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1.
Appl Microbiol Biotechnol ; 108(1): 386, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896257

ABSTRACT

Bacterial biofilms commonly cause chronic and persistent infections in humans. Bacterial biofilms consist of an inner layer of bacteria and an autocrine extracellular polymeric substance (EPS). Biofilm dispersants (abbreviated as dispersants) have proven effective in removing the bacterial physical protection barrier EPS. Dispersants are generally weak or have no bactericidal effect. Bacteria dispersed from within biofilms (abbreviated as dispersed bacteria) may be more invasive, adhesive, and motile than planktonic bacteria, characteristics that increase the probability that dispersed bacteria will recolonize and cause reinfection. The dispersants should be combined with antimicrobials to avoid the risk of severe reinfection. Dispersant-based nanoparticles have the advantage of specific release and intense penetration, providing the prerequisite for further antibacterial agent efficacy and achieving the eradication of biofilms. Dispersant-based nanoparticles delivered antimicrobial agents for the treatment of diseases associated with bacterial biofilm infections are expected to be an effective measure to prevent reinfection caused by dispersed bacteria. KEY POINTS: • Dispersed bacteria harm and the dispersant's dispersion mechanisms are discussed. • The advantages of dispersant-based nanoparticles in bacteria biofilms are discussed. • Dispersant-based nanoparticles for cutting off reinfection in vivo are highlighted.


Subject(s)
Anti-Bacterial Agents , Biofilms , Nanoparticles , Biofilms/drug effects , Biofilms/growth & development , Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Humans , Bacteria/drug effects , Bacterial Infections/prevention & control , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Reinfection/prevention & control , Extracellular Polymeric Substance Matrix/metabolism , Extracellular Polymeric Substance Matrix/chemistry , Extracellular Polymeric Substance Matrix/drug effects
2.
Sci Rep ; 14(1): 14048, 2024 06 18.
Article in English | MEDLINE | ID: mdl-38890454

ABSTRACT

Regarding several infectious diseases in fish, multiple vaccinations are not favorable. The chimeric multiepitope vaccine (CMEV) harboring several antigens for multi-disease prevention would enhance vaccine efficiency in terms of multiple disease prevention. Herein, the immunogens of tilapia's seven pathogens including E. tarda, F. columnare, F. noatunensis, S. iniae, S. agalactiae, A. hydrophila, and TiLV were used for CMEV design. After shuffling and annotating the B-cell epitopes, 5,040 CMEV primary protein structures were obtained. Secondary and tertiary protein structures were predicted by AlphaFold2 creating 25,200 CMEV. Proper amino acid alignment in the secondary structures was achieved by the Ramachandran plot. In silico determination of physiochemical and other properties including allergenicity, antigenicity, glycosylation, and conformational B-cell epitopes were determined. The selected CMEV (OSLM0467, OSLM2629, and OSLM4294) showed a predicted molecular weight (MW) of 70 kDa, with feasible sites of N- and O-glycosylation, and a number of potentially conformational B-cell epitope residues. Molecular docking, codon optimization, and in-silico cloning were tested to evaluate the possibility of protein expression. Those CMEVs will further elucidate in vitro and in vivo to evaluate the efficacy and specific immune response. This research will highlight the new era of vaccines designed based on in silico structural vaccine design.


Subject(s)
Epitopes, B-Lymphocyte , Fish Diseases , Molecular Docking Simulation , Tilapia , Animals , Tilapia/immunology , Fish Diseases/prevention & control , Fish Diseases/immunology , Fish Diseases/virology , Epitopes, B-Lymphocyte/immunology , Virus Diseases/prevention & control , Virus Diseases/immunology , Bacterial Vaccines/immunology , Viral Vaccines/immunology , Bacterial Infections/prevention & control , Bacterial Infections/immunology , Epitopes/immunology
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 906-910, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38926987

