Knowledge about risk factors and the correct treatment management is crucial for the survival of patients with invasive fungal infections.
Topics: Humans; Antifungal Agents; Candida; Voriconazole; Candidemia; Aspergillus; Invasive Fungal Infections; Pulmonary Aspergillosis; Candidiasis, Invasive
PubMed: 37644243
DOI: 10.1007/s00063-023-01051-6 -
Clinical Microbiology and Infection :... Dec 2023Antifungal susceptibility testing is mostly conducted on blood-cultured Candida spp isolates. Because the intra-abdominal cavity has been highlighted as a hidden...
OBJECTIVES
Antifungal susceptibility testing is mostly conducted on blood-cultured Candida spp isolates. Because the intra-abdominal cavity has been highlighted as a hidden echinocandin-resistant C. glabrata reservoir, we assessed whether testing sequential isolates from a given patient might increase the chances of detecting antifungal resistance.
METHODS
Intra-abdominal initial and sequential isolates from the same species from patients included in the CANDIdaemia in MADrid study (January 2019 to June 2022) were studied. We assessed antifungal susceptibility to amphotericin B, azoles, anidulafungin, micafungin, and ibrexafungerp using European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology and molecularly characterized resistant isolates.
RESULTS
We collected 308 isolates (C. albicans [n = 179/308; 58.1%], C. glabrata [n = 101/308; 32.8%], C. tropicalis [n = 17/308; 5.5%], and C. parapsilosis [n = 11/308; 3.6%]) from 112 patients distributed as incident (n = 125/308) and sequential (n = 183/308). Per patient resistance rates of fluconazole (13.4% [15/112] vs. 8% [9/112]); 5.4% proportions difference (95% CI, -2.7% to 13.5%, p 0.09) and echinocandins (8.9% [10/112] vs. 1.8% [2/112]); 7.1% proportions difference (95% CI; 1.2-12.9%; p 0.01) were higher when considering all available isolates than only incident isolates. Resistance was detected in 18 of 112 patients and would have been overlooked in 11 of 18 (61.1%) patients if only incident isolates had been studied. Of the patients who harboured fluconazole or echinocandin-resistant isolates, 14 of 15 and 8 of 10 had received or were receiving fluconazole or echinocandins, respectively.
DISCUSSION
Testing sequential Candida isolates from intra-abdominal samples is required to detect antifungal resistance, particularly to echinocandins, in patients whose incident isolates turned out to be susceptible. Furthermore, patients with echinocandin-resistant infections had frequently used echinocandins and had common secondary resistance acquisition.
Topics: Humans; Antifungal Agents; Candida; Fluconazole; Echinocandins; Amphotericin B; Candida albicans; Candida parapsilosis; Candida tropicalis; Candida glabrata; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 37640239
DOI: 10.1016/j.cmi.2023.08.021 -
Journal of Fungi (Basel, Switzerland) Aug 2023Echinocandins, used for the prevention and treatment of invasive fungal infections, have led to a rise in breakthrough infections caused by resistant species. Among...
Echinocandins, used for the prevention and treatment of invasive fungal infections, have led to a rise in breakthrough infections caused by resistant species. Among these species, those belonging to the complex are rare multidrug-resistant (MDR) yeasts that are frequently misidentified but have emerged as significant healthcare-associated pathogens causing invasive infections. The objectives of this study were to investigate the evolutionary pathways of echinocandin resistance in by identifying mutations in the gene and evaluating the impact of resistance on fitness. After subjecting a MDR clinical isolate of (named Ch4) to direct selection using increasing caspofungin concentrations, we successfully obtained an isolate (designated ) that exhibited a high level of resistance, with MIC values exceeding 16 mg/L for all tested echinocandin drugs (caspofungin, micafungin, and anidulafungin). Sequence analysis revealed a specific mutation in the resistant strain, leading to an arginine-histidine amino acid substitution (R1354H), occurring at the G4061A position of the HS2 region of the gene. Compared to the wild-type strain, exhibited significantly reduced growth proliferation, biofilm formation capability, and phagocytosis ratio, indicating a decrease in fitness. Transmission electron microscopy analysis revealed alterations in cell wall components, with a notable increase in cell wall thickness. The resistant strain also exhibited higher amounts (2.5-fold) of chitin, a cell wall-located molecule, compared to the wild-type strain. Furthermore, the resistant strain demonstrated attenuated virulence in the larval model. The evolved strain maintained its resistance profile in vivo since the treatment with either caspofungin or micafungin did not improve larval survival or reduce the fungal load. Taken together, our findings suggest that the acquisition of pan-echinocandin resistance occurred rapidly after drug exposure and was associated with a significant fitness cost in . This is particularly concerning as echinocandins are often the first-line treatment option for MDR species.
