RESUMO
PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. CONCLUSION: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.
Assuntos
Autoanticorpos , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Nocardiose , Humanos , Autoanticorpos/imunologia , Autoanticorpos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Nocardiose/imunologia , Nocardiose/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Proteinose Alveolar Pulmonar/imunologia , Proteinose Alveolar Pulmonar/diagnóstico , Cryptococcus gattii/imunologiaRESUMO
OBJECTIVE: We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. METHODS: This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. RESULTS: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32â mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15-29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45-141.82, P = 0.023). DISCUSSION: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32â mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality.
Assuntos
Bacteriemia , Infecções por Escherichia coli , Gammaproteobacteria , Humanos , Escherichia coli , Cefoperazona/uso terapêutico , Sulbactam/uso terapêutico , Klebsiella pneumoniae , Infecções por Escherichia coli/tratamento farmacológico , Bacteriemia/tratamento farmacológicoRESUMO
BACKGROUND: Infections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied. OBJECTIVES: This study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates. METHODS: This multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients' clinical outcomes and characteristics were collected and analyzed. RESULTS: In total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07-1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31-14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50-12.27; p = 0.006) were independently associated with unfavorable outcomes. CONCLUSION: Patients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes.
Assuntos
Antibacterianos , Bacteriemia , Cefoperazona , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Sulbactam , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Sulbactam/uso terapêutico , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/mortalidade , Infecções por Klebsiella/microbiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Idoso , Cefoperazona/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Taiwan , Idoso de 80 Anos ou mais , AdultoRESUMO
Meningitis caused by Cryptococcus tetragattii fungus is rare and has been found in specific geographic regions. We report a case of meningitis caused by C. tetragattii (molecular type VGIV) in an immunocompetent patient in Taiwan. The patient had traveled to Egypt and was positive for granulocyte-macrophage colony-stimulating factor autoantibody.
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Cryptococcus , Meningite Criptocócica , Meningite , Humanos , Taiwan , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , FungosRESUMO
Candidemia is a life-threatening infectious disease that has varying incidences. Previous studies revealed the differences in clinical characteristics and outcomes between non-hospital-onset (NHO) and hospital-onset (HO) candidemia. This 4-year retrospective research included adult patients with candidemia in a tertiary medical centre in Taiwan, and cases were categorised as NHO and HO candidemia. Survival analysis and risk factors associated with in-hospital mortality were performed using the Kaplan-Meier method and multivariate Cox proportional-hazards models. The analysis included 339 patients, and the overall incidence was 1.50 per 1,000 admission person-year. Of the cases, 82 (24.18%) were NHO candidemia, and 57.52% (195/339) of patients were diagnosed with at least one malignancy. C. albicans was the most commonly isolated species, accounting for 52.21%. Patients with NHO candidemia had a higher proportion of C. glabrata but a lower ratio of C. tropicalis in comparison to the HO group. The all-cause in-hospital mortality rate was 55.75%. Multivariate Cox proportional-hazards models showed that NHO candidemia was a better outcome predictor (adjusted hazard ratio, 0.44). The administration of antifungal therapy within 2 days was a protective factor. In conclusion, NHO candidemia showed distinct microbiological characteristics and a better outcome than HO candidemia.
Assuntos
Candidemia , Infecção Hospitalar , Adulto , Humanos , Antifúngicos/uso terapêutico , Candida , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Candidemia/microbiologia , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Infecção Hospitalar/epidemiologia , Taiwan/epidemiologiaRESUMO
BACKGROUND: The rare occurrence of human cryptococcosis caused by Cryptococcus gattii sensu lato leads to difficulties in establishing the antifungal susceptibility profile between species of this potentially lethal pathogen, which may be crucial for treating cryptococcosis. OBJECTIVE: To establish an antifungal susceptibility profile of C. gattii s.l. in Taiwan. METHODS: A total of 104 environmental C. gattii s.l. strains (including multilocal sequence typing ST7, ST106, ST274, ST328, ST546, ST548 and ST630) and 21 previously collected clinical strains (including ST7, ST44, ST06, ST274, ST328 and ST329) were included in this study. We determined the minimum inhibitory concentrations (MICs) of six antifungal agents (itraconazole, fluconazole, voriconazole, posaconazole, flucytosine and amphotericin B) against environmental C. gattii s.l. strains and compared the antifungal susceptibility profiles of environmental strains with those of clinical strains. RESULTS: The antifungal susceptibility data demonstrated that the MICs of antifungal agents against environmental strains were comparable to those against clinical strains. Compared with strains of Cryptococcus deuterogattii, those of C. gattii sensu stricto were more susceptible to azoles and flucytosine. The differences in antifungal susceptibility between the strains of each sequence type (ST) were significant. Correlation analysis of MICs revealed cross-resistance between azoles in environmental strains of C. gattii s.l. Geographic differences in the antifungal susceptibility of C. gattii s.l. isolated from different cities in Taiwan were observed in this study. CONCLUSION: Clinical and environmental strains were indistinguishable in antifungal susceptibility. The antifungal susceptibility of C. gattii s.l. is associated with STs. Therefore, establishing an ST-oriented domestic antifungal susceptibility database may help treat C. gattii s.l.-induced cryptococcosis.
