The emergence of the H3N2 influenza virus in 1968 marked a significant event as it crossed the species barrier. This shift led to a pandemic, resulting in the deaths of one million people globally and highlighting the virus's severe impact on older individuals due to antigenic drift. This review comprehensively examines the virological characteristics, evolutionary trends, and global epidemiology of the Influenza A (H3N2) virus. It delves into vaccination strategies, antiviral interventions, and emerging diagnostic approaches. The impact of antigenic variation on vaccine design and effectiveness, seasonal outbreak patterns, and pandemic potential are explored. Additionally, the interplay between viral factors and host immune responses is assessed. Researchers are actively investigating innovative strategies to enhance vaccine efficacy against H3N2 mutations, such as precise antigenic material administration, controlled release patterns, understanding immune system mechanisms, and glycan engineering. The ongoing mutational dynamics of the H3N2 virus necessitate regular vaccine updates, as advocated by the WHO. Research in the Western Pacific region underscores the need for heightened awareness and effective control strategies. Evaluating antiviral therapies and addressing drug resistance requires multidisciplinary approaches involving researchers, healthcare professionals, and policymakers. This comprehensive understanding of H3N2 is vital for improving public health interventions and preparing for future influenza challenges.

ABSTRACT Objective To investigate the effectiveness of oral antiviral agents – nirmatrelvir – ritonavir or molnupiravir in non-hospitalized COVID-19 patients aged <60 years. Methods This retrospective cohort study analyzed data of patients aged 18–60 years diagnosed with COVID-19 between 1 January 2022, and 30 June 2023. Propensity score matching was used to balance the demographic and clinical characteristics of patients receiving oral antivirals (nirmatrelvir – ritonavir or molnupiravir) and untreated controls. The primary outcome was a composite of all-cause emergency department visits, hospitalizations, or mortality within 30 days. The secondary outcomes included each individual component of the primary composite outcome. Results Two matched cohorts (antiviral group and control group) comprising 52,585 patients with balanced baseline characteristics were created using propensity score-matching. During follow-up period, the antiviral group demonstrated a lower risk of the primary outcome than the control group (hazard ratio [HR] 0.772, 95% confidence interval [CI] 0.736–0.808, p < 0.001). The antiviral group also exhibited a reduced risk of individual secondary outcomes, including emergency department visits (HR 0.780, 95% CI, 0.738–0.825), hospitalization (HR 0.755, 95% CI, 0.715–0.840), and mortality (HR 0.297, 95% CI, 0.147–0.600). Conclusion Oral antiviral agents were associated with lower risks of all-cause emergency department visits, hospitalizations, and mortality in non-hospitalized COVID-19 patients aged <60 years.

ABSTRACT Introduction The rising prevalence of difficult-to-treat, deep-seated invasive fungal diseases (IFD) has led to high mortality. Currently available antifungal treatments, administered predominantly orally or intravenously, may not sufficiently penetrate certain body sites, and/or are associated with systemic toxicity. Little is known about how to position alternative administration approaches such as inhalational and direct drug delivery routes. Areas covered This review provides an updated overview of unconventional drug delivery strategies for managing IFD, focusing on inhalational (to target the lungs) and direct delivery methods to the central nervous system, bone/joint, and eyes. Novel compounds (e.g. opelconazole) and existing antifungals with innovative drug delivery systems currently undergoing clinical trials and/or used off-label in the clinical setting are discussed. Expert opinion For both inhalational agents and direct delivery approaches, there are similar challenges that include the absence of: approved formulations for specific administration routes, delivery vehicles that are simple and safe to use whilst maintaining potency and efficiency of delivery, animal models suitable for investigating pharmacokinetic/pharmacodynamic profiles of inhaled antifungals, and consensus on the composite endpoints and intervals for of follow-up in clinical trials. To meet these challenges, cooperation of all stakeholders in drug development and regulation is required.

