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1.
Nanoscale Horiz ; 6(4): 330-340, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33599221

RESUMO

Bacterial infections are re-emerging as substantial threats to global health due to the limited selection of antibiotics that are capable of overcoming antibiotic-resistant strains. By deterring such mutations whilst minimizing the need to develop new pathogen-specific antibiotics, immunotherapy offers a broad-spectrum therapeutic solution against bacterial infections. In particular, pathology resulting from excessive immune response (i.e. fibrosis, necrosis, exudation, breath impediment) contributes significantly to negative disease outcome. Herein, we present a nanoparticle that is targeted to activated macrophages and loaded with siRNA against the Irf5 gene. This formulation is able to induce >80% gene silencing in activated macrophages in vivo, and it inhibits the excessive inflammatory response, generating a significantly improved therapeutic outcome in mouse models of bacterial infection. The versatility of the approach is demonstrated using mice with antibiotic-resistant Gram-positive (methicillin-resistant Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) muscle and lung infections, respectively. Effective depletion of the Irf5 gene in macrophages is found to significantly improve the therapeutic outcome of infected mice, regardless of the bacteria strain and type.


Assuntos
Portadores de Fármacos/química , Macrófagos/efeitos dos fármacos , Nanopartículas/química , Pneumonia Estafilocócica/terapia , RNA Interferente Pequeno/uso terapêutico , Animais , Imunoterapia , Fatores Reguladores de Interferon/antagonistas & inibidores , Fatores Reguladores de Interferon/genética , Pulmão/microbiologia , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Músculos/microbiologia , Porosidade , Pseudomonas aeruginosa/efeitos dos fármacos , RNA Interferente Pequeno/genética , Silício/química
2.
Future Microbiol ; 16(3): 135-142, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33538181

RESUMO

The ability of influenza A virus to evolve, coupled with increasing antimicrobial resistance, could trigger an influenza pandemic with great morbidity and mortality. Much of the 1918 influenza pandemic mortality was likely due to bacterial coinfection, including Staphylococcus aureus pneumonia. S. aureus resists many antibiotics. The lack of new antibiotics suggests alternative antimicrobials, such as bacteriophages, are needed. Potential delivery routes for bacteriophage therapy (BT) include inhalation and intravenous injection. BT has recently been used successfully in compassionate access pulmonary infection cases. Phage lysins, enzymes that hydrolyze bacterial cell walls and which are bactericidal, are efficacious in animal pneumonia models. Clinical trials will be needed to determine whether BT can ameliorate disease in influenza and S. aureus coinfection.


Assuntos
Bacteriófagos/fisiologia , Coinfecção/terapia , Vírus da Influenza A/fisiologia , Influenza Humana/terapia , Terapia por Fagos , Pneumonia Estafilocócica/terapia , Staphylococcus aureus/virologia , Animais , Coinfecção/microbiologia , Coinfecção/mortalidade , Coinfecção/virologia , Humanos , Vírus da Influenza A/genética , Influenza Humana/mortalidade , Influenza Humana/virologia , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/mortalidade , Staphylococcus aureus/genética , Staphylococcus aureus/fisiologia
3.
Bol. malariol. salud ambient ; 60(2): 111-115, dic.2020. tab., ilus.
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1509626

RESUMO

La neumonía es definida por la Organización Mundial de Salud (OMS) como una infección respiratoria aguda que afecta a los alvéolos pulmonares, dificultando la respiración y absorción de oxígeno afectando a la población infantil. Por eso se propuso analizar la neumonía estafilocócica complicada con enfoque clínico, radiológico y tratamiento en el paciente pediátrico para establecer elementos que ayuden a la elaboración de protocolos de diagnóstico y tratamiento. Se realizó un estudio de tipo documental, observacional y analítico mediante la entrevista directa con el paciente y familiares y el análisis clínico de los signos y síntomas presentados por el paciente. Mediante la valoración clínico, radiológico y oportuno tratamiento en el paciente pediátrico con neumonía estafilocócica complicada, se logró establecer elementos que podrán ayudar a la elaboración de un protocolo de diagnóstico y tratamiento de dicha patología(AU)


