RESUMO
Neutrophils are the first leukocytes to be recruited to sites of inflammation in response to chemotactic factors released by activated macrophages and pulmonary epithelial and endothelial cells in bacterial pneumonia, a common cause of acute respiratory distress syndrome (ARDS). Although neutrophilic inflammation facilitates the elimination of pathogens, neutrophils also may cause bystander tissue injury. Even though the presence of neutrophils in alveolar spaces is a key feature of acute lung injury and ARDS especially from pneumonia, their contribution to the pathogenesis of lung injury is uncertain. The goal of this study was to elucidate the role of neutrophils in a clinically relevant model of bacterial pneumonia. We investigated the effect of reducing neutrophils in a mouse model of pneumococcal pneumonia treated with antibiotics. Neutrophils were reduced with anti-lymphocyte antigen 6 complex locus G6D (Ly6G) monoclonal antibody 24 h before and immediately preceding infection. Mice were inoculated intranasally with Streptococcus pneumoniae and received ceftriaxone 12 h after bacterial inoculation. Neutrophil reduction in mice treated with ceftriaxone attenuated hypoxemia, alveolar permeability, epithelial injury, pulmonary edema, and inflammatory biomarker release induced by bacterial pneumonia, even though bacterial loads in the distal air spaces of the lung were modestly increased as compared with antibiotic treatment alone. Thus, when appropriate antibiotics are administered, lung injury in the early phase of bacterial pneumonia is mediated in part by neutrophils. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense.NEW & NOTEWORTHY Neutrophil accumulation is a key feature of ARDS, but their contribution to the pathogenesis is still uncertain. We investigated the effect of reducing neutrophils in a clinically relevant mouse model of pneumococcal pneumonia treated with antibiotics. When appropriate antibiotics were administered, neutrophil reduction with Ly6G antibody markedly attenuated lung injury and improved oxygenation. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense.
Assuntos
Camundongos Endogâmicos C57BL , Neutrófilos , Pneumonia Pneumocócica , Animais , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/patologia , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Camundongos , Streptococcus pneumoniae/patogenicidade , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/microbiologia , Modelos Animais de Doenças , Pulmão/patologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Lesão Pulmonar/patologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/tratamento farmacológico , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/imunologia , MasculinoRESUMO
Pneumonia caused by Streptococcus pneumoniae is a leading cause of death worldwide. A growing body of evidence indicates that the successful treatment of bacterial infections results from synergy between antibiotic-mediated direct antibacterial activity and the host's immune defenses. However, the mechanisms underlying the protective immune responses induced by amoxicillin, a ß-lactam antibiotic used as the first-line treatment of S. pneumoniae infections, have not been characterized. A better understanding of amoxicillin's effects on host-pathogen interactions might facilitate the development of other treatment options. Given the crucial role of neutrophils in the control of S. pneumoniae infections, we decided to investigate amoxicillin's impact on neutrophil development in a mouse model of pneumococcal superinfection. A single therapeutic dose of amoxicillin almost completely eradicated the bacteria and prevented local and systemic inflammatory responses. Interestingly, in this context, amoxicillin treatment did not impair the emergency granulopoiesis triggered in the bone marrow by S. pneumoniae. Importantly, treatment of pneumonia with amoxicillin was associated with a greater mature neutrophil count in the bone marrow; these neutrophils had specific transcriptomic and proteomic profiles. Furthermore, amoxicillin-conditioned, mature neutrophils in the bone marrow had a less activated phenotype and might be rapidly mobilized in peripheral tissues in response to systemic inflammation. Thus, by revealing a novel effect of amoxicillin on the development and functions of bone marrow neutrophils during S. pneumoniae pneumonia, our findings provide new insights into the impact of amoxicillin treatment on host immune responses.
Assuntos
Infecções Pneumocócicas , Pneumonia Pneumocócica , Camundongos , Animais , Pneumonia Pneumocócica/tratamento farmacológico , Neutrófilos , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Medula Óssea , Pulmão , Proteômica , Streptococcus pneumoniae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/microbiologiaRESUMO
Background: Necrotizing pneumonia rarely occurs in children, but when it does it can be complicated by bronchopleural fistula, empyema, pneumothorax, sepsis, and acute respiratory distress syndrome (ARDS). Antimicrobial therapy is the cornerstone of its management; however, surgery is necessary in some cases. Ideally, surgical interventions are kept to a minimum, but this is not always possible if there is a mass effect from air and fluid in the pleural space, pulmonary necrosis leading to massive hemoptysis, uncontrolled sepsis, or difficulties with assisted ventilation. Case Presentation: Herein we present a patient with refractory pyopneumothorax and ARDS due to pneumococcal necrotizing pneumonia complicated by a bronchopleural fistula. The patient's clinical condition deteriorated despite antibiotics, surgical drainage, and assisted ventilation. Owing to pneumothorax with a high percentage of air leakage, bilateral diffuse collapse of the lungs, and insufficient oxygenation, surgical treatment was considered, but because of the patient's lack of tolerance for surgery due to hemodynamic reasons and the complications associated with surgery, medical treatment was determined to be more appropriate. Surfactant treatment was administered to the patient, resulting in significant clinical improvement. Conclusion: To the best of our knowledge, this is the first report of the use of surfactant to treat ARDS due to necrotizing pneumonia. Based on the presented case, we think surfactant can be considered as a salvage treatment for such patients.
