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1.
PLoS One ; 15(1): e0227636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31917802

RESUMO

Serum markers that differentiate between tuberculous and non-tuberculous pneumonia would be clinically useful. However, few serum markers have been investigated for their association with either disease. In this study, serum levels of interferon gamma (IFN-γ), matrix metalloproteinases 1 and 9 (MMP-1 and MMP-9, respectively), and periostin were compared between 40 pulmonary tuberculosis (PTB) and 28 non-tuberculous pneumonia (non-PTB) patients. Diagnostic performance was assessed by analysis of receiver-operating characteristic (ROC) curves and classification trees. Serum IFN-γ and MMP-1 levels were significantly higher and serum MMP-9 levels significantly lower in PTB than in non-PTB patients (p < 0.001, p = 0.002, p < 0.001, respectively). No significant difference was observed in serum periostin levels between groups. ROC curve analysis could not determine the appropriate cut-off value with high sensitivity and specificity; therefore, a classification tree method was applied. This method identified patients with limited infiltration into three groups with statistical significance (p = 0.01), and those with MMP-1 levels < 0.01 ng/mL and periostin levels ≥ 118.8 ng/mL included only non-PTB patients (95% confidence interval 0.0-41.0). Patients with extensive infiltration were also divided into three groups with statistical significance (p < 0.001), and those with MMP-9 levels < 3.009 ng/mL included only PTB patients (95% confidence interval 76.8-100.0). In conclusion, the novel classification tree developed using MMP-1, MMP-9, and periostin data distinguished PTB from non-PTB patients. Further studies are needed to validate our cut-off values and the overall clinical usefulness of these markers.


Assuntos
Moléculas de Adesão Celular/sangue , Interferon gama/sangue , Metaloproteinase 1 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Pneumonia Bacteriana/sangue , Tuberculose Pulmonar/sangue , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico , Curva ROC , Sensibilidade e Especificidade , Tuberculose Pulmonar/diagnóstico
2.
BMC Infect Dis ; 20(1): 45, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941459

RESUMO

BACKGROUND: Acinetobacter baumannii is a gram-negative aerobic bacillus that is commonly causes of hospital-acquired infections. Community-acquired pneumonia caused by Acinetobacter baumannii (CAP-Ab) is rare but fatal if diagnosis and treatment are delayed. Conventional culture of clinical specimens is the main method for clinical diagnosis of A. baumannii infections which may suffer from limited positive rate and is time consuming. Timely and precise diagnosis of CAP-Ab remains challenging. CASE PRESENTATION: A 66-year-old man with 24 h history of acute fever and dyspnea was admitted to our hospital. He was diagnosed as severe community acquired pneumonia (CAP), septic shock, respiratory failure and acute kidney injury. Next-generation sequencing (NGS) was performed on the patient's sputum and blood, which identified numerous A. baumannii nucleotide sequences in the sample of sputum and led to the rapid diagnosis and treatment of community acquired pneumonia caused by A. baumannii. This result was confirmed by subsequent sputum culture. CONCLUSIONS: This case described that the successful application of the next generation sequencing assisting the speedy diagnosis of A. baumannii infection provides a new idea for the timely diagnosis of CAP-Ab and highlights that NGS is a promising tool in rapid etiological diagnosis of acute and severe infectious diseases.


Assuntos
Infecções por Acinetobacter/diagnóstico , Acinetobacter baumannii/genética , Infecções Comunitárias Adquiridas/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Pneumonia Bacteriana/diagnóstico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Lesão Renal Aguda/complicações , Idoso , Antibacterianos/uso terapêutico , China , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecção Hospitalar , Dispneia/complicações , Febre/complicações , Hospitalização , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/tratamento farmacológico , Insuficiência Respiratória/complicações , Choque Séptico/complicações , Escarro/microbiologia , Resultado do Tratamento
3.
Medicine (Baltimore) ; 98(38): e17215, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567977

RESUMO

The aim of the study is to explore whether monocyte-to-lymphocyte ratio (MLR) provides predictive value of the severity in patients with Klebsiella pneumonia infection (KPI).Patients in a tertiary medical center with Klebsiella pneumonia infection from 2014 to 2017 were recruited in this study. Patients with Klebsiella pneumonia infection were stratified into two groups based on the National Early Warning Score (NEWS). MLR was calculated by dividing monocytes count by lymphocytes count obtained from routine blood examination. The area under the curve (AUC) values was determined using the receiver-operating characteristic (ROC) curve. The correlation between the variables was tested with Pearson or Spearman correlation analysis. Ordinal logistic regression analysis was used to assess the relationship between MLR and the severity of Klebsiella pneumonia infection.One hundred fifty-two patients were finally enrolled for analysis. Among those, 43 (28.29%) cases had severe KPI. MLR was found to be an independent risk factor of the serious Klebsiella pneumonia infection (OR: 23.74, 95% CI: 5.41-104.11, P < .001). Besides, MLR was positively correlated with NEWS score (r = 0.57, P < .001). In the receiver-operating characteristic (ROC) curve analysis, MLR, with an optimal cut-off value of 0.665, predicted the severe coronary lesion with a sensitivity of 79.4% and specificity of 84.4%.MLR was an independent predictor of the severe Klebsiella pneumonia infection. Compared with neutrophil-to-lymphocyte ratio (NLR), MLR has a better performance to evaluate the severity of Klebsiella pneumonia infection.


