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Read only for medical professionals to accurately diagnose and treat culture-negative seps.
Know these poin.
Sepsis is a serious infectious disease that threatens life and heal.
Accurate and effective anti-infective treatment can improve the prognosis of patien.
In recent years, the proportion of culture-negative sepsis in sepsis has been increasing year by ye.
Unlike sepsis with positive culture results, culture-negative sepsis itself lacks the evidence of positive culture of pathogenic microorganisms and related information such as drug sensitivity, and the current There is a relative lack of understanding of its clinical characteristics and prognosis, and the treatment effect is often unsatisfacto.
At present, the method based on the culture of pathogenic bacteria is still the main method for the etiological diagnosis of sepsis, but the shortcomings of long detection time and low sensitivity brought by its own technical limitations cannot be ignor.
R&.
Some of these rapid etiological detection methods that do not rely on culture are expected to provide new and powerful support for the etiological diagnosis of seps.
The mortality rate of sepsis is still high, and clinical diagnosis and treatment strategies need to be improved urgent.
Sepsis is a group of syndromes in which severe organ dysfunction caused by infection-induced dysregulation of the host response can be life-threateni.
Sepsis not only seriously threatens human health, but also brings a huge economic burden to the world's health care system, and is a major global health care probl.
In addition, with the aging of the population, immunosuppression, and multidrug-resistant infections, the incidence of sepsis is increasing year by ye.
The number of new sepsis patients in the world exceeds 19 million each year, of which 6 million patients d.
more than 1/4[1-
In China, the vast majority of studies on sepsis morbidity and mortality come from patients admitted to the intensive care unit (IC.
A 2020 research report on ICUs in 44 hospitals across the country showed that about 1/5 of ICU patients developed sepsis, and the fatality rate of sepsis patients was 35%, and the fatality rate of severe sepsis was as high as 50% and 5
The above, and several related studies have shown that the fatality rate of sepsis in China is higher than that in developed countries [3-
Early initiation of effective antibiotic therapy can reduce mortality and improve prognosis in patients with sepsis [5-
In the past 20 years, sepsis treatment guidelines and protocols have been changed and improved several tim.
These guidelines widely recommend the use of one or more broad-spectrum antibiotics to fight infection beforehand, covering all possible pathoge.
Once the causative microorganisms are identified, Obtain the drug susceptibility results, or the clinical symptoms are sufficiently improved, and then select the corresponding narrow-spectrum antibiotics for further treatme.
Unfortunately, however, still about 28%-89% of sepsis patients do not have positive culture results, providing guidance for their anti-infective treatment [8-1
Currently, little is known about this type of culture-negative seps.
Therefore, this article focuses on: 1) the clinical features and outcomes of culture-negative sepsis; 2) the possible causes of culture-negative sepsis; 3) emerging technologies and methods for rapid diagnosis of sepsis etiology; 4) the causes of sepsis This paper summarizes the four aspects of antimicrobial drug selection, and hopes to improve clinicians' understanding of culture-negative sepsis and emerging technologies for rapid diagnosis of etiolo.
Clinical features and outcomes of patients with culture-negative sepsis Clinical features Sepsis without positive microbiological evidence of infection is termed culture-negative seps.
Clinically, the establishment of a culture-negative sepsis diagnosis is based on a clear diagnosis of sepsis itself, such as no positive pathogens in the culture of blood, sputum, body fluids or other tissues [1
Existing studies have not been able to draw uniform conclusions about the description of the clinical features and outcomes of culture-negative/positive seps.
Although the descriptions of the clinical features of culture-negative/positive sepsis summarized by different studies are different, most of them are summarized from the general situation of sepsis patients, the severity of the disease, and the differences in the source of infecti.
There are four main points:Baseline data: There is no significant difference in the gender, age and other general conditions of culture-negative/positive sepsis patients, and the age distribution generally fluctuates between 62-76 years old, and most of them are male[11-1
Clinical manifestations: Culture-positive sepsis patients are more prone to septic shock, high fever, leukocytosis, thrombocytopenia, procalcitonin and lactate levels; while culture-negative sepsis patients have fewer comorbidities and severe disease The degree is milder, and the level of procalcitonin is lower [11, 1
Severity of disease: APACHE-II and SOFA scores at admissi.
Routine scores of disease severity at admission, such as acute physiology and chronic health score (APACHE-II) and sequential organ failure score (SOFA), can help us Rapidly assess the patient's current basic condition, disease severity, and predict disease prognos.
The study by Li[16] et .
showed that the proportion of rapid sequential organ failure score (qSOFA)>2 was similar between culture-negative sepsis and culture-positive sepsis, while Liu and Phua J[11, 13] et al proposed Culture-negative sepsis patients had lower APACHE-II and SOFA scores and less severe disease on admissi.
Organ Dysfunction Scholars hold different views on the incidence of organ damage in culture-negative/positive sepsis patien.
Nannan Panday [12] et al believed that compared with culture-negative sepsis, patients with culture-positive sepsis were more likely to develop multiple organ damage, and were more prone to dysfunction of the cardiovascular system, liver, kidney, and metabolism, and proposed that cultured Positive sepsis was positively associated with involvement of 3 or more organ systems during sepsis infecti.
Contrary to this, Gupta et .
[9] argued that culture-negative patients with severe sepsis were more likely to have comorbidities and acute organ dysfunction (respiratory, cardiac, hepatic, and renal dysfunctio.
Different sources of infection and distribution of flora: For patients with culture-negative sepsis, respiratory tract infections are more common; while urogenital system infections, hepatobiliary tract infections, skin and soft tissue infections, infective endocarditis and primary For sepsis caused by bloodstream infection, e.
, positive culture results are more common [9,11,13,1
Regarding the differences in the distribution of bacteria in culture-positive sepsis patients, Kim et .
[15] showed that Escherichia coli, Klebsiella, and Staphylococcus ranked the top 3, accounting for the proportion of culture-positive sepsis bacteria respective.
33%, 18%, 2% of colum.
Prognosis of culture-negative sepsis patients Whether there is a difference in the prognosis of culture-negative/positive sepsis patients is also the focus of everyone’s attenti.
Several existing clinical studies have given different answers, which can be roughly divided into the following three categories: ( 1) The overall prognosis of culture-negative sepsis is better than that of culture-positive sepsis; (2) The overall prognosis of culture-negative sepsis is worse than that of culture-positive sepsis; (3) Culture-negative sepsis is the same as culture-positive seps.
