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1.
Saudi Med J ; 42(9): 1002-1008, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34470839

RESUMO

OBJECTIVES: To assess the mortality benefits of timely antibiotic treatment of adults present at the emergency department with sepsis and compare one-hour administration and 3-hour administration starting from the time of triage. METHODS: In this retrospective study, we used secondary data analysis to investigate the utility of the National Early Warning Score as a predictor of mortality in sepsis patients between July 2018 and June 2019, at the Emergency Department, King Saud Medical City, Riyadh, Saudi Arabia. The patients were grouped into 2 based on the time interval from triage to the first antibiotic administration: the immediate group received antibiotics within the first hour, and the early group received antibiotics between one and 3 hours. The primary outcome of interest was in-hospital mortality. RESULTS: Out of 495 septic patients, only 292 patients (mean age of 56.3 ± 23.6 years) met the inclusion criteria. Two hundred fifty (85.6%) patients received antibiotics within one hour of triage (immediate), while 42 (14.4%) patients received antibiotics between one and 3 hours (early). Overall, in-hospital mortality was 31.8%. The mortality rates among patients who received early antibiotic was 31.6% and who received immediate antibiotic was 33.3%, with a p-value of 0.823. CONCLUSION: Our findings did not support immediate antibiotic administration over early administration in patients with sepsis. However, further studies are recommended to investigate the effects of antibiotic timing on the outcome of severe sepsis patients.


Assuntos
Sepse , Choque Séptico , Adulto , Idoso , Antibacterianos/uso terapêutico , Serviço Hospitalar de Emergência , Mortalidade Hospitalar , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sepse/tratamento farmacológico
2.
J Trop Pediatr ; 67(4)2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34471923

RESUMO

Chromobacterium violaceum, a facultative anaerobic proteobacterium, is isolated from water and soil in tropical areas and has been implicated in infections like septicemia, visceral abscesses, skin and soft tissue infections, meningitis and diarrhea. Chromobacterium violaceum sepsis, a rarely reported phenomenon has a very high mortality rate. Here, we report a unique case of Chromobacterium sepsis in an infant. A 48-day-old baby boy was referred to our institution with h/o fever, loose stools and reduced activity. He was intubated and referred to us in septic shock. Radiological investigations revealed multiple abscesses in the liver, spleen and kidneys. The infant was successfully treated with trimethoprim-sulfamethoxazole and ciprofloxacin.


Assuntos
Infecções por Bactérias Gram-Negativas , Sepse , Antibacterianos/uso terapêutico , Chromobacterium , Ciprofloxacina/uso terapêutico , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Lactente , Masculino , Sepse/diagnóstico , Sepse/tratamento farmacológico
3.
AIDS Res Ther ; 18(1): 56, 2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-34481501

RESUMO

BACKGROUND: We report a case of sudden, lethal metabolic acidosis in a 70-year-old man on long-term nucleoside reverse transcriptase inhibitor (NRTI) -based antiretroviral therapy (ART) who had developed atypical necrotizing fasciitis 1 month after kidney transplantation. CASE PRESENTATION: The HIV infection of the patient was treated for the last four months with an integrase strand inhibitor (dolutegravir 50 mg/d) plus a NRTI backbone including lamivudine (150 mg/d) and abacavir (600 mg/d). In this renal transplant patient we hypothesize that the co-existence of sepsis, renal failure and an accumulation of lamivudine led to the development of fatal metabolic acidosis and hyperlactatemia. Although lamivudine is only rarely associated with hyperlactatemia, there is evidence that overdose may be a risk factor for developing it. In our patient the lamivudine concentration two days after stopping and during hemodiafiltration was more than 50 times higher than therapeutic target trough concentrations. Likely reasons for this were renal impairment and concurrent treatment with trimethoprim, known to inhibit the renal elimination of lamivudine. CONCLUSIONS: NRTIs could trigger the development of hyperlactatemia in septic patients. The use of NRTI sparing regimens might be considered in the presence of this critical condition.