Assuntos
Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae , Contagem de Leucócitos , Contagem de Linfócitos , Monócitos , Pneumonia Bacteriana/diagnóstico , Idoso , Feminino , Humanos , Infecções por Klebsiella/sangue , Infecções por Klebsiella/microbiologia , Masculino , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/microbiologia , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença
4.
Am J Med Sci ; 358(1): 33-44, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31084909

RESUMO

BACKGROUND: The optimal duration of antibiotic treatment has not been established for pneumonia patients. Some investigators reported procalcitonin (PCT)-guided antimicrobial stewardship reduces the duration of antibiotic use without increasing mortality in pneumonia patients. MATERIAL AND METHODS: We prospectively enrolled hospitalized community-acquired pneumonia or healthcare-associated pneumonia patients with PCT levels >0.20 ng/mL on admission, who were admitted between 2014 and 2017. PCT levels were measured on days 5, 8 and 11 and every 3 days thereafter if needed. Physicians were encouraged and strongly encouraged to discontinue antibiotics when PCT levels decreased below 0.20 ng/mL and 0.10 ng/mL, respectively. Those admitted between 2010 and 2014 were included in the study as historical controls. Primary endpoints were duration of antibiotic treatment and recurrence of pneumonia within 30 days after antibiotic discontinuation. RESULTS: The PCT-guided and control groups consisted of 116 patients each. Background factors including pneumonia severity and PCT levels did not differ between the 2 groups. Median duration of antibiotic treatment was 8.0 and 11 days in the PCT-guided and control groups, respectively (P < 0.001). Multivariable regression analysis revealed that PCT-guided antibiotic discontinuation (partial regression coefficient [PRC] -1.9319, P < 0.001), PCT (PRC 0.1501, P = 0.0059) and albumin (PRC -1.4398, P = 0.0096) were significantly related to duration of antibiotic treatment. Pneumonia recurrence within 30 days after antibiotic discontinuation was not statistically different between the 2 groups (4.3% vs. 6.0%, P = 0.5541). CONCLUSIONS: PCT-guided antibiotic discontinuation might be useful for shortening the duration of antibiotic treatment without increasing pneumonia recurrence.


Assuntos
Antibacterianos/administração & dosagem , Duração da Terapia , Pneumonia Bacteriana/tratamento farmacológico , Pró-Calcitonina/sangue , Idoso , Antibacterianos/uso terapêutico , Biomarcadores/sangue , Tomada de Decisão Clínica , Infecções Comunitárias Adquiridas , Infecção Hospitalar , Esquema de Medicação , Feminino , Humanos , Masculino , Pneumonia Bacteriana/sangue , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Recidiva , Resultado do Tratamento
5.
Clin Lab ; 65(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30969087

RESUMO

BACKGROUND: The differential diagnosis of pulmonary tuberculosis and bacterial community-acquired pneumonia is often a challenging phenomenon. The neutrophil to lymphocyte count ratio, a suitable indicator of inflammation, has been demonstrated to be a useful biomarker for predicting bacteremia. The main aim this study is to evaluate the role of neutrophil to lymphocyte count ratio in the differential diagnosis of pulmonary tuberculosis and bacterial Community-Acquired Pneumonia at Ayder and Mekelle hospitals, Mekelle, Ethiopia. METHODS: A hospital based cross-sectional study was conducted from February to May 2017 on a total of 146 patients at Ayder and Mekelle hospitals. After taking written informed consent, study participants were interviewed for a detailed history and 5 mL of blood was collected for hematological analysis. Pulmonary tuberculosis was diagnosed by using Ziehl-Neelsen and Gene X-pert. Community acquired pneumonia was diagnosed using sputum culture. Student's t-test, Pearson's chi-square test, and receiver operating characteristics curve analysis were used. A p-value < 0.05 was considered statistically significant. RESULTS: The neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate were significantly higher in pulmonary tuberculosis patients than bacterial community-acquired pneumonia patients. Neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate with cutoff values of ≥ 2.72 and ≥ 39, respectively, showed the highest area under the curve (AUC = 0.69; 95% CI: 0.62, 0.77). CONCLUSIONS: Neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate together at a time with their respective cutoff values gave a 69% accuracy in differentiating pulmonary tuberculosis from bacterial community-acquired pneumonia. Therefore, neutrophil to lymphocyte count ratio and erythrocyte sedimentation rate can be used in differentiating pulmonary tuberculosis from PTB patients from bacterial Community-acquired pneumonia, especially in resource-limited settings.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Contagem de Linfócitos , Neutrófilos/citologia , Pneumonia Bacteriana/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adulto , Sedimentação Sanguínea , Infecções Comunitárias Adquiridas/sangue , Estudos Transversais , Diagnóstico Diferencial , Etiópia , Feminino , Hospitalização , Humanos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Pneumonia Bacteriana/sangue , Curva ROC , Tuberculose Pulmonar/sangue , Adulto Jovem
6.
BMC Pulm Med ; 19(1): 71, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940126

