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1.
Proc Natl Acad Sci U S A ; 120(52): e2314808120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38134196

RESUMO

Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Eliminação de Partículas Virais , Formação de Anticorpos , Tempo de Reação , Anticorpos Antivirais , RNA Viral , Imunoglobulina G , Imunoglobulina A , Imunoglobulina A Secretora
2.
Proc Natl Acad Sci U S A ; 119(33): e2203437119, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35895716

RESUMO

The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1-expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)-containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.


Assuntos
COVID-19 , Pulmão , Cadeias Leves de Miosina , SARS-CoV-2 , Índice de Gravidade de Doença , Tromboinflamação , Vasculite , COVID-19/sangue , COVID-19/complicações , COVID-19/patologia , Humanos , Leucócitos Mononucleares , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Cadeias Leves de Miosina/sangue , RNA-Seq , SARS-CoV-2/isolamento & purificação , Análise de Célula Única , Espectrometria por Raios X , Tromboinflamação/patologia , Tromboinflamação/virologia , Vasculite/patologia , Vasculite/virologia
3.
J Clin Immunol ; 44(4): 104, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647550

RESUMO

PURPOSE: Auto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs. METHODS: We evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from the patients with auto-abs and conducted epitope mapping of the auto-abs. RESULTS: Three of 19 severe and 4 of 42 critical COVID-19 patients had neutralizing auto-abs to type I IFNs. Patients with auto-abs to type I IFNs showed no characteristic clinical features. scRNA-seq from 38 patients with COVID-19 revealed that IFN signaling in conventional dendritic cells and canonical monocytes was attenuated, and SARS-CoV-2-specific BCR repertoires were decreased in patients with auto-abs. Furthermore, auto-abs to IFN-α2 from COVID-19 patients with auto-abs recognized characteristic epitopes of IFN-α2, which binds to the receptor. CONCLUSION: Auto-abs to type I IFN found in COVID-19 patients inhibited IFN signaling in dendritic cells and monocytes by blocking the binding of type I IFN to its receptor. The failure to properly induce production of an antibody to SARS-CoV-2 may be a causative factor of COVID-19 severity.


Assuntos
Autoanticorpos , COVID-19 , Interferon Tipo I , Células Mieloides , Feminino , Humanos , Masculino , Autoanticorpos/imunologia , Autoanticorpos/sangue , COVID-19/imunologia , Células Dendríticas/imunologia , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Células Mieloides/imunologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Transdução de Sinais/imunologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-38842502

RESUMO

BACKGROUND: Stenotrophomonas maltophilia is a carbapenem-resistant Gram-negative pathogen increasingly responsible for difficult-to-treat nosocomial infections. OBJECTIVES: To describe the contemporary clinical characteristics and genome epidemiology of patients colonized or infected by S. maltophilia in a multicentre, prospective cohort. METHODS: All patients with a clinical culture growing S. maltophilia were enrolled at six tertiary hospitals across Japan between April 2019 and March 2022. The clinical characteristics, outcomes, antimicrobial susceptibility and genomic epidemiology of cases with S. maltophilia were investigated. RESULTS: In total, 78 patients were included representing 34 infection and 44 colonization cases. The median age was 72.5 years (IQR, 61-78), and males accounted for 53 cases (68%). The most common comorbidity was localized solid malignancy (39%). Nearly half of the patients (44%) were immunosuppressed, with antineoplastic chemotherapy accounting for 31%. The respiratory tract was the most common site of colonization (86%), whereas bacteraemia accounted for most infection cases (56%). The 30 day all-cause mortality rate was 21%, which was significantly higher in infection cases than colonization cases (35% versus 9%; adjusted HR, 3.81; 95% CI, 1.22-11.96). Susceptibility rates to ceftazidime, levofloxacin, minocycline and sulfamethoxazole/trimethoprim were 14%, 65%, 87% and 100%, respectively. The percentage of infection ranged from 13% in the unclassified group to 86% in genomic group 6A. The percentage of non-susceptibility to ceftazidime ranged from 33% in genomic group C to 100% in genomic groups 6 and 7 and genomic group geniculate. CONCLUSIONS: In this contemporary multicentre cohort, S. maltophilia primarily colonized the respiratory tract, whereas patients with bacteraemia had the highest the mortality from this pathogen. Sulfamethoxazole/trimethoprim remained consistently active, but susceptibility to levofloxacin was relatively low. The proportions of cases representing infection and susceptibility to ceftazidime differed significantly based on genomic groups.

