Expert Review of Anti-infective Therapy最新文献

Introduction: Cryptococcal meningoencephalitis (CM) is the leading cause of non-viral meningitis in the United States, reflecting both the rise in immunocompromised populations and the prevention of bacterial meningitis through vaccination. Formerly linked primarily to HIV-associated immunodeficiency, effective antiretroviral therapy has reshaped CM epidemiology: solid-organ transplant recipients and apparently healthy individuals now constitute the main risk groups, with mortality remaining 30-40%.

Areas covered: This review synthesizes emerging evidence on post-infectious inflammatory syndromes complicating CM, highlighting new insights into their pathogenesis, clinical recognition, and management. It also examines advances in rapid diagnostic approaches aimed at accelerating detection and guiding targeted therapy. Literature was identified through PubMed/MEDLINE and Embase searches, as detailed in the Introduction.

Expert opinion: Persistently high CM mortality stems from delayed or missed diagnosis and under-recognized post-infectious inflammatory injury. Current antifungal regimens, although microbiologically effective, are limited by toxicity and poor tolerability. Improving outcomes will require integration of rapid, sensitive diagnostic tools for both acute infection and inflammatory sequelae, alongside development of safer, orally bioavailable antifungal agents. These strategies offer the greatest potential to reduce mortality, preserve neurological function, and improve the long-term clinical course of this devastating disease.

Introduction: Antimicrobial resistance (AMR) remains one of the greatest threats to global health, requiring innovative approaches to antibiotic discovery, surveillance, diagnosis, and prescribing. In recent years, artificial intelligence (AI) has increasingly been applied across these domains, with the dual aim of accelerating research and strengthening antimicrobial stewardship.

Areas covered: This perspective summarizes current advances and challenges in applying AI for tackling AMR. We examine the role of AI in antibiotic discovery, laboratory surveillance, diagnosis of resistant infections, and clinical decision support systems. Finally, we address the ethical and regulatory landscape, data transparency, and liability concerns.

Expert opinion: AI offers unprecedented opportunities across the continuum of our efforts to counteract AMR, yet its adoption faces substantial hurdles. Some central challenges include the balance between model accuracy and explainability, the lack of widespread digital access, quality and transparency of training datasets, and usability for clinicians. Progress will depend on multidisciplinary collaboration, robust regulatory oversight, and the development of training programs equipping future healthcare professionals with AI-aware reasoning skills. Ultimately, AI should not replace but rather augment human reasoning in the fight against AMR, aligning innovation with ethical principles to ensure safer, more equitable AI-enhanced antibiotic prescribing and antimicrobial stewardship.

Introduction: Antimicrobial resistance (AMR) is a leading public health threat, the burden of which falls disparately on low- and middle-income countries (LMICs). Despite increasing efforts to slow the progress of AMR, gender, an important determinant of health, remains unaddressed in most major policy frameworks. This omission leaves gaps in our social understanding of AMR, undermining the efficacy of public health interventions.

Areas covered: We searched databases and gray literature, adopting a narrative approach to identify and present evidence. In this article, we examine three domains where gender impacts AMR. First, we analyze gendered healthcare access and antimicrobial use, identifying how gender norms can influence healthcare-seeking behaviors and create gendered diagnostic and antimicrobial usage disparities. Second, we explore differential AMR exposure associated with healthcare, childbearing, caregiving, agricultural, and sex-work occupational roles. Finally, we discuss how structural and systemic barriers, like poverty and healthcare access, perpetuate gender inequities in AMR and facilitate suboptimal antibiotic usage patterns.

Expert opinion: Current gender-blind AMR policies are insufficient at addressing the root social causes of AMR. Effective responses will require a shift to gender-responsive interventions, including the integration of sex-disaggregated data to AMR surveillance systems and reducing the structures that limit women's economic and healthcare autonomy.

Introduction: The COVID-19 pandemic has disproportionately affected immunocompromised individuals, who remain at risk for severe disease despite widespread vaccination efforts. Poor vaccine-induced humoral responses in this population necessitate additional preventive strategies. Sipavibart (AZD3152) is a next-generation long-acting monoclonal antibody designed to target the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein and provide broad-spectrum neutralization against divergent variants.

Areas covered: This review evaluates sipavibart's preclinical pharmacology, pivotal and supportive clinical trial data, and early real-world evidence, including the SUPERNOVA Phase 3 trial and national early-access programs. We discuss its safety profile, variant-specific activity, and resistance challenges.

Expert opinion: Sipavibart was the first monoclonal antibody to show efficacy and safety in preventing symptomatic COVID-19 among immunocompromised individuals, protecting for up to six months. However, the widespread circulation of variants harboring S:F456L currently limits its clinical utility, and use should be restricted. Maintaining access to Sipavibart remains justified, as future antigenic shifts could restore its activity. Its deployment should rely on genomic surveillance and local epidemiology. At the same time, next-generation mAbs should prioritize conserved spike regions and multi-epitope cocktails to counter viral evolution and prolong therapeutic value.

Introduction: MRSA bacteremia is associated with substantial clinical burden. Ceftaroline (CPT)-based combinations with vancomycin or daptomycin are increasingly utilized, but their added benefit remains uncertain. This meta-analysis compared the effectiveness and safety of CPT-based combination therapy versus vancomycin or daptomycin monotherapy.

Methods: MEDLINE, Scopus, and Cochrane Central were systematically searched. Primary outcomes were all-cause mortality and microbiological recurrence. Data were pooled using Review Manager, and meta-regression analyses were performed in RStudio. Heterogeneity was assessed using the I² statistic.