RESUMO

BACKGROUND: Differentiating bacterial from viral pneumonia is important for guiding targeted management and judicious use of antibiotics. We assessed if clinical characteristics and blood inflammatory biomarkers could be used to distinguish bacterial from viral pneumonia. METHODS: Western Australian children (≤17 years) hospitalized with radiologically-confirmed community-acquired pneumonia were recruited and clinical symptoms and management data were collected. C-reactive protein (CRP), white cell counts (WCC) and absolute neutrophil counts (ANC) were measured as part of routine care. Clinical characteristics and biomarker levels were compared between cases with definite bacterial pneumonia (clinical empyema and/or bacteria detected in blood or pleural fluid), presumed viral pneumonia (presence of ≥1 virus in nasopharyngeal swab without criteria for definite bacterial pneumonia), and other pneumonia cases (pneumonia in the absence of criteria for either definite bacterial or presumed viral pneumonia). The area-under-curve (AUC) of the receiver operating characteristic (ROC) curve for varying biomarker levels were used to characterise their utility for discriminating definite bacterial from presumed viral pneumonia. For biomarkers with AUC > 0.8 (fair discriminator), Youden index was measured to determine the optimal cut-off threshold, and sensitivity, specificity, predictive values (positive and negative) were calculated. We investigated whether better discrimination could be achieved by combining biomarker values with the presence/absence of symptoms. RESULTS: From May 2015 to October 2017, 230 pneumonia cases were enrolled: 30 with definite bacterial pneumonia, 118 with presumed viral pneumonia and 82 other pneumonia cases. Differences in clinical signs and symptoms across the groups were noted; more definite bacterial pneumonia cases required intravenous fluid and oxygen supplementation than presumed viral or other pneumonia cases. CRP, WCC and ANC were substantially higher in definite bacterial cases. For a CRP threshold of 72 mg/L, the AUC of ROC was 0.82 for discriminating definite bacterial pneumonia from presumed viral pneumonia. Combining the CRP with either the presence of fever (≥38οC) or the absence of rhinorrhea improved the discrimination. CONCLUSIONS: Combining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone. Further studies are required to explore combination of biomarkers and symptoms for use as definitive diagnostic tool.


Assuntos
Biomarcadores/sangue , Pneumonia Bacteriana/diagnóstico , Pneumonia Viral/diagnóstico , Área Sob a Curva , Austrália/epidemiologia , Bactérias/genética , Bactérias/isolamento & purificação , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/diagnóstico , Feminino , Humanos , Lactente , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pneumonia Bacteriana/sangue , Pneumonia Viral/sangue , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade
7.
Respir Res ; 20(1): 54, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30866951

RESUMO

BACKGROUND: Recently, lymphoid follicle-confined and circulating CD8+ T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, which was involved in anti-virus immune response. However, the dynamics and role of circulating CXCR5-expressing CD8+ T-cells during bacterial infection is unknown. So, we asked whether CXCR5+ CD8+ T cells were also generated during bacterial infections in lower respiratory tract. METHODS: The clinical data of 65 pneumonia patients were analyzed. The patients were divided into groups as tuberculosis, bronchiectasis and community or hospital acquired pneumonia (CAP, HAP). The sputum/bronchial secretion or bronchoalveolar lavage fluid (BALF) samples were taken for microbiological examination. The procalcitonin (PCT) was used to evaluate disease severity of these groups and compared among patients. We characterized the number and phenotype (PD-1 and CD103) of CXCR5 + CD8+ T cells in the peripheral circulation by flow cytometry in all individuals and analyzed their association with the serum PCT level and disease severity. RESULTS: Patients were mainly infected with Escherichia coli, Acinetobacter baumannii, Klebsiella pneumonia (K.p), Pseudomonas aeruginosa, and Staphylococcus aureus. Of note is the finding that PCT was weakly correlated with severity of respiratory infections. Furthermore, it was revealed an increase of CXCR5-expressing CD8+ T cells in peripheral blood of un-controlled CAP and progressive HAP compared controlled CAP and HAP, respectively (P < 0.05). Strikingly, the circulating CXCR5-expressing CD8+ T-cells in K.p-infected group was higher than that non-K.p-infected group (P < 0.05). Meanwhile, the ratio of CXCR5 + CD8+/CD8 was positively correlated with PCT level (P < 0.05). In clinic, the determination of CXCR5-expressing CD8+ T-cells showed better results compared to PCT and can be useful for the prediction of exacerbation of CAP or HAP. Phenotypically, CXCR5+ CD8 + T cell expressed comparable level of inhibitory molecules PD-1 and lower CD103 compared to their CXCR5- counterparts. CONCLUSION: The circulating CXCR5-expressing CD8+ T-cell has diagnostic value for current pneumonia severity, and could act as a biomarker for identifying a bacteria-associated exacerbation. These cells may provide novel insight for the pathogenesis of pneumonia.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/diagnóstico , Receptores CXCR5/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/genética , Receptores CXCR5/genética , Adulto Jovem
8.
Molecules ; 24(3)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717123