ABSTRACT

OBJECTIVE: To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor (G-CSF) or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT), and to analyze the length of hospital stay, hospitalization cost and post-transplant survival of the patients. METHODS: A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022, the febrile neutropenia, the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed. The length of hospital stay, total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared. RESULTS: A total of 102 cases were included in this study, including 57 cases of multiple myeloma, 36 cases of acute leukaemia, 7 cases of lymphoma, 3 cases of myelodysplastic syndrome, 1 case of light chain amyloidosis, and 1 case of POEMS syndrome. 47 patients received levofloxacin+ G-CSF antibacterial prophylaxis, and 55 patients received G-CSF supportive therapy. In the levofloxacin+ G-CSF group, 40 cases (85.11%) developed febrile neutropenia, and 13 cases (27.66%) were confirmed as bacterial infection. In the G-CSF group, 44 cases (80.00%) developed febrile neutropenia, and 16 cases (29.09%) were bacterial infection. There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups (χ2=0.46,P =0.50; χ2=0.03,P =0.87). The use rate of intravenous antibiotics in the levofloxacin+ G-CSF group was 85.11% (40/47), which was not statistically different from 85.45% (47/55) in the G-CSF group (χ2=0.04,P =0.84). The detection rates of levofloxacin-resistant bacteria in the levofloxacin+ G-CSF group and G-CSF group were 8.57% (3/35) and 21.43% (6/28), respectively, with no statistical difference (χ2=0.65, P >0.05). The median length and median cost of hospitalization in the levofloxacin+ G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan, with no statistically significant differences ( t =3.00,P =0.09; t =0.94,P =0.09). Within 90 days after transplantation, two cases (4.26%) died in the levofloxacin+ G-CSF group and one case (1.82%) died in the G-CSF group, with no statistically significant difference between the two groups (χ2=0.53,P =0.47). CONCLUSION: Application of levofloxacin+ G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.


Subject(s)
Granulocyte Colony-Stimulating Factor , Hematopoietic Stem Cell Transplantation , Levofloxacin , Transplantation, Autologous , Humans , Retrospective Studies , Bacterial Infections/prevention & control , Anti-Bacterial Agents , Male
4.
Lancet ; 403(10442): 2439-2454, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38797180

ABSTRACT

National action plans enumerate many interventions as potential strategies to reduce the burden of bacterial antimicrobial resistance (AMR). However, knowledge of the benefits achievable by specific approaches is needed to inform policy making, especially in low-income and middle-income countries (LMICs) with substantial AMR burden and low health-care system capacity. In a modelling analysis, we estimated that improving infection prevention and control programmes in LMIC health-care settings could prevent at least 337 000 (95% CI 250 200-465 200) AMR-associated deaths annually. Ensuring universal access to high-quality water, sanitation, and hygiene services would prevent 247 800 (160 000-337 800) AMR-associated deaths and paediatric vaccines 181 500 (153 400-206 800) AMR-associated deaths, from both direct prevention of resistant infections and reductions in antibiotic consumption. These estimates translate to prevention of 7·8% (5·6-11·0) of all AMR-associated mortality in LMICs by infection prevention and control, 5·7% (3·7-8·0) by water, sanitation, and hygiene, and 4·2% (3·4-5·1) by vaccination interventions. Despite the continuing need for research and innovation to overcome limitations of existing approaches, our findings indicate that reducing global AMR burden by 10% by the year 2030 is achievable with existing interventions. Our results should guide investments in public health interventions with the greatest potential to reduce AMR burden.