Assuntos
Fístula Brônquica , Empiema Pleural , Doenças Pleurais , Pneumonia Necrosante , Pneumonia Pneumocócica , Pneumotórax , Síndrome do Desconforto Respiratório , Sepse , Antibacterianos/uso terapêutico , Fístula Brônquica/complicações , Fístula Brônquica/cirurgia , Criança , Empiema Pleural/complicações , Empiema Pleural/tratamento farmacológico , Humanos , Doenças Pleurais/complicações , Doenças Pleurais/tratamento farmacológico , Pneumonia Necrosante/complicações , Pneumonia Necrosante/tratamento farmacológico , Pneumonia Pneumocócica/complicações , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/tratamento farmacológico , Pneumotórax/complicações , Pneumotórax/tratamento farmacológico , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/tratamento farmacológico , Sepse/complicações , Sepse/tratamento farmacológico , Streptococcus pneumoniae , TensoativosRESUMO
Streptococcus pneumonia is classified as a gram-positive bacterial pathogen that causes asymptomatic or symptomatic respiratory infections. This study aimed to evaluate the effects of designed encapsulated saponin by ferritin nanoparticles in the healing progression of experimental bacterial pneumonia. The saponin encapsulated by ferritin followed the disassembly-reassembly process. Pneumonia was induced by the preparation of Streptococcus pneumonia. A total of 50 NMRI mice were divided into control, pneumonia, pneumonia + ferritin, pneumonia + saponin, and pneumonia + encapsulated saponin by ferritin nanoparticles (Nano Saponin) groups. ELISA, Real-time PCR, and Western blotting were used to measure sera IL-4 level, tumor necrosis factor-alpha (Tnf-α), and protein cyclooxygenase-2 (COX-2) gene expression, respectively. COX-2 protein expression, Tnf-α gene expression, and serum levels of IL-4 reduced compared to the pneumonia group. The histopathology results revealed that the rates of inflammation, mucus secretion, pulmonary hemorrhage, thickening of the alveoli wall, and secretion of inflammatory cells were lower in the Nano Saponin group than in the other groups. This study suggests that Glycyrrhiza glabra saponin and encapsulated saponin by ferritin nanoparticles oral consumption with anti-Tnf-α effect besides decreasing protein expression of COX-2 allows mice with pneumonia to recover.
Assuntos
Nanopartículas , Pneumonia Pneumocócica , Pneumonia , Saponinas , Camundongos , Animais , Pneumonia Pneumocócica/tratamento farmacológico , Ciclo-Oxigenase 2/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ferritinas , Interleucina-4/metabolismo , Inibidores do Fator de Necrose Tumoral , Pneumonia/patologiaRESUMO
BACKGROUND Increased susceptibility to bacterial infections is a hallmark of multiple myeloma (MM). Invasive infections with Streptococcus pneumoniae may be the first manifestation of underlying MM. Clinicians treating patients with invasive S. pneumoniae infections may consider searching for underlying MM in the presence of certain diagnostic findings. CASE REPORT A previously healthy 60-year-old man was referred from his general physician because of fever, cough, and chills despite treatment with clarithromycin. The patient had experienced night sweats, weight loss, and recurrent episodes of fever and cough during the last 3 months. Examination was significant for left-sided pulmonary rales. A chest X-ray showed a retrocardiac consolidation of the left lower lobe. The patient was started on empirical antimicrobial therapy for community-acquired pneumonia. Subsequently, blood and sputum cultures were positive for S. pneumoniae. Given the history of night sweats and weight loss, the discrepancy between elevated total protein and low albumin levels, and the diagnosis of pneumococcal bacteremia, multiple myeloma (MM) was suspected and confirmed by immunofixation and bone marrow biopsy. CONCLUSIONS This case showed that clinicians should be vigilant for features of MM, which are encountered during history (e.g., weight loss, bone pain) or routine laboratory workup (e.g., unexplained anemia, renal failure, hypercalcemia, or a discrepancy between elevated total protein and low albumin levels) in elderly patients presenting with invasive pneumococcal disease.
