Differential transcriptomic host responses in the early phase of viral and bacterial infections in human lung tissue explants ex vivo.

BACKGROUND: The first 24 h of infection represent a critical time window in interactions between pathogens and host tissue. However, it is not possible to study such early events in human lung during natural infection due to lack of clinical access to tissue this early in infection. We, therefore, applied RNA sequencing to ex vivo cultured human lung tissue explants (HLTE) from patients with emphysema to study global changes in small noncoding RNA, mRNA, and long noncoding RNA (lncRNA, lincRNA) populations during the first 24 h of infection with influenza A virus (IAV), Mycobacterium bovis Bacille Calmette-Guerin (BCG), and Pseudomonas aeruginosa. RESULTS: Pseudomonas aeruginosa caused the strongest expression changes and was the only pathogen that notably affected expression of microRNA and PIWI-associated RNA. The major classes of long RNAs (> 100 nt) were represented similarly among the RNAs that were differentially expressed upon infection with the three pathogens (mRNA 77-82%; lncRNA 15-17%; pseudogenes 4-5%), but lnc-DDX60-1, RP11-202G18.1, and lnc-THOC3-2 were part of an RNA signature (additionally containing SNX10 and SLC8A1) specifically associated with IAV infection. IAV infection induced brisk interferon responses, CCL8 being the most strongly upregulated mRNA. Single-cell RNA sequencing identified airway epithelial cells and macrophages as the predominant IAV host cells, but inflammatory responses were also detected in cell types expressing few or no IAV transcripts. Combined analysis of bulk and single-cell RNAseq data identified a set of 6 mRNAs (IFI6, IFI44L, IRF7, ISG15, MX1, MX2) as the core transcriptomic response to IAV infection. The two bacterial pathogens induced qualitatively very similar changes in mRNA expression and predicted signaling pathways, but the magnitude of change was greater in P. aeruginosa infection. Upregulation of GJB2, VNN1, DUSP4, SerpinB7, and IL10, and downregulation of PKMYT1, S100A4, GGTA1P, and SLC22A31 were most strongly associated with bacterial infection. CONCLUSIONS: Human lung tissue mounted substantially different transcriptomic responses to infection by IAV than by BCG and P. aeruginosa, whereas responses to these two divergent bacterial pathogens were surprisingly similar. This HLTE model should prove useful for RNA-directed pathogenesis research and tissue biomarker discovery during the early phase of infections, both at the tissue and single-cell level.

Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.

Multidrug-resistant ESKAPE pathogens are the leading cause of hospital-acquired infections across the globe, posing challenges for clinicians. Random genetic mutations and constant exposure to antibiotics in healthcare settings result in strains resistant to commonly used antibiotics, creating life-threatening conditions. If the magic of "antibiotics" is to be sustained, a new class of antimicrobials against novel targets is urgently needed. This necessitates understanding and identifying novel biochemical pathways and bacterial virulence factors that can be targeted for therapeutic interventions. Keeping in view the unambiguous role of the kinome in bacterial survival and virulence, this review provides a survey of effector bacterial kinases involved in evading host immune responses and drug resistance. The formation of biofilms is a critical feature associated with the pathogenesis and survival of ESKAPE organisms in the hostile host milieu. Hence, kinases involved in the biofilm pathway are also elucidated for clinical relevance. In addition, endeavors in the development of therapeutics against ESKAPE kinases are also summarized to provide direction to researchers pursuing the field.

The potential use of bacteriophages as antibacterial agents in dental infection.

