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1.
Int J Infect Dis ; 92: 228-233, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31981766

RESUMO

OBJECTIVES: The usefulness of serial procalcitonin (PCT) measurements for predicting the prognosis and treatment efficacy for hospitalised community-acquired pneumonia (CAP) patients was investigated. METHODS: This prospective, multicentre, cohort study enrolled consecutive CAP patients who were hospitalised at 10 hospitals in western Japan from September 2013 to September 2016. PCT and C-reactive protein (CRP) were measured on admission (PCT D1 and CRP D1), within 48-72 h after admission (PCT D3 and CRP D3), and within 144-192 h after admission. CURB-65 and the Pneumonia Severity Index (PSI) were assessed on admission. The primary outcome was 30-day mortality; secondary outcomes were early and late treatment failure rates. RESULTS: A total of 710 patients were included. The 30-day mortality rate was 3.1%. On multivariate analysis, only PCT D3/D1 ratio >1 [odds ratio (95% confidence interval): 4.33 (1.46-12.82),P = 0.008] and PSI [odds ratio (95% confidence interval): 2.32 (1.07-5.03), P = 0.03] were significant prognostic factors. Regarding treatment efficacy, PCT D3/D1 >1 was a significant predictor of early treatment failure on multivariate analysis. PCT D3/D1 with the PSI significantly improved the prognostic accuracy over that of the PSI alone. CONCLUSIONS: PCT should be measured consecutively, not only on admission, to predict the prognosis and treatment efficacy in CAP.


Assuntos
Biomarcadores/sangue , Pneumonia/tratamento farmacológico , Pneumonia/mortalidade , Pró-Calcitonina/sangue , Adulto , Idoso , Proteína C-Reativa/análise , Estudos de Coortes , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/mortalidade , Feminino , Hospitalização , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pneumonia/sangue , Pneumonia/microbiologia , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença
2.
Nat Commun ; 11(1): 543, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992714

RESUMO

Health care-associated infections such as Pseudomonas aeruginosa bacteremia pose a major clinical risk for hospitalized patients. However, these systemic infections are presumed to be a "dead-end" for P. aeruginosa and to have no impact on transmission. Here, we use a mouse infection model to show that P. aeruginosa can spread from the bloodstream to the gallbladder, where it replicates to extremely high numbers. Bacteria in the gallbladder can then seed the intestines and feces, leading to transmission to uninfected cage-mate mice. Our work shows that the gallbladder is crucial for spread of P. aeruginosa from the bloodstream to the feces during bacteremia, a process that promotes transmission in this experimental system. Further research is needed to test to what extent these findings are relevant to infections in patients.


Assuntos
Bacteriemia/microbiologia , Bacteriemia/transmissão , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/transmissão , Pseudomonas aeruginosa/patogenicidade , Animais , Bacteriemia/patologia , Modelos Animais de Doenças , Epitélio/microbiologia , Fezes/microbiologia , Feminino , Vesícula Biliar/microbiologia , Vesícula Biliar/patologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/patologia , Humanos , Intestinos/microbiologia , Intestinos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pneumonia/microbiologia , Infecções por Pseudomonas/patologia , Sistemas de Secreção Tipo III
3.
Immunology ; 159(2): 156-166, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31631335

RESUMO

Host-microbiota interaction plays fundamental roles in the homeostasis of mucosal immunity. Dysbiosis of intestinal microbiota has been demonstrated to participate in various immune responses and many multifactorial diseases. Study of intestinal microbiota has moved beyond the consequences of dysbiosis to the causal microbiota associated with diseases. However, studies of pulmonary microbiota and its dysbiosis are still in their infancy. Improvement of culture-dependent and -independent techniques has facilitated our understanding of lung microbiota that not only exists in healthy lung tissue but also exerts great impact on immune responses under both physiological and pathological conditions. In this review, we summarize recent progresses of lung microbiota dysbiosis and its impact on the local immune system that determines the balance of tolerance and inflammation. We discuss the causal roles of pulmonary dysbiosis under disease settings, and propose that the interaction between lung microbiota and host is critical for establishing the immune homeostasis in lung.