Subject(s)
Developing Countries , Drug Resistance, Bacterial , Humans , Anti-Bacterial Agents/therapeutic use , Sanitation , Bacterial Infections/prevention & control , Hygiene
5.
Lancet ; 403(10443): 2534-2550, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38797178

ABSTRACT

The increasing number of bacterial infections globally that do not respond to any available antibiotics indicates a need to invest in-and ensure access to-new antibiotics, vaccines, and diagnostics. The traditional model of drug development, which depends on substantial revenues to motivate investment, is no longer economically viable without push and pull incentives. Moreover, drugs developed through these mechanisms are unlikely to be affordable for all patients in need, particularly in low-income and middle-income countries. New, publicly funded models based on public-private partnerships could support investment in antibiotics and novel alternatives, and lower patients' out-of-pocket costs, making drugs more accessible. Cost reductions can be achieved with public goods, such as clinical trial networks and platform-based quality assurance, manufacturing, and product development support. Preserving antibiotic effectiveness relies on accurate and timely diagnosis; however scaling up diagnostics faces technological, economic, and behavioural challenges. New technologies appeared during the COVID-19 pandemic, but there is a need for a deeper understanding of market, physician, and consumer behaviour to improve the use of diagnostics in patient management. Ensuring sustainable access to antibiotics also requires infection prevention. Vaccines offer the potential to prevent infections from drug-resistant pathogens, but funding for vaccine development has been scarce in this context. The High-Level Meeting of the UN General Assembly in 2024 offers an opportunity to rethink how research and development can be reoriented to serve disease management, prevention, patient access, and antibiotic stewardship.


Subject(s)
Anti-Bacterial Agents , COVID-19 , Drug Development , Humans , Anti-Bacterial Agents/therapeutic use , COVID-19/prevention & control , SARS-CoV-2 , Bacterial Infections/prevention & control , Bacterial Infections/drug therapy , Bacterial Infections/diagnosis , Drug Resistance, Bacterial , Health Services Accessibility
6.
Molecules ; 29(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38731407

ABSTRACT

The problem of bacterial resistance has become more and more common with improvements in health care. Worryingly, the misuse of antibiotics leads to an increase in bacterial multidrug resistance and the development of new antibiotics has virtually stalled. These challenges have prompted the need to combat bacterial infections with the use of radically different approaches. Taking lessons from the exciting properties of micro-/nano-natural-patterned surfaces, which can destroy cellular integrity, the construction of artificial surfaces to mimic natural functions provides new opportunities for the innovation and development of biomedicine. Due to the diversity of natural surfaces, functional surfaces inspired by natural surfaces have a wide range of applications in healthcare. Nature-inspired surface structures have emerged as an effective and durable strategy to prevent bacterial infection, opening a new way to alleviate the problem of bacterial drug resistance. The present situation of bactericidal and antifouling surfaces with natural and biomimetic micro-/nano-structures is briefly reviewed. In addition, these innovative nature-inspired methods are used to manufacture a variety of artificial surfaces to achieve extraordinary antibacterial properties. In particular, the physical antibacterial effect of nature-inspired surfaces and the functional mechanisms of chemical groups, small molecules, and ions are discussed, as well as the wide current and future applications of artificial biomimetic micro-/nano-surfaces. Current challenges and future development directions are also discussed at the end. In the future, controlling the use of micro-/nano-structures and their subsequent functions will lead to biomimetic surfaces offering great potential applications in biomedicine.


Subject(s)
Anti-Bacterial Agents , Nanostructures , Surface Properties , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Nanostructures/chemistry , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Humans , Bacteria/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control
7.
J Pediatr Hematol Oncol ; 46(5): 225-232, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38691084

ABSTRACT

Children with congenital or acquired asplenia or hyposplenism have an increased risk for severe and even life-threatening infections mainly due to encapsulated bacteria. Current practice focuses on preventing severe infections with timely administration of vaccinations, antibacterial prophylaxis when indicated, and urgent evaluation and treatment of febrile events. As new vaccines are now available for both children and adults with asplenia/hyposplenism, we present an up-to-date recommendation on the prevention and management of acute infections in children with asplenia/hyposplenism.