Assuntos
Bacteriemia , Mieloma Múltiplo , Infecções Pneumocócicas , Pneumonia Pneumocócica , Idoso , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Pneumonia Pneumocócica/complicações , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/tratamento farmacológico , Streptococcus pneumoniaeRESUMO
Current treatments for pneumonia (PNA) are focused on the pathogens. Mortality from PNA-induced acute lung injury (PNA-ALI) remains high, underscoring the need for additional therapeutic targets. Clinical and experimental evidence exists for potential sex differences in PNA survival, with males having higher mortality. In a model of severe pneumococcal PNA, when compared with male mice, age-matched female mice exhibited enhanced resolution characterized by decreased alveolar and lung inflammation and increased numbers of Tregs. Recognizing the critical role of Tregs in lung injury resolution, we evaluated whether improved outcomes in female mice were due to estradiol (E2) effects on Treg biology. E2 promoted a Treg-suppressive phenotype in vitro and resolution of PNA in vivo. Systemic rescue administration of E2 promoted resolution of PNA in male mice independent of lung bacterial clearance. E2 augmented Treg expression of Foxp3, CD25, and GATA3, an effect that required ERß, and not ERα, signaling. Importantly, the in vivo therapeutic effects of E2 were lost in Treg-depleted mice (Foxp3DTR mice). Adoptive transfer of ex vivo E2-treated Tregs rescued Streptococcus pneumoniae-induce PNA-ALI, a salutary effect that required Treg ERß expression. E2/ERß was required for Tregs to control macrophage proinflammatory responses. Our findings support the therapeutic role for E2 in promoting resolution of lung inflammation after PNA via ERß Tregs.
Assuntos
Estradiol/farmacologia , Receptor beta de Estrogênio/metabolismo , Pneumonia Pneumocócica/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Transferência Adotiva , Animais , Modelos Animais de Doenças , Estradiol/metabolismo , Receptor beta de Estrogênio/deficiência , Receptor beta de Estrogênio/genética , Feminino , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/metabolismo , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/imunologia , Alvéolos Pulmonares/patologia , Fatores Sexuais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: Streptococcus pneumoniae urinary antigen (u-Ag) testing has recently gained attention in the early diagnosis of severe and critical acute respiratory syndrome coronavirus-2/pneumococcal co-infection. The aim of this study is to assess the effectiveness of Streptococcus pneumoniae u-Ag testing in coronavirus disease 2019 (COVID-19) patients, in order to assess whether pneumococcal co-infection is associated with different mortality rate and hospital stay in these patients. MATERIALS AND METHODS: Charts, protocols, mortality, and hospitalization data of a consecutive series of COVID-19 patients admitted to a tertiary hospital in northern Italy during COVID-19 outbreak were retrospectively reviewed. All patients underwent Streptococcus pneumoniae u-Ag testing to detect an underlying pneumococcal co-infection. Covid19+/u-Ag+ and Covid19+/u-Ag- patients were compared in terms of overall survival and length of hospital stay using chi-square test and survival analysis. RESULTS: Out of 575 patients with documented pneumonia, 13% screened positive for the u-Ag test. All u-Ag+ patients underwent treatment with Ceftriaxone and Azithromycin or Levofloxacin. Lopinavir/Ritonavir or Darunavir/Cobicistat were added in 44 patients, and hydroxychloroquine and low-molecular-weight heparin (LMWH) in 47 and 33 patients, respectively. All u-Ag+ patients were hospitalized. Mortality was 15.4% and 25.9% in u-Ag+ and u-Ag- patients, respectively (p = 0.09). Survival analysis showed a better prognosis, albeit not significant, in u-Ag+ patients. Median hospital stay did not differ among groups (10 vs. 9 days, p = 0.71). CONCLUSIONS: The routine use of Streptococcus pneumoniae u-Ag testing helped to better target antibiotic therapy with a final trend of reduction in mortality of u-Ag+ COVID-19 patients having a concomitant pneumococcal infection. Randomized trials on larger cohorts are necessary in order to draw definitive conclusion.