Dental infections, such as apical Periodontitis, periodontitis, and peri-implantitis (PI), are closely associated with specific bacterial species, including Streptococcus mutans (S. mutans), Porphyromonas gingivalis (P. gingivalis), and Fusobacterium nucleatum (F. nucleatum), among others. Antibiotics are extensively utilized for prophylactic and therapeutic purposes in the treatment of dental infections and other dental-related issues. Unfortunately, the rapid emergence of antimicrobial resistance has accompanied the increased use of antibiotics in recent years. Specific bacterial pathogens have reached a critical stage of antibiotic resistance, characterized by the proliferation of pan-resistant strains and the scarcity of viable therapeutic alternatives. Therapeutic use of particular bacteriophage (phage) particles that target bacterial pathogens is one potential alternative to antibiotics that are now being seriously considered for treating bacterial illnesses. A kind of virus known as a phage is capable of infecting and eliminating bacteria. Because they can't infect cells in plants and animals, phages might be a harmless substitute for antibiotics. To control oral disorders including periodontitis and dental caries, several research have been conducted in this area to study and identify phages from human saliva and dental plaque. The capacity of these agents to disturb biofilms expands their effectiveness against dental plaque biofilms and oral pathogens in cases of periodontitis, PI, and apical periodontitis. This review summarizes the current antibacterial properties of phages used to treat a variety of dental infections, such as periodontitis, peri-implantitis, infected dentin, and apical periodontitis.

A search for bacteria identified from cerebrospinal fluid shunt infections in previous surgical events.

Shunt infections are a common complication when treating hydrocephalus by cerebrospinal fluid (CSF) shunt placement. The source of infecting pathogens is not well understood. One hypothesis, which we explored here, is that microorganisms persist chronically in the host long before a symptomatic infection occurs and may be detectable in surgical events preceding infection. A cohort of 13 patients was selected, for which CSF samples were available from an infection episode and from a previous surgery event, which was either an initial shunt placement or a revision. Microbiota were analyzed both directly from CSF and from isolates cultured from CSF on aerobic and anaerobic media. The detection and identification of bacteria was done with high throughput DNA sequencing methods and mass spectrometry. The presence of bacteria was confirmed in 4 infection samples, of which 2 were after initial placement and 2 after revision surgery. Taxonomic identification was consistent with clinical microbiology laboratory results. Bacteria were not detected in any of the CSF samples collected at the time of the previous surgical events. While our findings do not provide direct evidence for long-term persistence of pathogens, they suggest the need for consideration of additional source material, such as biofilm and environmental swabs, and/or the use of more sensitive and specific analytical methods.

Parasitological prevalence of scabies and secondary bacterial infections among scabies suspected patients at Borumeda General Hospital, Northeast Ethiopia.

BACKGROUND: Scabies disproportionately affects people in resource-poor areas. Clinical diagnosis risks misdiagnosis due to resemblance to other skin diseases, but laboratory confirmation improves accuracy. Scabies allow for secondary bacterial infections. Associated bacteria exacerbate scabies and antibiotic resistance. Ethiopian scabies diagnosis relies solely on clinical exams without confirming parasites or investigating secondary bacterial infections. This study aims to identify parasites via scraping, isolate secondary bacteria, and evaluate their antibiotic susceptibility profiles. METHODS: A hospital based cross-sectional study was conducted from September 2022 to July 2023 among scabies suspected patients who visited the dermatology clinic at Borumeda General Hospital in Northeast Ethiopia. A systematic random sampling technique was used to select 422 study participants. Socio-demographic, hygiene, and clinical characteristics data were collected via face-to-face interviews and observation. Skin scrapings for parasitological investigations and swab samples for microbiological investigations were collected and transported for analysis and drug susceptibility testing. Descriptive statistics and logistic regression analysis were employed to assess risk factors. RESULT: Among 422 skin scraping samples, 156 (37.0%) cases of scabies were microscopically confirmed. Bed-sharing and having contact history were independent predictors of microscopically confirmed scabies. The prevalence of secondary bacterial infections among scabies-confirmed patients was 35.9% (56/156). The most prevalent bacterial species were Staphylococcus aureus, coagulase-negative staphylococci, and Streptococcus pyogenes. Tetracycline for Gram-positive bacteria and ampicillin for Gram-negative bacteria showed the highest rate of resistance. In both Gram-positive and Gram-negative strains, multidrug resistance was also observed. CONCLUSION: This study found that over one-third of skin scrapings tested positive for scabies. Additionally, more than one-third of scabies cases were complicated by secondary bacterial infections. Improved scabies diagnosis and consideration of secondary bacterial infections are important for better controlling this neglected tropical disease.

