BACKGROUND Pediatric abdominal infection is a common but serious disease that requires timely and effective treatment.In surgical treatment,accurate diagnosis and rational application of antibiotics are the keys to im...BACKGROUND Pediatric abdominal infection is a common but serious disease that requires timely and effective treatment.In surgical treatment,accurate diagnosis and rational application of antibiotics are the keys to improving treatment effects.AIM To investigate the effect of broad-spectrum bacterial detection on postoperative antibiotic therapy.METHODS A total of 100 children with abdominal infection who received surgical treatment in our hospital from September 2020 to July 2021 were grouped.The observation group collected blood samples upon admission and sent them for broad-spectrum bacterial infection nucleic acid testing,and collected pus or exudate during the operation for bacterial culture and drug sensitivity testing;the control group only sent bacterial culture and drug sensitivity testing during the operation.RESULTS White blood cell count,C-reactive protein,procalcitonin,3 days after surgery,showed better postoperative index than the control group(P<0.05).The hospital stay in the observation group was significantly shorter than that in the control group.The hospitalization cost in the observation group was significantly lower than that in the control group,and the difference between the two groups was statistically significant(P<0.05).CONCLUSION Early detection of broad-spectrum bacterial infection nucleic acids in pediatric abdominal infections can help identify pathogens sooner and guide the appropriate use of antibiotics,improving treatment outcomes and reducing medical costs to some extent.展开更多
BACKGROUND Bacterial infections(BI)negatively affect the natural course of cirrhosis.The most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevan...BACKGROUND Bacterial infections(BI)negatively affect the natural course of cirrhosis.The most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical variables.METHODS We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care center.BIs were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two groups.RESULTS In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical BI.Atypical BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage Liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the disease.Hence,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.展开更多
Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients.Over the last two decades,various multidrug-resistant(MDR)pathogens have emerged as relevant causes of infect...Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients.Over the last two decades,various multidrug-resistant(MDR)pathogens have emerged as relevant causes of infection in this population.Although this fact reflects the spread of MDR pathogens in health care facilities worldwide,several factors relating to the care of transplant donor candidates and recipients render these patients particularly prone to the acquisition of MDR bacteria and increase the likelihood of MDR infectious outbreaks in transplant units.The awareness of this high vulnerability of transplant recipients to infection leads to the more frequent use of broad-spectrum empiric antibiotic therapy,which further contributes to the selection of drug resistance.This vicious cycle is difficult to avoid and leads to a scenario of increased complexity and narrowed therapeutic options.Infection by MDR pathogens is more frequently associated with a failure to start appropriate empiric antimicrobial ther-apy.The lack of appropriate treatment may contribute to the high mortality occurring in transplant recipients with MDR infections.Furthermore,high therapeutic failure rates have been observed in patients infected with extensively-resistant pathogens,such as carbapenemresistant Enterobacteriaceae,for which optimal treatment remains undefined.In such a context,the careful implementation of preventive strategies is of utmost importance to minimize the negative impact that MDR infections may have on the outcome of liver transplant recipients.This article reviews the current literature regarding the incidence and outcome of MDR infections in liver transplant recipients,and summarizes current preventive and therapeutic recommendations.展开更多
Recent advances in effective antimicrobial prophylactic strategies have led to a decline in the incidence of opportunistic infections in liver transplant recipients. However, morbidity and mortality due to infectious ...Recent advances in effective antimicrobial prophylactic strategies have led to a decline in the incidence of opportunistic infections in liver transplant recipients. However, morbidity and mortality due to infectious diseases remain as major problems. Bacterial infections occurring early after transplant are mainly related to the technical aspects of the procedure. By contrast, after the first postoperative days and beyond, the nature and variety of infectious complications change. Opportunistic bacterial infections are uncommon after 6 mo in patients receiving stable and reduced maintenance doses of immunosuppression with good graft function and little is documented about these cases in the literature. Transplant recipients may be more susceptible to some pathogens, such as the Nocardia species, Legionella species, Listeria monocytogenes , Mycoplasma species, Salmonella species or Rhodococcus equi. Respiratory infections due to capsulated bacteria, such as Streptococcus pneumoniae and Haemophilus intTuenza, can be life- threatening if not promptly treated in this population. These late bacterial infections may be very difficult to recognize and treat in this population. In this article, we review what has been described in the literature with regards to late bacterial infections following liver transplantation.展开更多
Recently, important changes have been reported regarding the epidemiology of bacterial infections in liver cirrhosis. There is an emergence of multiresistant bacteria in many European countries and also worldwide, inc...Recently, important changes have been reported regarding the epidemiology of bacterial infections in liver cirrhosis. There is an emergence of multiresistant bacteria in many European countries and also worldwide, including the United States and South Korea. The classic empirical antibiotic treatment(third-generation cephalosporins, e.g., ceftriaxone, cefotaxime or amoxicillin-clavulanic acid) is still effective in infections acquired in the community, but its failure rate in hospital acquired infections and in some health-care associated infections is high enough to ban its use in these settings. The current editorial focuses on the different epidemiology of bacterial infections in cirrhosis across countries and on its therapeutic implications.展开更多
Despite major advances in the knowledge and management of liver diseases achieved in recent decades,decompensation of cirrhosis still carries a high burden of morbidity and mortality.Bacterial infections are one of th...Despite major advances in the knowledge and management of liver diseases achieved in recent decades,decompensation of cirrhosis still carries a high burden of morbidity and mortality.Bacterial infections are one of the main causes of decompensation.It is very important for clinical management to be aware of the population with the highest risk of poor outcome.This review deals with the new determinants of prognosis in patients with cirrhosis and bacterial infections reported recently.Emergence of multiresistant bacteria has led to an increasing failure rate of the standard empirical antibiotic therapy recommended by international guidelines.Moreover,it has been recently reported that endothelial dysfunction is associated with the degree of liver dysfunction and,in infected patients,with the degree of sepsis.It has also been reported that relative adrenal insufficiency is frequent in the non-critically ill cirrhotic population and it is associated with a higher risk of developing infection,severe sepsis,hepatorenal syndrome and death.We advise a change in the standard empirical antibiotic therapy in patients with high risk for multiresistant infections and also to take into account endothelial and adrenal dysfunction in prognostic models in hospitalized patients with decompensated cirrhosis.展开更多
