Search Results (204)

The discovery of penicillin led to remarkable progress in the treatment of diseases and far-reaching advancements in novel antibiotics’ development and use. However, the uncontrolled use and abuse of antibiotics in subsequent years have led to the emergence of the antimicrobial resistance (AMR) crisis, which now threatens modern medicine. There is an increasing number of emerging and reemerging infectious diseases, which have worsened the state of AMR and pose a serious threat to global health. The World Health Organization (WHO) reports the inadequacy of the drug development pipeline to meet the needs of the pharmaceutical sector in the face of AMR, and this poses a significant challenge in the treatment of diseases. Natural products (NPs) represent a promising group of antibiotic alternatives that can potentially mitigate AMR, as they bypass the pharmacodynamics of traditional antibiotics, thereby making them immune to the mechanisms of AMR. NPs, including plant derivatives, bacteriophages, metals, antimicrobial peptides, enzymes, and immune modulators, as monotherapies or in synergism with existing antibiotics, are gaining attention in a bid to reconstruct the antibiotic pipeline. Harnessing these as antimicrobial agents to curb AMR can help to provide sufficient defence against these infectious pathogens. The current review provides a comprehensive overview of the state of AMR and the potential of the above-mentioned antibiotic alternatives. Additionally, we discuss progress made and research breakthroughs in the application of these alternative therapies in humans, exploring findings from clinical trials and experimental models. The review further evaluates the advancement in technology, interdisciplinary approaches to the formulation and utilisation of NPs, and collaborations in alternative drug development. The research gaps present in this ever-evolving field are highlighted and evaluated together with regulatory issues, safety concerns, and technical difficulties in implementation. Full article

Pseudomonas aeruginosa poses significant health threats due to its multidrug-resistant profile, particularly affecting immunocompromised individuals. The pathogen’s ability to produce virulence factors and antibiotic-resistant biofilms, orchestrated through quorum-sensing (QS) mechanisms, complicates conventional therapeutic interventions. This review aims to critically assess the potential of anti-QS strategies as alternatives to antibiotics against P. aeruginosa infections. Comprehensive literature searches were conducted using databases such as PubMed, Scopus, and Web of Science, focusing on studies addressing QS inhibition strategies published recently. Anti-QS strategies significantly attenuate bacterial virulence by disrupting QS-regulated genes involved in biofilm formation, motility, toxin secretion, and immune evasion. These interventions reduce the selective pressure for resistance and enhance antibiotic efficacy when used in combination therapies. Despite promising outcomes, practical application faces challenges, including specificity of inhibitors, pharmacokinetic limitations, potential cytotoxicity, and bacterial adaptability leading to resistance. Future perspectives should focus on multi-target QS inhibitors, advanced delivery systems, rigorous preclinical validations, and clinical translation frameworks. Addressing current limitations through multidisciplinary research can lead to clinically viable QS-targeted therapies, offering sustainable alternatives to traditional antibiotics and effectively managing antibiotic resistance. Full article

This review addresses the urgent need for alternative strategies to combat drug-resistant mycobacterial infections, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, as well as non-tuberculous mycobacterial (NTM) diseases. Traditional antibiotics are increasingly limited by resistance, toxicity, and poor efficacy, particularly in immunocompromised patients. A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar, covering publications primarily from 2000 to 2025. Only articles published in English were included to ensure consistency in data interpretation. Search terms included “mycobacteriophages,” “phage therapy,” “drug-resistant mycobacteria, “diagnostic phages,” and “phage engineering.” The review examines the therapeutic and diagnostic potential of mycobacteriophages—viruses that specifically infect mycobacteria—focusing on their molecular biology, engineering advances, delivery systems, and clinical applications. Evidence suggests that mycobacteriophages offer high specificity, potent bactericidal activity, and adaptability, positioning them as promising candidates for targeted therapy. Although significant obstacles remain—including immune interactions, limited host range, and regulatory challenges—rapid progress in synthetic biology and delivery platforms continues to expand their clinical potential. As research advances and clinical frameworks evolve, mycobacteriophages are poised to become a valuable asset in the fight against drug-resistant mycobacterial diseases, offering new precision-based solutions where conventional therapies fail. Full article

