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BACKGROUND & AIMS: Immune checkpoint inhibitors (ICIs) can restore exhausted T cell immunity not only for cancer treatment but also potentially for curing chronic hepatitis B (CHB). The impact of ICIs on Hepatitis B surface antigen (HBsAg) seroclearance in cancer patients was unclear. METHODS: Consecutive cancer patients from 2016 to 2020 (Cohort 1, n=118), and hepatocellular carcinoma (HCC) patients from 2020 to 2022 (Cohort 2, n=44, as validation) receiving ICIs and positive for HBsAg were retrospectively recruited. An additional hepatitis B virus (HBV)-HCC cohort (Cohort 3, n=85) without ICI served as a control group. Factors associated with HBsAg loss or combining HBsAg decline >1 log were analyzed. RESULTS: With median follow-up of 17.5 months, 8 (6.8%) in cohort 1 and 4 (9.1%) in cohort 2 achieved HBsAg seroclearance, and additional 4 in cohort 1 and 1 in cohort 2 had HBsAg decline >1 log. In multivariate analysis, HBsAg <100 IU/mL was associated with HBsAg seroclearance (HR=6.274, p=0.028). In the validation cohort, the cumulative incidence of HBsAg loss at months 12 and 24 was 13.0% and 38.4% for baseline HBsAg <100 IU/ml, which were significantly higher than those in the control group (p=0.0267). While no case in cohort 3 achieved HBsAg within 24 months. Of the 17 cases achieved HBsAg loss and decline >1 log, 16 (94.1%) had nucleos(t)ide analogs treatment. The median time to HBsAg loss or HBsAg decline was 16.5 months (ranged 9.6 to 27.5). CONCLUSIONS: ICIs may accelerate HBsAg seroclearance in cancer patients with baseline HBsAg <100 IU/ml. This finding provides important information for the design of future ICI trials to achieve functional cure in patients with CHB.
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BACKGROUND: Epidemiological knowledge is important to guide antifungal therapy. OBJECTIVE: This multicentre study aimed to investigate the species distribution and antifungal susceptibility of Aspergillus isolates in Taiwan. METHOD: Four hundred and ninety-two clinical Aspergillus isolates, collected during 2016-2020, were identified by calmodulin sequencing and tested for antifungal susceptibility using CLSI M38-A3. The Cyp51A sequences of azole-resistant Aspergillus fumigatus and Aspergillus flavus isolates were analysed. RESULTS: This collection comprised 30 species from eight Aspergillus sections-Flavi (33.5%), Nigri (26.0%), Fumigati (24.2%), Terrei (10.0%), Nidulantes (5.1%), Circumdati (0.8%), Restricti (0.2%) and Aspergillus (0.2%). Sections Fumigati, Flavi and Terrei were primarily represented by A. fumigatus (99.2%), A. flavus (95.8%) and A. terreus (100%), respectively. Section Nigri comprised nine species, mostly A. welwitschiae (60.2%), A. niger (12.5%), A. brunneoviolaceus (10.9%) and A. tubingensis (10.2%). A. fumigatus (39.6%) and A. flavus (26.4%) predominated among 53 isolates from lower respiratory samples, whereas section Nigri species (46.2%) and A. terreus (29.2%) predominated among 65 isolates from ear samples. Reduced susceptibility to amphotericin B (minimal inhibitory concentration (MIC) > 1 µg/mL) was noted in A. flavus (7.0%), A. terreus (6.1%), A. nidulans and section Circumdati (A. flocculosus, A. subramanianii and A. westerdijkiae) isolates. Acquired azole resistance was observed in seven A. fumigatus (5.9%), all of which carried TR34 /L98H or TR34 /L98H/S297T/F495I mutation, and three A. flavus (1.9%), one of which carried G441S mutation. Reduced susceptibility to itraconazole (MIC >1 µg/mL) was noted in 55.5% of section Nigri isolates, mainly in A. welwitschiae, A. niger and A. tubingensis, whereas A. brunneoviolaceus, A. aculeatinus and A. japonicus were hypersusceptible to azoles. Anidulafungin was active against all isolates except for one isolate. CONCLUSIONS: This study depicted the molecular epidemiology and species-specific characteristics of Aspergillus in Taiwan, which aids in appropriate antifungal therapy and underlines the need of speciation and susceptibility testing of disease-causing Aspergillus.