Assuntos
Disbiose , Pulmão/microbiologia , Microbiota , Pneumonia/microbiologia , Imunidade Adaptativa , Animais , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Pulmão/imunologia , Pulmão/metabolismo , Pneumonia/imunologia , Pneumonia/metabolismo
4.
Immunology ; 159(1): 121-129, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31606895

RESUMO

The transcription factor hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulator of the response and function of myeloid cells in hypoxic and inflammatory microenvironments. To define the role of HIF-1α in tuberculosis, the progression of aerosol Mycobacterium tuberculosis infection was analysed in mice deficient in HIF-1α in the myeloid lineage (mHIF-1α-/- ). We show that myeloid HIF-1α is not required for the containment of the infection, as both wild-type (WT) and mHIF-1α-/- mice mounted normal Th1 responses and maintained control of bacterial growth throughout infection. However, during chronic infection mHIF-1α-/- mice developed extensive lymphocytic inflammatory involvement of the interstitial lung tissue and died earlier than WT mice. These data support the hypothesis that HIF-1α activity coordinates the response of myeloid cells during M. tuberculosis infection to prevent excessive leucocyte recruitment and immunopathological consequences to the host.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pulmão/metabolismo , Mycobacterium tuberculosis/crescimento & desenvolvimento , Células Mieloides/metabolismo , Pneumonia/metabolismo , Tuberculose Pulmonar/metabolismo , Animais , Carga Bacteriana , Células Cultivadas , Modelos Animais de Doenças , Progressão da Doença , Interações Hospedeiro-Patógeno , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Pulmão/imunologia , Pulmão/microbiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mycobacterium tuberculosis/imunologia , Células Mieloides/imunologia , Células Mieloides/microbiologia , Pneumonia/genética , Pneumonia/imunologia , Pneumonia/microbiologia , Transdução de Sinais , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia
5.
Mol Immunol ; 116: 98-105, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31634816

RESUMO

Pseudomonas aeruginosa is a common nosocomial pathogen in burn patients, and rapidly acquires antibiotic resistance; thus, developing an effective therapeutic approach is the most promising strategy for combating infection. Type III secretion system (T3SS) translocates bacterial toxins into the cytosol of the targeted eukaryotic cells, which plays important roles in the virulence of P. aeruginosa infections in both acute pneumonia and burn wound models. The PcrV protein, a T3SS translocating protein, is required for T3SS function and is a well-validated target in animal models of immunoprophylactic strategies targeting P. aeruginosa. In the present study, we evaluated the protective efficacy of chicken egg yolk antibodies (IgY) raised against recombinant PcrV (r-PcrV) in both acute pneumonia and burn wound models. R-PcrV protein was generated by expressing the pcrV gene (cloned in pET-28a vector) in E. coli BL-21. Anti-PcrV IgY was obtained by immunization of hen. Anti-PcrV IgY induced greater protection in P. aeruginosamurine acute pneumonia and burn wound models than control IgY (C-IgY) and PBS groups. Anti-PcrV IgY improved opsonophagocytic killing and inhibition of bacterial invasion of host cells. Taken together, our data provide evidence that anti-PcrV IgY can be a promising therapeutic candidate for combating P. aeruginosa infections.


Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Queimaduras/imunologia , Imunoglobulinas/imunologia , Pneumonia/imunologia , Proteínas Citotóxicas Formadoras de Poros/imunologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Animais , Queimaduras/microbiologia , Galinhas/imunologia , Galinhas/microbiologia , Modelos Animais de Doenças , Feminino , Imunização/métodos , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia/microbiologia , Vacinação/métodos , Virulência/imunologia
6.
Rev Med Liege ; 74(10): 499-502, 2019 10.
Artigo em Francês | MEDLINE | ID: mdl-31609551

RESUMO

Measles is a highly contagious viral disease and one of the biggest causes of morbidity and mortality in the world. Transmission occurs from person to person through direct contact or by aerosolization of pharyngeal secretions. It can be responsible for severe respiratory and neurological complications. The diagnosis is clinical, confirmed by serology, PCR or culture of the measles virus. Treatment is symptomatic and prevention is based on a well conducted vaccination. In severe cases, the use of vitamin A is recommended by the World Health Organization, at least in chidren. Antivirals (ribavirin) have not been shown to be effective in clinical practice. We present a severe respiratory form of measles, affecting a young immunocompetent adult.