PubMed: 37623630
DOI: 10.3390/jof9080859 -
Epidemiology and Infection Aug 2023Antifungal susceptibility of species is decreasing. Successful treatment for antifungal-resistant candida infection is challenging and associated with significant... (Observational Study)
Observational Study
Antifungal susceptibility of species is decreasing. Successful treatment for antifungal-resistant candida infection is challenging and associated with significant mortality. We performed a prospective observational study to identify the species and antifungal susceptibilities of invasive isolates of species over a 5-year period at a university hospital in southern Thailand. Between 2017 and 2021, the species distribution was 39.1% , 24.8% , 20.3% complex, 10.5% , and 5.2% miscellaneous spp. Notable observations include elevated minimal inhibitory concentration (MIC) and decrease susceptibility of and to echinocandin and all tested triazoles. A shift of MIC value in the COVID-19 era was seen in and with azoles and echinocandins. Azole resistance increased among isolates, and echinocandin resistance also increased among and isolates. Novel alterations in 1 HS1 and HS2 were detected in both isolates of anidulafungin-resistant As species have become more resistant to azoles and less susceptible to echinocandin development, the need arose to observe the emergence of resistance to both antifungal classes in candida clinical isolates, for a more effective infection control in the hospital.
Topics: Humans; Candida; Fluconazole; Echinocandins; Antifungal Agents; COVID-19; Candidiasis, Invasive; Hospitals, University; Azoles; Disease Outbreaks
PubMed: 37622338
DOI: 10.1017/S0950268823001346 -
Infection and Drug Resistance 2023The emergence of resistance in to azoles and terbinafine has become increasingly evident in recent years, necessitating the development of novel antifungal drugs and...
INTRODUCTION
The emergence of resistance in to azoles and terbinafine has become increasingly evident in recent years, necessitating the development of novel antifungal drugs and the exploration of new indications for existing agents.
METHODS
In this study, we retrospectively evaluated the in vitro antifungal activity of 3 echinocandins (anidulafungin, caspofungin, and micafungin) against 73 clinical isolates of collected from a teaching hospital in Shanghai, China, using EUCAST E.DEF 9.3.1 with minor modification. We also reviewed the susceptibility of to echinocandins globally by literature searching.
RESULTS
Our findings revealed that micafungin exhibited the lowest modal minimum effective concentration (MEC) value (0.08 mg/L, n = 28) and the lowest geometric mean (GM) MEC value (0.014 mg/L) among the 73 isolates of tested, followed by anidulafungin with a modal MEC value of 0.016 mg/L (n = 67) and a GM of 0.018 mg/L. Caspofungin displayed a higher modal MEC value of 0.5 mg/L (n = 35) and a GM of 0.308 mg/L. Despite variations in methodologies, similar results were obtained from the review of five relevant studies included in our analysis.
DISCUSSION
Echinocandins exhibited excellent in vitro activity against isolates, with micafungin and anidulafungin demonstrating greater potency than caspofungin. These findings suggest that echinocandins could be considered as potential treatment options for managing recalcitrant dermatophytoses resulting from the emergence of resistance. However, it is important to note that the clinical efficacy of these in vitro findings has yet to be established and warrants further investigation.
PubMed: 37621698
DOI: 10.2147/IDR.S423735 -
Cureus Jul 2023We present a case of a 57-year-old male patient with a history of prolonged intensive care unit (ICU) stay for coronavirus disease 2019 (COVID-19) who developed fungal...
We present a case of a 57-year-old male patient with a history of prolonged intensive care unit (ICU) stay for coronavirus disease 2019 (COVID-19) who developed fungal spondylodiscitis, a rare complication. The patient initially presented complaining of respiratory symptoms and was subsequently treated with tocilizumab, remdesivir, enoxaparin, and dexamethasone. Following ICU discharge, he experienced recurrent infections, including extended-spectrum beta-lactamase urinary tract infection. Two months later, he developed back pain; magnetic resonance imaging (MRI) revealed inflammatory spondylodiscitis. Despite empirical antibiotic therapy, his condition did not improve, and a bone biopsy confirmed infection. Antifungal treatment with fluconazole and anidulafungin resulted in a significant clinical improvement. The patient achieved complete recovery after six months of therapy. This case highlights the rare occurrence of fungal spondylodiscitis in COVID-19 patients with a history of ICU stay and emphasizes the importance of early recognition and appropriate management to mitigate potential complications.