RESUMO

Colistin is administered as its inactive prodrug colistimethate (CMS). Selection of an individualized CMS dose for each patient is difficult due to its narrow therapeutic window, especially in patients with chronic kidney disease (CKD). Our aim was to analyze CMS use in patients with CKD. Secondary objectives were to assess the safety and efficacy of CMS in this special population. In this prospective observational cohort study of CMS-treated CKD patients, CKD was defined as the presence of a glomerular filtration rate (GFR) < 60 mL/min/m² for more than 3 months. The administered doses of CMS were compared with those recently published in the literature. Worsened CKD at the end of treatment (EOT) was evaluated with the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Colistin plasma concentrations (Css) were measured using high-performance liquid chromatography. Fifty-nine patients were included. Thirty-six (61.2%) were male. The median age was 76 (45⁻95) years and baseline GFR was 36.6 ± 13.6. The daily mean CMS dosage used was compared with recently recommended doses (3.36 vs. 6.07; p < 0.001). Mean Css was 0.9 (0.2⁻2.9) mg/L, and Css was <2 mg/L in 50 patients (83.3%). Clinical cure was achieved in 43 (72.9%) patients. Worsened renal function at EOT was present in 20 (33.9%) patients and was reversible in 10 (52.6%). The CMS dosages used in this cohort were almost half those currently recommended. The mean achieved Css were under the recommended target of 2 mg/dL. Despite this, clinical cure rate was high. In this patient cohort, the incidence of nephrotoxicity was similar to those found in other recent studies performed in the general population and was reversible in 52.6%. These results suggest that CMS is safe and effective in patients with CKD and may encourage physicians to adjust dosage regimens to recent recommendations in order to optimize CMS treatments.


Assuntos
Antibacterianos/farmacocinética , Bronquite/tratamento farmacológico , Colistina/análogos & derivados , Pneumonia Bacteriana/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/sangue , Antibacterianos/farmacologia , Bronquite/sangue , Bronquite/complicações , Bronquite/fisiopatologia , Colistina/sangue , Colistina/farmacocinética , Colistina/farmacologia , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/fisiopatologia , Estudos Prospectivos , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/fisiopatologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/patogenicidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Resultado do Tratamento , Infecções Urinárias/sangue , Infecções Urinárias/complicações , Infecções Urinárias/fisiopatologia
9.
J Cardiothorac Surg ; 14(1): 26, 2019 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-30696462

RESUMO

BACKGROUND: Allograft rejection and infection are the major sources of morbidity and mortality after heart transplant. Early differential diagnosis is clinically crucial but difficult. The aim of the study was to examine serum cytokine profiles associated with each entity and whether such profiles could help to differentiate between them. METHODS: Heart allografts from Wistar rats were transplanted to Lewis rats as described by Yokoyama. Cardiac rejection and pulmonary bacterial infection were induced by Cyclosporine cessation and bacteria bronchus injection, and pathologically confirmed. Ninety serological cytokines profiles of the study objects were then simultaneously measured using a biotin label-based cytokine array. The fold change (FC) was used for relative cytokine concentration comparison analysis. RESULTS: Four cytokines in cardiac rejection group were significantly dysregulated as compared to health controls (ß -Catenin, 0.51 FC; E-Selectin, 0.62 FC; IFN-gamma, 1.87 FC; and IL-13, 0.60 FC, respectively). In pulmonary infection animals, 11 cytokines were remarkably dysregulated in comparison with the control group (CINC-3, 0.57 FC; CNTF R alpha, 0.59 FC; E-Selectin, 0.58 FC; FSL1,0.62 FC; Hepassocin, 0.64 FC; IL-2, 0.26 FC; IL-13, 0.49 FC; NGFR, 0.57 FC; RAGE, 0.50 FC; TIMP-1, 0.49 FC; and IFN-gamma, 1.77 FC, respectively). Eleven cytokines were significantly up-regulated in cardiac rejection group comparing to the pulmonary infection animals (FSL1, 2.32FC; Fractalkine, 1.65FC; GFR alpha-1, 1.64FC; IL-2, 2.72FC; IL-5, 1.60FC; MMP-2, 1.71FC; NGFR, 2.25FC; TGF-beta1, 1.58FC; TGF-beta3, 1.58FC; Thrombospondin, 1.64FC, and TIMP-1, 1.52FC, respectively). CONCLUSIONS: The current study illustrated the disease-specific serological cytokine profiles of allograft rejection and pulmonary bacterial infection after cardiac transplant. Such disease associated cytokine portraits might have the potential for early discrimination diagnosis.


Assuntos
Citocinas/sangue , Rejeição de Enxerto/etiologia , Transplante de Coração , Pneumonia Bacteriana/etiologia , Aloenxertos , Animais , Modelos Animais de Doenças , Rejeição de Enxerto/sangue , Masculino , Pneumonia Bacteriana/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Ratos , Ratos Endogâmicos Lew , Ratos Wistar
10.
Drug Chem Toxicol ; 42(3): 309-316, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30257565

RESUMO

Rimulus cinnamon is the dried twig of Cinnamomum cassia Presl. It is widely used in China for the treatment of inflammatory processes, amenorrhea, and other diseases. We aimed to study the protective effects of ethyl acetate extracts of R. cinnamon (EAE) on systemic inflammation and lung injury in endotoxin-poisoned mice. EAE was administered 5 d prior to lipopolysaccharide (LPS) challenge with 15 mg/kg LPS. The administration of EAE increased the levels of interferon-γ (IFN-γ) and decreased the levels of interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) in the serum. Additionally, EAE relieved the pathological changes in the tissues of the lungs and spleen, and significantly reduced the number of neutrophils in the lung tissues. In addition, treatment with EAE decreased the mRNA expression of the NLR family, pyrin domain-containing protein 3 (NLRP3), caspase-1, and interleukin-1ß (IL-1ß) in the lungs, as well as the expression of NLRP3, caspase-1 (p20), and pro-IL-1ß proteins. These results demonstrated the promising anti-inflammatory effects of EAE in endotoxin-poisoned mice. Furthermore, EAE could alleviate the lung injury of endotoxin-poisoned mice by antagonizing the activation of the NLRP3 inflammasome.