Urinary tract infections (UTIs) are among the most prevalent bacterial infections in women, with high recurrence rates and growing concerns over antimicrobial resistance. The need for alternative or adjunctive therapies has spurred interest in plant-based treatments, which offer antimicrobial, anti-inflammatory, antioxidant, and immune-modulatory benefits. This review summarizes the mechanisms of action, clinical efficacy, and therapeutic potential of various medicinal plants and natural compounds for preventing and treating UTIs in women. Notable candidates include cranberry, bearberry, pomegranate, green tea, and other phytochemicals with proven anti-adhesive and biofilm-disrupting properties. Evidence from clinical trials and meta-analyses supports the role of cranberry natural products and traditional herbal medicines (THMs) in reducing UTI recurrence, especially when combined with antibiotics. Notably, A-type proanthocyanidins in cranberry and arbutin in bearberry are key bioactive compounds that exhibit potent anti-adhesive and biofilm-disrupting properties, offering promising adjunctive strategies for preventing recurrent urinary tract infections. Additionally, emerging therapies, such as platelet-rich plasma (PRP), show promise in restoring bladder function and reducing infection in women with lower urinary tract dysfunction. Overall, plant-based strategies represent a valuable and well-tolerated complement to conventional therapies and warrant further investigation through high-quality clinical trials to validate their efficacy, safety, and role in personalized UTI management. Full article

Antibiotic resistance presents a global threat, making the swift development of alternative treatments essential. Phage therapy, which employs bacterial viruses that specifically target bacteria, shows promise. Although this method has been utilized for over a century, primarily in Eastern Europe, its use in the US remains limited. This study aimed to assess the awareness and willingness of US healthcare providers to adopt phage therapy in response to the growing issue of antibiotic resistance. A survey of 196 healthcare providers, primarily MDs and DOs, found that while 99% were aware of antimicrobial resistance, only 49% were knowledgeable about phage therapy as a treatment for resistant bacterial infections. Nonetheless, 56% were open to considering phage therapy, and this willingness was associated with prior knowledge, concerns about antibiotic resistance, previous training, and confidence in recommending it (p < 0.05). Our study of U.S. healthcare providers revealed key findings about their views on phage therapy as a potential alternative for treating bacterial infections. Credible information is essential to promoting phage therapy use among U.S. providers via educational initiatives, clinical guidance, and research dissemination to promote phage therapy use among U.S. providers. Evidence-based education and clinical guidance help providers make sound decisions on the appropriate and safe use of phage therapy. Full article

The emergence of multidrug-resistant (MDR) bacteria and biofilm-associated infections has created a significant hurdle for conventional antibiotics, prompting the exploration of alternative strategies. Photodynamic therapy (PDT), a technique that utilizes photosensitizers activated by light to produce ROS, has emerged as a beacon of hope in the fight against MDR microorganisms. Among the natural photosensitizers, hypocrellins (A and B) have shown remarkable potential with their dual-mode photodynamic action, generating ROS via both Type I (electron transfer) and Type II (singlet oxygen) pathways. This unique action disrupts bacterial biofilms and inactivates MDR pathogens. The amphiphilic nature of hypocrellins further enhances their promise, enabling deep biofilm penetration and ensuring potent antibacterial effects even in hypoxic environments, surpassing the capabilities of synthetic photosensitizers. This study critically examines the antimicrobial properties of hypocrellin-based PDT, emphasizing its mechanisms, advantages over traditional antibiotics, and effectiveness against MDR pathogens. Comparative analysis with other photosensitizers, the role of nanotechnology-enhanced delivery systems, and future clinical applications are explored. Its combination with nanotechnology enhances therapeutic outcomes, providing a viable alternative to conventional antibiotics. Further clinical research is essential to optimize its application and integration into antimicrobial treatment protocols. Full article