Assuntos
Antifúngicos , Aspergillus , Humanos , Antifúngicos/farmacologia , Taiwan/epidemiologia , Itraconazol/farmacologia , Azóis/farmacologia , Aspergillus fumigatus , Testes de Sensibilidade Microbiana , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genéticaRESUMO
BACKGROUND: Lenvatinib combined with pembrolizumab showed a promising result in an early phase study for hepatocellular carcinoma (HCC). The efficacy and safety of lenvatinib plus pembrolizumab for patients with unresectable HCC (uHCC) beyond the first-line setting were unclear. METHODS: Seventy-one consecutive patients who received lenvatinib plus pembrolizumab for uHCC were prospectively enrolled. Effect of lenvatinib combinations on Albumin-Bilirubin (ALBI) score and factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: Of the 71 cases, 58 (81.7%) were in BCLC C. There were 44 (62%) for the first-line systemic treatment, and 27 (38%) had experienced targeted therapy or nivolumab treatment. The objective response rate and disease control rate (DCR) were 34.1% and 84.1% for the first-line setting, and 18.5% and 70.4% for systemic therapy-experienced cases (Response Evaluation Criteria in Solid Tumors version 1.1, RECIST v1.1), respectively. The mean ALBI score was stable during the treatment course. After a median of 9.3 months of follow-up, the median PFS was 9.3 months versus 4.4 months, and the median OS was not estimable yet versus 12 months for Child-Pugh A versus B patients, respectively. Prior nivolumab failure was the only significant factor associated with poorer PFS (HR = 3.253, p = 0.004). Child-Pugh class B (HR = 2.646, p = 0.039) and prior nivolumab failure (HR = 3.340, p = 0.014) were independent factors for poorer OS in multivariate analysis. CONCLUSIONS: A high DCR was observed by lenvatinib/pembrolizumab combination without adverse effect on ALBI score for systemic therapy-naïve and -experienced uHCC. Suboptimal response to prior nivolumab-failed patients requires further exploration.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Albuminas , Anticorpos Monoclonais Humanizados , Bilirrubina , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Nivolumabe/uso terapêutico , Compostos de Fenilureia , QuinolinasRESUMO
BACKGROUND: Epidemiological knowledge of mucormycosis obtained from national population-based databases is scarce. OBJECTIVES: This study aimed to depict the disease burden and demographics of mucormycosis in Taiwan by using the Taiwan National Health Insurance Research Database (NHIRD) and those of aspergillosis as a comparator. METHODS: Data from patients with either mucormycosis or aspergillosis from 2006 to 2017 identified with the International Classification of Diseases (ICD) codes were extracted from the NHIRD. The incidence, demographics and clinical data of both diseases were analysed. RESULTS: A total of 204 patients with mucormycosis and 2270 patients with aspergillosis who were hospitalised and treated with mould-active antifungals between 2006 and 2017 were identified. The average annual incidence of aspergillosis (0.81 cases per 100,000 population [0.81/100,000]) was 11-fold higher than that of mucormycosis (0.07/100,000). A significant increase in incidence was observed for aspergillosis (from 0.48/100,000 in 2006 to 1.19/100,000 in 2017, p < .0001) but not for mucormycosis (from 0.04/100,000 in 2006 to 0.11/100,000 in 2017, p = .07). The major underlying disease identified was diabetes mellitus (60.8%) for mucormycosis and malignant neoplasms (45.9%) for aspergillosis. The all-cause 90-day mortality rate was similar between mucormycosis and aspergillosis patients (39% vs. 37%, p = .60). For mucormycosis patients, multivariate analysis revealed that posaconazole use was associated with lower in-hospital mortality (aOR 0.38; 95% CI 0.15-0.97; p = .04). CONCLUSIONS: Mucormycosis is an uncommon fungal disease in Taiwan, occurring mostly in diabetic patients. However, the incidence might be underestimated due to limited diagnostics. Continuous surveillance might aid in delineating the evolving features of mucormycosis.