5.
Antimicrob Agents Chemother ; 67(10): e0051023, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37702483

RESUMO

Cefmetazole is active against extended-spectrum ß-lactamase-producing Escherichia coli (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter, observational study included patients hospitalized for invasive urinary tract infection due to ESBLEC between March 2020 and November 2021 at 10 facilities in Japan, for whom either cefmetazole or meropenem was initiated as a definitive therapy within 96 h of culture collection and continued for at least 3 d. Outcomes included clinical and microbiological effectiveness, recurrence within 28 d, and all-cause mortality (14 d, 30 d, in-hospital). Outcomes were adjusted for the inverse probability of propensity scores for receiving cefmetazole or meropenem. Eighty-one and forty-six patients were included in the cefmetazole and meropenem groups, respectively. Bacteremia accounted for 43% of the cefmetazole group, and 59% of the meropenem group. The crude clinical effectiveness, 14 d, 30 d, and in-hospital mortality for patients in the cefmetazole and meropenem groups were 96.1% vs 90.9%, 0% vs 2.3%, 0% vs 12.5%, and 2.6% vs 13.3%, respectively. After propensity score adjustment, clinical effectiveness, the risk of in-hospital mortality, and the risk of recurrence were similar between the two groups (P = 0.54, P = 0.10, and P = 0.79, respectively). In all cases with available data (cefmetazole : n = 61, meropenem : n = 22), both drugs were microbiologically effective. In all isolates, bla CTX-M was detected as the extended-spectrum ß-lactamase gene. The predominant CTX-M subtype was CTX-M-27 (47.6%). Cefmetazole showed clinical and bacteriological effectiveness comparable to meropenem against invasive urinary tract infection due to ESBLECs.


Assuntos
Infecções por Escherichia coli , Infecções Urinárias , Humanos , Cefmetazol/uso terapêutico , Cefmetazol/farmacologia , Meropeném/uso terapêutico , Meropeném/farmacologia , beta-Lactamases/farmacologia , Escherichia coli/genética , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia
6.
BMC Infect Dis ; 23(1): 653, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37789253

RESUMO

BACKGROUND: To validate Japanese claims-based disease-identifying algorithms for herpes zoster (HZ), Mycobacterium tuberculosis (MTB), nontuberculous mycobacteria infections (NTM), and Pneumocystis jirovecii pneumonia (PJP). METHODS: VALIDATE-J, a multicenter, cross-sectional, retrospective study, reviewed the administrative claims data and medical records from two Japanese hospitals. Claims-based algorithms were developed by experts to identify HZ, MTB, NTM, and PJP cases among patients treated 2012-2016. Diagnosis was confirmed with three gold standard definitions; positive predictive values (PPVs) were calculated for prevalent (regardless of baseline disease-free period) and incident (preceded by a 12-month disease-free period for the target conditions) cases. RESULTS: Of patients identified using claims-based algorithms, a random sample of 377 cases was included: HZ (n = 95 [55 incident cases]); MTB (n = 100 [58]); NTM (n = 82 [50]); and PJP (n = 100 [84]). PPVs ranged from 67.4-70.5% (HZ), 67.0-90.0% (MTB), 18.3-63.4% (NTM), and 20.0-45.0% (PJP) for prevalent cases, and 69.1-70.9% (HZ), 58.6-87.9% (MTB), 10.0-56.0% (NTM), and 22.6-51.2% (PJP) for incident cases, across definitions. Adding treatment to the algorithms increased PPVs for HZ, with a small increase observed for prevalent cases of NTM. CONCLUSIONS: VALIDATE-J demonstrated moderate to high PPVs for disease-identifying algorithms for HZ and MTB using Japanese claims data.


