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1.
JAMA ; 322(13): 1261-1270, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573637

RESUMO

Importance: Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS). Objective: To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. Design, Setting, and Participants: The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018. Interventions: Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. Main Outcomes and Measures: The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. Results: Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 µg/mL; difference, 7.94 µg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours. Conclusions and Relevance: In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS. Trial Registration: ClinicalTrials.gov Identifier: NCT02106975.


Assuntos
Ácido Ascórbico/administração & dosagem , Insuficiência de Múltiplos Órgãos/prevenção & controle , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Sepse/tratamento farmacológico , Vitaminas/administração & dosagem , Adulto , Idoso , Ácido Ascórbico/uso terapêutico , Biomarcadores/sangue , Proteína C-Reativa/análise , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Escores de Disfunção Orgânica , Síndrome do Desconforto Respiratório do Adulto/complicações , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Sepse/complicações , Sepse/mortalidade , Trombomodulina/sangue , Vitaminas/uso terapêutico
2.
Medicine (Baltimore) ; 98(39): e17354, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574878

RESUMO

INTRODUCTION: The incidence, mortality, and treatment costs of sepsis are high and, thus, present a major challenge for critical care medicine. Our previous studies suggest that intestinal metabolite granisetron has a potential therapeutic effect on sepsis. Granisetron is a clinically widely used antiemetic, which is safe, inexpensive, and reliable. However, its value in the treatment of sepsis remains unclear. This study aims to explore the efficacy and safety of granisetron in the treatment of sepsis. METHODS AND ANALYSIS: A single-center, single-blind, randomized, controlled clinical trial will be conducted on 154 patients with sepsis. Patients who meet sepsis 3.0 diagnostic criteria, aged ≥18 and ≤80 years, with PCT ≥ 2 ng/mL will be recruited. Patients will be randomized to receive intravenous granisetron 3 mg every 8 hours (n = 77) or an equal volume of normal saline (n = 77) for a treatment period of 4 days or to ICU discharge. The primary outcome is 28-day all-cause mortality. Secondary outcome measures include requirements for organ function support, changes of organ function, changes in infection biomarkers, changes in inflammatory and immune biomarkers, and the proportion of new organ failure. Adverse events and serious adverse events also will be observed closely. ETHICS AND DISSEMINATION: The study was approved by the Clinical Ethics Committee of Zhujiang Hospital of Southern Medical University (2018-ZZJHZX-009). The trial results will be disseminated at national and international conferences and through peer-reviewed journal. TRIAL REGISTRATION: NCT03924518.URL: www.clinicaltrials.gov. PROTOCOL DATE: 1 May 2019. version 2.1.


Assuntos
Granisetron/administração & dosagem , Sepse/tratamento farmacológico , Antagonistas da Serotonina/administração & dosagem , Choque Séptico/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/mortalidade , Choque Séptico/mortalidade , Método Simples-Cego , Resultado do Tratamento , Adulto Jovem
3.
Artigo em Inglês | MEDLINE | ID: mdl-31426735

RESUMO

The Australian Group on Antimicrobial Resistance (AGAR) performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2017 survey was the fifth year to focus on blood stream infections, and included Enterobacterales, Pseudomonas aeruginosa and Acinetobacter species. Seven thousand nine hundred and ten isolates, comprising Enterobacterales (7,100, 89.8%), P. aeruginosa (697, 8.8%) and Acinetobacter species (113, 1.4%), were tested using commercial automated methods. The results were analysed using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (January 2018). Of the key resistances, non-susceptibility to the third-generation cephalosporin, ceftriaxone, was found in 11.3%/11.3% of Escherichia coli (CLSI/EUCAST criteria), 8.8%/8.8% of Klebsiella pneumoniae, and 5.7%/5.7% of K. oxytoca. Non-susceptibility rates to ciprofloxacin were 12.1%/18.0% for E. coli, 4.4%/11.2% for K. pneumoniae, 1.3%/3.5% for K. oxytoca, 3.0%/8.5% for Enterobacter cloacae complex, and 5.1%/9.8% for P. aeruginosa. Resistance rates to piperacillin-tazobactam were 2.8%/5.9%, 3.7%/7.3%, 9.6%/11.0%, 22.5%/27.6%, and 6.4%/13.2% for the same five species respectively. Twenty-seven isolates from 25 patients were shown to harbour a carbapenemase gene: 12 blaIMP (11 patients), five blaOXA-181 (four patients), three blaOXA-23, two blaNDM, two blaKPC, two blaVIM, and one blaGES.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Sepse/tratamento farmacológico , Sepse/epidemiologia , Sepse/microbiologia , Relatórios Anuais como Assunto , Austrália/epidemiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Infecção Hospitalar/tratamento farmacológico , Infecções por Enterobacteriaceae/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Tipagem Molecular , Avaliação de Resultados da Assistência ao Paciente , Pseudomonas aeruginosa/efeitos dos fármacos , beta-Lactamases/genética , beta-Lactamases/metabolismo
4.
Adv Exp Med Biol ; 1145: 321-341, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364085