Assuntos
Antivirais , Hospedeiro Imunocomprometido , Sarampo , Pneumonia , Adulto , Humanos , Sarampo/complicações , Pneumonia/microbiologia , Reação em Cadeia da Polimerase , Vacinação
7.
Int J Infect Dis ; 89: 62-65, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31479761

RESUMO

BACKGROUND: Achieving a high degree of diagnostic accuracy of infections in the emergency department (ED) is crucial since a delay in diagnosis can lead to increased mortality, whereas overdiagnosis can lead to antibiotic overprescription. Limited data are available as to ED diagnostic accuracy of infections. The aim of this study was to demonstrate the degree of discordance of an ED diagnosis of pneumonia in relation to an internal medicine ward's discharge diagnosis of hospitalized adults. METHODS: We reviewed the records of all adults hospitalized in internal wards from November 2017-January 2018 diagnosed with an acute infection by an ED physician. The primary outcome was the discordance degree of an ED pneumonia diagnosis compared to the internal ward discharge diagnosis. The influence comorbidities and clinical characteristics on the diagnostic discordance were also evaluated. RESULTS: The study included 875 adults; 434 were admitted with an ED diagnosis of a specific infection. Pneumonia was the most frequent ED diagnosis (n = 195, 45%), of them, 56 (29%) were discordant diagnosis in the internal ward. CONCLUSION: Interpretation of chest X-rays with the assistance of a radiologist might help in reducing overdiagnosis and minimize antibiotic overprescription, thus improving the ED diagnostic accuracy of pneumonia.


Assuntos
Antibacterianos/uso terapêutico , Erros de Diagnóstico/estatística & dados numéricos , Serviço Hospitalar de Emergência/normas , Pneumonia/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Registros Eletrônicos de Saúde , Feminino , Hospitalização , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Médicos , Pneumonia/microbiologia , Radiografia , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
8.
BMC Infect Dis ; 19(1): 698, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387541

RESUMO

BACKGROUND: Candida albicans is an opportunistic pathogen, but since it also belongs to the normal fungal flora, positive sputum culture as the solely basis for the diagnosis of invasive Candida albicans pneumonia can easily lead to excessive antifungal therapy. Therefore, identification of a pneumonia biomarker might improve diagnostic accuracy. METHODS: A rabbit model was established by inoculating 5 × 107 cfu/mL C. albicans into the trachea of 20 rabbits with 20 rabbits as control group. Infection was monitored by chest thin-layer computed tomography (CT). 2 mL blood samples were collected daily during each infection and serum levels of potential biomarkers were measured by enzyme-linked immunosorbent assay (ELISA). Seven-day post-inoculation the rabbits were sacrificed by CO2 asphyxiation and lung tissue was histopathologically examined and blood was brought to culture. Data were statistically analyzed. RESULTS: Infection became evident as early as day 3 post-inoculation. The levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble hemoglobin-haptoglobin scavenger receptor (sCD163), procalcitonin (PCT) and tumor necrosis factor-α (TNF-α) were elevated in the experimental group compared to the control (P < 0.01), whereas the levels of C-reactive protein (CRP), interleukin-6 (IL-6), IL-8 and IL-10 showed no significant differences (P > 0.05). The dynamic curves of the levels of CRP, IL-6, IL-8, IL-10, SCD163 and TNF-α in both groups demonstrated a similar trend during infection but differences between the groups was observed only in the sTREM-1 levels. Receiver-operating characteristics (ROC) curve analysis showed that the sensitivity and specificity were 85 and 80% for sTREM-1 (cut-off value: 45.88 pg/mL) and 80 and 75% for SCD163 (cut-off value: 16.44 U/mL), respectively. The values of the area under the ROC curve (AUCROC) of sTREM-1 and SCD163 were 0.882 (95% CI: 0.922-0.976) and 0.814 (95% CI: 0.678-0.950), respectively. Other markers did not exhibit significant differences. CONCLUSION: sTREM-1 and SCD163 might be suitable biomarkers for pneumonia.


Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Biomarcadores/sangue , Pneumonia/sangue , Receptores de Superfície Celular/sangue , Receptor Gatilho 1 Expresso em Células Mieloides/sangue , Animais , Proteína C-Reativa/análise , Candida albicans/patogenicidade , Candidíase/sangue , Candidíase/microbiologia , Modelos Animais de Doenças , Masculino , Pneumonia/diagnóstico , Pneumonia/microbiologia , Curva ROC , Coelhos , Sensibilidade e Especificidade , Fator de Necrose Tumoral alfa/sangue
9.
BMJ Case Rep ; 12(8)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31377717

