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BACKGROUND AND OBJECTIVE: The identification of factors associated with long-term prognosis after community-onset pneumonia in elderly patients should be considered when initiating advance care planning (ACP). We aimed to identify these factors and develop a prediction score model. METHODS: Patients aged 65 years and older, who were hospitalized for pneumonia at nine collaborating institutions, were included. The prognosis of patients 180 days after the completion of antimicrobial treatment for pneumonia was prospectively collected. RESULTS: The total number of analysable cases was 399, excluding 7 outliers and 42 cases with missing data or unknown prognosis. These cases were randomly divided in an 8:2 ratio for score development and testing. The median age was 82 years, and there were 68 (17%) deaths. A multivariate analysis showed that significant factors were performance status (PS) ≥2 (Odds ratio [OR], 11.78), hypoalbuminemia ≤2.5 g/dL (OR, 5.28) and dementia (OR, 3.15), while age and detection of antimicrobial-resistant bacteria were not associated with prognosis. A scoring model was then developed with PS ≥2, Alb ≤2.5, and dementia providing scores of 2, 1 and 1 each, respectively, for a total of 4. The area under the curve was 0.8504, and the sensitivity and specificity were 94.6% and 61.7% at the cutoff of 2, respectively. In the test cases, the sensitivity and specificity were 91.7% and 63.1%, respectively, at a cutoff value of 2. CONCLUSION: Patients meeting this score should be considered near the end of life, and the initiation of ACP practices should be considered.
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Infecções Comunitárias Adquiridas , Pneumonia , Humanos , Feminino , Masculino , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Prognóstico , Idoso , Idoso de 80 Anos ou mais , Pneumonia/diagnóstico , Pneumonia/microbiologia , Pneumonia/tratamento farmacológico , Pneumonia/mortalidade , Estudos Prospectivos , Fatores de Risco , Antibacterianos/uso terapêutico , Valor Preditivo dos Testes , Demência/diagnóstico , Demência/epidemiologiaRESUMO
INTRODUCTION: The diagnostic tools of nucleic acid amplification tests and antigen tests have been extensively employed for the detection of Coronavirus disease 2019 (COVID-19). Although the reverse-transcriptase polymerase chain reaction (RT)-PCR test has high sensitivity and specificity, it is a time-consuming and labor-intensive process. On the other hand, antigen tests are simple and prompt, however, their low sensitivity and potential for false positives have been identified as limitations. In light of these factors, the development of novel tests that combine speed and clinical dependability is a promising prospect. METHODS: Surface plasmon field-enhanced fluorescence spectroscopy (SPFS) excites chromophores by means of an enhanced electromagnetic field induced on a gold film surface. It enables the highly sensitive measurement of biomarkers in a short and simple 20-min window. In this study, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) SPFS-based antigen test targeting the SARS-CoV-2 nucleocapsid protein was performed and evaluated in 25 patients with COVID-19 and 10 non-infected controls. RESULTS: A positive correlation was observed between antigen levels determined by SPFS and RNA levels determined via RT-PCR. The sensitivity values were 100 %, 92 %, and 62.5 %; and the specificity values were 100 %, 90 %, and 100 %; for nasopharyngeal swabs, nasal swabs, and saliva specimens when the cutoff values were set to 65.1, 0.2, and 1.5 pg/mL, respectively. No clinically problematic cross-reactivity with analogous coronaviruses was observed. CONCLUSIONS: The SARS-CoV-2 SPFS antigen test showed excellent clinical diagnostic accuracy for nasopharyngeal and nasal swabs, with a rapid turnaround.
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BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.