RESUMO

Polymyxin B is an antibiotic that shows strong bactericidal activity against Gram-negative bacteria, by binding to and inactivating endotoxin. Systemic administration of polymyxin B in humans is restricted because of its nephrotoxicity and neurotoxicity, and this compound was therefore considered a strong candidate ligand for the extracorporeal selective adsorption of circulating endotoxin in the blood. Toraymyxin® is a direct hemoperfusion column that uses polymyxin B attached to an insoluble carrier to bind endotoxin in the blood. In 1994, the Japanese National Health Insurance system approved the use of Toraymyxin for the treatment of endotoxemia and septic shock.In this chapter, we will review the development, clinical use, and efficacy of Toraymyxin, examine the structure of the Toraymyxin column, and comment on the current position of Toraymyxin in the treatment of severe sepsis and septic shock. We will also highlight some potential new applications of Toraymyxin for pulmonary diseases.


Assuntos
Antibacterianos/farmacologia , Endotoxinas/isolamento & purificação , Hemoperfusão , Polimixina B/farmacologia , Endotoxemia/tratamento farmacológico , Endotoxinas/sangue , Humanos , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico
5.
Rev Med Liege ; 74(7-8): 410-413, 2019 Jul.
Artigo em Francês | MEDLINE | ID: mdl-31373456

RESUMO

The occurrence of non-viral meningitis remains a heavy diagnosis carrying undeniable pejorative aspects that may vary according to several factors such as the age and the presence or absence of an immunodeficiency. In some cases, uncommon germs can also lead to a bad prognosis such as Listeria monocytogenes that can be responsible of an extremely severe septic state. We report the case of a girl with Listeria meningitis, whose evolution was unfortunately quickly negative.


Assuntos
Listeria monocytogenes , Listeriose , Meningite por Listeria , Sepse , Antibacterianos/uso terapêutico , Criança , Evolução Fatal , Feminino , Humanos , Imunocompetência , Listeria monocytogenes/patogenicidade , Listeriose/diagnóstico , Listeriose/tratamento farmacológico , Listeriose/microbiologia , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/microbiologia
6.
Life Sci ; 232: 116613, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265853

RESUMO

AIMS: Sepsis is a leading cause of death and disability worldwide. Autophagy may play a protective role in sepsis-induced myocardial dysfunction (SIMD). The present study investigated whether valproic acid (VPA), a class I histone deacetylase (HDAC) inhibitor, can attenuate SIMD by accelerating autophagy. MAIN METHODS: A sepsis model was established via the cecum ligation and puncture of male Sprague-Dawley rats. Cardiac injuries were measured using serum markers, echocardiographic cardiac parameters, and hematoxylin and eosin staining. Cardiac mitochondria injuries were detected with transmission electron microscopy, adenosine triphosphate (ATP) and cardiac mitochondrial DNA (mtDNA) contents. Cardiac oxidative levels were measured using redox markers in the cardiac homogenate. Real-time polymerase chain reaction (RT-PCR) and Western blot were performed to detect the expression levels of relative genes and proteins. HDAC binding to the phosphatase and tensin homolog deleted on chromosome ten (PTEN) promoters and histone acetylation levels of the PTEN promoters were analyzed via chromatin immunoprecipitation and quantitative RT-PCR. KEY FINDINGS: VPA can ameliorate SIMD by enhancing the autophagy level of the myocardium to reduce mitochondrial damage, oxidative stress, and myocardial inflammation in septic rats. Moreover, this study demonstrated that VPA induces autophagy by inhibiting HDAC1- and HDAC3-mediated PTEN expression in the myocardial tissues of septic rats. SIGNIFICANCE: This study found that VPA attenuates SIMD through myocardial autophagy acceleration by increasing PTEN expression and inhibiting the AKT/mTOR pathway. These findings preliminarily suggest that VPA may be a potential approach for the intervention and treatment of SIMD.


