Biofunctional lipid nanoparticles for precision treatment and prophylaxis of bacterial infections.

The lack of bacterial-targeting function in antibiotics and their prophylactic usage have caused overuse of antibiotics, which lead to antibiotic resistance and inevitable long-term toxicity. To overcome these issues, we develop neutrophil-bacterial hybrid cell membrane vesicle (HMV)-coated biofunctional lipid nanoparticles (LNP@HMVs), which are designed to transport antibiotics specifically to bacterial cells at the infection site for the effective treatment and prophylaxis of bacterial infection. The dual targeting ability of HMVs to inflammatory vascular endothelial cells and homologous Gram-negative bacterial cells results in targeted accumulation of LNP@HMVs in the site of infections. LNP@HMVs loaded with the antibiotic norfloxacin not only exhibit enhanced activity against planktonic bacteria and bacterial biofilms in vitro but also achieve potent therapeutic efficacy in treating both systemic infection and lung infection. Furthermore, LNP@HMVs trigger the activation of specific humoral and cellular immunity to prevent bacterial infection. Together, LNP@HMVs provide a promising strategy to effectively treat and prevent bacterial infection.

Phage therapy as a glimmer of hope in the fight against the recurrence or emergence of surgical site bacterial infections.

PURPOSE: Over the last decade, surgery rates have risen alarmingly, and surgical-site infections are expanding these concerns. In spite of advances in infection control practices, surgical infections continue to be a significant cause of death, prolonged hospitalization, and morbidity. As well as the presence of bacterial infections and their antibiotic resistance, biofilm formation is one of the challenges in the treatment of surgical wounds. METHODS: This review article was based on published studies on inpatients and laboratory animals receiving phage therapy for surgical wounds, phage therapy for tissue and bone infections treated with surgery to prevent recurrence, antibiotic-resistant wound infections treated with phage therapy, and biofilm-involved surgical wounds treated with phage therapy which were searched without date restrictions. RESULTS: It has been shown in this review article that phage therapy can be used to treat surgical-site infections in patients and animals, eliminate biofilms at the surgical site, prevent infection recurrence in wounds that have been operated on, and eradicate antibiotic-resistant infections in surgical wounds, including multi-drug resistance (MDR), extensively drug resistance (XDR), and pan-drug resistance (PDR). A cocktail of phages and antibiotics can also reduce surgical-site infections more effectively than phages alone. CONCLUSION: In light of these encouraging results, clinical trials and research with phages will continue in the near future to treat surgical-site infections, biofilm removal, and antibiotic-resistant wounds, all of which could be used to prescribe phages as an alternative to antibiotics.

Stopping antibacterial prophylaxis in pediatric allogeneic hematopoietic cell transplantation: An internal audit.

BACKGROUND: Antibacterial prophylaxis in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) is controversial and not recommended by international guidelines. We analyzed relevant posttransplant outcomes following discontinuation of antibacterial prophylaxis at a major European pediatric transplant center. METHODS: The single-center retrospective audit included all pediatric allogeneic HCT patients (pts) transplanted between 2011 and 2020 before (≤2014) and after (≥2015) stopping routine antibacterial prophylaxis with penicillin, metronidazole, and ciprofloxacin upon start of the conditioning regimen. The primary endpoint was overall survival until the first hospital discharge. Secondary endpoints included the occurrence of fever; bacterial infections; and cumulative days with antibacterial agents until discharge. RESULTS: A total of 257 HCT procedures were performed in 249 pts (median age: 10 years, range, 0.2-22.5) for leukemia/lymphoma (n = 150) and nonmalignant disorders (n = 107). Of these, 104 procedures were performed before (cohort 1) and 153 after (cohort 2) stopping prophylaxis. Overall survival until discharge was 90.4% in cohort 1 and 96.1% in cohort 2 (p = .06). No differences were observed in the occurrence of fever (92.3 vs. 94.1%; p = .57) and bacterial infections (34.6 vs. 25.5%; p = .11). The median number of days on antibacterial agents was significantly lower in cohort 2 (39 vs. 34; p = .002). Detection rates of resistant organisms were overall low. CONCLUSION: In this single-center audit, the stop of routine antibacterial prophylaxis had no effect on the occurrence of fever, bacterial infections, resistant organisms, and GVHD. Overall antibiotic use was significantly reduced, and survival was noninferior to the historical control cohort.