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Antibacterianos , Fluoroquinolonas , Pneumonia Associada a Assistência à Saúde , Humanos , Masculino , Feminino , Idoso de 80 Anos ou mais , Idoso , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/administração & dosagem , Japão , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/microbiologia , Resultado do Tratamento , Administração Oral , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Cryptococcal meningitis (CM) is an invasive fungal infection with a poor prognosis that often occurs in both healthy individuals and compromised hosts, such as patients infected with human immunodeficiency virus (HIV). Unlike CM in HIV patients, evidence regarding CM in non-HIV patients is limited to small retrospective studies. OBJECTIVE: To identify the pretreatment prognostic factors for CM in non-HIV patients. METHODS: We conducted a large retrospective analysis of CM in non-HIV patients using data from a nationwide Japanese database. The study included hospitalized patients diagnosed with CM between 1 April 2010 and 31 March 2017. All-cause mortality was compared between patients with CM with and without HIV infection. Poor diagnostic factors were analysed in the non-HIV CM group. RESULTS: Overall, 533 (64 HIV and 469 non-HIV) patients met the criteria. The mortality rate at 90 days was significantly lower in the HIV group (6.3% vs. 25.4% p = .0002). In a logistic regression analysis of the non-HIV group, age ≥ 65 y (odds ratio [OR] 2.37, 95% CI 1.17-4.78), impaired consciousness (Japan Coma Scale ≥1) (OR 2.25, 95% CI 1.29-3.93), haemodialysis (OR 3.53, 95% CI 1.12-11.20) and previous corticosteroid usage (OR 2.40, 95% CI 1.37-4.19) were associated with poor prognosis at 30 days after diagnosis. CONCLUSION: More caution is suggested when treating non-HIV with CM in older patients with impaired consciousness, previous corticosteroid usage and haemodialysis.
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Infecções por HIV , Meningite Criptocócica , Humanos , Idoso , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/complicações , Infecções por HIV/complicações , HIV , Estudos Retrospectivos , Prognóstico , CorticosteroidesRESUMO
Exophiala dermatitidis is an emerging black fungus that causes pulmonary infections that may be underestimated by conventional culture methods. We encountered one case that initially appeared to be yeast and was misidentified as Rhodotorula spp. using a commercial identification kit. Thus, genetic identification and clinical background investigations were conducted on 46 strains of Rhodotorula spp. The sequences of the internal transcribed spacer and large-subunit RNA genes (D1/D2 regions) of 43 isolates, excluding two environmental isolates and one difficult-to-culture isolate, were determined and genetically identified. Notably, 22 isolates were identified as E. dermatitidis and misidentified as Rhodotorula spp. using the conventional method. Based on the exclusion criteria, the clinical information of 11 patients was retrospectively reviewed. Five cases (definite) had definite exacerbation of pulmonary infections due to E. dermatitidis, and six cases (possible) had undeniable infections. Of the 11 cases of pulmonary infection suggested to be caused by E. dermatitidis, comorbidities included two cases of chronic pulmonary aspergillosis (CPA), three cases of pulmonary non-tuberculous mycobacterial (NTM) infection and one case of pulmonary nocardiosis, suggesting a trend towards simultaneous detection of chronic pulmonary infections. Steroid and immunosuppressive drug use was observed in five cases, and ß-D-glucan elevation was observed in three of five definite cases of pulmonary infections due to E. dermatitidis. The possibility of E. dermatitidis infection should be considered when Rhodotorula spp. are isolated from cultures of airway-derived specimens, and, in addition to CPA and NTM, identification of E. dermatitidis may be important in chronic pulmonary infections.
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Exophiala , Pneumopatias Fúngicas , Feoifomicose , Rhodotorula , Rhodotorula/isolamento & purificação , Rhodotorula/genética , Rhodotorula/classificação , Humanos , Exophiala/genética , Exophiala/isolamento & purificação , Exophiala/classificação , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Feoifomicose/microbiologia , Feoifomicose/diagnóstico , Estudos Retrospectivos , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/diagnóstico , Erros de Diagnóstico , Adulto , DNA Fúngico/genética , Idoso de 80 Anos ou mais , Análise de Sequência de DNA , DNA Espaçador Ribossômico/genéticaRESUMO
Factor XIII deficiency is an extremely rare autosomal recessive genetic disorder, occurring in 1 of 3-5 million people, and is associated with perinatal complications, such as habitual abortion and prolonged bleeding. Although plasma-derived factor XIII (Fibrogamin®) carries a risk of infection and contains very low concentrated forms of factor XIII (FXIII) used for a pregnant woman with congenital coagulation factor XIII deficiency, recombinant factor XIII (rFXIII, Novo Thirteen®; Tretten®, Novo Nordisk, Bagsvaerd, Denmark), which has no risk of infection and is highly concentrated, has emerged as a novel formulation. Herein, we report the first case of a Japanese pregnant woman with congenital coagulation factor XIII deficiency successfully managed by rFXIII. She had a good perinatal course without pregnancy-related complications and transfusion through the perinatal period.
