Current Opinion in Infectious Diseases最新文献

Purpose of review: This article reviews recent and ongoing randomized controlled trials (RCTs) investigating novel antibiotics and treatment strategies for severe Gram-negative infections, particularly those caused by multidrug-resistant (MDR) organisms. It discusses how these trials are reshaping clinical practice and outlines current limitations in their applicability to real-world scenarios.

Recent findings: Several novel β-lactams and β-lactam/β-lactamase inhibitor combinations have shown efficacy in RCTs targeting infections like complicated urinary tract infections, intra-abdominal infections, and hospital-acquired pneumonia. Additional considerations on the results of recent RCTs challenge the necessity of combination regimens, and a growing body of evidence from other RCTs support shorter treatment durations for selected Gram-negative infections, overall potentially reinforcing antimicrobial stewardship. However, limitations include small sample sizes in pathogen-specific subgroups, frequent exclusion of critically ill or immunocompromised patients, and a focus on sites and types of infections within narrow regulatory definitions.

Summary: Current RCTs have enriched clinical management of severe Gram-negative infections by validating new agents and supporting more personalized, safer, and shorter treatments. Nevertheless, gaps persist regarding their generalizability to high-risk populations and real-world infections. Complementary pathogen-focused trials, adaptive designs, and observational studies are needed to expand the evidence base, also for treatment duration in MDR infections, combination regimens, and resistance development. Integrating trial data with clinical judgment remains essential in bridging the gap between trial conditions and bedside care in line with the principles of precision medicine.

Purpose of review: Sulbactam-durlobactam (SUL-DUR) is a novel β-lactam/β-lactamase inhibitor combination recently approved for carbapenem-resistant Acinetobacter baumannii (CRAB) infections. This review summarizes current knowledge on the optimal use of SUL-DUR, whether administered alone or in combination with carbapenems, particularly imipenem.

Recent findings: Data from registrational trial demonstrate that SUL-DUR is an effective and well tolerated treatment option for CRAB severe infections. However, this trial assessed the efficacy of SUL-DUR exclusively in combination with imipenem. Real-world reports have described successful use of SUL-DUR in combination with carbapenems and other agents, particularly in complex or drug-resistant cases. Microbiological data suggest synergistic effects between SUL-DUR and carbapenems due to complementary inhibition of different penicillin-binding proteins.

Summary: Combination therapy of SUL-DUR with carbapenems remains the preferred strategy in critically ill or high-risk patients. Future trials should specifically evaluate the comparative efficacy of monotherapy vs. combination regimens and establish which could be the best companion in the treatment of CRAB infections.

Purpose of review: Diagnostic stewardship (DS) aims to optimise the use of laboratory testing to improve patient care while reducing unnecessary tests. This review examines recent evidence on DS interventions to optimise the use of resources, focusing on three key areas: reducing unnecessary testing, maximising the impact of existing tests, and avoiding the overdiagnosis of hospital-acquired infections.

Recent findings: Multiple interventions have demonstrated effectiveness in reducing unnecessary blood and urine culture testing, including clinical decision support tools, education programs, and multidisciplinary approaches. Studies on optimising existing tests have focused on blood culture workflows, reporting of nonsterile samples, and implementation of multiplex PCR panels. Interventions to reduce overdiagnosis of catheter-associated urinary tract infections and Clostridioides difficile infection have shown promise. However, the monitoring of unintended consequences varies across studies. Most publications were retrospective cohort studies, with few randomized trials.

Summary: DS can safely reduce inappropriate testing and maximise test effectiveness. Successful implementation requires multidisciplinary engagement and careful monitoring of the unintended consequences. Further high-quality studies, especially randomised trials, are needed to assess the clinical impact of DS interventions robustly.

Purpose of review: Plasma metagenomic next-generation sequencing (mNGS) enables detection of microbial cell-free deoxyribonucleic acid (mcfDNA) in blood without the need for culture or organism-specific primers. Here, we review clinical performance, methodological variability, and real-world application of plasma mNGS for infectious disease diagnosis in immunocompromised hosts (ICHs).

Recent findings: Plasma mNGS has rapidly gained attention as a novel diagnostic tool for infections in ICHs, offering broad-range pathogen detection from a noninvasive blood sample. A growing number of observational studies have assessed its diagnostic yield, clinical impact, and potential to reduce invasive procedures or time to diagnosis. However, results remain variable, with significant differences in study design, patient populations, and adjudication methods. While some studies report meaningful added value, others highlight challenges related to clinical interpretation, limited standardization, and uncertain cost-effectiveness. Moreover, although mNGS offers a wide organismal scope, its sensitivity is influenced by pathogen type, immune status, and technical limitations - particularly in fungal infections and low-burden diseases. Overall, mNGS has yet to find a clearly defined role in routine diagnostic workflows.