Assuntos
PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sepse/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Ácido Valproico/farmacologia , Disfunção Ventricular/tratamento farmacológico , Animais , Autofagia/efeitos dos fármacos , Ceco/metabolismo , Modelos Animais de Doenças , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Masculino , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Sepse/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Disfunção Ventricular/microbiologia , Disfunção Ventricular/patologia
7.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2691-2700, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359679

RESUMO

Guizhi Decoction is a resolving agent,which is a classic prescription for traditional Chinese medicine. It is effective in the treatment of sepsis in clinical practice. However,due to the complexity of the prescription,its anti-sepsis mechanism is difficult to be clarified. The " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair,as the classic compatibility for medicinal and medicinal herbs,is the core of Guizhi Decoction. In this study,Cinnamomi Ramulus-Paeoniae Radix Alba drug pair was used as the research object and the molecular mechanism of its treatment of sepsis was investigated by analyzing the chemical compositions with integrative pharmacology platform( TCMIP,http://www.tcmip.cn/),predicting disease target,analyzing gene function and pathway of " Cinnamomi Ramulus-Paeoniae Radix Alba" in treatment of sepsis,and establishing a multi-dimensional network relationship of " Chinese medicine-chemical components-core targets-key pathways". The prediction results of " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair showed that its anti-sepsis effect was associated with 45 active components,and the active components played an anti-sepsis role through multiple targets and pathways,involving inflammatory targets such as PF4,MyD88,TLR4,BDKRB2,CD14,and NOS3. The sepsis was relieved mainly by regulating Toll like signaling pathway,Fox O signaling pathway,chemokines signaling pathway,thyroid and insulin endocrine signaling pathways and biological processes. This study provides a scientific basis for further development of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair and Guizhi Decoction against sepsis.


Assuntos
Cinnamomum/química , Medicamentos de Ervas Chinesas/farmacologia , Paeonia/química , Sepse/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa , Plantas Medicinais/química
8.
Medicine (Baltimore) ; 98(26): e16248, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261589

RESUMO

INTRODUCTION: Community-acquired (CA) carbapenem-susceptible Acinetobacter baumannii (CSAB) enterogenic sepsis is very rare but has a high mortality. Although CA A. baumannii bloodstream infections have been known to develop from respiratory tract, urinary tract, and intravenous device-related infections, CA A. baumannii bloodstream infections from the gastrointestinal tract have not yet been reported. PATIENT CONCERNS: A 73-year-old male with the chief presentation of gastrointestinal symptoms was initially diagnosed with acute gastroenteritis and showed poor clinical response to empirical antibiotic therapy. DIAGNOSES: The diagnosis of CSAB enterogenic sepsis was established based on results of blood culture, elevated serum procalcitonin level, and specific hemodynamic changes related to septic shock. INTERVENTIONS: The patient initially received empirical antibiotic treatment (cefodizime 2.0 q12 hours plus moxifloxacin 0.4 qd); then, treatment was changed to the conventional dose of carbapenem (imipenem 0.5 q6 hour). OUTCOMES: Finally, CSAB was eliminated from the bloodstream, and the patient was discharged. LESSONS: Although severe, CA CSAB enterogenic sepsis is often misdiagnosed because of its clinical rarity. Early diagnosis and appropriate initial empirical antibiotic therapy are crucial for treating such cases.