Assuntos
Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Humanos , Antifúngicos/farmacologia , Flucitosina , Taiwan , Farmacorresistência Fúngica , Criptococose/microbiologia , Fluconazol/farmacologia , Azóis , Testes de Sensibilidade MicrobianaRESUMO
PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP. METHODS: Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP. RESULTS: High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results. CONCLUSION: Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs.
Assuntos
Criptococose , Proteinose Alveolar Pulmonar , Humanos , Autoanticorpos , Criptococose/diagnóstico , Criptococose/epidemiologia , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/etiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologiaRESUMO
BACKGROUND: The rare occurrence of cryptococcosis caused by Cryptococcus gattii sensu lato (C. gattii s.l.) leads to the difficulties in studying the molecular epidemiology of this globally emerging disease. OBJECTIVES: To establish the molecular epidemiological profile of C. gattii s.l. in Taiwan, and understand the genetic relationship between locally endemic and global isolates. METHODS: A nationwide survey on environmental C. gattii s.l. in Taiwan was conducted from 2017 to 2019. The geographic distribution and molecular epidemiology based on multilocus sequence typing (MLST) data of the environmental isolates were compared with 18 previously collected clinical isolates. Phylogenetic analysis was performed to elucidate the genetic relationship between the global isolates and the isolates endemic to Taiwan. RESULTS: From a total of 622 environmental samples, 104 (16.7%) were positive for C. gattii s.l.. Seven sequence types were identified among the environmental isolates. The genetic population structure showed that the environmental and clinical isolates were closely linked by sequence types and geographical locations. Phylogenetic analysis revealed the association between the C. gattii s.l. isolates in Taiwan and those from South America and South Asia. The recombination test suggested that, in Taiwan, the C. gattii sensu stricto (C. gattii s.s). isolates undergo clonal reproduction and sexual recombination, whereas C. deuterogattii isolates were clonal. CONCLUSIONS: The molecular epidemiology of environmental C. gattii s.l. isolates is closely linked to the clinical isolates. Phylogenetic analysis of the environmental isolates provides an insight into the mechanisms underlying reproduction and dispersal of C. gattii s.l. in Taiwan.
Assuntos
Criptococose/epidemiologia , Cryptococcus gattii/genética , Microbiologia Ambiental , Filogenia , Criptococose/microbiologia , Cryptococcus gattii/classificação , DNA Fúngico/genética , Variação Genética , Genótipo , Geografia , Saúde Global , Humanos , Tipagem de Sequências Multilocus/estatística & dados numéricos , Técnicas de Tipagem Micológica/estatística & dados numéricos , Taiwan/epidemiologiaRESUMO
BACKGROUND: We aimed to identify associations between the risk of acute respiratory failure (ARF) and types of antihypertensive agents in patients with viral pneumonia. METHODS: In this case-control study, data extracted from the Taiwan National Health Insurance Research Database were analysed. The base population comprised patients with viral pneumonia treated from 2000 to 2013. The case group comprised patients with ARF and the control group comprised participants without ARF. Adjusted odds ratios (ORs) were calculated using a multivariable logistic regression model. RESULTS: In total, 4427 viral pneumonia patients with ARF and 4427 matched control participants without ARF were recruited. Patients with diabetes, alcohol-related disease, asthma, chronic kidney disease or end-stage renal disease, chronic obstructive pulmonary disease, cancer, congestive heart failure, stroke, acute pulmonary oedema and shock had increased odds of developing ARF, especially shock (adjusted OR = 49.3; 95% CI = 27.4, 88.7), cancer (12.6; 8.67, 18.2) and stroke (7.51; 5.32, 10.6). Increasing odds of developing ARF were noted in patients using potassium-sparing diuretics (2.95; 1.54, 5.64), loop diuretics (68.2; 48.1, 96.6), calcium channel blockers (1.64; 1.26, 2.13) and angiotensin-converting enzyme inhibitors (1.70; 1.15, 2.53). Patients with prescriptions of α-blockers (0.44; 0.26, 0.74), ß-blockers (0.37; 0.26, 0.52), thiazides (0.38; 0.25, 0.59) and angiotensin receptor blockers (0.65; 0.51, 0.83) had lower odds of having ARF. CONCLUSION: Patients with viral pneumonia who received α-blockers, ß-blockers, thiazides or angiotensin receptor blockers during hospitalisation had a lower risk of developing ARF.
