Retrospective study of the incidence, risk factors, treatment outcomes of bacterial infections at uncommon sites in cirrhotic patients

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.

Rice Bacterial Infection Detection Using Ensemble Technique on Unmanned Aerial Vehicles Images

Establishing a system for measuring plant health and bacterial infection is critical in agriculture.Previously,the farmers themselves,who observed them with their eyes and relied on their experience in analysis,which could have been incorrect.Plant inspection can determine which plants reflect the quantity of green light and near-infrared using infrared light,both visible and eye using a drone.The goal of this study was to create algorithms for assessing bacterial infections in rice using images from unmanned aerial vehicles(UAVs)with an ensemble classification technique.Convolution neural networks in unmanned aerial vehi-cles image were used.To convey this interest,the rice’s health and bacterial infec-tion inside the photo were detected.The project entailed using pictures to identify bacterial illnesses in rice.The shape and distinct characteristics of each infection were observed.Rice symptoms were defined using machine learning and image processing techniques.Two steps of a convolution neural network based on an image from a UAV were used in this study to determine whether this area will be affected by bacteria.The proposed algorithms can be utilized to classify the types of rice deceases with an accuracy rate of 89.84 percent.

Bacterial infection triggers and complicates acute-on-chronic liver failure in patients with hepatitis B virus-decompensated cirrhosis: A retrospective cohort study

BACKGROUND Reports on bacterial infection(BI)in decompensated cirrhosis(DC)is mainly from alcoholic cirrhosis.The role of BI as a trigger or complication of acute-onchronic liver failure(ACLF)in patients with hepatitis B virus decompensated cirrhosis(HBV-DC)remains to be investigated.AIM To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF.METHODS This retrospective study included patients with HBV-DC admitted to two tertiary centers in China.In-hospital overall survival,90-d transplant-free survival,5-year post-discharge survival,and cumulative incidence of ACLF were evaluated.Risk factors for death were analyzed considering liver transplantation as a competing event.RESULTS A total of 1281 hospitalized HBV-DC patients were included;284 had ACLF at admission.The overall prevalence of BI was 28.1%.The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without,in both the patients admitted with and without ACLF.The presence of BI significantly increased the risk of developing ACLF[subdistribution hazard ratio(sHR)=2.52,95%CI:1.75-3.61,P<0.001]in the patients without ACLF.In the patients discharged alive,those who had an episode of BI had a significantly lower 5-year transplant-free survival.BI was an independent risk factor for death in the patients admitted without ACLF(sHR=3.28,95%CI:1.93-5.57),while in ACLF admissions,the presence of pneumonia,but not other type of BI,independently increased the risk of death(sHR=1.87,95%CI:1.24-2.82).CONCLUSION BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival.HBV-DC patients should be monitored carefully for the development of BI,especially pneumonia,to avoid an adverse outcome.

Risk factors of intra-abdominal bacterial infection after liver transplantation in patients with hepatocellular carcinoma

Objective： To explore the risk factors of intra-abdominal bacterial infection （IAI） after liver transplantation （LT） in patients with hepatocellular carcinoma （HCC）. Methods： A series of 82 HCC patients who received LT surgeries in our department between March 2004 and April 2010 was recruited in this study. Then we collected and analyzed the clinical data retrospectively. Statistical analysis system （SPSS） software was adopted to perform statistical analysis. Chi-square test, t-test and Wilcoxon rank sum test were used to analyze the clinical data and compute the significance of the incidences of early-stage IAI after LT for HCC patients. Binary logistic regression was performed to screen out the risk factors, and multiple logistic regression analyses were performed to compute the independent risk factors. Results： A series of 13 patients （13/82, 15.9%） had postoperative IAI. The independent risk factors of postoperative intra-abdominal bacterial infections after LT for HCC patients were preoperative anemia [Hemoglobin （HGB） 〈90 g/L] and postoperative abdominal hemorrhage （72 hours 〉400 mL）, with the odds ratios at 8.121 （95% CI, 1.417 to 46.550, P=0.019） and 5.911 （95% CI, 1.112 to 31.432, P=0.037）. Conclusions： Postoperative IAI after LT in patients with HCC was a common complication. Preoperative moderate to severe anemia, as well as postoperative intra-abdominal hemorrhage more than 400 mL within the first 72 hours might independently indicate high risk of IAI for these patients.