Assuntos
Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Coinfecção/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Mortalidade Hospitalar , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Antígenos de Bactérias/urina , Azitromicina/uso terapêutico , Betacoronavirus , COVID-19 , Ceftriaxona/uso terapêutico , Cobicistat/uso terapêutico , Coinfecção/urina , Infecções por Coronavirus/complicações , Estudos Transversais , Darunavir/uso terapêutico , Combinação de Medicamentos , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Tempo de Internação/estatística & dados numéricos , Levofloxacino/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Pandemias , Pneumonia Pneumocócica/complicações , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/urina , Pneumonia Viral/complicações , Estudos Retrospectivos , Ritonavir/uso terapêutico , SARS-CoV-2 , Streptococcus pneumoniae/imunologia , Tratamento Farmacológico da COVID-19RESUMO
Streptococcus pneumoniae is often isolated from patients with community-acquired pneumonia. Antibiotics are the primary line of treatment for pneumococcal pneumonia; however, rising antimicrobial resistance is becoming more prevalent. Hinokitiol, which is isolated from trees in the cypress family, has been demonstrated to exert antibacterial activity against S. pneumoniae in vitro regardless of antimicrobial resistance. In this study, the efficacy of hinokitiol was investigated in a mouse pneumonia model. Male 8-week-old BALB/c mice were intratracheally infected with S. pneumoniae strains D39 (antimicrobial susceptible) and NU4471 (macrolide resistant). After 1 h, hinokitiol was injected via the tracheal route. Hinokitiol significantly decreased the number of S. pneumoniae in the bronchoalveolar lavage fluid (BALF) and the concentration of pneumococcal DNA in the serum, regardless of whether bacteria were resistant or susceptible to macrolides. In addition, hinokitiol decreased the infiltration of neutrophils in the lungs, as well as the concentration of inflammatory cytokines in the BALF and serum. Repeated hinokitiol injection at 18 h intervals showed downward trend in the number of S. pneumoniae in the BALF and the concentration of S. pneumoniae DNA in the serum with the number of hinokitiol administrations. These findings suggest that hinokitiol reduced bacterial load and suppressed excessive host immune response in the pneumonia mouse model. Accordingly, hinokitiol warrants further exploration as a potential candidate for the treatment of pneumococcal pneumonia.
Assuntos
Anti-Infecciosos/farmacologia , Monoterpenos/farmacologia , Pneumonia Pneumocócica/patologia , Streptococcus pneumoniae/isolamento & purificação , Tropolona/análogos & derivados , Animais , Anti-Infecciosos/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Quimiocina CXCL1/sangue , Quimiocina CXCL1/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Farmacorresistência Bacteriana , Interleucina-6/sangue , Interleucina-6/metabolismo , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Monoterpenos/uso terapêutico , Infiltração de Neutrófilos , Neutrófilos/citologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/patogenicidade , Tropolona/farmacologia , Tropolona/uso terapêuticoRESUMO
BACKGROUND: In the context of the COVID-19 pandemic the risk of misdiagnosis of other causes of respiratory infection is likely. In this work we aim to describe the clinical characteristics, treatment and outcome of pneumococcal infection in COVID-19 patients. PATIENTS AND METHODS: Every COVID-19 patient presenting with concomitant pneumococcal pneumonia during March 2020 in a tertiary teaching Hospital In Barcelona, Spain. RESULTS: Five patients with PCR confirmed COVID19 or clinical and radiological suspicion were diagnosed of pneumococcal infection. In all cases chest X-ray were abnormal, with unilateral or bilateral infiltrates. Procalcitonin showed to be not sensitive enough to detect pneumococcal infection. Antibiotherapy was promptly started in all five cases with subsequent satisfactory evolution. CONCLUSION: International guidelines do not include the universal screening for bacterial co-infection. Radiological pattern of COVID-19 can be indistinguishable from that of pneumococcus pneumonia and frequency of co-infection is not well stablished, therefore clinicians should be aware of the possible SARS-CoV-2-pneumococcus association to avoid misdiagnosis and delay antibiotic therapy.
