RESUMO
Pseudomonas aeruginosa is a frequent cause of antimicrobial-resistant hospital-acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro-resolving actions of angiotensin-(1-7) [Ang-(1-7)] signaling through the G protein-coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang-(1-7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor-deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas-infected mice with Ang-(1-7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro-inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang-(1-7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang-(1-7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang-(1-7) pathway during infection is a potential strategy for the development of host-directed therapies to promote mechanisms of resistance and resilience to pneumonia.
Assuntos
Angiotensina I , Antibacterianos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos , Proto-Oncogene Mas , Infecções por Pseudomonas , Pseudomonas aeruginosa , Receptores Acoplados a Proteínas G , Animais , Angiotensina I/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Camundongos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/microbiologia , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/patologia , Pneumonia Bacteriana/metabolismo , Citocinas/metabolismo , Camundongos Knockout , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Pneumonia/microbiologia , Masculino , Pulmão/microbiologia , Pulmão/metabolismo , Pulmão/patologia , Transdução de Sinais/efeitos dos fármacos , Infiltração de Neutrófilos/efeitos dos fármacosRESUMO
BACKGROUND: Risk scores facilitate the assessment of mortality risk in patients with community-acquired pneumonia (CAP). Despite their utilities, there is a scarcity of evidence comparing the various RS simultaneously. This study aims to evaluate and compare multiple risk scores reported in the literature for predicting 30-day mortality in adult patients with CAP. METHODS: A retrospective cohort study on patients diagnosed with CAP was conducted across two hospitals in Colombia. The areas under receiver operating characteristic curves (ROC-curves) were calculated for the outcome of survival or death at 30 days using the scores obtained for each of the analyzed questionnaires. RESULTS: A total of 7454 potentially eligible patients were included, with 4350 in the final analysis, of whom 15.2% (662/4350) died within 30 days. The average age was 65.4 years (SD: 21.31), and 59.5% (2563/4350) were male. Chronic kidney disease was 3.7% (9.2% vs. 5.5%; p < 0.001) (OR: 1.85) higher in subjects who died compared to those who survived. Among the patients who died, 33.2% (220/662) presented septic shock compared to 7.3% (271/3688) of the patients who survived (p < 0.001). The best performances at 30 days were shown by the following scores: PSI, SMART-COP and CURB 65 scores with the areas under ROC-curves of 0.83 (95% CI: 0.8-0.85), 0.75 (95% CI: 0.66-0.83), and 0.73 (95% CI: 0.71-0.76), respectively. The RS with the lowest performance was SIRS with the area under ROC-curve of 0.53 (95% CI: 0.51-0.56). CONCLUSION: The PSI, SMART-COP and CURB 65, demonstrated the best diagnostic performances for predicting 30-day mortality in patients diagnosed with CAP. The burden of comorbidities and complications associated with CAP was higher in patients who died.
Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Curva ROC , Humanos , Infecções Comunitárias Adquiridas/mortalidade , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pneumonia/mortalidade , Pessoa de Meia-Idade , Colômbia/epidemiologia , Idoso de 80 Anos ou mais , Medição de Risco/métodos , Fatores de Risco , Adulto , PrognósticoRESUMO
La infección por SARS-CoV-2 puede generar síndrome de dificultad respiratoria aguda del adulto. El único trata-miento que demostró disminuir la mortalidad es la dexa-metasona. El tocilizumab es prometedor al inhibir la IL-6. La ausencia de evidencia local sobre su eficacia motivó este estudio restrospectivo, analítico y observacional, realizado desde 1/6/21 al 28/2/23 y que tiene como obje-tivos analizar mortalidad, requerimiento de oxígeno, días de internación y complicaciones de pacientes internados con COVID-19 grave que recibieron tocilizumab respec-to a un grupo control que recibió cuidados estándar. Se incluyeron 27 pacientes que recibieron tocilizumab y 69 en el grupo control. El promedio de días de enfermedad al recibir tocilizumab fue de 11,96. Encontramos una ten-dencia no estadísticamente significativa de menor mor-talidad (29 vs. 14,8% p=0,19), días de internación en UTI (13 vs. 19 p=0,6), requerimiento de oxígeno a alto flujo (22 vs. 45 p=0,11), asistencia mecánica respiratoria (5 vs. 21 p=0,23), complicaciones infecciosas (18,5 vs. 27,5% p=0,35) y no infecciosas (11 vs. 21,7% p=0,23) en el grupo que recibió tocilizumab con tendencia al aumento de PAFI y disminución de proteína C reactiva a las 48 horas de su infusión. El uso de tocilizumab podría asociarse a menor mortalidad, días de internación en UTI, necesidad de ARM y de complicaciones durante la internación, en pacientes grave, lo que impresiona estar en relación con una mejo-ría del estado hiperinflamatorio. Debido a que es un estu-dio unicéntrico y con bajo número de pacientes, debería ampliarse para obtener mayor evidencia de dicho efecto.