Studying host genetic background effects on multimorbidity of intestinal cancer development,type 2 diabetes and obesity in response to oral bacterial infection and high-fat diet using the collaborative cross(CC)lines

Background:Multimorbidity of intestinal cancer(IC),type 2 diabetes(T2D)and obesity is a complex set of diseases,affected by environmental and genetic risk factors.High-fat diet(HFD)and oral bacterial infection play important roles in the etiology of these diseases through inflammation and various biological mechanisms.Methods:To study the complexity of this multimorbidity,we used the collaborative cross(CC)mouse genetics reference population.We aimed to study the multimorbidity of IC,T2D,and obesity using CC lines,measuring their responses to HFD and oral bacterial infection.The study used 63 mice of both sexes generated from two CC lines(IL557 and IL711).For 12 weeks,experimental mice were maintained on specific dietary regimes combined with co-infection with oral bacteria Porphyromonas gingivalis and Fusobacterium nucleatum,while control groups were not infected.Body weight(BW)and results of a intraperitoneal glucose tolerance test(IPGTT)were recorded at the end of 12 weeks,after which length and size of the intestines were assessed for polyp counts.Results:Polyp counts ranged between 2 and 10 per CC line.The combination of HFD and infection significantly reduced(P<.01)the colon polyp size of IL557 females to 2.5 cm 2,compared to the other groups.Comparing BW gain,IL557 males on HFD gained 18 g,while the females gained 10 g under the same conditions and showed the highest area under curve(AUC)values of 40000-45000(min mg/dL)in the IPGTT.Conclusion:The results show that mice from different genetic backgrounds respond differently to a high fat diet and oral infection in terms of polyp development and glucose tolerance,and this effect is gender related.

Development of a novel score for the diagnosis of bacterial infection in patients with acute-on-chronic liver failure

BACKGROUND The diagnosis of bacterial infection is difficult in patients with acute-on-chronic liver failure(ACLF).AIM To evaluate the diagnostic accuracy of widely used parameters for bacterial infection in ACLF and to develop a simple scoring system to improve diagnostic efficiency.METHODS This was a retrospective study.Procalcitonin(PCT),white blood cells(WBC),proportion of neutrophils(N%),and C-reactive protein(CRP)were examined.Logistic regression was used to select variables for the scoring models and receiver operating characteristic curve(ROC)analysis was used to evaluate the diagnostic value of different indices.RESULTS This study included 386 patients with ACLF,169(43.78%)of whom had bacterial infection on admission.The area under the ROC(AUROC)of PCT,CRP,WBC and N%for the diagnosis of bacterial infection ranged from 0.637 to 0.692,with no significant difference between them.Logistic regression showed that only N%,PCT,and CRP could independently predict infection.A novel scoring system(infection score)comprised of N%,PCT and CRP was developed.The AUROC of the infection score was 0.740,which was significantly higher than that for the other four indices(infection score vs N%,PCT,CRP,and WBC,P=0.0056,0.0001,0.0483 and 0.0008,respectively).The best cutoff point for the infection score was 4 points,with a sensitivity of 78.05%,a specificity of 55.29%,a positive predictive value of 57.91%and a negative predictive value of 76.16%.CONCLUSION The infection score is a simple and useful tool for discriminating bacterial infection in ACLF.

Comparison on Serum Levels of Procalcitonin of Children with Viral and Bacterial Infection

Objective To compare and analyze serum levels of procalcitonin (PCT) of children with viral and bacterial infection and probe into the importance of determining the level of serum PCT in the diagnosis of bacterial infection in order to provide evidences of the clinical use of antibiotics. Methods A total of 85 cases of children with an average age of 8.9 years (10 months-12 years) were enrolled in this study, 53 cases were with viral infection and 32 cases with bacterial infection. We determined serum levels of PCT by semi-quantitative solid phase immunoassay, and the serum levels of PCT were divided into four grades as<0.5μg/L,≥ 0.5μg/L,≥2.0μg/L and≥10μg/L forχ2 test and Ridit analysis. Results The serum level of PCT of the group with bacterial infection were signiifcantly higher than that of the group with viral infection (P<0.001). The sensitivity of diagnosis of bacterial infection in children with determination of serum levels of PCT was 87.50%while the speciifcity was 92.13%, and positive predictive value was 73.68%while negative predictive value was 91.49%, and positive likelihood ratio was 4.65 while negative likelihood ratio was 0.15, and the diagnostic accuracy was 83.53%. Conclusions Serum PCT is a bacterial sensitive marker of bacterial infection in children, and the determination of the level of serum PCT is helpful for the diagnosis of bacterial infection, which can also be a basis for the use of antibiotics.