AIMS To establish the prevalence of bacterial infection in cir- rhotic patients with hepatocellular carcinoma(HCC). METHODS All 719 cirrhotic patients with HCC were investigat- ed retrospectively for the prevalence of...AIMS To establish the prevalence of bacterial infection in cir- rhotic patients with hepatocellular carcinoma(HCC). METHODS All 719 cirrhotic patients with HCC were investigat- ed retrospectively for the prevalence of bacterial infections. RESULTS The incidence of bacterial infection was 15.4% (111/719).According to Child-Pugh classification,the inci- dences of bacterial infection in class A,B and C were 2.3%,8. 0%,and 26.4 %,respectively.The bacterial infection increased with the severity of cirrhosis and severe bacterial infections usual- ly occurred in Child-Pugh class B and C patients. CONCLUSIONS The susceptibility of HCC patients to bacterial infection is mainly due to the underlying cirrhosis and not to the HCC itself.展开更多
Objective:The clinical diagnostic accuracy of C-reactive protein(CRP)for bacterial infections in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)is still controversial.This study evaluated its accur...Objective:The clinical diagnostic accuracy of C-reactive protein(CRP)for bacterial infections in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)is still controversial.This study evaluated its accuracy through Meta-analysis.Methods:Studies on the diagnostic value of CRP for bacterial infections in AECOPD were searched form Web of Science,PubMed,Cochrane library,EMBASE,WANFANG DATA,CNKI and China Biology Medicine disc.The included studies were evaluated according to QUADAS-2 assessment tool.Stata 12.0 software was used for meta analyses to summarize the sensitivity and the specificity of the included studies,and the heterogeneity test was conducted.The symmetric receiver operating characteristic curves(SROC)was drawn and the area under the curve(AUC)was calculated,and the funnel plot was drawn to determine publication bias.Results:664 studies were initially identified,20 of which met the inclusion criteria(9 in English and 11 in Chinese).Meta-analysis results showed that the summary sensitivity and specificity of CRP in diagnosing bacterial infections in AECOPD were 0.84,95%CI(0.77-0.90)and 0.76,95%CI(0.67-0.82),respectively.The AUC of SROC was 0.87,95%CI(0.83-0.89).Conclusion:CRP has high accuracy,sensitivity and specificity in distinguishing AECOPD bacterial infections from non-bacterial infection.展开更多
Bacterial infection in the first month after liver transplantation is a frequent complication that poses a serious risk for liver transplant recipients as contributes substantially to increased length of hospitalizati...Bacterial infection in the first month after liver transplantation is a frequent complication that poses a serious risk for liver transplant recipients as contributes substantially to increased length of hospitalization and hospital costs being a leading cause of death in this period. Most of these infections are caused by gramnegative bacilli, although gram-positive infections, especially Enterococcus sp. constitute an emerging infectious problem. This high rate of early postoperative infections after liver transplant has generated interest in exploring various prophylactic approaches to surmount this problem. One of these approaches is selective intestinal decontamination(SID). SID is a prophylactic strategy that consists of the administration of antimicrobials with limited anaerobicidal activity in order to reduce the burden of aerobic gram-negative bacteria and/or yeast in the intestinal tract and so prevent infections caused by these organisms. The majority of studies carried out to date have found SID to be effective in the reduction of gram-negative infection, but the effect on overall infection is limited due to a higher number of infection episodes by pathogenic enterococci and coagulase-negative staphylococci. However, difficulties in general extrapolation of the favorable results obtained in specific studies together with the potential risk of selection of multirresistant microorganisms has conditioned controversy about the routinely application of these strategies in liver transplant recipients.展开更多
AIM To determine risk factors, causative organisms and antimicrobial resistance of bacterial infections following living-donor liver transplantation(LDLT) in cirrhotic patients.METHODS This prospective study included ...AIM To determine risk factors, causative organisms and antimicrobial resistance of bacterial infections following living-donor liver transplantation(LDLT) in cirrhotic patients.METHODS This prospective study included 45 patients with hepatitis C virus-related end-stage liver disease who underwent LDLT at Ain Shams Center for Organ Transplant, Cairo, Egypt from January 2014 to November 2015. Patients were followed-up for the first 3 mo after LDLT for detection of bacterial infections. All patients were examined for the possible risk factors suggestive of acquiring infection pre-, intra-and post-operatively. Positive cultures based on clinical suspicion and patterns of antimicrobial resistance were identified. RESULTS Thirty-three patients(73.3%) suffered from bacterial infections; 21 of them had a single infection episode, and 12 had repeated infection episodes. Bile was the most common site for both single and repeated episodes of infection(28.6% and 27.8%, respectively). The most common isolated organisms were gramnegative bacteria. Acinetobacter baumannii was the most common organism isolated from both single and repeated infection episodes(19% and 33.3%, respectively), followed by Escherichia coli for repeated infections(11.1%), and Pseudomonas aeruginosa for single infections(19%). Levofloxacin showed high sensitivity against repeated infection episodes(P = 0.03). Klebsiella, Acinetobacter and Pseudomonas were multi-drug resistant(MDR). Pre-transplant hepatocellular carcinoma(HCC) and duration of drain insertion(in days) were independent risk factors for the occurrence of repeated infection episodes(P = 0.024).CONCLUSION MDR gram-negative bacterial infections are common post-LDLT. Pre-transplant HCC and duration of drain insertion were independent risk factors for the occurrence of repeated infection episodes.展开更多
Acute-on-chronic liver failure(ACLF)is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease,often leading to multi-organ failures and significant short-term mortalities.B...Acute-on-chronic liver failure(ACLF)is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease,often leading to multi-organ failures and significant short-term mortalities.Bacterial infection is one of the most frequent triggers for ACLF and a common complication following its onset.The impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ failures.In addition,the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use,as well as accurate and prompt microbiological diagnosis.This review provided an update on recent advances in the epidemiology,diagnosis,pathogenesis,and management of bacterial infections in ACLF.展开更多
