Treatment Of Septic Patients Research Articles

Effectiveness and safety of Shenfu injection in septic patients with hypoperfusion: A multi-center, open-label, randomized, controlled trial

BackgroundTo evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion. MethodThis study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization. ResultsA total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P=0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days–6.0 days vs. median=5.0 days, IQR: 3.0 days–8.0 days, respectively; P=0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3–2.0 mmol/L vs. median=0.0 mmol/L, IQR: −0.2 to 0.8 mmol/L, respectively; P <0.001) and 24 h (median=1.4 mmol/L, IQR: 0.3–2.2 mmol/L vs. median=0.4 mmol/L, IQR: −0.4 to 1.6 mmol/L, respectively; P=0.001). ConclusionSFI plus standard therapy did not significantly decrease 28-day all-cause mortality for septic patients with hypoperfusion and TCM syndrome with Yang-Qi deficiency.Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR1800020435

The Omics Complexity in Sepsis: The Limits of the Personalized Medicine Approach.

Sepsis is one of the most common causes of morbidity and mortality worldwide. Despite the remarkable advances in modern medicine throughout the last century, the mortality rates associated with sepsis have remained significantly elevated, both in high- and low-income countries. The main difficulty in the diagnosis and treatment of septic patients is the tremendous heterogeneity of this condition. The vast heterogeneity that characterizes sepsis ranges from the clinical presentation to the biological aspects of the disease. Evidence-based medicine approaches sepsis as a homogenous syndrome and does not consider the individual discrepancies between septic patients. This approach may contribute to the poor outcomes of septic patients. In recent years, personalized medicine has gained significant interest. This novel form of medicine underlines the importance of understanding the genetic, epigenetic, and molecular basis of a disease in order to provide a more tailored approach for the patient. The study of "omics", such as cytomics, genomics, epigenomics, transcriptomics, proteomics, and metabolomics, provides a deeper comprehension of the complex interactions between the host, the disease, and the environment. The aim of this review is to summarize the potential role of a personalized approach in sepsis management, considering the interactions between various "omics".

Utility of Previous Culture Results for Guiding Empirical Treatment of Sepsis in The Emergency Department

Background: Sepsis is a serious medical condition and a major cause of morbidity and mortality, and poses challenges in terms of recognition and management. Although studies have investigated the early identification of sepsis and early use of broad-spectrum antibiotics, no clear criteria exist to identify those patients needing additional coverage for resistant organisms. Aims: This study aims to evaluate the utility of previous positive blood or urine culture results in predicting the presence of resistant organisms in septic patients in the emergency department (ED). Methods: This retrospective observational study was conducted at King Fahad Medical City (KFMC), a tertiary care centre in Riyadh, Saudi Arabia, between March and August 2021. Patients aged 18 years or older, who visited the ED at KFMC during the study period, were included if they had a positive blood or urine culture and met the sepsis definition. Result: A total of 133 patients were enrolled (mean age 61.6 [18.3] years), of whom approximately half were male (67, 50.4%). We found that previous colonisation with resistant organisms was more likely in patients with resistant organisms at the time of the enrolled visit (n = 17, 77.3%) than in patients with non-resistant organisms (n = 22, 19.8%, p &lt; .05). Therefore, one statically significant predictor of a current resistant organism is a prior colonisation with a resistant organism (OR = 13.8; 95% CIs 3.6, 51.9; p &lt; .05). Conclusion: Previous cultures, from within the last 12 months, are useful predictors of current resistant organisms, and are therefore essential in guiding empirical antibiotic treatment in septic patients in the ED. Further more extensive and prospective cohort studies on this subject are now needed to mitigate the burden of sepsis on healthcare systems worldwide.