The clinical analysis of three methods in the treatment of intracranial bacterial infection

Objective To analyze the effect of three therapeutic methods to find an optimal approach to the treatment of intracranial bacterial infection by retrospectively reviewing 33 intracranial bacterial infection patients who were admitted from 1995 to 2008 in our hospital.Methods The treatments by intermittent lumbar puncture,continuous lumbar subarachnoid space drainage,and embedment of Ommaya cyst for continuous drainage from the ventricles were performed in 15 cases,12 cases,and 6 cases respectively along with intravenous application of full dose of antibiotics.Results Nineteen cases were cured and the best prognosis was from the group of Ommaya cyst embedment and continuous drainage from the ventricles.Conclusion Management goals are prompt recognition of the central nervous system(CNS)infection,rapid identification of causative organisms and initiation of treatment with the optimal management methods for complications.Embedment of Ommaya cyst for continuous drainage from the ventricle is a safe and effective treatment for intracranial bacterial infection.

Bacterial infections post-living-donor liver transplantation in Egyptian hepatitis C virus-cirrhotic patients: A singlecenter study

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.

Diagnostic accuracy of C-reactive protein for bacterial infections in acute exacerbation of chronic obstructive pulmonary disease: A meta-analysis

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.

Mesenchymal Stem Cells: Potential Role against Bacterial Infection

The worldwide spread of bacterial resistance makes finding new therapeutics to overcome this ongoing problem an urgent need. Mesenchymal stem cells (MSCs) exert potential inhibiting activity against bacterial infections. The antimicrobial activity of MSCs relies on direct and indirect effects by secreting paracrine factors with potential inhibiting activity against bacterial growth or stimulating the phagocytic activity of the immune cells. These effects appeared when MSCs or its secreted factors are administrated therapeutically. Therefore, MSCs based cell therapy could be considered as a novel promising strategy to enhance the antibiotic activity in multidrug resistant (MDR) infections.

The value of the INFECTIONS scoring system in identifying bacterial infections among patients presenting at the emergency department of a middle-income country:A pilot study

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.

Oxygen vacancy boosting Fenton reaction in bone scaffold towards fighting bacterial infection

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.

Engineering Janus gold nanorod–titania heterostructures with enhanced photocatalytic antibacterial activity against multidrugresistant bacterial infection

Photocatalytic antibacterial approach shows great potential in treating multidrug-resistant bacterial infections.However,the bactericidal efficiency heavily depends on the photocatalytic activity of semiconductor materials,which is limited by the fast recombination of photogenerated electron–hole pairs.Janus nano-heterostructures with spatial control growth of TiO_(2)nanoparticles(NPs)at one end of gold nanorods(Au NRs)are designed via surface ligand regulation for photocatalytic sterilization and infected wound healing.The asymmetric nanostructure of Janus gold nanorod-titanium dioxide nanoparticles(Janus AuNR-TiO_(2) NPs)promotes the directional migration of charge carriers and is more conducive to the spatial separation of electron–hole pairs.Moreover,the injection of hot electrons and enhancement of plasmon near-fields from the surface plasmon resonance(SPR)effect further improve the photocatalytic efficiency of Janus AuNR-TiO_(2) NPs.Under simulated sunlight irradiation,large amounts of reactive oxygen species(ROS)are generated for photocatalytic antibacterial activity.Enhanced bactericidal efficiency up to 99.99%against methicillin-resistant Staphylococcus aureus(MRSA)is achieved in vitro.Furthermore,Janus AuNR-TiO_(2) NPs exhibit superior biocompatibility,structural stability,and also remarkably accelerate MRSA-infected wound healing.Taking the above all into consideration,Janus AuNR-TiO_(2) NPs,as an efficient antibacterial photocatalyst,offers a promising strategy for MRSA infectious therapy.

On a diffusive bacteriophage dynamical model for bacterial infections

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.