Pneumonia is defined by the World Health Organization (WHO) as an acute respiratory infection that affects the pulmonary alveoli, making it difficult to breathe and absorb oxygen, affecting the child population. Therefore, it was proposed to analyze complicated staphylococcal pneumonia with a clinical, radiological and treatment approach in the pediatric patient to establish elements that help to develop diagnostic and treatment protocols. A documentary, observational and analytical study was conducted through a direct interview with the patient and family members and the clinical analysis of the signs and symptoms presented by the patient. By means of the clinical, radiological evaluation and timely treatment in the pediatric patient with complicated staphylococcal pneumonia, it was possible to establish elements that may help to elaborate a protocol for the diagnosis and treatment of said pathology(AU)


Assuntos
Humanos , Masculino , Criança , Pneumonia/epidemiologia , Pneumonia Estafilocócica/diagnóstico , Pneumonia Estafilocócica/terapia
4.
Toxins (Basel) ; 12(11)2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33218049

RESUMO

Pneumonia is an acute pulmonary infection associated with high mortality and an immense financial burden on healthcare systems. Staphylococcus aureus is an opportunistic pathogen capable of inducing S. aureus pneumonia (SAP), with some lineages also showing multidrug resistance. Given the high level of antibiotic resistance, much research has been focused on targeting S. aureus virulence factors, including toxins and biofilm-associated proteins, in an attempt to develop effective SAP therapeutics. Despite several promising leads, many hurdles still remain for S. aureus vaccine research. Here, we review the state-of-the-art SAP therapeutics, highlight their pitfalls, and discuss alternative approaches of potential significance and future perspectives.


Assuntos
Pneumonia Estafilocócica/terapia , Staphylococcus aureus , Fatores de Virulência , Animais , Vacinas Bacterianas/uso terapêutico , Biofilmes , Genômica , Humanos , Metabolômica , Pneumonia Estafilocócica/genética , Pneumonia Estafilocócica/metabolismo , Staphylococcus aureus/patogenicidade , Staphylococcus aureus/fisiologia
5.
JAMA Netw Open ; 3(9): e2012741, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32997125

RESUMO

Importance: Carriage of Staphylococcus aureus is associated with S aureus infection. However, associations between S aureus carriage and the development of S aureus intensive care unit (ICU) pneumonia (SAIP) have not been quantified accurately, and interpretation of available data is hampered because of variations in definitions. Objective: To quantify associations of patient-related and contextual factors, including S aureus colonization status, with the occurrence of SAIP. Design, Setting, and Participants: This cohort study was conducted in ICUs of 30 hospitals in 11 European countries, geographically spread across 4 regions. Among patients with an anticipated length of stay 48 hours or longer who were undergoing mechanical ventilation at ICU admission, S aureus colonization was ascertained in the nose and lower respiratory tract. From this group, S aureus-colonized and noncolonized patients were enrolled into the study cohort in a 1:1 ratio. Data analysis was performed from May to November 2019. Main Outcomes and Measures: SAIP was defined as any pneumonia during the ICU stay developing 48 hours or more after ICU admission with S aureus isolated from lower respiratory tract specimens or blood samples. The incidence of SAIP was derived in the study cohort and estimated on the weighted incidence calculation for the originating overarching population, while taking competing events into account. Weighted risk factor analysis was performed using Cox multivariable regression. Results: The study cohort consisted of 1933 patients (mean [SD] age, 62.0 [16.0] years); 1252 patients (64.8%) were men, and 950 patients (49.1%) were S aureus carriers at ICU admission. In all, 304 patients (15.7%) developed ICU-acquired pneumonia, of whom 131 patients (6.8%) had SAIP. Weighted SAIP incidences were 11.7 events per 1000 patient-days in the ICU for S aureus-colonized patients and 2.9 events per 1000 patient-days in the ICU for noncolonized patients (overall incidence, 4.9 events per 1000 patient-days in the ICU). The only factor independently associated with SAIP was S aureus colonization status at ICU admission (cause-specific hazard ratio, 3.6; 95% CI, 2.2-6.0; P < .001). There were marked regional differences in SAIP incidence and cause-specific hazard ratios for colonization status. Conclusions and Relevance: SAIP incidence was 4.9 events per 1000 ICU patient-days for patients undergoing mechanical ventilation at ICU admission (or shortly thereafter). The daily risk of SAIP was 3.6 times higher in patients colonized with S aureus at ICU admission compared with noncolonized patients.