SARS-CoV-2 infection can lead to adult acute respirato-ry distress syndrome. The only treatment that has been shown to reduce mortality is dexamethasone. Tocilizum-ab shows promise in inhibiting IL-6. The absence of local evidence on its efficacy motivated this retrospective, an-alytical and observational study, from 6/1/21 to 2/28/23, which aims to analyze mortality, oxygen requirement, days of hospitalization and complications of hospitalized patients with COVID19. patients who received tocilizumab compared to a control group who received standard care. Twenty-seven patients who received tocilizumab and 69 in the control group were included. The average number of sick days when receiving tocilizumab was 11.96. We found a non-statistically significant trend of lower mor-tality (29 vs 14.8% p=0.19), days of ICU hospitalization (13 vs 19 p=0.6), high-flow oxygen requirement (22 vs 45 p =0.11), respiratory mechanical assistance (5 vs 21 p=0.23), infectious complications (18.5 vs 27.5% p=0.35) and non-infectious (11 vs 21.7% p=0 ,23), in the group that received tocilizumab with a tendency to increase PAFI and decrease C-reactive protein 48 hours after its infusion. The use of tocilizumab could be associated with lower mortality, days spent in the ICU, need for MRA, and complications during hospitalization, in seriously ill pa-tients, which seems to be related to an improvement in the hyperinflammatory state. Since it is a single-center study with a low number of patients, it should be expand-ed to obtain more evidence of this effect.
Assuntos
Humanos , Masculino , Feminino , Pneumonia/terapia , COVID-19/terapia , Inibidores de Interleucina-6/uso terapêutico , Mortalidade , Tempo de Internação/estatística & dados numéricosRESUMO
OBJECTIVE: This study investigated the effects of N-Acetylcysteine (NAC) combined with Ambroxol Hydrochloride (AH) on clinical symptoms, C-Reactive Protein (CRP), and Procalcitonin (PCT) levels in children with pneumonia. METHODS: A total of 98 children with pneumonia were assigned to the control group and observation group by random number table method. NAC was administered to the observation group and AH was given to the control group. The therapeutic effect was observed, the disappearance time of clinical symptoms and levels of inflammatory factors, lung function parameters, blood gas analysis parameters, and immunoglobulin were measured. The incidence of adverse reactions was statistically analyzed. RESULTS: A higher effective rate was observed in the observation group than in the control group (p < 0.05). Antipyretic time, cough disappearance time, and lung rale disappearance time in the observation group were shorter than those in the control group (p < 0.05). After treatment, CRP and PCT were lower (p < 0.05), FVC, FEV1, and FEV1/FVC were higher, PaCO2 was lower, PaO2 and SaO2 were higher, and IgA, IgG, IgM, and C3 were higher in the observation group than those in the control group (p < 0.05). The incidence of adverse reactions between the two groups was not significantly different (p > 0.05). CONCLUSION: NAC combined with AH is effective in the treatment of pediatric pneumonia by effectively alleviating clinical symptoms, reducing inflammatory factors, and improving lung function and immune function.
Assuntos
Acetilcisteína , Ambroxol , Proteína C-Reativa , Quimioterapia Combinada , Expectorantes , Pneumonia , Pró-Calcitonina , Humanos , Ambroxol/uso terapêutico , Ambroxol/administração & dosagem , Proteína C-Reativa/análise , Acetilcisteína/uso terapêutico , Feminino , Masculino , Pró-Calcitonina/sangue , Pré-Escolar , Expectorantes/uso terapêutico , Expectorantes/efeitos adversos , Pneumonia/tratamento farmacológico , Criança , Resultado do Tratamento , Lactente , GasometriaRESUMO
Five adult Greater Caribbean manatees Trichechus manatus manatus were found stranded on various coasts of Puerto Rico; 2 stranded alive and 3 stranded dead. Clinical signs observed in live-stranded manatees included emaciation, weakness, bradypnea, arrhythmia, and nasal mucus discharge. Postmortem examinations revealed serosanguinous, mucohemorrhagic, or suppurative exudate in bronchi associated with luminal adult Pulmonicola cochleotrema (range: 18-182 trematodes), accompanied by pulmonary abscesses in 2 cases. Histologically, we observed eosinophilic bronchopneumonia of varying severity (n = 4) and chronic erosive to eosinophilic tracheobronchitis (n = 4) with squamous metaplasia (n = 3) and intralesional trematodes and eggs. The trematode identity was confirmed and compared through molecular analysis for the amplified 18S rDNA fragment. Comorbidities included enteric chiorchosis (n = 5), gastric heterocheilosis (n = 4), malnutrition (n = 4), trauma related to watercraft collision (n = 3), systemic toxoplasmosis (n = 1), acute bacterial peritonitis (n = 1), and interstitial nephritis (n = 1), suggesting that immunosuppression was a predisposing factor for lower respiratory tract pulmonicolosis. Based on lesion severity, clinical signs, and the presence and absence of other findings to explain death, this condition was considered the primary cause of death in 1 manatee, a contributory cause of death in 3 manatees, and an incidental finding in 1 individual. These clinicopathological descriptions will facilitate the diagnosis and clinical management of pulmonicolosis in T. manatus, a species endangered with extinction.