Extracorporeal immune cell therapy of sepsis: ex vivo results

BackgroundImmune cell dysfunction plays a central role in sepsis-associated immune paralysis. The transfusion of healthy donor immune cells, i.e., granulocyte concentrates (GC) potentially induces tissue damage via local effects of neutrophils. Initial clinical trials using standard donor GC in a strictly extracorporeal bioreactor system for treatment of septic shock patients already provided evidence for beneficial effects with fewer side effects, by separating patient and donor immune cells using plasma filters. In this ex vivo study, we demonstrate the functional characteristics of a simplified extracorporeal therapy system using purified granulocyte preparations.MethodsPurified GC were used in an immune cell perfusion model prefilled with human donor plasma simulating a 6-h treatment. The extracorporeal circuit consisted of a blood circuit and a plasma circuit with 3 plasma filters (PF). PF1 is separating the plasma from the patient’s blood. Plasma is then perfused through PF2 containing donor immune cells and used in a dead-end mode. The filtrated plasma is finally retransfused to the blood circuit. PF3 is included in the plasma backflow as a redundant safety measure. The donor immune cells are retained in the extracorporeal system and discarded after treatment. Phagocytosis activity, oxidative burst and cell viability as well as cytokine release and metabolic parameters of purified GCs were assessed.ResultsCells were viable throughout the study period and exhibited well-preserved functionality and efficient metabolic activity. Course of lactate dehydrogenase and free hemoglobin concentration yielded no indication of cell impairment. The capability of the cells to secret various cytokines was preserved. Of particular interest is equivalence in performance of the cells on day 1 and day 3, demonstrating the sustained shelf life and performance of the immune cells in the purified GCs.ConclusionResults demonstrate the suitability of a simplified extracorporeal system. Furthermore, granulocytes remain viable and highly active during a 6-h treatment even after storage for 3 days supporting the treatment of septic patients with this system in advanced clinical trials.

305 The Frequency of Point-of-Care Ultrasound Use in the Treatment of Sepsis in the Emergency Department: A Retrospective Cohort Study

A role for point-of-care ultrasound (POCUS) in the care of septic patients has been previously proposed; however, the degree to which POCUS has been integrated into sepsis care in the community emergency department (ED) is unknown. Our aim was to better understand the current role of POCUS in sepsis care by examining its frequency of use and the types of exams performed. This retrospective cohort study analyzed 5, 264 ED visits for sepsis across two community hospitals from January 2014 to December 2018. Patients 18 years or older with an ED diagnosis of sepsis and either lactate ≥4 mmol, a documented mean arterial pressure < 65mmHg, or a systolic blood pressure < 90mmHg were eligible for inclusion. Eligible encounters underwent chart review to determine if POCUS was used during their ED evaluation. Primary outcomes were frequency of POCUS use in the cohort, change in frequency of POCUS use over the study period, and the types of exams performed. Odds ratios (OR), confidence intervals (CI), and p-values (p) were calculated to assess relationships between variables and POCUS use. POCUS was used in 21% of encounters meeting inclusion criteria and was positively correlated with ED arrival year (OR=1.09; 95% CI: 1.04 - 1.15; p=0.001). The most common POCUS exam was for central venous catheter (CVC) placement (37%); however, use of this exam did not increase over the study period. The second and third most common exams performed were cardiac (18%) and inferior vena cava (IVC) exams (11%), respectively. Only the frequency of cardiac, IVC, lung and Focused Assessment with Sonography for Trauma (FAST) exams increased significantly over the study period. Certain patient characteristics, including obese BMI (OR=1.28; 95% CI: 1.10 - 1.49; p=0.002) and increased Charlson comorbidity index (OR=1.03; 95% CI: 1.00 - 1.05; p=0.03), were associated with increased odds of receiving POCUS. A code status of DNR prior to ED arrival conferred lower odds of receiving POCUS (OR=0.74; 95% CI: 0.62 - 0.90; p=0.002). POCUS use increased significantly over time in this cohort of septic patients. This suggests increasing incorporation of ultrasound into sepsis care and a potential role for cardiac, IVC, and lung exams in the evaluation and treatment of septic patients. Further studies are needed to assess the generalizability of these findings, and determine if POCUS use affects treatment decisions or patient outcomes.

Comparison of Antimicrobial Susceptibility Test Results of Disk Diffusion, Gradient Strip, and Automated Dilution with Broth Microdilution for Piperacillin-Tazobactam.

In the treatment of septic patients, the prediction of a pathogen's susceptibility to piperacillin-tazobactam can be crucial. Commercial tests are available to measure the pathogen's susceptibility to piperacillin-tazobactam, but there is conflicting evidence regarding their accuracy. Therefore, this study compared the accuracy of disk diffusion, gradient strip, and automated dilution with the accepted standard broth microdilution. Testing was performed on 150 blood culture isolates from hospitalized patients at the University Hospital Bonn. The most recent Escherichia coli (n = 50), Klebsiella pneumoniae (n = 50), and Pseudomonas aeruginosa (n = 50) isolates were chosen. All measurements were performed strictly according to the manufacturer's instructions. Minimal inhibitory concentrations were primarily interpreted based on EUCAST (European Committee on Antimicrobial Susceptibility Testing) 8.1 and supplementarily based on CLSI (Clinical and Laboratory Standards Institute) 28th. The results of automated dilution showed a categorical agreement of 93.3% and presented five minor errors, four major errors, and one very major error. The results for gradient strip and disk diffusion were similar, except for the three additional major errors in the gradient strip and two additional very major errors in disk diffusion. Most of the major errors and very major errors were associated with P. aeruginosa. In conclusion, there was no relevant difference in accuracy between the three compared tests. Their overall categorical agreement ranged from 90.7% to 93.3% and was therefore at the lower end of the threshold. The possibly increased error rate for P. aeruginosa could be relevant in the preparation of empirical antibiotic guidelines and the treatment of septic patients. Universal Trial Number: U1111-1224-0035.