Infections in decompensated cirrhosis: Pathophysiology, management, and research agenda.

Bacterial infections in patients with cirrhosis lead to a 4-fold increase in mortality. Immune dysfunction in cirrhosis further increases the risk of bacterial infections, in addition to alterations in the gut microbiome, which increase the risk of pathogenic bacteria. High rates of empiric antibiotic use contribute to increased incidence of multidrug-resistant organisms and further increases in mortality. Despite continous advances in the field, major unknowns regarding interactions between the immune system and the gut microbiome and strategies to reduce infection risk and improve mortality deserve further investigation. Here, we highlight the unknowns in these major research areas and make a proposal for a research agenda to move toward improving disease progression and outcomes in patients with cirrhosis and infections.

Phenotypic heterogeneity in bacteria: the rise of antibiotic persistence, clinical implications, and therapeutic opportunities.

The rising incidence of antimicrobial resistance (AMR) and the diminishing antibiotics discovery pipeline have created an unprecedented scenario where minor infections could become untreatable. AMR phenomenon is genetically encoded, and various genetic determinants have been implicated in their emergence and spread. Nevertheless, several non-genetic phenomena are also involved in antibiotic treatment failure which requires a systematic investigation. It has been observed that in an isogenic population of bacteria, not all cells behave or respond the same way to an antibiotic, because of the inherent heterogeneity among them. This heterogeneity is not always heritable but rather phenotypic. Three distinct types of phenotypic heterogeneity, namely tolerance, persistence, and heteroresistance have been observed in bacteria having significant clinical implications influencing the treatment outcome. While tolerance is when a population can survive high doses of antibiotics without changing the minimum inhibitory concentration (MIC) of the drug, persistence occurs in a subpopulation of bacteria that can survive exposure to high antibiotic doses. In contrast, when a subpopulation shows a very high MIC in comparison to the rest of the population, the phenomenon is called heteroresistance. In this article, we have highlighted bacterial persistence with a focus on their emergence and the underlying molecular mechanisms. Moreover, we have tried to associate the genome-wide methylation status with that of the heterogeneity at a single-cell level that may explain the role of epigenetic mechanisms in the development of persistence.

Review: Known, Emerging, and Remerging Pharyngitis Pathogens.

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents-yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This article (part 1 of 3) summarizes the impact of acute pharyngitis on the health care system and reviews the etiologic agents of acute pharyngitis, including both emerging and reemerging pathogens that health care providers should consider when evaluating their patients. Finally, it sets the stage for parts 2 and 3, which discuss the current and evolving state of diagnostic testing for acute pharyngitis.

Molecular characterisation of virulence genes in bacterial pathogens from daycare centres in Ile-Ife, Nigeria: implications for infection control.

BACKGROUND: Daycare centres play a critical role in early childhood development but are high-risk environments for infectious disease transmission due to close physical contact, shared toys, inadequate hygiene, and poor ventilation. These risks are especially concerning in low- and middle-income countries (LMICs) like Nigeria, where resources for infection control may be limited. This study aimed to identify and characterise virulence genes in bacterial isolates from daycare centres in Ile-Ife, Nigeria, to assess infection risks. METHODS: Between November 2017 and July 2019, 233 samples were collected from 76 children, 33 daycare workers, and 124 fomites in 17 daycare centres. The bacterial isolates were analysed using conventional PCR and RAPD analysis to detect the presence of virulence genes. The frequency of crucial virulence genes and the prevalence of each bacterial species were recorded. RESULTS: Key virulence genes were detected, including fimH in Klebsiella species (22.73% of Gram-negative isolates), algD in Pseudomonas aeruginosa (50%), and icaA and cna in Staphylococcus aureus (16.67%). Staphylococcus aureus was the most prevalent species (35%), followed by Klebsiella (28%) and Pseudomonas aeruginosa (20%). CONCLUSION: This study highlights the presence of virulent bacterial pathogens in daycare environments, posing a severe infection risk to children. To mitigate these risks, it is essential to implement enhanced infection control measures, such as regular microbial screening, improved hand hygiene practices, and disinfection protocols for fomites. Training programs for daycare workers on hygiene practices and routine monitoring could also significantly reduce infection transmission. These interventions are vital for safeguarding the health of daycare children in Nigeria and similar settings globally.