Assuntos
Trematódeos , Infecções por Trematódeos , Animais , Trematódeos/isolamento & purificação , Trematódeos/classificação , Porto Rico/epidemiologia , Infecções por Trematódeos/veterinária , Infecções por Trematódeos/epidemiologia , Infecções por Trematódeos/parasitologia , Masculino , Bronquite/veterinária , Bronquite/parasitologia , Pneumonia/veterinária , Pneumonia/parasitologia , Trichechus manatus , FemininoRESUMO
Objetivo: Describir los hallazgos imagenológicos en radiografías de tórax y ecografías pulmonares de pacientes con síndrome post-COVID-19. Métodos: estudio descriptivo, prospectivo y transversal que incluyó pacientes con síndrome post-COVID-19, sometidos a radiografías de tórax y ecografías pulmonares en el Servicio de Neumonología Clínica del Hospital Dr. José Ignacio Baldo, entre enero y octubre de 2022, con la finalidad de establecer su evolución imagenológica pulmonar. Se utilizó estadística descriptiva, chi-cuadrado de Pearson y prueba kappa de concordancia, considerando significativo un valor de p < 0,05. Resultados: La muestra consistió en 58 pacientes con una edad media de 55 ± 13 años, predominando el sexo femenino (58,6%). El 60,3% mostró alteraciones en la radiografía de tórax; un 74,3% con patrón intersticial bilateral y un 25,7% con patrón intersticial unilateral. La ecografía reveló patrón intersticial en el 43,1% de los casos y se observaron dos microconsolidaciones subpleurales. Conclusiones: Las radiografías de tórax y las ecografías pulmonares son herramientas imagenológicas eficaces, accesibles y económicas para detectar alteraciones en pacientes con síndrome post-COVID-19. (AU)
Objective: To describe imaging findings in chest radiographs and lung ultrasounds of patients with post-COVID-19 syndrome. Methods: A descriptive, prospective, and cross-sectional study was carried out that included patients with post-COVID-19 syndrome, who underwent chest radiographs and lung ultrasounds at the Clinical Pneumonology Service of Dr. José Ignacio Baldo Hospital, between January and October 2022. Descriptive statistics, Pearson's chi-square, and kappa concordance test were used, considering a p-value < 0.05 significant. Results: The sample consisted of 58 patients with an average age of 55 ± 13 years, with a predominance of females (58.6%). 60.3% showed alterations in the chest radiograph; 74.3% with a bilateral interstitial pattern and 25.7% with a unilateral interstitial pattern. The ultrasound revealed an interstitial pattern in 43.1% of the cases and two subpleural microconsolidations were observed. Conclusions: Chest radiographs and lung ultrasounds are effective, accessible, and economical imaging tools to detect alterations in patients with post-COVID-19 syndrome. (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Radiografia Torácica , COVID-19/diagnóstico , Síndrome de COVID-19 Pós-Aguda/tratamento farmacológico , Pneumonia/patologia , Qualidade de Vida , Estudos Prospectivos , Doenças Pulmonares Intersticiais/tratamento farmacológicoRESUMO
Since human angiotensin-converting enzyme 2 (ACE2) serves as a primary receptor for SARS-CoV-2, characterizing ACE2 regions that allow SARS-CoV-2 to enter human cells is essential for designing peptide-based antiviral blockers and elucidating the pathogenesis of the virus. We identified and synthesized a 25-mer mimetic peptide (encompassing positions 22-46 of the ACE2 alpha-helix α1) implicated in the S1 receptor-binding domain (RBD)-ACE2 interface. The mimetic (wild-type, WT) ACE2 peptide significantly inhibited SARS-CoV-2 infection of human pulmonary Calu-3 cells in vitro. In silico protein modeling predicted that residues F28, K31, F32, F40, and Y41 of the ACE2 alpha-helix α1 are critical for the original, Delta, and Omicron strains of SARS-CoV-2 to establish the Spike RBD-ACE2 interface. Substituting these residues with alanine (A) or aspartic acid (D) abrogated the antiviral protective effect of the peptides, indicating that these positions are critical for viral entry into pulmonary cells. WT ACE2 peptide, but not the A or D mutated peptides, exhibited significant interaction with the SARS-CoV-2 S1 RBD, as shown through molecular dynamics simulations. Through identifying the critical amino acid residues of the ACE2 alpha-helix α1, which is necessary for the Spike RBD-ACE2 interface and mobilized during the in vitro viral infection of cells, we demonstrated that the WT ACE2 peptide protects susceptible K18-hACE2 mice against in vivo SARS-CoV-2 infection and is effective for the treatment of COVID-19.
Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Peptídeos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/química , Humanos , Animais , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , Camundongos , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/uso terapêutico , Tratamento Farmacológico da COVID-19 , Antivirais/farmacologia , Antivirais/química , Linhagem Celular , Pneumonia/tratamento farmacológico , Pneumonia/virologia , Pneumonia/prevenção & controle , Pulmão/virologia , Pulmão/patologia , FemininoRESUMO
BACKGROUND: Risk scores (RS) evaluate the likelihood of short-term mortality in patients diagnosed with community-acquired pneumonia (CAP). However, there is a scarcity of evidence to determine the risk of long-term mortality. This article aims to compare the effectiveness of 16 scores in predicting mortality at three, six, and twelve months in adult patients with CAP. METHODS: A retrospective cohort study on individuals diagnosed with CAP was conducted across two hospitals in Colombia. Receiver Operating Characteristic (ROC) curves were constructed at 3, 6, and 12 months to assess the predictive ability of death for the following scoring systems: CURB-65, CRB-65, SCAP, CORB, ADROP, NEWS, Pneumonia Shock, REA-ICU, PSI, SMART-COP, SMRT-CO, SOAR, qSOFA, SIRS, CAPSI, and Charlson Comorbidity Index (CCI). RESULTS: A total of 3688 patients were included in the final analysis. Mortality at 3, 6, and 12 months was 5.2%, 8.3%, and 16.3% respectively. At 3 months, PSI, CCI, and CRB-65 scores showed ROC curves of 0.74 (95% CI: 0.71-0.77), 0.71 (95% CI: 0.67-0.74), and 0.70 (95% CI: 0.66-0.74). At 6 months, PSI and CCI scores showed performances of 0.74 (95% CI: 0.72-0.77) and 0.72 (95% CI: 0.69-0.74), respectively. Finally at 12 months, all evaluated scores showed poor discriminatory capacity, including PSI, which decreased from acceptable to poor with an ROC curve of 0.64 (95% CI: 0.61-0.66). CONCLUSION: When predicting mortality in patients with CAP, at 3 months, PSI, CCI, and CRB-65 showed acceptable predictive performances. At 6 months, only PSI and CCI maintained acceptable levels of accuracy. For the 12-month period, all evaluated scores exhibited very limited discriminatory ability, ranging from poor to almost negligible.
Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Curva ROC , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Colômbia/epidemiologia , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/diagnóstico , Pneumonia/mortalidade , Pneumonia/diagnóstico , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Índice de Gravidade de Doença , Fatores de TempoRESUMO
OBJECTIVE: Antibiotic resistance is increasing globally, associated with many failures in pneumonia treatment. This study aimed to evaluate antibiotic use in children treated for outpatient CAP (Community-Acquired Pneumonia). METHODS: A cross-sectional descriptive retrospective study was conducted, focusing on data from outpatient prescriptions for pneumonia in patients aged 2â192 months in 2019â2021. RESULTS: All antibiotic prescriptions are considered empiric as no documented bacterial and viral tests exist for children with non-severe CAP. Single antibiotic therapy (66%) had a 2-fold higher rate than combination therapy (34%). Amoxicillin/clavulanic acid (50.77%) and azithromycin (30.74%) were the most commonly prescribed in both single and combination therapies, thus determining antibiotic cost (80.15%). Besides, azithromycin (97.92%), cefuroxime (86.26%), and cefpodoxime (60.48%) were prescribed with high adherence to dose guidelines, except for amoxicillin (34.57%). These medicines are prescribed highly compliant (>83%) with dosing interval guidelines. Furthermore, significantly more brand-name antibiotics (56.5%) are prescribed than generic antibiotics (43.5%). In particular, antibiotic class, antibiotic origin, and antibiotic therapies showed significant association with rational antibiotic prescriptions for dose and dose interval (p < 0.05). CONCLUSIONS: Amoxicillin/clavulanic acid is the most frequently prescribed medicine and the most inappropriate due to non-compliance with dose guidelines for CAP treatment. Generic antibiotic use for single therapy should be encouraged based on rapid and accurate diagnostic testing for viruses and bacteria to reduce antibiotic resistance in developing countries. Moreover, the study result has also shown that therapies and antibiotics (class and origin) exhibited significant association with rational prescriptions for CAP treatment for pediatrics.
Assuntos
Antibacterianos , Infecções Comunitárias Adquiridas , Humanos , Antibacterianos/uso terapêutico , Estudos Transversais , Estudos Retrospectivos , Pré-Escolar , Criança , Lactente , Feminino , Masculino , Vietnã , Infecções Comunitárias Adquiridas/tratamento farmacológico , Adolescente , Pacientes Ambulatoriais/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , Assistência Ambulatorial/estatística & dados numéricosRESUMO
BACKGROUND: The primary aim of this study is to assess the survival rates of individuals diagnosed with Community-Acquired Pneumonia (CAP) post-hospitalization in Colombia. Additionally, explore potential risk factors associated with decreased long-term survival. METHODS: A retrospective cohort study was conducted in a hospital in Colombia, evaluating survival at 3, 6 and 12 months in CAP patients, using the Kaplan-Meier method. Stratifications were made by age, sex, comorbidity, and severity. The comparison of survival curves was performed using the Log-Rank test, a multivariate analysis with Cox regression was performed to study possible risk factors that affected 12-month survival in patients with CAP. RESULTS: 3688 subjects were admitted, with a mortality of 16.3 % per year. Survival at three, six, and twelve months was 92.9 % (95 % CI 92-93 %), 88.8 % (95 % CI 87-90 %), and 84.2 % (95 % CI 82-85 %), respectively. Analysis stratified by pneumonia severity index, 12-month survival was 98.7 % in Class I, 95.6 % in Class II, 87.41 % in Class III, 77.1 % in Class IV, and 65.8 % in class-V (p < 0.001). Cox-regression showed that being male (HR = 1.44; 95 % CI 1.22â1.70; p < 0.001), an elevated pneumonia severity index (HR = 4.22; 95 % CI 1.89â9.43; p < 0.001), a high comorbidity index (HR = 2.29; 95 % CI 1.89â2.84; p < 0.001) and vasopressor requirement (HR = 2.22; 95 % CI < 0.001) were associated with a lower survival at twelve months of follow-up. CONCLUSION: Survival in patients with CAP who require hospitalization decreases at 3, 6, and 12 months of follow-up, being lower in patients older than 65 years, men, high comorbidity, and in subjects with severe presentation of the disease.
Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Índice de Gravidade de Doença , Humanos , Infecções Comunitárias Adquiridas/mortalidade , Estudos Retrospectivos , Masculino , Colômbia/epidemiologia , Feminino , Pessoa de Meia-Idade , Idoso , Pneumonia/mortalidade , Fatores de Risco , Adulto , Fatores de Tempo , Estimativa de Kaplan-Meier , Taxa de Sobrevida , Idoso de 80 Anos ou mais , Comorbidade , Adulto Jovem , Hospitalização/estatística & dados numéricosRESUMO
OBJECTIVE: To assess whether a two-phase intervention was associated with improvements in antibiotic prescribing among nonhospitalized children with community-acquired pneumonia. STUDY DESIGN: In a large health care organization, a first intervention phase was implemented in September 2020 directed at antibiotic choice and duration for children 2 months through 17 years of age with pneumonia. Activities included clinician education and implementation of a pneumonia-specific order set in the electronic health record. In October 2021, a second phase comprised additional education and order set revisions. A narrow spectrum antibiotic (eg, amoxicillin) was recommended in most circumstances. Electronic health record data were used to identify pneumonia cases and antibiotics ordered. Using interrupted time series analyses, antibiotic choice and duration after phase one (September 2020-September 2021) and after phase two (October 2021-October 2022) were compared with a preintervention prepandemic period (January 2016-early March 2020). RESULTS: Overall, 3570 cases of community-acquired pneumonia were identified: 3246 cases preintervention, 98 post-phase one, and 226 post-phase two. The proportion receiving narrow spectrum monotherapy increased from 40.6% preintervention to 68.4% post-phase one to 69.0% post-phase two (P < .001). For children with an initial narrow spectrum antibiotic, duration decreased from preintervention (mean duration 9.9 days, SD 0.5 days) to post-phase one (mean 8.2, SD 1.9) to post-phase two (mean 6.8, SD 2.3) periods (P < .001). CONCLUSIONS: A two-phase intervention with educational sessions combined with clinical decision support was associated with sustained improvements in antibiotic choice and duration among children with community-acquired pneumonia.
Assuntos
Antibacterianos , Infecções Comunitárias Adquiridas , Pneumonia , Padrões de Prática Médica , Humanos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Lactente , Adolescente , Feminino , Masculino , Pneumonia/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Assistência Ambulatorial , Registros Eletrônicos de Saúde , Análise de Séries Temporais Interrompida , Gestão de Antimicrobianos/métodos , Pacientes Ambulatoriais , Melhoria de QualidadeRESUMO
Cefepime and piperacillin/tazobactam are antimicrobials recommended by IDSA/ATS guidelines for the empirical management of patients admitted to the intensive care unit (ICU) with community-acquired pneumonia (CAP). Concerns have been raised about which should be used in clinical practice. This study aims to compare the effect of cefepime and piperacillin/tazobactam in critically ill CAP patients through a targeted maximum likelihood estimation (TMLE). A total of 2026 ICU-admitted patients with CAP were included. Among them, (47%) presented respiratory failure, and (27%) developed septic shock. A total of (68%) received cefepime and (32%) piperacillin/tazobactam-based treatment. After running the TMLE, we found that cefepime and piperacillin/tazobactam-based treatments have comparable 28-day, hospital, and ICU mortality. Additionally, age, PTT, serum potassium and temperature were associated with preferring cefepime over piperacillin/tazobactam (OR 1.14 95% CI [1.01-1.27], p = 0.03), (OR 1.14 95% CI [1.03-1.26], p = 0.009), (OR 1.1 95% CI [1.01-1.22], p = 0.039) and (OR 1.13 95% CI [1.03-1.24], p = 0.014)]. Our study found a similar mortality rate among ICU-admitted CAP patients treated with cefepime and piperacillin/tazobactam. Clinicians may consider factors such as availability and safety profiles when making treatment decisions.
Assuntos
Antibacterianos , Cefepima , Infecções Comunitárias Adquiridas , Estado Terminal , Unidades de Terapia Intensiva , Combinação Piperacilina e Tazobactam , Humanos , Cefepima/uso terapêutico , Cefepima/administração & dosagem , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/mortalidade , Combinação Piperacilina e Tazobactam/uso terapêutico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Funções Verossimilhança , Pneumonia/tratamento farmacológico , Pneumonia/mortalidade , Piperacilina/uso terapêuticoRESUMO
COVID-19 has affected more than half a billion people worldwide, with more than 6.3 million deaths, but the pathophysiological mechanisms involved in lethal cases and the host determinants that determine the different clinical outcomes are still unclear. In this study, we assessed lung autopsies of 47 COVID-19 patients and examined the inflammatory profiles, viral loads, and inflammasome activation. Additionally, we correlated these factors with the patient's clinical and histopathological conditions. Robust inflammasome activation was detected in the lungs of lethal cases of SARS-CoV-2. Experiments conducted on transgenic mice expressing hACE2 and infected with SARS-CoV-2 showed that Nlrp3-/- mice were protected from disease development and lethality compared to Nlrp3+/+ littermate mice, supporting the involvement of this inflammasome in disease exacerbation. An analysis of gene expression allowed for the classification of COVID-19 patients into two different clusters. Cluster 1 died with higher viral loads and exhibited a reduced inflammatory profile than Cluster 2. Illness time, mechanical ventilation time, pulmonary fibrosis, respiratory functions, histopathological status, thrombosis, viral loads, and inflammasome activation significantly differed between the two clusters. Our data demonstrated two distinct profiles in lethal cases of COVID-19, thus indicating that the balance of viral replication and inflammasome-mediated pulmonary inflammation led to different clinical outcomes. We provide important information to understand clinical variations in severe COVID-19, a process that is critical for decisions between immune-mediated or antiviral-mediated therapies for the treatment of critical cases of COVID-19.