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Aspergilose , Mucormicose , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Efeitos Psicossociais da Doença , Mortalidade Hospitalar , Humanos , Mucormicose/tratamento farmacológico , Mucormicose/epidemiologia , Taiwan/epidemiologiaRESUMO
BACKGROUND/PURPOSE: Hepatocellular carcinoma (HCC) is a highly recurrent tumor. Antiviral therapy with nucleos(t)ide analogues (NUCs) may reduce the risk of recurrence in hepatitis B virus (HBV)-related HCC. The risk factors associated with recurrence in HCC patients after surgical resection and with NUCs treatment should be delineated. METHODS: Consecutive 339 HBV-related HCC patients receiving surgical resection of HCC with NUCs therapy (including 256 entecavir, 36 tenofovir, and 18 lamivudine) after the surgery were retrospectively reviewed. Factors related to the recurrence-free survival (RFS) and overall survival (OS) were evaluated. RESULTS: After a median of 48.5 months of follow-up, 183 (54%) patients developed HCC recurrence, with the 5-year RFS of 42.8% and OS of 79%. Male gender (HR = 1.736, p = 0.037), baseline HBsAg level >200 IU/ml (HR = 1.748, p = 0.008), platelet count â¦100 (109/L) (HR = 1.592, p = 0.023), presence of microscopic vascular invasion (MVI) (HR = 1.499, p = 0.026), safety cut margin of â¦0.5 cm (HR = 1.507, p = 0.013), and Ishak fibrosis score 5-6 (HR = 1.579, p = 0.009) were independent factors associated with RFS in multivariate analysis. While tumor burden, platelet count, MVI, and safety cut margin were factors associated with early recurrence; baseline HBsAg level, and platelet count were independent factors associated with late recurrence. Ishak fibrosis score 5-6, poor differentiation, MVI, diabetes mellitus were factors associated with OS in multivariate analysis. CONCLUSION: For HBV-HCC patients on NUCs treatment, tumor factors are associated with early recurrence, while HBsAg level and thrombocytopenia determines late recurrence. For patient with a high baseline HBsAg level, warning of higher risk of recurrence is required even under NUCs treatment.
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Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
In a multicenter study, we determined a prevalence rate of 4% for azole-resistant Aspergillus fumigatus in Taiwan. Resistance emerged mainly from the environment (TR34/L98H, TR34/L98H/S297T/F495I, and TR46/Y121F/T289A mutations) but occasionally during azole treatment. A high mortality rate observed for azole-resistant aspergillosis necessitates diagnostic stewardship in healthcare and antifungal stewardship in the environment.
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Aspergillus fumigatus , Azóis , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergillus fumigatus/genética , Azóis/farmacologia , Farmacorresistência Fúngica , Proteínas Fúngicas/genética , Testes de Sensibilidade Microbiana , Taiwan/epidemiologiaRESUMO
The present study aimed to isolate Aeromonas from fish sold in the markets as well as in sushi and seafood shops and compare their virulence factors and antimicrobial characteristics with those of clinical isolates. Among the 128 fish isolates and 47 clinical isolates, Aeromonas caviae, A. dhakensis, and A. veronii were the principal species. A. dhakensis isolates carried at least 5 virulence genes, more than other Aeromonas species. The predominant genotype of virulence genes was hlyA lip alt col ela in both A. dhakensis and A. hydrophila isolates, alt col ela in A. caviae isolates, and act in A. veronii isolates. A. dhakensis, A. hydrophila, and A. veronii isolates more often exhibited hemolytic and proteolytic activity and showed greater virulence than A. caviae isolates in Caenorhabditis elegans and the C2C12 cell line. However, the link between the genotypes and phenotypes of the studied virulence genes in Aeromonas species was not evident. Among the four major clinical Aeromonas species, nearly all (99.0%) A. dhakensis, A. hydrophila, and A. veronii isolates harbored blaCphA, which encodes a carbapenemase, but only a minority (6.7%, 7/104) were nonsusceptible to carbapenem. Regarding AmpC ß-lactamase genes, blaAQU-1 was exclusively found in A. dhakensis isolates, and blaMOX3 was found only in A. caviae isolates, but only 7.6% (n = 6) of the 79 Aeromonas isolates carrying blaAQU-1 or blaMOX3 exhibited a cefotaxime resistance phenotype. In conclusion, fish Aeromonas isolates carry a variety of combinations of virulence and ß-lactamase resistance genes and exhibit virulence phenotypes and antimicrobial resistance profiles similar to those of clinical isolates.IMPORTANCEAeromonas species can cause severe infections in immunocompromised individuals upon exposure to virulent pathogens in the environment, but the characteristics of environmental Aeromonas species remain unclear. Our study showed that several pathogenic Aeromonas species possessing virulence traits and antimicrobial resistance similar to those of Aeromonas isolates causing clinical diseases were present in fish intended for human consumption in Tainan City, Taiwan.