Assuntos
Infecção Hospitalar , Unidades de Terapia Intensiva/estatística & dados numéricos , Pneumonia Estafilocócica , Staphylococcus aureus/isolamento & purificação , Estudos de Coortes , Contagem de Colônia Microbiana/estatística & dados numéricos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nariz/microbiologia , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Estafilocócica/diagnóstico , Pneumonia Estafilocócica/epidemiologia , Pneumonia Estafilocócica/terapia , Sistema Respiratório/microbiologia , Medição de Risco
6.
Emerg Infect Dis ; 26(8): 1939-1941, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32298228
7.
Pak J Pharm Sci ; 32(4): 1621-1630, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31608882

RESUMO

Staphylococcus aureus and Pseudomonas aeruginosa are largely the cause of morbidity and mortality in both hospital and community settings. These pathogens remain the important cause of pulmonary infections in patients with cystic fibrosis with a worldwide prevalence. Although, antibiotics are efficient measures of treating bacterial lung infections, the occurrence of antibiotic resistant bacteria has been encouraging the researchers to explore novel therapeutic approaches. It has been discovered that certain lactic acid bacteria possess protective effects against bacterial and viral respiratory infections. The aim of present study was to investigate the capability of orally administered L. acidophilus to ameliorate S. aureus and P. aeruginosa pulmonary infections. Animals were exposed to aerosol of pathogenic suspension. After 24 hours of infection, L. acidophilus treatment was administered orally for 7 consecutive days. Evaluation of tissue bacteriology, histopathology and serum cytokinomics were performed. In parallel, human alveolar A549 cells were utilized to determine possible role of probiotic on pulmonary infections. Oral administration of L. acidophilus significantly (P<0.05) alleviate lung bacterial load and severity of infection as depicted by our histopathological studies. Results obtained from cytokinomics revealed that pro-inflammatory cytokines induced due to lung infection were suppressed in oral probiotic treatment groups. In addition, treatment with L. acidophilus induced murine lung anti inflammatory, IL-10 cytokine level. Current work suggests that orally administered L. acidophilus in mice is able to attenuate S. aureus and P. aeruginosa induced lung cytotoxicity by modulation of host immune response.


Assuntos
Lactobacillus acidophilus , Pneumonia Estafilocócica/terapia , Probióticos/farmacologia , Infecções por Pseudomonas/terapia , Células A549 , Administração Oral , Animais , Citocinas/sangue , Citocinas/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/metabolismo , Pneumonia Estafilocócica/patologia , Probióticos/administração & dosagem , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa
8.
Transfusion ; 59(12): 3628-3638, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31639229

RESUMO

BACKGROUND: During sepsis, higher plasma cell-free hemoglobin (CFH) levels portend worse outcomes. In sepsis models, plasma proteins that bind CFH improve survival. In our canine antibiotic-treated Staphylococcus aureus pneumonia model, with and without red blood cell (RBC) exchange transfusion, commercial human haptoglobin (Hp) concentrates bound and compartmentalized CFH intravascularly, increased CFH clearance, and lowered iron levels, improving shock, lung injury, and survival. We now investigate in our model how very high CFH levels and treatment time affect Hp's beneficial effects. MATERIALS AND METHODS: Two separate canine pneumonia sepsis Hp studies were undertaken: one with exchange transfusion of RBCs after prolonged storage to raise CFH to very high levels and another with rapidly lethal sepsis alone to shorten time to treat. All animals received continuous standard intensive care unit supportive care for 96 hours. RESULTS: Older RBCs markedly elevated plasma CFH levels and, when combined with Hp therapy, created supraphysiologic CFH-Hp complexes that did not increase CFH or iron clearance or improve lung injury and survival. In a rapidly lethal bacterial challenge model without RBC transfusion, Hp binding did not increase clearance of complexes or iron or show benefits seen previously in the less lethal model. DISCUSSION: High-level CFH-Hp complexes may impair clearance mechanisms and eliminate Hp's beneficial effect during sepsis. Rapidly lethal sepsis narrows the therapeutic window for CFH and iron clearance, also decreasing Hp's beneficial effects. In designing clinical trials, dosing and kinetics may be critical factors if Hp infusion is used to treat sepsis.