The prognosis is simil.
The studies of Hazwani, Nannan Panday, Liu, Phua.
et al [11-14] suggested that the overall prognosis of culture-negative sepsis patients was better, and the mortality and organ dysfunction of culture-positive patients were higher, but Phua The study by J[13] further mentioned that a positive culture result was not an independent predictor of dea.
On the contrary, Gupta et .
[9] concluded that patients with culture-negative sepsis have a poor overall prognosis for the following reasons: (1) Delayed or inadequate antibiotic therapy and lack of specific culture guidance, leading to Inappropriate antibiotic treatme.
Since inappropriate and inadequate antibiotic treatment is associated with higher mortality in patients with severe sepsis, these patients may be converted to culture-negative severe sepsis cohorts with increased mortality; (2) severe sepsis Severe disease at the onset of the disease prompts clinicians to use antibiotics early without obtaining appropriate cultures, resulting in a culture-negative state; (3) antibiotics have been used before progression to severe sepsis, On the one hand, it will lead to the conversion of some culture status to negative, on the other hand, it may reduce antimicrobial susceptibility and increase mortality; (4) Some patients with culture-negative sepsis are not found with severe sepsis until hospitalization, which may lead to worse 's prognos.
Some articles also put forward a third point of view, arguing that there is no significant difference in the prognosis of patients with culture-negative/positive sepsis, who have similar ICU length of stay, mechanical ventilation demand rate, and renal replacement therapy demand rate, but also proposed that culture-positive sepsis The length of hospital stay and the duration of mechanical ventilation in patients with sepsis were longer than those in patients with culture-negative sepsis, and these differences may be due to differences in patient population, proportion of infection sites, and bacterial resistance to antibiotics [15-1
There is still no generally accepted conclusion about the clinical outcome of patients with culture-negative/positive seps.
Therefore, further research and research are need.
The possible causes of culture-negative sepsis The current research cannot explain the difference between culture-negative sepsis and culture-positive sepsis from the perspective of mechanism and pathology, but the possible causes can be further explored from the following four aspects: (1) Cultures are not sufficiently sensitive to identify pathogenic bacteria,.
false negatives exi.
Presumed reasons include the use of antibiotics before testing, insufficient blood cultures, poor transport conditions, slow growth, and the presence of fastidious bacteria [1
(2) The pathogenic microorganisms may be atypical pathogens, including fungi, viruses and some parasit.
Studies have shown that the proportion of sepsis/septic shock caused by atypical pathogens may be increasing, and routine pathogenic microbiological examination methods, including culture, mostly focus on the detection of bacteria, but are limited by technology-related issues and have not been widely us.
Covered to detect fungi and viruses [1
(3) The frequency of culture positive/negative is related to the nature of some infectio.
As mentioned above, multiple studies have shown that respiratory infections are more common in patients with culture-negative sepsis; urogenital infections, hepatobiliary tract infections, skin and soft tissue infections, infective endocarditis, and primary For sepsis caused by bloodstream infection, e.
, positive culture results are more common [9,11,13,1
(4) The culture-negative sepsis patients included in the study may actually have some false positives, unrelated to infecti.
Since there is currently no "gold standard" for the diagnosis of sepsis, it is difficult for medical staff to make differential diagnosis of sepsis patients with organ dysfunction alo.
In fact, one third or more of patients initially diagnosed with sepsis subsequently prove non-infectious disease [1
The causes of organ dysfunction may be metabolic disorders, tissue damage, inflammatory diseases, adverse drug reactions, malignant tumors and subarachnoid hemorrhage [2
The emerging technologies for rapid diagnosis of sepsis etiology focus on the detection rate, timeliness, functional index analysis and rapid qualitative analysis of unknown pathogens for the detection of infectious diseas.
Blood culture (BC) is the most direct and objective method to confirm pathogenic bacteria, and it is still the "gold standard" for the diagnosis of infectious diseas.
The diagnosis of sepsis also largely depends on the positive blood culture resul.
However, this method also has certain limitations, such as long testing time, high blood collection volume, treatment interference, limited types of detectable pathogens, and contamination, e.
, which may lead to delays, insufficient antibiotic treatment, and inappropriate selection of antibioti.
Appropria.
Therefore, many emerging rapid pathogen detection technologies have emerged, including polymerase chain reaction (PCR) related detection technologies, including real-time quantitative PCR, digital PCR, and the gradually mature and popular second-generation sequencing technology (Next Generation Sequencing, NGS) and microfluidic chip technology, as follows: The polymerase chain reaction PCR test is a reliable non-culture microbial detection method, which is widely used in laboratories around the world to detect a variety of microbial pathoge.
PCR diagnosis is based on PCR technology to complete the amplification of pathogen-specific gene fragments to determine the presence of pathogens in the samp.
At present, the second and third generation PCR technology is mainly used, and the second generation PCR is the fluorescence quantitative PCR technolo.
Commonly used in infectious disease pathogen detection, disease resistance gene research and so .
The technical operation process is simpler, cost-effective, and requires a very small amount of DNA and RNA samples, but there are problems such as easy contamination, especially due to the aerosol contamination caused by PCR amplification, an extremely small amount of contamination can cause false positiv.
produ.
The third-generation PCR technology is called digital P.
Compared with the second-generation technology, digital PCR has higher sensitivity, more accurate quantification, and stronger anti-interference ability, but requires higher template quality and primer specifici.
Currently, digital PCR technology can be used to detect viral and bacterial infections, especially the rapid identification of bacteria in positive blood culture bottles of common culture, which can guide the selection of anti-infective treatment 1-2 days before the results of routine drug susceptibility testi.
While actively performing blood culture testing, it can also shorten the length of ICU stay and reduce 30-day mortality [2
The PCR-related technology also has its own limitatio.
On the one hand, PCR-based etiological detection technology can only detect known pathogenic microorganisms, and it lacks the distinction between colonization and infecti.
The interpretation of the results is highly dependent on clinical experience, which will affect the accuracy of the conclusions to a certain exte.
On the other hand, there is a lack of data on antibiotic susceptibility in the positive results obtained by PCR-related detection technology to assist the targeted therapy of antibiotics [22-2
Sequencing-based method—the detection of metagenomic infectious diseases focuses on detection rate, timeliness, functional index analysis and rapid qualitative analysis of unknown pathoge.