Assuntos
Acidose Láctica , Fármacos Anti-HIV , Infecções por HIV , Hiperlactatemia , Transplante de Rim , Sepse , Acidose Láctica/induzido quimicamente , Acidose Láctica/tratamento farmacológico , Idoso , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Hiperlactatemia/tratamento farmacológico , Transplante de Rim/efeitos adversos , Lamivudina/efeitos adversos , Masculino , Sepse/tratamento farmacológico
4.
BMJ Case Rep ; 14(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426432

RESUMO

The underlying mechanisms of coronary spastic angina (CSA) is not well understood. It is unclear if an infection can trigger coronary vasospasm; the co-occurrence of sepsis and CSA has rarely been reported. We describe the case of a 47-year-old man who suddenly developed a complete atrioventricular block and an episode of cardiac arrest while undergoing treatment for sepsis secondary to invasive group A streptococci. Emergency coronary angiography and provocation revealed spasm of the right coronary artery, which had led to the atrioventricular block. The spasm was relieved following administration of calcium-channel blockade, and no subsequent recurrence was documented. Due to several underlying mechanisms, sepsis may be a potential risk factor of coronary spasm and episodes of this condition have been missed or misdiagnosed. Physicians should be aware of CSA as a potential complication during treatment of sepsis.


Assuntos
Vasoespasmo Coronário , Sepse , Angina Pectoris , Angiografia Coronária , Vasoespasmo Coronário/complicações , Vasoespasmo Coronário/diagnóstico , Vasoespasmo Coronário/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular , Sepse/complicações , Sepse/tratamento farmacológico
6.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(7): 815-820, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34412750

RESUMO

OBJECTIVE: To investigate the clinical effect of Jiedu Limai decoction in septic patients with syndrome of heat-toxin exuberance. METHODS: A prospective randomized controlled trial was conducted. From March 2019 to April 2020, septic patients with syndrome of heat-toxin exuberance admitted to intensive care unit (ICU) of Shanghai General Hospital and Songjiang Branch of Shanghai General Hospital were enrolled as the research objects, and they were divided into routine treatment group and Jiedu Limai decoction group by the random number table method. Patients in both groups were given standard treatment in accordance with the guidelines, and patients in the Jiedu Limai decoction group were given Jiedu Limai decoction in addition to the standard treatment, once a day for 14 days. The 28-day survival of patients of the two groups were recorded, the acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, coagulation indexes, infection indexes, inflammatory cytokines and organ function indicators before treatment and 7 days after treatment in both groups were recorded, and the prognosis of the two groups were recorded. RESULTS: A total of 259 patients with infection or clinical diagnosis of infection admitted during the experimental observation period were included, and those who did not meet the Sepsis-3 diagnostic criteria, more than 80 years old or less than 18 years old, with multiple tumor metastases, autoimmune system diseases, with length of ICU stay less than 24 hours, with acute active gastrointestinal bleeding and with incomplete data were excluded. One hundred patients were finally enrolled, with 50 patients in the routine treatment group and 50 patients in the Jiedu Limai decoction group. There were no statistically significant differences in coagulation indexes, infection indicators, inflammatory cytokines and organ function indicators before treatment between the two groups. After 7 days of treatment, the coagulation indexes, infection biomarkers and inflammatory cytokines in the Jiedu Limai decoction group were significantly lower than those in the routine treatment group [D-dimer (mg/L): 2.2 (1.8, 8.5) vs. 4.0 (1.5, 8.7), fibrinogen (Fib, g/L): 3.7 (3.4, 4.3) vs. 4.2 (3.7, 4.3), fibrinogen degradation product (FDP, mg/L): 7.2 (5.4, 10.2) vs. 13.2 (9.2, 15.2), procalcitonin (PCT, µg/L): 0.4 (0.2, 2.9) vs. 0.5 (0.2, 0.9), C-reactive protein (CRP, mg/L): 50.1 (9.5, 116.0) vs. 75.1 (23.5, 115.2), interleukin-6 (IL-6, ng/L): 31.6 (21.6, 81.0) vs. 44.1 (14.0, 71.3), all P < 0.05], and the levels of B-type brain natriuretic peptide (BNP) and kidney injury molecule-1 (KIM-1) were significantly lowered [BNP (ng/L): 261.1 (87.5, 360.3) vs. 347.3 (128.8, 439.4), KIM-1 (µg/L): 0.86 (0.01, 1.40) vs. 1.24 (1.05, 1.57), both P < 0.05]. Compared with the routine treatment group, the number of new organ failure in the Jiedu Limai decoction group was decreased (30.0% vs. 50.0%, P < 0.05). Although there was no significant difference in 28-day mortality between the two groups (P > 0.05), the 28-day mortality in the Jiedu Limai decoction group was lower than that in the routine treatment group (18.0% vs. 24.0%). CONCLUSIONS: Combining Jiedu Limai decoction to the sepsis guideline in treating syndrome of heat-toxin exuberance can effectively improve patients' coagulation function, the situation of heart and renal injury, reduce the level of inflammatory cytokines, and fewer people develop new organ failure after treatment.