Purpose:To investigate which scoring system is the most accurate tool in predicting mortality among the infected patients who present to the emergency department in a middle-income country,and to validate a new scorin...Purpose:To investigate which scoring system is the most accurate tool in predicting mortality among the infected patients who present to the emergency department in a middle-income country,and to validate a new scoring system to predict bacterial infections.Methods:This was a retrospective,single-center study among patients who were admitted via the emergency department of a public hospital.All patients who were started on antibiotics were included in the study,while patients aged<18 years were excluded.Data collected includeding patients'demographics,vital signs and basic laboratory parameters like white blood cell count and creatinine.The sensitivity and specificity of different scoring systems were calculated as well as their negative and positive predictive values.Logistic regression was used to derive a novel early warning system for bacterial infections.The area under the receiver operating characteristic(AUROC)was computed for each scoring model.Results:In total,109 patients were included in this study.The quick sequential organ failure assessment(qSOFA),search out severity and rapid acute physiology score had the highest AUROC(≥0.89)for predicting mortality,while qSOFA and universal vital assessment were the simplest scoring systems with an AUROC>0.85;however,these scoring systems failed to predict whether patients were truly infected.The INFECTIONS(short for impaired mental status,not conscious,fast heart rate,elevated creatinine,high temperature,on inotrope,low oxygen,high neutrophils and high sugar)model reached an AUROC of 0.88 to more accurately predict the infectious state of a patient.Conclusions:Middle-income countries should use the qSOFA or universal vital assessment score to identify the sickest patients in emergency department.The INFECTIONS score may help recognize patients with bacterial infections,but it should be further validated in multiple countries prior to widely use.展开更多
Bacteriophages or phages are viruses that infect bacteria and are increasingly used to control bacterial infections.We develop a reaction-diffusion model coupling the interactive dynamic of phages and bacteria with an...Bacteriophages or phages are viruses that infect bacteria and are increasingly used to control bacterial infections.We develop a reaction-diffusion model coupling the interactive dynamic of phages and bacteria with an epidemiological bacteria-borne disease model.For the submodel without phage absorption,the basic reproduction number Ro is computed.The disease-free equilibrium(DFE)is shown to be globally asymptotically stable whenever Ro is less than one,while a unique globally asymptotically endemic equilibrium is proven whenever Ro exceeds one.In the presence of phage absorption,the above stated classical condition based on Ro,as the average number of secondary human infections produced by susceptible/lysogen bacteria during their entire lifespan,is no longer suficient to guarantee the global stability of the DFE.We thus derive an additional threshold No,which is the average offspring number of lysogen bacteria produced by one infected human during the phage-bacteria interactions,and prove that the DFE is globally asymptotically stable whenever both Ro and No are under unity,and infections persist uniformly whenever Ro is greater than one.Finally,the discrete counterpart of the continuous partial differential equation model is derived by constructing a nonstandard finite difference scheme which is dynamically consistent.This consistency is shown by constructing suitable discrete Lyapunov functionals thanks to which the global stability results for the continuous model are replicated.This scheme is implemented in MatLab platform and used to assess the impact of spatial distribution of phages,on the dynamic of bacterial infections.展开更多
Bacterial infection is a major issue after artificial bone transplantation due to the absence of antibacterial function of bone scaffold,which seriously causes the transplant failure and even amputation in severe case...Bacterial infection is a major issue after artificial bone transplantation due to the absence of antibacterial function of bone scaffold,which seriously causes the transplant failure and even amputation in severe cases.In this study,oxygen vacancy(OV)defects Fe-doped Ti O2(OV-FeTiO2)nanoparticles were synthesized by nano TiO2and Fe3O4via high-energy ball milling,which was then incorporated into polycaprolactone/polyglycolic acid(PCLGA)biodegradable polymer matrix to construct composite bone scaffold with good antibacterial activities by selective laser sintering.The results indicated that OV defects were introduced into the core/shell-structured OV-FeTiO2nanoparticles through multiple welding and breaking during the high-energy ball milling,which facilitated the adsorption of hydrogen peroxide(H2O2)in the bacterial infection microenvironment at the bone transplant site.The accumulated H2O2could amplify the Fenton reaction efficiency to induce more hydroxyl radicals(·OH),thereby resulting in more bacterial deaths through·OH-mediated oxidative damage.This antibacterial strategy had more effective broad-spectrum antibacterial properties against Gram-negative Escherichia coli(E.coli)and Gram-positive Staphylococcus aureus(S.aureus).In addition,the PCLGA/OV-FeTiO2scaffold possessed mechanical properties that match those of human cancellous bone and good biocompatibility including cell attachment,proliferation and osteogenic differentiation.展开更多
BACKGROUND Spontaneous bacterial peritonitis(SBP)is one of the most important complications of patients with liver cirrhosis entailing high morbidity and mortality.Making an accurate early diagnosis of this infection ...BACKGROUND Spontaneous bacterial peritonitis(SBP)is one of the most important complications of patients with liver cirrhosis entailing high morbidity and mortality.Making an accurate early diagnosis of this infection is key in the outcome of these patients.The current definition of SBP is based on studies performed more than 40 years ago using a manual technique to count the number of polymorphs in ascitic fluid(AF).There is a lack of data comparing the traditional cell count method with a current automated cell counter.Moreover,current international guidelines do not mention the type of cell count method to be employed and around half of the centers still rely on the traditional manual method.AIM To compare the accuracy of polymorph count on AF to diagnose SBP between the traditional manual cell count method and a modern automated cell counter against SBP cases fulfilling gold standard criteria:Positive AF culture and signs/symptoms of peritonitis.METHODS Retrospective analysis including two cohorts:Cross-sectional(cohort 1)and case-control(cohort 2),of patients with decompensated cirrhosis and ascites.Both cell count methods were conducted simultaneously.Positive SBP cases had a pathogenic bacteria isolated on AF and signs/symptoms of peritonitis.RESULTS A total of 137 cases with 5 positive-SBP,and 85 cases with 33 positive-SBP were included in cohort 1 and 2,respectively.Positive-SBP cases had worse liver function in both cohorts.The automated method showed higher sensitivity than the manual cell count:80%vs 52%,P=0.02,in cohort 2.Both methods showed very good specificity(>95%).The best cutoff using the automated cell counter was polymorph≥0.2 cells×10^(9)/L(equivalent to 200 cells/mm^(3))in AF as it has the higher sensitivity keeping a good specificity.CONCLUSION The automated cell count method should be preferred over the manual method to diagnose SBP because of its higher sensitivity.SBP definition,using the automated method,as polymorph cell count≥0.2 cells×10^(9)/L in AF would need to be considered in patients admitted with decompensated cirrhosis.展开更多