The shortcomings of insufficient analytical capacity and difficult to achieve broad-spectrum detection, and gene sequencing provides a new way to solve these proble.
In recent years, NGS has become more and more mature and popular, providing a new and powerful means for etiological diagnos.
NGS is a new sequencing method relative to next-generation DNA sequencing technology, which can simultaneously measure millions or even hundreds of millions of DNA or RNA sequenc.
During the sequencing process, all nucleic acid fragments in the specimen are directly extracted and detected, and the type of nucleic acid contained in the specimen can be identified by bioinformatics analysis, and quantitative analysis data such as the sequence number and coverage of pathogens can be obtain.
When using NGS, specimens do not need to be cultured before detection, avoiding missed detection of difficult-to-culture pathoge.
During the detection, all nucleic acid fragments can be directly and non-specifically determined, without the need to select the detection range in advance (ie, unbiased), thus avoiding missed detection to the greatest exte.
The advantages of NGS lie in high sequencing throughput, high sensitivity, early identification of pathogens and short time, not only that, but also the detection of special pathogens to make up for the shortcomings of traditional detection techniqu.
However, NGS still has shortcomings such as the lack of recognized interpretation standards to effectively distinguish pathogenic bacteria from background bacteria, the unstandardized technology and database, the difficulty in detecting drug resistance genes, and the unclear relationship between sequencing results and treatme.
A comparative validation of the method on a larger scale [24-2
Other emerging technologies Some emerging detection technologies are gradually being studied by more and more scientists, such as microfluidic chip technolo.
The efficacy of microfluidic chip technology in medical applications has been confirmed, and it is currently being gradually applied in basic medical research on stem cell growth and its function, cell aging process, cell microenvironment and its related transmitters and many other aspec.
In clinical medical research, microfluidic technology has also been developed in the fields of early diagnosis of sepsis and other diseases, screening of antimicrobial-resistant bacterial infections, assisted reproductive technology, and clinical tumor classificati.
Unlike PCR technology, microfluidic technology does not multiply substances such as DNA or cytokines to produce amplification effects, but more through factors such as size, shape, density, deformability, electrical/magnetic susceptibility, and hydrodynami.
Cells or pathogens with special physical and chemical properties are screened, isolated and enriched to achieve the purpose of definite diagnosis or auxiliary diagnosis [2
Zhou et .
[27] carried out a study using microfluidic chips to capture CD64 and CD69 on the cell surface of clinical blood samples to detect culture-negative seps.
Combined with previous studies, CD64 and CD69 were shown to be the early and early stage of seps.
valid mark.
Zhou's research shows that the microfluidic chip is used for the detection of early sepsis, and its accuracy is higher than that of traditional blood cultu.
A multi-parameter chip developed by his team measures a combined panel of CD25, CD64 and CD69, which can be used to diagnose sepsis with a considerable diagnostic performance (97
In addition, microfluidics has the advantages of shorter time, convenient fabrication, less sample loading, low complexity, portability, e.
, and has great potential as a bedside sepsis detection meth.
Antibacterial treatment of sepsis After early identification of sepsis, clinical intervention can be time.
In adult patients with a high likelihood of sepsis or possible septic shock, guidelines recommend the immediate use of antimicrobials, preferably within 1 hour of identificati.
For adult patients with multidrug resistance (MDR) at high risk of sepsis/septic shock, empiric therapy with a combination of two different types of antibiotics that cover Gram-negative bacteria is recommended, rather than just one that targets the blue-negative bacter.
Once the pathogen and drug susceptibility results are clear, it is recommended to no longer use two anti-Gram-negative bacteria drugs in combinati.
A systematic review of 10 randomized controlled trials (RCTs) confirmed the mortality and other important outcomes of empiric monotherapy or multidrug therapy in ICU adults with severe sepsis or septic shock There was no difference (no difference in disease severit.
Among them, the results of the largest RCT included in the meta-analysis (comparison of moxifloxacin with meropenem and meropenem alone in a low-risk setting) were consistent with the results of the meta-analys.
Prolonged infusion time is recommended when using β-lactams, which may change important pharmacokinetic parameters in sepsis and septic shock, resulting in lower plasma concentrations/ or too hi.
Compared to intermittent dosing (infusion time ≤30 minutes), prolonged intravenous administration, either prolonged or continuous, resulted in sustained beta-lactam concentratio.
Before prolonged administration, it is necessary to give a loading dose of antibacterial drug, which can avoid delay and achieve effective β-lactam concentration [2
Summary Sepsis is a serious life-threatening infectious disease, and the proportion of sepsis patients with negative culture status in the total number of sepsis patients is increasing year by year, and the mortality rate remains hi.
Current studies have not been able to draw uniform conclusions on the clinical characteristics and outcomes of culture-negative sepsis patien.
Due to the lack of culture-positive relevant data and the uncertainty of their diagnosis, these patients should provide early clinical intervention and accurate diagnos.
Chemotherapeutic anti-infective treatment brings certain difficulties, and some emerging technologies for accurate and rapid etiological diagnosis, such as fluorescent PCR, digital PCR and NGS, can also help clinicians optimize the use of antimicrobial dru.
Early identification of this type of "special" sepsis patients in clinical work and timely intervention to obtain better clinical prognosis requires further explorati.
Expert Profile Professor Wu Benquan Chief Physician, Doctor of Medicine, Doctoral Supervisor; Director of the MICU of the Third Affiliated Hospital of Sun Yat-sen University, Deputy Director of the Department of Critical Care Medicine of the Third Affiliated Hospital of Sun Yat-sen University, Director of the Medical Department of the Third Affiliated Hospital of Sun Yat-sen University; Guangdong Provincial Society of Pathophysiology Deputy Director of the Critical Care Branch, Member of the Tuberculosis Society of the Guangdong Medical Association, Member of the Respiratory Society of the Guangdong Medical Association, Member of the Standing Committee of the Critical Care Branch of the Guangdong Health Management Society, and Member of the Respiratory Society of the Guangdong Health Management Society; good at respiratory diseases and critical illnesses He has published more than 60 related papers and more than 10 SCI papers, edited a monograph "Basic and Clinical of MRSA", and presided over two National Natural Science Foundation of China and a number of provincial and bureau-level scientific research projec.