Assuntos
Doenças Transmissíveis , Herpes Zoster , Infecções por Mycobacterium não Tuberculosas , Humanos , Micobactérias não Tuberculosas , Japão/epidemiologia , Estudos Retrospectivos , Estudos Transversais , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/epidemiologia , Hospedeiro Imunocomprometido
7.
J Infect Chemother ; 29(9): 916-918, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37217004

RESUMO

We report two the cases of patients with imported Plasmodium falciparum malaria during the COVID-19 pandemic. One was coinfected with COVID-19 and the other was misdiagnosed with COVID-19; either way, the diagnosis of malaria was delayed. These cases suggest that physicians should beware of cognitive biases during pandemics and carefully evaluate febrile patients. Malaria should be considered in any febrile patient returning from a malaria-endemic area.


Assuntos
COVID-19 , Malária Falciparum , Malária , Humanos , Pandemias , COVID-19/diagnóstico , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Malária/diagnóstico , Malária/tratamento farmacológico , Malária/epidemiologia , Febre , Erros de Diagnóstico , Cognição , Plasmodium falciparum , Viagem
8.
J Infect Chemother ; 29(9): 869-874, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37178973

RESUMO

BACKGROUND: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5. RESULTS: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group. CONCLUSIONS: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.


Assuntos
COVID-19 , Humanos , COVID-19/terapia , SARS-CoV-2 , Japão , Soroterapia para COVID-19 , Imunização Passiva/efeitos adversos , Resultado do Tratamento
9.
BMC Infect Dis ; 22(1): 520, 2022 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-35659262

RESUMO

BACKGROUND: Catheter-related bloodstream infection (CRBSI), caused by rapidly growing mycobacteria (RGM), is a rare infectious complication in hematopoietic stem cell transplant (HSCT) recipients and can often be misdiagnosed as Gram-positive rod (GPR) bacteremia. CASE PRESENTATION: We present a case of CRBSI caused by Mycobacterium wolinskyi, a rare RGM, in a 44-year-old female patient who received an umbilical cord blood transplant. CONCLUSIONS: Rapidly growing mycobacteria can stain as GPRs and may grow in routine blood culture media after 3-4 days of incubation. These features are not widely known to clinicians, and acid-fast staining is therefore recommended when unidentifiable GPRs are detected in blood cultures, especially in immunocompromised patients, such as those with hematologic malignancies or intravascular devices.


Assuntos
Bacteriemia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Mycobacterium , Mycobacterium , Adulto , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Catéteres , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Feminino , Humanos , Mycobacteriaceae , Infecções por Mycobacterium/microbiologia
10.
J Infect Chemother ; 28(2): 319-320, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34794870

RESUMO

The quantitative antigen test based on the chemiluminescent enzyme immunoassay for SARS-CoV-2 has been used in international airports for quarantine in Japan. While cases of false-positive rapid antigen tests for SARS-CoV-2 were reported, false-positive cases of the quantitative antigen test with clinical information are rare. Here, we report a case of acute respiratory infection whose quantitative antigen test for SARS-CoV-2 was suspected to be false positive. A 9-month-old boy who presented with fever and rhinorrhea was admitted to our hospital under the Quarantine Act. He was diagnosed with COVID-19 based on the quantitative antigen test for SARS-CoV-2 performed at the quarantine station. None of the accompanying family members were positive for COVID-19. Nucleic acid amplification tests (NAAT) for SARS-CoV-2 were all negative, and multiplex polymerase chain reaction detected human rhinovirus or enterovirus infection. This case suggests that the results of the quantitative antigen test should be interpreted together with clinical information, and NAAT should be performed when false-positive results are suspected to avoid unnecessary isolation.