How Antibiotics Stewardship Can Be Safely Implemented in Patients with Septic Shock?

In critically ill patients with sepsis and septic shock, the need for prompt and adequate antibiotic therapy is balanced by the risk of excessive antibiotic exposure that leads to emergence of multidrug-resistant pathogens. As such, antibiotic stewardship programs propose a set of operating rules from antibiotic treatment initiation to de-escalation and finally cessation. In this review, we will describe the rationale for early antibiotic treatment in septic patients, how to optimize initial antibiotic treatment, rules for early treatment discontinuation in pathogen-negative sepsis, and optimal duration of antimicrobial therapy.

Immunotherapy-on-Chip Against an Experimental Sepsis Model.

Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG)-pre-activated vaccine-on-chip technology in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2μg/g LPS, allowing longer survival, necessary for a therapeutic treatment application. A novel immunotherapy technology, the so-called vaccine-on-chip, consists of a 3-dimensional laser micro-textured silicon (Si) scaffold loaded with macrophages and activated in vitro with 1μg/ml PG, which has been previously shown to exert a mild immunostimulatory activity upon subcutaneous implantation. The LPS treatment significantly decreased CD4 + and CD8 + cells, while increasing CD11b + , Gr1 + , CD25 + , Foxp3 + , and class II + cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and C-reactive protein (CRP), procalcitonin (PCT), IL-6, TNF-a, IL-10, and IL-18 in the serum, while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated implant significantly increased the percentage of CD4 + and CD8 + cells, while decreasing the percentage of Gr1 + , CD25 + , CD11b + , Foxp3 + cells, and arginase-1 activity in the spleen of LPS-treated animals, as well as all serum markers tested, allowing survival and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a novel immunotherapy technology based on PG pre-activated micro-texture Si scaffolds in LPS endotoxemia, supporting thus its potential use in the treatment of septic patients.

β-Sitosterol Alters the Inflammatory Response in CLP Rat Model of Sepsis by Modulation of NFκB Signaling.

Purpose Sepsis originates from the host inflammatory response, especially to bacterial infections, and is considered one of the main causes of death in intensive care units. Various agents have been developed to inhibit mediators of the inflammatory response; one prospective agent is β-sitosterol (βS), a phytosterol with a structure similar to cholesterol. This study is aimed at evaluating the effects of βS on the biomarkers of inflammation and liver function in cecal ligation and puncture- (CLP-) induced septic rats. Methods Thirty male Wistar rats were divided equally into six groups as follows: sham, CLP, CLP+dexamethasone (DX, 0.2 mg/kg), CLP+βS (1 mg/kg), CLP+imipenem (IMI, 20 mg/kg), and CLP+IMI (20 mg/kg)+βS (1 mg/kg). Serum levels of IL-1β, IL-6, IL-10, AST, ALT, and liver glutathione (GSH) were assessed by ELISA. Liver expression levels of TNF-α and NF-κBi mRNAs were evaluated by RT-qPCR. Results Serum concentrations of IL-1β, IL-6, IL-10, ALT, and AST and mRNA levels of TNF-α and NF-κBi were all significantly higher in septic rats than in normal rats (p < 0.05). Liver GSH content was markedly lower in the CLP group than that in the sham group. βS-treated rats had remarkably lower levels of IL-1β, IL-6, IL-10, TNF-α, NF-κBi, AST, and ALT (51.79%, 62.63%, 41.46%, 54.35%, 94.37%, 95.30%, 34.87%, and 46.53% lower, respectively) and greater liver GSH content (35.71% greater) compared to the CLP group (p < 0.05). Conclusion βS may play a protective role in the septic process by mitigating inflammation. This effect is at least partly mediated by inhibition of the NF-κB signaling pathway. Thus, βS can be considered as a supplementary treatment in septic patients.