Results: A total of 22,938 patients were included from 10 cohort studies and one randomized controlled trial, with mean age 53 years, Pitt bacteremia score 2.0, and Charlson Comorbidity Index 2.6. CPT-based combination therapy showed mortality comparable to monotherapy (17.2% vs. 17.2%; RR 1.13; 95% CI 0.80-1.59; p = 0.50; I² = 4%), and the slight increase in microbiological recurrence (2.9% vs 1.4%; RR 0.86; 95% CI 0.51-1.47; p = 0.59; I² = 17%) was not significant. Meta-regression identified no covariate significantly modifying treatment effect.

Conclusion: CPT-based combination therapy conferred no significant mortality benefit over vancomycin or daptomycin monotherapy in patients with MRSA bacteremia, and timing of initiation did not influence outcomes.

Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD420251084876.

Introduction: The global rise in MDR bacterial infections has made the treatment of chronic and acute wound infections increasingly challenging. Conventional antibiotics often fail, leading to delay healing, more complications, and higher healthcare costs.

Areas covered: This review explores the current state of phage therapy as an alternative or adjunct to antibiotics for MDR-infected wounds. It summarizes types of wound infections, current treatment protocols, and recent clinical studies using phage therapy. This review also discusses the advantages of personalized phage preparations and highlights innovative local delivery methods. References were identified through a structured search of recent peer-reviewed studies and case reports in PubMed.

Expert opinion: Phage therapy shows promise against antimicrobial-resistant wound infections. Although clinical outcomes are encouraging, its widespread use is limited by legal, technical, and awareness barriers. Future success in the treatment of wound infections with phage therapy will depend on the development of standardized protocols, rapid diagnostics tools, and large-scale clinical trials - challenges that also apply broadly to phage therapy in other clinical contexts. Phage therapy, especially in local applications, aligns well with the principles of personalized medicine and may become a valuable component of modern wound care within the next decade.

Introduction: Invasive fusariosis is a rare but devastating mold infection in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT). Its clinical impact stems from delayed and challenging diagnosis, often made when fungal burden is already high; frequent dissemination with fungemia; and the limited availability of reliably effective antifungal agents. Together with the profound influence of host immune status on outcome, these factors drive persistently high mortality despite advances in antifungal therapy and supportive care, underscoring the urgent need for better diagnostic tools and novel therapeutic strategies.

Areas covered: We searched PubMed (1990-2025) for studies reporting the epidemiology, clinical presentation, diagnostic approaches, and management of fusariosis in transplant recipients. Key topics include the trimodal timing of fusariosis after HCT, species distribution across geographic regions, diagnostic challenges with culture and nonspecific biomarkers, and therapeutic outcomes with amphotericin B formulations and voriconazole. Emerging agents such as fosmanogepix and novel molecular platforms are also discussed.

Expert opinion: Despite its rarity, fusariosis poses a disproportionate threat to transplant recipients due to diagnostic delays, lack of randomized trials, and few effective antifungal options. Incorporating rapid molecular diagnostics, next-generation antifungals, and immune-directed strategies will be critical to improving real-world outcomes and survival.

Introduction: The COVID-19 pandemic has intensified global health challenges, including a silent but escalating crisis: multidrug-resistant organisms (MDROs). As healthcare systems strained under viral outbreaks, infection control and antimicrobial stewardship efforts suffered, accelerating the spread of antimicrobial resistance (AMR).

Areas covered: This review examines the indirect effects of the COVID-19 pandemic on AMR, emphasizing changes in antibiotic utilization, healthcare-associated infections, and resistance trends. Global and regional epidemiological data are presented, with a special focus on Taiwan's evolving MDROs landscape, clinical burden, and strategic responses.

Expert opinion: COVID-19 has both exposed and intensified vulnerabilities in AMR control. While the pandemic fostered certain infection control practices, it also disrupted antimicrobial oversight, leading to surges in MDROs prevalence. Taiwan's experience underscores the value of coordinated guidelines, real-time diagnostics, and artificial intelligence-driven stewardship. Rebuilding and future-proofing AMR responses requires integrated global policies, sustained surveillance, and innovation in diagnostics and therapeutics. Unless comprehensive action is taken, MDROs may emerge as the defining post-pandemic threat to modern medicine.

Introduction: COVID-19 convalescent plasma with high anti-SARS-CoV-2 antibody levels transfused within 6 months from donor collection was formally approved by the Food and Drug Administration in December 2024 for COVID-19 treatment in immunocompromised patients. Here we summarize the safety and efficacy data submitted for the Biologics License Application.

Areas covered: Safety evaluation in over 100,000 individuals in the expanded access program and 24,000 in randomized controlled trials, showed no serious adverse event increases. Robust randomized controlled trials established efficacy in four distinct disease stages-outpatient, inpatient, newly mechanically ventilated and in those immunocompromised to prevent acute disease progression or eliminate persistent viral carriage. Pharmacokinetics revealed a three-liter distribution volume with viral specific antibody effective dose near 2-50 milligrams. Major SARS-CoV-2 antibody-mediated antiviral actions included direct neutralization by viral binding interference to cell receptors and fragment-crystallizable mediated antiviral effects that reduce virions. Virus neutralization correlated with high anti-Spike antibody levels and antibody levels in the top donor plasma deciles retains therapeutic neutralization against future variants.

Expert opinion: With pandemic progression, the COVID-19 convalescent plasma safety and efficacy evidence quality increased. Ultimate regulatory approval required robust randomized control efficacy data. Future infectious disease outbreaks require randomized controlled trials in the convalescent plasma roadmap.