Background and Aims:Patients with cirrhosis are immunocompromised and at higher risk of developing infections compared to the general population.The aim of this study was to assess the incidence of infections in cirrh...Background and Aims:Patients with cirrhosis are immunocompromised and at higher risk of developing infections compared to the general population.The aim of this study was to assess the incidence of infections in cirrhotic patients in a large academic liver center and investigate potential associations between infections,bacteria isolated,therapeutic regimens used,and mortality.Methods:This was a retrospective chart review study,including 192 patients.All patients had a diagnosis of cirrhosis and were admitted to University Hospital.Information collected included demographics,etiology of cirrhosis,identification of bacteria from cultures,multidrug-resistant(MDR)status,antibiotics administered,intensive care unit(ICU)admission,and patient mortality.Results:Infections were present in 105(54.6%)patients,and 60(31.2%)patients had multiple infections during a hospitalization(s)for infections.A total of 201 infections were identified.Urinary tract infections(UTIs)were the most common infection(37.8%),followed by bacteremia(20.4%),pneumonia(12.9%),spontaneous bacterial peritonitis(SBP)(11.9%),abscess/cellulitis(6.0%),infectious diarrhea(6.0%),and other(5.0%).Escherichia coli was the most common bacteria isolated(13.4%),both among sensitive and MDR infections.MDR bacteria were the cause for 41.3%of all infections isolated.Fungi accounted for 9.5%of infections.21.9%of patients had decompensation from their infection(s)that required ICU care,and 14.6%of patients died during hospitalization or soon after discharge.Conclusions:The incidence of infections in cirrhotic patients is much higher than in their non-cirrhotic counterparts(54.6%),even higher than prior studies suggest.As many of these infections are caused by MDR bacteria and fungal organisms,stronger empiric antibiotics and antifungals should be considered when initially treating this immunocompromised population.However,once organism sensitivities are discovered,narrowing of antibiotic regimens must occur to maintain good antibiotic stewardship.展开更多
Objective:To ascertain the feasibility of using sustainable natural resources in maintaining disease free fish in such establishments.Methods:causative bacteria were identified by morphology and biochemical techniques...Objective:To ascertain the feasibility of using sustainable natural resources in maintaining disease free fish in such establishments.Methods:causative bacteria were identified by morphology and biochemical techniques.The antibacterial activity and disease resistant capability of mangrove plant leaf extract were investigated against fish pathogens.Results:The infected marine ornamental fishes were collected from the hatchery condition and inhibition activity at the concentration of 220,200,175 and 150μg/mL against Pseudomonas fluorescens,Pseudomonas aeruginosa,Vibrio parahaemolyticus,and Vibrio anguillarum respectively.The experimental trial reveals feeding marine ornamental fish with feed incorporated with a methanol leaf extract of Avicennia marina,increases their survival and reduces their susceptibility to infections from the isolated bacteria.Based on the in vitro assay,methanol extract of Avicennia marina was exhibited good Conclusions:The mangrove leaves have potential to control the infections caused by Pseudomonas fluorescens,Pseudomonas aeruginosa,Vibrio parahaemolyticus and Vibrio anguillarum.展开更多
Considering the WHO warning about the emergence of a’post-antibiotic’era during the 21st century in which common infections and minor injuries will have a dramatic impact on human death toll,search for new potential...Considering the WHO warning about the emergence of a’post-antibiotic’era during the 21st century in which common infections and minor injuries will have a dramatic impact on human death toll,search for new potential antibacterial drug targets became a necessary need.Targets that are extensively explored concern the modulation展开更多
Multidrug-resistant(MDR)bacterial infections exert a tremendous burden on the public health system throughout the developing and developedworld.Slowing development of novel antibiotic scaffolds,over-prescription of an...Multidrug-resistant(MDR)bacterial infections exert a tremendous burden on the public health system throughout the developing and developedworld.Slowing development of novel antibiotic scaffolds,over-prescription of antibiotics,extensive agricultural antibiotic use,and the increasingly complex hospitalized patient populations undergoing treatment,all fuel the rise of highly MDR“superbugs.”Unfortunately,host-directed therapies to boost immune resistance to infection are not currently available for treatment of MDR pathogens.Hematopoietic cells are endowed with a variety ofmechanismsto control microbial invasion.Macrophages in particular have long been appreciated as potent antimicrobial immune cells equipped with several receptors that allow for rapid recognition,phagocytosis,and killing of pathogenic microbes,coupled to secretion of immunostimulatory cytokines to further orchestrate a robust multifaceted antibacterial immune response.To investigate the utility of macrophages as a cell therapy for MDR bacterial infections,we developed a therapeutically translatable process to generate,harvest,and cryopreserve monocyte-derived macrophages(ICONIMACTM).These cells effectively killed both Gram-positive and Gram-negative MDR pathogens in vitro,and conferred protection in vivo against experimental lethal peritonitis and lung infection.Our discoveries provide a proof-of-concept for a novel immunotherapeutic approach against MDR bacterial infections,urgently needed to supplement the diminishing antibiotic pipeline.展开更多
Importance: The current lack of reliable rapid tests for distinguishing between bacterial and viral infections has contributed to antibiotic misuse.Objective: This study aimed to develop a novel biomarker assay that i...Importance: The current lack of reliable rapid tests for distinguishing between bacterial and viral infections has contributed to antibiotic misuse.Objective: This study aimed to develop a novel biomarker assay that integratesFAM89A andIFI44L measurements to assist in differentiating between bacterial and viral infections.Methods: This prospective study recruited children with febrile illness from two hospitals between July 1, 2018, and June 30, 2019. A panel of three experienced pediatricians performed reference standard diagnoses of all patients (i.e., bacterial or viral infection) using available clinical and laboratory data, including a 28-day follow-up assessment. Assay operators were blinded to the reference standard diagnoses. The expression levels ofFAM89A andIFI44L were determined by quantitative real-time polymerase chain reaction assessment.Results: Of 133 potentially eligible patients with suspected bacterial or viral infection, 35 were excluded after the application of exclusion criteria. The resulting cohort included 98 patients: 59 with viral diagnoses and 39 with bacterial diagnoses. The areas under the curve (AUCs) of diagnoses usingFAM89A andIFI44L were 0.694 [95% confidence interval (CI): 0.583-0.804] and 0.751 (95%CI: 0.651-0.851), respectively. The disease risk score (DRS) [log2(FAM89A expression) - log2(IFI44L expression)] signature achieved an improved area under the receiver operating characteristic curve (AUC, 0.825;95%CI: 0.735-0.915), compared with the AUC generated from individual host RNA. A combination of the DRS and the C-reactive protein (CRP) level achieved an AUC of 0.896 (95%CI: 0.825-0.966). Optimal cutoffs for the DRS and CRP level were -3.18 and 19.80 mg/L, respectively.Interpretation: The DRS was significantly more accurate than the CRP level in distinguishing between bacterial and viral infections;the combination of these two parameters exhibited greater sensitivity and specificity. This study provides information that could be useful for the clinical application ofFAM89A andIFI44L in terms of distinguishing between viral and bacterial infections.展开更多
基金Zhangjiakou Science and Technology Tackling Program,No.2021099D.