Maternal immune factors involved in the prevention or facilitation of neonatal bacterial infections.

Newborns, whether born prematurely or at term, have a fully formed but naive immune system that must adapt to the extra-uterine environment to prevent infections. Maternal immunity, transmitted through the placenta and breast milk, protects newborns against infections, primarily via immunoglobulins (IgG and IgA) and certain maternal immune cells also known as microchimeric cells. Recently, it also appeared that the maternal gut microbiota played a vital role in neonatal immune maturation via microbial compounds impacting immune development and the establishment of immune tolerance. In this context, maternal vaccination is a powerful tool to enhance even more maternal and neonatal health. It involves the transfer of vaccine-induced antibodies to protect both mother and child from infectious diseases. In this work we review the state of the art on maternal immune factors involved in the prevention of neonatal bacterial infections, with particular emphasis on the role of maternal vaccination in protecting neonates against bacterial disease.

Biopsia en ortopedia y riesgo de contaminación bacteriana durante el muestreo de tejidos: hechos y estrategias / Biopsy in orthopaedics and risk of bacterial contamination during tissue sampling: facts and strategies

Las biopsias en el campo de la ortopedia se utilizan para guiar las opciones de diagnóstico y tratamiento para el proceso de la enfermedad que puede estar ocurriendo. La preparación de la piel de estas biopsias sigue la preparación estándar para un procedimiento quirúrgico, con el objetivo de disminuir la cantidad de microbiota que podría conducir a la contaminación del tejido de la biopsia e incluso a una posible infección. El tejido obtenido de la biopsia a menudo se somete a un studio histopatológico y cultivo. La tasa de contaminación bacteriana informada es aproximadamente inferior al 4%. Esta revisión cuestiona si las muestras de las biopsias se contaminan con la microbiota que permanece en la piel y cómo puede afectar el manejo. Además, qué técnicas o pasos pueden disminuir la tasa de contaminación al realizar una biopsia. Nuestra revisión bibliográfica identificó pocos estudios sobre la contaminación bacteriana de las biopsias. Identificamos diferentes factores implicados en el conocimiento de la microbiota de la piel: técnicas y soluciones de preparación de la piel, variación de la microbiota típica que coloniza la piel según la región anatómica, retención preoperatoria versus administración profiláctica de antibióticos y uso de diferentes hojas de bisturí para la piel superficial y para tejidos profundos, entre otros. Aunque no pudimos identificar ningún dato que proporcionara respuestas a nuestra pregunta original y cuantificar cada factor individualmente, la mayoría de los estudios en diferentes campos ortopédicos proporcionaron hallazgos significativos hasta cierto punto. Describimos algunas recomendaciones prácticas basadas en el consenso y la efectividad teórica para disminuir la tasa de contaminación. Se necesitan más investigaciones en el campo de la ortopedia que impliquen la contaminación por microbiota de la piel de una biopsia

Biopsies in the field of orthopaedics are used to guide diagnostics and treatment options for the disease process that may be occurring such as a tumor or infection. Skin preparation of these biopsies follows the standard skin preparation for a surgical procedure, with the aim to decrease the amount of microbiota that could lead to contamination of the tissue biopsy and even possible infection. The tissue obtained from the biopsy often undergoes pathology and culture. The reported bacterial contamination rate is roughly below 4%. This review questions how samples from the biopsies are getting contaminated by microbiota that remains on the skin and how it affects infection management. In addition, which techniques or steps can decrease the rate of contamination when performing a biopsy. Our review identified little to no data on investigating bacterial contamination of biopsies. In doing this, the review identified different factors implicated in skin microbiota awareness: skin preparation techniques and solutions, variation of typical microbiota that colonize the skin based on the anatomical region, preoperative withholding versus administrating antibiotics prophylactically and using different scalpel blades for superficial and deep incisions, among others. Although we failed to identify any data that provided answers to our original question and quantify each factor individually, most studies in different orthopaedic fields provided significant findings to some extent. We outline some practical recommendations based on consensus and theoretical effectiveness in decreasing the contamination rate. Further research entailing skin microbiota contamination of a biopsy is needed in the field of orthopaedics.