Assuntos
Temperatura Alta , Sepse , Adolescente , Idoso de 80 Anos ou mais , China , Humanos , Escores de Disfunção Orgânica , Estudos Prospectivos , Sepse/tratamento farmacológico
7.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(7): 866-870, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34412759

RESUMO

OBJECTIVE: To observe the protective effect and mechanism of different doses of Baicalin (BAI) on acute kidney injury (AKI) in septic mice. METHODS: According to the random number table, 100 mice were divided into sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis model group (CLP group) and BAI pretreatment groups. The mice in BAI pretreatment groups were divided into low-, medium- and high-dose groups (BAI-L+CLP, BAI-M+CLP, BAI-H+CLP groups), with 20 mice in each group. A murine sepsis associated-acute kidney injury (SA-AKI) model was reproduced using CLP. The mice in the Sham group were only opened and closed the abdomen, without ligating or perforating the cecum. The mice in the BAI pretreatment groups were given BAI 25, 50 and 100 mg/kg daily for 3 days, and CLP was performed at 6 hours after administration of BAI at the 3rd day to reproduce sepsis model. The mice in the Sham group and CLP group were given the same amount of distilled water as control. Ten mice were sacrificed at 24 hours after operation to collect orbital blood for renal function determination [serum creatinine (SCr), blood urea nitrogen (BUN), plasma neutrophil gelatinase-associated lipocalin (pNGAL) and plasma kidney injury molecule-1 (pKIM-1)] by enzyme linked immunosorbent assay (ELISA). The kidney tissue was collected to observe the kidney tissue injury under light microscope after hematoxylin-eosin (HE) staining. The TdT-mediated dUTP nick-end labeling (TUNEL) was used to detect the apoptosis of renal tubular epithelial cells. Western blotting was used to detect the expression of cell FLICE like inhibitory protein (c-FLIP) in renal tissue. The remaining 10 mice in each group were used to calculate the survival rate of 7 days after operation. RESULTS: The renal tubular epithelial cells in the CLP group were massively degenerated with necrosis, the renal tubular lumen was significantly expanded, and inflammatory cells were widely infiltrated in the renal interstitium. Furthermore, the renal function deteriorated rapidly. Compared with the CLP group, the renal function of mice pretreated with low dose of BAI was improved, but the difference was not significant. Compared with the CLP group, the renal function in the mice pretreated with medium and high doses of BAI was significantly improved, the SCr, BUN, pNGAL and pKIM-1 were significantly reduced [SCr (µmol/L): 135.16±5.18, 125.70±5.26 vs. 170.42±5.42; BUN (mmol/L): 33.59±1.77, 27.29±1.61 vs. 45.68±1.39; pNGAL (µg/L): 91.29±4.68, 73.40±3.77 vs. 131.50±6.55; pKIM-1 (µg/L): 6.34±0.30, 5.51±0.35 vs. 8.03±0.29; all P < 0.01], the pathological injury of renal tissue was significantly decreased, the apoptotic number of renal tubular epithelial cells was significantly reduced (cells/HP: 16.20±0.49, 13.10±0.66 vs. 29.60±0.49, both P < 0.01), and the expression of c-FLIP protein in renal tissue was significantly increased [c-FLIP protein (c-FLIP/GAPDH): 0.35±0.02, 0.46±0.02 vs. 0.21±0.01, both P < 0.01]. No mouse in the Sham group died within 7 days. Compared with the CLP group, the average survival time of the mice within 7 days in the BAI-L+CLP, BAI-M+CLP and BAI-H+CLP groups was significantly prolonged with a dose-dependent manner (days: 3.5±2.5, 5.4±2.2, 5.9±1.9 vs. 2.1±1.2; Log-Rank test: χ2 = 73.410, P < 0.001). CONCLUSIONS: Pretreatment with medium and high doses of BAI can significantly improve the renal function in mice with SA-AKI, decrease the pathological damage and increase the survival of mice, and its mechanism may be related to promoting the increase of c-FLIP protein expression and inhibiting cell apoptosis.