Assuntos
Anti-Inflamatórios/uso terapêutico , Cinnamomum aromaticum/química , Medicamentos de Ervas Chinesas/uso terapêutico , Lipopolissacarídeos/toxicidade , Lesão Pulmonar/prevenção & controle , Pneumonia Bacteriana/prevenção & controle , Acetatos/química , Animais , Anti-Inflamatórios/isolamento & purificação , Citocinas/sangue , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Lesão Pulmonar/sangue , Lesão Pulmonar/imunologia , Masculino , Camundongos Endogâmicos , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/imunologia
11.
Cytokine ; 113: 272-276, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30055898

RESUMO

BACKGROUND: The serum cytokine levels among 45 mechanically ventilated, intensive care unit (ICU)-treated severe community-acquired pneumonia (SCAP) patients with known microbial etiology in three different etiology groups were assessed. METHODS: Blood samples for C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-5, IL-6, IL-10, human interferon gamma induced protein (IP)-10, and TNF-α (tumor necrosis factor alpha) were collected at time points 0, 12, 24, 48, 72 and 96 h after study inclusion. RESULTS: There were 21 (43%) pure bacterial infections (bacterial group, BG), 5 (10%) pure viral infections (viral group, VG), and 19 (39%) mixed bacterial-viral infections (mixed group, MG) among 45 mechanically ventilated SCAP patients. CRP and PCT levels were significantly higher in the MG and values decreased with time in all groups. PCT differed also in time and group analysis (P = 0.001), the highest being in the MG. IL-5 levels were significantly higher in the VG compared to others (Ptime = 0.001, Pgroup = 0.051 and Ptimexgroup = 0.016). IL-6 and IP-10 levels decreased over time (Ptime = 0.003 and Ptime = 0.021), but there were no differences between groups. CONCLUSION: SCAP patients with viral etiology have higher IL-5 levels. Patients with mixed viral and bacterial group have higher PCT compared to other etiologies.


Assuntos
Proteína C-Reativa/metabolismo , Quimiocina CXCL10/sangue , Infecções Comunitárias Adquiridas , Interleucina-5/sangue , Interleucina-6/sangue , Pneumonia Bacteriana , Pneumonia Viral , Pró-Calcitonina/sangue , Respiração Artificial , Adulto , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/terapia , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Fatores de Tempo
12.
PLoS One ; 13(10): e0205521, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30296305

RESUMO

Platelets have been implicated in pulmonary inflammation following exposure to bacterial stimuli. The mechanisms involved in the platelet-mediated host response to respiratory bacterial infection remain incompletely understood. In this study, we demonstrate that platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) plays critical roles in a mouse model of acute bacterial pneumonia using Pseudomonas aeruginosa. Platelets are activated during P. aeruginosa infection, and mice depleted of platelets display markedly increased mortality and impaired bacterial clearance. CXCL4 deficiency impairs bacterial clearance and lung epithelial permeability, which correlate with decreased neutrophil recruitment to BALF. Interestingly, CXCL4 deficiency selectively regulates chemokine production, suggesting that CXCL4 has an impact on other chemokine expression. In addition, CXCL4 deficiency reduces platelet-neutrophil interactions in blood following P. aeruginosa infection. Further studies revealed that platelet-derived CXCL4 contributes to the P. aeruginosa-killing of neutrophils. Altogether, these findings demonstrate that CXCL4 is a vital chemokine that plays critical roles in bacterial clearance during P. aeruginosa infection through recruiting neutrophils to the lungs and intracellular bacterial killing.


Assuntos
Interações entre Hospedeiro e Microrganismos/imunologia , Fator Plaquetário 4/metabolismo , Pneumonia Bacteriana/imunologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa , Animais , Plaquetas/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Regulação da Expressão Gênica , Pulmão/imunologia , Pulmão/microbiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/imunologia , Fator Plaquetário 4/genética , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/mortalidade , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/mortalidade
13.
BMJ Case Rep ; 20182018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30262540

RESUMO

A 5-month-old baby presented with a low-grade fever and tachypnoea and was found to have right upper lobe consolidation on chest radiograph. He was admitted with the diagnosis of bronchopneumonia and the treatment protocol for pneumonia was initiated. Blood culture samples were collected, and he was started on a course of intravenous amoxicillin-clavulanate. Blood culture results displayed pansensitive Gemella morbillorum bacteraemia and he was continued on intravenous antibiotic to which he responded in a short period and was discharged in good condition on the fourth day.