PubMed: 37602130
DOI: 10.7759/cureus.42079 -
Medical Mycology Sep 2023Aspergillus species is a widespread environmental mould that can cause aspergillosis. The purpose of this study was to investigate the antifungal susceptibility profile...
In vitro antifungal susceptibility profile and genotypic characterization of clinical Aspergillus isolates in Eastern China on behalf of Eastern China Invasive Fungi Infection Group.
Aspergillus species is a widespread environmental mould that can cause aspergillosis. The purpose of this study was to investigate the antifungal susceptibility profile and genotypic characterization of clinical Aspergillus isolates from different provinces in Eastern China. The data included the antifungal susceptibility distributions with eight common antifungal drugs, cyp51A gene mutations of triazole-resistant Aspergillus fumigatus sensu stricto, and the genotypic relationships among the A. fumigatus sensu stricto isolates based on microsatellite typing. A. fumigatus sensu lato was the most common clinical Aspergillus species (n = 252), followed by A. flavus (n = 169), A. terreus (n = 37), A. niger (n = 29), and A. nidulans (n = 4). The modal minimum effective concentration values of micafungin and anidulafungin were lower than those of caspofungin for all Aspergillus species. The in vitro efficacy of isavuconazole was similar to that of voriconazole against most Aspergillus species. Sequencing revealed cyp51A gene mutations TR34/L98H, TR34/L98H/S297T/F495I, and TR46/Y121F/T289A in four triazole-resistant A. fumigatus sensu stricto. Phylogenetic analyses using microsatellite markers of A. fumigatus sensu stricto revealed that 211 unique genotypes clustered into two clades. The data demonstrate the diversity of clinically relevant Aspergillus species in Eastern China. Routine antifungal susceptibility testing should be performed to monitor the antifungal resistance and guide clinical therapy.
Topics: Animals; Antifungal Agents; Aspergillus fumigatus; Phylogeny; Fungal Proteins; Azoles; Drug Resistance, Fungal; Aspergillus; Triazoles; Genotype; Invasive Fungal Infections; Microbial Sensitivity Tests
PubMed: 37580143
DOI: 10.1093/mmy/myad082 -
The Journal of Infection Nov 2023The objectives of this study were to assess Candida spp. distribution and antifungal resistance of candidaemia across Europe. Isolates were collected as part of the...
The objectives of this study were to assess Candida spp. distribution and antifungal resistance of candidaemia across Europe. Isolates were collected as part of the third ECMM Candida European multicentre observational study, conducted from 01 to 07-07-2018 to 31-03-2022. Each centre (maximum number/country determined by population size) included ∼10 consecutive cases. Isolates were referred to central laboratories and identified by morphology and MALDI-TOF, supplemented by ITS-sequencing when needed. EUCAST MICs were determined for five antifungals. fks sequencing was performed for echinocandin resistant isolates. The 399 isolates from 41 centres in 17 countries included C. albicans (47.1%), C. glabrata (22.3%), C. parapsilosis (15.0%), C. tropicalis (6.3%), C. dubliniensis and C. krusei (2.3% each) and other species (4.8%). Austria had the highest C. albicans proportion (77%), Czech Republic, France and UK the highest C. glabrata proportions (25-33%) while Italy and Turkey had the highest C. parapsilosis proportions (24-26%). All isolates were amphotericin B susceptible. Fluconazole resistance was found in 4% C. tropicalis, 12% C. glabrata (from six countries across Europe), 17% C. parapsilosis (from Greece, Italy, and Turkey) and 20% other Candida spp. Four isolates were anidulafungin and micafungin resistant/non-wild-type and five resistant to micafungin only. Three/3 and 2/5 of these were sequenced and harboured fks-alterations including a novel L657W in C. parapsilosis. The epidemiology varied among centres and countries. Acquired echinocandin resistance was rare but included differential susceptibility to anidulafungin and micafungin, and resistant C. parapsilosis. Fluconazole and voriconazole cross-resistance was common in C. glabrata and C. parapsilosis but with different geographical prevalence.
PubMed: 37549695
DOI: 10.1016/j.jinf.2023.08.001