Odontogenic abscesses are a frequent and challenging clinical issue in pet rabbits, often requiring a comprehensive diagnostic and therapeutic approach. This review collates current evidence on the etiology, diagnosis, and treatment of rabbit odontogenic abscesses, with a focus on imaging advances, microbial diversity, and local antimicrobial therapies. Predisposing factors include congenital conformation, inappropriate diet (insufficient abrasiveness, calcium or Vit D deficiencies, etc.), trauma, and neoplasia. Imaging techniques such as CT and cone-beam CT (CBCT) enable early detection and surgical planning, while traditional radiography remains useful in general practice. Treatment includes systemic antibiotics, surgical curettage, and the use of localized delivery systems such as antibiotic-impregnated polymethyl methacrylate (AIPMMA) beads. Adjunctive therapies like Manuka honey are also discussed. Two original heatmaps summarize bacterial prevalence and antimicrobial resistance from six peer-reviewed studies. These visualizations highlight the polymicrobial nature of these infections and the emergence of multidrug-resistant strains. Preventive strategies focus on optimal diet, regular dental checks, and owner education. The review also identifies key gaps in the literature, including the underreporting of anaerobes and lack of standardized treatment protocols. This article aims to support veterinary professionals in delivering evidence-based, individualized care to improve outcomes in rabbits with odontogenic abscesses. Full article

Clostridioides difficile is a leading pathogen involved in healthcare-associated diarrhea. With its increasing incidence, mortality, and antibiotic resistance, there is an urgent need for novel therapeutic strategies to address the infection and prevent its recurrence. Gegen Qinlian Decoction (GQD) is a traditional Chinese medicine for the treatment of diarrhea, but its main active ingredient is not known. Therefore, in this study, we evaluated the biological activity of berberine (BER) and baicalein (BAI), key components of GQD, against C. difficile. Time–kill curves and scanning electron microscopy were employed to assess their effects on C. difficile growth, while Enzyme-Linked Immunosorbnent Assay (ELISA) and cytotoxicity assays were used to examine their impact on toxin production. We also employed Quantitative Reverse Transcription PCR (qRT-PCR) to examine how BER and BAI influenced the expression of toxin-associated genes. At sub-inhibitory concentrations, these compounds exerted antibacterial activity against C. difficile by disrupting the integrity of the cell membrane and cell wall. Furthermore, BER and BAI also suppressed toxin production, demonstrating effects comparable to those of vancomycin. This suppression likely resulted from their bactericidal activity and the inhibition of toxin gene expression. This study not only highlights the potential application of GQD in treating C. difficile infections but also offers promising options for developing drugs targeting the growth and virulence of this pathogen. C. difficile infection (CDI) is a leading cause of severe diarrhea, and its treatment remains challenging due to limited drug options and its high recurrence rate. BAI and BER, the main active components of the traditional Chinese medicinal formula GQD, inhibited the growth of C. difficile by disrupting its cellular structure and significantly reduced the production of toxins associated with disease severity. Furthermore, the effects of BAI and BER on C. difficile were comparable to those of conventional antibiotics, suggesting that these compounds could be potential alternative therapies for CDI. This study not only highlights the therapeutic potential of GQD in treating CDI but also provides a replicable research strategy for the development of novel anti-CDI agents. Full article

Background/Objectives: Antibiotic resistance is a significant and escalating challenge that limits available therapeutic options. This issue is further exacerbated by the decreasing number of new antibiotics being developed. Our study aims to describe the epidemiology and pattern of antibiotic resistance in Gram-negative infections isolated from a cohort of hospitalized patients and to analyze the distribution of infections within the hospital setting. Methods: A retrospective study was conducted on all patients admitted to Vito Fazzi Hospital in Lecce, Italy, who required an infectious disease consultation due to the isolation of Gram-negative bacteria from 1 January 2018 to 31 December 2022. Results: During the study period, 402 isolates obtained from 382 patients (240 men and 142 women) with infections caused by Gram-negative bacteria were identified. Among these isolated, 226 exhibited multidrug resistance, defined as resistance to at least one antimicrobial agent from three or more different classes. In 2018, the percentage of multidrug-resistant isolates peaked at 87.6%, before decreasing to the lowest level (66.2%) in 2021. Overall, of the 402 isolates, 154 (38.3%) displayed resistance to carbapenems, while 73 (18.1%) were resistant to extended-spectrum beta-lactamases (ESBLs). Among the resistant microorganisms, Klebsiella pneumoniae showed the highest resistance to carbapenems, accounting for 85.2% of all resistant strains. Escherichia coli exhibited the greatest resistance to ESBLs, with a rate of 86.7%. Among carbapenem-resistant K. pneumoniae isolates, the following resistance rates were observed: KPC-1 at 98.2%, IMP-1 at 0.9%, VIM-1 at 0.9%, and NDM-1 at 0.9%. Conclusions: Patients with infections caused by multidrug-resistant bacteria have limited treatment options and are therefore at an increased risk of death, complications, and longer hospital stays. Rapid diagnostic techniques and antimicrobial stewardship programs—especially for ESBLs and carbapenemases—can significantly shorten the time needed to identify the infection and initiate appropriate antimicrobial therapy compared to traditional methods. Additionally, enhancing surveillance of antimicrobial resistance within populations is crucial to address this emerging public health challenge. Full article

