Expert Review of Anti-infective Therapy最新文献

Introduction: Despite 70+ years of research, the etiology of bacterial vaginosis (BV), the most common vaginal infection, is unknown. Numerous studies suggest that BV-associated bacteria (BVAB) are sexually transmitted. Additionally, a recent male partner treatment trial found that the addition of combination oral and topical antimicrobial therapy for regular male sexual partners to treatment of women with BV resulted in a lower rate of recurrence at 12 weeks. However, unlike other common sexually transmitted infections such as chlamydia and trichomoniasis, no sole infectious pathogen has been identified as the causative agent of BV. In addition, non-sexual factors (e.g. smoking, copper intrauterine device use, douching, and testosterone use) have been associated with an increased risk of BV in some studies. These findings underscore the complexity of BV pathogenesis and make it challenging to counsel patients on infection acquisition and prevention of recurrent disease.

Areas covered: This work summarizes the evidence for and against sexual transmission of BVAB.

Expert opinion: A large body of data provide substantial evidence suggesting that sexual activity is the predominant mode of initial BV acquisition. There are no data showing a direct causal association between non-sexual factors and BV development. Additional research investigating BV etiology is imperative.

Introduction: Urogenital tuberculosis (UGT) is a common manifestation of extrapulmonary tuberculosis and can affect all organs of the urinary tract and male genital tract. The actual main problem of UGT is late diagnosis and a high prevalence of urogenital organ destruction. Little progress has been made in preventing the disease from progressing to more destructive forms. Knowledge diffusion of critical insights of UGT is the objective of this revision.

Areas covered: A narrative review of urogenital tuberculosis was performed in the databases of PubMed, Embase, and Scielo without time and language restriction. Terms used in the review were: 'Tuberculosis'; 'Urogenital Tuberculosis'; 'Prostate tuberculosis'; 'Kidney Tuberculosis' and 'Bladder tuberculosis.'

Expert opinion: The actual problem of UGT is late diagnosis and the evolution to destructive forms of disease with high proportion of kidney loss, surgeries, chronic infection of the urinary tract and urologic related chronic renal failure. This problem solution is based on three key actions: 1) correct UGT features knowledge; 2) creation of diagnostic guidelines and 3) knowledge diffusion. The knowledge of UGT features and the knowledge diffusion are the main objectives of this review. The creation of liable guidelines is a task in progress and the objective of further studies.

Introduction: Pegylated interferon alpha-2a (PEG-IFN) has been used off-label as chronic hepatitis delta (CHD) treatment since the 1990s. However, it has not received formal approval for this indication. Bulevirtide (BLV), a first-in-class entry inhibitor, is the first drug approved for the treatment of compensated CHD. Since its conditional approval in 2020, data from clinical trials and real-world studies have emerged. Literature search included PubMed (last accessed July 2025), European Medicines Agency official reports, and international conference abstract books.

Areas covered: Several evidence gaps remain unmet, including the definition of treatment endpoints, the impact of therapy on clinical outcomes, optimal therapy duration, and the potential benefits of combination with PEG-IFN. This review aims to provide a comprehensive overview of the current evidence regarding the use of BLV, both as monotherapy and in combination with PEG-IFN.

Expert opinion: Bulevirtide 2 mg is an effective treatment for CHD in patients with and without advanced chronic liver disease, as demonstrated in clinical trials and real-world cohorts. In addition, long-term therapy appears to enhance response rates and may even promote the loss of HDV-infected hepatocytes, potentially leading to a sustained off-therapy response. However, new therapeutic strategies are needed for patients who do not respond.

Introduction: Intra-abdominal infections (IAIs) pose significant challenges to clinicians. The increasing prevalence of multidrug-resistant (MDR) organisms with evolving resistance patterns adds to the difficulty in managing IAIs.

Areas covered: This review synthesizes the latest evidence and recommendations from major global guidelines. Key topics include novel antimicrobial agents, empirical and targeted therapy strategies, and the role of antimicrobial stewardship in optimizing antibiotic use. Furthermore, advances in diagnostic tools, such as metagenomic next-generation sequencing and rapid resistance detection assays, are highlighted. Updates in therapy duration, emphasizing shorter courses guided by biomarkers and source control, are critically analyzed.

Expert opinion: The management of IAIs has advanced significantly, with updated guidelines highlighting the importance of early and appropriate antimicrobial therapy tailored to the infection's severity and resistance patterns, along with effective source control. Novel antibiotics such as ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, eravacycline, and cefiderocol have broadened treatment options for MDR pathogens. Shorter antibiotic courses, guided by source control and biomarkers, have shown to be as effective as traditional longer regimens. Future research should focus on understanding of global resistance patterns, expanding real-world evidence for novel antibiotics, refining biomarker-guided strategies, enhancing rapid diagnostics, and applying artificial intelligence for more personalized and precise management of IAIs.

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.