Assuntos
Injúria Renal Aguda , Sepse , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Animais , Flavonoides , Rim , Ligadura , Camundongos , Sepse/complicações , Sepse/tratamento farmacológico
8.
Int J Clin Pract ; 75(10): e14701, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34351692

RESUMO

BACKGROUND: As the susceptibility pattern of different pathogens varies among different settings, the evaluation of appropriate clinical diagnosis and timely initiation of the empirical antibiotic treatment based on the local susceptibility data is crucial in the management of sepsis. METHODS: A retrospective study was conducted among adult patients with sepsis at a charitable hospital in Mangaluru. The essential details such as patient demographics, culture specimens, organisms, resistance/susceptibility pattern, laboratory data, empirical therapy and clinical outcomes were collected from the medical records. Descriptive statistics were used in analysing the data. RESULTS: A total of 425 patients diagnosed with sepsis during the study period were screened to meet the sample size of 373 positive cultures, among which 367 (91.3%) samples yielded the bacterial isolates, of which 250 (68.1%) and 117 (31.9%) were gram-negative and gram-positive organisms, respectively. The most common gram-negative organisms isolated were K pneumoniae (19.9%), A baumannii (19.6%) and E coli (12.8%); while Coagulase-negative staphylococcus (14.4%) and S aureus (8.4%) were the predominant gram-positive organisms. The isolated pathogens showed a resistance rate of >50% to the most commonly used antibiotics. CONCLUSION: The present study provides information on the prevalence of the most common pathogens and their resistance pattern to different antibiotics, which plays a vital role in the selection and timely initiation of the appropriate empirical antibiotic therapy.


Assuntos
Antibacterianos , Sepse , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Escherichia coli , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Sepse/tratamento farmacológico
10.
Am J Case Rep ; 22: e932544, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34373441

RESUMO

BACKGROUND Fusarium spp. is a rare cause of opportunistic life-threatening fungal infections. It has a remarkably high resistance profile with few effective antifungal agents, mostly limited to voriconazole and liposomal amphotericin B. Drug-induced liver injury (DILI) by 1 of these 2 antifungal agents further complicates the management of these infections. CASE REPORT A 38-year-old woman with short bowel syndrome presented to the hospital with concerns of abdominal pain and loose stools. An abdominal CT was negative for inflammatory or ischemic bowel disease, and there was no evidence of liver disease. She tested positive for SARS-CoV-2 and required transfer to the ICU due to hypotension requiring fluid resuscitation and vasopressors. On day 43 of her admission, the patient developed a low-grade fever, for which she underwent central-line and peripheral-blood cultures that were positive for Fusarium dimerum. The central line was removed and i.v. voriconazole started. After 3 days of treatment, the patient's liver enzymes rose abruptly. Voriconazole was discontinued and replaced with liposomal amphotericin B, and the liver enzymes improved significantly. The patient completed 14 days of therapy and was discharged from the hospital. CONCLUSIONS This is a case of F. dimerum infection followed by DILI from voriconazole treatment. Her infection was resolved after switching to liposomal amphotericin B, with improvement in liver enzymes on day 1 after discontinuing voriconazole. This observation demonstrates that altering antifungal classes may be an appropriate strategy when confronted with DILI.