Assuntos
COVID-19 , Pulmão , SARS-CoV-2 , Carga Viral , Replicação Viral , COVID-19/virologia , COVID-19/mortalidade , COVID-19/imunologia , COVID-19/patologia , Animais , Humanos , Camundongos , Feminino , Masculino , Pulmão/virologia , Pulmão/patologia , Pulmão/imunologia , Pessoa de Meia-Idade , Inflamassomos/imunologia , Inflamassomos/metabolismo , Idoso , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Camundongos Transgênicos , Pneumonia/virologia , Pneumonia/mortalidade , Pneumonia/imunologia , Pneumonia/patologia , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Camundongos Knockout , AdultoRESUMO
PURPOSE: Patients with hematologic malignancies (HM) are at high risk of invasive lung fungal infections (ILFI). To describe the main characteristics, treatment, and outcomes for five years in adult patients with HM and fungal pneumonia. METHODS: We conducted a retrospective study at Instituto Nacional de Cancerología (INCan), a referral tertiary care oncology hospital with 135 beds in Mexico City, Mexico. We included all cases of fungal pneumonia in patients with HM from January 1, 2017, to December 31, 2022. Cases were classified as proven, probable, and possible according to EORTC/MSG criteria 2021. RESULTS: Two hundred ten patients were included; the mean age was 40 years. The most frequent HM was acute lymphoblastic leukemia (n = 74) and acute myeloid leukemia (n = 68). One hundred forty patients (66.7%) had severe neutropenia for a median of 16 days. All patients had a CT thorax scan; in 132 (62.9%), multiple nodules were documented. Serum galactomannan (GM) was positive in 21/192 (10.9%) and bronchoalveolar lavage in 9/36 (25%). Fifty-three patients (25.2%) died in the first month. In the multivariate analysis for mortality in the first 30 days, hypoalbuminemia, shock, possible ILFI, and inappropriate antifungal treatment were statistically associated. CONCLUSIONS: In high-risk HM patients, CT thorax scan and GM help diagnose ILFI. An appropriate antifungal improves mortality.
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Neoplasias Hematológicas , Humanos , Adulto , Masculino , Estudos Retrospectivos , Feminino , Neoplasias Hematológicas/complicações , Pessoa de Meia-Idade , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/complicações , Adulto Jovem , Antifúngicos/uso terapêutico , México/epidemiologia , Idoso , Pneumonia/microbiologia , Adolescente , Galactose/análogos & derivados , Mananas/sangue , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/mortalidade , Infecções Fúngicas Invasivas/diagnósticoRESUMO
Introducción: La neumonía por COVID-19 puede presentarse con dos patrones radio-lógicos: daño alveolar difuso o neumonía organizativa. Estos patrones tienen diferente evolución y pronóstico en pacientes sin infección por COVID-19. Nuestro objetivo fue evaluar la prevalencia del patrón radiológico de neumonía organizativa y su asociación con los desenlaces clínicos.Métodos: Se realizó un estudio de cohorte retrospectivo que incluyó a pacientes adultos hospitalizados por COVID-19 grave/crítica a los que se les realizó una tomografía computarizada de tórax en los 21 días posteriores al diagnóstico. Los patrones radiológicos fueron revisados y clasificados por dos radiólogos expertos. Resultados: De los 80 pacientes incluidos, el 89% (n=71) presentaron un patrón compatible con neumonía organizativa. Los principales hallazgos radiológicos fueron la distribución multilobar (98,7%) y bilateral (97,6%) con opacidades en vidrio esmerilado (97,6%). El 44% (n=33) de los sujetos requirió ingreso en cuidados intensivos, de los cuales el 24% (n=19) recibió ventilación mecánica. La presencia de neumonía organizativa se asoció de forma independiente con una disminución de las probabilidades de ventilación mecánica o muerte (Odds ratio 0,14; intervalo de confianza del 95%: 0,02 - 0,96; valor de p 0,045) en un modelo multivariado que incluía la edad, el sexo, el IMC y la afectación pulmonar en la TC.Conclusiones: Un patrón radiológico de neumonía organizativa es altamente prevalen-te en pacientes con COVID-19 grave/crítico y se asocia con mejores resultados clínico
Introduction: COVID-19 pneumonia can present with two distinct radiologic patterns: diffuse alveolar damage or organizing pneumonia. These patterns have been linked to different outcomes in non-COVID-19 settings. We sought to assess the prevalence of organizing pneumonia radiologic pattern and its association with clinical outcomes. Methods: We performed a retrospective cohort study including adult patients hospita- lized for severe/critical COVID-19 who underwent chest computed tomography within 21 days of diagnosis. Radiologic patterns were reviewed and classified by two expert radiologists. Results: Among 80 patients included, 89% (n=71) presented a pattern consistent with organizing pneumonia. The main radiologic findings were multilobar (98.7%) and bilateral (97.6%) distribution with ground glass opacities (97.6%). Intensive care admission was required for 44% (n=33) of subjects, of which 24% (n=19) received mechanical ventilation. The presence of organizing pneumonia was independently associated with a decreased odds of mechanical ventilation or death (Odds ratio 0.14; 95% confidence interval 0.02 - 0.96; p value 0.045) in a multivariate model including age, gender, BMI and lung involvement on CT. Conclusion: A radiologic pattern of organizing pneumonia is highly prevalent in patients with severe/critical COVID-19 and is associated with improved clinical outcomes.