Assuntos
Haptoglobinas/uso terapêutico , Hemoglobinas/metabolismo , Pneumonia Estafilocócica/tratamento farmacológico , Pneumonia Estafilocócica/metabolismo , Choque Séptico/tratamento farmacológico , Choque Séptico/metabolismo , Animais , Modelos Animais de Doenças , Cães , Transfusão de Eritrócitos , Pneumonia Estafilocócica/terapia , Sepse/tratamento farmacológico , Sepse/metabolismo , Sepse/terapia , Choque Séptico/terapia
9.
Biosci Rep ; 39(9)2019 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31484796

RESUMO

The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 1010 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO2, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (P<0.01), decreasing pulmonary auscultation, and reduction of IL-8, IL-6, CRP, and TNF-α concentrations in plasma (P<0.01) compared with the pneumonia model group at 48 and 168 h. Compared with LZD group, co-administration of hUMSCs (1 × 106/kg for two times at 6 and 72 h after MRSA instillation) and LZD further increased the body weight (P<0.05). The changes we observed from chest imaging, bronchoscopic manifestations and pathology revealed that co-administration of hUMSCs and LZD reduced lung inflammation more significantly than that of LZD group. The plasma levels of IL-8, IL-6, CRP, and TNF-α in combined group decreased dramatically compared with the LZD group (P<0.05). In conclusion, hUMSCs administration significantly improved therapeutic effects of LZD on pneumonia resulted from MRSA infection in a rabbit model.


Assuntos
Antibacterianos/uso terapêutico , Linezolida/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pneumonia Estafilocócica/terapia , Animais , Células Cultivadas , Terapia Combinada , Citocinas/sangue , Modelos Animais de Doenças , Humanos , Pulmão/patologia , Masculino , Células-Tronco Mesenquimais/citologia , Neutrófilos/imunologia , Coelhos
10.
Paediatr Respir Rev ; 32: 3-9, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31422032

RESUMO

OBJECTIVES: To review epidemiology, aetiology and management of childhood pneumonia in low-and-middle-income countries. DESIGN: Review of published English literature between 2013 and 2019. RESULTS: Pneumonia remains a major cause of morbidity and mortality. Risk factors include young age, malnutrition, immunosuppression, tobacco smoke or air pollution exposure. Better methods for specimen collection and molecular diagnostics have improved microbiological diagnosis, indicating that pneumonia results from several organisms interacting. Induced sputum increases microbiologic yield for Bordetella pertussis or Mycobacterium tuberculosis, which has been associated with pneumonia in high TB prevalence areas. The proportion of cases due to Streptococcus pneumoniae and Haemophilus influenzae b has declined with new conjugate vaccines; Staphylococcus aureus and H. influenzae non-type b are the commonest bacterial pathogens; viruses are the most common pathogens. Effective interventions comprise antibiotics, oxygen and non-invasive ventilation. New vaccines have reduced severity and incidence of disease, but disparities exist in uptake. CONCLUSION: Morbidity and mortality from childhood pneumonia has decreased but a considerable preventable burden remains. Widespread implementation of available, effective interventions and development of novel strategies are needed.


Assuntos
Países em Desenvolvimento , Pneumonia/epidemiologia , Fatores Etários , Poluição do Ar/estatística & dados numéricos , Antibacterianos/uso terapêutico , Transtornos da Nutrição Infantil/epidemiologia , Pré-Escolar , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/prevenção & controle , Infecções por Haemophilus/terapia , Humanos , Lactente , Recém-Nascido , Ventilação não Invasiva/métodos , Oxigenoterapia/métodos , Pneumonia/microbiologia , Pneumonia/prevenção & controle , Pneumonia/terapia , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/prevenção & controle , Pneumonia Pneumocócica/terapia , Pneumonia Estafilocócica/epidemiologia , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/terapia , Fatores de Risco , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/prevenção & controle , Tuberculose Pulmonar/terapia , Vacinas/uso terapêutico , Coqueluche/epidemiologia , Coqueluche/microbiologia , Coqueluche/prevenção & controle , Coqueluche/terapia
11.
Acta Clin Belg ; 74(6): 456-459, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30444192