Evaluation of plasma levels of meropenem in septic patients during extracorporeal blood purification

The relevance. Meropenem is a broad-spectrum carbapenem antibiotic widely used to treat patients with sepsis / septic shock. Critically ill patients are usually supported with one of the forms extracorporeal blood purification. However, data on the effect of various extracorporeal support techniques on the pharmacokinetics and pharmacodynamics of meropenem are insufficient or contradictory.&#x0D; Aim: To evaluate the effectiveness of meropenem dosage regimens in the treatment of septic patients during extracorporeal blood purification.&#x0D; Materials and methods. Plasma concentrations of meropenem were monitored in three critically ill patients with sepsis or septic shock. Patients were treated using various extracorporeal support techniques. Meropenem was used as empirical antibacterial mono- or complex therapy (1 g every 8 or 12 hours). Meropenem concentrations in plasma were determined by validated assay methods on Acquity ultraefficient liquid chromatography (UPLC) H-Class system.&#x0D; Results. It is shown that the meropenem plasma concentration in critically ill patients changes significantly. It was found that the standard meropenem dosing regimens in patients with sepsis / septic shock during continuous hemodiafiltration do not ensure the achievement of the PK/PD target of 100% TMIC for sensitive strains (MIC2 mg/L) and for intermediate resistance pathogens (2MIC8 mg/L). Continuous hemofiltration and selective adsorption of lipopolysaccharide have a less pronounced effect on the clearance of meropenem.&#x0D; Conclusion. To increase the effectiveness of antibacterial therapy, it is necessary to conduct research aimed at developing protocols for dosing antibacterial drugs for the treatment of sepsis during extracorporeal blood purification.

Vancomycin and daptomycin modulate the innate immune response in a murine model of LPS-induced sepsis.

Sepsis is a leading cause of death worldwide, despite the use of multimodal therapies. Common antibiotic regimens are being affected by a rising number of multidrug-resistant pathogens, and new therapeutic approaches are therefore needed. Antibiotics have immunomodulatory properties which appear to be beneficial in the treatment of sepsis. We hypothesized that the last-resort antibiotics vancomycin (VAN) and daptomycin (DMC) modulate cell migration, phagocytosis, and protein cytokine levels in a murine model of lipopolysaccharide (LPS)-induced sepsis. Ten to twelve-week-old C57BL/6 mice (n = 4–6 animals per group) were stimulated with LPS for 20 h, followed by the administration of VAN or DMC. The outcome parameters were leukocyte accumulation and effector function. Quantification of the immune cells in the peritoneal lavage was performed using flow cytometry analysis. Phagocytosis was measured using pHrodo E. coli BioParticles. The response of the cytokines TNFα, IL-6, and IL-10 was measured in vitro using murine peritoneal macrophages stimulated with LPS and VAN or DMC. VAN decreased both the peritoneal macrophage and the dendritic cell populations following LPS stimulation. DMC reduced the dendritic cell population in the peritoneal cavity in LPS-infected mice. Both antibiotics increased the phagocytic activity in peritoneal macrophages, but this effect was diminished in response to LPS. Phagocytosis of dendritic cells was increased in LPS-infected animals treated with VAN. VAN and DMC differently modulated the levels of pro-and anti-inflammatory cytokines. In a murine model of LPS-induced sepsis, VAN and DMC exhibit immunomodulatory effects on cells involved in innate immunity. The question of whether these antibiotics exhibit synergistic effects in the treatment of septic patients, beyond their bactericidal properties, should be further evaluated in future studies.

Managed clinical protocol: impact of implementation on sepsis treatment quality indicators.

to assess the impact of the implementation of a managed sepsis protocol on quality indicators of treatment for septic patients in an emergency department of a university hospital. an observational epidemiological study involving septic patients. The study was divided into two phases, pre-intervention and intervention, resulting from the implementation of the managed sepsis protocol. The study variables included sepsis treatment quality indicators. The results were statistically analyzed using the program Epi InfoTM. the study sample included 631 patients, 95 from pre-intervention phase and 536 from intervention phases. Implementing the protocol increased patients' chances of receiving the recommended treatment by 14 times. Implementing the protocol reduced the hospitalization period by 6 days (p <0.001) and decreased mortality (p <0.001). this study showed that implementing the managed protocol had an impact on the improvement of sepsis treatment quality indicators.