Assuntos
Hipertensão , Pneumonia Viral , Insuficiência Respiratória , Antagonistas de Receptores de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos de Casos e Controles , Hospitalização , Humanos , Hipertensão/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologiaRESUMO
BACKGROUND/PURPOSE: Invasive Trichosporon infections are emerging, but association of different therapeutic management of Trichosporon fungemia and clinical outcomes were rarely reported. This study investigates the epidemiology, species distribution and genotypes of trichosporonosis in Taiwan, and identified the predictors of clinical outcomes in patients with Trichosporon fungemia. METHODS: Strains collected from four medical centers in Taiwan, during 2010-2018. Species identification was confirmed by sequencing of IGS1 region, and antifungal susceptibility was performed using Sensititre YeastOne panel. RESULTS: Among 115 isolates, Trichosporon asahii was the leading species (73.0%), followed by Trichosporon dermatis (11.3%), Trichosporon faecales (6.1%), and Trichosporon montevideense (5.2%). Of the 84 T. asahii isolates, genotype 1 was the predominant (41.7%). High fluconazole minimal inhibitory concentration (MICs,â§8 µg/mL) were observed for 70.2% T. asahii isolates and 16.1% non-asahii Trichosporon isolates. Posaconazole and voriconazole possess the most potent antifungal activity against all Trichosporon isolates, with geometric mean values of 0.251 µg/mL and 0.111 µg/mL, respectively. Fifty-three isolates collected from blood cultures, and 42 patients with fungemia enrolled for the Kaplan-Meier plot which revealed that voriconazole treatment had a significantly better survival rate compared with those without (p = 0.042). In multivariate analysis, source control (odds ratio [OR]: 0.13 95%CI [confidence interval]: 0.02-0.83, p = 0.031) and voriconazole use (OR: 0.11 95%CI: 0.02-0.74, p = 0.023) are independent predictors of 14-day mortality. CONCLUSION: This is the largest series of Trichosporon fungemia up till the present moment. Voriconazole therapy and source control play important roles in 14-day mortality.
Assuntos
Fungemia , Trichosporon , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Basidiomycota , DNA Fúngico , Fungemia/tratamento farmacológico , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Trichosporon/genética , VoriconazolRESUMO
BACKGROUND: Candidemia caused by uncommon Candida species is increasing and misidentification may compromise optimal antifungal therapy. This multicenter study aimed to evaluate the accuracy of species-level identification of uncommon Candida. METHODS: Uncommon causative species of candidemia identified in routine laboratories using CHROMagar, API-32C and VITEK-2 Yeast ID system were collected from July 2011 to June 2014. These isolates were further identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system and sequencing of the internal transcribed spacer and 28S rRNA gene. Susceptibility of the isolates was determined. RESULTS: Of 85 isolates evaluated, Candida guilliermondii (n = 36) was the most common, followed by Candid sake (n = 7) and Candida famata (n = 4). Using DNA-sequencing analysis as standard, none of C. sake and C. famata was correct, while VITEK MS correctly identified 10 of the 11 isolates. With the exclusion of one unspecified Candida by DNA-sequencing methods, the accuracy of conventional methods and VITEK MS was 64.3% and 86.9%, respectively (p = 0.001). Eight isolates were confirmed to be yeasts other than Candida. Compared with other Candida species, C. guilliermondii showed elevated minimal inhibitory concentration of echinocandins. CONCLUSION: Misidentification of uncommon Candida species was common using the conventional methods, especially for C. sake and C. famata. MALDI-TOF MS assisted by DNA-sequencing methods should be considered.