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Aeromonas/classificação , Aeromonas/genética , Aeromonas/isolamento & purificação , Peixes/microbiologia , Genótipo , Fenótipo , Alimentos Marinhos/microbiologia , Aeromonas/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Caenorhabditis elegans , Linhagem Celular , Feminino , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Prevalência , Taiwan/epidemiologia , Virulência/genética , Fatores de Virulência/genética , Resistência beta-Lactâmica/genética , beta-Lactamases/genéticaRESUMO
Poor clinical outcomes for invasive aspergillosis are associated with antifungal resistance. Performing antifungal susceptibility tests on clinically relevant Aspergillus isolates from patients and environmental regions with known azole resistance is recommended. The aim of the study was to assess the presence of azole resistance in clinical Aspergillus spp. isolates and those from hospital environments and farmlands within a 40 km radius of the hospital. Clinical Aspergillus spp. isolates were cultured, as well as environmental Aspergillus spp. isolates obtained from air samples. Samples were subcultured in azole-containing agar plates. Isolates with a positive screening test were subjected to YeastOne methods to determine their minimum inhibitory concentrations of antifungals. Resistance mechanisms were investigated in the azole-resistant Aspergillus spp. isolates. No azole-resistant clinical or environmental A flavus, A oryaze, A niger or A terreus isolates were found in the present study. All A fumigatus clinical isolates were azole-susceptible. Seven A fumigatus environmental isolates were associated with cyp51A mutations, including two that harboured TR34 /L98H mutations with S297T/F495I substitutions, two with TR34 /L98H mutations and three with TR46 /Y121F/T289A mutations. One of these isolates was collected from farmland, one was from A ward and five were from B ward. The proportion of azole-resistant A fumigatus was 10.2% (6/59) and 3.2% (1/31) in the hospital environments and the farmlands near the hospital, respectively. The results showed that azole-resistant A fumigatus existed within hospital environments. This emphasises the importance of periodic surveillance in hospital environments and monitoring for the emergence of azole-resistant A fumigatus clinical isolates.
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Antifúngicos/farmacologia , Aspergilose/epidemiologia , Aspergillus/efeitos dos fármacos , Azóis/farmacologia , Farmacorresistência Fúngica Múltipla , Monitoramento Epidemiológico , Aspergilose/microbiologia , Aspergillus/genética , Aspergillus/isolamento & purificação , Sistema Enzimático do Citocromo P-450/genética , Fazendas , Proteínas Fúngicas/genética , Genótipo , Hospitais , Humanos , Testes de Sensibilidade Microbiana , Mutação , Taiwan/epidemiologiaRESUMO
Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of azole-resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of azole fungicides. Of the 2760 air and soil samples screened from 2014 to 2016, 451 A. fumigatus isolates were recovered from 266 samples and 34 isolates from 29 samples displayed resistance to medical azoles (itraconazole, voriconazole or posaconazole). The resistance prevalence was 10.9% and 7.5% in A. fumigatus-positive samples and isolates respectively. Most (29, 85.3%) azole-resistant isolates harboured TR34 /L98H mutations, which were widely distributed, clustered genetically with clinical isolates, and had growth rates that were similar to those of the wild-type isolates. Microsatellite genotyping revealed both the global spread of the TR34 /L98H isolates and the occurrence of TR34 /L98H/S297T/F495I isolates belonging to local microsatellite genotypes. AfuMDR3 and atrF, two efflux transporter genes, were constitutively upregulated in two individual resistant isolates without cyp51A mutations, highlighting their potential roles in azole resistance. These results emphasize the need for periodic environmental surveillance at the molecular level in regions in which azole fungicides are applied, and agricultural fungicide management strategies that generate less selective pressure should be investigated.