Assuntos
COVID-19 , SARS-CoV-2 , Criança , Família , Humanos , Testes Imunológicos , Lactente , Masculino , Sensibilidade e Especificidade
11.
Pharmacoepidemiol Drug Saf ; 30(9): 1153-1161, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33960542

RESUMO

PURPOSE: Real-world data from large administrative claims databases in Japan have recently become available, but limited evidence exists to support their validity. VALIDATE-J validated claims-based algorithms for selected cancers in Japan. METHODS: VALIDATE-J was a multicenter, cross-sectional, retrospective study. Disease-identifying algorithms were used to identify cancers diagnosed between January or March 2012 and December 2016 using claims data from two hospitals in Japan. Positive predictive values (PPVs), specificity, and sensitivity were calculated for prevalent (regardless of baseline cancer-free period) and incident (12-month cancer-free period; with claims and registry periods in the same month) cases, using hospital cancer registry data as gold standard. RESULTS: 22 108 cancers were identified in the hospital claims databases. PPVs (number of registry cases) for prevalent/incident cases were: any malignancy 79.0% (25 934)/73.1% (18 119); colorectal 84.4% (3519)/65.6% (2340); gastric 87.4% (3534)/76.8% (2279); lung 88.1% (2066)/79.9% (1636); breast 86.4% (4959)/59.9% (3185); pancreatic 87.1% (582)/80.4% (508); melanoma 48.7% (46)/42.9% (36); and lymphoma 83.6% (1457)/77.8% (1035). Specificity ranged from 98.3% to 100% (prevalent)/99.5% to 100% (incident); sensitivity ranged from 39.1% to 67.6% (prevalent)/12.5% to 31.4% (incident). PPVs of claims-based algorithms for several cancers in patients ≥66 years of age were slightly higher than those in a US Medicare population. CONCLUSIONS: VALIDATE-J demonstrated high specificity and modest-to-moderate sensitivity for claims-based algorithms of most malignancies using Japanese claims data. Use of claims-based algorithms will enable identification of patient populations from claims databases, while avoiding direct patient identification. Further research is needed to confirm the generalizability of our results and applicability to specific subgroups of patient populations.


Assuntos
Neoplasias , Algoritmos , Estudos Transversais , Bases de Dados Factuais , Humanos , Incidência , Japão/epidemiologia , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Estudos Retrospectivos
12.
J Infect Chemother ; 27(4): 632-638, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33309629

RESUMO

INTRODUCTION: The epidemiology of infectious diseases in Japan remains undefined despite the increasing tourism. GeoSentinel, an epidemiological surveillance system for reporting imported infectious diseases, has only two participating facilities in Japan. Although the number of infectious diseases is reported by the National Institute of Infectious Diseases, there is no detailed clinical information about these cases. Therefore, we established J-RIDA (Japan Registry for Infectious Diseases from Abroad) to clarify the status of imported infectious diseases in Japan and provide detailed information. METHODS: J-RIDA was started as a registry of imported infectious diseases. Case registration began in October 2017. Between October 2017 and September 2019, 15 medical institutions participated in this clinical study. The registry collected information about the patient's age, sex, nationality, chief complaint, consultation date, date of onset, whether visit was made to a travel clinic before travel, blood test results (if samples were collected), travel history, and final diagnosis. RESULTS: Of the 3046 cases included in this study, 46.7% to Southeast Asia, 13.0% to Africa, 13.7% to East Asia, 11.5% to South Asia, 7.5% to Europe, 3.8% to Central and South America, 4.6% to North America, 3.9% to Oceania, and 2.8% to Central and west Asia. More than 85% of chief complaints were fever and general symptoms, gastrointestinal symptoms, respiratory symptoms, or dermatologic problems. The most common diseases were travelers' diarrhea, animal bite, upper respiratory infection, influenza, and dengue fever. CONCLUSIONS: We summarized two-year cases registered in Japan's imported infectious disease registry. These results will significantly contribute to the epidemiology in Japan.