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pneumonia/diagnóstico por imagem , SARS-CoV-2 , COVID-19/epidemiologia , Argentina/epidemiologia , Respiração Artificial , Comorbidade , Diagnóstico Clínico , Reação em Cadeia da Polimerase/métodos , Prevalência , Estudos de Coortes , Estado Terminal , Teste Sorológico para COVID-19RESUMO
Introducción: SARS-CoV-2 ha causado millones de muertes a nivel global desde su primer caso reportado en China. En Guatemala existen pocos estudios que describan los factores pronósticos. Nuestro objetivo fue determinar los factores asociados de mortalidad a 30 días en pacientes con neumonía (Nm) por SARS-CoV-2 y construir un modelo predictor. Material y Métodos: Estudio retrospectivo en 144 sujetos en el Hospital Roosevelt de marzo a diciembre 2020 con criterios de Nm por SARS-CoV-2. Se revisó el expediente médico para datos clínicos y de laboratorio desde ingreso hasta alta hospitalaria o muerte. Resultados: Se evaluaron 105 hombres y 39 mujeres con media de edad 53 años. El 47% tenía comorbilidades como diabetes mellitus 2 e hipertensión arterial sistémica. Promedio de días de hospitalización: 13. Cuadros leves a moderados de Síndrome de Distrés Respiratorio Agudo (SDRA): 92%. Se indicó ventilación mecánica invasiva (VMI) a 46 pacientes. La mortalidad general fue 35%. Factores asociados a mortalidad a 30 días: edad ≥50 años, inicio de síntomas ≥7 días, SDRA severo, radio NL >4,4, recibir VMI, alteración en LDH y procalcitonina. Nuestro modelo mostró que los mejores predictores de mortalidad eran alteración en procalcitonina (OR: 4,45), recibir VMI (OR: 112) y días de estancia hospitalaria (OR: 1,12) con precisión de 91,5% y área bajo la curva de 94,4%. Conclusiones: Los factores pronósticos de mortalidad en pacientes guatemaltecos con Nm por SARS-CoV-2 son múltiples e incluyen rasgos demográficos, clínicos y serológicos; identificarlos y contar con un modelo pronóstico ayudará a brindar atención médica de precisión.
Introduction: SARS-CoV-2 has caused millions of deaths globally since its first case was reported in China. In Guatemala, few studies describe prognostic factors. Our objective was to determine the factors associated with 30 day mortality in patients with Pneumonia (Nm) due to SARS-CoV-2 and to build a predictor model. Material and Methods: Retrospective study in 144 subjects at Roosevelt Hospital from March to December 2020 with Nm criteria for SARS-CoV-2. The medical record was rviewed, obtaining clinical and laboratory data from admission to hospital discharge or death. Results: 105 men and 39 women with an average age of 53 years were evaluated. 47% had comorbidities, with type 2 diabetes mellitus and systemic arterial hypertension being common. The average number of days of hospitalization was 13. 92% had mild to moderate acute respiratory distress syndrome (ARDS). Invasive mechanical ventila-tion (IMV) was indicated for 46 patients. Overall mortality was 35%. The factors asso-ciated with 30-day mortality were age ≥50 years, the onset of symptoms ≥7 days, severe ARDS, N/L ratio >4.4, receiving IMV, alterations in LDH, and procalcitonin. Our model showed that the best predictors of mortality were altered procalcitonin (OR: 4.45), receiving IMV (OR: 112), and days of hospital stay (OR: 1.12) with precision of 91.5% and area under the curve of 94.4%. Conclusions: The prognostic factors of mortality in Guatemalan patients with Nm due to SARS-CoV-2 are multiple and include demographic, clinical and serological features; identifying them and having a prognostic model will help provide precision medical care.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Pneumonia/mortalidade , Prognóstico , SARS-CoV-2 , COVID-19/epidemiologia , Oxigenoterapia , Respiração Artificial , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidade , Comorbidade , Reação em Cadeia da Polimerase , Ultrassonografia , Fatores Etários , Guatemala/epidemiologiaRESUMO
La bronquitis plástica es una enfermedad infrecuente y poco estudiada. Se caracteriza por la obstrucción parcial o total de la vía aérea inferior por moldes o yesos gomosos y firmes, compuestos por múltiples sustancias como fibrina, mucina y otros, que se acumulan en la luz bronquial. En la actualidad, no hay un consenso de la fisiopatología real. Puede presentarse con síntomas leves como tos, sibilancias y disnea, hasta eventos fatales de insuficiencia respiratoria. Se clasifican en tipo I (inflamatorios) y tipo II (acelulares). La presencia de la bronquitis plástica es una complicación de varias enfermedades y está relacionada con procedimientos correctivos de cardiopatías congénitas (procedimiento de Fontan). El diagnóstico se hace a través de la identificación de los yesos bronquiales, ya sea cuando el paciente los expectora o por broncoscopía. Se han utilizado múltiples terapias que solo tienen evidencias anecdóticas. En los últimos años se han observado buenos resultados con el uso de heparinas, así como el alteplasa nebulizado e instilado por broncoscopia.