RESUMO

We present a case of a 55-year-old Filipino man who was transferred from another institution where he was recently diagnosed with Crohn's disease but not started on any immunosuppressants. He underwent laparoscopic cholecystectomy with T-tube placement a few weeks prior to admission. On workup, abdominal CT scan was unremarkable, but blood cultures on the third hospital day grew Burkholderia cepacia Antibiotic regimen was shifted to ceftazidime and levofloxacin. The bacteraemia and febrile episodes persisted despite removal of the central line and T tube. White blood cell scan and chest CT scan showed left-sided consolidation pneumonia. Blood cultures continued to grow B. cepacia despite shifting to meropenem and trimethoprim-sulfamethoxazole. Meropenem nebulisation at 250 mg every 12 hours was added to the regimen on the third week then oral minocycline was added on the fourth week due to persistence of bacteraemia. He subsequently developed a small vegetation on the aortic valve, so amikacin was added. Fever lysed on the sixth week, but the B. cepacia bacteraemia persisted, clearing only on the 51st hospital day. The patient was discharged with a plan to continue antibiotics, including meropenem nebulisation, for 6 more weeks. On follow-up, the patient had no recurrence of fever. There was also resolution of consolidation on chest CT scan and disappearance of vegetation on echocardiography.


Assuntos
Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Infecções por Burkholderia/tratamento farmacológico , Meropeném/administração & dosagem , Pneumonia/tratamento farmacológico , Antibacterianos/uso terapêutico , Burkholderia cepacia/isolamento & purificação , Quimioterapia Combinada/métodos , Humanos , Masculino , Meropeném/uso terapêutico , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Pneumonia/microbiologia , Resultado do Tratamento
10.
Diagn Microbiol Infect Dis ; 95(3): 114843, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31416647

RESUMO

We report Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) program data for ceftaroline and comparators against isolates collected from identified lower respiratory tract sources in 2015 and 2016. MICs and susceptibility were determined using CLSI broth microdilution methodology and EUCAST breakpoints. Ceftaroline susceptibility among penicillin-resistant Streptococcus pneumoniae (MIC≥4 mg/L [nonmeningitis breakpoint]) ranged from 77.4% (Asia, 72/93) to 100% (Oceania, 16/16; Latin America, 15/15). Among MRSA, ceftaroline susceptibility ranged from 72.3% (Asia, 553/765) to 100% (Oceania, 39/39). Among ß-lactamase-positive Haemophilus influenzae, ceftaroline susceptibility ranged from 69.2% (Asia, 36/52) to 100% (Oceania, 19/19). Susceptibility to ceftaroline against non-ESBL-producing Klebsiella pneumoniae was between 91.4% (Europe, 659/721) and 100% (Oceania, 55/55) and for Escherichia coli between 85.7% (Africa/Middle East, 42/49) and 92.1% (Oceania, 35/38). Ceftaroline is not active against ESBL producers. In this study, susceptibility to ceftaroline was high among the S. pneumoniae, Staphylococcus aureus, ß-lactamase-negative H. influenzae, and ESBL-negative K. pneumoniae and E. coli collected.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Cefalosporinas/farmacologia , Pneumonia/microbiologia , Infecções Comunitárias Adquiridas/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Vigilância em Saúde Pública
11.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414743

RESUMO

BACKGROUND: We report an invasive pulmonary aspergillosis (IPA) with negative (1,3)-ß-D-glucan and dynamically elevated white blood cells combined with procalcitonin proven by bronchoalveolar lavage fluid (BALF) culture. METHODS: Appropriate laboratory tests are carried out. Chest CTs were performed to assess the lungs. The cause of infection was determined using BALF culture. RESULTS: Serum (1,3)-ß-D-glucan was negative, white blood cells and procalcitonin were significantly higher than normal. The bronchoscopy revealed obvious necrotic detritus and pseudo membrane in the trachea, left and right main bronchi, and branches. BALF culture revealed the presence of Aspergillus. CONCLUSIONS: Negative (1,3)-ß-D-glucan is not safe to rule out invasive pulmonary aspergillosis. BALF culture is critical for IPA diagnosis.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Complicações do Diabetes/diagnóstico , Aspergilose Pulmonar Invasiva/diagnóstico , Pneumonia/diagnóstico , Pró-Calcitonina/sangue , beta-Glucanas/sangue , Aspergillus/isolamento & purificação , Aspergillus/fisiologia , Complicações do Diabetes/sangue , Complicações do Diabetes/microbiologia , Diagnóstico Diferencial , Humanos , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/microbiologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/microbiologia
12.
Gastroenterology ; 157(6): 1530-1543.e4, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31445037