Relationship between Intrauterine Bacterial Infection and Early Embryonic Developmental Arrest

Background： Early embryonic developmental arrest is the most commonly understudied adverse outcome of pregnancy. The relevance of intrauterine infection to spontaneous embryonic death is rarely studied and remains unclear. This study aimed to investigate the relationship between intrauterine bacterial infection and early embryonic developmental arrest. Methods： Embryonic chorion tissue and uterine swabs for bacterial detection were obtained from 33 patients who underwent artificial abortion （control group） and from 45 patients who displayed early embryonic developmental arrest （trial group）. Results： Intrauterine bacterial infection was discovered in both groups. The infection rate was 24.44% （11/45） in the early embryonic developmental arrest group and 9.09% （3/33） in the artificial abortion group. Classification analysis revealed that the highest detection rate for Micrococcus luteus in the early embryonic developmental arrest group was 13.33% （6/45）, and none was detected in the artificial abortion group. M. luteus infection was significantly different between the groups （P 〈 0.05 as shown by Fisher＇s exact test）. In addition, no correlation was found between intrauterine bacterial infection and history of early embryonic developmental arrest. Conelusions： IV/. luteus infection is related to early embryonic developmental arrest and might be one of its causative factors.

Surface modification of titanium implants with micro–nanotopography and NIR photothermal property for treating bacterial infection and promoting osseointegration

A double acid corrosion and subsequent hydrothermal treatment were used to fabricate a micro–nano-structured Ti substrates(Ti–M–N).Afterward,the mesoporous polydopamine(MPDA)nanoparticles as photothermal agent were prepared and immobilized on the surface of Ti–M–N samples,in order to obtain Ti–M–NMPDA sample.Unique micro–nanostructure properties and the photothermal effect of the modified Ti implant caused physical stress on the bacteria and the bacterial membrane damage,and eventually led to bacteria death.More importantly,based on excellent bioactivity and cytocompatibility of mussel-inspired materials,MPDA promoted adhesion,proliferation and osteogenic differentiation of mesenchymal stem cells in vitro.Furthermore,animal experiments in vivo further confirmed that the modified Ti implants could enhance osseointegration.

Macrophage-Mediated Defensive Mechanisms Involving Zinc Homeostasis in Bacterial Infection

Zinc homeostasis in macrophages is essential for maintaining their antimicrobial functions,and a growing body of evidence indicates that both zinc depletion and excess zinc in myeloid cells decrease bacterial survival.In macrophages,maintaining intracellular and extracellular zinc levels via zinc transporter proteins,including Slc30a and Slc39a family members,plays an important role in the response to immunological signals and infection.Recently,studies have found that macrophages utilize a variety of zinc-modulating mechanisms,thus expanding our knowledge regarding the role that zinc plays in response to bacterial infection.Here,we review recent progress with respect to altered zinc metabolism in macrophages and the consequences with respect to fighting invading pathogens.

Wrapping collagen-based nanoparticle with macrophage membrane for treating multidrug-resistant bacterial infection

Nowadays,multidrug-resistant(MDR)bacterial infectious diseases has become a thorny issue in the healthcare field.Owning to its intrinsic merits,photodynamic therapy(PDT)shows tremendous strengths in fighting against MDR bacterial infections.However,most photodynamic nanoplatforms exhibit unsatisfactory targeting efficiency towards bacteria and infection site,which may compromise the bactericidal effect of PDT.Herein,we firstly reported a bacteria-targeted collagen-based nanoparticle,named Ce6/Col/MM,for treating methicillin-resistant Staphylococ-cus aureus(MRSA)-infected wound.Ce6/Col/MM was fabricated by wrapping chlorin e6(Ce6)-loaded collagen-based nanoparticles with macrophage membrane(MM),showing excellent photodynamic activity and good biocompat-ibility.In vitro studies demonstrated that Ce6/Col/MM could target to bacteria and then exhibit prominent antibacterial capacity against planktonic MRSA under light irradiation.Furthermore,the treatment of MRSA-infected wound in mice with Ce6/Col/MM plus light illumination resulted in potent bacterial inactivation and accelerated wound healing,accompanied by favorable histological compatibility.Collectively,Ce6/Col/MM with superior targeting ability towards bacteria,effective photodynamic antibacterial potency and minimal safety concerns,might be a powerful bactericidal nanoagent for treating infections caused by MDR bacteria。

Protection Against Lethal Multidrug-Resistant Bacterial Infections Using Macrophage Cell Therapy

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.