Current Opinion in Infectious Diseases最新文献

Purpose of review: Host and pathogen biomarkers may lead to improved management of fever in children with cancer and post hematopoietic cell transplant (HCT). This review summarizes current evidence on biomarkers for predicting infections.

Recent findings: Host biomarkers show promise for distinguishing between infectious and noninfectious causes of fever in patients with cancer or post HCT. Combining multiple biomarkers and integrating them into risk-stratification clinical scores may enhance predictive accuracy with the potential of individualizing antimicrobial treatment. Molecular diagnostic methods like multiplex PCR provide rapid detection of many pathogens. Emerging technologies such as transcriptomics, metabolomics, and microbial metagenomic next-generation sequencing demonstrate potential but require further evaluation. Large prospective studies are needed to validate standardized cutoffs and algorithms incorporating biomarkers into clinical decision-making. The integration of host and pathogen biomarkers holds the promise of optimizing antimicrobial therapy by tailoring treatment when indicated and minimizing unnecessary antimicrobials, ultimately enhancing patient outcomes.

Summary: Targeted biomarker-based strategies have the potential to improve antimicrobial stewardship and outcomes in immunocompromised pediatric patients.

Purpose of review: Scrub typhus, caused by the intracellular bacterium Orientia tsutsugamushi , presents a significant global health threat, contributing to a high burden of febrile illnesses, especially in endemic regions. This review aims to detail the neurological complications associated with scrub typhus and discuss its pathogenesis, diagnosis, management, and prevention.

Recent findings: Research has demonstrated an expanding geographical distribution of scrub typhus beyond its traditional Asia-Pacific epicentre, with an increasing incidence reported in regions such as Africa, the Arabian Peninsula, and South America. Neurological complications, notably encephalitis and meningitis, have emerged as significant clinical manifestations, considerably affecting morbidity and mortality rates among affected individuals. The pathogenesis of scrub typhus involves intricate interactions, with Orientia tsutsugamushi selectively targeting dermal and endothelial cells, facilitating systemic dissemination and subsequent neurological implications. These findings highlight the imperative for heightened awareness and recognition of these severe complications to enhance patient outcomes and inform effective management strategies.

Summary: Scrub typhus remains a growing public health challenge, necessitating enhanced awareness and diagnostic capabilities to mitigate case under-reporting. Recognizing neurological manifestations is crucial, highlighting the need for further research into the disease's mechanisms and management strategies. Timely interventions and preventive measures are essential, particularly in emerging regions.

Purpose of review: Travellers' diarrhoea remains one of the most common diseases amongst international travellers. However, significant uncertainty remains about the most effective strategies for its prevention and management. This review summarises recent advances in travellers' diarrhoea epidemiology, diagnostics, and management, focusing on new severity definitions, the impact of molecular diagnostics, antimicrobial resistance, and postinfectious sequelae.

Recent findings: The incidence of travellers' diarrhoea remains substantial although much of this is attributable to mild disease. Viral travellers' diarrhoea is more frequently recognised due to the improved sensitivity of molecular diagnostics. Advances in microbiome research reveal both acute and persistent disruption to the microbiota following travellers' diarrhoea and antibiotic use. New severity definitions incorporating functional impairment offer improved clinical relevance but consensus over use remains lacking. Nonabsorptive antibiotics and probiotics show promise for treatment and prevention, but antimicrobial resistance continues to rise. Postinfectious irritable bowel syndrome (IBS) significantly impacts the recovery of some travellers' diarrhoea patients.

Summary: Consensus on severity definitions is needed to support successful research into new vaccines and therapeutics. Surveillance of resistance, research into microbiome disruption and recovery, and development of vaccines and probiotics are key priorities. Better pathophysiological understanding and new intervention strategies are required to help alleviate the suffering of post-travellers' diarrhoea IBS.