Assuntos
COVID-19/complicações , Coinfecção/complicações , Pneumonia Pneumocócica/complicações , SARS-CoV-2 , Superinfecção/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Biomarcadores/sangue , Coinfecção/diagnóstico , Feminino , Humanos , Masculino , Pneumonia Pneumocócica/diagnóstico por imagem , Pneumonia Pneumocócica/tratamento farmacológico , Pró-Calcitonina/sangue , Espanha , Superinfecção/diagnóstico , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Shen-ling-bai-zhu-san (SLBZS) regulates inflammation and gut microbiota which are associated with Streptococcus pneumoniae (Spn)-induced pneumonia. So, we studied the therapeutic effect of SLBZS and evaluated whether gut microbiota is associated with the effects of SLBZS in improving Spn-induced pneumonia. METHODS: Spn-induced pneumonia NIH mice were treated by SLBZS and cefixime. A CT scan was performed and Myeloperoxidase (MPO) activity in lung homogenates was determined using the MPO Colorimetric Assay Kit. Inflammation levels in lung homogenates were measured using ELISA. Bacterial load was coated on a TSAII sheep blood agar. Intestinal gut microbiota information was analyzed according to sequencing libraries. RESULTS: SLBZS decreased bacterial load, reduced wet/dry weight ratio, inhibited myeloperoxidase activity, reduced the neutrophils count, and ameliorated lung injury. Furthermore, SLBZS inhibited interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, IL-2, IL-8, IL-12, and interferon-γ secretion and enhanced IL-10 secretion. These results suggest that SLBZS ameliorates lung injury in mice with Spn-induced pneumonia. Moreover, SLBZS reduced inflammatory cytokine levels in a concentration-dependent manner and increased gut microbiota abundance and diversity. After SLBZS treatment, bacteria such as Epsilonbacteraeota, Bacteroidetes, Actinobacteria, Proteobacteria, and Patescibacteria were significantly reduced, while Tenericutes and Firmicutes were significantly increased. CONCLUSION: SLBZS ameliorates inflammation, lung injury, and gut microbiota in mice with S. pneumoniae-induced pneumonia.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Lesão Pulmonar/tratamento farmacológico , Pneumonia Pneumocócica/tratamento farmacológico , Animais , China , Modelos Animais de Doenças , Inflamação/microbiologia , Lesão Pulmonar/microbiologia , Masculino , Camundongos , Streptococcus pneumoniae/efeitos dos fármacosRESUMO
Inhaled granulocyte/macrophage colony-stimulating factor (GM-CSF) shows promise as a therapeutic to treat viral and bacterial pneumonia, but no mouse model of inhaled GM-CSF has been described. We sought to 1) develop a mouse model of aerosolized recombinant mouse GM-CSF administration and 2) investigate the protection conferred by inhaled GM-CSF during influenza A virus (IAV) infection against secondary bacterial infection with pneumococcus. To assess lower respiratory tract delivery of aerosolized therapeutics, mice were exposed to aerosolized fluorescein (FITC)-labeled dextran noninvasively via an aerosolization tower or invasively using a rodent ventilator. The efficiency of delivery to the lower respiratory tracts of mice was 0.01% noninvasively compared with 0.3% invasively. The airway pharmacokinetics of inhaled GM-CSF fit a two-compartment model with a terminal phase half-life of 1.3 h. To test if lower respiratory tract levels were sufficient for biological effect, mice were infected intranasally with IAV, treated with aerosolized recombinant mouse GM-CSF, and then secondarily infected with Streptococcus pneumoniae. Inhaled GM-CSF conferred a significant survival benefit to mice against secondary challenge with S. pneumoniae (P < 0.05). Inhaled GM-CSF did not reduce airway or lung parenchymal bacterial growth but significantly reduced the incidence of S. pneumoniae bacteremia (P < 0.01). However, GM-CSF overexpression during influenza virus infection did not affect lung epithelial permeability to FITC-dextran ingress into the bloodstream. Therefore, the mechanism of protection conferred by inhaled GM-CSF appears to be locally mediated improved lung antibacterial resistance to systemic bacteremia during IAV infection.
Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Pulmão/efeitos dos fármacos , Infecções por Orthomyxoviridae/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Pneumocócica/tratamento farmacológico , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Animais , Vírus da Influenza A/efeitos dos fármacos , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/virologia , Pneumonia Bacteriana/virologia , Pneumonia Pneumocócica/virologiaRESUMO
Serogroup 6 remains common in the pneumococcal-conjugated vaccine era in Bulgaria; therefore, we investigated its clonal and serotype dynamics. The antibiotic susceptibilities were assessed by broth microdilution. Strains identified as serogroup 6 with latex agglutination method were subjected to serotype-specific PCRs. Erythromycin-resistant strains were analyzed by PCR for presence of ermB and mefE genes. MLST was performed to define clonal composition of the sequence types (STs). Serogroup 6 was represented by 40 (13.3%) from 301 invasive and non-invasive Streptococcus pneumoniae isolates. Molecular serotyping revealed new emerging serotype 6C (6.6%), not detected in pre-vaccine era. Among unvaccinated patients, mostly we observed serotypes 6Ð (57.1%) and 6Ð (28.6%). Serotype 6C was distinctive for vaccinated children (64%), followed by 6A (24%). Penicillin and ceftriaxone non-susceptible serogroup 6 strains were 65% and 5%, respectively; erythromycin- and clindamycin-resistant were 70.0% and 52.5%, respectively. Multidrug-resistant strains were 57.5%. Prevalent genetic determinant for macrolide resistance was ermB gene (75%). MLST revealed 17 STs into 5 clonal complexes and 7 singletons. Predominant genetic lineage was CC386, represented by MDR-6C non-invasive strains. Serotype 6B, principally responsible for invasive diseases in the pre-vaccine era, retreated this position to serotype 6A.