文摘BACKGROUND Pediatric abdominal infection is a common but serious disease that requires timely and effective treatment.In surgical treatment,accurate diagnosis and rational application of antibiotics are the keys to improving treatment effects.AIM To investigate the effect of broad-spectrum bacterial detection on postoperative antibiotic therapy.METHODS A total of 100 children with abdominal infection who received surgical treatment in our hospital from September 2020 to July 2021 were grouped.The observation group collected blood samples upon admission and sent them for broad-spectrum bacterial infection nucleic acid testing,and collected pus or exudate during the operation for bacterial culture and drug sensitivity testing;the control group only sent bacterial culture and drug sensitivity testing during the operation.RESULTS White blood cell count,C-reactive protein,procalcitonin,3 days after surgery,showed better postoperative index than the control group(P<0.05).The hospital stay in the observation group was significantly shorter than that in the control group.The hospitalization cost in the observation group was significantly lower than that in the control group,and the difference between the two groups was statistically significant(P<0.05).CONCLUSION Early detection of broad-spectrum bacterial infection nucleic acids in pediatric abdominal infections can help identify pathogens sooner and guide the appropriate use of antibiotics,improving treatment outcomes and reducing medical costs to some extent.
文摘BACKGROUND Bacterial infections(BI)negatively affect the natural course of cirrhosis.The most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical variables.METHODS We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care center.BIs were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two groups.RESULTS In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical BI.Atypical BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage Liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the disease.Hence,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.
文摘Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients.Over the last two decades,various multidrug-resistant(MDR)pathogens have emerged as relevant causes of infection in this population.Although this fact reflects the spread of MDR pathogens in health care facilities worldwide,several factors relating to the care of transplant donor candidates and recipients render these patients particularly prone to the acquisition of MDR bacteria and increase the likelihood of MDR infectious outbreaks in transplant units.The awareness of this high vulnerability of transplant recipients to infection leads to the more frequent use of broad-spectrum empiric antibiotic therapy,which further contributes to the selection of drug resistance.This vicious cycle is difficult to avoid and leads to a scenario of increased complexity and narrowed therapeutic options.Infection by MDR pathogens is more frequently associated with a failure to start appropriate empiric antimicrobial ther-apy.The lack of appropriate treatment may contribute to the high mortality occurring in transplant recipients with MDR infections.Furthermore,high therapeutic failure rates have been observed in patients infected with extensively-resistant pathogens,such as carbapenemresistant Enterobacteriaceae,for which optimal treatment remains undefined.In such a context,the careful implementation of preventive strategies is of utmost importance to minimize the negative impact that MDR infections may have on the outcome of liver transplant recipients.This article reviews the current literature regarding the incidence and outcome of MDR infections in liver transplant recipients,and summarizes current preventive and therapeutic recommendations.
文摘Recent advances in effective antimicrobial prophylactic strategies have led to a decline in the incidence of opportunistic infections in liver transplant recipients. However, morbidity and mortality due to infectious diseases remain as major problems. Bacterial infections occurring early after transplant are mainly related to the technical aspects of the procedure. By contrast, after the first postoperative days and beyond, the nature and variety of infectious complications change. Opportunistic bacterial infections are uncommon after 6 mo in patients receiving stable and reduced maintenance doses of immunosuppression with good graft function and little is documented about these cases in the literature. Transplant recipients may be more susceptible to some pathogens, such as the Nocardia species, Legionella species, Listeria monocytogenes , Mycoplasma species, Salmonella species or Rhodococcus equi. Respiratory infections due to capsulated bacteria, such as Streptococcus pneumoniae and Haemophilus intTuenza, can be life- threatening if not promptly treated in this population. These late bacterial infections may be very difficult to recognize and treat in this population. In this article, we review what has been described in the literature with regards to late bacterial infections following liver transplantation.
文摘Recently, important changes have been reported regarding the epidemiology of bacterial infections in liver cirrhosis. There is an emergence of multiresistant bacteria in many European countries and also worldwide, including the United States and South Korea. The classic empirical antibiotic treatment(third-generation cephalosporins, e.g., ceftriaxone, cefotaxime or amoxicillin-clavulanic acid) is still effective in infections acquired in the community, but its failure rate in hospital acquired infections and in some health-care associated infections is high enough to ban its use in these settings. The current editorial focuses on the different epidemiology of bacterial infections in cirrhosis across countries and on its therapeutic implications.
文摘Despite major advances in the knowledge and management of liver diseases achieved in recent decades,decompensation of cirrhosis still carries a high burden of morbidity and mortality.Bacterial infections are one of the main causes of decompensation.It is very important for clinical management to be aware of the population with the highest risk of poor outcome.This review deals with the new determinants of prognosis in patients with cirrhosis and bacterial infections reported recently.Emergence of multiresistant bacteria has led to an increasing failure rate of the standard empirical antibiotic therapy recommended by international guidelines.Moreover,it has been recently reported that endothelial dysfunction is associated with the degree of liver dysfunction and,in infected patients,with the degree of sepsis.It has also been reported that relative adrenal insufficiency is frequent in the non-critically ill cirrhotic population and it is associated with a higher risk of developing infection,severe sepsis,hepatorenal syndrome and death.We advise a change in the standard empirical antibiotic therapy in patients with high risk for multiresistant infections and also to take into account endothelial and adrenal dysfunction in prognostic models in hospitalized patients with decompensated cirrhosis.