ABSTRACT Introduction Despite the existence of antivirals that potently and efficiently inhibit the replication of herpes simplex virus 1 and 2 (HSV-1, −2), their ability to establish and maintain, and reactivate from, latency has precluded the development of curative therapies. Several groups are exploring the opportunities of targeting epigenetic regulation to permanently silence latent HSV genomes or induce their simultaneous reactivation in the presence of antivirals to flush the latent reservoirs, as has been explored for HIV. Areas Covered This review covers the basic principles of epigenetic regulation with an emphasis on those mechanisms relevant to the regulation of herpes simplex viruses, as well as the current knowledge on the regulation of lytic infections and the establishment and maintenance of, and reactivation from, latency, with an emphasis on epigenetic regulation. The differences with the epigenetic regulation of viral and cellular gene expression are highlighted as are the effects of known epigenetic regulators on herpes simplex viruses. The major limitations of current models to the development of novel antiviral strategies targeting latency are highlighted. Expert Opinion We provide an update on the epigenetic regulation during lytic and latent HSV-1 infection, highlighting the commonalities and differences with cellular gene expression and the potential of epigenetic drugs as antivirals, including the opportunities, challenges, and potential future directions.

ABSTRACT Objectives This study assessed the clinical effectiveness of the combination of nirmatrelvir and ritonavir (NMV-r) in treating nonhospitalized patients with COVID-19 who have preexisting psychiatric disorders. Methods Patients diagnosed with COVID-19 and psychiatric disorders between 1 March 2020, and 1 December 2022, were included using the TriNetX network. The primary outcome was the composite outcome of all-cause emergency department (ED) visits, hospitalization, or death within 30 days. Results Propensity score matching yielded two cohorts of 20,633 patients each. The composite outcome of all-cause ED visits, hospitalization, or death within 30 days was 3.57% (737 patients) in the NMV-r cohort and 5.69% (1176) in the control cohort, resulting in a reduced risk in the NMV-r cohort (HR: 0.657; 95% confidence interval (CI): 0.599–0.720). The NMV-r cohort exhibited a lower risk of all-cause hospitalization (HR: 0.385; 95% CI: 0.328–0.451) and all-cause death (HR: 0.110; 95% CI: 0.053–0.228) compared with the control group. Conclusion NMV-r could mitigate the risk of adverse outcomes in nonhospitalized patients with COVID-19 and preexisting psychiatric disorders. However, only a limited number of patients in this population received adequate treatment, thus emphasizing the importance of promoting its appropriate use.

ABSTRACT Introduction Patients with hematological malignancies (PHMs) are at increased risk for infections caused by carbapenem-resistant organisms (CROs) due to frequent exposure to broad-spectrum antibiotics and prolonged hospital stays. These infections result in high mortality and morbidity rates along with delays in chemotherapy, longer hospitalizations, and increased health care costs. Areas covered Treatment alternatives for CRO infections in PHMs. Expert opinion The best available treatment option for KPC and OXA-48 producers is ceftazidime/avibactam. Imipenem/cilastatin/relebactam and meropenem/vaborbactam remain as the alternative options. They can also be used as salvage therapy in KPC-positive Enterobacterales infections resistant to ceftazidime/avibactam, if in vitro susceptibility is shown. Treatment of metallo-β-lactamase producers is an unmet need. Ceftazidime/avibactam plus aztreonam or aztreonam/avibactam seems to be the most reliable option for metallo-β-lactamase producers. As a first-line option for carbapenem-resistant Pseudomonas aeruginosa infections, ceftolozane/tazobactam is preferable and ceftazidime/avibactam and imipenem/cilastatin/relebactam constitute alternative regimens. Although sulbactam/durlobactam is the most reliable option against carbapenem-resistant Acinetobacter baumannii infections, its utility as monotherapy and in PHMs is not yet known. Cefiderocol can be selected as a ‘last-resort’ option for CRO infections. New risk score models supported by artificial intelligence algorithms can be used to predict the exact risk of infections in previously colonized patients.

ABSTRACT Introduction Urinary tract infection (UTI) is a major global health concern. While acute UTIs can usually be effectively treated, recurrent UTIs (rUTI) impact patients for years causing significant morbidity and can become refractory to front-line antibiotics. Areas covered This review discusses the risk factors associated with rUTI, current rUTI treatment paradigms, prophylactic strategies, and challenges in rUTI diagnostics. We specifically discuss common risk factors for rUTI, including biological sex, age, menopause status, and diabetes mellitus. We also review recently available evidence for commonly used treatments, from oral antibiotic therapy to intravesical antimicrobials, electrofulguration of chronic cystitis, and the last-resort treatment, cystectomy. We discuss the most current literature evaluating prophylactic strategies for rUTI including long-term antibiotic prophylaxis, estrogen hormone therapy and dietary supplements. Finally, we address the important role of UTI diagnostics in effective rUTI management and review the strengths and limitations of both current and emerging UTI diagnostic platforms as well as their ability to operate at point-of-care. Expert opinion We discuss current challenges faced by clinicians in managing rUTI in women and steps that should be taken so that clinicians, scientists, and patients can work together to better understand this disease and develop better strategies for its management.