Assuntos
Doenças Transmissíveis Importadas , Doenças Transmissíveis , Animais , Ásia , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis Importadas/diagnóstico , Doenças Transmissíveis Importadas/epidemiologia , Diarreia , Europa (Continente) , Humanos , Japão/epidemiologia , América do Norte , Sistema de Registros , Viagem
13.
Antimicrob Agents Chemother ; 64(12)2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-32958718

RESUMO

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).


Assuntos
Amidas/administração & dosagem , Antivirais/administração & dosagem , Tratamento Farmacológico da COVID-19 , Pirazinas/administração & dosagem , SARS-CoV-2/efeitos dos fármacos , Carga Viral/efeitos dos fármacos , Adolescente , Adulto , Amidas/efeitos adversos , Antivirais/efeitos adversos , Doenças Assintomáticas , COVID-19/fisiopatologia , COVID-19/virologia , Feminino , Hospitalização , Humanos , Hiperuricemia/induzido quimicamente , Hiperuricemia/diagnóstico , Hiperuricemia/fisiopatologia , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirazinas/efeitos adversos , Distribuição Aleatória , SARS-CoV-2/patogenicidade , Prevenção Secundária/organização & administração , Índice de Gravidade de Doença , Tempo para o Tratamento/organização & administração , Resultado do Tratamento
14.
J Antimicrob Chemother ; 75(3): 697-708, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31789374

RESUMO

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are classified as carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE; the majority of CPE in Japan produce IMP carbapenemase. OBJECTIVES: We evaluated the clinico-epidemiological and microbiological information and effects of IMP-type carbapenemase production in CRE. METHODS: Patients with isolations of CRE (MICs of meropenem ≥2 mg/L, imipenem ≥2 mg/L or cefmetazole ≥64 mg/L) from August 2016 to March 2018 were included. Microbiological analyses and WGS were conducted and clinical parameters were compared between groups. Independent predictors for the isolation of CPE from patients were identified by logistic regression. For comparing clinical outcomes, a stabilized inverse probability weighting method was used to conduct propensity score-adjusted analysis. RESULTS: Ninety isolates (27 CPE and 63 non-CPE) were collected from 88 patients (25 CPE and 63 non-CPE). All CPE tested positive for IMP carbapenemase. Antibiotic resistance (and the presence of resistance genes) was more frequent in the CPE group than in the non-CPE group. Independent predictors for CPE isolation were residence in a nursing home or long-term care facility, longer prior length of hospital stay (LOS), use of a urinary catheter and/or nasogastric tube, dependent functional status and exposure to carbapenem. Although in-hospital and 30 day mortality rates were similar between the two groups, LOS after CRE isolation was longer in the CPE group. CONCLUSIONS: IMP-CPE were associated with prolonged hospital stays and had different clinical and microbiological characteristics compared with non-CPE. Tailored approaches are necessary for the investigational and public health reporting, and clinical and infection prevention perspectives for IMP-CPE and non-CPE.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , beta-Lactamases/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Estudos Prospectivos
15.
J Infect Chemother ; 25(2): 141-146, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30100399

RESUMO

Lactococcus lactis is a rare causative organism in humans. Cases of L. lactis infection have only rarely been reported. However, because it is often difficult to identify by conventional commercially available methods, its incidence may be underestimated. We herein report the case of a 70-year-old man with cholangiocarcinoma who developed L. lactis cholangitis and review previously reported cases of L. lactis infection. Our case was confirmed by matrix-assisted desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). This case shows L. lactis is a potential causative pathogen of cholangitis and that MALDI-TOF MS can be useful for the rapid and accurate identification of L. lactis infection. We searched the literature for published case reports on cholangitis and any other infections caused by L. lactis, and thereby identified 36 cases, including our case. At least 66.7% (n = 24) of the cases had significant underlying conditions; 15 of the cases involved patients with an immunocompromised status. At least 41.7% (n = 15) had a significant food consumption history, such as the consumption of unpasteurized dairy products. The clinical sources of L. lactis were diverse and endocarditis was the most common diagnosis (n = 8), followed by hepatobiliary infection (n = 6), central nervous system infection (n = 5), and peritonitis (n = 4). The prognosis was favorable in most cases.