How nanomaterials act against bacterial structures? a narrative review focusing on nanoparticle molecular mechanisms.

OBJECTIVE: In recent years, significant progress has been made in the field of nanotechnology for the treatment and prevention of biofilm formation and Multidrug-resistant bacteria (MDR). MDR bacteria challenges is hazardous when microorganisms induce the formation of biofilms, which amplify resistance to antibiotics and promote the development of multidrug-resistant conditions. The unique physicochemical properties of certain nanomaterials make nanotechnology a promising option for combating MDR infections. Several studies have introduced nanomaterials with different antibacterial mechanisms that can effectively destroy MDR bacteria and their biofilms. This study reviews the research results, focusing on the various nanoparticle mechanisms that target bacterial structures. METHOD: To accomplish this study, we conducted investigations to gather articles and relevant studies from validated medical databases such as Scopus, PubMed, Google Scholar, and Web of Science. The selected publications from 2007 to 2023. In this review, we provide a brief overview of nanoparticles, their mechanisms, and how they function against the structure of bacteria. Furthermore, we discuss the recent advancements in using certain nanoparticles to combat infection-induced biofilms and complications caused by multidrug resistance. FINDING: Our findings demonstrate that various nanoparticles have the potential to effectively overcome bacterial infectious diseases by targeting biofilms and antibiotic-resistant strains. Additionally, the development of a new drug delivery approach based on nanosystems shows promise in overcoming antibiotic resistance and biofilms.

Emerging strategies for treating medical device and wound-associated biofilm infections.

Bacterial infections represent a significant global threat to human health, leading to considerable economic losses through increased healthcare costs and reduced productivity. One major challenge in treating these infections is the presence of biofilms - structured bacterial communities that form protective barriers, making traditional treatments less effective. Additionally, the rise of antibiotic-resistant bacteria has exacerbated treatment difficulties. To address these challenges, researchers are developing and exploring innovative approaches to combat biofilm-related infections. This mini-review highlights recent advancements in the following key areas: surface anti-adhesion technologies, electricity, photo/acoustic-active materials, endogenous mimicking agents, and innovative drug delivery systems. These strategies aim to prevent biofilm formation, disrupt existing biofilms, and enhance the efficacy of antimicrobial treatments. Currently, these approaches show great potential for applications in medical fields such as medical device and wound - associated biofilm infections. By summarizing these developments, this mini-review provides a comprehensive resource for researchers seeking to advance the management and treatment of biofilm-associated infections.

Mechanistic Insights into Clinically Relevant Ribosome-Targeting Antibiotics.

Antibiotics targeting the bacterial ribosome are essential to combating bacterial infections. These antibiotics bind to various sites on the ribosome, inhibiting different stages of protein synthesis. This review provides a comprehensive overview of the mechanisms of action of clinically relevant antibiotics that target the bacterial ribosome, including macrolides, lincosamides, oxazolidinones, aminoglycosides, tetracyclines, and chloramphenicol. The structural and functional details of antibiotic interactions with ribosomal RNA, including specific binding sites, interactions with rRNA nucleotides, and their effects on translation processes, are discussed. Focus is placed on the diversity of these mechanisms and their clinical implications in treating bacterial infections, particularly in the context of emerging resistance. Understanding these mechanisms is crucial for developing novel therapeutic agents capable of overcoming bacterial resistance.

Zebrafish as an effective model for evaluating phage therapy in bacterial infections: a promising strategy against human pathogens.