Purpose of review: Indications for pediatric solid organ (SOT) and hematopoietic cell transplantation (HCT) have expanded concurrently with a repertoire of new biologics and transplant-related immunosuppression regimens, leading to a growing population of immunocompromised children who remain at risk for infections. Immunization of these children is fundamental in preventing and mitigating the risk of vaccine-preventable diseases (VPD), yet remains suboptimal. This review summarizes emerging pediatric data, including new vaccine formulations, guidance updates, and evolving immunization strategies aimed at optimizing vaccine-mediated protection in pediatric transplant recipients, while highlighting ongoing knowledge gaps.

Recent findings: Despite published recommendations, immunization remains an underutilized prevention strategy resulting in pediatric SOT and HCT candidates and recipients remaining sub-optimally vaccinated and at risk for VPD. New immunizations, including recombinant hepatitis B, higher-valency pneumococcal conjugate, recombinant zoster, meningococcal b and polyvalent meningitis vaccines, and long-acting RSV monoclonal antibodies, show promise in providing enhanced immunogenicity and vaccine efficacy, but remain largely off-label or insufficiently studied in pediatric transplant recipients. Emerging evidence support the safety and immunogenicity of live attenuated viral vaccines (MMR, varicella) in selected pediatric SOT recipients and high-dose inactivated influenza vaccine in pediatric allogeneic HCT recipients. Inclusion of transplant recipients in vaccine clinical trials is essential, as is additional research to improve our understanding of mechanisms of vaccine immunogenicity and evaluation of both humoral and cell-mediated immune responses that could best serve as surrogates of protective immunity in this population and inform individual vaccine recommendations.

Summary: Recent advances in immunizations offer new opportunities to prioritize vaccination both before and after SOT and HCT to enhance the protection against VPD in pediatric transplant recipients and improve their clinical outcomes. Future research should prioritize inclusion of pediatric transplant recipients in clinical trials and studies aimed at improving our understanding of vaccine safety, efficacy, and effectiveness in this population.

Purpose of review: Although considered a rare disease, neonatal HSV infection represents a disease in urgent need of preventive strategies, as it results in substantial neonatal morbidity and mortality. This review summarizes its current epidemiology and discusses guidances on the management of the asymptomatic neonate born to mothers with active genital HSV infection.

Recent findings: Timely detection and early high-dose acyclovir treatment of neonatal HSV infection decreases mortality. All neonates born to mothers with active genital HSV infection in the third trimester or at delivery should be tested for HSV infection. The newborn management has depended on whether the mother has experienced a primary or recurrent genital HSV infection based on maternal serologic testing and PCR testing of the genital lesion. An alternative strategy on neonatal management is proposed that is based on type of maternal HSV infection and perinatal risk factors.

Summary: The incidence of neonatal HSV infection is increasing with more infections due to HSV-1 than HSV-2. Guidances addressing management of the asymptomatic newborn exposed to active maternal genital HSV infection are discussed.

Purpose of review: Cryptococcus neoformans was recently declared a top priority fungal pathogen because of its propensity to cause a life-threatening meningoencephalitis, which continues to have high mortality and morbidity despite antifungal therapy. Our goal is to review recent developments in antifungal therapy while synthesizing how these are integrated into advances in understanding the pathophysiology of cryptococcosis.

Recent findings: The therapeutic outcomes for cryptococcosis continue to improve but the disease still carries an unacceptably high mortality and morbidity. Advances in therapy have largely come from optimizing the use of existing antifungal drugs, management of intracerebral and early diagnosis. A major development in the past decade was the recognition that immune responses contributed to damage in cryptococcosis, which has led to new research on the use of adjunctive immune modulators.

Summary: While progress continues to be made in the therapy of cryptococcosis by finding better ways to use existing antifungal agents and improve clinical management it is possible that this strategy is reaching its asymptote. Consequently, transformative reductions in mortality and morbidity are likely to require new antifungal agents and/or adjunctive immunotherapies. Fortunately, there are there several promising approaches in the horizon that will hopefully future drive clinical investigation.