RESUMO

BACKGROUND & AIMS: Dysregulation of the microbiome has been associated with development of complex diseases, such as obesity and diabetes. However, no method has been developed to control disease-associated commensal microbes. We investigated whether immunization with microbial antigens, using CpG oligodeoxynucleotides and/or curdlan as adjuvants, induces systemic antigen-specific IgA and IgG production and affects development of diseases in mice. METHODS: C57BL/6 mice were given intramuscular injections of antigens (ovalbumin, cholera toxin B-subunit, or pneumococcal surface protein A) combined with CpG oligodeoxynucleotides and/or curdlan. Blood and fecal samples were collected weekly and antigen-specific IgG and IgA titers were measured. Lymph nodes and spleens were collected and analyzed by enzyme-linked immunosorbent assay for antigen-specific splenic T-helper 1 cells, T-helper 17 cells, and memory B cells. Six weeks after primary immunization, mice were given a oral, nasal, or vaginal boost of ovalbumin; intestinal lamina propria, bronchial lavage, and vaginal swab samples were collected and antibodies and cytokines were measured. Some mice were also given oral cholera toxin or intranasal Streptococcus pneumoniae and the severity of diarrhea or pneumonia was analyzed. Gnotobiotic mice were gavaged with fecal material from obese individuals, which had a high abundance of Clostridium ramosum (a commensal microbe associated with obesity and diabetes), and were placed on a high-fat diet 2 weeks after immunization with C ramosum. Intestinal tissues were collected and analyzed by quantitative real-time polymerase chain reaction. RESULTS: Serum and fecal samples from mice given injections of antigens in combination with CpG oligodeoxynucleotides and curdlan for 3 weeks contained antigen-specific IgA and IgG, and splenocytes produced interferon-gamma and interleukin 17A. Lamina propria, bronchial, and vaginal samples contained antigen-specific IgA after the ovalbumin boost. This immunization regimen prevented development of diarrhea after injection of cholera toxin, and inhibited lung colonization by S pneumoniae. In gnotobiotic mice colonized with C ramosum and placed on a high-fat diet, the mice that had been immunized with C ramosum became less obese than the nonimmunized mice. CONCLUSIONS: Injection of mice with microbial antigens and adjuvant induces antigen-specific mucosal and systemic immune responses. Immunization with S pneumoniae antigen prevented lung infection by this bacteria, and immunization with C ramosum reduced obesity in mice colonized with this microbe and placed on a high-fat diet. This immunization approach might be used to protect against microbe-associated disorders of intestine.


Assuntos
Disbiose/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade nas Mucosas , Mucosa Intestinal/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Proteínas de Bactérias/imunologia , Toxina da Cólera/imunologia , Diarreia/diagnóstico , Diarreia/imunologia , Diarreia/microbiologia , Modelos Animais de Doenças , Disbiose/microbiologia , Feminino , Vida Livre de Germes , Humanos , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Pneumonia/diagnóstico , Pneumonia/imunologia , Pneumonia/microbiologia , Índice de Gravidade de Doença
13.
BMC Res Notes ; 12(1): 497, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405369

RESUMO

OBJECTIVE: Sporadic fatal adverse events have been reported during treatment of multiple sclerosis with alemtuzumab. To provide a systematic overview, we searched the centralized European Medicines Agency database of suspected adverse reactions related to medicinal products (EudraVigilance) for fatal adverse events associated with treatment with alemtuzumab (Lemtrada®) for multiple sclerosis. Four independent reviewers with expertise on MS, clinical immunology, infectious diseases and clinical pharmacology reviewed the reports, and scored the likelihood for causality. RESULTS: We identified nine cases with a probable and one case with a possible causal relationship between alemtuzumab treatment and a fatal adverse event. Six of these patients died within one month after treatment; one from intracerebral hemorrhage, two from acute multiple organ failure and septic shock, one from listeriosis, one from pneumonia and one from agranulocytosis. Four patients died several months after administration of alemtuzumab from either autoimmune hepatitis, immune-mediated thrombocytopenia, autoimmune hemolytic anemia or agranulocytosis. Four of the 10 cases had been published previously in case reports or congress abstracts. Fatal adverse events related to treatment with alemtuzumab occur more frequently than previously published in the literature. A significant proportion occurs in the first month after treatment.