The escalating prevalence of antibiotic-resistant bacterial infections necessitates urgent alternative therapeutic strategies. Phage therapy, which employs bacteriophages to specifically target pathogenic bacteria, emerges as a promising solution. This review examines the efficacy of phage therapy in zebrafish models, both embryos and adults, which are proven and reliable for simulating human infectious diseases. We synthesize findings from recent studies that utilized these models to assess phage treatments against various bacterial pathogens, including Enterococcus faecalis, Pseudomonas aeruginosa, Mycobacterium abscessus, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli. Methods of phage administration, such as circulation injection and bath immersion, are detailed alongside evaluations of survival rates and bacterial load reductions. Notably, combination therapies of phages with antibiotics show enhanced efficacy, as evidenced by improved survival rates and synergistic effects in reducing bacterial loads. We also discuss the transition from zebrafish embryos to adult models, emphasizing the increased complexity of immune responses. This review highlights the valuable contribution of the zebrafish model to advancing phage therapy research, particularly in the face of rising antibiotic resistance and the urgent need for alternative treatments.

Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050.

BACKGROUND: Antimicrobial resistance (AMR) poses an important global health challenge in the 21st century. A previous study has quantified the global and regional burden of AMR for 2019, followed with additional publications that provided more detailed estimates for several WHO regions by country. To date, there have been no studies that produce comprehensive estimates of AMR burden across locations that encompass historical trends and future forecasts. METHODS: We estimated all-age and age-specific deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 22 pathogens, 84 pathogen-drug combinations, and 11 infectious syndromes in 204 countries and territories from 1990 to 2021. We collected and used multiple cause of death data, hospital discharge data, microbiology data, literature studies, single drug resistance profiles, pharmaceutical sales, antibiotic use surveys, mortality surveillance, linkage data, outpatient and inpatient insurance claims data, and previously published data, covering 520 million individual records or isolates and 19 513 study-location-years. We used statistical modelling to produce estimates of AMR burden for all locations, including those with no data. Our approach leverages the estimation of five broad component quantities: the number of deaths involving sepsis; the proportion of infectious deaths attributable to a given infectious syndrome; the proportion of infectious syndrome deaths attributable to a given pathogen; the percentage of a given pathogen resistant to an antibiotic of interest; and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden attributable to and associated with AMR, which we define based on two counterfactuals; respectively, an alternative scenario in which all drug-resistant infections are replaced by drug-susceptible infections, and an alternative scenario in which all drug-resistant infections were replaced by no infection. Additionally, we produced global and regional forecasts of AMR burden until 2050 for three scenarios: a reference scenario that is a probabilistic forecast of the most likely future; a Gram-negative drug scenario that assumes future drug development that targets Gram-negative pathogens; and a better care scenario that assumes future improvements in health-care quality and access to appropriate antimicrobials. We present final estimates aggregated to the global, super-regional, and regional level. FINDINGS: In 2021, we estimated 4·71 million (95% UI 4·23-5·19) deaths were associated with bacterial AMR, including 1·14 million (1·00-1·28) deaths attributable to bacterial AMR. Trends in AMR mortality over the past 31 years varied substantially by age and location. From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years yet increased by over 80% for adults 70 years and older. AMR mortality decreased for children younger than 5 years in all super-regions, whereas AMR mortality in people 5 years and older increased in all super-regions. For both deaths associated with and deaths attributable to AMR, meticillin-resistant Staphylococcus aureus increased the most globally (from 261 000 associated deaths [95% UI 150 000-372 000] and 57 200 attributable deaths [34 100-80 300] in 1990, to 550 000 associated deaths [500 000-600 000] and 130 000 attributable deaths [113 000-146 000] in 2021). Among Gram-negative bacteria, resistance to carbapenems increased more than any other antibiotic class, rising from 619 000 associated deaths (405 000-834 000) in 1990, to 1·03 million associated deaths (909 000-1·16 million) in 2021, and from 127 000 attributable deaths (82 100-171 000) in 1990, to 216 000 (168 000-264 000) attributable deaths in 2021. There was a notable decrease in non-COVID-related infectious disease in 2020 and 2021. Our forecasts show that an estimated 1·91 million (1·56-2·26) deaths attributable to AMR and 8·22 million (6·85-9·65) deaths associated with AMR could occur globally in 2050. Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean. Increases in deaths attributable to AMR will be largest among those 70 years and older (65·9% [61·2-69·8] of all-age deaths attributable to AMR in 2050). In stark contrast to the strong increase in number of deaths due to AMR of 69·6% (51·5-89·2) from 2022 to 2050, the number of DALYs showed a much smaller increase of 9·4% (-6·9 to 29·0) to 46·5 million (37·7 to 57·3) in 2050. Under the better care scenario, across all age groups, 92·0 million deaths (82·8-102·0) could be cumulatively averted between 2025 and 2050, through better care of severe infections and improved access to antibiotics, and under the Gram-negative drug scenario, 11·1 million AMR deaths (9·08-13·2) could be averted through the development of a Gram-negative drug pipeline to prevent AMR deaths. INTERPRETATION: This study presents the first comprehensive assessment of the global burden of AMR from 1990 to 2021, with results forecasted until 2050. Evaluating changing trends in AMR mortality across time and location is necessary to understand how this important global health threat is developing and prepares us to make informed decisions regarding interventions. Our findings show the importance of infection prevention, as shown by the reduction of AMR deaths in those younger than 5 years. Simultaneously, our results underscore the concerning trend of AMR burden among those older than 70 years, alongside a rapidly ageing global community. The opposing trends in the burden of AMR deaths between younger and older individuals explains the moderate future increase in global number of DALYs versus number of deaths. Given the high variability of AMR burden by location and age, it is important that interventions combine infection prevention, vaccination, minimisation of inappropriate antibiotic use in farming and humans, and research into new antibiotics to mitigate the number of AMR deaths that are forecasted for 2050. FUNDING: UK Department of Health and Social Care's Fleming Fund using UK aid, and the Wellcome Trust.