Assuntos
Vacinas Pneumocócicas/uso terapêutico , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/prevenção & controle , Streptococcus pneumoniae , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bulgária , Ceftriaxona/uso terapêutico , Criança , Pré-Escolar , Clindamicina/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Eritromicina/uso terapêutico , Humanos , Lactente , Recém-Nascido , Metiltransferases/genética , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Penicilinas/uso terapêutico , Sorotipagem , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Adulto JovemRESUMO
OBJECTIVES: To present results of preclinical studies that supported further development of lefamulin for treating patients with community-acquired bacterial pneumonia (CABP). METHODS: The effect of bovine lung surfactant on the antibacterial activity of lefamulin against Streptococcus pneumoniae and Staphylococcus aureus was determined by broth microdilution assay. In vitro accumulation of lefamulin was evaluated in J774 mouse macrophages. Pharmacokinetics was assessed in female BALB/c (Bagg albino) mice treated with subcutaneous lefamulin (35 or 70 mg/kg). In neutropenic lung infection experiments, BALB/c mice received intraperitoneal cyclophosphamide before challenge with single S. pneumoniae or S. aureus strains; subcutaneous lefamulin (1.25-160 mg/kg) was given twice daily post-infection. Hill models described relationships between AUC/MIC ratios and changes in log10 cfu. RESULTS: Lung surfactant did not significantly increase lefamulin MIC values against test strains. Lefamulin uptake in macrophages was rapid (a plateau was reached in â¼3 h). In mice, distribution of lefamulin [plasma to epithelial lining fluid (ELF)] was rapid, showing an â¼2-fold increase in lefamulin exposure in the ELF during the 5.5 h period. Median plasma AUC/MIC ratios associated with 1 and 2 log10 cfu reductions from baseline were 1.37 and 2.15, respectively, for S. pneumoniae and 2.13 and 6.24 for S. aureus. Corresponding ELF results were 14.0 and 22.0 for S. pneumoniae and 21.7 and 63.9 for S. aureus. CONCLUSIONS: Overall, lefamulin displays desirable pharmacokinetic/pharmacodynamic relationships that are predictive of the clinical effectiveness of lefamulin and other antibacterial agents used to treat CABP.
Assuntos
Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Diterpenos/farmacocinética , Diterpenos/uso terapêutico , Neutropenia/microbiologia , Pneumonia Pneumocócica/tratamento farmacológico , Compostos Policíclicos/farmacocinética , Compostos Policíclicos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Tioglicolatos/farmacocinética , Tioglicolatos/uso terapêutico , Animais , Área Sob a Curva , Bovinos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Ciclofosfamida/administração & dosagem , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Injeções Subcutâneas , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Neutropenia/induzido quimicamente , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Tensoativos/farmacologiaRESUMO
CASE PRESENTATION: A 51-year-old man presented to the clinic 8 weeks after a 6-day hospital admission for severe multilobar pneumonia caused by Streptococcus pneumoniae. His productive cough resolved after antibiotics, but he reported persistent dyspnea. He recounted a lifelong history of recurrent sinusitis but no previous episodes of pneumonia. The patient denied fever, weight loss, or tobacco, alcohol, or drug use. He worked as an upholstery craftsman with no work-related exposures. He had no bird or exotic animal exposures, and no history of travel outside Sacramento, California, where he lived. Aside from the recently completed 2-week course of levofloxacin, he was not taking any medications.