Subject(s)
Practice Guidelines as Topic , Humans , Child , Splenectomy , Spleen/abnormalities , Infections/etiology , Infections/complications , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Bacterial Infections/prevention & control
8.
Gut Microbes ; 16(1): 2356279, 2024.
Article in English | MEDLINE | ID: mdl-38778521

ABSTRACT

Repeated exposure to antibiotics and changes in the diet and environment shift the gut microbial diversity and composition, making the host susceptible to pathogenic infection. The emergence and ongoing spread of AMR pathogens is a challenging public health issue. Recent evidence showed that probiotics and prebiotics may play a role in decolonizing drug-resistant pathogens by enhancing the colonization resistance in the gut. This review aims to analyze available evidence from human-controlled trials to determine the effect size of probiotic interventions in decolonizing AMR pathogenic bacteria from the gut. We further studied the effects of prebiotics in human and animal studies. PubMed, Embase, Web of Science, Scopus, and CINAHL were used to collect articles. The random-effects model meta-analysis was used to pool the data. GRADE Pro and Cochrane collaboration tools were used to assess the bias and quality of evidence. Out of 1395 citations, 29 RCTs were eligible, involving 2871 subjects who underwent either probiotics or placebo treatment to decolonize AMR pathogens. The persistence of pathogenic bacteria after treatment was 22%(probiotics) and 30.8%(placebo). The pooled odds ratio was 0.59(95% CI:0.43-0.81), favoring probiotics with moderate certainty (p = 0.0001) and low heterogeneity (I2 = 49.2%, p = 0.0001). The funnel plot showed no asymmetry in the study distribution (Kendall'sTau = -1.06, p = 0.445). In subgroup, C. difficile showed the highest decolonization (82.4%) in probiotics group. Lactobacillus-based probiotics and Saccharomyces boulardii decolonize 71% and 77% of pathogens effectively. The types of probiotics (p < 0.018) and pathogens (p < 0.02) significantly moderate the outcome of decolonization, whereas the dosages and regions of the studies were insignificant (p < 0.05). Prebiotics reduced the pathogens from 30% to 80% of initial challenges. Moderate certainty of evidence suggests that probiotics and prebiotics may decolonize pathogens through modulation of gut diversity. However, more clinical outcomes are required on particular strains to confirm the decolonization of the pathogens. Protocol registration: PROSPERO (ID = CRD42021276045).


Subject(s)
Bacteria , Gastrointestinal Microbiome , Prebiotics , Probiotics , Probiotics/administration & dosage , Probiotics/therapeutic use , Probiotics/pharmacology , Humans , Prebiotics/administration & dosage , Gastrointestinal Microbiome/drug effects , Bacteria/classification , Bacteria/isolation & purification , Animals , Treatment Outcome , Anti-Bacterial Agents/pharmacology , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , Gastrointestinal Tract/microbiology
9.
Surg Infect (Larchmt) ; 25(4): 272-290, 2024 May.
Article in English | MEDLINE | ID: mdl-38700753

ABSTRACT

Background: Improvements in liver transplant (LT) outcomes are attributed to advances in surgical techniques, use of potent immunosuppressants, and rigorous pre-LT testing. Despite these improvements, post-LT infections remain the most common complication in this population. Bacteria constitute the most common infectious agents, while fungal and viral infections are also frequently encountered. Multi-drug-resistant bacterial infections develop because of polymicrobial overuse and prolonged hospital stays. Immediate post-LT infections are commonly caused by viruses. Conclusions: Appropriate vaccination, screening of both donor and recipients before LT and antiviral prophylaxis in high-risk individuals are recommended. Antimicrobial drug resistance is common in high-risk LT and associated with poor outcomes; epidemiology and management of these cases is discussed. Additionally, we also discuss the effect of coronavirus disease 2019 (COVID-19) infection and monkeypox in the LT population.