Increasing trends of antibiotic resistance in Uganda: analysis of the national antimicrobial resistance surveillance data, 2018-2021.

BACKGROUND: Continuous monitoring of antimicrobial resistance (AMR) in Uganda involves testing bacterial isolates from clinical samples at national and regional hospitals. Although the National Microbiology Reference Laboratory (NMRL) analyzes these isolates for official AMR surveillance data, there's limited integration into public health planning. To enhance the utilization of NMRL data to better inform drug selection and public health strategies in combating antibiotic resistance, we evaluated the trends and spatial distribution of AMR to common antibiotics used in Uganda. METHODS: We analyzed data from pathogenic bacterial isolates from blood, cerebrospinal, peritoneal, and pleural fluid from AMR surveillance data for 2018-2021. We calculated the proportions of isolates that were resistant to common antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR resistance over the study period. RESULTS: Out of 537 isolates with 15 pathogenic bacteria, 478 (89%) were from blood, 34 (6.3%) were from pleural fluid, 21 (4%) were from cerebrospinal fluid, and 4 (0.7%) were from peritoneal fluid. The most common pathogen was Staphylococcus aureus (20.1%), followed by Salmonella species (18.8%). The overall change in resistance over the four years was 63-84% for sulfonamides, fluoroquinolones macrolides (46-76%), phenicols (48-71%), penicillins (42-97%), ß-lactamase inhibitors (20-92%), aminoglycosides (17-53%), cephalosporins (8.3-90%), carbapenems (5.3-26%), and glycopeptides (0-20%). There was a fluctuation in resistance of Staphylococcus aureus to methicillin (60%-45%) (using cefoxitin resistance as a surrogate for oxacillin resistance) Among gram-negative organisms, there were increases in resistance to tetracycline (29-78% p < 0.001), ciprofloxacin (17-43%, p = 0.004), ceftriaxone (8-72%, p = 0.003), imipenem (6-26%, p = 0.004), and meropenem (7-18%, p = 0.03). CONCLUSION: The study highlights a concerning increase in antibiotic resistance rates over four years, with significant increase in resistance observed across different classes of antibiotics for both gram-positive and gram-negative organisms. This increased antibiotic resistance, particularly to commonly used antibiotics like ceftriaxone and ciprofloxacin, makes adhering to the WHO's Access, Watch, and Reserve (AWaRe) category even more critical. It also emphasizes how important it is to guard against the growing threat of antibiotic resistance by appropriately using medicines, especially those that are marked for "Watch" or "Reserve."