15(1): Published 2017 Jandoi:11186/s12951-016-0235-4[27] Zhou Y, Zhang Y, Johnson A, Venable A, Griswold J, Pappas.
Detection of culture-negative sepsis in clinical blood samples using a microfluidic assay for combined CD64 and CD69 cell captu.
Anal Chim Ac.
2019;1062:110-11 doi:11016.
a.
2010039[28] Laura Evans, et .
Intensive Care M.
2021 Nov;47(11):1181-124 The author of this article: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-sen University Highlights of past issues:Anti-infective treatment strategies for severe nosocomial infection (Part 1): Do a good job of sepsisAnti-infective treatment strategies for severe nosocomial infection (Part II): appropriate selection and optimization of antibioticsIn severe patients with gram-negative bacterial infection, the optimal treatment plan of β-lactam antibioticsIn severe patients with gram-negative bacterial infection, continuous infusion of β-lactam antibiotics can achieve satisfactory PK/PD goals , The latest research, non-CP-CRE infection death risk is 4 times higher than CP-CRE!In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsisCarbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy?The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Zhang Y, Johnson A, Venable A, Griswold J, Pappas.
Detection of culture-negative sepsis in clinical blood samples using a microfluidic assay for combined CD64 and CD69 cell captu.
Anal Chim Ac.
2019;1062:110-11 doi :11016.
a.
2010039[28] Laura Evans, et .
Intensive Care M.
2021 Nov; 47(11): 1181-124 Author: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-Sen University Review:Anti-infective treatment strategies for severe nosocomial infection (Part 1): early identification and differential diagnosis of sepsisAnti-infective treatment strategies for severe nosocomial infection (Part 2): appropriate selection and optimization of antibiotics , Drug monitoring of meropenem and piperacillin in the treatment of critically ill patients, experience and recommendations of routine clinical practice Infection, continuous infusion of β-lactam antibiotics can achieve satisfactory PK/PD goalsThe latest research shows that the risk of death from non-CP-CRE infection is 4 times higher than CP-CRE!In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsisCarbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy?The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Zhang Y, Johnson A, Venable A, Griswold J, Pappas.
Detection of culture-negative sepsis in clinical blood samples using a microfluidic assay for combined CD64 and CD69 cell captu.
Anal Chim Ac.
2019;1062:110-11 doi :11016.
a.
2010039[28] Laura Evans, et .
Intensive Care M.
2021 Nov; 47(11): 1181-124 Author: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-Sen University Review:Anti-infective treatment strategies for severe nosocomial infection (Part 1): early identification and differential diagnosis of sepsis Anti-infective treatment strategies for severe nosocomial infection (Part 2): appropriate selection and optimization of antibiotics , Drug monitoring of meropenem and piperacillin in the treatment of critically ill patients, experience and recommendations of routine clinical practice Infection, continuous infusion of β-lactam antibiotics can achieve satisfactory PK/PD goals The latest research shows that the risk of death from non-CP-CRE infection is 4 times higher than CP-CRE! In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis Carbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy? The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Detection of culture-negative sepsis in clinical blood samples using a microfluidic assay for combined CD64 and CD69 cell captu.
Anal Chim Ac.
2019;1062:110-11 doi:11016.
a.
2010039[28] Laura Evans , et .
Intensive Care M.
2021 Nov;47(11):1181-124 The author of this article: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-sen University Highlights of past issues: Anti-infective treatment strategies for severe nosocomial infections (Part 1 ): early identification and differential diagnosis of sepsis Anti-infective treatment strategies for severe nosocomial infection (Part 2): Appropriate selection and optimization of antibiotics Drug monitoring in critically ill patients treated with meropenem and piperacillin, routine Experiences and suggestions from clinical practice In severe patients with gram-negative bacterial infection, the optimal treatment plan of β-lactam antibiotics In severe patients with gram-negative bacterial infection, continuous infusion of β-lactam antibiotics can be satisfactory The PK/PD goal of 6, the latest research, non-CP-CRE infection mortality risk is 4 times higher than CP-CRE! In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis Carbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy? The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Detection of culture-negative sepsis in clinical blood samples using a microfluidic assay for combined CD64 and CD69 cell captu.
Anal Chim Ac.
2019;1062:110-11 doi:11016.
a.
2010039[28] Laura Evans , et .
Intensive Care M.
2021 Nov;47(11):1181-124 The author of this article: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-sen University Highlights of past issues: Anti-infective treatment strategies for severe nosocomial infections (Part 1 ): early identification and differential diagnosis of sepsis Anti-infective treatment strategies for severe nosocomial infection (Part 2): Appropriate selection and optimization of antibiotics Drug monitoring in critically ill patients treated with meropenem and piperacillin, routine Experiences and suggestions from clinical practice In severe patients with gram-negative bacterial infection, the optimal treatment plan of β-lactam antibiotics In severe patients with gram-negative bacterial infection, continuous infusion of β-lactam antibiotics can be satisfactory The PK/PD goal of 6, the latest research, non-CP-CRE infection mortality risk is 4 times higher than CP-CRE! In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis Carbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy? The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Author of this article: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-Sen University Highlights of past issues: Anti-infective treatment strategies for severe nosocomial infection (Part 1): early identification and differential diagnosis of sepsis Infection treatment strategy (Part 2): appropriate selection and optimization of antibiotics The best treatment plan for antibiotic-like drugs In severe patients with Gram-negative bacterial infection, continuous infusion of beta-lactam antibiotics can achieve satisfactory PK/PD goals -CRE is 4 times higher! In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis Carbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy? The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Author of this article: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-Sen University Highlights of past issues: Anti-infective treatment strategies for severe nosocomial infection (Part 1): early identification and differential diagnosis of sepsis Infection treatment strategy (Part 2): appropriate selection and optimization of antibiotics The best treatment plan for antibiotic-like drugs In severe patients with Gram-negative bacterial infection, continuous infusion of beta-lactam antibiotics can achieve satisfactory PK/PD goals -CRE is 4 times higher! In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis Carbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy? The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease are.
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Know these poin.
Sepsis is a serious infectious disease that threatens life and heal.
Accurate and effective anti-infective treatment can improve the prognosis of patien.
In recent years, the proportion of culture-negative sepsis in sepsis has been increasing year by ye.