Assuntos
Candida , Sepse , Candida/genética , Humanos , Saccharomycetales , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Candida auris is a recently identified multi-resistant Candida species, first reported in Japan in 2009, and poses a serious global health threat. Lack of awareness of this new Candida species and difficulties with laboratory identification have impacted significantly on outbreak detection and management, and compromised patient outcome. Accordingly, there is an urgent need to raise awareness of healthcare personnel to this emerging pathogen and determine its prevalence, impact, and challenges to the Taiwan healthcare system. Enhanced laboratory testing strategies are needed to differentiate C. auris from other Candida species to provide accurate diagnosis and implement control measures early enough to prevent hospital outbreaks. In this report, we review the key epidemiological, microbiological and clinical characteristics of C. auris and provide the results of a multicenter surveillance study of C. auris in Taiwan. We also conducted a web-based survey to determine awareness of the medical community to C. auris and the capability of Taiwanese hospital laboratories to identify this microorganism. C. auris has not yet been isolated from humans in Taiwan, but the unique features of this microorganism and its ability to reach across international boundaries justify the importance of these initiatives in Taiwan.
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Antifúngicos/farmacologia , Candida/patogenicidade , Candidíase/epidemiologia , Controle de Infecções/métodos , Candida/efeitos dos fármacos , Candidíase/prevenção & controle , Infecção Hospitalar/prevenção & controle , Farmacorresistência Fúngica Múltipla , Humanos , Estudos Multicêntricos como Assunto , Taiwan/epidemiologiaRESUMO
INTRODUCTION: Autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) can cause acquired pulmonary alveolar proteinosis (PAP). Cases of acquired PAP susceptible to typical respiratory pathogens and opportunistic infections have been reported. Anti-GM-CSF autoantibodies have been reported in a few patients with cryptococcal meningitis. This study evaluated the presence of neutralizing anti-GM-CSF autoantibodies in patients without known congenital or acquired immunodeficiency with severe pulmonary or extrapulmonary cryptococcal infection but without PAP. METHODS: We took a clinical history and performed an immunologic evaluation and screening of anti-cytokine autoantibodies in patients with cryptococcal meningitis. The impact of autoantibodies to GM-CSF on immune function was assessed by intracellular staining of GM-CSF-induced STAT5 phosphorylation and MIP-1α production in normal peripheral blood mononuclear cells incubated with plasma from patients or normal control subjects. RESULTS: Neutralizing anti-GM-CSF autoantibodies were identified in four patients with disseminated cryptococcosis, none of whom exhibited PAP. Plasma from patients blocked GM-CSF signaling and inhibited STAT5 phosphorylation and production of MIP-1α. One patient died of disseminated cryptococcosis involving the central nervous system, which was associated with defective GM-CSF activity. CONCLUSIONS: Anti-GM-CSF autoantibodies increase susceptibility to cryptococcal infection in adults without PAP. Cryptococcal central nervous system infection associated with anti-GM-CSF autoantibodies could result in neurological sequelae or be life-threatening. Therefore, timely detection of neutralizing anti-GM-CSF autoantibodies and development of an effective therapy are necessary to prevent deterioration of cryptococcal infection in these patients.
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Autoanticorpos/imunologia , Criptococose/etiologia , Criptococose/microbiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Antifúngicos/uso terapêutico , Autoanticorpos/sangue , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Quimiocina CCL3/biossíntese , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Cryptococcus neoformans/imunologia , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunofenotipagem , Contagem de Leucócitos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/etiologia , Infecções Oportunistas/microbiologia , Fosforilação , Proteinose Alveolar Pulmonar/etiologia , Radiografia Torácica , Fator de Transcrição STAT5/metabolismo , Tomografia Computadorizada por Raios XRESUMO
Adult patients with disseminated nontuberculous mycobacterial (dNTM) infections usually have severe immune system defects. Recently, several studies have shown that anti-IFN-γ autoantibodies may play an important role in the pathogenicity of dNTM infections. A considerable proportion of reported cases of anti-IFN-γ autoantibodies show either clinical or laboratory evidence of autoimmune disease. In the present study, we identified 19 formerly healthy adults who later developed dNTM infections, of whom 17 were further investigated immunologically. High-titer anti-IFN-γ autoantibodies capable of inhibiting IL-12 production in vitro were found in the plasma of all of these patients. In addition to dNTM infection, 35% and 71% of our patients also suffered from salmonellosis and herpes zoster, respectively. This observation suggests that IFN-γ may be crucial in controlling salmonella infection and reactivating latent varicella-zoster virus infection in humans. 2 HLA alleles, DRB1*16:02 DQB1*05:02 (odds ratio 8.68; 95% confidence interval, 3.47-21.90; P = 1.1 × 10(-6); Pc = 3.08 × 10(-5) and odds ratio 7.16; 95% confidence interval, 3.02-17.05; P = 1 × 10(-7); Pc = 1.4 × 10(-6), respectively), were found in 82% (14 of 17) of our patients. In conclusion, our data suggest that anti-IFN-γ autoantibodies may play a critical role in the pathogenesis of dNTM infections and reactivation of latent varicella-zoster virus infection and are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02.