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Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Azóis/uso terapêutico , Farmacorresistência Fúngica/genética , Microbiologia do Ar , Aspergilose/microbiologia , Aspergillus fumigatus/isolamento & purificação , Sistema Enzimático do Citocromo P-450/genética , Proteínas Fúngicas/genética , Genótipo , Humanos , Itraconazol/uso terapêutico , Testes de Sensibilidade Microbiana , Repetições de Microssatélites/genética , Mutação/genética , Prevalência , Microbiologia do Solo , Taiwan/epidemiologia , Triazóis/uso terapêutico , Voriconazol/uso terapêuticoRESUMO
This study compared the YeastOne and reference CLSI M38-A2 broth microdilution methods for antifungal susceptibility testing of Aspergillus species. The MICs of antifungal agents were determined for 100 Aspergillus isolates, including 54 Aspergillus fumigatus (24 TR34/L98H isolates), 23 A. flavus, 13 A. terreus, and 10 A. niger isolates. The overall agreement (within 2 2-fold dilutions) between the two methods was 100%, 95%, 92%, and 90% for voriconazole, posaconazole, itraconazole, and amphotericin B, respectively. The voriconazole geometric mean (GM) MICs were nearly identical for all isolates using both methods, whereas the itraconazole and posaconazole GM MICs obtained using the YeastOne method were approximately 1 dilution lower than those obtained using the reference method. In contrast, the amphotericin B GM MIC obtained using the YeastOne method was 3.3-fold higher than that observed using the reference method. For the 24 A. fumigatus TR34/L98H isolates assayed, the categorical agreement (classified according to the CLSI epidemiological cutoff values) was 100%, 87.5%, and 83.3% for itraconazole, voriconazole, and posaconazole, respectively. For four A. niger isolates, the itraconazole MICs were >8 µg/ml using the M38-A2 method due to trailing growth, whereas the corresponding itraconazole MICs obtained using the YeastOne method were all ≤0.25 µg/ml without trailing growth. These data suggest that the YeastOne method can be used as an alternative for azole susceptibility testing of Aspergillus species and for detecting the A. fumigatus TR34/L98H isolates but that this method fails to detect A. niger isolates exhibiting trailing growth with itraconazole. Additionally, for isolates with azole MICs that approach or that are at susceptibility breakpoints or with high amphotericin B MICs detected using the YeastOne method, further MIC confirmation using the reference CLSI method is needed.
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Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/normas , Anfotericina B/farmacologia , Aspergilose/microbiologia , Aspergillus/classificação , Aspergillus/isolamento & purificação , Tolerância a Medicamentos , Humanos , Itraconazol/farmacologia , Padrões de Referência , Especificidade da Espécie , Triazóis/farmacologia , Voriconazol/farmacologiaRESUMO
OBJECTIVES: This study investigated the trend in antimicrobial resistance among group B Streptococcus (GBS) from a national surveillance programme in Taiwan and delineated characteristics of and factors associated with levofloxacin-resistant isolates. METHODS: Clinical isolates of all sample types and patient groups were collected from multiple hospitals biennially between 2002 and 2012. Susceptibilities to different antibiotics were determined by broth microdilution. Molecular studies of levofloxacin-resistant isolates included serotyping, PFGE, mutations in the QRDRs and MLST. RESULTS: A total of 1559 isolates were tested and all remained susceptible to penicillin, cephalosporins, meropenem and vancomycin. However, levofloxacin resistance increased from 2.2% (range 0%-3.3%) in 2002-06 to 6.2% (5.9%-7.5%) in 2008-12 (P = 0.016). Among the 88 levofloxacin-resistant isolates, the majority (79.5%) had the GyrA(S81L)+ParC(S79F/Y) double mutations and most (54.5%) were also resistant to clindamycin, erythromycin and tetracycline. The predominant genotype of the levofloxacin-resistant isolates was ST19/serotype III (43.2%). Four previously unreported genotypes, ST1 and its single-locus variants (ST920 and ST922)/serotype VI (28.4%) and ST1/serotype II (18.2%), were found to have circulated locally. Serotype III isolates were predominately from urine and female genital tract specimens and <65-year-old adult outpatients, while serotype II and VI isolates were mostly from respiratory and urine samples and >65-year-old inpatients. Multivariate analysis revealed that elderly age and respiratory samples were independent factors associated with levofloxacin resistance. CONCLUSIONS: Multiclonal emergence and dissemination of levofloxacin-resistant GBS isolates occurred in healthcare and community settings in Taiwan. Continuous molecular-level surveillance is important to detect new epidemic trends.
