Expert Review of Anti-infective Therapy最新文献

Introduction: Despite improvements in the prevention of HIV mother-to-child transmission in recent years, the elimination of pediatric HIV remains elusive. Extended postnatal prophylaxis (ePNP) could be key to achieving this goal.

Area covered: Key questions surrounding timing of ePNP administration are: How long should ePNP be administered for? Should antiretroviral drugs with a long half-life be favored? Could ePNP be improved using long-acting injectable products adapted for use with neonates, infants, and children? In the search strategy (four databases), only articles published in English between 1990 and 2025 were included.

Expert opinion: As there is a risk of HIV transmission throughout breastfeeding, if ePNP is initiated - guided or not by maternal HIV viral load -, it should be administered until breastfeeding has ceased completely. Determining the plasma/tissue level of antiretroviral drugs or broadly neutralizing HIV antibodies (bNAbs) required to protect against HIV acquisition through breastfeeding is a research priority. Long-acting antiretroviral drugs are currently unavailable for prophylaxis or treatment in neonates and children. Several studies are currently evaluating the safety and pharmacokinetics of bNAbs in neonates and children exposed to HIV. These bNAbs could represent a significant advance in the prevention of postnatal HIV acquisition in the future.

Introduction: There is a growing acknowledgment of the importance of stewardship initiatives in solid organ transplant given the increased potential for morbidity and mortality. Antiviral stewardship, particularly as it pertains to cytomegalovirus (CMV), has been most extensively studied.

Areas covered: This review outlines the history and development of stewardship interventions in the solid organ transplant population with a focus on antiviral stewardship of CMV. Obstacles and proposed solutions to these obstacles from the vantage point of the UW Health experience are shared. Proposed future applications of the antiviral stewardship framework and structure are discussed. A systematic review of English language studies published since 2000 was performed. Search terms included solid organ transplant, antimicrobial stewardship, antiviral stewardship, post-transplant viral infections, and cytomegalovirus.

Expert commentary: Antimicrobial stewardship has a role in the immunocompromised host, and CMV antiviral stewardship is a unique application in solid organ transplant. Utilization of this initiative can improve outcomes related to CMV, particularly in the high-risk population providing a proactive, dedicated effort with a well-established infrastructure for effective surveillance after prophylaxis. Targeted quality improvement initiatives can further personalize the initiative to address issues unique to each transplant center. Large scale or all-encompassing efforts are not required to obtain substantial benefit.

Introduction: Tuberculous meningitis is frequently associated with significant mortality and persistent neurological sequelae. Diagnosis is often delayed due to nonspecific symptoms and the low sensitivity of cerebrospinal fluid (CSF) tests. Standard pulmonary tuberculosis regimens are suboptimal for central nervous system involvement due to poor drug penetration and prolonged treatment. Emerging resistance, particularly to rifampicin and isoniazid, further complicates the management.

Areas covered: This review synthesizes recent data particularly on diagnostic tools, drug treatment, host-directed treatments, and supportive care in tuberculous meningitis. We summarize updated WHO recommendations and explore the pharmacokinetics and CSF penetration of antituberculosis drugs. Emphasis is placed on high-dose rifampicin, linezolid, and novel oxazolidinones such as sutezolid and delpazolid. Special populations, including children, pregnant women, those with human immunodeficiency virus, and drug-resistant disease are reviewed separately. The latest information of a variety of host-directed therapies is discussed. The utility of artificial intelligence for diagnosis and prognostication is also discussed.

Expert commentary: Despite advances, tuberculous meningitis remains a clinical challenge. Early diagnosis, optimized dosing, and host-directed therapy are key priorities. Individualized regimens based on pharmacokinetics, drug resistance, and host factors are urgently needed. Precision diagnostics, new therapeutic agents, and artificial intelligence - driven tools may reduce mortality and improve outcomes.

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.