The continued rise in antimicrobial resistance poses a serious threat to public health worldwide. The use of phages that can have bactericidal activity without disrupting the normal flora represents a promising alternative treatment method. This practice has been successfully applied for decades, mainly in Eastern Europe, and has recently been used as an emergency therapy for compassionate care in the United States. Here, we provide a comprehensive review of the pre-clinical and clinical applications of phage therapy concerning three major Gram-negative pathogens: Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. The advantages and the challenges of expanding the usage of phages as an alternative or adjunctive treatment for antimicrobial-resistant bacterial infections are discussed. We emphasize the virologic complexities of using the highly adaptable phage populations as molecular tools, along with antibiotic chemical compounds, to effectively combat rapidly coevolving pathogenic bacteria in the host microenvironment. Pre-clinical studies, isolated clinical reports and a few randomized clinical trials have shown that bacteriophages can be effective in treating multidrug-resistant bacterial infections. The ability of some phages to revert the resistance against antibiotics, and possibly also against the human complement and other phages, appears to be a great advantage of phage therapy despite the inevitable emergence of phage-resistant strains. Bacteriophages (or specific phage-derived products) can enhance antimicrobial efficacy by reducing bacterial virulence via the alteration of basic bacterial structures, primarily of the cellular wall and membrane. Although several issues remain open regarding their effective clinical application, it appears that phage-based therapeutics in combination with antibiotics can provide an effective solution to the spread of antimicrobial resistance.

Respiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children and the elderly. RSV vaccine development puzzled vaccinologists for years. Safety concerns of initial formulations, the lack of an absolute correlate of protection, and the need for selecting appropriate virus attenuation and antigen–adjuvant combinations contributed to delayed vaccine production. The recent stabilization of the RSV-F glycoprotein in the prefusion (preF) conformation that constitutes the primary target of RSV-neutralizing antibodies was key for efficient vaccine design. Two protein subunit vaccines (GSK’s Arexvy and Pfizer’s Abrysvo) and one mRNA RSV vaccine (Moderna’s mRESVIA) are now available. This article aims to provide a comparative overview of the safety and efficacy of novel RSV vaccines that are approved for the prevention of RSV-lower respiratory tract disease (LRTD) in adults 60 years of age and older, with updated recommendations calling for the expansion of vaccination to all adults at increased risk for severe RSV disease. Abrysvo is the only vaccine indicated for use in pregnancy to prevent RSV-LRTD in infants from birth to 6 months of age. We provide a comparative assessment of the efficacy of approved RSV vaccines over a maximum of three seasons, summarizing currently available data. We conclude that despite the decreasing vaccine efficacy over time, which should be anticipated for a virus that is characterized by short-term immunity, efficacy was clinically meaningful over placebo. The increased risk of Guillain–Barré syndrome post vaccination with Abrysvo or Arexvy, which prompted the FDA to require the inclusion of such warnings in the prescribing information of these two RSV vaccines, should be prioritized and investigated thoroughly. Furthermore, ongoing vaccine surveillance and further evaluation, particularly among immunocompromised patients, frail elderly subjects, and young infants that were under- or not represented in pivotal clinical trials, are necessary. As in the success story of combined pediatric vaccines, combination vaccines, conferring protection against several respiratory illnesses in one dose, could help improve vaccine acceptance and coverage rates in older adults.

Carbapenem-resistant Gram-negative bacterial infections are a major public health threat due to the limited therapeutic options available. The introduction of the new β-lactam/β-lactamase inhibitors (BL/BLIs) has, however, altered the treatment options for such pathogens. Thus, four new BL/BLI combinations—namely, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, and ceftolozane/tazobactam—have been approved for infections attributed to carbapenem-resistant Enterobacterales species and Pseudomonas aeruginosa. Nevertheless, although these antimicrobials are increasingly being used in place of other drugs such as polymyxins, their optimal clinical use is still challenging. Furthermore, there is evidence that resistance to these agents might be increasing, so urgent measures should be taken to ensure their continued effectiveness. Therefore, clinical laboratories play an important role in the judicious use of these new antimicrobial combinations by detecting and characterizing carbapenem resistance, resolving the presence and type of carbapenemase production, and accurately determining the minimum inhibitor concentrations (MICs) for BL/BLIs. These three targets must be met to ensure optimal BL/BLIs use and prevent unnecessary exposure that could lead to the development of resistance. At the same time, laboratories must ensure that results are interpreted in a timely manner to avoid delays in appropriate treatment that might be detrimental to patient safety. Thus, we herein present an overview of the indications and current applications of the new antimicrobial combinations and explore the diagnostic limitations regarding both carbapenem resistance detection and the interpretation of MIC results. Moreover, we suggest the use of alternative narrower-spectrum antibiotics based on susceptibility testing and present data regarding the effect of synergies between BL/BLIs and other antimicrobials. Finally, in order to address the absence of a standardized approach to using the novel BL/BLIs, we propose a diagnostic and therapeutic algorithm, which can be modified based on local epidemiological criteria. This framework could also be expanded to incorporate other new antimicrobials, such as cefiderocol, or currently unavailable BL/BLIs such as aztreonam/avibactam and cefepime/taniborbactam.