RESUMO

Pneumonia is one of the leading causes of death in older people, with high mortality rates (> 80%). One of the bacterial pathogens causing pneumonia is Staphylococcus aureus. The unique adaptive ability of S. aureus to a broad range of antibiotics has led to the emergence of methicillin-resistant S. aureus (MRSA) strain. MRSA pneumonia remains a relatively uncommon infection in older people, but it is associated with a very high mortality rate. We report two cases of MRSA pneumonia that highlight the severe clinical presentation and virulence of MRSA infections in geriatric population. MRSA pneumonia can present with mostly an uncontrollable clinical evolution and an infaust prognosis. Therefore, clinicians should be aware of MRSA pneumonia in patients with comorbidities, recent hospitalization with antibiotic treatment, previous MRSA infections and also in patients residing in nursing homes/revalidation centers. Low prevalence of MRSA combined with a lack of highly distinctive clinical features makes accurate targeting of empirical treatment with antibiotics very difficult. Currently, monotherapy with linezolid or vancomycin remain the first choice, in adult patients with proven MRSA infection. Despite the higher age related mortality rates, there are no specific treatment guidelines for older patients.


Assuntos
Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pneumonia Estafilocócica , Vancomicina/administração & dosagem , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/classificação , Hemocultura/métodos , Infecção Hospitalar/microbiologia , Infecção Hospitalar/fisiopatologia , Infecção Hospitalar/terapia , Diagnóstico Diferencial , Evolução Fatal , Humanos , Masculino , Avaliação das Necessidades , Casas de Saúde , Seleção de Pacientes , Pneumonia Estafilocócica/diagnóstico , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/fisiopatologia , Pneumonia Estafilocócica/terapia , Prognóstico , Fatores de Risco , Tempo para o Tratamento
12.
Nat Commun ; 9(1): 1969, 2018 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-29773788

RESUMO

The incidence of adverse effects and pathogen resistance encountered with small molecule antibiotics is increasing. As such, there is mounting focus on immunogene therapy to augment the immune system's response to infection and accelerate healing. A major obstacle to in vivo gene delivery is that the primary uptake pathway, cellular endocytosis, results in extracellular excretion and lysosomal degradation of genetic material. Here we show a nanosystem that bypasses endocytosis and achieves potent gene knockdown efficacy. Porous silicon nanoparticles containing an outer sheath of homing peptides and fusogenic liposome selectively target macrophages and directly introduce an oligonucleotide payload into the cytosol. Highly effective knockdown of the proinflammatory macrophage marker IRF5 enhances the clearance capability of macrophages and improves survival in a mouse model of Staphyloccocus aureus pneumonia.


Assuntos
Antibacterianos/farmacologia , Terapia Genética/métodos , Macrófagos/efeitos dos fármacos , Pneumonia Estafilocócica/terapia , Staphylococcus aureus/fisiologia , Animais , Antibacterianos/uso terapêutico , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Farmacorresistência Bacteriana/genética , Técnicas de Silenciamento de Genes , Terapia Genética/efeitos adversos , Humanos , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/imunologia , Lipossomos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/química , Peptídeos Cíclicos/administração & dosagem , Pneumonia Estafilocócica/imunologia , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/mortalidade , Células RAW 264.7 , Interferência de RNA/imunologia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Staphylococcus aureus/efeitos dos fármacos , Análise de Sobrevida , Resultado do Tratamento
13.
Transfusion ; 57(10): 2338-2347, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28656646

RESUMO

BACKGROUND: No studies have been performed comparing intravenous (IV) iron with transfused red blood cells (RBCs) for treating anemia during infection. In a previous report, transfused older RBCs increased free iron release and mortality in infected animals when compared to fresher cells. We hypothesized that treating anemia during infection with transfused fresh RBCs, with minimal free iron release, would prove superior to IV iron therapy. STUDY DESIGN AND METHODS: Purpose-bred beagles (n = 42) with experimental Staphylococcus aureus pneumonia rendered anemic were randomized to be transfused RBCs stored for 7 days or one of two IV iron preparations (7 mg/kg), iron sucrose, a widely used preparation, or ferumoxytol, a newer formulation that blunts circulating iron levels. RESULTS: Both irons increased the alveolar-arterial oxygen gradient at 24 to 48 hours (p = 0.02-0.001), worsened shock at 16 hours (p = 0.02-0.003, respectively), and reduced survival (transfusion 56%; iron sucrose 8%, p = 0.01; ferumoxytol 9%, p = 0.04). Compared to fresh RBC transfusion, plasma iron measured by non-transferrin-bound iron levels increased with iron sucrose at 7, 10, 13, 16, 24, and 48 hours (p = 0.04 to p < 0.0001) and ferumoxytol at 7, 24, and 48 hours (p = 0.04 to p = 0.004). No significant differences in cardiac filling pressures or performance, hemoglobin (Hb), or cell-free Hb were observed. CONCLUSIONS: During canine experimental bacterial pneumonia, treatment of mild anemia with IV iron significantly increased free iron levels, shock, lung injury, and mortality compared to transfusion of fresh RBCs. This was true for iron preparations that do or do not blunt circulating free iron level elevations. These findings suggest that treatment of anemia with IV iron during infection should be undertaken with caution.