Unlike sepsis with positive culture results, culture-negative sepsis itself lacks the evidence of positive culture of pathogenic microorganisms and related information such as drug sensitivity, and the current There is a relative lack of understanding of its clinical characteristics and prognosis, and the treatment effect is often unsatisfacto.
At present, the method based on the culture of pathogenic bacteria is still the main method for the etiological diagnosis of sepsis, but the shortcomings of long detection time and low sensitivity brought by its own technical limitations cannot be ignor.
R&.
Some of these rapid etiological detection methods that do not rely on culture are expected to provide new and powerful support for the etiological diagnosis of seps.
The mortality rate of sepsis is still high, and clinical diagnosis and treatment strategies need to be improved urgent.
Sepsis is a group of syndromes in which severe organ dysfunction caused by infection-induced dysregulation of the host response can be life-threateni.
Sepsis not only seriously threatens human health, but also brings a huge economic burden to the world's health care system, and is a major global health care probl.
In addition, with the aging of the population, immunosuppression, and multidrug-resistant infections, the incidence of sepsis is increasing year by ye.
The number of new sepsis patients in the world exceeds 19 million each year, of which 6 million patients d.
more than 1/4[1-
In China, the vast majority of studies on sepsis morbidity and mortality come from patients admitted to the intensive care unit (IC.
A 2020 research report on ICUs in 44 hospitals across the country showed that about 1/5 of ICU patients developed sepsis, and the fatality rate of sepsis patients was 35%, and the fatality rate of severe sepsis was as high as 50% and 5
The above, and several related studies have shown that the fatality rate of sepsis in China is higher than that in developed countries [3-
Early initiation of effective antibiotic therapy can reduce mortality and improve prognosis in patients with sepsis [5-
In the past 20 years, sepsis treatment guidelines and protocols have been changed and improved several tim.
These guidelines widely recommend the use of one or more broad-spectrum antibiotics to fight infection beforehand, covering all possible pathoge.
Once the causative microorganisms are identified, Obtain the drug susceptibility results, or the clinical symptoms are sufficiently improved, and then select the corresponding narrow-spectrum antibiotics for further treatme.
Unfortunately, however, still about 28%-89% of sepsis patients do not have positive culture results, providing guidance for their anti-infective treatment [8-1
Currently, little is known about this type of culture-negative seps.
Therefore, this article focuses on: 1) the clinical features and outcomes of culture-negative sepsis; 2) the possible causes of culture-negative sepsis; 3) emerging technologies and methods for rapid diagnosis of sepsis etiology; 4) the causes of sepsis This paper summarizes the four aspects of antimicrobial drug selection, and hopes to improve clinicians' understanding of culture-negative sepsis and emerging technologies for rapid diagnosis of etiolo.
Clinical features and outcomes of patients with culture-negative sepsis Clinical features Sepsis without positive microbiological evidence of infection is termed culture-negative seps.
Clinically, the establishment of a culture-negative sepsis diagnosis is based on a clear diagnosis of sepsis itself, such as no positive pathogens in the culture of blood, sputum, body fluids or other tissues [1
Existing studies have not been able to draw uniform conclusions about the description of the clinical features and outcomes of culture-negative/positive seps.
Although the descriptions of the clinical features of culture-negative/positive sepsis summarized by different studies are different, most of them are summarized from the general situation of sepsis patients, the severity of the disease, and the differences in the source of infecti.
There are four main points:Baseline data: There is no significant difference in the gender, age and other general conditions of culture-negative/positive sepsis patients, and the age distribution generally fluctuates between 62-76 years old, and most of them are male[11-1
Clinical manifestations: Culture-positive sepsis patients are more prone to septic shock, high fever, leukocytosis, thrombocytopenia, procalcitonin and lactate levels; while culture-negative sepsis patients have fewer comorbidities and severe disease The degree is milder, and the level of procalcitonin is lower [11, 1
Severity of disease: APACHE-II and SOFA scores at admissi.
Routine scores of disease severity at admission, such as acute physiology and chronic health score (APACHE-II) and sequential organ failure score (SOFA), can help us Rapidly assess the patient's current basic condition, disease severity, and predict disease prognos.
The study by Li[16] et .
showed that the proportion of rapid sequential organ failure score (qSOFA)>2 was similar between culture-negative sepsis and culture-positive sepsis, while Liu and Phua J[11, 13] et al proposed Culture-negative sepsis patients had lower APACHE-II and SOFA scores and less severe disease on admissi.
Organ Dysfunction Scholars hold different views on the incidence of organ damage in culture-negative/positive sepsis patien.
Nannan Panday [12] et al believed that compared with culture-negative sepsis, patients with culture-positive sepsis were more likely to develop multiple organ damage, and were more prone to dysfunction of the cardiovascular system, liver, kidney, and metabolism, and proposed that cultured Positive sepsis was positively associated with involvement of 3 or more organ systems during sepsis infecti.
Contrary to this, Gupta et .
[9] argued that culture-negative patients with severe sepsis were more likely to have comorbidities and acute organ dysfunction (respiratory, cardiac, hepatic, and renal dysfunctio.
Different sources of infection and distribution of flora: For patients with culture-negative sepsis, respiratory tract infections are more common; while urogenital system infections, hepatobiliary tract infections, skin and soft tissue infections, infective endocarditis and primary For sepsis caused by bloodstream infection, e.
, positive culture results are more common [9,11,13,1
Regarding the differences in the distribution of bacteria in culture-positive sepsis patients, Kim et .
[15] showed that Escherichia coli, Klebsiella, and Staphylococcus ranked the top 3, accounting for the proportion of culture-positive sepsis bacteria respective.
33%, 18%, 2% of colum.
Prognosis of culture-negative sepsis patients Whether there is a difference in the prognosis of culture-negative/positive sepsis patients is also the focus of everyone’s attenti.
Several existing clinical studies have given different answers, which can be roughly divided into the following three categories: ( 1) The overall prognosis of culture-negative sepsis is better than that of culture-positive sepsis; (2) The overall prognosis of culture-negative sepsis is worse than that of culture-positive sepsis; (3) Culture-negative sepsis is the same as culture-positive seps.
The prognosis is simil.