ABSTRACT Introduction Mucormycosis, popularly known as the black fungus, has become a worldwide concern in the continuing COVID-19 pandemic, causing increased morbidity and death in immunocompromised people. Due to multi-drug resistance and the limited number of antifungals, surgical interventions, ‎including the excision of infected tissue, remain a standard treatment option‎. Surgical treatment usually results in the loss of organs or their function, long-term intensive care, and a significant risk of reinfection during the procedure. A comprehensive approach is needed to treat the disease, and nanomaterials can be a powerful alternative therapeutic approach. Areas covered We searched PubMed, Scopus, and Google Scholar with the keywords ‘emerging role of nanomaterials,’ and ‘combating COVID-19-related mucormycosis,’ and reviewed the related research paper. Antifungal nanomaterials and their delivery can significantly impact the treatment of COVID-19-related fungal infections like mucormycosis. However, the therapeutic options for mucormycosis are limited and drug resistance is also reported. Expert opinion The current review encompasses a detailed overview of the recent developments in antifungal/antiviral nanomaterials and the properties of these therapeutic nanomaterials that may contribute to formulating an efficient strategy against invasive mucormycosis. Further extensive research is needed to develop nano-based therapeutics for the management of mucormycosis-viral coinfection with a definitive end-point.

ABSTRACT Background Irrational use of antibiotics is a major driver of antimicrobial resistance. Self-medication with antibiotics (SMA) may exacerbate antimicrobial resistance in the community without professional diagnosis by physicians, due to the complexity of the pharmacological mechanisms. There is still a lack of assessment of the global prevalence of SMA. We have evaluated the global prevalence of SMA and its associated factors, which could provide more reliable data to support global action. Methods We searched PubMed, Embase, Web of Science, and EBSCO CINAHL Plus. Quantitative studies were combined using meta-analysis with random-effects models, and qualitative synthesis was performed using interpretive meta-ethnographic methods. Results A total of 242 studies were included in this study. The pooled prevalence of SMA was 27.7% (95%CI: 24.9%-30.5%). Quantitative studies indicate that high income level, having family members working in the healthcare system, storing antibiotics at home, and purchasing antibiotics without prescriptions were associated with a greater likelihood of SMA. Qualitative findings revealed the following four factors: individual characteristics, healthcare, pharmacy, and social networks. Conclusions The prevalence of global SMA among the public remains high level. Multisectoral and community-based interventions are needed to reduce SMA, including targeted health education, improved access to healthcare, and regulation of antibiotics sales in pharmacies. Registration PROSPERO (CRD42023402206)

ABSTRACT Introduction Modern antiretroviral therapy is associated with reduced rates of HIV-related morbidity and mortality. HIV viral suppression and retention in care are critically important outcomes requiring successful continuous patient engagement. However, barriers to such engagement are complex and require innovative solutions. Areas covered A multistakeholder group of experts comprising clinicians and service delivery researchers assembled to clarify what constitutes engagement in HIV care and identify overarching themes that inform strategies in this field. This article captures this expert opinion and adds relevant literature on selected current best practices. Expert opinion The multistakeholder group felt strongly that a better understanding of the facilitators of continuous care engagement was critical. Unlike ‘retention in care,’ ‘engagement in care’ for an individual is nuanced, flexible, evolves and requires ongoing communication between patients, providers, and other key stakeholders. The following approaches highlight care engagement strategies at different stakeholder levels: 1) patient-level: personalized care and incentivization; 2) clinic-level: wraparound, co-localized, patient-centered low-barrier care, a diverse multidisciplinary team, patient support networks, and expanded use of telemedicine; 3) healthcare system-level: utilization of external partnerships. We propose a series of diverse and complementary approaches based on a more nuanced understanding of the qualitative aspects of engagement in care.