文摘AIMS To establish the prevalence of bacterial infection in cir- rhotic patients with hepatocellular carcinoma(HCC). METHODS All 719 cirrhotic patients with HCC were investigat- ed retrospectively for the prevalence of bacterial infections. RESULTS The incidence of bacterial infection was 15.4% (111/719).According to Child-Pugh classification,the inci- dences of bacterial infection in class A,B and C were 2.3%,8. 0%,and 26.4 %,respectively.The bacterial infection increased with the severity of cirrhosis and severe bacterial infections usual- ly occurred in Child-Pugh class B and C patients. CONCLUSIONS The susceptibility of HCC patients to bacterial infection is mainly due to the underlying cirrhosis and not to the HCC itself.
文摘Objective:The clinical diagnostic accuracy of C-reactive protein(CRP)for bacterial infections in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)is still controversial.This study evaluated its accuracy through Meta-analysis.Methods:Studies on the diagnostic value of CRP for bacterial infections in AECOPD were searched form Web of Science,PubMed,Cochrane library,EMBASE,WANFANG DATA,CNKI and China Biology Medicine disc.The included studies were evaluated according to QUADAS-2 assessment tool.Stata 12.0 software was used for meta analyses to summarize the sensitivity and the specificity of the included studies,and the heterogeneity test was conducted.The symmetric receiver operating characteristic curves(SROC)was drawn and the area under the curve(AUC)was calculated,and the funnel plot was drawn to determine publication bias.Results:664 studies were initially identified,20 of which met the inclusion criteria(9 in English and 11 in Chinese).Meta-analysis results showed that the summary sensitivity and specificity of CRP in diagnosing bacterial infections in AECOPD were 0.84,95%CI(0.77-0.90)and 0.76,95%CI(0.67-0.82),respectively.The AUC of SROC was 0.87,95%CI(0.83-0.89).Conclusion:CRP has high accuracy,sensitivity and specificity in distinguishing AECOPD bacterial infections from non-bacterial infection.
文摘Bacterial infection in the first month after liver transplantation is a frequent complication that poses a serious risk for liver transplant recipients as contributes substantially to increased length of hospitalization and hospital costs being a leading cause of death in this period. Most of these infections are caused by gramnegative bacilli, although gram-positive infections, especially Enterococcus sp. constitute an emerging infectious problem. This high rate of early postoperative infections after liver transplant has generated interest in exploring various prophylactic approaches to surmount this problem. One of these approaches is selective intestinal decontamination(SID). SID is a prophylactic strategy that consists of the administration of antimicrobials with limited anaerobicidal activity in order to reduce the burden of aerobic gram-negative bacteria and/or yeast in the intestinal tract and so prevent infections caused by these organisms. The majority of studies carried out to date have found SID to be effective in the reduction of gram-negative infection, but the effect on overall infection is limited due to a higher number of infection episodes by pathogenic enterococci and coagulase-negative staphylococci. However, difficulties in general extrapolation of the favorable results obtained in specific studies together with the potential risk of selection of multirresistant microorganisms has conditioned controversy about the routinely application of these strategies in liver transplant recipients.
文摘AIM To determine risk factors, causative organisms and antimicrobial resistance of bacterial infections following living-donor liver transplantation(LDLT) in cirrhotic patients.METHODS This prospective study included 45 patients with hepatitis C virus-related end-stage liver disease who underwent LDLT at Ain Shams Center for Organ Transplant, Cairo, Egypt from January 2014 to November 2015. Patients were followed-up for the first 3 mo after LDLT for detection of bacterial infections. All patients were examined for the possible risk factors suggestive of acquiring infection pre-, intra-and post-operatively. Positive cultures based on clinical suspicion and patterns of antimicrobial resistance were identified. RESULTS Thirty-three patients(73.3%) suffered from bacterial infections; 21 of them had a single infection episode, and 12 had repeated infection episodes. Bile was the most common site for both single and repeated episodes of infection(28.6% and 27.8%, respectively). The most common isolated organisms were gramnegative bacteria. Acinetobacter baumannii was the most common organism isolated from both single and repeated infection episodes(19% and 33.3%, respectively), followed by Escherichia coli for repeated infections(11.1%), and Pseudomonas aeruginosa for single infections(19%). Levofloxacin showed high sensitivity against repeated infection episodes(P = 0.03). Klebsiella, Acinetobacter and Pseudomonas were multi-drug resistant(MDR). Pre-transplant hepatocellular carcinoma(HCC) and duration of drain insertion(in days) were independent risk factors for the occurrence of repeated infection episodes(P = 0.024).CONCLUSION MDR gram-negative bacterial infections are common post-LDLT. Pre-transplant HCC and duration of drain insertion were independent risk factors for the occurrence of repeated infection episodes.
基金supported by the National Key Research and Development Program of China(No.2022YFC2304501 and No.2021YFC2301800)the Fundamental Research Funds for the Central Universities(2023QZJH50)+1 种基金Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(No.2022RC141)the Chinese National Natural Science Foundation(No.81870425).
文摘Acute-on-chronic liver failure(ACLF)is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease,often leading to multi-organ failures and significant short-term mortalities.Bacterial infection is one of the most frequent triggers for ACLF and a common complication following its onset.The impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ failures.In addition,the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use,as well as accurate and prompt microbiological diagnosis.This review provided an update on recent advances in the epidemiology,diagnosis,pathogenesis,and management of bacterial infections in ACLF.
文摘Purpose:To investigate which scoring system is the most accurate tool in predicting mortality among the infected patients who present to the emergency department in a middle-income country,and to validate a new scoring system to predict bacterial infections.Methods:This was a retrospective,single-center study among patients who were admitted via the emergency department of a public hospital.All patients who were started on antibiotics were included in the study,while patients aged<18 years were excluded.Data collected includeding patients'demographics,vital signs and basic laboratory parameters like white blood cell count and creatinine.The sensitivity and specificity of different scoring systems were calculated as well as their negative and positive predictive values.Logistic regression was used to derive a novel early warning system for bacterial infections.The area under the receiver operating characteristic(AUROC)was computed for each scoring model.Results:In total,109 patients were included in this study.The quick sequential organ failure assessment(qSOFA),search out severity and rapid acute physiology score had the highest AUROC(≥0.89)for predicting mortality,while qSOFA and universal vital assessment were the simplest scoring systems with an AUROC>0.85;however,these scoring systems failed to predict whether patients were truly infected.The INFECTIONS(short for impaired mental status,not conscious,fast heart rate,elevated creatinine,high temperature,on inotrope,low oxygen,high neutrophils and high sugar)model reached an AUROC of 0.88 to more accurately predict the infectious state of a patient.Conclusions:Middle-income countries should use the qSOFA or universal vital assessment score to identify the sickest patients in emergency department.The INFECTIONS score may help recognize patients with bacterial infections,but it should be further validated in multiple countries prior to widely use.