Subject(s)
COVID-19 , Liver Transplantation , Transplant Recipients , Humans , Liver Transplantation/adverse effects , COVID-19/epidemiology , Bacterial Infections/epidemiology , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , SARS-CoV-2 , Mycoses/epidemiology , Mycoses/drug therapy , Virus Diseases/epidemiology , Virus Diseases/prevention & control
10.
Emerg Infect Dis ; 30(6): 1069-1076, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38781679

ABSTRACT

Antimicrobial resistance in healthcare-associated bacterial pathogens and the infections they cause are major public health threats affecting nearly all healthcare facilities. Antimicrobial-resistant bacterial infections can occur when colonizing pathogenic bacteria that normally make up a small fraction of the human microbiota increase in number in response to clinical perturbations. Such infections are especially likely when pathogens are resistant to the collateral effects of antimicrobial agents that disrupt the human microbiome, resulting in loss of colonization resistance, a key host defense. Pathogen reduction is an emerging strategy to prevent transmission of, and infection with, antimicrobial-resistant healthcare-associated pathogens. We describe the basis for pathogen reduction as an overall prevention strategy, the evidence for its effectiveness, and the role of the human microbiome in colonization resistance that also reduces the risk for infection once colonized. In addition, we explore ideal attributes of current and future pathogen-reducing approaches.


Subject(s)
Anti-Bacterial Agents , Cross Infection , Drug Resistance, Bacterial , Humans , Cross Infection/prevention & control , Cross Infection/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbiota/drug effects , Bacterial Infections/prevention & control , Bacterial Infections/microbiology , Infection Control/methods , Bacteria/drug effects
11.
Sci Adv ; 10(14): eadk9754, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38578994

ABSTRACT

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.


Subject(s)
Bacterial Infections , Nanoparticles , Humans , Endothelial Cells , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Liposomes
12.
Acta Biomater ; 180: 154-170, 2024 05.
Article in English | MEDLINE | ID: mdl-38621600

ABSTRACT

Bacterial infection remains a significant problem associated with orthopaedic surgeries leading to surgical site infection (SSI). This unmet medical need can become an even greater complication when surgery is due to malignant bone tumor. In the present study, we evaluated in vitro titanium (Ti) implants subjected to gallium (Ga) and silver (Ag)-doped thermochemical treatment as strategy to prevent SSI and improve osteointegration in bone defects caused by diseases such as osteoporosis, bone tumor, or bone metastasis. Firstly, as Ga has been reported to be an osteoinductive and anti-resorptive agent, its performance in the mixture was proved by studying human mesenchymal stem cells (hMSC) and pre-osteoclasts (RAW264.7) behaviour. Then, the antibacterial potential provided by Ag was assessed by resembling "The Race for the Surface" between hMSC and Pseudomonas aeruginosa in two co-culture methods. Moreover, the presence of quorum sensing molecules in the co-culture was evaluated. The results highlighted the suitability of the mixture to induce osteodifferentiation and reduce osteoclastogenesis in vitro. Furthermore, the GaAg surface promoted strong survival rate and retained osteoinduction potential of hMSCs even after bacterial inoculation. Therefore, GaAg-modified titanium may be an ideal candidate to repair bone defects caused by excessive bone resorption, in addition to preventing SSI. STATEMENT OF SIGNIFICANCE: This article provides important insights into titanium for fractures caused by osteoporosis or bone metastases with high incidence in surgical site infection (SSI) because in this situation bacterial infection can become a major disaster. In order to solve this unmet medical need, we propose a titanium implant modified with gallium and silver to improve osteointegration, reduce bone resorption and avoid bacterial infection. For that aim, we study osteoblast and osteoclast behavior with the main novelty focused on the antibacterial evaluation. In this work, we recreate "the race for the surface" in long-term experiments and study bacterial virulence factors (quorum sensing). Therefore, we believe that our article could be of great interest, providing a great impact on future orthopedic applications.