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Aborto Habitual , Deficiência do Fator XIII , Gravidez , Feminino , Humanos , Fator XIII , Deficiência do Fator XIII/complicações , Deficiência do Fator XIII/tratamento farmacológico , Proteínas Recombinantes , Coagulação SanguíneaRESUMO
INTRODUCTION: Glycemic control is essential for improving the prognosis of cardiac surgery, although precise recommendations have not yet been established. Under a constant blood glucose level, the insulin infusion rate correlates with insulin resistance during glycemic control using an artificial pancreas (AP). We conducted this retrospective study to elucidate changes in intraoperative insulin sensitivity as a first step to creating glycemic control guidelines. METHODS: Fifty-five cardiac surgery patients at our hospital who underwent intraoperative glycemic control using an AP were enrolled. Twenty-three patients undergoing surgical procedures requiring cardiac arrest under hypothermic cardiopulmonary bypass (CPB) with minimum rectal temperatures lower than 32°C, 13 patients undergoing surgical procedures requiring cardiac arrest under hypothermic CPB with minimum rectal temperatures of 32°C, eight patients undergoing on-pump beating coronary artery bypass grafting and 11 patients undergoing off-pump coronary artery bypass were assigned to groups A, B, C and D, respectively. We analyzed the time course of changes in the data derived from glycemic control using the AP. RESULTS: Significant time course changes were observed in groups A and B, but not in groups C and D. Insulin resistance was induced after the start of hypothermic CPB in groups A and B, and the induced change was not resolved by the rewarming procedure, remaining sustained until the end of surgery. CONCLUSIONS: Hypothermia is the predominant factor of the induced insulin resistance during cardiac surgery. Thus, careful glycemic management during hypothermic CPB is important. Prospective clinical studies are required to confirm the findings of this study.
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Ponte de Artéria Coronária sem Circulação Extracorpórea , Parada Cardíaca , Hipotermia Induzida , Resistência à Insulina , Pâncreas Artificial , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Ponte Cardiopulmonar/métodosRESUMO
The surface pre-reacted glass ionomer (S-PRG) filler is a type of bioactive functional glass that releases six different ions. This study examined the effects of the S-PRG filler eluate on Streptococcus mutans in the presence of sucrose. In a solution containing S. mutans, the concentrations of BO33-, Al3+, Sr2+, and F- were significantly higher in the presence of the S-PRG filler eluate than in its absence (p < 0.001). The concentrations of these ions further increased in the presence of sucrose. Additionally, the S-PRG filler eluate significantly reduced glucan formation by S. mutans (p < 0.001) and significantly increased the pH of the bacterial suspension (p < 0.001). Bioinformatic analyses revealed that the S-PRG filler eluate downregulated genes involved in purine biosynthesis (purC, purF, purL, purM, and purN) and upregulated genes involved in osmotic pressure (opuAa and opuAb). At a low pH (5.0), the S-PRG filler eluate completely inhibited the growth of S. mutans in the presence of sucrose and significantly increased the osmotic pressure of the bacterial suspension compared with the control (p < 0.001). These findings suggest that ions released from the S-PRG filler induce gene expression changes and exert an inhibitory effect on S. mutans in the presence of sucrose.
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Streptococcus mutans , Sacarose , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/crescimento & desenvolvimento , Sacarose/farmacologia , Sacarose/química , Concentração de Íons de Hidrogênio , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Glucanos/farmacologia , Glucanos/química , Propriedades de Superfície , Pressão Osmótica/efeitos dos fármacos , Resinas Acrílicas , Dióxido de SilícioRESUMO
Candida auris is resistant to multiple antifungal agents. This study investigated its antifungal susceptibility and explored FKS1 mutations across the isolates from mice enterically colonized with wild-type C. auris and treated with echinocandin. Resistant C. auris with FKS1 mutations, including S639F, S639Y, D642Y, R1354H, or R1354Y, were isolated and found to be micafungin- and caspofungin-resistant in vivo; however, the MICs of isolates with mutation in R1354 remained below the micafungin breakpoint in vitro.