The studies of Hazwani, Nannan Panday, Liu, Phua.
et al [11-14] suggested that the overall prognosis of culture-negative sepsis patients was better, and the mortality and organ dysfunction of culture-positive patients were higher, but Phua The study by J[13] further mentioned that a positive culture result was not an independent predictor of dea.
On the contrary, Gupta et .
[9] concluded that patients with culture-negative sepsis have a poor overall prognosis for the following reasons: (1) Delayed or inadequate antibiotic therapy and lack of specific culture guidance, leading to Inappropriate antibiotic treatme.
Since inappropriate and inadequate antibiotic treatment is associated with higher mortality in patients with severe sepsis, these patients may be converted to culture-negative severe sepsis cohorts with increased mortality; (2) severe sepsis Severe disease at the onset of the disease prompts clinicians to use antibiotics early without obtaining appropriate cultures, resulting in a culture-negative state; (3) antibiotics have been used before progression to severe sepsis, On the one hand, it will lead to the conversion of some culture status to negative, on the other hand, it may reduce antimicrobial susceptibility and increase mortality; (4) Some patients with culture-negative sepsis are not found with severe sepsis until hospitalization, which may lead to worse 's prognos.
Some articles also put forward a third point of view, arguing that there is no significant difference in the prognosis of patients with culture-negative/positive sepsis, who have similar ICU length of stay, mechanical ventilation demand rate, and renal replacement therapy demand rate, but also proposed that culture-positive sepsis The length of hospital stay and the duration of mechanical ventilation in patients with sepsis were longer than those in patients with culture-negative sepsis, and these differences may be due to differences in patient population, proportion of infection sites, and bacterial resistance to antibiotics [15-1
There is still no generally accepted conclusion about the clinical outcome of patients with culture-negative/positive seps.
Therefore, further research and research are need.
The possible causes of culture-negative sepsis The current research cannot explain the difference between culture-negative sepsis and culture-positive sepsis from the perspective of mechanism and pathology, but the possible causes can be further explored from the following four aspects: (1) Cultures are not sufficiently sensitive to identify pathogenic bacteria,.
false negatives exi.
Presumed reasons include the use of antibiotics before testing, insufficient blood cultures, poor transport conditions, slow growth, and the presence of fastidious bacteria [1
(2) The pathogenic microorganisms may be atypical pathogens, including fungi, viruses and some parasit.
Studies have shown that the proportion of sepsis/septic shock caused by atypical pathogens may be increasing, and routine pathogenic microbiological examination methods, including culture, mostly focus on the detection of bacteria, but are limited by technology-related issues and have not been widely us.
Covered to detect fungi and viruses [1
(3) The frequency of culture positive/negative is related to the nature of some infectio.
As mentioned above, multiple studies have shown that respiratory infections are more common in patients with culture-negative sepsis; urogenital infections, hepatobiliary tract infections, skin and soft tissue infections, infective endocarditis, and primary For sepsis caused by bloodstream infection, e.
, positive culture results are more common [9,11,13,1
(4) The culture-negative sepsis patients included in the study may actually have some false positives, unrelated to infecti.
Since there is currently no "gold standard" for the diagnosis of sepsis, it is difficult for medical staff to make differential diagnosis of sepsis patients with organ dysfunction alo.
In fact, one third or more of patients initially diagnosed with sepsis subsequently prove non-infectious disease [1
The causes of organ dysfunction may be metabolic disorders, tissue damage, inflammatory diseases, adverse drug reactions, malignant tumors and subarachnoid hemorrhage [2
The emerging technologies for rapid diagnosis of sepsis etiology focus on the detection rate, timeliness, functional index analysis and rapid qualitative analysis of unknown pathogens for the detection of infectious diseas.
Blood culture (BC) is the most direct and objective method to confirm pathogenic bacteria, and it is still the "gold standard" for the diagnosis of infectious diseas.
The diagnosis of sepsis also largely depends on the positive blood culture resul.
However, this method also has certain limitations, such as long testing time, high blood collection volume, treatment interference, limited types of detectable pathogens, and contamination, e.
, which may lead to delays, insufficient antibiotic treatment, and inappropriate selection of antibioti.
Appropria.
Therefore, many emerging rapid pathogen detection technologies have emerged, including polymerase chain reaction (PCR) related detection technologies, including real-time quantitative PCR, digital PCR, and the gradually mature and popular second-generation sequencing technology (Next Generation Sequencing, NGS) and microfluidic chip technology, as follows: The polymerase chain reaction PCR test is a reliable non-culture microbial detection method, which is widely used in laboratories around the world to detect a variety of microbial pathoge.
PCR diagnosis is based on PCR technology to complete the amplification of pathogen-specific gene fragments to determine the presence of pathogens in the samp.
At present, the second and third generation PCR technology is mainly used, and the second generation PCR is the fluorescence quantitative PCR technolo.
Commonly used in infectious disease pathogen detection, disease resistance gene research and so .
The technical operation process is simpler, cost-effective, and requires a very small amount of DNA and RNA samples, but there are problems such as easy contamination, especially due to the aerosol contamination caused by PCR amplification, an extremely small amount of contamination can cause false positiv.
produ.
The third-generation PCR technology is called digital P.
Compared with the second-generation technology, digital PCR has higher sensitivity, more accurate quantification, and stronger anti-interference ability, but requires higher template quality and primer specifici.
Currently, digital PCR technology can be used to detect viral and bacterial infections, especially the rapid identification of bacteria in positive blood culture bottles of common culture, which can guide the selection of anti-infective treatment 1-2 days before the results of routine drug susceptibility testi.
While actively performing blood culture testing, it can also shorten the length of ICU stay and reduce 30-day mortality [2
The PCR-related technology also has its own limitatio.
On the one hand, PCR-based etiological detection technology can only detect known pathogenic microorganisms, and it lacks the distinction between colonization and infecti.
The interpretation of the results is highly dependent on clinical experience, which will affect the accuracy of the conclusions to a certain exte.
On the other hand, there is a lack of data on antibiotic susceptibility in the positive results obtained by PCR-related detection technology to assist the targeted therapy of antibiotics [22-2
Sequencing-based method—the detection of metagenomic infectious diseases focuses on detection rate, timeliness, functional index analysis and rapid qualitative analysis of unknown pathoge.
The shortcomings of insufficient analytical capacity and difficult to achieve broad-spectrum detection, and gene sequencing provides a new way to solve these proble.