Subject(s)
Coculture Techniques , Gallium , Mesenchymal Stem Cells , Osteogenesis , Pseudomonas aeruginosa , Silver , Titanium , Titanium/chemistry , Titanium/pharmacology , Silver/pharmacology , Silver/chemistry , Humans , Gallium/pharmacology , Gallium/chemistry , Mice , Mesenchymal Stem Cells/drug effects , Animals , Osteogenesis/drug effects , Pseudomonas aeruginosa/drug effects , Bone Resorption/pathology , Surface Properties , RAW 264.7 Cells , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacterial Infections/prevention & control
13.
Int J Mol Sci ; 25(8)2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38673971

ABSTRACT

Targeted therapy represents a real opportunity to improve the health and lives of patients. Developments in this field are confirmed by the fact that the global market for drug carriers was worth nearly $40 million in 2022. For this reason, materials engineering and the development of new drug carrier compositions for targeted therapy has become a key area of research in pharmaceutical drug delivery in recent years. Ceramics, polymers, and metals, as well as composites, are of great interest, as when they are appropriately processed or combined with each other, it is possible to obtain biomaterials for hard tissues, soft tissues, and skin applications. After appropriate modification, these materials can release the drug directly at the site requiring a therapeutic effect. This brief literature review characterizes routes of drug delivery into the body and discusses biomaterials from different groups, options for their modification with clindamycin, an antibiotic used for infections caused by aerobic and anaerobic Gram-positive bacteria, and different methods for the final processing of carriers. Examples of coating materials for skin wound healing, acne therapy, and bone tissue fillers are given. Furthermore, the reasons why the use of antibiotic therapy is crucial for a smooth and successful recovery and the risks of bacterial infections are explained. It was demonstrated that there is no single proven delivery scheme, and that the drug can be successfully released from different carriers depending on the destination.


Subject(s)
Anti-Bacterial Agents , Bacterial Infections , Biocompatible Materials , Clindamycin , Drug Delivery Systems , Humans , Clindamycin/therapeutic use , Clindamycin/administration & dosage , Biocompatible Materials/chemistry , Drug Delivery Systems/methods , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Drug Carriers/chemistry , Animals
14.
J Med Chem ; 67(9): 7487-7503, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38688020

ABSTRACT

Although bactericidal cationic antimicrobial peptides (AMPs) have been well characterized, less information is available about the antibacterial properties and mechanisms of action of nonbactericidal AMPs, especially nonbactericidal anionic AMPs. Herein, a novel anionic antimicrobial peptide (Gy-CATH) with a net charge of -4 was identified from the skin of the frog Glyphoglossus yunnanensis. Gy-CATH lacks direct antibacterial effects but exhibits significantly preventive and therapeutic capacities in mice that are infected with Staphylococcus aureus, Enterobacteriaceae coli, methicillin-resistant Staphylococcus aureus (MRSA), or carbapenem-resistant E. coli (CREC). In vitro and in vivo investigations proved the regulation of Gy-CATH on neutrophils and macrophages involved in the host immune defense against infection. Moreover, Gy-CATH significantly reduced the extent of pulmonary fibrin deposition and prevented thrombosis in mice, which was attributed to the regulatory role of Gy-CATH in physiological anticoagulants and platelet aggregation. These findings show that Gy-CATH is a potential candidate for the treatment of bacterial infection.


Subject(s)
Anti-Bacterial Agents , Antimicrobial Peptides , Animals , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Antimicrobial Peptides/therapeutic use , Anura , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Escherichia coli/drug effects , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/chemistry , Fibrinolytic Agents/therapeutic use , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Immunologic Factors/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Thrombosis/prevention & control , Thrombosis/drug therapy
15.
JAMA ; 331(18): 1544-1557, 2024 05 14.
Article in English | MEDLINE | ID: mdl-38557703

ABSTRACT

Importance: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. Objective: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. Design, Setting, and Participants: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. Exposures: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). Main Outcomes and Measures: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). Results: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). Conclusions and Relevance: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths.