Assuntos
Infecções por Acinetobacter/diagnóstico , Acinetobacter baumannii/efeitos dos fármacos , Carbapenêmicos/farmacologia , Sepse/diagnóstico , Infecções por Acinetobacter/tratamento farmacológico , Idoso , Carbapenêmicos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Humanos , Enteropatias/diagnóstico , Enteropatias/tratamento farmacológico , Enteropatias/microbiologia , Masculino , Testes de Sensibilidade Microbiana , Sepse/tratamento farmacológico
9.
BMC Infect Dis ; 19(1): 584, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349818

RESUMO

BACKGROUND: Community-acquired sepsis is a life-threatening systemic reaction, which starts within ≤72 h of hospital admittance in an infected patient without recent exposure to healthcare risks. Our aim was to evaluate the characteristics and the outcomes concerning community-acquired sepsis among patients admitted to a Hungarian high-influx national medical center. METHODS: A retrospective, observational cohort study of consecutive adult patients hospitalized with community-acquired sepsis during a 1-year period was executed. Clinical and microbiological data were collected, patients with pre-defined healthcare associations were excluded. Sepsis definitions and severity were given according to ACCP/SCCM criteria. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were intensive care unit (ICU) admittance, length-of-stay (LOS), source control and bacteraemia rates. Statistical differences were explored with classical comparison tests, predictors of in-hospital all-cause mortality were modelled by multivariate logistic regression. RESULTS: 214 patients (median age 60.0 ± 33.1 years, 57% female, median Charlson score 4.0 ± 5.0) were included, 32.7% of them (70/214) had severe sepsis, and 28.5% (61/214) had septic shock. Prevalent sources of infections were genitourinary (53/214, 24.8%) and abdominal (52/214, 24.3%). The causative organisms were dominantly E. coli (60/214, 28.0%), S. pneumoniae (18/214, 8.4%) and S. aureus (14/214, 6.5%), and bacteraemia was documented in 50.9% of the cases (109/214). In-hospital mortality was high (30/214, 14.0%), and independently associated with shock, absence of fever, male gender and the need for ICU admittance, but source control and de-escalation of empirical antimicrobial therapy were protective. ICU admittance was 27.1% (58/214), source control was achieved in 18.2% (39/214). Median LOS was 10.0 ± 8.0, ICU LOS was 8.0 ± 10.8 days. CONCLUSIONS: Community-acquired sepsis poses a significant burden of disease with characteristic causative agents and sources. Patients at a higher risk for poor outcomes might be identified earlier by the contributing factors shown above.


Assuntos
Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Coortes , Infecções Comunitárias Adquiridas , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Hungria , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Sepse/microbiologia , Sepse/mortalidade , Choque Séptico/microbiologia , Choque Séptico/mortalidade , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Adulto Jovem
10.
Expert Rev Clin Pharmacol ; 12(9): 893-900, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31295413

RESUMO

Introduction: Despite considerable advances in our understanding of how sepsis develops and multiple clinical trials of potential therapies, no new pharmacologic agent has been consistently shown to improve survival. Areas covered: We reviewed relevant publications identified through PubMed and from the authors' knowledge of this field. We discuss the main reasons why clinical trials on new therapeutic interventions have failed in the past, including heterogeneity of study populations and choice of outcome measures. We discuss how changes in study design and in patient selection could help improve identification of effective agents in the future. Expert opinion: The search for new sepsis therapies must continue but lessons must be learned from previous clinical trials so that the same mistakes are not repeated. Rather than grouping all patients with sepsis together, we should study only those most likely to benefit from the intervention. Better characterization of patients will be facilitated using modern 'omics technology and analysis of the increasingly large quantities of clinical data available, enabling more personalized patient selection for trial inclusion. New clinical trial design and inclusion of other endpoints in addition to mortality will also aid our search for the elusive positive clinical trial and effective interventions for sepsis.