Assuntos
Anemia/terapia , Transfusão de Eritrócitos , Ferro/administração & dosagem , Pneumonia Bacteriana/complicações , Anemia/complicações , Anemia/etiologia , Anemia/mortalidade , Animais , Modelos Animais de Doenças , Cães , Transfusão de Eritrócitos/normas , Compostos Férricos/administração & dosagem , Compostos Férricos/uso terapêutico , Óxido de Ferro Sacarado , Óxido Ferroso-Férrico/administração & dosagem , Óxido Ferroso-Férrico/uso terapêutico , Ácido Glucárico/administração & dosagem , Ácido Glucárico/uso terapêutico , Ferro/efeitos adversos , Ferro/uso terapêutico , Lesão Pulmonar , Mortalidade , Pneumonia Estafilocócica/terapia
14.
Eur J Clin Microbiol Infect Dis ; 36(3): 523-528, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27815777

RESUMO

Early-onset pneumonia (EOP) is frequent after burn trauma, increasing morbidity in the critical resuscitation phase, which may preclude early aggressive management of burn wounds. Currently, however, preemptive treatment is not recommended. The aim of this study was to identify predictive factors for EOP that may justify early empirical antibiotic treatment. Data for all burn patients requiring ≥4 h mechanical ventilation (MV) who were admitted between January 2001 and October 2012 were extracted from the hospital's computerized information system. We reviewed EOP episodes (≤7 days) among patients who underwent endotracheal aspiration (ETA) within 5 days after admission. Univariate and multivariate analyses were performed to identify independent factors associated with EOP. Logistic regression was used to identify factors predicting EOP development. During the study period, 396 burn patients were admitted. ETA was performed within 5 days in 204/290 patients receiving ≥4 h MV. One hundred and eight patients developed EOP; 47 cases were caused by Staphylococcus aureus, 37 by Haemophilus influenzae, and 23 by Streptococcus pneumoniae. Among the 33 patients showing S. aureus positivity on ETA samples, 16 (48.5 %) developed S. aureus EOP. Among the 156 S. aureus non-carriers, 16 (10.2 %) developed EOP. Staphylococcus aureus carriage independently predicted EOP (p < 0.0001). We identified S. aureus carriage as an independent and strong predictor of EOP. As rapid point-of-care testing for S. aureus is readily available, we recommend testing of all patients at admission for burn trauma and the consideration of early preemptive treatment in all positive patients. Further studies are needed to evaluate this new strategy.


Assuntos
Queimaduras/complicações , Portador Sadio/microbiologia , Pneumonia Estafilocócica/epidemiologia , Staphylococcus aureus/isolamento & purificação , Ferimentos e Lesões/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/terapia , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco
16.
Ann Am Thorac Soc ; 13(10): 1789-1793, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27420604

RESUMO

Independent lung ventilation is an infrequently used ventilation strategy in the pediatric intensive care unit but can be beneficial in unique patient subsets, such as patients who have asymmetric pulmonary pathology. Independent lung ventilation allows for the independent delivery of the appropriate effective tidal volume to each lung on the basis of individual compliance and pathology. In theory, it may help avoid alveolar overdistension and ventilator-induced lung injury in the nondiseased lung. In addition, it allows for targeted interventions. Here, we describe a child with unilateral lung disease requiring veno-venous extracorporeal membrane oxygenation who rapidly improved, allowing decannulation within 24 hours, after the application of independent lung ventilation and unilateral surfactant administration.