The global rise of carbapenem-resistant Acinetobacter baumannii (CRAB) strains poses a critical challenge to healthcare systems due to limited therapeutic options and high mortality rates, especially in intensive care settings. This review explores the epidemiological landscape and molecular mechanisms driving carbapenem resistance, including the production of diverse beta-lactamases (particularly OXA-type enzymes), porin loss, efflux pump overexpression, and mutations in antibiotic targets. Emerging treatment strategies are discussed, such as the use of new beta-lactam–beta-lactamase inhibitor combinations (e.g., sulbactam–durlobactam), siderophore cephalosporins, next-generation polymyxins, as well as novel agents like zosurabalpin and rifabutin (BV100). Alternative approaches—including phage therapy, antimicrobial peptides, CRISPR-based gene editing, and nanoparticle-based delivery systems—are also evaluated for their potential to bypass traditional resistance mechanisms. Furthermore, advances in artificial intelligence and multi-omics integration are highlighted as tools for identifying novel drug targets and predicting resistance profiles. Together, these innovations represent a multifaceted strategy to overcome CRAB infections, yet their successful implementation requires further clinical validation and coordinated surveillance efforts. This analysis highlights the urgent need for continued investment in innovative treatments and effective resistance monitoring to limit the spread of CRAB and protect the effectiveness of last-line antibiotics. Full article

Medical research is at the forefront of addressing pressing global challenges, including preventing and treating cardiovascular, autoimmune, and oncological diseases, neurodegenerative disorders, and the growing resistance of pathogens to antibiotics. Understanding the molecular mechanisms underlying these diseases, using advanced medical approaches and cutting-edge technologies, structure-based drug design, and personalized medicine, is critical for developing effective therapies, specifically anticancer treatments. Background/Objectives: One of the key drivers of cancer at the cellular level is the abnormal activity of protein enzymes, specifically serine, threonine, or tyrosine residues, through a process known as phosphorylation. While tyrosine kinase-mediated phosphorylation constitutes a minor fraction of total cellular phosphorylation, its dysregulation is critically linked to carcinogenesis and tumor progression. Methods: Small-molecule inhibitors, such as imatinib or erlotinib, are designed to halt this process, restoring cellular equilibrium and offering targeted therapeutic approaches. However, challenges persist, including frequent drug resistance and severe side effects associated with these therapies. Nanomedicine offers a transformative potential to overcome these limitations. Results: By leveraging the unique properties of nanomaterials, it is possible to achieve precise drug delivery, enhance accumulation at target sites, and improve therapeutic efficacy. Examples include nanoparticle-based delivery systems for TKIs and the combination of nanomaterials with photothermal or photodynamic therapies to enhance treatment effectiveness. Combining nanomedicine with traditional treatments holds promise and perspective for synergistic and more effective cancer management. Conclusions: This review delves into recent advances in understanding tyrosine kinase activity, the mechanisms of their inhibition, and the innovative integration of nanomedicine to revolutionize cancer treatment strategies. Full article