Assuntos
Ensaios Clínicos como Assunto/métodos , Projetos de Pesquisa , Sepse/tratamento farmacológico , Desenvolvimento de Medicamentos/métodos , Humanos , Avaliação de Resultados (Cuidados de Saúde) , Seleção de Pacientes
11.
Dtsch Med Wochenschr ; 144(11): 729-733, 2019 06.
Artigo em Alemão | MEDLINE | ID: mdl-31163470

RESUMO

In 2018, the PEG-recommendations for calculated initial parenteral treatment of bacterial diseases in adults were updated to a consensus-based S2k-guideline.This summary of guidelines deals with the classification of new antibiotic substances such as cephalosporin/betalactamase inhibitor combinations and MRSA-effective cephalosporines and with a need for further therapeutic drug monitoring.Due to their influence as major disease entities in intensive care, we also outline core issues regarding respiratory infections and sepsis. With this update, latest recommendations on a high scientific level are available for intensive care units and - if applied consistently - might improve the chances of critically ill patients.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Cuidados Críticos , Adulto , Idoso , Cefalosporinas/uso terapêutico , Estado Terminal , Humanos , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Pneumonia Bacteriana/tratamento farmacológico , Guias de Prática Clínica como Assunto , Sepse/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico
12.
Int J Infect Dis ; 85: 158-166, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31229612

RESUMO

BACKGROUND: Optimizing antibiotic therapy has an important impact on the management of critically ill patients. Procalcitonin (PCT) is considered to be of possible use in the guidance of antibiotic stewardship; however, its efficacy remains controversial. Thus, a meta-analysis was performed to determine the efficacy of PCT-guided antibiotic therapy in critically ill patients. METHODS: The relevant literature was searched in PubMed, Embase, Web of Science, and the Cochrane Library covering the period from 2004 to August 2018. Randomized controlled trials (RCTs) were included if critically ill patients were treated with PCT-guided antibiotic therapy or standard care. The primary outcome was short-term mortality; secondary endpoints were the duration of antibiotic treatment, intensive care unit (ICU) length of stay (LOS), and hospital LOS. RESULTS: Sixteen RCTs enrolling 6452 critically ill patients were included in this analysis. The pooled analysis demonstrated a comparable short-term mortality (rate ratio (RR) 0.90, 95% confidence interval (CI) 0.80-1.01; p= 0.07), ICU LOS (mean difference (MD) 0.38, 95% CI -0.05 to 0.81; p=0.09), and hospital LOS (MD 0.19, 95% CI -1.56 to 1.95; p= 0.83) for PCT-guided antibiotic therapy and standard antibiotic therapy, and an antibiotic duration shorter by 0.99 days (95% CI -1.85 to -0.13 days; p= 0.02) for PCT-guided antibiotic therapy. In the subgroup analysis, patients with an average Sequential Organ Failure Assessment (SOFA) score of <8 in the PCT-guided cessation of antibiotics group had a lower short-term mortality compared with the standard care group (RR 0.81, 95% CI 0.66-0.99; p= 0.04), while no difference was found in the subgroup with an average SOFA score of >8 (RR 0.85, 95% CI 0.66-1.11; p=0.23). CONCLUSIONS: PCT-guided antibiotic therapy fails to decrease the mortality or LOS of critically ill patients with suspected or confirmed sepsis. PCT-guided cessation of antibiotic therapy could reduce the mortality in patients with an average SOFA score of <8, but not in those with an average SOFA score of >8.


Assuntos
Antibacterianos/uso terapêutico , Estado Terminal/mortalidade , Pró-Calcitonina/análise , Sepse/tratamento farmacológico , Gestão de Antimicrobianos , Biomarcadores/análise , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Escores de Disfunção Orgânica
13.
Chemotherapy ; 64(1): 17-21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31167190

RESUMO

Prolonged intermittent renal replacement therapy (PIRRT) is an increasingly adopted method of renal replacement in critically ill patients. Like continuous renal replacement therapy, PIRRT can alter the pharmacokinetics (PK) of many drugs. In this setting, dosing data for antibiotics like benzylpenicillin are lacking. In order to enable clinicians to prescribe benzylpenicillin safely and effectively, knowledge of the effects of PIRRT on the plasma PK of benzylpenicillin is required. Herein, we describe the PK of benzylpenicillin in 2 critically ill patients on PIRRT for the treatment of penicillin-susceptible Staphylococcus aureus bacteremia complicated by infective endocarditis. Blood samples were taken for each patient taken over dosing periods during PIRRT and off PIRRT. Two-compartment PK models described significant differences in the mean clearance of benzylpenicillin with and without PIRRT (6.61 vs. 3.04 L/h respectively). We would suggest a benzylpenicillin dose of 1,800 mg (3 million units) every 6-h during PIRRT therapy as sufficient to attain PK/pharmacodynamic target.