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Candida auris , Equinocandinas , Animais , Camundongos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Farmacorresistência Fúngica/genética , Equinocandinas/farmacologia , Equinocandinas/genética , Trato Gastrointestinal , Micafungina/farmacologia , Testes de Sensibilidade Microbiana , Mutação/genéticaRESUMO
OBJECTIVE: Ultra-high-resolution CT (UHR-CT), which can be applied normal resolution (NR), high-resolution (HR), and super-high-resolution (SHR) modes, has become available as in conjunction with multi-detector CT (MDCT). Moreover, deep learning reconstruction (DLR) method, as well as filtered back projection (FBP), hybrid-type iterative reconstruction (IR), and model-based IR methods, has been clinically used. The purpose of this study was to directly compare lung CT number and airway dimension evaluation capabilities of UHR-CT using different scan modes with those of MDCT with different reconstruction methods as investigated in a lung density and airway phantom design recommended by QIBA. MATERIALS AND METHODS: Lung CT number, inner diameter (ID), inner area (IA), and wall thickness (WT) were measured, and mean differences between measured CT number, ID, IA, WT, and standard reference were compared by means of Tukey's HSD test between all UHR-CT data and MDCT reconstructed with FBP as 1.0-mm section thickness. RESULTS: For each reconstruction method, mean differences in lung CT numbers and all airway parameters on 0.5-mm and 1-mm section thickness CTs obtained with SHR and HR modes showed significant differences with those obtained with the NR mode on UHR-CT and MDCT (p < 0.05). Moreover, the mean differences on all UHR-CTs obtained with SHR, HR, or NR modes were significantly different from those of 1.0-mm section thickness MDCTs reconstructed with FBP (p < 0.05). CONCLUSION: Scan modes and reconstruction methods used for UHR-CT were found to significantly affect lung CT number and airway dimension evaluations as did reconstruction methods used for MDCT. KEY POINTS: ⢠Scan and reconstruction methods used for UHR-CT showed significantly higher CT numbers and smaller airway dimension evaluations as did those for MDCT in a QIBA phantom study (p < 0.05). ⢠Mean differences in lung CT number for 0.25-mm, 0.5-mm, and 1.0-mm section thickness CT images obtained with SHR and HR modes were significantly larger than those for CT images at 1.0-mm section thickness obtained with MDCT and reconstructed with FBP (p < 0.05). ⢠Mean differences in inner diameter (ID), inner area (IA), and wall thickness (WT) measured with SHR and HR modes on 0.5- and 1.0-mm section thickness CT images were significantly smaller than those obtained with NR mode on UHR-CT and MDCT (p < 0.05).
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Aprendizado Profundo , Humanos , Imagens de Fantasmas , Tomografia Computadorizada por Raios X/métodos , Pulmão/diagnóstico por imagem , Tórax , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , AlgoritmosRESUMO
Data on antifungal susceptibility of Cryptococcus neoformans are limited in Japan. A total of 89 C. neoformans strains isolated from 83 non-human immunodeficiency virus-infected patients with cryptococcosis between 1997 and 2021 in Nagasaki, Japan, were investigated. Using the reference method M27-Ed4 by the Clinical and Laboratory Standards Institute, the minimum inhibitory concentration for 90% of isolates of fluconazole, itraconazole, voriconazole, amphotericin B, and flucytosine were 4, 0.125, 0.06, 0.5, and 4 µg/ml, respectively, which were below the reported epidemiological cutoff values, without any detectable non-wild-type strains. Our findings imply no increasing trend of antifungal-resistant C. neoformans in Nagasaki, Japan.
Cryptococcus neoformans strains obtained from non-human immunodeficiency virus-infected patients were observed to maintain good antifungal susceptibility to fluconazole, itraconazole, voriconazole, amphotericin B, and flucytosine over a 25-year-long period in Nagasaki, Japan.
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A 65-year-old Japanese woman repeatedly withdrew and resumed antibiotics against pulmonary non-tuberculous mycobacterial infection caused by Mycobacterium intracellulare for more than 10 years. Although she continued to take medications, her respiratory symptoms and chest computed tomography indicated an enlarged infiltrative shadow in the lingular segment of the left lung that gradually worsened over the course of a year or more. Bronchoscopy was performed and mycobacterial culture of the bronchial lavage fluid was negative, whereas Exophiala dermatitidis was detected. After administration of oral voriconazole was initiated, the productive cough and infiltrative shadow resolved. There are no characteristic physical or imaging findings of E. dermatitidis, and it often mimics other chronic respiratory infections. Thus, when confronting refractory non-tuberculous mycobacterial cases, it might be better to assume other pathogenic microorganisms, including E. dermatitidis, and actively perform bronchoscopy.