Assuntos
Infecções por Bactérias Gram-Positivas/diagnóstico , Pneumonia Bacteriana/diagnóstico , Administração Intravenosa , Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Antibacterianos/administração & dosagem , Bacteriemia/sangue , Gemella/isolamento & purificação , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Lactente , Pulmão/diagnóstico por imagem , Masculino , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/tratamento farmacológico
14.
Sci Rep ; 8(1): 14250, 2018 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-30250258

RESUMO

Obesity has been identified as a risk factor for adverse outcomes of various diseases. However, information regarding the difference between the response of obese and normal subjects to pulmonary inflammation is limited. Mice were fed with the control or high-fat diet to establish the lean and diet-induced obese (DIO) mice. Escherichia coli was intranasally instilled to reproduce non-fatal acute pneumonia model. After infection, serum samples and lung tissues were obtained at 0, 12, 24, and 72 h. DIO mice exhibited increased serum triglyceride (TG) and total cholesterol (TC) contents as well as pulmonary resistin, IL-6, and leptin levels compared with lean mice. E. coli infection caused an acute suppurative inflammation in the lung with increased lung index and serum TG and TC contents; elevated pulmonary tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-8, and leptin levels; and oxidative stress in mice. Interestingly, almost all the above-mentioned parameters peaked at 12 h after infection in the lean-E. coli group but after 12 h in the DIO-E. coli group. These results indicated that the DIO mice presented a delayed inflammatory response and oxidative stress in non-fatal acute pneumonia induced by E. coli infection.


Assuntos
Inflamação/sangue , Lesão Pulmonar/sangue , Obesidade/sangue , Pneumonia Bacteriana/sangue , Animais , Colesterol/sangue , Citocinas/sangue , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Escherichia coli/patogenicidade , Humanos , Inflamação/microbiologia , Inflamação/fisiopatologia , Interleucinas/sangue , Leptina/sangue , Lesão Pulmonar/microbiologia , Lesão Pulmonar/fisiopatologia , Camundongos , Obesidade/microbiologia , Obesidade/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/fisiopatologia , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa
15.
Ann Hematol ; 97(11): 2061-2070, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30091024

RESUMO

Neutropenic patients with hematological diseases are prone to severe infections. Granulocyte transfusion therapy (GTX) is considered as a logical therapeutic approach for these problems. However, the efficacy and complications of GTX have not been well identified. We retrospectively analyzed the clinical outcomes of GTX therapy in our hospital from 2009 to 2015. After 117 granulocyte transfusions for 47 patients, 72.3% of these patients' infections were effectively improved, and the overall survival rates at 30 and 120 days were 66.0 and 57.5%, respectively. The patients who experienced neutrophil recovery within 10 days after their therapy initiation had a better response and long-term survival period (14/15, 93.3%, vs 20/32, 62.5%, P = 0.037). Higher-dose granulocytes (> 2.55 × 108/kg) might improve the effective rate of infection in the patients who had more than 10 days neutrophil recovery time (17/23, 73.9%, vs 3/9, 33.3%, P = 0.049). In addition, GTX benefited the patients who suffered from pulmonary bacterial infections (16/20, 80%) compared with the bloodstream infection group (7/12, 58.3%) and skin or mucous infection group (1/5, 20%). The primary data showed that GTX did not affect the incidence of graft-versus-host disease (GVHD) and cytomegalovirus viremia when patients received further HSCT treatment. Collectively, GTX was an adjunct treatment modality for severely neutropenic patients who were likely to experience hematopoietic recovery. More randomized trials are needed to verify the efficacy and complications of GTX therapy.


Assuntos
Transfusão de Leucócitos , Neutropenia/terapia , Pneumonia Bacteriana/terapia , Dermatopatias Bacterianas/terapia , Adolescente , Adulto , Idoso , Criança , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutropenia/sangue , Neutropenia/complicações , Neutropenia/microbiologia , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/etiologia , Pneumonia Bacteriana/microbiologia , Estudos Retrospectivos , Dermatopatias Bacterianas/sangue , Dermatopatias Bacterianas/etiologia , Dermatopatias Bacterianas/microbiologia , Taxa de Sobrevida
16.
Arterioscler Thromb Vasc Biol ; 38(8): 1772-1784, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29930006

RESUMO

Objective- Nbeal2-/- mice, a model of human gray platelet syndrome, have reduced neutrophil granularity and impaired host defense against systemic Staphylococcus aureus infection. We here aimed to study the role of Nbeal2 deficiency in both leukocytes and platelets during gram-negative pneumonia and sepsis. Approach and Results- We studied the role of Nbeal2 in platelets and leukocytes during murine pneumonia and sepsis by Klebsiella pneumoniae. Apart from platelet α-granule deficiency and reduced neutrophil granularity, also monocyte granularity was reduced in Nbeal2-/- mice, whereas plasma levels of MPO (myeloperoxidase), elastase, NGAL (neutrophil gelatinase-associated lipocalin), and MMP-9 (matrix metalloproteinase 9), and leukocyte CD11b expression were increased. Nbeal2-/- leukocytes showed unaltered in vitro antibacterial response and phagocytosis capacity against Klebsiella, and unchanged reactive nitrogen species and cytokine production. Also during Klebsiella pneumonia and sepsis, Nbeal2-/- mice had similar bacterial growth in lung and distant body sites, with enhanced leukocyte migration to the bronchoalveolar space. Despite similar infection-induced inflammation, organ damage was increased in Nbeal2-/- mice, which was also seen during endotoxemia. Platelet-specific Nbeal2 deficiency did not influence leukocyte functions, indicating that Nbeal2 directly modifies leukocytes. Transfusion of Nbeal2-/- but not of Nbeal2+/+ platelets into thrombocytopenic mice was associated with bleeding in the lung but similar host defense, pointing at a role for platelet α-granules in maintaining vascular integrity but not host defense during Klebsiella pneumosepsis. Conclusions- These data show that Nbeal2 deficiency-resulting in gray platelet syndrome-affects platelets, neutrophils, and monocytes, with intact host defense but increased organ damage during gram-negative pneumosepsis.