基金The second author(B.T.),acknowledges the support of the University of Pretoria Senior Postdoctoral Program Grant(2018-2020).
文摘Bacteriophages or phages are viruses that infect bacteria and are increasingly used to control bacterial infections.We develop a reaction-diffusion model coupling the interactive dynamic of phages and bacteria with an epidemiological bacteria-borne disease model.For the submodel without phage absorption,the basic reproduction number Ro is computed.The disease-free equilibrium(DFE)is shown to be globally asymptotically stable whenever Ro is less than one,while a unique globally asymptotically endemic equilibrium is proven whenever Ro exceeds one.In the presence of phage absorption,the above stated classical condition based on Ro,as the average number of secondary human infections produced by susceptible/lysogen bacteria during their entire lifespan,is no longer suficient to guarantee the global stability of the DFE.We thus derive an additional threshold No,which is the average offspring number of lysogen bacteria produced by one infected human during the phage-bacteria interactions,and prove that the DFE is globally asymptotically stable whenever both Ro and No are under unity,and infections persist uniformly whenever Ro is greater than one.Finally,the discrete counterpart of the continuous partial differential equation model is derived by constructing a nonstandard finite difference scheme which is dynamically consistent.This consistency is shown by constructing suitable discrete Lyapunov functionals thanks to which the global stability results for the continuous model are replicated.This scheme is implemented in MatLab platform and used to assess the impact of spatial distribution of phages,on the dynamic of bacterial infections.
基金supported by the following funds:The Natural Science Foundation of China(52275393,51935014,82072084)Hunan Provincial Natural Science Foundation of China(2021JJ20061)+4 种基金Jiangxi Provincial Natural Science Foundation of China(20224ACB204013)The Project of State Key Laboratory of Precision Manufacturing for Extreme Service PerformanceTechnology Innovation Platform Project of Shenzhen Institute of Information Technology 2020(PT2020E002)Guangdong Province Precision Manufacturing and Intelligent production education Integration Innovation Platform(2022CJPT019)Independent Exploration and Innovation Project of Central South University(1053320220553)。
文摘Bacterial infection is a major issue after artificial bone transplantation due to the absence of antibacterial function of bone scaffold,which seriously causes the transplant failure and even amputation in severe cases.In this study,oxygen vacancy(OV)defects Fe-doped Ti O2(OV-FeTiO2)nanoparticles were synthesized by nano TiO2and Fe3O4via high-energy ball milling,which was then incorporated into polycaprolactone/polyglycolic acid(PCLGA)biodegradable polymer matrix to construct composite bone scaffold with good antibacterial activities by selective laser sintering.The results indicated that OV defects were introduced into the core/shell-structured OV-FeTiO2nanoparticles through multiple welding and breaking during the high-energy ball milling,which facilitated the adsorption of hydrogen peroxide(H2O2)in the bacterial infection microenvironment at the bone transplant site.The accumulated H2O2could amplify the Fenton reaction efficiency to induce more hydroxyl radicals(·OH),thereby resulting in more bacterial deaths through·OH-mediated oxidative damage.This antibacterial strategy had more effective broad-spectrum antibacterial properties against Gram-negative Escherichia coli(E.coli)and Gram-positive Staphylococcus aureus(S.aureus).In addition,the PCLGA/OV-FeTiO2scaffold possessed mechanical properties that match those of human cancellous bone and good biocompatibility including cell attachment,proliferation and osteogenic differentiation.
文摘BACKGROUND Spontaneous bacterial peritonitis(SBP)is one of the most important complications of patients with liver cirrhosis entailing high morbidity and mortality.Making an accurate early diagnosis of this infection is key in the outcome of these patients.The current definition of SBP is based on studies performed more than 40 years ago using a manual technique to count the number of polymorphs in ascitic fluid(AF).There is a lack of data comparing the traditional cell count method with a current automated cell counter.Moreover,current international guidelines do not mention the type of cell count method to be employed and around half of the centers still rely on the traditional manual method.AIM To compare the accuracy of polymorph count on AF to diagnose SBP between the traditional manual cell count method and a modern automated cell counter against SBP cases fulfilling gold standard criteria:Positive AF culture and signs/symptoms of peritonitis.METHODS Retrospective analysis including two cohorts:Cross-sectional(cohort 1)and case-control(cohort 2),of patients with decompensated cirrhosis and ascites.Both cell count methods were conducted simultaneously.Positive SBP cases had a pathogenic bacteria isolated on AF and signs/symptoms of peritonitis.RESULTS A total of 137 cases with 5 positive-SBP,and 85 cases with 33 positive-SBP were included in cohort 1 and 2,respectively.Positive-SBP cases had worse liver function in both cohorts.The automated method showed higher sensitivity than the manual cell count:80%vs 52%,P=0.02,in cohort 2.Both methods showed very good specificity(>95%).The best cutoff using the automated cell counter was polymorph≥0.2 cells×10^(9)/L(equivalent to 200 cells/mm^(3))in AF as it has the higher sensitivity keeping a good specificity.CONCLUSION The automated cell count method should be preferred over the manual method to diagnose SBP because of its higher sensitivity.SBP definition,using the automated method,as polymorph cell count≥0.2 cells×10^(9)/L in AF would need to be considered in patients admitted with decompensated cirrhosis.