Assuntos
COVID-19 , Doença Hepática Induzida por Substâncias e Drogas , Fusarium , Sepse , Adulto , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Humanos , SARS-CoV-2 , Sepse/tratamento farmacológico , Voriconazol/efeitos adversos
11.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361008

RESUMO

The emergence of multidrug-resistant (MDR) bacteria through the abuse and long-term use of antibiotics is a serious health problem worldwide. Therefore, novel antimicrobial agents that can cure an infection from MDR bacteria, especially gram-negative bacteria, are urgently needed. Antimicrobial peptides, part of the innate immunity system, have been studied to find bactericidal agents potent against MDR bacteria. However, they have many problems, such as restrained systemic activity and cytotoxicity. In a previous study, we suggested that the K58-R78 domain of Romo1, a mitochondrial protein encoded by the nucleus, was a promising treatment candidate for sepsis caused by MDR bacteria. Here, we performed sequence optimization to enhance the antimicrobial activity of this peptide and named it as AMPR-22 (antimicrobial peptide derived from Romo1). It showed broad-spectrum antimicrobial activity against 17 sepsis-causing bacteria, including MDR strains, by inducing membrane permeabilization. Moreover, treatment with AMPR-22 enabled a remarkable survival rate in mice injected with MDR bacteria in a murine model of sepsis. Based on these results, we suggest that AMPR-22 could be prescribed as a first-line therapy (prior to bacterial identification) for patients diagnosed with sepsis.


Assuntos
Proteínas de Membrana/química , Proteínas Mitocondriais/química , Fragmentos de Peptídeos/uso terapêutico , Proteínas Citotóxicas Formadoras de Poros/uso terapêutico , Sepse/tratamento farmacológico , Animais , Células Cultivadas , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células HEK293 , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Domínios Proteicos , Sepse/microbiologia
13.
Rev Med Inst Mex Seguro Soc ; 59(3): 216-223, 2021 Aug 13.
Artigo em Espanhol | MEDLINE | ID: mdl-34369942

RESUMO

Background: Early onset neonatal sepsis (EOS) is a public health problem; antibiotic treatment is often unnecessary and can increase morbimortality. EOS risk calculator are available that allows limiting the use of antibiotics. Objective: To compare the patterns of antibiotic use and hospitalization time in infant newborns (NB) ≥ 34 weeks of gestational age (GA) in a historical cohort attended from November 2017 to April 2018 vs. a prospective cohort from November 2018 to April 2019, before and after implementing the use of an EOS risk calculator, respectively. Material and methods: Ambispective, observational, longitudinal, analytical study in infants NB ≥ 34 GA attended before and after implementing the use of an EOS risk calculator. The patterns of antibiotic´s use were compared. Simple frequencies and proportions, means and standard deviations or medians with ranges, Mann-Whitney U Test and Chi square test with SPSS V. 20.0 statistical package were used; considering significant values of p < 0.05. Results: Thirty patients were included, 15 NB for each period, the gestational age average was 36.8 ± 2.3 GA. there was no statistically significant difference in the frequency of diagnosis of EOS with blood culture or days of hospital stay. Antibiotics were beginning in all the infants attended before the implementation of the EOS risk calculator, unlike 46.7% of the infants after its implementation (p = 0.001). Conclusions: The EOS risk calculator is an easy tool to use, and demonstrated to be useful in decreasing unnecessary use of antibiotics.