Assuntos
Agranulocitose/induzido quimicamente , Alemtuzumab/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Fatores Imunológicos/efeitos adversos , Listeriose/induzido quimicamente , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Pneumonia/induzido quimicamente , Adulto , Agranulocitose/mortalidade , Agranulocitose/patologia , Alemtuzumab/administração & dosagem , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/patologia , Evolução Fatal , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Listeriose/microbiologia , Listeriose/mortalidade , Listeriose/patologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/patologia , Esclerose Múltipla Recidivante-Remitente/patologia , Pneumonia/microbiologia , Pneumonia/mortalidade , Pneumonia/patologia
14.
BMJ Case Rep ; 12(8)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31420430

RESUMO

A male patient in his mid-60s presented with a severe pneumonia following return to the UK after travel to Crete. He was diagnosed with Legionnaire's disease (caused by an uncommon serogroup of Legionella pneumophila). He was pancytopenic on admission, and during a long stay on critical care he was diagnosed with a disseminated Aspergillus infection. Bone marrow aspiration revealed an underlying hairy cell leukaemia that undoubtedly contributed to his acute presentation and subsequent invasive fungal infection.


Assuntos
Aspergillus , Legionella pneumophila , Doença dos Legionários/microbiologia , Pneumonia/microbiologia , Doença Relacionada a Viagens , Aspergilose/microbiologia , Grécia , Humanos , Leucemia de Células Pilosas/microbiologia , Masculino , Pessoa de Meia-Idade , Reino Unido
15.
Tohoku J Exp Med ; 248(3): 209-216, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31366819

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation and may manifest as interstitial pneumonia (IP). Methotrexate (MTX) is one of the main therapeutic drugs used for RA, but MTX could cause severe side effects, including Pneumocystis jirovecii pneumonia (PCP) and IP. Owing to similar symptoms, it is sometimes difficult to discriminate MTX therapy-associated PCP (MTX-PCP) and MTX therapy-associated IP (MTX-IP). Soluble interleukin-2 receptor (sIL-2R) is considered a marker of T-cell activation, and serum sIL-2R levels are elevated in RA and PCP. This led us to hypothesize that serum sIL-2R is a potential biomarker for discriminating MTX-PCP and MTX-IP. Accordingly, we carried out a retrospective analysis of 20 MITX-PCP cases, 30 MTX-IP cases, and as controls, 16 patients with RA-associated IP (RA-IP) and 13 patients with PCP without MTX treatment (PCP group). C-reactive protein and alveolar-arterial oxygen differences were higher in the MTX-PCP group than those in the RA-IP and MTX-IP groups. Importantly, serum levels of sIL-2R in MTX-PCP were significantly higher than those in other three groups. Based on the receiver operating characteristic curve, the cut-off level of sIL-2R resulting in the highest diagnostic accuracy for MTX-PCP was 1,311.5 U/mL, discriminating between MTX-PCP and other groups with 91.7% sensitivity and 78.6% specificity. Thus, patients with MTX-PCP show a higher degree of systemic inflammation, severe hypoxemia, and increased sIL-2R levels compared with those in MTX-IP cases. In conclusion, serum sIL-2R could be a biomarker for PCP diagnosis among patients with RA under MTX therapy.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Pneumocystis carinii/fisiologia , Pneumonia/sangue , Pneumonia/complicações , Receptores de Interleucina-2/sangue , Idoso , Artrite Reumatoide/diagnóstico por imagem , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Pneumonia/microbiologia , Curva ROC , Solubilidade , Tomografia Computadorizada por Raios X
16.
Chin Med J (Engl) ; 132(16): 1894-1902, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31408445