Polyreactive Transformation of Class G Immunoglobulins as a Vector for Search of Potential Means for Improving the Activity of Anti-endotoxin Immunity

Short-term in vitro exposure of a chaotropic reagent to native class G immunoglobulins can significantly increase the activity of anti-endotoxin immunity and cause a decrease in the ability of effector cells for enterobacteria lipopolysaccharides (LPS). This leads to reducing the LPS-dependent activation of these cells and subsequent inflammation. This can be useful not only for the treatment of septic patients, but also for the prevention of the progression of diseases of atherosclerotic nature, because LPS is considered to be the most important factor in the induction of atherogenesis. The polyreactive transformation mechanism of native class G immunoglobulins under the influence of a chaotropic reagent remains unknown. It can consist in the induction of intramolecular conformational rearrangements of native γ-globulins. As a result, “ancestral” sites of low-affinity multispecific binding appear on Fab fragments, which determines the appearance of complementarity to evolutionarily stable molecular structures of pathogens. The results indicate the need for further investigation of the polyreactive transformation mechanisms of native class G immunoglobulins and the search for nontoxic chaotropic agents that could potentially be used in clinical practice.

Xuebijing Injection Alleviates Pam3CSK4-Induced Inflammatory Response and Protects Mice From Sepsis Caused by Methicillin-Resistant Staphylococcus aureus

A leading cause of death worldwide is sepsis that develops as a dysregulated immune response to infection. Serious infection caused by methicillin-resistant Staphylococcus aureus (MRSA) increases the difficulty of treatment in septic patients. Host-directed therapy (HDT) is an emerging approach to bacterial infections. Xuebijing injection (XBJ), a commercialized injectable prescription from traditional Chinese medicine, has been used as adjuvant therapy for sepsis with a history of 15 years. Whether it plays a protective role in severe infection caused by antibiotic-resistant bacteria is still unknown. In this study, XBJ significantly improved the survival of MRSA-induced sepsis mice. In MRSA-infected mouse model, XBJ down-regulated the expression of inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, MCP-1, MIP-2, and IL-10 in sera. Besides that, it decreased the bacterial load in spleens, livers, and alleviated tissue damage of lung, liver, and kidney. The combination of XBJ with vancomycin or dexamethasone exhibited a better down-regulatory role of the inflammatory response. Then, the protective mechanism of XBJ was further investigated. XBJ inhibited heat-killed MRSA-induced IL-6 and TNF-α production in mouse macrophages. XBJ also decreased Pam3CSK4 (a synthetic tripalmitoylated lipopeptide mimicking bacterial lipoproteins)-stimulated expression of IL-6, TNF-α, IL-1β, IL-12, etc. in mouse macrophages. Furthermore, XBJ down-regulated the activation of NF-κB, MAPK, and PI3K/Akt pathways in Pam3CSK4-stimulated mouse macrophages. In conclusion, our findings demonstrated that XBJ played a protective role in MRSA-challenged mice and down-regulated the inflammatory response and the activation of signaling pathways initiated by Pam3CSK4. It enlarged the clinical application of XBJ in the treatment of severe bacterial infection, e.g. caused by MRSA.

Neuroendocrine immune network and sepsis

Sepsis is a life-threatening organ dysfunction caused by unregulated host response to infection. During sepsis, the body presents immune system disorder, and impaired hypothalamus-pituitary-adrenal (HPA) axis, which results in unregulated hormone secretion. Although a great number of studies have demonstrated the pivotal role of HPA axis and adrenal gland mircoenvironment in the progression of sepsis, its molecular mechanisms are not clarified. This review is designed to discuss the role of neuroendocrine immune network during the progression of sepsis. This review described the condition of HPA axis dysfunction and the relative adrenal insufficiency during sepsis, systematically introduces how neuroendocrine immune network are involved in the progress and prognosis of sepsis, and to further elaborate the changes in HPA axis and adrenal gland microenvironment and explore possible molecular mechanisms. The molecular mechanism of neuroendocrine immune network during sepsis is important and is helpful to provide new approaches to treatment of septic patients. Key words: Sepsis; Neuroendocrine immune network; Adrenal gland; Hypothalamus-pituitary-adrenal axis

What happens when we establish full code treatment for septic patients admitted to the intensive care unit with previous dementia?

What happens when we establish full code treatment for septic patients admitted to the intensive care unit with previous dementia?

Impact of rapid identification of positive blood cultures using the Verigene system on antibiotic prescriptions: A prospective study of community-onset bacteremia in a tertiary hospital in Japan.