Assuntos
Sepse Neonatal , Sepse , Antibacterianos/uso terapêutico , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Sepse Neonatal/diagnóstico , Sepse Neonatal/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sepse/diagnóstico , Sepse/tratamento farmacológico
14.
BMJ Case Rep ; 14(8)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380674

RESUMO

We report a case of cellulitis of the soft tissue of the neck with group B streptococcus (GBS) sepsis in a 4-week-old baby boy presented with a 1-day history of fever, irritability and feed refusal. While in the hospital, a left-sided submandibular swelling extending to preauricular area started emerging, which progressed dramatically. Ultrasound scan of the neck confirmed inflammation of the underlying soft tissue while revealing multiple enlarged lymph nodes without any abscess formation and overlying soft tissue oedema. Blood cultures were flagged positive at 9 hours for GBS. The infant was treated with intravenous antibiotics for 2 weeks. GBS is considered a common cause of early-onset sepsis in neonates. However, it can also lead to late-onset sepsis in infancy with variable presentations. In our case, GBS sepsis manifested with cellulitis of the soft tissue of the neck along with swelling of local lymph nodes.


Assuntos
Sepse , Infecções Estreptocócicas , Celulite (Flegmão)/tratamento farmacológico , Humanos , Recém-Nascido , Masculino , Pescoço , Sepse/diagnóstico , Sepse/tratamento farmacológico , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus agalactiae
15.
Front Cell Infect Microbiol ; 11: 705087, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368018

RESUMO

Introduction: Hepcidin is the systemic master regulator of iron metabolism as it degrades the cellular iron exporter ferroportin. In bacterial infections, hepcidin is upregulated to limit circulating iron for pathogens, thereby increasing iron retention in macrophages. This mechanism withholds iron from extracellular bacteria but could be of disadvantage in infections with intracellular bacteria. We aimed to understand the role of hepcidin in infections with intra- or extracellular bacteria using different hepcidin inhibitors. Methods: For the experiments LDN-193189 and oversulfated heparins were used, which interact with the BMP6-SMAD pathway thereby inhibiting hepcidin expression. We infected male C57BL/6N mice with either the intracellular bacterium Salmonella Typhimurium or the extracellular bacterium Escherichia coli and treated these mice with the different hepcidin inhibitors. Results: Both inhibitors effectively reduced hepcidin levels in vitro under steady state conditions and upon stimulation with the inflammatory signals interleukin-6 or lipopolysaccharide. The inhibitors also reduced hepcidin levels and increased circulating iron concentration in uninfected mice. However, both compounds failed to decrease liver- and circulating hepcidin levels in infected mice and did not affect ferroportin expression in the spleen or impact on serum iron levels. Accordingly, both BMP-SMAD signaling inhibitors did not influence bacterial numbers in different organs in the course of E.coli or S.Tm sepsis. Conclusion: These data indicate that targeting the BMP receptor or the BMP-SMAD pathway is not sufficient to suppress hepcidin expression in the course of infection with both intra- or extracellular bacteria. This suggests that upon pharmacological inhibition of the central SMAD-BMP pathways during infection, other signaling cascades are compensatorily induced to ensure sufficient hepcidin formation and iron restriction to circulating microbes.


Assuntos
Proteína Morfogenética Óssea 6/metabolismo , Bactérias Gram-Negativas/patogenicidade , Hepcidinas , Sepse , Proteínas Smad/metabolismo , Animais , Ferro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sepse/tratamento farmacológico
16.
Nutrients ; 13(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371879

