Expert Review of Anti-infective Therapy最新文献

Introduction: The global burden of invasive fungal infections (IFIs) is increasing, with the threat of disease exacerbated by the emergence of antifungal resistance. While antifungals remain the mainstay for the treatment of IFIs, there is a growing recognition of the many patient variables, particularly in challenging situations (e.g. critically ill patients), that can impact the exposure of antifungals.

Areas covered: This narrative review focuses on the changing epidemiology of Candida species in Asia Pacific and evidence for optimizing antifungal dosing in challenging clinical scenarios, based on a symposium held at the International Society for Human and Animal Mycology Asia Congress in Bangkok, Thailand, on 1 August 2024.

Expert opinion: Antifungal resistance is common and increasing among fungal pathogens (e.g. Candida species) in the Asia Pacific. Optimal drug selection and dosing of antifungals is critical for achieving the best therapeutic outcomes and limiting resistance emergence, particularly in challenging clinical scenarios. Current 'standard' doses of antifungals do not account for pharmacokinetic variations in critically ill patients and can lead to suboptimal exposures, highlighting the need for better dosing regimens in these patients. Therapeutic drug monitoring is a valuable strategy for optimizing antifungal therapy, and its use is encouraged, particularly in critically ill patients.

Introduction: Urinary tract infection (UTI) is the most common infectious complication in kidney transplant recipients (KTRs). Beyond attributable morbidity and related costs, post-transplant UTI appears to exert a deleterious effect on graft outcomes. Uncertainties on the significance of asymptomatic bacteriuria (ASB) and the increasing role as uropathogens of multidrug-resistant organisms (MDROs) further complicate the therapeutic approach.

Areas covered: Following a contextualizing introduction on the epidemiology, risk factors and consequences of post-transplant UTI, we reviewed the rationale underlying the 'screen-and-treat' strategy for ASB and the recently generated evidence. Most appropriate regimens for the empirical treatment of cystitis and pyelonephritis are discussed in light of recent microbiological trends. The role of novel antibiotics against MDROs is considered, as well as the management of recurrent UTI and the feasibility of dedicated antibiotic stewardship programs (ASPs). Finally, future directions and unmet needs are addressed in the present narrative review.

Expert opinion: Despite advances to clarify the management of ASB and recent additions to the antibiotic armamentarium, research is needed to optimize the empirical and definitive therapy for post-transplant UTI. This should include the validation of predictive scores for MDRO infection, the effectiveness and safety of novel antibiotics, and the implementation of ASPs in KTRs.

Introduction: Invasive fungal diseases (IFD) cause significant morbidity and mortality in children, who have unique risk factors like premature birth, genetic conditions, and immunodeficiencies. They also share adult risk factors, such as antineoplastic treatments and intensive care. This narrative review summarizes epidemiology and focus on diagnosis, and treatment of IFD in pediatric patients.

Area covered: Diagnosing IFD in children is challenging due to the difficulties in obtaining sufficient blood or CSF for cultures from small patients. Additionally, antigen detection methods often perform poorly, except perhaps beta-glucan in newborns and galactomannan in neutropenic patients or samples from the infection site. Nonspecific imaging findings further complicate diagnosis. Therapeutic complexities arise from age- or disease-dependent pharmacokinetics, limited availability of child-friendly drug formulations, and frequent drug-drug and food-drug interactions, often requiring therapeutic drug monitoring for optimal outcomes.

Expert opinion: There is and will be further needed therapeutic drug monitoring for all antifungal drugs in children. Prioritizing pediatric-specific research and developing standardized treatment protocols are crucial. Furthermore, regulatory reforms are essential to expedite access to new diagnostic and treatment strategies for IFD in children.

Introduction: SARS-CoV-2 can have long-term health consequences that persist beyond acute infection. While this is evident in adults and the elderly, the impact on children and adolescents remains under recognized. Here we navigate the second-order post-acute effects that the COVID-19 has had on the pediatric populations, with the exception of the mental health implication of social restrictions.

Areas covered: We outline common scenarios related with SARS-CoV-2 infection encountered in pediatric clinical practice, such as in the Multisystem inflammatory syndrome (MIS-C), Long Covid, neurological and autoimmune complications of Covid-19, immunological impact of the viral infection, as well as epidemiological and public health consequences associated with the implementation of non-pharmacological interventions.

Expert opinion: SARS-CoV-2 has had several second-order effects on child health, from a biological, epidemiological, and public health perspective, highlighting the complexity of dealing with new infections and the urgent need to implement multidisciplinary interventions that support the health of people at single person and societal level. Funding on modern surveillance system, preventing strategies and research to better understand and cure post-acute complications of viral infections should be a priority of every funding agency.

Introduction: The community of microorganisms that colonize the intestine plays a vital role in regulating human metabolism and immune system function. According to translational medicine studies, administering antibiotics disrupts the balance of microorganisms in the gastrointestinal system, increasing the risk of multiple diseases. Dysregulation and reduction of the biodiversity of intestinal microbiota increase the risk of developing unhealthy conditions for the host. In this review, we tried to offer a current vision regarding the use of antibiotics and the modification of the intestinal microbiota.