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Exophiala , Feoifomicose , Pneumonia , Humanos , Feminino , Idoso , Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico , Feoifomicose/microbiologia , Micobactérias não Tuberculosas , Voriconazol/uso terapêutico , Pneumonia/tratamento farmacológico , Pulmão/diagnóstico por imagem , Pulmão/patologiaRESUMO
Inhaled liposomal antimicrobials are known to cause hypersensitivity pneumonitis. Amikacin liposome inhalation suspension (ALIS) is a promising novel antimicrobial agent against refractory Mycobacterium avium complex infections. The frequency of drug-induced lung injury caused by ALIS is relatively high. To date, no reports of ALIS-induced organizing pneumonia diagnosed by bronchoscopy are available. We report a case of a 74-year-old female patient presenting with non-tuberculous mycobacterial pulmonary disease (NTM-PD). She was treated with ALIS for refractory NTM-PD. Fifty-nine days after starting ALIS, the patient developed a cough, and her chest radiographs indicated deterioration. She was diagnosed with organizing pneumonia based on pathological findings of the lung tissues obtained by bronchoscopy. After switching from ALIS to amikacin infusion, her organizing pneumonia improved. It is difficult to distinguish between organizing pneumonia and an exacerbation of NTM-PD based on chest radiography alone. Therefore, it is essential to perform an active bronchoscopy for diagnosis.
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Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Infecção por Mycobacterium avium-intracellulare , Pneumonia em Organização , Pneumonia , Humanos , Feminino , Idoso , Amicacina/efeitos adversos , Lipossomos/uso terapêutico , Antibacterianos/efeitos adversos , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Complexo Mycobacterium avium , Pneumonia/tratamento farmacológico , Pneumopatias/microbiologia , Micobactérias não Tuberculosas , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológicoRESUMO
Congenital myasthenic syndromes (CMS) is a group of diseases that causes abnormalities at the neuromuscular junction owing to genetic anomalies. The pathogenic variant in ALG14 results in a severe pathological form of CMS causing end-plate acetylcholine receptor deficiency. Here, we report the cases of two siblings with CMS associated with a novel variant in ALG14. Immediately after birth, they showed hypotonia and multiple joint contractures with low Apgar scores. Ptosis, low-set ears, and high-arched palate were noted. Deep tendon reflexes were symmetrical. They showed worsening swallowing and respiratory problems; hence, nasal feeding and tracheotomy were performed. Cranial magnetic resonance imaging scans revealed delayed myelination and cerebral atrophy. Exome sequencing indicated that the siblings had novel compound heterozygous missense variants, c.590T>G (p.Val197Gly) and c.433G>A (p.Gly145Arg), in exon 4 of ALG14. Repetitive nerve stimulation test showed an abnormal decrease in compound muscle action potential. After treatment with pyridostigmine, the time off the respirator increased. Their epileptic seizures were well controlled by anti-epileptic drugs. Their clinical course is stable even now at the ages of 5 and 2 years, making them the longest reported survivors of a severe form of CMS with the ALG14 variant thus far.
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Síndromes Miastênicas Congênitas , Éxons , Humanos , Mutação , Síndromes Miastênicas Congênitas/complicações , Síndromes Miastênicas Congênitas/diagnóstico , Síndromes Miastênicas Congênitas/genética , Irmãos , Sobreviventes , Sequenciamento do ExomaRESUMO
BACKGROUND: The recent increase in cases of azole-resistant Aspergillus fumigatus (ARAf) infections is a major clinical concern owing to its treatment limitations. Patient-derived ARAf occurs after prolonged azole treatment in patients with aspergillosis and involves various cyp51A point mutations or non-cyp51A mutations. The prognosis of patients with chronic pulmonary aspergillosis (CPA) with patient-derived ARAf infection remains unclear. In this study, we reported the case of a patient with ARAf due to HapE mutation, as well as the virulence of the isolate. CASE PRESENTATION: A 37-year-old male was presented with productive cough and low-grade fever. The patient was diagnosed with CPA based on the chronic course, presence of a fungus ball in the upper left lobe on chest computed tomography (CT), positivity for Aspergillus-precipitating antibody and denial of other diseases. The patient underwent left upper lobe and left S6 segment resection surgery because of repeated haemoptysis during voriconazole (VRC) treatment. The patient was postoperatively treated with VRC for 6 months. Since then, the patient was followed up without antifungal treatment but relapsed 4 years later, and VRC treatment was reinitiated. Although an azole-resistant isolate was isolated after VRC treatment, the patient did not show any disease progression in either respiratory symptoms or radiological findings. The ARAf isolated from this patient showed slow growth, decreased biomass and biofilm formation in vitro, and decreased virulence in the Galleria mellonella infection model compared with its parental strain. These phenotypes could be caused by the HapE splice site mutation. CONCLUSIONS: This is the first to report a case demonstrating the clinical manifestation of a CPA patient infected with ARAf with a HapE splice site mutation, which was consistent with the in vitro and in vivo attenuated virulence of the ARAf isolate. These results imply that not all the ARAf infections in immunocompetent patients require antifungal treatment. Further studies on the virulence of non-cyp51A mutations in ARAf are warranted.