The role of marine pollution on the emergence of fish bacterial diseases.

Marine pollution and bacterial disease outbreaks are two closely related dilemmas that impact marine fish production from fisheries and mariculture. Oil, heavy metals, agrochemicals, sewage, medical wastes, plastics, algal blooms, atmospheric pollutants, mariculture-related pollutants, as well as thermal and noise pollution are the most threatening marine pollutants. The release of these pollutants into the marine aquatic environment leads to significant ecological degradation and a range of non-infectious disorders in fish. Marine pollutants trigger numerous fish bacterial diseases by increasing microbial multiplication in the aquatic environment and suppressing fish immune defense mechanisms. The greater part of these microorganisms is naturally occurring in the aquatic environment. Most disease outbreaks are caused by opportunistic bacterial agents that attack stressed fish. Some infections are more serious and occur in the absence of environmental stressors. Gram-negative bacteria are the most frequent causes of these epizootics, while gram-positive bacterial agents rank second on the critical pathogens list. Vibrio spp., Photobacterium damselae subsp. Piscicida, Tenacibaculum maritimum, Edwardsiella spp., Streptococcus spp., Renibacterium salmoninarum, Pseudomonas spp., Aeromonas spp., and Mycobacterium spp. Are the most dangerous pathogens that attack fish in polluted marine aquatic environments. Effective management strategies and stringent regulations are required to prevent or mitigate the impacts of marine pollutants on aquatic animal health. This review will increase stakeholder awareness about marine pollutants and their impacts on aquatic animal health. It will support competent authorities in developing effective management strategies to mitigate marine pollution, promote the sustainability of commercial marine fisheries, and protect aquatic animal health.

Bacterial diseases in marine fish species: current trends and future prospects in disease management.

The fisheries sub-sector of aquaculture-i.e., the pisciculture industry, contributes significantly to a country's economy, employing a sizable proportion of the population. It also makes important contributions to household food security because the current demand for animal protein cannot be fulfilled by harvesting wild fish from riverines, lakes, dams, and oceans. For good pond management techniques and sustaining fish health, the fisherfolk, and the industry require well-established regulatory structures, efficient disease management strategies, and other extended services. In rearing marine fish, infections resulting from disease outbreaks are a weighty concern because they can cause considerable economic loss due to morbidity and mortality. Consequently, to find effective solutions for the prevention and control of the major diseases limiting fish production in aquaculture, multidisciplinary studies on the traits of potential fish pathogens, the biology of the fish as hosts, and an adequate understanding of the global environmental factors are fundamental. This review highlights the various bacterial diseases and their causative pathogens prevalent in the pisciculture industry and the current solutions while emphasising marine fish species. Given that preexisting methods are known to have several disadvantages, other sustainable alternatives like antimicrobial peptides, synthetic peptides, probiotics, and medicinal treatments have emerged to be an enormous potential solution to these challenges.

Alternatives to animal models to study bacterial infections.