Assuntos
Antibacterianos/farmacocinética , Penicilina G/farmacocinética , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/complicações , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Relação Dose-Resposta a Droga , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Penicilina G/farmacologia , Penicilina G/uso terapêutico , Terapia de Substituição Renal , Sepse/complicações , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento
14.
J Sci Food Agric ; 99(13): 5870-5880, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31206687

RESUMO

BACKGROUND: Sepsis is a set of serious organic manifestations caused by an infection, whose progression culminates in exacerbated inflammation and oxidative stress, poor prognosis, and high hospital costs. Antioxidants used against sepsis have been evaluated, including essential oils such as ß-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The aim of this study was to evaluate the anti-inflammatory activity of the association of these two compounds. RESULTS: Treatment with BCP-DHA, at a dose of 200 µL/animal, significantly inhibited the migration of neutrophils in a Cg-induced peritonitis model. After Staphylococcus aureus infection, in the groups treated with BCP-DHA there was a significant decrease in the total and differential count of leukocytes, increased expression of cytokines TNF-α and IFN-γ in treated groups, an increase of IL-4 and IL-5 in B/D and B/D + SA groups, and an augmentation of IL-6 and IL-12 groups in B/D + SA groups. Histological and bacterial analysis revealed lower neutrophil migration and lower bacterial load in the infected and treated groups. CONCLUSION: In general, the BCP-DHA association presented anti-inflammatory activity against two different models of acute inflammation and infection, showing promising potential as a therapeutic adjuvant in sepsis. © 2019 Society of Chemical Industry.


Assuntos
Anti-Inflamatórios/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Peritonite/tratamento farmacológico , Sepse/tratamento farmacológico , Sesquiterpenos/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Quimioterapia Combinada , Humanos , Interleucina-12/genética , Interleucina-12/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Peritonite/genética , Peritonite/imunologia , Peritonite/microbiologia , Sepse/genética , Sepse/imunologia , Sepse/microbiologia , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
15.
Arq Bras Cir Dig ; 32(2): e1431, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31038556

RESUMO

BACKGROUND: Sepsis is an important public health issue and is associated with high treatment costs and high mortality rates. Glutamine supplementation has proven to be beneficial to the functions of the immune system, acting beneficially in the evolution of patients in severe catabolic states. AIM: To evaluate the effect of glutamine supplementation via intraperitoneal in rats, induced sepsis, considering the following organs: intestines, liver, kidneys and lungs. METHODS: Male Wistar rats subjected to sepsis by ligature and cecal puncture were divided into two groups: control C (n=6) and glutamine G (n=11), in which were administered dipeptiven 20% at a dose of 2 ml/kg/day (equivalent to 0.4g N(2)-L-alanyl-L-glutamine/kg) intraperitoneally 48 h prior to sepsis induction. After 48 h they were euthanized and intestine, liver, lung and kidney were removed for histological analysis. RESULTS: Intestinal epithelial desquamation of the control group was more intense compared to the glutamine group (p=0.008). In the kidneys, degenerative tubular epithelial changes were less severe in the animals that received glutamine (p=0.029). Regarding to the liver, glutamine group showed lower levels of cell swelling than the control group (p=0.034). In the lung there were no results with statistical significance. CONCLUSION: Prior intraperitoneal supplementation with glutamine in experimental animals is able to reduce the damage to the intestinal mucosa, to the kidneys and liver's histoarchitecture.