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Aspergillus fumigatus/genética , Azóis/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Proteínas Fúngicas/genética , Aspergilose Pulmonar/microbiologia , Adulto , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/isolamento & purificação , Aspergillus fumigatus/patogenicidade , Azóis/uso terapêutico , Doença Crônica , Humanos , Masculino , Testes de Sensibilidade Microbiana , Mutação , Fenótipo , Aspergilose Pulmonar/tratamento farmacológico , Virulência/genética , Voriconazol/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the annual variation in the frequency of patient-acquired azole-resistant Aspergillus fumigatus (ARAf), and correlate it to the amount of oral triazole prescribed, in Nagasaki, Japan. METHODS: A. fumigatus isolates from respiratory specimens collected in the Nagasaki University Hospital (NUH) between 1996 and 2017 were included in the study. The amount of oral triazole prescribed in NUH since 2001 was obtained from the medical ordering system. Mutations in cyp51A, hmg1, and erg6 genes of ARAf were also analysed. RESULTS: From a total of 240 ARAf strains, 12 (5%), 6 (2.5%), 15 (6.25%), and 3 (1.25%) strains were resistant to itraconazole (ITC), voriconazole (VRC), to either ITC or VRC, and both triazoles, respectively. The amount of prescribed VRC increased annually, and was three times as large as that of ITC in 2017. All eleven patients harbouring ITC-resistant strains had a history of prior ITC treatment, while only one of six patients harbouring VRC-resistant strains had a history of prior VRC treatment. cyp51A mutations were recorded in 10 strains; however, tandem repeat mutations of the promoter region of cyp51A were not observed. Several azole-resistant strains had non-cyp51A mutations. CONCLUSIONS: The frequency of patient-acquired ARAf is not increasing in Nagasaki, Japan. Furthermore, the prevalence of VRC-induced ARAf was rare despite the remarkable increase in the amount of prescribed VRC. Mutations in genes other than cyp51A should also be considered when ARAf strains are obtained from patients treated with azole antifungals.
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Aspergillus fumigatus , Triazóis , Antifúngicos/farmacologia , Aspergillus fumigatus/genética , Azóis/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genética , Humanos , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária , Triazóis/farmacologiaRESUMO
BACKGROUND: Studies on the acute management of extremely low birthweight (ELBW) infants reveal a high incidence of intraventricular hemorrhage (IVH) in infants with high-grade internal cerebral vein perfusion waveform fluctuations. In this prospective observational study we investigated the Doppler perfusion waveform fluctuations in the great cerebral vein, straight sinus, and internal cerebral veins of ELBW infants. METHODS: We evaluated perfusion waveforms after birth every 12 h until 120 h in 73 ELBW infants (<1,000 g) at our hospital. Fluctuations were categorized into four patterns of increasing magnitude, Grades 0-3. RESULTS: The maximum grades of perfusion waveform fluctuations of the internal cerebral veins were 0, 1, 2, and 3 detected in 12, 38, 13, and 10 infants, respectively; those of the great cerebral vein were 0, 1, 2, and 3 detected in 5, 17, 20, and 31 infants, respectively; and those of the straight sinus were 0, 1, 2, and 3 detected in 1, 5, 17, and 50 infants, respectively. Only one of 803 simultaneous measurements of the Doppler perfusion waveforms showed stronger fluctuations of the peripheral vein than those of the central side veins. Intraventricular hemorrhage was associated with high-grade fluctuations in the internal cerebral veins but not in the great cerebral vein or straight sinus. CONCLUSIONS: Most infants had high-grade fluctuations in the great cerebral vein and straight sinus, with lower grade fluctuations in the internal cerebral vein, but IVH was not associated with those markers. Intraventricular hemorrhage was correlated with high-grade fluctuations only in the internal cerebral veins.