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Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Genótipo , Levofloxacino/farmacologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Infecção Hospitalar/microbiologia , Análise Mutacional de DNA , Eletroforese em Gel de Campo Pulsado , Feminino , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Sorotipagem , Streptococcus agalactiae/classificação , Streptococcus agalactiae/isolamento & purificação , Taiwan , Adulto JovemRESUMO
Cumulative evidence described the emergence and geographical expansion of azole-resistant A. fumigatus associated with azole treatment failure. To investigate the status of azole resistance in A. fumigatus in Taiwan, we studied 38 A. fumigatus clinical isolates cultivated from 31 patients at two teaching hospitals from 2011 to 2014. Three isolates obtained from respiratory samples of two azole-naïve patients with pulmonary aspergillosis were found to display multi-azole resistance and cross resistance to agricultural azole fungicides, and all carried TR34/L98H mutations in cyp51A gene. The prevalence rates of azole resistance were 7.9% and 6.5% based on isolates and patients respectively. A phylogenetic analysis suggested genetic diversity of the TR34/L98H isolates in Taiwan, including a unique genotype distinct from strains outside Taiwan. The result underlines the emergence of such isolates in Taiwan as well, emphasising the importance of further surveillance for azole-resistant A. fumigatus and implementation of strategies that prevent fungicide-driven resistance selection.
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Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica Múltipla/genética , Proteínas Fúngicas/genética , Mutação , Aspergillus fumigatus/isolamento & purificação , Azóis , Variação Genética , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Filogenia , Aspergilose Pulmonar/epidemiologia , Aspergilose Pulmonar/microbiologia , Estudos Retrospectivos , Taiwan/epidemiologia , Fatores de TempoRESUMO
Among 217 Aeromonas isolates identified by sequencing analysis of their rpoB genes, the accuracy rates of identification of A. dhakensis, A. hydrophila, A. veronii, and A. caviae were 96.7%, 90.0%, 96.7%, and 100.0%, respectively, by the cluster analysis of spectra generated by matrix-assisted laser desorption ionization-time of flight mass spectrometry.
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Aeromonas/química , Aeromonas/classificação , Técnicas Bacteriológicas/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , RNA Polimerases Dirigidas por DNA/genética , Humanos , Análise de Sequência de DNARESUMO
PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was compared with culture for pathogen detection in peritoneal dialysis (PD)-related peritonitis. Of 21 samples of PD effluent, PCR/ESI-MS identified microorganisms in 18 (86%) samples, including Mycobacterium tuberculosis in 1 culture-negative sample. Of 15 double-positive samples, PCR/ESI-MS and culture reached levels of agreement of 100% (15/15) and 87.5% (7/8) at the genus and species levels, respectively. PCR/ESI-MS can be used for rapid pathogen detection in PD-related peritonitis.
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Bactérias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Candida/isolamento & purificação , Candidíase/diagnóstico , Soluções para Diálise , Técnicas Microbiológicas/métodos , Peritonite/diagnóstico , Adulto , Idoso , Infecções Bacterianas/microbiologia , Candidíase/microbiologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/efeitos adversos , Peritonite/microbiologia , Reação em Cadeia da Polimerase/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Adulto JovemRESUMO
An 85 year-old male initially admitted for septic shock due to urinary tract infection experienced Clostridium difficile-associated diarrhea during hospitalization and was treated by oral vancomycin. His clinical course was complicated by cytomegalovirus colitis and then vancomycin-resistant Clostridium innocuum bacteremia, which was cured by uneventfully parenteral piperacillin-tazobactam therapy.