BackgroundRapid identification of positive blood cultures is important for initiation of optimal treatment in septic patients. Effects of automated, microarray-based rapid identification systems on antibiotic prescription against community-onset bacteremia (COB) remain unclear.MethodsWe prospectively enrolled 177 patients with 185 COB episodes (occurring within 72 h of admission) over 17 months. Bacteremia episodes due to gram-positive bacteria (GP) and gram-negative bacteria (GN) in the same patient were counted separately. For GP bacteremia, patients with ≥2 sets of positive blood cultures were included. The primary study objective was evaluating the rates of antibiotic prescription changes within 2 days of rapid identification using the Verigene system.ResultsBacteremia due to GN and GP included 144/185 (77.8%) and 41/185 (22.2%) episodes, respectively. Antibiotic prescription changes occurred in 51/185 cases (27.6% [95%CI:21.3–34.6%]) after Verigene analysis and 70/185 cases (37.8% [30.8–45.2%]) after conventional identification and susceptibility testing. Prescription changes after Verigene identification were more frequent in GP (17/41[41.5%]) than in GN (34/144[23.5%]). Among bacteremia due to single pathogen targeted by Verigene test, bacterial identification agreement between the two tests was high (GP: 38/39[97.4%], GN: 116/116[100%]). The Verigene test correctly predicted targeted antimicrobial resistance. The durations between the initiation of incubation and reporting of the results for the Verigene system and conventional test was 28.3 h (IQR: 25.8–43.4 h) and 90.6 h (68.3–118.4 h), respectively. In only four of the seven episodes of COB in which two isolates were identified by conventional tests, the Verigene test correctly identified both organisms.ConclusionWe observed a high rate of antibiotic prescription changes after the Verigene test in a population with COB especially in GP. The Verigene test would be a useful tool in antimicrobial stewardship programs among patients with COB.

Lipid testing in infectious diseases: possible role in diagnosis and prognosis.

Acute infections lead to significant alterations in metabolic regulation including lipids and lipoproteins, which play a central role in the host immune response. In this regard, several studies have investigated the role of lipid levels as a marker of infection severity and prognosis. We review here the role of lipids in immune response and the potential mechanisms underneath. Moreover, we summarize studies on lipid and lipoprotein alterations in acute bacterial, viral and parasitic infections as well as their diagnostic and prognostic significance. Chronic infections (HIV, HBV, HCV) are also considered. All lipid parameters have been found to be significantly dearranged during acute infection. Common lipid alterations in this setting include a decrease of total cholesterol levels and an increase in the concentration of triglyceride-rich lipoproteins, mainly very low-density lipoproteins. Also, low-density lipoprotein cholesterol, apolipoprotein A1, low-density lipoprotein cholesterol and apolipoprotein-B levels decrease. These lipid alterations may have prognostic and diagnostic role in certain infections. Lipid testing may be of help to assess response to treatment in septic patients and those with various acute infections (such as pneumonia, leptospirosis and others). Diagnostically, new onset of altered lipid levels should prompt the clinician to test for underlying infection (such as leishmaniasis).

Homeopathic treatment of septic patients

Homeopathic treatment of septic patients

Diagnosis of Sepsis with Cell-free DNA by Next-Generation Sequencing Technology in ICU Patients

Bacteremia is a common serious manifestation of disease in the intensive care unit (ICU), which requires quick and accurate determinations of pathogens to select the appropriate antibiotic treatment. To overcome the shortcomings of traditional bacterial culture (BC), we have adapted next-generation sequencing (NGS) technology to identify pathogens from cell-free plasma DNA. In this study, 78 plasma samples from ICU patients were analyzed by both NGS and BC methods and verified by PCR amplification/Sanger sequencing and ten plasma samples from healthy volunteers were analyzed by NGS as negative controls to define or calibrate the threshold of the NGS methodology. Overall, 1578 suspected patient samples were found to contain bacteria or fungi by NGS, whereas ten patients were diagnosed by BC. Seven samples were diagnosed with bacterial or fungal infection both by NGS and BC. Among them, two samples were diagnosed with two types of bacteria by NGS, whereas one sample was diagnosed with two types of bacteria by BC, which increased the detectability of bacteria or fungi from 11 with BC to 17 with NGS. Most interestingly, 14 specimens were also diagnosed with viral infection by NGS. The overall diagnostic sensitivity was significantly increased from 12.82% (10/78) by BC alone to 30.77% (24/78) by NGS alone for ICU patients, which provides more useful information for establishing patient treatment plans. NGS technology can be applied to detect bacteria in clinical blood samples as an emerging diagnostic tool rich in information to determine the appropriate treatment of septic patients.