文摘Background and Aims:Patients with cirrhosis are immunocompromised and at higher risk of developing infections compared to the general population.The aim of this study was to assess the incidence of infections in cirrhotic patients in a large academic liver center and investigate potential associations between infections,bacteria isolated,therapeutic regimens used,and mortality.Methods:This was a retrospective chart review study,including 192 patients.All patients had a diagnosis of cirrhosis and were admitted to University Hospital.Information collected included demographics,etiology of cirrhosis,identification of bacteria from cultures,multidrug-resistant(MDR)status,antibiotics administered,intensive care unit(ICU)admission,and patient mortality.Results:Infections were present in 105(54.6%)patients,and 60(31.2%)patients had multiple infections during a hospitalization(s)for infections.A total of 201 infections were identified.Urinary tract infections(UTIs)were the most common infection(37.8%),followed by bacteremia(20.4%),pneumonia(12.9%),spontaneous bacterial peritonitis(SBP)(11.9%),abscess/cellulitis(6.0%),infectious diarrhea(6.0%),and other(5.0%).Escherichia coli was the most common bacteria isolated(13.4%),both among sensitive and MDR infections.MDR bacteria were the cause for 41.3%of all infections isolated.Fungi accounted for 9.5%of infections.21.9%of patients had decompensation from their infection(s)that required ICU care,and 14.6%of patients died during hospitalization or soon after discharge.Conclusions:The incidence of infections in cirrhotic patients is much higher than in their non-cirrhotic counterparts(54.6%),even higher than prior studies suggest.As many of these infections are caused by MDR bacteria and fungal organisms,stronger empiric antibiotics and antifungals should be considered when initially treating this immunocompromised population.However,once organism sensitivities are discovered,narrowing of antibiotic regimens must occur to maintain good antibiotic stewardship.
基金Supported by University Grants Commission(UGC),New Delhi for providing the financial assistance.Reference No.U.G.C.No.33-384/2007(SR).
文摘Objective:To ascertain the feasibility of using sustainable natural resources in maintaining disease free fish in such establishments.Methods:causative bacteria were identified by morphology and biochemical techniques.The antibacterial activity and disease resistant capability of mangrove plant leaf extract were investigated against fish pathogens.Results:The infected marine ornamental fishes were collected from the hatchery condition and inhibition activity at the concentration of 220,200,175 and 150μg/mL against Pseudomonas fluorescens,Pseudomonas aeruginosa,Vibrio parahaemolyticus,and Vibrio anguillarum respectively.The experimental trial reveals feeding marine ornamental fish with feed incorporated with a methanol leaf extract of Avicennia marina,increases their survival and reduces their susceptibility to infections from the isolated bacteria.Based on the in vitro assay,methanol extract of Avicennia marina was exhibited good Conclusions:The mangrove leaves have potential to control the infections caused by Pseudomonas fluorescens,Pseudomonas aeruginosa,Vibrio parahaemolyticus and Vibrio anguillarum.
文摘Considering the WHO warning about the emergence of a’post-antibiotic’era during the 21st century in which common infections and minor injuries will have a dramatic impact on human death toll,search for new potential antibacterial drug targets became a necessary need.Targets that are extensively explored concern the modulation
文摘Multidrug-resistant(MDR)bacterial infections exert a tremendous burden on the public health system throughout the developing and developedworld.Slowing development of novel antibiotic scaffolds,over-prescription of antibiotics,extensive agricultural antibiotic use,and the increasingly complex hospitalized patient populations undergoing treatment,all fuel the rise of highly MDR“superbugs.”Unfortunately,host-directed therapies to boost immune resistance to infection are not currently available for treatment of MDR pathogens.Hematopoietic cells are endowed with a variety ofmechanismsto control microbial invasion.Macrophages in particular have long been appreciated as potent antimicrobial immune cells equipped with several receptors that allow for rapid recognition,phagocytosis,and killing of pathogenic microbes,coupled to secretion of immunostimulatory cytokines to further orchestrate a robust multifaceted antibacterial immune response.To investigate the utility of macrophages as a cell therapy for MDR bacterial infections,we developed a therapeutically translatable process to generate,harvest,and cryopreserve monocyte-derived macrophages(ICONIMACTM).These cells effectively killed both Gram-positive and Gram-negative MDR pathogens in vitro,and conferred protection in vivo against experimental lethal peritonitis and lung infection.Our discoveries provide a proof-of-concept for a novel immunotherapeutic approach against MDR bacterial infections,urgently needed to supplement the diminishing antibiotic pipeline.
基金This study was supported by the Special Fund of the National Science and Technology Major Project of China(No. 2018ZX10305409)Beijing Hospital Authority "Dengfeng" Talent Training Plan(DFL 20181201)Sanming Project of Medicine in Shenzhen(SZSM201512030)
文摘Importance: The current lack of reliable rapid tests for distinguishing between bacterial and viral infections has contributed to antibiotic misuse.Objective: This study aimed to develop a novel biomarker assay that integratesFAM89A andIFI44L measurements to assist in differentiating between bacterial and viral infections.Methods: This prospective study recruited children with febrile illness from two hospitals between July 1, 2018, and June 30, 2019. A panel of three experienced pediatricians performed reference standard diagnoses of all patients (i.e., bacterial or viral infection) using available clinical and laboratory data, including a 28-day follow-up assessment. Assay operators were blinded to the reference standard diagnoses. The expression levels ofFAM89A andIFI44L were determined by quantitative real-time polymerase chain reaction assessment.Results: Of 133 potentially eligible patients with suspected bacterial or viral infection, 35 were excluded after the application of exclusion criteria. The resulting cohort included 98 patients: 59 with viral diagnoses and 39 with bacterial diagnoses. The areas under the curve (AUCs) of diagnoses usingFAM89A andIFI44L were 0.694 [95% confidence interval (CI): 0.583-0.804] and 0.751 (95%CI: 0.651-0.851), respectively. The disease risk score (DRS) [log2(FAM89A expression) - log2(IFI44L expression)] signature achieved an improved area under the receiver operating characteristic curve (AUC, 0.825;95%CI: 0.735-0.915), compared with the AUC generated from individual host RNA. A combination of the DRS and the C-reactive protein (CRP) level achieved an AUC of 0.896 (95%CI: 0.825-0.966). Optimal cutoffs for the DRS and CRP level were -3.18 and 19.80 mg/L, respectively.Interpretation: The DRS was significantly more accurate than the CRP level in distinguishing between bacterial and viral infections;the combination of these two parameters exhibited greater sensitivity and specificity. This study provides information that could be useful for the clinical application ofFAM89A andIFI44L in terms of distinguishing between viral and bacterial infections.