Assuntos
Plaquetas/metabolismo , Proteínas Sanguíneas/deficiência , Síndrome da Plaqueta Cinza/metabolismo , Infecções por Klebsiella/metabolismo , Klebsiella pneumoniae/patogenicidade , Insuficiência de Múltiplos Órgãos/metabolismo , Pneumonia Bacteriana/metabolismo , Sepse/metabolismo , Animais , Plaquetas/microbiologia , Proteínas Sanguíneas/genética , Antígeno CD11b/sangue , Modelos Animais de Doenças , Feminino , Síndrome da Plaqueta Cinza/sangue , Síndrome da Plaqueta Cinza/genética , Interações Hospedeiro-Patógeno , Infecções por Klebsiella/sangue , Infecções por Klebsiella/genética , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/crescimento & desenvolvimento , Lipocalina-2/sangue , Masculino , Metaloproteinase 9 da Matriz/sangue , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/metabolismo , Monócitos/microbiologia , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/genética , Insuficiência de Múltiplos Órgãos/microbiologia , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Elastase Pancreática/sangue , Peroxidase/sangue , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Transfusão de Plaquetas , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/genética , Pneumonia Bacteriana/microbiologia , Sepse/sangue , Sepse/genética , Sepse/microbiologia
17.
BMC Nephrol ; 19(1): 138, 2018 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-29902982

RESUMO

BACKGROUND: Severe infections are common complications of immunosuppressive treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal involvement. We investigated the clinical characteristics and risk factors of severe infection in Chinese patients with AAV after immunosuppressive therapy. METHODS: A total of 248 patients with a new diagnosis of ANCA-associated vasculitis were included in this study. The incidence, time, site, and risk factors of severe infection by the induction therapies were analysed. Multivariate Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS: A total of 103 episodes of severe infection were identified in 86 (34.7%, 86/248) patients during a median follow-up of 15 months. The incidence of infection during induction therapy was 38.5% for corticosteroids (CS), 39.0% for CS+ intravenous cyclophosphamide (IV-CYC), 33.8% for CS+ mycophenolate mofetil and 22.5% for CS + tripterygium glycosides, 76 (73.8%) infection episodes occurred within 6 months, while 66 (64.1%) occurred within 3 months. Pneumonia (71.8%, 74/103) was the most frequent type of infection, and the main pathogenic spectrum included bacteria (78.6%), fungi (12.6%), and viruses (8.7%). The risk factors associated with infection were age at the time of diagnosis (HR = 1.003, 95% CI = 1.000-1.006), smoking (HR = 2.338, 95% CI = 1.236-4.424), baseline secrum creatinine (SCr) ≥5.74 mg/dl (HR = 2.153, 95% CI = 1.323-3.502), CD4+ T cell< 281 µl (HR = 1.813, 95% CI = 1.133-2.900), and intravenous cyclophosphamide regimen (HR = 1.951, 95% CI =1.520-2.740). Twelve (13.9%) patients died of severe pneumonia. CONCLUSION: The infection rate during induction therapy was high in patients with AAV. Bacterial pneumonia was the main type of infection encountered. Age at the time of diagnosis, smoking, baseline SCr ≥5.74 mg/dl, CD4+ T cell< 281 µl, and IV-CYC therapy were identified as risk factors for infection.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Imunossupressores/uso terapêutico , Pneumonia Bacteriana/epidemiologia , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Estudos de Coortes , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/diagnóstico , Estudos Retrospectivos , Fatores de Risco
18.
Proteomics Clin Appl ; 12(6): e1800030, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29785832

RESUMO

PURPOSE: Etiological diagnosis of pediatric patients with community-acquired pneumonia is difficult. For therapy, one of the major problems is the difficulty in separating bacterial pneumonia which would benefit from antibiotics from nonbacterial pneumonia. Therefore, to identify potential biomarkers for distinguishing nonbacterial pneumonia from bacterial pneumonia are sought . EXPERIMENTAL DESIGN: Lectin microarray containing 91 lectins is used to screen serums from pediatric patients with pneumonia. Lectin-based pull-down assay combined with LC-MS/MS is used to identify the potential biomarkers. RESULTS: SNA-I, a lectin binding preferentially to α2-6 linked sialic acid residues, shows higher binding signals (near 42 kDa) in the mycoplasma pneumonia group, when compared with the other groups. A total of 18 proteins are identified with LC-MS/MS. By western blot analysis, the authors confirm that the expression of haptoglobin-related protein (HPR) is elevated in pediatric patients with pneumonia compared with normal children (p < 0.001). Furthermore, HPR is higher in the mycoplasma pneumonia group (p < 0.01) and the viral pneumonia group (p < 0.05), when compared with the bacterial pneumonia group. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that HPR is a potential serologic biomarker which can differentiate between bacterial pneumonia and nonbacterial pneumonia. Detection of serum HPR might be useful for clinical diagnosis.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores/sangue , Pneumonia Bacteriana/sangue , Pneumonia/sangue , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Haptoglobinas , Humanos , Lactente , Lectinas/sangue , Masculino , Espectrometria de Massas , Análise em Microsséries/métodos , Ácido N-Acetilneuramínico/genética , Lectinas de Plantas/genética , Pneumonia/patologia , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/patologia , Ligação Proteica , Proteínas Inativadoras de Ribossomos/genética
19.
J Infect Chemother ; 24(8): 602-609, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29628384