In recent years, NGS has become more and more mature and popular, providing a new and powerful means for etiological diagnos.
NGS is a new sequencing method relative to next-generation DNA sequencing technology, which can simultaneously measure millions or even hundreds of millions of DNA or RNA sequenc.
During the sequencing process, all nucleic acid fragments in the specimen are directly extracted and detected, and the type of nucleic acid contained in the specimen can be identified by bioinformatics analysis, and quantitative analysis data such as the sequence number and coverage of pathogens can be obtain.
When using NGS, specimens do not need to be cultured before detection, avoiding missed detection of difficult-to-culture pathoge.
During the detection, all nucleic acid fragments can be directly and non-specifically determined, without the need to select the detection range in advance (ie, unbiased), thus avoiding missed detection to the greatest exte.
The advantages of NGS lie in high sequencing throughput, high sensitivity, early identification of pathogens and short time, not only that, but also the detection of special pathogens to make up for the shortcomings of traditional detection techniqu.
However, NGS still has shortcomings such as the lack of recognized interpretation standards to effectively distinguish pathogenic bacteria from background bacteria, the unstandardized technology and database, the difficulty in detecting drug resistance genes, and the unclear relationship between sequencing results and treatme.
A comparative validation of the method on a larger scale [24-2
Other emerging technologies Some emerging detection technologies are gradually being studied by more and more scientists, such as microfluidic chip technolo.
The efficacy of microfluidic chip technology in medical applications has been confirmed, and it is currently being gradually applied in basic medical research on stem cell growth and its function, cell aging process, cell microenvironment and its related transmitters and many other aspec.
In clinical medical research, microfluidic technology has also been developed in the fields of early diagnosis of sepsis and other diseases, screening of antimicrobial-resistant bacterial infections, assisted reproductive technology, and clinical tumor classificati.
Unlike PCR technology, microfluidic technology does not multiply substances such as DNA or cytokines to produce amplification effects, but more through factors such as size, shape, density, deformability, electrical/magnetic susceptibility, and hydrodynami.
Cells or pathogens with special physical and chemical properties are screened, isolated and enriched to achieve the purpose of definite diagnosis or auxiliary diagnosis [2
Zhou et .
[27] carried out a study using microfluidic chips to capture CD64 and CD69 on the cell surface of clinical blood samples to detect culture-negative seps.
Combined with previous studies, CD64 and CD69 were shown to be the early and early stage of seps.
valid mark.
Zhou's research shows that the microfluidic chip is used for the detection of early sepsis, and its accuracy is higher than that of traditional blood cultu.
A multi-parameter chip developed by his team measures a combined panel of CD25, CD64 and CD69, which can be used to diagnose sepsis with a considerable diagnostic performance (97
In addition, microfluidics has the advantages of shorter time, convenient fabrication, less sample loading, low complexity, portability, e.
, and has great potential as a bedside sepsis detection meth.
Antibacterial treatment of sepsis After early identification of sepsis, clinical intervention can be time.
In adult patients with a high likelihood of sepsis or possible septic shock, guidelines recommend the immediate use of antimicrobials, preferably within 1 hour of identificati.
For adult patients with multidrug resistance (MDR) at high risk of sepsis/septic shock, empiric therapy with a combination of two different types of antibiotics that cover Gram-negative bacteria is recommended, rather than just one that targets the blue-negative bacter.
Once the pathogen and drug susceptibility results are clear, it is recommended to no longer use two anti-Gram-negative bacteria drugs in combinati.
A systematic review of 10 randomized controlled trials (RCTs) confirmed the mortality and other important outcomes of empiric monotherapy or multidrug therapy in ICU adults with severe sepsis or septic shock There was no difference (no difference in disease severit.
Among them, the results of the largest RCT included in the meta-analysis (comparison of moxifloxacin with meropenem and meropenem alone in a low-risk setting) were consistent with the results of the meta-analys.
Prolonged infusion time is recommended when using β-lactams, which may change important pharmacokinetic parameters in sepsis and septic shock, resulting in lower plasma concentrations/ or too hi.
Compared to intermittent dosing (infusion time ≤30 minutes), prolonged intravenous administration, either prolonged or continuous, resulted in sustained beta-lactam concentratio.
Before prolonged administration, it is necessary to give a loading dose of antibacterial drug, which can avoid delay and achieve effective β-lactam concentration [2
Summary Sepsis is a serious life-threatening infectious disease, and the proportion of sepsis patients with negative culture status in the total number of sepsis patients is increasing year by year, and the mortality rate remains hi.
Current studies have not been able to draw uniform conclusions on the clinical characteristics and outcomes of culture-negative sepsis patien.
Due to the lack of culture-positive relevant data and the uncertainty of their diagnosis, these patients should provide early clinical intervention and accurate diagnos.
Chemotherapeutic anti-infective treatment brings certain difficulties, and some emerging technologies for accurate and rapid etiological diagnosis, such as fluorescent PCR, digital PCR and NGS, can also help clinicians optimize the use of antimicrobial dru.
Early identification of this type of "special" sepsis patients in clinical work and timely intervention to obtain better clinical prognosis requires further explorati.
Expert Profile Professor Wu Benquan Chief Physician, Doctor of Medicine, Doctoral Supervisor; Director of the MICU of the Third Affiliated Hospital of Sun Yat-sen University, Deputy Director of the Department of Critical Care Medicine of the Third Affiliated Hospital of Sun Yat-sen University, Director of the Medical Department of the Third Affiliated Hospital of Sun Yat-sen University; Guangdong Provincial Society of Pathophysiology Deputy Director of the Critical Care Branch, Member of the Tuberculosis Society of the Guangdong Medical Association, Member of the Respiratory Society of the Guangdong Medical Association, Member of the Standing Committee of the Critical Care Branch of the Guangdong Health Management Society, and Member of the Respiratory Society of the Guangdong Health Management Society; good at respiratory diseases and critical illnesses He has published more than 60 related papers and more than 10 SCI papers, edited a monograph "Basic and Clinical of MRSA", and presided over two National Natural Science Foundation of China and a number of provincial and bureau-level scientific research projec.
15(1): Published 2017 Jandoi:11186/s12951-016-0235-4[27] Zhou Y, Zhang Y, Johnson A, Venable A, Griswold J, Pappas.
