Expert Review of Anti-infective Therapy最新文献

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.

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.

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).

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.

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.

Introduction: Urinary tract infection (UTI) is a major global health concern. While acute UTIs can usually be effectively treated, recurrent UTIs (rUTIs) 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 the current challenges faced by clinicians in managing rUTI in women and the steps that should be taken so that clinicians, scientists, and patients can work together to better understand the disease and develop better strategies for its management.

Introduction: Acinetobacter baumannii complex (Abc) is currently a significant cause of difficult-to-treat pneumonia. Due to the high prevalence rates of carbapenem- and extensively drug-resistant (CR, XDR) phenotypes, limited antibiotic options are available for the effective treatment of pneumonia caused by CR/XDR-Abc.

Areas covered: In vitro susceptibility data, relevant pharmacokinetic profiles (especially the penetration ratios from plasma into epithelial-lining fluid), and pharmacodynamic indices of key antibiotics against CR/XDR-Abc are reviewed.

Expert opinion: Doubling the routine intravenous maintenance dosages of conventional tigecycline (100 mg every 12 h) and minocycline (200 mg every 12 h) might be recommended for the effective treatment of pneumonia caused by CR/XDR-Abc. Nebulized polymyxin E, novel parenteral rifabutin BV100, and new polymyxin derivatives (SPR206, MRX-8, and QPX9003) could be considered supplementary combination options with other antibiotic classes. Regarding other novel antibiotics, the potency of sulbactam-durlobactam (1 g/1 g infused over 3 h every 6 h intravenously) combined with imipenem-cilastatin, and the β-lactamase inhibitor xeruborbactam, is promising. Continuous infusion of full-dose cefiderocol is likely an effective treatment regimen for CR/XDR-Abc pneumonia. Zosurabalpin exhibits potent anti-CR/XDR-Abc activity in vitro, but its practical use in clinical therapy remains to be evaluated. The clinical application of antimicrobial peptides and bacteriophages requires validation.

Background: The optimal strategy for using hydroxychloroquine to prevent coronavirus disease 2019 (COVID-19) in patients, either before or after exposure, remains unclear. We evaluated the safety and efficacy of different doses and treatment durations of hydroxychloroquine for COVID-19 prevention.

Method: Databases including PubMed, Web of Science, Cochrane Library, EMBASE, Medline, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) comparing different doses of hydroxychloroquine for COVID-19 prevention, from their inception to February 2024.

Results: A total of 20 RCTs involving 12,372 patients were included. Meta-analysis results showed no significant difference between the hydroxychloroquine and control groups in reducing the incidence of syndrome coronavirus type 2 (SARS-CoV-2) positivity (OR = 0.83, 95% CI = 0.67, 1.03). However, the subgroup receiving a daily dose of 200-400 mg (OR = 0.62, 95% CI = 0.51, 0.75) and a treatment duration of 5-8 weeks (OR = 0.52, 95% CI = 0.31, 0.88) showed statistically significant reductions in SARS-CoV-2 positivity. According to the surface under the cumulative ranking curve (SUCRA), the most effective intervention was a 200-400 mg dose for 5-8 weeks.  .

Conclusions: A hydroxychloroquine dose of 200-400 mg for a duration of 5-8 weeks may moderately reduce the risk of COVID-19 with a relatively low risk of adverse events.

Introduction: The threat of new, emerging, and multidrug-resistant microbes is increasing which has created the necessity for new antimicrobials. In this regard, nanotechnology can be an alternative for the treatment of infectious microbes. Curcumin has been used since ancient times as antimicrobials; however, it has limitations due to its less aqueous solubility, bioavailability, and biocompatibility. This problem can be solved by curcumin-derived carbon nanodots, which are emerging antimicrobials of <10 nm size, water-soluble, biocompatible, less toxic, and fluorescent.

Areas covered: The review discusses the application of curcumin-derived carbon nanodots against various pathogenic microbes including bacteria and dreaded viruses like SARS-CoV-2. In addition, the role of curcumin carbon nanodots in biolabelling of pathogenic microbes, mechanism of action, bioimaging, and therapy has been critically examined.

Expert opinion: Carbon nanodots play an important role in combating pathogenic microbes by early diagnosis, bioimaging, nanocarrier for antimicrobial drugs, and therapy of infectious diseases. Curcumin carbon nanodots have already demonstrated their benefits of being water soluble, bioavailable, and biocompatible. However, more thorough research is needed to understand the efficacy and safety of curcumin carbon nanodots. In the future, curcumin-derived carbon nanodots can be used as alternative antimicrobial agents to fight microbial infections including multidrug-resistant microbes.

Introduction: Hepatitis B virus (HBV) affects hundreds of millions globally, with many cases stemming from perinatal transmission. Chronic hepatitis B (CHB) in children can progress to cirrhosis and hepatocellular carcinoma (HCC) in adulthood. Treatment options include interferons and nucleos(t)ide reverse transcriptase inhibitors (N[t]RTIs) such as tenofovir alafenamide (TAF).

Areas covered: This review covers the epidemiology of pediatric CHB and current treatments, with a focus on tenofovir-based therapies, particularly tenofovir disoproxil fumarate (TDF) and TAF. TDF has been used for years, but its risks of bone mineral density loss and renal impairment have raised concerns. TAF, with lower systemic exposure, appears to mitigate these risks. Ongoing trials are evaluating TAF's safety in younger children. There are knowledge gaps in long-term safety and the potential for combination therapies.

Expert opinion: TAF offers a safer alternative to TDF for children with CHB, showing high antiviral efficacy and fewer side effects. However, more data is needed on its use in younger children and long-term safety. The future of CHB treatment in pediatrics may include combination therapies and personalized approaches, potentially improving outcomes and minimizing risks over a lifetime of treatment. As research progresses, TAF is likely to become a cornerstone in pediatric CHB management.