Assuntos
Antibacterianos/administração & dosagem , Bacteriemia/microbiologia , Infecções por Clostridium/tratamento farmacológico , Clostridium/classificação , Clostridium/efeitos dos fármacos , Resistência a Vancomicina , Vancomicina/administração & dosagem , Administração Oral , Idoso de 80 Anos ou mais , Clostridium/isolamento & purificação , Infecções por Clostridium/complicações , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Infecções por Citomegalovirus/diagnóstico , Humanos , Masculino , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/análogos & derivados , Piperacilina/administração & dosagem , Combinação Piperacilina e Tazobactam , Resultado do TratamentoRESUMO
The ascomycete filamentous fungus Neurospora intermedia is commonly used in the food industry and considered nonpathogenic to humans. This study characterizes four N. intermedia isolates recovered from three patients. The first patient had a mediastinal germ cell tumor with multiple metastases. N. intermedia was recovered from his endotracheal aspirate and from the endobronchial mass obtained by bronchoscopic forceps biopsy. Histopathology of the biopsy tissue revealed necrotic tissue mixed with septate fungal hyphae with right-angle branching. An endobronchial mass caused by N. intermedia was thus diagnosed. Another two N. intermedia isolates were recovered from the endotracheal aspirates of two critically ill patients. In vitro, N. intermedia grows rapidly and forms orange, conidiating colonies composed of septate hyphae. Two isolates from the first patient belong to mating type a; the other two isolates belong to mating type A. Coculture of isolates of opposite mating types yielded dark ascomata containing ascospores, supporting that N. intermedia is a heterothallic fungus. N. intermedia isolates cross-reacted with the Aspergillus galactomannan antigen assay and were susceptible to amphotericin B and voriconazole. In conclusion, this report describes the first human infection (endobronchial mass) caused by N. intermedia, highlighting its potential to invade the human respiratory tract.
Assuntos
Antifúngicos , Neurospora , Humanos , Masculino , Neurospora/isolamento & purificação , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Pessoa de Meia-Idade , Adulto , Micoses/diagnóstico , Micoses/microbiologia , Anfotericina B/uso terapêuticoRESUMO
Facing a 40% mortality rate in candidemia patients, drug-resistant Candida and their petite mutants remain a major treatment challenge. Antimicrobial photodynamic therapy (aPDT) targets multiple fungal structures, unlike antibiotics/antifungals, potentially thwarting resistance. Traditional methods for inducing petite colonies rely on ethidium bromide or fluconazole, which can influence drug susceptibility and stress responses. This study investigated the application of green light (peak 520 nm) and rose bengal (RB) photosensitizer to combat a drug-resistant Candida glabrata isolate. The findings revealed that aPDT treatment significantly inhibited cell growth (≥99.9% reduction) and effectively induced petite colony formation, as evidenced by reduced size and loss of mitochondrial redox indicator staining. This study provides initial evidence that aPDT can induce petite colonies in a multidrug-resistant C. glabrata strain in vitro, offering a potentially transformative approach for combating resistant fungal infections.
Assuntos
Candida , Fotoquimioterapia , Humanos , Rosa Bengala/farmacologia , Candida glabrata , Fármacos Fotossensibilizantes/farmacologiaRESUMO
BACKGROUND: The benefits of HCV eradication on distinct recurrence patterns and long-term hepatic outcomes in patients with hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) remain uncertain. This study aims to assess the impact of HCV eradication on HCC recurrence patterns and long-term hepatic outcomes after RFA and to identify predictors of recurrence in patients achieving sustained virological response (SVR). METHODS: We retrospectively enrolled 274 patients receiving RFA for HCV-related HCC, including 73 and 88 patients treated with interferon-based (IFN) and direct-acting antivirals (DAA) therapy, respectively. We analysed factors associated with local tumour progression (LTP), distant recurrence, overall survival, and hepatic decompensation. RESULTS: SVR was achieved in 49.3% of patients undergoing IFN therapy and 93.2% of patients undergoing DAA therapy. HCV eradication was not associated with LTP but significantly correlated with reduced risk of distant recurrence (by DAA: hazard ratio (HR) = 0.449, p = 0.006), overall survival (by IFN: HR = 0.242, p < 0.001; by DAA: HR = 0.274, p < 0.001) and hepatic decompensation (by IFN: HR = 0.313, p = 0.004; by DAA: HR = 0.281, p < 0.001). The benefits of achieving SVR in terms of overall survival and hepatic decompensation remained significant in subgroups of patients with and without recurrence. Patients with SVR showed a significant decline in FIB-4 score and a higher proportion of ALBI grade improvement. Among SVR patients, the IMbrave050 criteria predicted LTP but not distant recurrence, whereas the FIB-4 score after SVR, rather than the baseline FIB-4, predicted distant recurrence. CONCLUSIONS: HCV eradication was associated with a significant reduction in distant recurrence, mortality and hepatic decompensation following RFA in patients with HCV-related HCC.