Assuntos
Autoanticorpos/imunologia , Cadeias beta de HLA-DQ/imunologia , Cadeias HLA-DRB1/imunologia , Herpes Zoster/imunologia , Interferon gama/imunologia , Infecções por Mycobacterium não Tuberculosas/imunologia , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Autoanticorpos/genética , Coinfecção/genética , Coinfecção/imunologia , Coinfecção/mortalidade , Feminino , Frequência do Gene , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Herpes Zoster/genética , Herpes Zoster/mortalidade , Herpesvirus Humano 3/imunologia , Teste de Histocompatibilidade , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Interferon gama/sangue , Subunidade p40 da Interleucina-12/sangue , Subunidade p40 da Interleucina-12/imunologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/genética , Infecções por Mycobacterium não Tuberculosas/mortalidade , Estudos Soroepidemiológicos , Latência Viral/imunologiaAssuntos
Hemorragia Cerebral/diagnóstico por imagem , Endocardite/microbiologia , Micoses/diagnóstico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Volvariella/isolamento & purificação , Adulto , Hemorragia Cerebral/patologia , Evolução Fatal , Feminino , Humanos , Micoses/microbiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Tomografia Computadorizada por Raios X , Volvariella/patogenicidadeRESUMO
A prospective, cross-sectional study was conducted at a medical center in central Taiwan to understand the prevalence, associated factors, and microbiologic features for oropharyngeal yeast colonization in human immunodeficiency virus-infected outpatients. Oral yeast colonization was detected in 127 (45 %) patients, including 21 (16.5 %) colonized by more than one species. Of the 154 isolates, Candida albicans was the most common species (114, 74 %), followed by Candida dubliniensis (10, 6.5 %), Candida glabrata (10, 6.5 %), Candida tropicalis (7, 4.5 %), and 13 others. We found that receiving antituberculous drug (p = 0.046) or atazanavir (p = 0.045) was two predictors for patients colonized by non-C. albicans species (p = 0.005) and risking mixed yeast colonization (p = 0.009). Even though our data showed that clinical antifungal drugs remained effective in vitro against the colonizing yeasts, the increased mixed yeast colonization indicates a potential issue for controlling mixed infections in hospital settings.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Candida/isolamento & purificação , Candidíase/microbiologia , Orofaringe/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Antifúngicos/uso terapêutico , Contagem de Linfócito CD4 , Candida/classificação , Candida/efeitos dos fármacos , Candida/genética , Candidíase/tratamento farmacológico , Candidíase/imunologia , Estudos Transversais , Feminino , Fluconazol/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , TaiwanRESUMO
This study examined the geographic distribution of minimum inhibitory concentrations (MICs) of antifungals against Cryptococcus isolates. Data were collected on the MICs of specific antifungals (amphotericin B, 5-flucytosine, fluconazole, voriconazole, posaconazole, and isavuconazole) against various Cryptococcus species for the period 2010 to 2020 from the Antimicrobial Testing Leadership and Surveillance database. Cryptococcus isolates were collected from samples of blood and cerebrospinal fluid (CSF) from patients hospitalized in different regions worldwide. We applied the epidemiological cutoff values (ECVs) of antifungals against various Cryptococcus species to distinguish wild-type (WT) from non-WT Cryptococcus isolates. A total of 395 isolates of Cryptococcus species cultured from blood (n = 201) or CSF (n = 194) were analyzed. C. grubii (n = 270), C. neoformans (n = 111), and C. gattii (n = 11) were the three predominant species causing bloodstream infections (BSI) or meningitis/meningoencephalitis (MME). The proportion of MICs above the ECV (1 mg/L) for amphotericin B among C. neoformans isolates was significantly lower than that among C. gattii isolates (MICs >0.5 mg/L; P < 0.001), as evaluated using the chi-square test. For most isolates of the three predominant Cryptococcus species, the MICs of new triazoles were ≤0.25 mg/L. The MICs of fluconazole and amphotericin B in the BSI/MME-causing Cryptococcus isolates collected from patients hospitalized in the Asia-Western Pacific region and Europe were significantly lower (i.e., the distributions were more leftward) than those in North America and Latin America. Ongoing monitoring of MIC data for important antifungals against cryptococcosis is crucial.
