Expert Review of Anti-infective Therapy最新文献

Introduction: Mpox (formerly monkeypox), a systemic infection caused by the mpox virus (MPXV), has become a global problem of increasing concern. There are currently no antiviral treatments that have been shown to be safe and effective for the treatment of mpox.

Areas covered: Brincidofovir is a lipid-modified acyclic nucleotide with in vitro and in vivo activity against multiple DNA viruses, including MPXV. It is licensed in the US and Canada for the treatment of human smallpox disease in adults and children, including neonates. It has been used under FDA-authorized emergency use for patients in the US with severe mpox. The authors review the antiviral activity, clinical development, pharmacokinetics, safety and efficacy of brincidofovir and its potential as an mpox treatment. A comprehensive review was conducted in PubMed, Science Direct, Embase and Google Scholar.

Expert opinion: Research is needed to better understand mpox epidemiology, natural history, antiviral therapy and vaccines. Brincidofovir is being evaluated in a randomized, double-blind, placebo-controlled trial under the Mpox Study in Africa (MOSA) protocol. Additional studies will assist in clarification of single vs. combination therapy, safety and populations most likely to benefit, as well as the management of treatment complications such as immune reconstitution inflammatory syndrome (IRIS).

Introduction: Naegleria fowleri is a rare but fatal free-living ameba with > 97% mortality rate. Despite advances in clinical and scientific understanding, therapeutic options remain limited, and diagnosis is often delayed, presenting significant public health challenges.

Areas covered: We reviewed recent literature from the last decade, using Google Scholar and PubMed  on N. fowleri treatment, emerging drug candidates, repurposed therapeutics, and innovative delivery strategies. Advancements in drug screening are highlighted, unveiling novel therapeutic targets and mechanisms of action. Additionally, the role of climate change and environmental factors in geographic expansion and increased incidence of infections is explored, posing a growing public health risk.

Expert opinion: Effective management of N. fowleri infections hinges on early detection and addressing research gaps, particularly in understanding transmission/disease mechanisms. Recent advances in therapeutics, diagnostics, and water treatment to reduce environmental contamination by N. fowleri show promise for lowering infection risk and improving outcomes for primary amebic meningoencephalitis. Collaboration among academic institutions, pharmaceutical companies, and water industries is essential, with research advancing treatments and vaccines, and water industries contributing by reducing environmental contamination/human exposure to N. fowleri. A combination of treatment strategies and stringent surveillance will be crucial to limit future outbreaks and improve patient prognosis.

Introduction: HIV late presentation, defined as a CD4+ cell count below 350 cells/μL or the presence of an AIDS-defining condition at diagnosis, represents a significant global challenge, accounting for approximately 50% new HIV diagnoses worldwide. This phenomenon is associated with suboptimal clinical outcomes, increased morbidity and mortality, and elevated transmission risks due to prolonged undiagnosed infection.

Areas covered: This review examines the definitions, risk factors, epidemiology, and clinical implications of late presentation in HIV. It highlights evidence supporting the timely initiation of antiretroviral therapy (ART), discusses the choice of optimal therapeutic regimens, and addresses the management of opportunistic infections in late presenters. Special attention is given to challenges posed by advanced disease, including immune reconstitution inflammatory syndrome, and drug-drug interactions in the context of opportunistic infections.

Expert opinion: Late HIV presenters face unique clinical and therapeutic challenges. High-risk groups, including older individuals, women, people who inject drugs, and migrants, require tailored prevention efforts to improve early diagnosis and care access. While INSTI-based ART regimens are preferred due to their efficacy and tolerability, evidence gaps persist regarding optimal ART strategies and timing in severe opportunistic conditions, such as cryptococcal and tuberculous meningitis. Further studies are needed to address these gaps.

Introduction: Human babesiosis is an emerging tick-borne disease caused by intraerythrocytic Babesia protozoa. Most cases are due to Babesia microti, which is endemic in the northeastern and upper Midwestern United States. Other Babesia spp. cases are endemic in China and/or sporadically reported in the United States, Europe, Asia, and elsewhere in the Northern Hemisphere. Cases in immunocompetent hosts are typically mild to moderate, while disease in immunocompromised hosts is often severe.

Areas covered: A historical perspective of compounds that are effective against Babesia spp. is provided. The current management of mild, moderate, and severe babesiosis is discussed, as is the genetic basis of antimicrobial resistance associated with relapsing babesiosis. The use of red blood cell exchange transfusion is reviewed.

Expert opinion/commentary: Most cases of human babesiosis are successfully treated with atovaquone plus azithromycin or clindamycin plus quinine. A major research topic is the management of immunocompromised hosts, especially those experiencing severe or relapsing babesiosis. Two immediate goals are, (i) to develop new antimicrobial agents that target Babesia spp. through novel mechanisms and can overcome resistance to currently recommended antimicrobial agents and, (ii) to gain a better understanding of the efficacy of red blood cell exchange transfusion and indications for its use.

Introduction: Acinetobacter baumannii clinical isolates commonly have high antimicrobial resistance levels. We evaluated the risk factors associated with colistin-resistant, extensively drug-resistant (XDR), and pan-drug-resistant (PDR) Acinetobacter baumannii.