Animal testing has made a significant and unequalled contribution to important discoveries and advancements in the fields of research, medicine, vaccine development, and drug discovery. Each year, millions of animals are sacrificed for various experiments, and this is an ongoing process. However, the debate on the ethical and sensible usage of animals in in vivo experimentation is equally important. The need to explore and adopt newer alternatives to animals so as to comply with the goal of reduce, refine, and replace needs attention. Besides the ever-increasing debate on ethical issues, animal research has additional drawbacks (need of trained labour, requirement of breeding area, lengthy protocols, high expenses, transport barriers, difficulty to extrapolate data from animals to humans, etc.). With this scenario, the present review has been framed to give a comprehensive insight into the possible alternative options worth exploring in this direction especially targeting replacements for animal models of bacterial infections. There have been some excellent reviews discussing on the alternate methods for replacing and reducing animals in drug research. However, reviews that discuss the replacements in the field of medical bacteriology with emphasis on animal bacterial infection models are purely limited. The present review discusses on the use of (a) non-mammalian models and (b) alternative systems such as microfluidic chip-based models and microdosing aiming to give a detailed insight into the prospects of these alternative platforms to reduce the number of animals being used in infection studies. This would enlighten the scientific community working in this direction to be well acquainted with the available new approaches and alternatives so that the 3R strategy can be successfully implemented in the field of antibacterial drug research and testing.

Preventing bacterial disease in poultry in the post-antibiotic era: a case for innate immunity modulation as an alternative to antibiotic use.

The widespread use of antibiotics in the poultry industry has led to the emergence of antibiotic-resistant bacteria, which pose a significant health risk to humans and animals. These public health concerns, which have led to legislation limiting antibiotic use in animals, drive the need to find alternative strategies for controlling and treating bacterial infections. Modulation of the avian innate immune system using immunostimulatory compounds provides a promising solution to enhance poultry immune responses to a broad range of bacterial infections without the risk of generating antibiotic resistance. An array of immunomodulatory compounds have been investigated for their impact on poultry performance and immune responses. However, further research is required to identify compounds capable of controlling bacterial infections without detrimentally affecting bird performance. It is also crucial to determine the safety and effectiveness of these compounds in conjunction with poultry vaccines. This review provides an overview of the various immune modulators known to enhance innate immunity against avian bacterial pathogens in chickens, and describes the mechanisms involved.

Global and regional burden of attributable and associated bacterial antimicrobial resistance avertable by vaccination: modelling study.

INTRODUCTION: Antimicrobial resistance (AMR) is a global health threat with 1.27 million and 4.95 million deaths attributable to and associated with bacterial AMR, respectively, in 2019. Our aim is to estimate the vaccine avertable bacterial AMR burden based on existing and future vaccines at the regional and global levels by pathogen and infectious syndromes. METHODS: We developed a static proportional impact model to estimate the vaccination impact on 15 bacterial pathogens in terms of reduction in age-specific AMR burden estimates for 2019 from the Global Research on Antimicrobial Resistance project in direct proportion to efficacy, coverage, target population for protection, and duration of protection of existing and future vaccines. RESULTS: The AMR burden avertable by vaccination in 2019 was highest for the WHO Africa and South-East Asia regions, for lower respiratory infections, tuberculosis, and bloodstream infections by infectious syndromes, and for Mycobacterium tuberculosis and Streptococcus pneumoniae by pathogen. In the baseline scenario for vaccination of primary age groups against 15 pathogens, we estimated vaccine-avertable AMR burden of 0.51 (95% UI 0.49-0.54) million deaths and 28 (27-29) million disability-adjusted life-years (DALYs) associated with bacterial AMR, and 0.15 (0.14-0.17) million deaths and 7.6 (7.1-8.0) million DALYs attributable to AMR globally in 2019. In the high-potential scenario for vaccination of additional age groups against seven pathogens, we estimated vaccine-avertable AMR burden of an additional 1.2 (1.18-1.23) million deaths and 37 (36-39) million DALYs associated with AMR, and 0.33 (0.32-0.34) million deaths and 10 (9.8-11) million DALYs attributable to AMR globally in 2019. CONCLUSION: Increased coverage of existing vaccines and development of new vaccines are effective means to reduce AMR, and this evidence should inform the full value of vaccine assessments.

Adherence to vaccination guidelines of patients with complete splenectomy in Norway, 2008-2020.