Purpose of review: Infections caused by New Delhi metallo-β-lactamase (NDM) and OXA-48-producing Enterobacterales pose a critical threat due to increasing global prevalence and limited therapeutic options. This review provides an updated overview of evolving epidemiological trends, clinical implications, and both current and emerging treatment options.

Recent findings: In the past decade, the epidemiology of carbapenem-resistant Enterobacterales (CRE) has changed, with NDM and OXA-48 replacing KPC in several regions. Outcomes of infections caused by NDM-producing CRE remain poor, due to limited treatment options. Ceftazidime/avibactam and aztreonam is the first-line therapeutic option, whereas cefiderocol represents an alternative if susceptibility is confirmed. Resistance to both aztreonam/avibactam and cefiderocol has been reported among NDM-5-producing Escherichia coli , raising concerns in the scientific community. New agents, including cefepime-zidebactam and cefepime-taniborbactam, are currently in development and may expand the future treatment landscape. For OXA-48-producing CRE, ceftazidime/avibactam and cefiderocol are currently available therapeutic options, whereas cefepime/enmetazobactam may become available in the next future.

Summary: Optimal management of NDM- and OXA-48-producing Enterobacterales requires individualized approach guided by pathogen type, resistance profile, and patient characteristics. Improved diagnostics and surveillance are essential to guide early treatment, while novel agents may enhance therapeutic options in the near future.

Purpose of review: This review provides an updated overview of diagnostic strategies for viral meningoencephalitis, with a focus on molecular techniques currently used in clinical practice and the emerging role of next-generation sequencing technologies.

Recent findings: The clinical and laboratory presentation of viral meningoencephalitis is often nonspecific, making timely and accurate diagnosis challenging. While PCR and multiplex RT-PCR assays have become widely used, they have notable limitations, including reduced sensitivity in low-viral-load cases and the requirement for prior pathogen suspicion. Newer platforms like QIAstat-Dx allow interpretation through cycle threshold values, but false positives and false negatives remain concerns. mNGS offers a hypothesis-free approach with improved diagnostic yield - especially in immunocompromised hosts and atypical presentations - and has proven valuable for detecting rare, emerging, or unexpected pathogens. However, practical limitations such as cost, long turnaround times, and the need for expert interpretation currently restrict its routine use.

Summary: The integration of mNGS into routine diagnostic workflows could significantly improve the diagnostic yield for viral meningoencephalitis, especially in cases with negative or inconclusive results from traditional methods. However, further studies are necessary to refine its clinical application, optimize cost-effectiveness, and establish guidelines for its use in the diagnostic management of meningoencephalitis.

Purpose of review: This review summarizes recent and emerging advances in tuberculosis (TB) treatment, focusing on new therapeutics, repurposed agents, and shortened treatment regimens. It aims to contextualize key developments within the evolving TB treatment landscape and assess their potential to transform clinical management of both drug-susceptible and drug-resistant disease.

Recent findings: Evidence from landmark trials, including Nix-TB, ZeNix, TB-PRACTECAL, STREAM, Study 31/A5349, SHINE, TRUNCATE-TB, endTB and BEAT-TB has supported the use of licensed, repurposed, and novel agents as new treatment strategies. These studies have demonstrated the feasibility of treatment-shortening regimens for drug-susceptible TB and improved outcomes for multidrug-resistant TB. Progress has expanded the therapeutic armamentarium, with promising regimens incorporating new agents, higher-dose rifamycins, and safer, all-oral combinations.

Summary: These advances have direct implications for clinical practice, offering shorter, safer, and more effective treatment options. Adoption of these new regimens into treatment guidelines will allow us to reduce treatment burden, improve adherence, and lower the risk of adverse effects. Continued optimization of drug combinations, dosing strategies, and safety profiles will be essential to achieving durable, scalable treatment options. Future research should prioritize regimen simplification, host-directed therapies, and tools for predicting and monitoring treatment response to support personalized, globally accessible TB care.