RESUMO

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the important pathogens causing pneumonia. This study aimed to investigate the clinical characteristics and molecular epidemiology of ESBL-producing E. coli and K. pneumoniae causing pneumonia at a large teaching hospital in China. METHODS: We collected patient's clinical data and ESBL-producing E. coli and K. pneumoniae strains causing pneumonia (from December 2015 to June 2016) at a hospital in Wuhan. The susceptibilities, multi-locus sequence typing, homologous analysis, ESBL genes by polymerase chain reaction and sequencing were determined. RESULTS: A total of 59 ESBL-producing strains (31 E. coli and 28 K. pneumoniae) isolated from patients with pneumonia were analyzed. The majority of strains were isolated from patients were with hospital-acquired pneumonia (37/59, 62.7%), followed by community-acquired pneumonia (13/59, 22.0%), and ventilator-related pneumonia (9/59, 15.3%). The E. coli ST131 (9 isolates, 29.0%) and K. pneumoniae ST11 (5 isolates, 17.9%) were the predominant sub-types. The most prevalent ESBL gene was CTX-M-14, followed by SHV-77, CTX-M-3, SHV-11, and CTX-M-27. At least 33 (55.9%) of the ESBL-producing strains carried two or more ESBL genes. The ISEcp1 and IS26 were found upstream of all blaCTX-M (CTX-Ms) and of most blaSHV (SHVs) (57.6%), respectively. Moreover, three ESBL-producing K. pneumoniae ST11 strains which were resistant to carbapenems carried the blaNDM-1 and blaKPC-2, two of which also bearing blaOXA-48 were resistant to all antibiotics (including Tigecycline). CONCLUSIONS: Hospital-acquired pneumonia is more likely correlated with ESBL-producing E. coli and K. pneumoniae. ESBL-producing E. coli ST131 and multi-drug resistance ESBL-producing, as well as New Delhi metallo-ß-lactamase-1 (NDM-1) and Klebsiella pneumoniae carbapenemases-2 (KPC-2) bearing K. pneumoniae ST11 are spreading in patients with pneumonia in hospital.


Assuntos
Escherichia coli/enzimologia , Escherichia coli/patogenicidade , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/patogenicidade , Pneumonia/epidemiologia , Pneumonia/microbiologia , beta-Lactamases/metabolismo , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/transmissão , Humanos , Infecções por Klebsiella/transmissão , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , beta-Lactamases/genética
17.
Inflammation ; 42(5): 1741-1753, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31267272

RESUMO

Streptococcus pneumoniae (S. pneumoniae) and viruses are considered as primary risks of community-acquired pneumonia (CAP), and the effects of co-infection bacterial and virus in the prognosis of patients with severe CAP (SCAP) are poorly described. Therefore, this study is conducted to investigate the regulation of Beclin1-PI3K/AKT axis in reinfection of S. pneumoniae after influenza A virus in mice model of bronchoalveolar lavage fluid (BALF). Samples of sputum and BALF were collected from patients with SCAP for etiological detection. The expression of each gene was determined by RT-qPCR and western blot analysis. Influenza A/PR/8/34 and S. pneumoniae were used to establish the mice model of reinfection pneumonia. The virus quantity, expression levels of inflammatory factors, bacterial load, and myeloperoxidase (MPO) activity were tested. HE staining was applied to observe histopathology of lung tissue. The expression of Beclin1 was downregulated and the PI3K/AKT pathway was activated in viral pneumonia. In vivo experiment, the reinfection of S. pneumoniae following influenza A virus infection increased the number of S. pneumoniae population, the activity of MPO, and the expression of TNF-α, IL-6, and IFN-γ in BALF of mice. In contrast, inhibition of the PI3K/AKT pathway or overexpression of Beclin1 reduced the number of S. pneumoniae population, the activity of MPO, and the expression of TNF-α, IL-6, and IFN-γ in BALF of mice reinfected with S. pneumoniae after influenza A virus infection. Collectively, our study demonstrates that inhibition of the PI3K/AKT signaling pathway or overexpressed Beclin1 alleviates reinfection of S. pneumoniae after influenza A virus infection in SCAP.


Assuntos
Proteína Beclina-1/metabolismo , Infecções Comunitárias Adquiridas , Influenza Humana/complicações , Infecções Pneumocócicas/prevenção & controle , Pneumonia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/prevenção & controle , Infecções Comunitárias Adquiridas/virologia , Modelos Animais de Doenças , Humanos , Vírus da Influenza A , Influenza Humana/virologia , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Infecções Pneumocócicas/patologia , Infecções Pneumocócicas/virologia , Pneumonia/microbiologia , Pneumonia/prevenção & controle , Pneumonia/virologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Recidiva , Prevenção Secundária , Streptococcus pneumoniae
18.
BMC Infect Dis ; 19(1): 603, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291896