Detection of culture-negative sepsis in clinical blood samples using a microfluidic assay for combined CD64 and CD69 cell captu.
Anal Chim Ac.
2019;1062:110-11 doi:11016.
a.
2010039[28] Laura Evans, et .
Intensive Care M.
2021 Nov;47(11):1181-124 The author of this article: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-sen University Highlights of past issues:Anti-infective treatment strategies for severe nosocomial infection (Part 1): Do a good job of sepsisAnti-infective treatment strategies for severe nosocomial infection (Part II): appropriate selection and optimization of antibioticsIn severe patients with gram-negative bacterial infection, the optimal treatment plan of β-lactam antibioticsIn severe patients with gram-negative bacterial infection, continuous infusion of β-lactam antibiotics can achieve satisfactory PK/PD goals , The latest research, non-CP-CRE infection death risk is 4 times higher than CP-CRE!In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsisCarbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy?The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Zhang Y, Johnson A, Venable A, Griswold J, Pappas.
Detection of culture-negative sepsis in clinical blood samples using a microfluidic assay for combined CD64 and CD69 cell captu.
Anal Chim Ac.
2019;1062:110-11 doi :11016.
a.
2010039[28] Laura Evans, et .
Intensive Care M.
2021 Nov; 47(11): 1181-124 Author: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-Sen University Review:Anti-infective treatment strategies for severe nosocomial infection (Part 1): early identification and differential diagnosis of sepsisAnti-infective treatment strategies for severe nosocomial infection (Part 2): appropriate selection and optimization of antibiotics , Drug monitoring of meropenem and piperacillin in the treatment of critically ill patients, experience and recommendations of routine clinical practice Infection, continuous infusion of β-lactam antibiotics can achieve satisfactory PK/PD goalsThe latest research shows that the risk of death from non-CP-CRE infection is 4 times higher than CP-CRE!In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsisCarbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy?The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Zhang Y, Johnson A, Venable A, Griswold J, Pappas.
Detection of culture-negative sepsis in clinical blood samples using a microfluidic assay for combined CD64 and CD69 cell captu.
Anal Chim Ac.
2019;1062:110-11 doi :11016.
a.
2010039[28] Laura Evans, et .
Intensive Care M.
2021 Nov; 47(11): 1181-124 Author: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-Sen University Review:Anti-infective treatment strategies for severe nosocomial infection (Part 1): early identification and differential diagnosis of sepsis Anti-infective treatment strategies for severe nosocomial infection (Part 2): appropriate selection and optimization of antibiotics , Drug monitoring of meropenem and piperacillin in the treatment of critically ill patients, experience and recommendations of routine clinical practice Infection, continuous infusion of β-lactam antibiotics can achieve satisfactory PK/PD goals The latest research shows that the risk of death from non-CP-CRE infection is 4 times higher than CP-CRE! In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis Carbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy? The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Detection of culture-negative sepsis in clinical blood samples using a microfluidic assay for combined CD64 and CD69 cell captu.
Anal Chim Ac.
2019;1062:110-11 doi:11016.
a.
2010039[28] Laura Evans , et .
Intensive Care M.
2021 Nov;47(11):1181-124 The author of this article: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-sen University Highlights of past issues: Anti-infective treatment strategies for severe nosocomial infections (Part 1 ): early identification and differential diagnosis of sepsis Anti-infective treatment strategies for severe nosocomial infection (Part 2): Appropriate selection and optimization of antibiotics Drug monitoring in critically ill patients treated with meropenem and piperacillin, routine Experiences and suggestions from clinical practice In severe patients with gram-negative bacterial infection, the optimal treatment plan of β-lactam antibiotics In severe patients with gram-negative bacterial infection, continuous infusion of β-lactam antibiotics can be satisfactory The PK/PD goal of 6, the latest research, non-CP-CRE infection mortality risk is 4 times higher than CP-CRE! In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis Carbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy? The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Detection of culture-negative sepsis in clinical blood samples using a microfluidic assay for combined CD64 and CD69 cell captu.
Anal Chim Ac.
2019;1062:110-11 doi:11016.
a.
2010039[28] Laura Evans , et .
Intensive Care M.
2021 Nov;47(11):1181-124 The author of this article: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-sen University Highlights of past issues: Anti-infective treatment strategies for severe nosocomial infections (Part 1 ): early identification and differential diagnosis of sepsis Anti-infective treatment strategies for severe nosocomial infection (Part 2): Appropriate selection and optimization of antibiotics Drug monitoring in critically ill patients treated with meropenem and piperacillin, routine Experiences and suggestions from clinical practice In severe patients with gram-negative bacterial infection, the optimal treatment plan of β-lactam antibiotics In severe patients with gram-negative bacterial infection, continuous infusion of β-lactam antibiotics can be satisfactory The PK/PD goal of 6, the latest research, non-CP-CRE infection mortality risk is 4 times higher than CP-CRE! In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis Carbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy? The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Author of this article: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-Sen University Highlights of past issues: Anti-infective treatment strategies for severe nosocomial infection (Part 1): early identification and differential diagnosis of sepsis Infection treatment strategy (Part 2): appropriate selection and optimization of antibiotics The best treatment plan for antibiotic-like drugs In severe patients with Gram-negative bacterial infection, continuous infusion of beta-lactam antibiotics can achieve satisfactory PK/PD goals -CRE is 4 times higher! In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis Carbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy? The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease areas Author of this article: Wang Ruochen Wu Benquan The Third Affiliated Hospital of Sun Yat-Sen University Highlights of past issues: Anti-infective treatment strategies for severe nosocomial infection (Part 1): early identification and differential diagnosis of sepsis Infection treatment strategy (Part 2): appropriate selection and optimization of antibiotics The best treatment plan for antibiotic-like drugs In severe patients with Gram-negative bacterial infection, continuous infusion of beta-lactam antibiotics can achieve satisfactory PK/PD goals -CRE is 4 times higher! In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis Carbapenem-resistant Enterobacteriaceae infections make treatment more difficu.
What are the advantages of combined therapy? The demand for combined application of antibacterial drugs is becoming more and more urge.
Do you know all of these four in vitro combined drug susceptibility tests? 1 Meropenem and therapeutic drug monitoring, these issues are worth knowing! Copyright Notice: This information is intended to help healthcare professionals better understand the latest developments in related disease are.
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