Assuntos
Oxigenação por Membrana Extracorpórea , Pneumonia Estafilocócica/terapia , Respiração Artificial , Insuficiência Respiratória/terapia , Criança , Feminino , Humanos , Unidades de Terapia Intensiva Pediátrica , Pulmão/fisiopatologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Surfactantes Pulmonares/administração & dosagem , Radiografia Torácica , Volume de Ventilação Pulmonar
17.
Mol Ther ; 24(10): 1873-1880, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27456061

RESUMO

Chronic granulomatous disease (CGD) is a primary immunodeficiency due to a deficiency in one of the subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. CGD patients are characterized by an increased susceptibility to bacterial and fungal infections, and to granuloma formation due to the excessive inflammatory responses. Several gene therapy approaches with lentiviral vectors have been proposed but there is a lack of in vivo data on the ability to control infections and inflammation. We set up a mouse model of acute infection that closely mimic the airway infection in CGD patients. It involved an intratracheal injection of a methicillin-sensitive reference strain of S. aureus. Gene therapy, with hematopoietic stem cells transduced with regulated lentiviral vectors, restored the functional activity of NADPH oxidase complex (with 20-98% of dihydrorhodamine positive granulocytes and monocytes) and saved mice from death caused by S. aureus, significantly reducing the bacterial load and lung damage, similarly to WT mice even at low vector copy number. When challenged, gene therapy-treated XCGD mice showed correction of proinflammatory cytokines and chemokine imbalance at levels that were comparable to WT. Examined together, our results support the clinical development of gene therapy protocols using lentiviral vectors for the protection against infections and inflammation.


Assuntos
Terapia Genética/métodos , Doença Granulomatosa Crônica/complicações , Transplante de Células-Tronco Hematopoéticas/métodos , Glicoproteínas de Membrana/genética , NADPH Oxidases/genética , Pneumonia Estafilocócica/terapia , Staphylococcus aureus/fisiologia , Animais , Carga Bacteriana , Células Cultivadas , Quimiocinas/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Vetores Genéticos/administração & dosagem , Doença Granulomatosa Crônica/genética , Células-Tronco Hematopoéticas/virologia , Humanos , Lentivirus/genética , Camundongos , NADPH Oxidase 2 , Pneumonia Estafilocócica/genética , Pneumonia Estafilocócica/microbiologia
18.
Med Mal Infect ; 46(6): 314-7, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27210282

RESUMO

OBJECTIVE: To describe two cases of Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) necrotizing pneumonia treated with ECMO, and complete pulmonary evaluation at six months. METHODS: Retrospective analysis of two patients presenting with severe PVL-SA pneumonia who both underwent complete respiratory function testing and chest CT scan six months after hospital discharge. RESULTS: Indications for ECMO were refractory hypoxia and left ventricular dysfunction associated with right ventricular dilatation. Patients were weaned off ECMO after 52 and 5 days. No ECMO-related hemorrhagic complication was observed. Pulmonary function tests performed at six months were normal and the CT scan showed complete regression of pulmonary injuries. CONCLUSION: PVL-SA pneumonia is characterized by extensive parenchymal injuries, including necrotic and hemorrhagic complications. ECMO may be used as a salvage treatment without any associated hemorrhagic complication, provided anticoagulant therapy is carefully monitored, and may lead to complete pulmonary recovery at six months.


Assuntos
Toxinas Bacterianas/análise , Exotoxinas/análise , Oxigenação por Membrana Extracorpórea , Leucocidinas/análise , Pneumonia Necrosante/terapia , Pneumonia Estafilocócica/terapia , Staphylococcus aureus/química , Adolescente , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/induzido quimicamente , Pneumopatias/etiologia , Pneumopatias/prevenção & controle , Staphylococcus aureus Resistente à Meticilina/química , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pneumonia Necrosante/complicações , Pneumonia Necrosante/diagnóstico por imagem , Pneumonia Necrosante/microbiologia , Pneumonia Estafilocócica/complicações , Pneumonia Estafilocócica/diagnóstico por imagem , Pneumonia Estafilocócica/microbiologia , Indução de Remissão , Testes de Função Respiratória , Estudos Retrospectivos , Terapia de Salvação , Staphylococcus aureus/isolamento & purificação , Tomografia Computadorizada por Raios X , Vasoconstritores/uso terapêutico
19.
Transfusion ; 55(11): 2564-75, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26469998