Assuntos
Bacteriemia/diagnóstico , Colangite/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Lactococcus lactis , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Idoso , Humanos , Masculino , Tipagem Molecular
16.
J Infect Chemother ; 25(10): 806-810, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30982728

RESUMO

Microbacterium species are coryneform gram-positive rods that are widely distributed in the environment and have been recently recognized as rare pathogens in humans. However, information about the epidemiologic and clinical characteristics of Microbacterium species is scarce. We herein reported an 11-year-old girl with acute leukemia who was found to have catheter-related bloodstream infection in her neutropenic phase. Gram-positive bacilli repeatedly grew on the blood cultures and were later confirmed by 16S rRNA analysis as Microbacterium paraoxydans. A literature review found available clinical courses in 21 cases (7 pediatric cases) of Microbacterium spp. bacteremia. Our case and those in literature suggested that Microbacterium spp. bacteremia often occurs in patients with indwelling central venous catheters; the literature review further suggested that removal of central venous catheters is required in most cases and that 16S rRNA sequence was useful in identifying in detail the species of Microbacterium.


Assuntos
Actinobacteria/isolamento & purificação , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bacteriemia/diagnóstico , Infecções Relacionadas a Cateter/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Actinobacteria/genética , Actinobacteria/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bacteriemia/imunologia , Bacteriemia/microbiologia , Infecções Relacionadas a Cateter/imunologia , Infecções Relacionadas a Cateter/microbiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Cateteres Venosos Centrais/efeitos adversos , Criança , DNA Bacteriano/isolamento & purificação , Feminino , Humanos , Hospedeiro Imunocomprometido , Microbacterium , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , RNA Ribossômico 16S/genética
17.
J Infect Chemother ; 24(10): 845-848, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29534850

RESUMO

Although vancomycin administration is recommended for the treatment of infective endocarditis (IE) caused by methicillin-resistant Staphylococcus aureus (MRSA), it is unclear whether an alternative agent, daptomycin, can be used to treat IE with pulmonary complications. A 26-year-old female who had undergone surgical repair of a ventricular septal defect as an early teenager presented with fever, headache, and vomiting. She was admitted to our hospital and diagnosed with right-sided IE with septic pulmonary embolism caused by MRSA. Vancomycin, rifampicin, and gentamicin were administered; however, exacerbation of drug eruption due to the antimicrobial agents on the 11th day led us to switch from vancomycin and rifampicin to daptomycin. Furthermore, we included linezolid to treat lung abscesses that accompanied the septic pulmonary embolism. We confirmed negative blood cultures on the 18th day. On the same day, a patch closure for the ventricular septal defect and tricuspid valve replacement were performed. She was discharged on the 65th day with an uneventful postoperative course. This experience suggests that daptomycin and linezolid are effective salvage therapies for right-sided IE caused by MRSA and accompanied by pulmonary complications.


Assuntos
Daptomicina/administração & dosagem , Endocardite/tratamento farmacológico , Linezolida/administração & dosagem , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Embolia Pulmonar/tratamento farmacológico , Terapia de Salvação , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Daptomicina/uso terapêutico , Endocardite/sangue , Endocardite/diagnóstico , Feminino , Febre , Cefaleia , Humanos , Linezolida/uso terapêutico , Abscesso Pulmonar/sangue , Abscesso Pulmonar/diagnóstico , Abscesso Pulmonar/tratamento farmacológico , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Vômito
18.
J Infect Chemother ; 24(7): 579-582, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29373263

RESUMO

Legionella pneumophila is recognized as a common causative organism for community-acquired pneumonia, but it is rarely a causative organism for hospital-acquired pneumonia, except in cases of hospital outbreak. Recently, most of the Legionella cases have been diagnosed using the urine antigen test. However, this test can reliably detect only L. pneumophila serogroup 1. Here we report a 63-year-old male patient who was recently diagnosed with acute leukemia and treated with chemotherapy and who developed pneumonia on hospital day 8 during the nadir phase. He was later diagnosed with Legionella pneumonia by culture despite a negative urine antigen test. This case suggests that Legionella pneumonia is an important differential diagnosis for pneumonia in inpatients in the early phase of hospitalization and that when Legionella infection is clinically suspected, culture using selective media or molecular tests should be performed even if the urine antigen test is negative.