RESUMO
A fungal polymerase chain reaction (PCR) amplifies conserved genes across diverse species, combined with the subsequent hybridization of amplicons using a specific oligonucleotide microarray, allowing for the rapid detection of pathogens at the species level. However, the performance of microarrays in diagnosing invasive mold infections (IMI) from infected tissue samples is rarely reported. During the 4-year study period, all biopsied tissue samples from patients with a suspected IMI sent for microarray assays were analyzed. A partial segment of the internal transcribed spacer (ITS) region was amplified by nested PCR after DNA extraction. Amplicons were hybridized with specific probes for a variety of mold species using an in-house oligonucleotide microarray. A total of 80 clinical samples from 74 patients were tested. A diagnosis of an IMI was made in 10 patients (4 proven, 1 probable, 3 possible, 2 clinical suspicion). The PCR/microarray test was positive for three out of four proven IMIs, one probable IMI, and one out of three possible IMIs. Two patients with positive PCR/microarray findings were considered to have clinical suspicion of an IMI, and their responsible physicians initiated antifungal therapy despite the absence of supporting microbiological and histological evidence. Clinical diagnoses were categorized into non-IMI and IMI groups (including proven, probable, possible, and clinical suspicion). The sensitivity and specificity of the microarray in diagnosing the IMIs were 70% and 95.7%, respectively, while the sensitivity and specificity of the culture and histological findings were 10%/96.3% and 40.0%/100%, respectively. PCR-based methods provide supportive microbiological evidence when culture results are inconclusive. The combination of a microarray with fungal culture and histology promotes the precise diagnosis of IMIs in difficult-to-diagnose patients.
RESUMO
Free voluntary counseling and testing (VCT) has been available in Taiwan as a part of HIV surveillance and prevention program since 1999, but related data were seldom reported. We aimed to examine characteristics of individuals who attended anonymous client-initiated VCT service and factors associated with HIV infection. The study population consisted of clients at two large VCT sites located in northern and southern Taiwan in 2004- 2008. Information on socio-demographic factors and potential risk behaviors was obtained by a questionnaire. Of 5671 clients, 65.1% were younger than 30 years; 42.0%, 41.2%, and 16.8% were men who ever had sex with men (MSM), non-MSM males, and women with HIV seropositivity of 8.0%, 1.2%, and 1.5%, respectively. The proportion of clients who confirmed having a prior HIV test was 66.5% in MSM, followed by 43% in non-MSM, and 30.2% in women. Correlates of HIV seropositivity differed between genders: ever engaging in commercial sex, being married or less educated were associated with increased risks among women but not for men. Different independent predictors were revealed among three groups of clients by multivariable analyses: illicit drug use, anal sex behavior, sexual partner(s) with HIV, and one-night stand in MSM; injection drug use and history of sexually transmitted infections in non-MSM; and injection drug use, sexual partner(s) with HIV and trading sex in women. Of all three groups, illicit drug or injection drug use was associated with the highest risks among all independent predictors. In this population of VCT clients in Taiwan, risk profiles of HIV infection differed according to gender and MSM experience, and different prevention strategies are needed to target different risk groups. In women, risk factors related to low social demographic and relationship power deserves attention in planning future prevention efforts.