Assuntos
Anti-Infecciosos , Cryptococcus gattii , Cryptococcus neoformans , Endrin/análogos & derivados , Humanos , Antifúngicos/farmacologia , Anfotericina B , Fluconazol/farmacologia , LiderançaRESUMO
Bacillus Calmette-Guérin (BCG) therapy is an adjuvant treatment for urothelial carcinomas of the upper urinary tract (UTUC). BCG therapy can result in various side effects. We present a case of a 67-year-old female with a history of UTUC who developed disseminated tuberculosis following BCG instillation into the upper urinary tract after conservative management. This complex clinical scenario required a multidisciplinary approach, including antibiotic therapy, immunoglobulin infusion, and tailored tuberculosis treatment. The case underscores the importance of vigilance, early detection, and tailored interventions in managing disseminated tuberculosis arising from BCG therapy and rare complications like hemophagocytic syndrome.
RESUMO
BACKGROUND: Cytolethal distending toxin (CDT) belongs to the genotoxin family and is closely related to Campylobacter jejuni-associated gastroenteritis. We recently reported that CDT triggers the danger-associated molecular pattern (DAMP) signaling to exert deleterious effects on host cells. However, how CDT traffics in cells and the mechanism of CDT intoxication remain to be elucidated. METHODS: Recombinant CDT subunits (CdtA, CdtB, and CdtC) were purified, and their activity was characterized in gastrointestinal cells. Molecular approaches and image tracking were employed to analyze the delivery of CDT in host cells. RESULTS: In this study, we found that CDT interacts with the receptor of advanced glycation end products (RAGE) and high mobility group box 1 (HMGB1) to enter the cells. Our results further showed that CdtB transport in cells through the dynamin-dependent endocytic pathway and lysosome is involved in this process. Conversely, blockage of RAGE signaling resulted in a reduction in CDT-arrested cell cycles, indicating that RAGE is involved in CDT intracellular transport and its subsequent pathogenesis. CONCLUSION: Our results demonstrate that RAGE is important for CDT trafficking in the cells. These findings expand our understanding of important issues related to host cell intoxication by C. jejuni CDT.
RESUMO
BACKGROUND: The emergence of SARS-CoV-2 in late 2019 sparked the global COVID-19 pandemic, leading to varied vaccine policies worldwide. The evolving patterns of respiratory pathogens, aside from SARS-CoV-2, during the pandemic have had a significant impact on the development of vaccine strategies. METHODS: This study explores the landscape of respiratory pathogens, encompassing SARS-CoV-2, respiratory syncytial virus (RSV), and influenza viruses, through a retrospective analysis of data obtained from the BioFire Respiratory Panel 2.1 (RP 2.1) at China Medical University Hospital (Taichung, Taiwan) spanning from January 2020 to November 2023. RESULTS: Among the 7950 respiratory samples studied, pediatric cases exhibited higher positivity (64.9%, 2488/3835) and mixed detection rates (43.8%, 1090/2488) than adults. Annual mixed detection rates increased (27.9-48%). Prevalence analysis revealed diverse patterns across age groups, with higher rates in pediatrics. Notably, human rhinovirus/enterovirus predominated (48.1%). Mixed detection illustrated viral co-detections, notably with parainfluenza viruses and adenovirus. Government policies and pandemic dynamics influenced infection patterns, with RSV resurgence after May 2022. Age-specific RSV detection demonstrated a shift, influencing vaccine considerations. Amid global vaccine initiatives, RSV's increasing trend in adults warrants attention. CONCLUSIONS: This comprehensive analysis emphasizes the importance of multiplex PCR testing in shaping targeted vaccination strategies during evolving respiratory pathogen landscapes.