Areas covered: A literature review was done using three electronic resources, encompassing 18 observational studies with 2,462 participants. Our study examined the association between risk factors and infections caused by colistin-resistant (6 studies, 847 participants), XDR (10 studies, 1413 participants), and PDR Acinetobacter baumannii (3 studies, 202 participants). The most common independent risk factor identified for all three resistance phenotypes was prior use of antibiotics, with adjusted odds ratios (aORs) ranging from 1.3 to 155.9. Additional contributing factors included mechanical ventilation, prolonged stays in the intensive care unit (ICU), and use of invasive devices, such as urinary catheters, central line catheters, and hemodialysis catheters. The severity of illness was also linked to these infections, as indicated by high scores on the APACHE II, SOFA, or SAPS II scales.

Expert opinion: Certain risk factors, particularly prior use of antibiotics, have been consistently associated with the development of three resistant phenotypes. Future research should focus on multicenter studies with well-defined criteria for resistance, identifying risk factors, and guiding intervention strategies more effectively.

Introduction: Diagnostic stewardship, the optimization of diagnostic testing to improve patient outcomes, is a rapidly evolving field; however, data relating to immunocompromised hosts are scarce.

Areas covered: This review examines recent advances in diagnostic stewardship and explores best practice principles for key clinical scenarios in immunocompromised patients, including febrile neutropenia, central nervous system infections, invasive fungal infections, cytomegalovirus, and Clostridioides difficile infection.

Expert opinion: Key challenges remain, including optimizing test utilization without compromising patient safety, interpreting advanced diagnostics in the context of immunosuppression, and demonstrating cost-effectiveness. A multidisciplinary approach incorporating both diagnostic and antimicrobial stewardship principles is essential to improve outcomes in this complex patient population. Future research should focus on prospective evaluation of diagnostic stewardship interventions and their impact on clinical and economic outcomes in immunocompromised hosts.

Introduction: Neurocysticercosis remains the leading parasitic infection of the human central nervous system and a primary cause of epilepsy in low- and middle-income regions. Although advances in magnetic resonance imaging, serologic assays, and antiparasitic regimens have improved disease recognition and lesion targeting, major clinical questions remain unresolved regarding optimal diagnosis and management.

Areas covered: This Perspective critically reviews current diagnostic and therapeutic approaches in neurocysticercosis, emphasizing the role of high-resolution imaging and evolving immunologic tools. The literature search methodology included searches of PubMed and Google Scholar databases, focusing on publications related to neurocysticercosis diagnosis, clinical manifestations, treatment, and public health interventions. It discusses treatment selection based on cyst location, stage, and host immune profile, and explores the evidence supporting albendazole and praziquantel in parenchymal, ventricular, subarachnoid, and disseminated forms. Pediatric, pregnant, and immunocompromised patients are examined as distinct clinical populations.

Expert opinion: The management of neurocysticercosis demands individualized, lesion-specific strategies rather than uniform protocols. While advances in imaging and immunotherapy hold promise, implementation barriers persist in endemic areas. Future priorities include robust randomized trials for extraparenchymal disease, validation of immunologic biomarkers, and integrated public health measures to reduce the disease burden globally.

Introduction: Treatment failure is a critical outcome in community-acquired pneumonia (CAP), especially in severe cases, where it increases the risk of complications, prolonged hospital stays and mortality. Treatment failure was reported between 4% and 32% in severe CAP cases. Identifying causes and risk factors for treatment failure is crucial as it enables timely modifications to antibiotic treatment, accurate identification of patients who may require admission to the intensive care unit, and implementation of appropriate management strategies. Understanding the underlying mechanisms and host responses leading to treatment failure is essential for improving patient outcomes.

Areas covered: The authors discuss the latest scientific evidence on treatment failure focusing on definition, risk factors, causes, etiology, and the role of biomarkers. This article is based on the available literature from PubMed.

Expert opinion: Early detection and timely initiation of proper antimicrobial therapy are key elements to prevent treatment failure and complications, ultimately reducing CAP-associated mortality. However, treatment failure requires a more nuanced approach: identifying and categorizing complications, understanding its timing (early vs. late), and recognizing main risk factors and biomarkers that could help predict, diagnose and monitor treatment failure as early as possible. A multidisciplinary approach is essential in the prevention of treatment failure.

Introduction: HIV remains a major global health concern. Unexpected disruptions in antiretroviral drug supply chains carry increased mortality and transmission risks. The integrase strand transfer inhibitor dolutegravir plays an increasingly critical role in the global fight against the epidemic. Its high barrier to resistance has been extensively documented in rich countries. Recent reports of resistance cases after dolutegravir failure in resource-limited cohorts raise concerns about whether its high barrier to resistance will hold in low-income countries.

Areas covered: For this review, we performed a search on the recent published literature and conference communications focused on acquired drug resistance against dolutegravir in low- and middle-income countries.

Expert opinion: Overall, the data unsurprisingly showed that resistance against dolutegravir emerged mainly from unsuppressed individuals with treatment adherence issues. This emergence happened at a population rate below 1% despite structural challenges. Almost half of the resistance cases involved the R263K substitution, which did not always preclude re-suppression with dolutegravir. Minor adjustments in the programmatic large-scale rollout of dolutegravir could further improve these outcomes. Continued treatment adherence support and the preservation of antiretroviral drug supply chains remain crucial for the success of HIV treatment.