Assuntos
Glutamina/administração & dosagem , Sepse/tratamento farmacológico , Animais , Infusões Parenterais , Intestinos/efeitos dos fármacos , Intestinos/patologia , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Sepse/patologia , Resultado do Tratamento
16.
Medicine (Baltimore) ; 98(18): e15469, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045827

RESUMO

BACKGROUND: This meta-analysis aimed to evaluate the effect of dexmedetomidine on prognosis in patients with sepsis. METHODS: Computer-related electronic databases were searched, including PubMed, Embase, Web of Science, the Cochrane Library, and the China National Knowledge Infrastructure, from the date of database construction to January 2019. Stata 12.0 was used to perform a meta-analysis of short-term mortality [intensive care unit (ICU) mortality or 28-day mortality], ICU length of stay, and mechanical ventilation. Mortality was expressed using risk ratio (RR) and 95% confidence interval (CI). ICU length of stay and mechanical ventilation were expressed as weighted mean difference (WMD) and 95% CIs. RESULTS: We finally included 8 randomized controlled trials in this meta-analysis. Compared with the control group, the dexmedetomidine group had a lower occurrence of 28-day mortality (RR, 0.49; 95% CI, 0.35 to 0.69; P = .000) and ICU mortality (RR, 0.44; 95% CI, 0.23 to 0.84; P = .013). However, there was no statistically significant difference for the length of hospital stay (WMD, -0.05; 95% CI, -0.59 to 0.48; P = .840) and mechanical ventilation time (WMD, 1.05; 95% CI, -0.27 to 2.37; P = .392) between dexmedetomidine group and control group. CONCLUSIONS: In patients with sepsis, dexmedetomidine can reduce the short-term mortality of patients, but could not shorten the ICU length of stay and mechanical ventilation time. More clinical randomized controlled trials are needed to verify the efficacy and safety of dexmedetomidine on the length of hospital stay and mechanical ventilation time.


Assuntos
Dexmedetomidina/uso terapêutico , Mortalidade Hospitalar , Unidades de Terapia Intensiva/estatística & dados numéricos , Sepse/tratamento farmacológico , Sepse/mortalidade , Idoso , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/estatística & dados numéricos
17.
Molecules ; 24(9)2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31052373

RESUMO

Antimicrobial peptides (AMPs) are considered as potential therapeutic sources of future antibiotics because of their broad-spectrum activities and alternative mechanisms of action compared to conventional antibiotics. Although AMPs present considerable advantages over conventional antibiotics, their clinical and commercial development still have some limitations, because of their potential toxicity, susceptibility to proteases, and high cost of production. To overcome these drawbacks, the use of peptides mimics is anticipated to avoid the proteolysis, while the identification of minimalist peptide sequences retaining antimicrobial activities could bring a solution for the cost issue. We describe here new polycationic ß-amino acids combining these two properties, that we used to design small dipeptides that appeared to be active against Gram-positive and Gram-negative bacteria, selective against prokaryotic versus mammalian cells, and highly stable in human plasma. Moreover, the in vivo data activity obtained in septic mice reveals that the bacterial killing effect allows the control of the infection and increases the survival rate of cecal ligature and puncture (CLP)-treated mice.


Assuntos
Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/síntese química , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/síntese química , Sepse/tratamento farmacológico , Aminoácidos/química , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Modelos Animais de Doenças , Desenho de Drogas , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Mimetismo Molecular , Proteólise , Sepse/etiologia , Sepse/microbiologia
18.
Vnitr Lek ; 65(3): 204-209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31088097

RESUMO

The article summarizes the known facts regarding the selection of antibiotics for the treatment of sepsis and similar serious infections, their mechanism of action, dosage and mode of administration. Particular attention is paid to early antibiotic therapy: a delay of several hours in the onset of antibiotic therapy can be tolerated if it helps to clarify the aethiology and to refine the treatment. However, in case of the very acute infections it is necessary to start antibiotic treatment immediately; diagnostic procedures are mentioned that can be used for the selection of the appropriate drug.