RESUMO

Sepsis is an extremely complex clinical syndrome, usually involving an excessive inflammatory response including an overshooting cytokine release that damages tissue and organs of the patient. Due to the severity of this condition, it is estimated that over 11 million people die from sepsis each year. Despite intensive research in the field, there is still no specific therapy for sepsis. Many sepsis patients show a marked deficiency of vitamin C. 9 out of 10 sepsis patients have a hypovitaminosis C, and every third patient even shows a clinical deficiency in the scurvy range. In addition, low vitamin C levels of intensive care sepsis patients correlate with a higher need for vasopressors, higher Sequential Organ Failure Assessment (SOFA) scores, and increased mortality. Based on this observation and the conducted clinical trials using vitamin C as sepsis therapy in intensive care patients, the aim of the present ex vivo study was to evaluate the effects of high-dose vitamin C alone and in a triple combination supplemented with vitamin B1 (thiamine) and hydrocortisone on the lipopolysaccharide (LPS)-induced cytokine response in peripheral blood mononuclear cells (PBMCs) from healthy human donors. We found that all corticosteroid combinations strongly reduced the cytokine response on RNA- and protein levels, while high-dose vitamin C alone significantly diminished the PBMC mediated secretion of the cytokines interleukin (IL)-10, IL-23, and monocyte chemo-attractant protein (MCP-1), which mediate the inflammatory response. However, vitamin C showed no enhancing effect on the secretion of further cytokines studied. This data provides important insights into the possible immunomodulatory function of vitamin C in an ex vivo setting of human PBMCs and the modulation of their cytokine profile in the context of sepsis. Since vitamin C is a vital micronutrient, the restoration of physiologically adequate concentrations should be integrated into routine sepsis therapy, and the therapeutic effects of supraphysiological concentrations of vitamin C in sepsis patients should be further investigated in clinical trials.


Assuntos
Anti-Inflamatórios/farmacologia , Ácido Ascórbico/farmacologia , Hidrocortisona/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Sepse/tratamento farmacológico , Tiamina/farmacologia , Adulto , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Quimioterapia Combinada , Feminino , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Sepse/metabolismo , Adulto Jovem
17.
Antimicrob Agents Chemother ; 65(9): e0044121, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34228533

RESUMO

Decisions regarding which rapid diagnostic test (RDT) for bloodstream infections to implement remain challenging given the diversity of organisms detected by different platforms. We used the desirability of outcome ranking management of antimicrobial therapy (DOOR-MAT) as a framework to compare two RDT platforms on potential desirability of antimicrobial therapy decisions. An observational study was performed at University of Maryland Medical System comparing Verigene blood culture (BC) to GenMark Dx ePlex blood culture ID (BCID) (research use only) panels on blood cultures from adult patients. Positive percent agreement (PPA) between each RDT platform and Vitek MS was calculated for comparison of on-panel targets. Theoretical antimicrobial decisions were made based on RDT results, taking into consideration patient parameters, antimicrobial stewardship practices, and local infectious diseases epidemiology. DOOR-MAT with a partial credit scoring system was applied to these decisions, and mean scores were compared across platforms using a paired t test. The study consisted of 160 unique patients. The Verigene BC PPA was 98.6% (95% confidence interval [CI], 95.1 to 99.8), and ePlex BCID PPA was 98% (95% CI, 94.3 to 99.6). Among the 31 organisms not on the Verigene BC panels, 61% were identified by the ePlex BCID panels. The mean (standard deviation [SD]) DOOR-MAT score for Verigene BC was 86.8 (28.5), while that for ePlex BCID was 91.9 (23.1) (P = 0.01). Both RDT platforms had high PPA for on-panel targets. The ePlex BCID was able to identify more organisms than Verigene, resulting in higher mean DOOR-MAT scores.


Assuntos
Anti-Infecciosos , Bacteriemia , Sepse , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Hemocultura , Humanos , Técnicas de Diagnóstico Molecular , Sepse/tratamento farmacológico
18.
Antimicrob Agents Chemother ; 65(9): e0069821, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34228539