RESUMO

PURPOSE: This study aimed to elucidate factors related to 30-day mortality of pneumonia occurring outside hospital by comprehensively analyzing data considered relevant to prognosis. METHODS: Data considered relevant to prognosis were retrospectively examined from clinical charts and chest X-ray images of all patients with pneumonia occurring outside hospital admitted to our hospital from 2010 to 2016. The primary outcome was 30-day mortality. RESULTS: Data were collected from 534 patients (317 community-acquired pneumonia and 217 nursing- and healthcare associated pneumonia patients; 338 men (63.3%); mean age, 76.2 years-old). Eighty-three patients (9.9%) died from pneumonia within 30 days from the date of admission. The numbers of patients with pneumonia severity index (PSI) classes of I/II/III/IV/V and age, dehydration, respiratory failure, orientation disturbance, pressure (A-DROP) scores of 0/1/2/3/4/5 were 29/66/127/229/83, and 71/107/187/132/30/7, respectively. Mean (standard deviation) body mass index (BMI), serum albumin, blood procalcitonin, white blood cell and C-reactive protein were 20.00 (4.12) kg/m2, 3.16 (0.60) g/dL, 3.69 (13.15) ng/mL, 11559.4 (5656.9)/mm3, and 10.92 (8.75) mg/dL, respectively. Chest X-ray images from 152 patients exhibited a pneumonia shadow over a quarter of total lung field. Logistic regression analysis revealed that PSI class or A-DROP score, BMI, serum albumin, and extent of pneumonia shadow were related to 30-day mortality. Receiver operating characteristics curve analysis revealed that serum albumin was superior to PSI class or A-DROP score for predicting 30-day mortality. CONCLUSION: Serum albumin is not less important than PSI class or A-DROP score for predicting 30-day mortality in hospitalized patients with pneumonia occurring outside hospital.


Assuntos
Infecções Comunitárias Adquiridas/sangue , Infecção Hospitalar/sangue , Pneumonia Bacteriana/sangue , Albumina Sérica/análise , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Proteína C-Reativa/análise , Calcitonina/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/mortalidade , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/mortalidade , Feminino , Humanos , Japão/epidemiologia , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/mortalidade , Prognóstico , Curva ROC , Radiografia , Estudos Retrospectivos , Índice de Gravidade de Doença
20.
Drug Deliv ; 25(1): 909-915, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29649952

RESUMO

The aim of this study was to prepare cefquinome-loaded polylactic acid microspheres and to evaluate their in vitro and in vivo characteristics and pharmacodynamics for the therapy of pneumonia in a rat model. Microspheres were prepared using a 0.7 mm two-fluid nozzle spray drier in one step resulting in spherical and smooth microspheres of uniform size (9.8 ± 3.6 µm). The encapsulation efficiency and drug loading of cefquinome were 91.6 ± 2.6% and 18.7 ± 1.2%, respectively. In vitro release of cefquinome from the microspheres was sustained for 36 h. Cefquinome-loaded polylactic acid microspheres as a drug delivery system was successful for clearing experimental Klebsiella pneumonia lung infections. A decrease in inflammatory cells and an inhibition of inflammatory cytokines TNF-α, IL-1ß and IL-8 after microspheres treatment was found. Changes in cytokine levels and types are secondary manifestations of drug bactericidal effects. Rats were considered to be microbiologically cured because the bacterial load was less than 100 CFU/g. These results also indicated that the spray-drying method of loading therapeutic drug into polylactic acid microspheres is a straightforward and safe method for lung-targeting therapy in animals.


Assuntos
Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Portadores de Fármacos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pneumonia Bacteriana/tratamento farmacológico , Poliésteres/química , Animais , Antibacterianos/química , Carga Bacteriana , Cefalosporinas/química , Modelos Animais de Doenças , Composição de Medicamentos , Liberação Controlada de Fármacos , Interações Hospedeiro-Patógeno , Mediadores da Inflamação/sangue , Interleucina-1beta/sangue , Interleucina-8/sangue , Infecções por Klebsiella/sangue , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/patologia , Klebsiella pneumoniae/patogenicidade , Pulmão/microbiologia , Pulmão/patologia , Masculino , Microesferas , Tamanho da Partícula , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/patologia , Ratos Wistar , Propriedades de Superfície , Tecnologia Farmacêutica/métodos , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue
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