Areas covered: Research has also shown that, in addition to antibiotics, the composition and balance of the intestinal microbiota depend on diet from the first days of life (breastfeeding or formula) and the mode of delivery (vaginal birth or cesarean section). Having this in mind, we performed an extensive literature search in PubMed, Scopus, Embase, and Web of Science on the relationships between human microbiota and antibiotics.

Expert opinion: Effective antimicrobial stewardship programs are urgently needed to reduce the misuse of antibiotics to avoid bacteria becoming more resistant, resulting in the ineffectiveness of antibiotics. Alternatives to antibiotics, e.g., targeted probiotics or bacteriophages, are increasingly considered as a strategy to preserve the intestinal microbiota diversity and maintain a good health status.

Introduction: Postoperative Staphylococcus aureus (S. aureus) infections are associated with increased morbidity and mortality. This systematic review and meta-analysis aimed to summarize the incidence of postoperative S. aureus infections.

Methods: We searched MEDLINE, CENTRAL, and Embase (2008-2023) for studies reporting S. aureus infections after hip or knee replacement, spinal surgery, craniotomy, coronary artery bypass surgery (CABG), open colon surgery, abdominal hysterectomy, cesarean section, peripheral vascular bypass, or elective plastic surgery in selected developed countries were considered. We conducted meta-analysis with a generalized linear mixed model and assessed risk of bias. This study is registered with PROSPERO,CRD42023416876.

Results: Data from 224 studies indicated a cumulative incidence of deep S. aureus infection after hip surgery 5.05 infections/1000 procedures (95% CI 3.29-7.74), 5.59 (95% CI 3.62-8.63) after knee surgery, 11.74 (95% CI 9.08-15.16) after spinal surgery, and 7.23 (95% CI 1.63-31.86) after CABG surgery. S. aureus infections were associated with increased all-cause mortality among CABG, hip, knee, and spinal surgeries. Patients cohorts who received antibiotic prophylaxis and/or underwent decolonization demonstrated lower incidence of S. aureus infections.

Conclusions: The incidence of S. aureus infections varies by procedure, with highest rates seen after spinal surgeries and hysterectomies. Findings highlight the importance of standardized prevention across surgical settings.

Introduction: Cryptococcal meningitis (CM) is the second leading cause of AIDS-related mortality where the burden of advanced HIV disease is concentrated. Advances in diagnostics and treatment, including cryptococcal antigen (CrAg) screening and short-course antifungal regimens, have improved clinical outcomes in trials, but replicating these same benefits in routine care has proven more difficult.

Areas covered: This review outlines the biological rationale for CrAg screening and examines the major operational barriers to effective CM diagnosis in low-income countries. An exploratory literature review identified peer-reviewed articles published before May 2025. We assess challenges for CD4 testing, CrAg screening, lumbar puncture (LP) performance, and routine surveillance. Novel approaches, including risk stratification with semi-quantitative CrAg testing are also described.

Expert opinion: The impact of recent diagnostic and treatment advances for cryptococcal disease has been constrained by gaps in implementation. Closing the diagnostic gap requires strengthening decentralized CD4 testing; expanding reflex and point-of-care CrAg, including use of semi-quantitative CrAg assays to prioritize those at highest risk for urgent LP and/or enhanced antifungal treatment; strengthening healthcare provider training, referral systems, LP access, and enhancing community engagement. Integration of these measures into national HIV programs alongside operational research could reduce mortality for patients and costs for health systems.

Introduction: Candidiasis comprises a spectrum of infections ranging from superficial mucosal to life-threatening systemic infections caused by the opportunistic yeast, Candida, a genus containing several species of heterogeneous behavior and unique pathogenesis in the human host. Candida albicans is the most prevalent species. The aim of this review is to provide an update on pathogenesis, resistance and emerging therapeutic strategies in candidiasis, with a focus on C. albicans.

Areas covered: We discuss recent advancements that have deepened our understanding of Candida pathogenesis, particularly the roles of morphological plasticity, metabolic flexibility, biofilm formation, multidrug resistance and gut dysbiosis. We interrogated three major databases, mainly PubMed, Scopus and Google Scholar for the latest (with emphasis on the works published in the last 5 years) developments in antifungal resistance trends, diagnostic innovations, and novel therapeutic strategies, including next-generation antifungals, combination therapies and nanopharmaceuticals. Additionally, we explore emerging strategies, such as probiotics, vaccines, and antifungal stewardship, and discuss the impact of post-COVID-19 immunosuppression, cancer therapies, and climate change on candidiasis epidemiology.

Expert opinion: The future of C. albicans management lies in personalized approaches, leveraging genomics, host-pathogen interactions and advanced drug-delivery platforms to combat resistance, overcome the limitations of current systemic therapy and improve patient outcomes.