Phenotypic and genotypic perspectives on detection methods for bacterial antimicrobial resistance in a One Health context: research progress and prospects.

The widespread spread of bacterial antimicrobial resistance (AMR) and multidrug-resistant bacteria poses a significant threat to global public health. Traditional methods for detecting bacterial AMR are simple, reproducible, and intuitive, requiring long time incubation and high labor intensity. To quickly identify and detect bacterial AMR is urgent for clinical treatment to reduce mortality rate, and many new methods and technologies were required to be developed. This review summarizes the current phenotypic and genotypic detection methods for bacterial AMR. Phenotypic detection methods mainly include antimicrobial susceptibility tests, while genotypic detection methods have higher sensitivity and specificity and can detect known or even unknown drug resistance genes. However, most of the current tests are either genotypic or phenotypic and rarely combined. Combining the advantages of phenotypic and genotypic methods, combined with the joint application of multiple rapid detection methods may be the trend for future AMR testing. Driven by rapid diagnostic technology, big data analysis, and artificial intelligence, detection methods of bacterial AMR are expected to constantly develop and innovate. Adopting rational detection methods and scientific data analysis can better address the challenges of bacterial AMR and ensure human health and social well-being.

Antimicrobial peptide-based strategies to overcome antimicrobial resistance.

Antibiotic resistance has emerged as a global threat, rendering the existing conventional treatment strategies ineffective. In view of this, antimicrobial peptides (AMPs) have proven to be potent alternative therapeutic interventions with a wide range of applications in clinical health. AMPs are small peptides produced naturally as a part of the innate immune responses against a broad range of bacterial, fungal and viral pathogens. AMPs present a myriad of advantages over traditional antibiotics, including their ability to target multiple sites, reduced susceptibility to resistance development, and high efficacy at low doses. These peptides have demonstrated notable potential in inhibiting microbes resistant to traditional antibiotics, including the notorious ESKAPE pathogens, recognized as the primary culprits behind nosocomial infections. AMPs, with their multifaceted benefits, emerge as promising candidates in the ongoing efforts to combat the escalating challenges posed by antibiotic resistance. This in-depth review provides a detailed discussion on AMPs, encompassing their classification, mechanism of action, and diverse clinical applications. Focus has been laid on combating newly emerging drug-resistant organisms, emphasizing the significance of AMPs in mitigating this pressing challenge. The review also illuminates potential future strategies that may be implemented to improve AMP efficacy, such as structural modifications and using AMPs in combination with antibiotics and matrix-inhibiting compounds.

An escape from ESKAPE pathogens: A comprehensive review on current and emerging therapeutics against antibiotic resistance.

The rise of antimicrobial resistance has positioned ESKAPE pathogens as a serious global health threat, primarily due to the limitations and frequent failures of current treatment options. This growing risk has spurred the scientific community to seek innovative antibiotic therapies and improved oversight strategies. This review aims to provide a comprehensive overview of the origins and resistance mechanisms of ESKAPE pathogens, while also exploring next-generation treatment strategies for these infections. In addition, it will address both traditional and novel approaches to combating antibiotic resistance, offering insights into potential new therapeutic avenues. Emerging research underscores the urgency of developing new antimicrobial agents and strategies to overcome resistance, highlighting the need for novel drug classes and combination therapies. Advances in genomic technologies and a deeper understanding of microbial pathogenesis are crucial in identifying effective treatments. Integrating precision medicine and personalized approaches could enhance therapeutic efficacy. The review also emphasizes the importance of global collaboration in surveillance and stewardship, as well as policy reforms, enhanced diagnostic tools, and public awareness initiatives, to address resistance on a worldwide scale.