RESUMO

Bloodstream infections (BSIs) attributable to carbapenem-resistant Enterobacterales (CRE-BSIs) are dangerous and a major cause of mortality in clinical settings. This study was therefore designed to define risk factors linked to 30-day mortality in CRE-BSI patients and to examine the relative efficacies of different antimicrobial treatment regimens in affected individuals. Data pertaining to 187 CRE-BSI cases from four teaching hospitals in China collected between January 2018 and December 2020 were retrospectively analyzed. For the 187 patients analyzed in this study, the 30-day mortality of CRE-BSI was 41.7% (78/187). Multivariate logistic regression analyses revealed that Pitt bacteremia score, immunocompromised status, meropenem MIC of ≥8 mg/liter,absence of source control of infection, and appropriate empirical therapy were independent predictors of CRE-BSI patient 30-day mortality. After controlling for potential confounding factors relative to ceftazidime-avibactam (CAZ-AVI) treatment, combination therapies including CAZ-AVI (odds ratio [OR], 1.287; 95% confidence interval [CI], 0.124 to 13.403; P = 0.833) were not related to any significant change in patient mortality risk, whereas the 30-day mortality risk was higher for patients administered other antimicrobial regimens (OR, 12.407; 95% CI, 1.684 to 31.430; P = 0.011). When patients were treated with antimicrobial regimens not containing CAZ-AVI, combination therapy (OR, 0.239; 95% CI, 0.077 to 0.741; P = 0.013) was related to a decreased 30-day mortality risk relative to monotherapy treatment. The mortality-related risk factors and relative antimicrobial regimen efficacy data demonstrated in this study may guide the management of CRE-BSI patients.


Assuntos
Bacteriemia , Sepse , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Carbapenêmicos/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Fatores de Risco , Sepse/tratamento farmacológico
20.
Front Cell Infect Microbiol ; 11: 667680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249774

RESUMO

Background: Sepsis contributes significantly to morbidity and mortality globally. In Australia, 20,000 develop sepsis every year, resulting in 5,000 deaths, and more than AUD$846 million in expenditure. Prompt, appropriate antibiotic therapy is effective in improving outcomes in sepsis. Conventional culture-based methods to identify appropriate therapy have limited yield and take days to complete. Recently, nanopore technology has enabled rapid sequencing with real-time analysis of pathogen DNA. We set out to demonstrate the feasibility and diagnostic accuracy of pathogen sequencing direct from clinical samples, and estimate the impact of this approach on time to effective therapy when integrated with personalised software-guided antimicrobial dosing in children and adults on ICU with sepsis. Methods: The DIRECT study is a pilot prospective, non-randomized multicentre trial of an integrated diagnostic and therapeutic algorithm combining rapid direct pathogen sequencing and software-guided, personalised antibiotic dosing in children and adults with sepsis on ICU. Participants and interventions: DIRECT will collect microbiological and pharmacokinetic samples from approximately 200 children and adults with sepsis admitted to one of four ICUs in Brisbane. In Phase 1, we will evaluate Oxford Nanopore Technologies MinION sequencing direct from blood in 50 blood culture-proven sepsis patients recruited from consecutive patients with suspected sepsis. In Phase 2, a further 50 consecutive patients with suspected sepsis will be recruited in whom MinION sequencing will be combined with Bayesian software-guided (ID-ODS) personalised antimicrobial dosing. Outcome measures: The primary outcome is time to effective antimicrobial therapy, defined as trough drug concentrations above the MIC of the pathogen. Secondary outcomes are diagnostic accuracy of MinION sequencing from whole blood, time to pathogen identification and susceptibility testing using sequencing direct from whole blood and from positive blood culture broth. Discussion: Rapid pathogen sequencing coupled with antimicrobial dosing software has great potential to overcome the limitations of conventional diagnostics which often result in prolonged inappropriate antimicrobial therapy. Reduced time to optimal antimicrobial therapy may reduce sepsis mortality and ICU length of stay. This pilot study will yield key feasibility data to inform further, urgently needed sepsis studies. Phase 2 of the trial protocol is registered with the ANZCTR (ACTRN12620001122943). Trial registration: Registered with the Australia New Zealand Clinical Trials Registry Number ACTRN12620001122943.


Assuntos
Sepse , Adulto , Antibacterianos/uso terapêutico , Austrália , Teorema de Bayes , Criança , Humanos , Estudos Multicêntricos como Assunto , Projetos Piloto , Estudos Prospectivos , Sepse/diagnóstico , Sepse/tratamento farmacológico , Resultado do Tratamento
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