The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of traumatic events or oncological and hematological conditions. These patients are at higher risk of developing diseases caused by encapsulated bacteria throughout their lives. Thus, immunisations are advised for splenectomised persons to prevent infection caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). This study assessed vaccination coverage (VC) among Norwegian patients with surgical asplenia. Using the Nomesco Classification of Surgical Procedures codes, patient information (age, sex, date of initial diagnosis and date of surgery) was acquired from the Norwegian Patient Registry. The National Immunization Register provided information on vaccination status and data of any subsequent invasive bacterial infections were obtained from the Norwegian Surveillance System for Communicable Diseases. From the total population of Norway, 3155 patients who had undergone complete splenectomy were identified. Of these, 914 (29.0%) had received at least one dose of pneumococcal conjugate vaccine (PCV), 1324 (42.0%) at least one dose of pneumococcal polysaccharide vaccine and 589 (18.7%) had received both. Only 4.2% of the patients had received two doses of a meningococcal ACWY conjugate vaccine, while 8.0% of 1467 patients splenectomised after 2014 had received at least two doses of a serogroup B meningococcal vaccine. The VC for Hib was 18.7%. Nearly all splenectomised children under the age of 10 were vaccinated with Hib and PCV as these vaccines are included in the childhood immunisation program. For all vaccines, VC decreased with age. Twenty-nine invasive bacterial infections were registered post-splenectomy in 25 patients. Vaccination according to national recommendations could have prevented at least 8 (28%) of these infections. Our study showed that efforts are required to increase VC of splenectomised individuals in Norway.

Multi-functional approach in the design of smart surfaces to mitigate bacterial infections: a review.

Advancements in biomedical devices are ingenious and indispensable in health care to save millions of lives. However, microbial contamination paves the way for biofilm colonisation on medical devices leading to device-associated infections with high morbidity and mortality. The biofilms elude antibiotics facilitating antimicrobial resistance (AMR) and the persistence of infections. This review explores nature-inspired concepts and multi-functional approaches for tuning in next-generation devices with antibacterial surfaces to mitigate resistant bacterial infections. Direct implementation of natural inspirations, like nanostructures on insect wings, shark skin, and lotus leaves, has proved promising in developing antibacterial, antiadhesive, and self-cleaning surfaces, including impressive SLIPS with broad-spectrum antibacterial properties. Effective antimicrobial touch surfaces, photocatalytic coatings on medical devices, and conventional self-polishing coatings are also reviewed to develop multi-functional antibacterial surfaces to mitigate healthcare-associated infections (HAIs).

Most hospital patients at risk for bacterial infection undergo an anesthetic: implications for infection control practices related to the anesthesia workspace.

PURPOSE: Even with nearly 100% compliance with prophylactic antibiotic protocols, many surgical patients (> 5%) develop surgical site infections, some caused by pathogens transmitted from the anesthesia workspace (e.g., anesthesia machine), including multidrug-resistant Staphylococcus aureus. Reducing contamination of the anesthesia workspace substantively reduces the risk of surgical site infections. We estimated the percentage of hospital patients at risk for health care-associated infections who may benefit from the application of basic preventive measures under the control of anesthesia practitioners (e.g., their hand hygiene). METHODS: We conducted a retrospective cohort study which included every patient admitted to the University of Miami Health System from April 2021 through March 2022 for hospitalization, surgery, emergency department visits, or outpatient visits. Lists were created for the start date and times of every parenteral antibiotic administered and every anesthetic. RESULTS: Among 28,213 patient encounters including parenteral antibiotic(s), more than half (64.3%) also included an anesthetic (99% confidence interval, 62.2 to 66.6). The hypothesis that most antibiotics were administered during encounters when a patient underwent an anesthetic was accepted (P < 0.001). This observation may seem counterintuitive because parenteral antibiotics were administered for fewer than half of the 53,235 anesthetics (34.2%). The result was a consequence of most anesthetics (63.5%) at the health system being conducted in nonoperating room locations, and only 7.2% of such patients received a parenteral antibiotic. CONCLUSIONS: Because approximately two-thirds of patients who receive an intravenous antibiotic also undergo an anesthetic, greater use of effective infection control measures in the anesthesia operating room workspace has the potential to substantively reduce overall rates of hospital infections.