Assuntos
Imunodeficiência de Variável Comum/diagnóstico por imagem , Imunodeficiência de Variável Comum/patologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Pneumonia Pneumocócica/complicações , Streptococcus pneumoniae , Antibacterianos/uso terapêutico , Imunodeficiência de Variável Comum/etiologia , Humanos , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Pneumocócica/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
Background: Bacteremic pneumococcal pneumonia (BPP) is a preventable disease with high morbimortality. Aim: To evaluate clinical aspects and mortality on BPP patients admitted to a Chilean regional hospital. Patients and Methods: We looked for adult patients with Streptococcus pneumoniae isolated from blood cultures between 2010 and 2014 years and reviewed clinical records of those who were admitted with pneumonia. Results: We identified 70 BPP patients: 58% were men, mean age was 56 years, 30% were > 65 years, 70% with basic public health insurance, 26% were alcoholics, 86% had comorbidities. Only two patients were vaccinated against S. pneumoniae. CURB-65 severity index for community acquired pneumonia was > 3 in 37% of patients. Twenty-four patients were admitted to ICU, twenty required mechanical ventilation and twenty-four died (34%). Mortality was associated with an age over 65 years, presence of comorbidities and complications of pneumonia. A total of 22 serotypes of S. pneumoniae were identified, five of them (1,3,7F,14 y 9V) were present in 57% of cases. Conclusions: Elevated mortality of our BNN patients was associated with comorbidities and possibly with socio economic factors, which conditioned a late access to medical care.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Pneumonia Pneumocócica/mortalidade , Bacteriemia/mortalidade , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/tratamento farmacológico , Fatores Socioeconômicos , Streptococcus pneumoniae/isolamento & purificação , Índice de Gravidade de Doença , Ceftriaxona/uso terapêutico , Comorbidade , Chile/epidemiologia , Fatores de Risco , Mortalidade Hospitalar , Bacteriemia/microbiologia , Bacteriemia/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/tratamento farmacológico , Antibacterianos/uso terapêuticoRESUMO
Resumen: El Síndrome de Austrian, corresponde al cuadro clínico descrito por Robert Austrian en 1957, definido por la triada de Neumonía, Endocarditis Infecciosa (EI) y Meningitis, causado por Streptococcus pneumoniae. En la mayoría de los casos el vicio valvular presente, es la insuficiencia valvular aórtica, cuyo tratamiento médico y resolución quirúrgica de acuerdo con su gravedad, deben ser realizados precoz y oportunamente. Un paciente de 51 años, sin antecedentes de valvulopatía, con historia de poli consumo de alcohol y cocaína comenzó dos semanas previo a su ingreso hospitalario con síndrome febril, neumonía, y meningitis bacteriana por Streptococcus pneumoniae. Sus hemocultivos fueron negativos. El ecocardiograma transesofágico (ETE) fue compatible con EI valvular aórtica con insuficiencia moderada a severa. Se trató como EI a microorganismo desconocido y se efectuó un reemplazo valvular aórtico electivo con prótesis biológica a la 5° semana después de terminado el tratamiento médico antibiótico, cuyo resultado fue exitoso.
Abstract: A syndrome including Infective endocarditis, pneumonia and Meningitis caused by S pneumoniae was described by Robert Austrian in 1957. The aortic valve is affected in most cases. Medical followed by surgical treatment should be promptly implemented. The clinical case of a 51 year old man with a history of multiple drug consumption developing fever, pneumonia, and meningitis caused by S pneumoniae is presented. Blood cultures were negative and trans esophageal echocardiography showed aortic valve vegetations and moderate regurgitation. After multiple antibiotic treatment the patient underwent aortic valve replacement and recovered satisfactorily. Clinical and epidemiological characteristics of this syndrome are discussed.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Pneumocócica/cirurgia , Endocardite Bacteriana/cirurgia , Meningite Pneumocócica/cirurgia , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/tratamento farmacológico , Streptococcus pneumoniae , Síndrome , Ecocardiografia Transesofagiana , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Meningite Pneumocócica/diagnóstico , Meningite Pneumocócica/tratamento farmacológico , Antibacterianos/uso terapêuticoRESUMO
Evidence is accumulating that exposure to cigarette smoke (CS) increases the risk of developing acute respiratory distress syndrome (ARDS). Streptococcus pneumoniae is the most common cause of bacterial pneumonia, which in turn is the leading cause of ARDS. Chronic smokers have increased rates of pneumococcal colonization and develop more severe pneumococcal pneumonia than nonsmokers; yet mechanistic connections between CS exposure, bacterial pneumonia, and ARDS pathogenesis remain relatively unexplored. We exposed mice to 3 wk of moderate whole body CS or air, followed by intranasal inoculation with an invasive serotype of S. pneumoniae. CS exposure alone caused no detectable lung injury or bronchoalveolar lavage (BAL) inflammation. During pneumococcal infection, CS-exposed mice had greater survival than air-exposed mice, in association with reduced systemic spread of bacteria from the lungs. However, when mice were treated with antibiotics after infection to improve clinical relevance, the survival benefit was lost, and CS-exposed mice had more pulmonary edema, increased numbers of BAL monocytes, and elevated monocyte and lymphocyte chemokines. CS-exposed antibiotic-treated mice also had higher serum surfactant protein D and angiopoietin-2, consistent with more severe lung epithelial and endothelial injury. The results indicate that acute CS exposure enhances the recruitment of immune cells to the lung during bacterial pneumonia, an effect that may provide microbiological benefit but simultaneously exposes the mice to more severe inflammatory lung injury. The inclusion of antibiotic treatment in preclinical studies of acute lung injury in bacterial pneumonia may enhance clinical relevance, particularly for future studies of current or emerging tobacco products.