Assuntos
Legionella pneumophila/isolamento & purificação , Doença dos Legionários/diagnóstico , Pneumonia Bacteriana/diagnóstico , Antibacterianos/uso terapêutico , Antígenos de Bactérias/urina , Antineoplásicos/uso terapêutico , Evolução Fatal , Humanos , Doença dos Legionários/tratamento farmacológico , Doença dos Legionários/microbiologia , Leucemia/complicações , Leucemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Sorotipagem , Escarro/microbiologia
19.
J Antimicrob Chemother ; 72(4): 1221-1226, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28077673

RESUMO

Objectives: Healthcare facilities internationally have grown outpatient parenteral antibiotic administration services for the last few decades. The literature contains publications from dozens of countries describing systematized processes with specialist oversight and their levels of service provision and outcomes. Such descriptions are absent in the majority of Asian countries. We sought to elucidate the extent and nature of outpatient parenteral antibiotic therapy (OPAT) in Asia and to consider the ramifications and opportunities for improvement. Methods: Utilizing colleagues and their personal networks, we surveyed healthcare facilities across 17 countries in Asia to ascertain the current means (if any) of providing OPAT. In that survey we also sought to explore the capacity and interest of these facilities in developing systematized OPAT services. Results: Responses were received from 171 different healthcare facilities from 17 countries. Most (97/171, 57%) stated that they administer outpatient parenteral antibiotics, but only 5 of 162 facilities (3%) outside of Singapore described comprehensive services with specialist oversight. Conclusions: There is very likely a large unrecognized problem of unchecked outpatient parenteral antibiotic administration in Asia. Developing comprehensive and systematized OPAT in Asia is needed as a priority in an environment in which the infectious diseases community is demanding broad stewardship approaches. There are nonetheless challenges in establishing and sustaining OPAT programmes. Local champions and leverage off identified local incentives and needs are key to regional advancement.


Assuntos
Assistência Ambulatorial , Antibacterianos/administração & dosagem , Doenças Transmissíveis/tratamento farmacológico , Infusões Parenterais , Pacientes Ambulatoriais , Assistência Ambulatorial/normas , Assistência Ambulatorial/estatística & dados numéricos , Antibacterianos/uso terapêutico , Ásia/epidemiologia , Doenças Transmissíveis/epidemiologia , Humanos , Singapura/epidemiologia
20.
J Infect Chemother ; 23(2): 111-113, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27600175

RESUMO

Listeria monocytogenes is a well-known cause of meningitis, colitis, and bacteremia; however, obstructive pyelonephritis caused by L. monocytogenes has never been reported. We herein report on a 90-year-old Japanese woman with obstructive pyelonephritis and bacteremia due to uterus carcinoma invading the ureter. She was admitted to our hospital complaining of fever and chills, and her physical examination revealed left costovertebral angle tenderness. Computed tomography showed hydronephrosis and complete ureteral obstruction due to tumor invasion. Blood and urine cultures upon nephrostomy revealed the growth of L. monocytogenes. We treated the patient with two weeks of intravenous ampicillin and an additional one-week treatment of oral sulfamethoxazole/trimethoprim. This case shows the importance to recognize L. monocytogenes as a potential causative agent of urinary tract infection.


Assuntos
Bacteriemia/microbiologia , Listeria monocytogenes/isolamento & purificação , Listeriose , Pielonefrite/microbiologia , Idoso de 80 Anos ou mais , Ampicilina/administração & dosagem , Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Feminino , Humanos , Pielonefrite/diagnóstico , Pielonefrite/terapia , Neoplasias Uterinas/complicações
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