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Veias Cerebrais , Doenças do Prematuro , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Veias Cerebrais/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Recém-Nascido PrematuroRESUMO
The Aspergillus-specific lateral-flow device (AspLFD) test is a newly developed point-of-care diagnostic method for invasive pulmonary aspergillosis. However, evidence of the diagnostic performance of the AspLFD for chronic pulmonary aspergillosis (CPA) is limited. Therefore, we conducted a retrospective study to investigate this in comparison with the galactomannan (GM) ß-d-glucan (BDG) test. Fifty patients with chronic pulmonary aspergillosis and 65 patients with respiratory disease, as a control, were enrolled in this study. The majority of the CPA disease entities were chronic pulmonary aspergillosis (64.0%, n = 32), followed by subacute invasive pulmonary aspergillosis (IPA) (20.0%, n = 10) and simple pulmonary aspergilloma (SPA) (16.0%, n = 8). The sensitivity and specificity of the AspLFD test in serum samples were 62.0% and 67.7%, respectively. The GM test (cutoff index, 1.54) showed a sensitivity of 22% and a specificity of 92.3%, while the sensitivity and specificity of the BDG test (cutoff, 19.3 pg/ml) were 48% and 90.8%, respectively. In bronchoalveolar lavage fluid samples, the AspLFD test showed a sensitivity of 66.7% and a specificity of 69.2%, while those of the GM test (cutoff index, 0.6) were 72.7% and 83.1%, respectively. The Aspergillus precipitating antibody test had 70% sensitivity. Unlike the Aspergillus precipitating antibody test, the AspLFD on serum samples showed similar sensitivity to non-fumigatus Aspergillus species. Patients with false-positive results for the AspLFD on serum samples were of a significantly higher age and had a higher prevalence of cavitary lesions in chest computed tomography than patients with negative results in the control group. Given the results in this study, the performance of the AspLFD using serum was acceptable as a point-of-care test for the diagnosis of CPA.
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Líquido da Lavagem Broncoalveolar/microbiologia , Testes Imediatos , Aspergilose Pulmonar/diagnóstico , Soro/microbiologia , Idoso , Idoso de 80 Anos ou mais , Antígenos de Fungos/imunologia , Aspergillus/genética , Ação Capilar , Feminino , Galactose/análogos & derivados , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Masculino , Mananas/sangue , Mananas/imunologia , Pessoa de Meia-Idade , Aspergilose Pulmonar/sangue , Estudos Retrospectivos , Sensibilidade e Especificidade , Testes Sorológicos/instrumentação , Testes Sorológicos/métodosRESUMO
BACKGROUND: There is a high incidence of intraventricular hemorrhage in extremely low-birthweight (ELBW) infants of low gestational age with high-grade fluctuations in the perfusion waveform of the internal cerebral vein. This study investigated changes in the hemodynamic status of ELBW infants during initial strong fluctuations in the perfusion waveform of the internal cerebral vein. METHODS: We evaluated the perfusion waveform of the internal cerebral vein in 192 ELBW infants from birth, every 8 h for a total of 120 h. Sixty-seven infants had high-grade fluctuations. On the basis of the presence of patent ductus arteriosus (PDA), patients were subdivided into PDA(-) (n = 32) and PDA(+) (n = 35) groups. RESULTS: During the first high-grade fluctuation, the PDA(-) group had significant increases in systolic, diastolic, and mean blood pressure (P < 0.001 for all). The PDA(+) group did not have significant changes in blood pressure but did have significant increases in the number of interruptions or regurgitations of diastolic renal arterial blood flow (P = 0.04) and end-diastolic left pulmonary arterial flow velocity (P < 0.001), indicating increased left-to-right shunt. CONCLUSIONS: Blood pressure elevation may underlie fluctuations in the perfusion waveform of the internal cerebral vein and lead to the first high-grade increases during acute management of ELBW infants. When no elevation in blood pressure occurred, hemodynamically significant PDA was considered a potential underlying factor.