Assuntos
Infecções Bacterianas , Sepse , Antibacterianos , Infecções Bacterianas/tratamento farmacológico , Humanos , Sepse/tratamento farmacológico
19.
Ulus Travma Acil Cerrahi Derg ; 25(3): 213-221, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31135951

RESUMO

BACKGROUND: The aim of this study was to evaluate the possible protective effects of dapagliflozin in an experimental sepsis model in rats. METHODS: Saline (1 mL/kg, p.o.) or dapagliflozin (10 mg/kg, p.o.) was administered to Sprague-Dawley rats for 5 days prior to the surgical procedures. Under anesthesia, sepsis was induced by cecal ligation puncture, while sham control groups underwent laparotomy only. Blood urea nitrogen, creatinine, and glucose levels were measured in serum samples and the levels of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor alpha, interleukin 1 beta, caspase 8, and caspase 9 were determined in tissue samples (kidney, liver, and lung). Histological evaluation was also performed. RESULTS: The administration of dapagliflozin in a sepsis model reduced oxidative stress (MDA), increased antioxidant levels (GSH), and reduced inflammation (MPO) in the kidney (p<0.05). Dapagliflozin also decreased oxidative stress (MDA) in lung tissue and decreased inflammation (MPO) in lung and liver tissue (p<0.05). Caspase 8 and 9 levels in kidney, lung, and liver tissue were increased (p<0.05) in the dapagliflozin group compared with the sepsis group. According to the histopathological results, sepsis was moderately improved in renal tissue and slightly attenuated in lung and liver tissue with the administration of dapagliflozin. CONCLUSION: Dapagliflozin had a preventive effect on sepsis-induced kidney damage, but the protective effect was mild in lung and liver tissue in the present study.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Sepse , Animais , Compostos Benzidrílicos/farmacocinética , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/uso terapêutico , Modelos Animais de Doenças , Glucosídeos/farmacocinética , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Ratos , Sepse/sangue , Sepse/tratamento farmacológico , Sepse/fisiopatologia , Distribuição Tecidual
20.
J Med Microbiol ; 68(5): 711-719, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30994430

RESUMO

PURPOSE: Antimicrobial resistance (AMR) is of increasing global concern, threatening to undermine recent progress in reducing child and neonatal mortality. Repurposing older antimicrobials is a prominent strategy to combat multidrug-resistant sepsis. A potential agent is fosfomycin, however, there is scarce data regarding its in vitro activity and pharmacokinetics in the paediatric population. METHODOLOGY: We analysed a contemporary, systematically collected archive of community-acquired (CA) and hospital-acquired (HA) paediatric Gram-negative bacteraemia isolates for their susceptibility to fosfomcyin. MICs were determined using agar serial dilution methods and validated by disk diffusion testing where breakpoints are available. Disk diffusion antimicrobial susceptibility testing was also conducted for current empirical therapies (ampicillin, gentamicin, ceftriaxone) and amikacin (proposed in the literature as a new combination empirical therapeutic option). RESULTS: Fosfomycin was highly active against invasive Gram-negative isolates, including 90  % (202/224) of Enterobacteriaceae and 96  % (22/23) of Pseudomonas spp. Fosfomycin showed high sensitivity against both CA isolates (94 %, 142/151) and HA isolates (81 %, 78/96; P =0.0015). CA isolates were significantly more likely to be susceptible to fosfomycin than the current first-line empirical therapy (96  % vs 59  %, P <0.0001). Extended spectrum ß-lactamases (ESBL) production was detected in 34  % (85/247) of isolates with no significant difference in fosfomycin susceptibility between ESBL-positive or -negative isolates [73/85 (86  %) vs 147/162 (91  %) respectively, P =0.245]. All isolates were susceptible to a fosfomycin-amikacin combination. CONCLUSION: Gram-negative paediatric bacteraemia isolates are highly susceptible to fosfomycin, which could be combined with aminoglycosides as a new, carbapenem-sparing regimen to achieve excellent coverage to treat antimicrobial-resistant neonatal and paediatric sepsis.


Assuntos
Antibacterianos/farmacologia , Fosfomicina/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bacteriemia/tratamento farmacológico , Pré-Escolar , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Lactente , Recém-Nascido , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Pseudomonas/efeitos dos fármacos , Sepse/tratamento farmacológico , Sepse/microbiologia
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