Assuntos
Lesão Pulmonar Aguda , Antibacterianos/farmacologia , Pneumonia Bacteriana , Pneumonia Pneumocócica , Streptococcus pneumoniae/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Feminino , Camundongos , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/metabolismo , Pneumonia Bacteriana/patologia , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/metabolismo , Pneumonia Pneumocócica/patologia , Edema Pulmonar/tratamento farmacológico , Edema Pulmonar/metabolismo , Edema Pulmonar/patologiaRESUMO
BACKGROUND: Among the different serotypes of Streptococcus pneumoniae, serotype 3 has received global attention. We report the fatal case of a 76-year-old Japanese man who had an invasive pneumococcal disease associated with pneumonia caused by serotype 3 S. pneumoniae. CASE PRESENTATION: The patient had a history of hypertension, laryngeal cancer, chronic obstructive pulmonary disease, and type 2 diabetes mellitus. Following a cerebral arteriovenous malformation hemorrhage, he underwent surgery to remove the hematoma and began rehabilitation. On day 66 of hospitalization, he suddenly developed a fever, and coarse crackles and wheezes were heard in his right lung. A diagnosis of hospital-acquired aspiration pneumonia was made, and initial treatment with piperacillin/tazobactam was started. Teicoplanin was added after S. pneumoniae was isolated from the blood culture, however, the patient died 5 days later. The S. pneumoniae detected in the sputum smear was serotype 3, showed mucoid colonies and susceptibility to penicillins, cephalosporins, carbapenems, and levofloxacin, but resistance to erythromycin. CONCLUSION: We experienced a fatal case of pneumonia caused by mucoid serotype 3 S. pneumoniae with a thick capsule. Serotype 3-associated pneumonia may develop a wider pulmonary infiltrative shadow, a prolonged therapeutic or hospitalization course, and a poor outcome. Careful observation and intervention are required, and the use of additional antibiotics or intravenous immunoglobulins should be considered in such cases. Pneumococcal immunization is also an important public health measure to minimize the development of severe infections caused by serotype 3 strains.
Assuntos
Pneumonia Pneumocócica/diagnóstico , Streptococcus pneumoniae/isolamento & purificação , Idoso , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Cefalosporinas/uso terapêutico , Eritromicina/uso terapêutico , Hospitalização , Humanos , Japão , Levofloxacino/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Penicilinas/uso terapêutico , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/microbiologia , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/classificação , Resultado do TratamentoRESUMO
The use of glucocorticoids to reduce inflammatory responses is largely based on the knowledge of the physiological action of the endogenous glucocorticoid, cortisol. Corticotropin-releasing hormone (CRH) is a neuropeptide released from the hypothalamic-pituitary-adrenal axis of the central nervous system. This hormone serves as an important mediator of adaptive physiological responses to stress. In addition to its role in inducing downstream cortisol release that in turn regulates immune suppression, CRH has also been found to mediate inflammatory responses in peripheral tissues. Streptococcus pneumoniae is a microorganism commonly present among the commensal microflora along the upper respiratory tract. Transmission of disease stems from the resident asymptomatic pneumococcus along the nasal passages. Glucocorticoids are central mediators of immune suppression and are the primary adjuvant pharmacological treatment used to reduce inflammatory responses in patients with severe bacterial pneumonia. However, controversy exists in the effectiveness of glucocorticoid treatment in reducing mortality rates during S. pneumoniae infection. In this study, we compared the effect of the currently utilized pharmacologic glucocorticoid dexamethasone with CRH. Our results demonstrated that intranasal administration of CRH increases survival associated with a decrease in inflammatory cellular immune responses compared to dexamethasone independent of neutrophils. Thus, providing evidence of its use in the management of immune and inflammatory responses brought on by severe pneumococcal infection that could reduce mortality risks.
Assuntos
Hormônio Liberador da Corticotropina/administração & dosagem , Hormônios/administração & dosagem , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia/tratamento farmacológico , Sobrevida/fisiologia , Administração Intranasal , Animais , Quimiocina CXCL1/metabolismo , Hormônio Liberador da Corticotropina/farmacologia , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/farmacologia , Hormônios/farmacologia , Hidrocortisona/metabolismo , Hidrocortisona/farmacologia , Sistema Hipotálamo-Hipofisário/fisiologia , Camundongos , Sistema Hipófise-Suprarrenal/fisiologia , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/fisiologiaRESUMO
Mounier-Kuhn syndrome (MKS) is a rare disease of unknown etiology characterized by abnormal pathologic dilatation of tracheabronchial tree. The diagnosis of MKS is normally made on CT scan of chest on the basis of enlarged diameters of trachea and main stem bronchi. We are presenting histologically confirmed case of MKS, where the diameter of right main bronchus is below minimum diameter (mean+3 SD) required for the diagnosis. We suggest that the diagnosis of MKS should not be solely based on fixed criteria such as the diameter of airways, but on the basis of the overall clinical, pathologic, and radiologic profile.