RESUMO

BACKGROUND: This study aims to investigate the pathogen distribution and drug resistance in patients with acute cerebral infarction complicated with diabetes mellitus and nosocomial pulmonary infection. METHODS: From August 2015 to December 2017, 172 pathogenic bacterial strains from patients with acute cerebral infarction complicated with diabetes mellitus and nosocomial pulmonary infection in our hospital were identified, and the drug sensitivity was analyzed. RESULTS: Among these 172 strains of pathogenic bacteria, gram negative bacteria was the main cause of pulmonary infection in hospitalized patients with acute cerebral infarction, accounting for 75.6% of all pathogens. Furthermore, 80% of diabetic patients with cerebral infarction had lung infection induced by gram negative bacteria, which was significantly higher than that in non-diabetic patients (72.2%). Moreover, the drug resistance rate in the diabetic group (68.3%) was significantly higher than that in the non-diabetic group (54.3%). Gram positive bacteria accounted for 19.1% of all pathogenic bacteria. The infection rate of gram-positive bacteria in diabetic patients with cerebral infarction was 14.7%, which was lower than that in the non-diabetic group (22.6%). The drug-resistance rate was higher in the diabetic group (45.5%) than in the non-diabetic group (28.2%). Furthermore, the fungal infection rate in patients with lung infection in these two groups was 5.3 and 5.2%, respectively, and fungi presented with high sensitivity to commonly used antifungal agents. CONCLUSION: In patients with acute cerebral infarction complicated with diabetes mellitus and nosocomial pulmonary infection, the majority of pathogens are multidrug-resistant gram negative bacilli. Pathogen culture should be conducted as soon as possible before using antibiotics, and antimicrobial agents should be reasonably used according to drug sensitivity test results.


Assuntos
Infarto Cerebral/complicações , Infecção Hospitalar/microbiologia , Complicações do Diabetes/microbiologia , Resistência Microbiana a Medicamentos , Pneumonia/microbiologia , Doença Aguda , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/microbiologia , Infecção Hospitalar/tratamento farmacológico , Complicações do Diabetes/tratamento farmacológico , Feminino , Fungos/classificação , Fungos/efeitos dos fármacos , Fungos/isolamento & purificação , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pneumonia/tratamento farmacológico
19.
Infect Immun ; 87(9)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31262980

RESUMO

Pneumonia due to Gram-negative bacteria is associated with high mortality. Acinetobacter baumannii is a Gram-negative bacterium that is associated with hospital-acquired and ventilator-associated pneumonia. Bacteria have been described to release outer membrane vesicles (OMVs) that are capable of mediating systemic inflammation. The mechanism by which A. baumannii OMVs mediate inflammation is not fully defined. We sought to investigate the roles that Toll-like receptors (TLRs) play in A. baumannii OMV-mediated pulmonary inflammation. We isolated OMVs from A. baumannii cultures and intranasally introduced the OMVs into mice. Intranasal introduction of A. baumannii OMVs mediated pulmonary inflammation, which is associated with neutrophil recruitment and weight loss. In addition, A. baumannii OMVs increased the release of several chemokines and cytokines in the mouse lungs. The proinflammatory responses were partially inhibited in TLR2- and TLR4-deficient mice compared to those of wild-type mice. This study highlights the important roles of TLRs in A. baumannii OMV-induced pulmonary inflammation in vivo.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Pneumonia/microbiologia , Vesículas Secretórias/fisiologia , Receptor 2 Toll-Like/fisiologia , Receptor 4 Toll-Like/fisiologia , Infecções por Acinetobacter/metabolismo , Animais , Proteínas da Membrana Bacteriana Externa , Quimiocinas/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos
20.
Future Microbiol ; 14: 927-939, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31333062

RESUMO

Despite the increasing availability of antibiotics with activity against pathogens that cause community-acquired pneumonia (CAP), CAP remains a major cause of morbidity, hospital admissions and re-admissions, and mortality. Lefamulin is a novel pleuromutilin antibiotic with potent in vitro activity against both typical and atypical CAP pathogens. In this review of the medical literature, we summarize the available information, including mounting clinical evidence, about lefamulin and its potential value in CAP.


Assuntos
Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Pneumonia/tratamento farmacológico , Compostos Policíclicos/farmacologia , Compostos Policíclicos/uso terapêutico , Tioglicolatos/farmacologia , Tioglicolatos/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/isolamento & purificação , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Diterpenos/efeitos adversos , Diterpenos/química , Humanos , Estrutura Molecular , Pneumonia/microbiologia , Compostos Policíclicos/efeitos adversos , Compostos Policíclicos/química , Subunidades Ribossômicas Maiores de Bactérias/efeitos dos fármacos , Tioglicolatos/efeitos adversos , Tioglicolatos/química , Resultado do Tratamento
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