RESUMO

BACKGROUND: Massive exchange transfusion of 42-day-old red blood cells (RBCs) in a canine model of Staphylococcus aureus pneumonia resulted in in vivo hemolysis with increases in cell-free hemoglobin (CFH), transferrin-bound iron (TBI), non-transferrin-bound iron (NTBI), and mortality. We have previously shown that washing 42-day-old RBCs before transfusion significantly decreased NTBI levels and mortality, but washing 7-day-old RBCs increased mortality and CFH levels. We now report the results of altering volume, washing, and age of RBCs. STUDY DESIGN AND METHODS: Two-year-old purpose-bred infected beagles were transfused with increasing volumes (5-10, 20-40, or 60-80 mL/kg) of either 42- or 7-day-old RBCs (n = 36) or 80 mL/kg of either unwashed or washed RBCs with increasing storage age (14, 21, 28, or 35 days; n = 40). RESULTS: All volumes transfused (5-80 mL/kg) of 42-day-old RBCs resulted in alike (i.e., not significantly different) increases in TBI during transfusion as well as in CFH, lung injury, and mortality rates after transfusion. Transfusion of 80 mL/kg RBCs stored for 14, 21, 28, and 35 days resulted in increased CFH and NTBI in between levels found at 7 and 42 days of storage. However, washing RBCs of intermediate ages (14-35 days) does not alter NTBI and CFH levels or mortality rates. CONCLUSIONS: Preclinical data suggest that any volume of 42-day-old blood potentially increases risks during established infection. In contrast, even massive volumes of 7-day-old blood result in minimal CFH and NTBI levels and risks. In contrast to the extremes of storage, washing blood stored for intermediate ages does not alter risks of transfusion or NTBI and CFH clearance.


Assuntos
Eritrócitos/fisiologia , Transfusão Total/métodos , Pneumonia Estafilocócica/terapia , Animais , Preservação de Sangue/efeitos adversos , Modelos Animais de Doenças , Cães , Transfusão de Eritrócitos/efeitos adversos , Eritrócitos/citologia , Transfusão Total/efeitos adversos , Fatores de Tempo
20.
In Vivo ; 28(5): 961-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25189914

RESUMO

BACKGROUND: Panton-Valentine leukocidin (PVL) is a cytotoxin that causes leukocyte destruction and lung necrosis. Managing respiratory failure and acute respiratory distress syndrome secondary to PVL-expressing Staphylococcus aureus pneumonia and its associated lung necrosis with mechanical ventilation is challenging. We report a patient with life-threatening PVL-expressing S. aureus-associated pneumonia who was rescued using extracorporeal membrane oxygenation (ECMO). CASE REPORT: We examined the case of a woman who presented to our Emergency Department with septic shock due to PVL-expressing S. aureus-associated pneumonia. A 27-year-old Filipino woman was transferred to our hospital due to severe dyspnea, hemosputum, and high-grade fever. She had a medical history of osteosarcoma of the leg and hyperthyroidism. On arrival, her vital signs indicated septic shock, with a white blood cell count of 3.5×10(3)/µl. Because a Gram stain of her sputum indicated SA, therapy with antibiotics, including meropenem and vancomycin, was started. Hypoxemia necessitated intubation and ventilation. Because the patient's PaO2/FiO2 remained less than 60 mmHg and her blood pressure was unstable despite aggressive conventional management, venoarterial ECMO was administered approximately 11 h after her arrival. The ECMO circuit was changed to veno-venous ECMO on day 7 and the patient was successfully weaned off ECMO after 12 days of treatment. She was discharged from the hospital 104 days after admission. CONCLUSION: This case demonstrates that early induction of ECMO support can be a reasonable therapeutic option for PVL-S. aureus-associated pneumonia. This patient's successful outcome might be attributable to early establishment of ECMO to prevent ventilation-induced lung injury.


Assuntos
Toxinas Bacterianas/genética , Coinfecção , Exotoxinas/genética , Oxigenação por Membrana Extracorpórea , Influenza Humana , Leucocidinas/genética , Pneumonia Estafilocócica/terapia , Staphylococcus aureus/genética , Adulto , Feminino , Humanos , Contagem de Leucócitos , Pneumonia Estafilocócica/diagnóstico , Pneumonia Estafilocócica/microbiologia , Radiografia Torácica , Resultado do Tratamento
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