The share of the elderly population is growing worldwide as life expectancy increases. Immunosenescence and comorbidities increase infectious diseases’ morbidity and mortality in older adults. Here, we aimed to summarize the latest findings on vaccines for the elderly against herpes zoster, influenza, respiratory syncytial virus (RSV), COVID-19, and pneumococcal disease and to examine vaccine recommendation differences for this age group in Europe and the United States. PubMed was searched using the keywords “elders” and “vaccine” alongside the disease/pathogen in question and paraphrased or synonymous terms. Vaccine recommendations were also sought in the European and US Centers for Disease Control and Prevention databases. Improved vaccines, tailored for the elderly, mainly by using novel adjuvants or by increasing antigen concentration, are now available. Significant differences exist between immunization policies, especially between European countries, in terms of the recipient’s age, number of doses, vaccination schedule, and implementation (mandatory or recommended). Understanding the factors that influence the immune response to vaccination in the elderly may help to design vaccines that offer long-term protection for this vulnerable age group. A consensus-based strategy in Europe could help to fill the gaps in immunization policy in the elderly, particularly regarding vaccination against RSV and pneumococcus.

Antimicrobial resistance (AMR) poses a severe global health threat, necessitating alternatives to conventional antibiotics, which are increasingly ineffective. Phages play a dual role in both propagating and potentially mitigating AMR. They facilitate AMR dissemination primarily through transduction, with emerging evidence suggesting indirect involvement in conjugation and transformation. Phage–plasmids, a dynamic entity bridging phages and plasmids, have gained increasing attention for their role in AMR evolution. Conversely, phage therapy has demonstrated promise in targeting MDR pathogens and disrupting biofilms through lytic activity and enzymatic degradation. However, challenges, such as phage resistance, host specificity and regulatory constraints, must be addressed to enable widespread clinical implementation. While regulatory frameworks for phage therapy remain underdeveloped in many regions, initiatives such as the EMA workshop in 2015 have sought to establish pathways for regulatory approval, addressing issues related to phage standardization, phage production, quality control, clinical validation and product monitoring. Leveraging the extensive experience of Eastern European countries, where phage therapy has been successfully integrated into medical practice, may accelerate its acceptance in Western healthcare systems. Integrating phages with existing antimicrobial strategies may provide a viable approach to combating AMR. Phages thus connect the biological dots of AMR by contributing to its generation and spread, but possibly also to its resolution, likely in combination with antibiotics.

As antimicrobial resistance continues to undermine the efficacy of antibiotics, the global medical community is increasingly turning to alternative treatment modalities. Among these, phage therapy has re-emerged as a promising strategy for managing multidrug-resistant bacterial infections. Herein, we present and briefly discuss eight essential attributes of clinically relevant phages for therapy, which may be categorized broadly into virological and pharmacological characteristics. Virological attributes include a broad host range, a strictly lytic life cycle and the ability to manage the emergence of bacterial resistance to phages. Comprehensive genomic and proteomic characterization forms the foundation for selecting and engineering such candidates, ensuring both safety and predictability. From a pharmacological standpoint, phages should ideally show safety across relevant formulations and routes of administration, favorable pharmacokinetics, stability during storage and scalability in manufacturing. Advances in genomic analysis, artificial intelligence-driven phage selection and formulation technologies have further accelerated the translational potential of phage therapy. By systematically addressing each of these critical attributes, this work aims to inform the rational selection and development of therapeutic phages suitable for integration into the clinical practice.