RéSUMé: OBJECTIF: Même avec un respect de près de 100 % des protocoles antibiotiques prophylactiques, bon nombre de patients et patientes en chirurgie (> 5 %) développent des infections du site opératoire, dont certaines sont causées par des agents pathogènes transmis par l'espace de travail anesthésique (p. ex. appareil d'anesthésie), y compris un staphylocoque doré multirésistant. La réduction de la contamination de l'espace de travail anesthésique réduit considérablement le risque d'infections du site opératoire. Nous avons estimé le pourcentage de patientes et patients hospitalisé·es à risque d'infections associées aux soins de santé qui pourraient bénéficier de l'application de mesures préventives de base sous le contrôle de praticiens et praticiennes d'anesthésie (par exemple, leur hygiène des mains). MéTHODE: Nous avons mené une étude de cohorte rétrospective qui comprenait toutes les personnes admises au Système de santé de l'Université de Miami d'avril 2021 à mars 2022 pour une hospitalisation, une intervention chirurgicale, des visites aux urgences ou des consultations externes. Des listes ont été créées pour la date et l'heure de début de chaque antibiotique parentéral administré et de chaque anesthésique. RéSULTATS: Parmi les 28 213 consultations avec les patient·es comprenant des antibiotiques parentéraux, plus de la moitié (64,3 %) comportaient également un anesthésique (intervalle de confiance à 99 %, 62,2 à 66,6). L'hypothèse selon laquelle la plupart des antibiotiques étaient administrés lors de rencontres lorsqu'une personne bénéficiait d'une anesthésie a été acceptée (P < 0,001). Cette observation peut sembler contre-intuitive, car des antibiotiques parentéraux ont été administrés pour moins de la moitié des 53 235 anesthésiques (34,2 %). En effet, la plupart des anesthésies (63,5 %) ont été administrées en dehors de la salle d'opération, et seulement 7,2 % de cette patientèle a reçu un antibiotique parentéral. CONCLUSION: Étant donné qu'environ les deux tiers des patientes et patients qui reçoivent un antibiotique par voie intraveineuse bénéficient également d'une anesthésie, une plus grande utilisation de mesures efficaces de contrôle des infections dans l'espace de travail anesthésique de la salle d'opération pourrait réduire considérablement les taux globaux d'infections hospitalières.

A mathematical model for the impact of disinfectants on the control of bacterial diseases.

Here, we investigate a mathematical model to assess the impact of disinfectants in controlling diseases that spread in the population via direct contacts with the infected persons and also due to bacteria present in the environment. We find that the disease-free and endemic equilibria of the system are related via a transcritical bifurcation whose direction is forward. Our numerical results show that controlling the transmissions of disease through direct contacts and bacteria present in the environment can help in reducing the disease prevalence. Moreover, fostering the recovery rate and the death rate of bacteria play significant roles in disease eradication. Our numerical observations convey that reducing the bacterial density at the source discharged by the infected population through the use of chemicals has prominent effect in disease control. Overall, our findings manifest that the disinfectants of high quality can completely control the bacterial density and the disease outbreak.

Real-world efficacy of antibiotic prophylaxis for upper gastrointestinal bleeding in cirrhotic patients in Japan.