Chemical exchange saturation transfer (CEST) MRI is a novel technique that allows for the specific imaging of certain molecules that contain exchangeable protons. Neuroimaging is a major contributor to diagnosing and monitoring infections of the central nervous system (CNS). This review focuses on summarizing the current literature surrounding the use of CEST MRI imaging in diagnosing, monitoring, and treating CNS infections. BacCEST is a new technique to detect bacterial infection in organs at profound levels. This technique allows for the specific pathogen causing the infection to be understood, allowing for tailored antibiotic therapies. The bacCEST signal is also directly proportional to the number of bacterial cells; this means it can be used over periods to track response to treatment via cell numbers. The results show that most of the research in this area has focused on infections of the brain parenchyma (e.g., encephalitis) and that most studies investigate the use of CEST in animal models, with a minority exploring the application of CEST to human participants. The common neuroinfectious disease presentations relevant to clinical medicine are also briefly described, as well as the traditional and modern imaging techniques used to visualize them. Full article

Periprosthetic joint infections (PJI) present significant challenges in orthopedic surgery, largely due to the complexity of treating antibiotic-resistant infections. Phage therapy, which utilizes bacteriophages to target bacterial pathogens, offers a promising supplement to traditional antimicrobial methods. This review discusses the current applications of phage therapy in the management of PJI, exploring its underlying mechanisms, clinical outcomes, and practical considerations. We also explore advances in phage therapy technology, including the development of phage cocktails, bioengineered phages, and combination therapies with antibiotics, which enhance the specificity and effectiveness of treatments. Furthermore, we address the future potential of phage therapy to be integrated into standard treatment protocols, focusing on ongoing innovations and research areas.The regulatory and ethical aspects of phage therapy in clinical settings are also discussed. By offering a comprehensive evaluation of both the current state and prospects of phage therapy, this review aims to inform clinical practice and stimulate further research into this innovative treatment modality for PJI management. Full article

Background/Objectives: Urinary tract infections (UTIs) are the most common bacterial infections and one of the most common diseases worldwide. These infections induce an enormous financial and economic burden. The most frequent pathogen in UTIs is Escherichia coli (E. coli), which is responsible for over 85% of cases of cystitis and over 60% of recurrent cases. Repeated antibiotic prescriptions increase the risk of bacteria developing resistance, reducing treatment efficacy and limiting long-term therapeutic options. When traditional preventive methods fail to provide protection, other strategies may be necessary. To investigate the effectiveness of vaccination with Uro-Vaxom for the prevention of UTIs based on currently available studies. Methods: Systematic literature search. Results: The available studies focus almost exclusively on the female sex. Uro-Vaxom decreased the recurrence of UTIs, was overall well tolerated, and reduced the need for antibiotic therapies. Conclusions: Uro-Vaxom is a potential effective and well-tolerated option for reducing the recurrence of UTIs in patients prone to frequent infections. Nevertheless, the retrospective nature of several studies, combined with methodological limitations and variability in study design, precluded a reliable quantitative estimation of the treatment effect. Full article

The appropriate use of antibiotics is crucial and involves selecting an optimal dosing regimen based on pharmacokinetic (PK) and pharmacodynamic (PD) indicators. Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool that integrates drugs’ physicochemical properties with anatomical and physiological data to predict PK behavior. In pediatric populations, PBPK modeling accounts for developmental changes in organ function, making it particularly useful for optimizing antibiotic dosing across different age groups, from neonates to adolescents. In recent decades, PBPK modeling has been widely applied to predict antibiotic disposition in pediatric patients for various clinical and research purposes. Model-informed precision dosing (MIPD) is an evolving approach that enhances traditional therapeutic drug monitoring by integrating multiple information sources into a mathematical framework. By incorporating PBPK modeling, MIPD could offer a more optimized antibiotic dosing that accounts for PK/PD parameters at the site of infection, improving therapeutic outcomes while minimizing toxicity. This review summarizes currently published pediatric PBPK modeling studies on antibiotics, covering various objectives such as evaluating drug–drug interactions, PK/PD analyses in targeted tissues, predicting PK in specific populations (e.g., maternal/fetal, renal impairment, obesity), and PK predictions for preterm neonates. Based on these reports, the review discusses the implications of PBPK modeling for MIPD in pediatric antibiotic therapy. Full article