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Journal of Clinical Laboratory Analysis Oct 2023Viral pneumonia such as COVID-19-associated aspergillosis could increase susceptibility to fungal super-infections in critically ill patients. (Review)
Review
BACKGROUND
Viral pneumonia such as COVID-19-associated aspergillosis could increase susceptibility to fungal super-infections in critically ill patients.
METHODS
Here we report a pediatric case of Aspergillus quadrilineatus cerebral infection in a recently diagnosed COVID-19-positive patient underlying acute lymphocytic leukemia. Morphological, molecular methods, and sequencing were used to identify this emerging species.
RESULTS
Histopathological examination showed a granulomatous necrotic area containing dichotomously branching septate hyphae indicating a presumptive Aspergillus structure. The species-level identity of isolate growing on brain biopsy culture was confirmed by PCR sequencing of the β-tubulin gene as A. quadrilineatus. Using the CLSI M38-A3 broth microdilution methodology, the in vitro antifungal susceptibility testing demonstrated 0.032 μg/mL MIC for posaconazole, caspofungin, and anidulafungin and 8 μg/mL against amphotericin B. A combination of intravenous liposomal amphotericin B and caspofungin therapy for 8 days did not improve the patient's condition. The patient gradually continued to deteriorate and expired.
CONCLUSIONS
This is the first COVID-19-associated cerebral aspergillosis due to A. quadrilineatus in a pediatric patient with acute lymphocytic leukemia. However, comprehensive screening studies are highly recommended to evaluate its frequency and antifungal susceptibility profiles. Before being recommended as first-line therapy in high-risk patients, more antifungal susceptibility data are needed.
Topics: Humans; Child; Antifungal Agents; Caspofungin; COVID-19; Aspergillus; Aspergillosis; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Central Nervous System; Microbial Sensitivity Tests
PubMed: 37798858
DOI: 10.1002/jcla.24971 -
Antibiotics (Basel, Switzerland) Aug 2023Significant increases in antibacterial use were observed during the COVID-19 pandemic. However, subsequent analyses found this increase in antibiotic use to be excessive...
Significant increases in antibacterial use were observed during the COVID-19 pandemic. However, subsequent analyses found this increase in antibiotic use to be excessive in comparison with the relatively low rates of bacterial coinfection. Although patients who are critically ill with COVID-19 may be at an increased risk for pulmonary aspergillosis, antifungal use in these populations remained underreported, particularly in later phases of the pandemic. This single-center, population-level cohort analysis compares the monthly use rates of mold-active antifungal drugs in the medical intensive care unit during April 2019-March 2020 (baseline) with those during April 2020-November 2022. The antifungal drugs included in the analysis were liposomal amphotericin B, anidulafungin, isavuconazonium, posaconazole, and voriconazole. We found that during 2020-2022, the usage of antifungal drugs was not significantly different from baseline for all included agents except isavuconazonium, which was used significantly more ( = 0.009). There were no changes in diagnostic modalities between the two time periods. The reported prevalence of and mortality from COVID-19-associated pulmonary aspergillosis (CAPA) may have resulted in higher rates of prescribing antifungal drugs for critically ill patients with COVID-19. Antimicrobial stewardship programs should develop and apply tools to facilitate more effective and appropriate antifungal use.
PubMed: 37760649
DOI: 10.3390/antibiotics12091352 -
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 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 -
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 -
Infection and Drug Resistance 2023Candidemia and antifungal resistance are major healthcare challenges. The aim of this study is to describe the frequency of candidemia cases, distribution of spp., and...
PURPOSE
Candidemia and antifungal resistance are major healthcare challenges. The aim of this study is to describe the frequency of candidemia cases, distribution of spp., and the associated risk factors for mortality in an academic institution in Saudi Arabia over an 18-month period. We also evaluated the susceptibility patterns of blood isolates.
METHODS
Candidemia cases were collected from King Fahad Hospital of the University over the period between July 1st, 2020 through December 31st, 2021. They were prospectively reviewed for the preceding risk factors and antifungal (AF) susceptibility, testing results to fluconazole (FL), voriconazole (VO), itraconazole (IT), posaconazole (PO), caspofungin (CASP), anidulafungin (AND), micafungin (MYC), flucytosine (FLC) and amphotericin B (AMPB) using a broth microdilution kit (Sensititre™ YeastOne).
RESULTS
A total of 48 candidemia isolates were included that were isolated from 43 patients. The median age of cases was 62 ± 23.3 years (60.4% males and 83% ICU patients). Independent risk factors for mortality at 30 days in candidemia patients were age, COVID-19 co-infection, and use of tocilizumab. The most commonly isolated species were and (22.9% each) followed by (18.75%). AF resistance for ≥1 antifungal was detected in 39.3% of 33 cases tested, with no cross-resistance identified. Resistance rates for each AF were as follows: FL (18%), VO (6%), IT (6%), PO (9%) and AMPB (3%). No resistance was seen for echinocandins apart from one strain showing an intermediate result for CASP.
CONCLUSION
The study showed an overall high rate of non-, with the predominance of and , representing a therapeutic challenge. AF resistance rate was high which emphasizes the importance of continuing surveillance and providing accurate and reliable tools in the laboratories for rapid speciation and susceptibility testing.
PubMed: 37457797
DOI: 10.2147/IDR.S411865 -
Emerging Microbes & Infections Dec 2023is becoming a predominant non- cause of invasive candidiasis (IC). Echinocandins are the preferred choice for IC treatment and prophylaxis. Resistance to echinocandins...
is becoming a predominant non- cause of invasive candidiasis (IC). Echinocandins are the preferred choice for IC treatment and prophylaxis. Resistance to echinocandins in has emerged in several countries, but little is known about the susceptibility profile in China or about mechanisms of resistance. Here, we investigated the echinocandin susceptibilities of 2523 isolates collected from China and further explored the resistance mechanism among echinocandin-resistant isolates. Anidulafungin exhibited the highest MICs (MIC, 1 and 2 µg/mL; GM, 0.948 µg/mL), while caspofungin showed better activity (0.5 and 1 µg/mL; 0.498 µg/mL). Significantly higher echinocandin MICs were observed among blood-derived isolates compared to others, especially for caspofungin (GM, 1.348 µg/mL vs 0.478 µg/mL). Isolates from ICU and surgical wards also showed higher MICs. Twenty isolates showed intermediate phenotypes for at least one echinocandin. One was resistant to all three echinocandins, fluconazole and voriconazole, which caused breakthrough IC during long-term exposure to micafungin. WGS revealed this isolate carried a mutation S656P in hotspot1 region of Fks1. Bioinformatics analyses suggested that this mutation might lead to an altered protein conformation. CRISPR Cas9-mediated introduction of this mutation into a susceptible reference strain increased MICs of all echinocandins 64-fold, with similar results found in the subspecies, and . This is the first report of a multi-azole resistant and pan-echinocandin resistant isolate, and the identification of a conferring pan-echinocandin resistance. Our study underscores the necessity of rigorous management of antifungal use and of monitoring for antifungal susceptibility.
Topics: Antifungal Agents; Candida parapsilosis; Candidemia; Caspofungin; China; Echinocandins; Microbial Sensitivity Tests; Humans; Drug Resistance, Fungal
PubMed: 36440795
DOI: 10.1080/22221751.2022.2153086