BACKGROUND AND AIMS: Antibiotic prophylaxis is recommended for cirrhotic patients with upper gastrointestinal bleeding (UGIB). However, the frequency of bacterial infection in such patients has remarkably decreased over the decades, which has reduced the necessity for prophylaxis. Therefore, here we investigated the real-world adherence and effectiveness of antibiotic prophylaxis in cirrhotic patients with UGIB in Japan. METHODS: This population-based study was conducted with a Japanese real-world database of the Health, Clinic, and Education Information Evaluation Institute. We enrolled cirrhotic patients who were hospitalized for UGIB between April 2010 and March 2020. After those who died within 24 h and who had aspiration pneumonia at admission were excluded, 1232 patients were analyzed. Rates of 6-week mortality, in-hospital bacterial infection, 30-day readmission, and length of hospital stay were evaluated. RESULTS: Prophylactic antibiotics were prescribed in 142 (11.5%) patients. Multivariate analysis revealed that antibiotic prophylaxis was not significantly associated with either 6-week mortality or bacterial infection. After propensity score matching, the rates of 6-week mortality (7.2% vs. 8.4%, P = 0.810), bacterial infection (9.6% vs. 4.2%, P = 0.082), and 30-day unexpected readmission (7.2% vs. 7.8%, P = 1.000) were similar in patients with and without prophylaxis, whereas the median length of hospital stay was significantly longer in patients with prophylaxis (17 days vs. 13 days, P = 0.013). CONCLUSIONS: Under current real-world circumstances in Japan, prophylactic antibiotics were prescribed in only 11.5% of cirrhotic patients with UGIB and were not associated with better clinical outcomes.

Structured Immune Workup in Healthy Children With a First Episode of Severe Bacterial Infection: A 7-year Single-Center Study.

BACKGROUND: Severe bacterial infections (SBIs) in otherwise healthy children are rare and may represent an underlying impairment of the immune system, including primary immunodeficiency. However, it is unclear whether and how children should be assessed. METHODS: We retrospectively analyzed data from hospital records of previously healthy children aged 3 days to 18 years with SBI, including pleuropneumonia, meningitis, and/or sepsis. Patients were diagnosed or immunologically followed up between 1 January 2013 and 31 March 2020. RESULTS: Among 432 children with SBI, findings could be analyzed in 360. Follow-up data were available for 265 children (74%), of whom 244 (92%) underwent immunological testing. Laboratory abnormalities were found in 51 of 244 patients (21%), with 3 deaths (1%). Fourteen children (6%) had immunodeficiency considered clinically relevant (3 complement deficiencies, 1 autoimmune neutropenia, 10 humoral immunodeficiencies), and 27 (11%) had milder humoral abnormalities or findings suggestive of delayed adaptive immune maturation. CONCLUSIONS: A substantial proportion of children with SBI may benefit from routine immunological testing, revealing (potentially) clinically relevant impaired immune function in 6%-17% of children. The identification of immune abnormalities allows for specific counseling of families and optimization of preventive measures, such as booster vaccinations, to avoid future SBI episodes.

Immunostimulatory DNA Hydrogel Enhances Protective Efficacy of Nanotoxoids against Bacterial Infection.

While vaccines have been highly successful in protecting against various infections, there are still many high-priority pathogens for which there are no clinically approved formulations. To overcome this challenge, researchers have explored the use of nanoparticulate strategies for more effective antigen delivery to the immune system. Along these lines, nanotoxoids are a promising biomimetic platform that leverages cell membrane coating technology to safely deliver otherwise toxic bacterial antigens in their native form for antivirulence vaccination. Here, in order to further boost their immunogenicity, nanotoxoids formulated against staphylococcal α-hemolysin are embedded into a DNA-based hydrogel with immunostimulatory CpG motifs. The resulting nanoparticle-hydrogel composite is injectable and improves the in vivo delivery of vaccine antigens while simultaneously stimulating nearby immune cells. This leads to elevated antibody production and stronger antigen-specific cellular immune responses. In murine models of pneumonia and skin infection caused by methicillin-resistant Staphylococcus aureus, mice vaccinated with the hybrid vaccine formulation are well-protected. This work highlights the benefits of combining nanoparticulate antigen delivery systems with immunostimulatory hydrogels into a single platform, and the approach can be readily generalized to a wide range of infectious diseases.