Plastic bronchitis is a rare and little-studied disease. It is characterized by partial or total obstruction of the lower airway by rubbery and firm molds or plasters, made up of multiple substances that accumulate in the bronchial lumen. Currently, there is no consensus on real pathophysiology. It can present itself with mild symptoms such as cough, wheezing and dyspnea, to fatal events of respiratory failure. They are classified into type I (inflammatory) and type II (acellular). The presence of plastic bronchitis is a complication of several diseases and in corrective procedures for congenital heart disease (Fontan procedure). Diagnosis is made by identifying bronchial casts, either by the patient expectorating them or by bronchoscopy. Multiple therapies have been used that only have anecdotal evidence. In recent years, good results have been observed with the use of heparins and tPA nebulized and instilled by bronchoscop.
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Humanos , Feminino , Adulto , Bronquite/diagnóstico , Broncoscopia , Técnica de Fontan , Pneumonia , Insuficiência Respiratória , Choque Séptico , Fibrina , Traqueostomia , Sons Respiratórios , Tosse , Obstrução das Vias Respiratórias/diagnóstico , DispneiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis poses one of the biggest public health problems, necessitating the search for new therapeutic alternatives. For centuries, propolis has been widely used in folk medicine to treat various inflammatory and infectious diseases. Given its extensive use, it has excellent potential as an adjuvant treatment for patients with sepsis. OBJECTIVE: This study evaluated prophylactic treatment with standardized propolis extract (EPP-AF®) and followed the prognosis of sepsis induced by ligation and cecal ligation and puncture (CLP). METHODS: Initially, for survival assessment, Swiss mice were separated into five groups: Sham (false operated), control (PBS), ATB (received antibiotic, 8 mg/kg), P10 (received EPP-AF®, 10 mg/kg), and P100 (received EPP-AF®, 100 mg/kg). The animals received PBS, antibiotic, or EPP-AF® by the subcutaneous route 6 h before the CLP procedure. Animal survival was assessed every 12 h for five days when all of them were euthanized. RESULTS: We show that the treatment with EPP-AF® significantly increased the life expectancy of animals with sepsis compared to the control group. Interestingly, prophylactic treatment with EPP-AF® showed no effect on the number of colony-forming units in the peritoneum, blood, or lung. However, there was a decrease in cellular influx in the peritoneum. This alteration was unrelated to the number of bone marrow cells or the differential counting of peripheral blood cells. The coagulogram remained unchanged, including the number of platelets and prothrombin time-activated partial thromboplastin time. However, the inflammatory infiltrate and bleeding in the lung tissue were lower in the animals that received EPP-AF®. CONCLUSION: Thus, it was possible to conclude that prophylactic treatment with EPP-AF® preserved the lung parenchyma, resulting in an increased lifespan of mice with sepsis. It can be a helpful adjuvant in prophylactic treatment with antibiotics in presurgical conditions.
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Própole , Sepse , Animais , Própole/farmacologia , Sepse/tratamento farmacológico , Sepse/mortalidade , Camundongos , Masculino , Abelhas , Pneumonia/prevenção & controle , Pneumonia/tratamento farmacológico , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/patologiaRESUMO
BACKGROUND: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. OBJECTIVE: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. METHODS: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. OUTCOMES: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. CONCLUSION: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.
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Infecções Comunitárias Adquiridas , Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório , Humanos , Brasil/epidemiologia , Colômbia/epidemiologia , Infecções Comunitárias Adquiridas/terapia , Unidades de Terapia Intensiva , Pneumonia/terapia , Respiração com Pressão Positiva/métodos , Estudos Prospectivos , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/fisiopatologia , Volume de Ventilação Pulmonar , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
OBJECTIVE: To assess differences in the sputum microbiota of community-acquired pneumonia (CAP) patients with either COPD or asthma, specifically focusing on a patient population in Turkey. METHODS: This retrospective study included hospitalized patients > 18 years of age with a diagnosis of pneumonia between January of 2021 and January of 2023. Participants were recruited from two hospitals, and three patient groups were considered: CAP patients with asthma, CAP patients with COPD, and CAP patients without COPD or asthma. RESULTS: A total of 246 patients with CAP were included in the study, 184 (74.8%) and 62 (25.2%) being males and females, with a mean age of 66 ± 14 years. Among the participants, 52.9% had COPD, 14.2% had asthma, and 32.9% had CAP but no COPD or asthma. Upon analysis of sputum cultures, positive sputum culture growth was observed in 52.9% of patients. The most commonly isolated microorganisms were Pseudomonas aeruginosa (n = 40), Acinetobacter baumannii (n = 20), Klebsiella pneumoniae (n = 16), and Moraxella catarrhalis (n = 8). CAP patients with COPD were more likely to have a positive sputum culture (p = 0.038), a history of antibiotic use within the past three months (p = 0.03), utilization of long-term home oxygen therapy (p < 0.001), and use of noninvasive ventilation (p = 0.001) when compared with the other patient groups. Additionally, CAP patients with COPD had a higher CURB-65 score when compared with CAP patients with asthma (p = 0.004). CONCLUSIONS: This study demonstrates that CAP patients with COPD tend to have more severe presentations, while CAP patients with asthma show varied microbial profiles, underscoring the need for patient-specific management strategies in CAP.