Nature-Inspired Micro/Nano-Structured Antibacterial Surfaces.

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.

Epidemiology and Management of Infections in Liver Transplant Recipients.

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.

Decolonization and Pathogen Reduction Approaches to Prevent Antimicrobial Resistance and Healthcare-Associated Infections.

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.

Burden of bacterial antimicrobial resistance in low-income and middle-income countries avertible by existing interventions: an evidence review and modelling analysis.

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.

The use of probiotics and prebiotics in decolonizing pathogenic bacteria from the gut; a systematic review and meta-analysis of clinical outcomes.

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).

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.

Gallium and silver-doped titanium surfaces provide enhanced osteogenesis, reduce bone resorption and prevent bacterial infection in co-culture.

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.

Targeted Clindamycin Delivery Systems: Promising Options for Preventing and Treating Bacterial Infections Using Biomaterials.

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.

A Nonbactericidal Anionic Antimicrobial Peptide Provides Prophylactic and Therapeutic Efficacies against Bacterial Infections in Mice by Immunomodulatory-Antithrombotic Duality.

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.

Reducing Hospitalizations and Multidrug-Resistant Organisms via Regional Decolonization in Hospitals and Nursing Homes.

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.

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.