Subject(s)
Anti-Infective Agents, Local , Bacterial Infections , Cross Infection , Drug Resistance, Multiple, Bacterial , Health Facilities , Infection Control , Aged , Humans , Administration, Intranasal , Anti-Infective Agents, Local/administration & dosage , Anti-Infective Agents, Local/therapeutic use , Bacterial Infections/economics , Bacterial Infections/microbiology , Bacterial Infections/mortality , Bacterial Infections/prevention & control , Baths/methods , California/epidemiology , Chlorhexidine/administration & dosage , Chlorhexidine/therapeutic use , Cross Infection/economics , Cross Infection/microbiology , Cross Infection/mortality , Cross Infection/prevention & control , Health Facilities/economics , Health Facilities/standards , Health Facilities/statistics & numerical data , Hospitalization/economics , Hospitalization/statistics & numerical data , Hospitals/standards , Hospitals/statistics & numerical data , Infection Control/methods , Iodophors/administration & dosage , Iodophors/therapeutic use , Nursing Homes/economics , Nursing Homes/standards , Nursing Homes/statistics & numerical data , Patient Transfer , Quality Improvement/economics , Quality Improvement/statistics & numerical data , Skin Care/methods , Universal Precautions
17.
Trends Mol Med ; 30(6): 524-526, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38485647

ABSTRACT

Bacterial infections are an urgent public health priority. The application of mRNA vaccine technology to prevent bacterial infections is a promising therapeutic strategy undergoing active development. This article discusses recent advances and limitations of mRNA vaccines to prevent bacterial diseases and provides perspectives on future research directions.


Subject(s)
Bacterial Infections , mRNA Vaccines , Humans , Bacterial Infections/prevention & control , Bacterial Infections/immunology , Animals , Bacterial Vaccines/immunology , Vaccines, Synthetic/immunology , RNA, Messenger/genetics , RNA, Messenger/immunology , Vaccine Development/methods
18.
Environ Res ; 252(Pt 1): 118720, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38537740

ABSTRACT

Bovine mastitis (BM) is mainly caused by bacterial infection that has a highly impact on dairy production, affecting both economic viability and animal well-being. A cross-sectional study was conducted in dairy farms to investigate the prevalence and antimicrobial resistance patterns of bacterial pathogens associated with BM. The analysis revealed that Staphylococcus (49%), Escherichia (16%), Pseudomonas (11%), and Klebsiella (6%) were the primary bacterial pathogens associated with mastitis. A significant proportion of Staphylococcus strains displayed multiple drug resistance. The use of disinfectants is an important conventional measure to control the pathogenic bacteria in the environment. Bacteriophages (Phages), possessing antibacterial properties, are natural green and effective disinfectants. Moreover, they mitigate the risk of generating harmful disinfection byproducts, which are commonly associated with traditional disinfection methods. Based on the primary bacterial pathogens associated with mastitis in the investigation area, a phage cocktail, named SPBC-SJ, containing seven phages capable of lysing S. aureus, E. coli, and P. aeruginosa was formulated. SPBC-SJ exhibited superior bactericidal activity and catharsis effect on pollutants (glass surface) compared to chemical disinfectants. Clinical trials confirmed that the SPBC-SJ-based superimposed disinfection group (phage combined with chemical disinfectants) not only cut down the dosage of disinfectants used, but significantly reduced total bacterial counts on the ground and in the feeding trough of dairy farms. Furthermore, SPBC-SJ significantly reduced the abundance of Staphylococcus and Pseudomonas in the environment of the dairy farm. These findings suggest that phage-based superimposed disinfection is a promising alternative method to combat mastitis pathogens in dairy farms due to its highly efficient and environmentally-friendly properties.


Subject(s)
Bacteriophages , Dairying , Disinfection , Mastitis, Bovine , Cattle , Animals , Mastitis, Bovine/prevention & control , Mastitis, Bovine/microbiology , Disinfection/methods , Female , Cross-Sectional Studies , Disinfectants/pharmacology , Bacterial Infections/prevention & control , Bacterial Infections/veterinary
20.
Infection ; 52(2): 385-402, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38308075

ABSTRACT

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.


Subject(s)
Bacterial Infections , Phage Therapy , Surgical Wound , Humans , Animals , Bacteria , Surgical Wound Infection/prevention & control , Bacterial Infections/prevention & control , Anti-Bacterial Agents/therapeutic use
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