Summary: Understanding the current evidence, limitations, and variability surrounding plasma mNGS is essential to guide its appropriate clinical use and to inform future integration into diagnostic pathways for ICHs.

Purpose of review: The limitations of pathogen-directed therapies include growing antimicrobial resistance or the complete lack of any effective antimicrobial agents. This review highlights the potential for host-directed immunotherapies.

Recent findings: This review provides a current status of host-directed immunotherapies to fight infectious diseases (HIFI), defining the concept and existing modalities. Drawing on large-scale viral studies - most of which are historical with limited recent research - the review highlights key lessons for its future clinical application.

Summary: HIFI represents a paradigm shift in infectious disease management, moving beyond pathogen-targeting to harnessing and modulating host immunity. This approach requires better mechanistic and pharmacologic understanding of existing modalities, development of newer agents based on tractable immunobiology, and robust clinical studies.

Purpose of review: This review examines the interplay between biological and anthropogenic factors in the development and persistence of antimicrobial resistance (AMR) within building plumbing systems, which is of particular concern in high risk setting such as healthcare facilities. The review highlights the role of biofilms and amoeba as reservoirs for AMR and explores how engineering and design decisions, governance structures, and cleaning protocols influence microbial resistance dynamics.

Recent findings: Biofilms provide a protective environment that facilitates horizontal gene transfer and enhances bacterial resistance to disinfection. Amoeba-hosted bacteria can evade standard cleaning practices, further promoting AMR persistence. Emerging technologies, such as digital twin modelling, offer new opportunities to optimize risk mitigation strategies. However, more consideration is needed to be given to design or management decision that may have unintended consequences, such as unintended design outcomes, such as increased biofilm growth from tap mixers and low-flow fixtures, and ineffective cleaning protocols, which can inadvertently worsen AMR.

Summary: Effectively managing AMR in plumbing systems requires a multidisciplinary approach that integrates microbiology, engineering, and policy. Data driven risk assessments can identify high-risk areas that may require design changes but also can enable targeted cleaning strategies, reducing reliance on widespread disinfection that may drive resistance. Future policies must consider system-wide implications to prevent unintended consequences. By addressing both biological and anthropogenic drivers, we can develop sustainable solutions to mitigate AMR risks in healthcare and beyond.

Purpose of review: Whole genome sequencing (WGS) has transformed bacterial strain typing, an essential tool for outbreak detection, antimicrobial resistance surveillance, and tracking clonal emergence across clinical, research, and public health settings. Herein, we will review recent advances in WGS-based bacterial strain typing methods for purposes of comparison and classification with a focus on improvements in variant identification, strain classification, and transmission assessment.

Recent findings: Advances in sequencing technologies as well as variant calling methodologies and parameter optimization have enhanced the precision and accuracy of single nucleotide variant identification. Hierarchical clustering of gene-by-gene strain typing, combined with novel data management and classification strategies, has improved standardized pathogen typing schemes in an effort to streamline inter-laboratory comparison. Additionally, novel approaches to defining transmission thresholds now better account for species-specific traits, while progress in metagenomic sequencing enables strain identification and tracking within mixed microbial communities.

Summary: Recent developments have enhanced the accuracy, portability, scalability, and standardization of bacterial typing methods, integrating variant calling and gene-by-gene approaches into unified genotyping systems. However, challenges still remain in nomenclature consistency, inter-laboratory variant calling compatibility, and capturing bacterial heterogeneity. Future work should focus on refining genotyping frameworks to enhance surveillance and optimize detection of pathogen transmission while accounting for microbial diversity across various environments.

Purpose of review: Respiratory syncytial virus (RSV) poses a significant threat to immunocompromised individuals, yet preventive strategies and treatments remain largely unstudied in this population. New vaccines, mAbs, and antiviral agents are becoming available, with implications for high-risk patients.

Recent findings: RSV in immunocompromised individuals often leads to severe disease, prolonged illness, and treatment delays. Diagnostic challenges and the heterogeneity of immunosuppression complicate management. Recent advances include preF-based vaccines and monoclonal antibodies, though current recommendations exclude many immunocompromised patients. Early vaccine trials showed mixed immunogenicity results in this group and real-world effectiveness remains unclear. Antiviral agents are also under investigation, though efficacy data in immunocompromised hosts are limited. Infection prevention strategies remain critical in this high-risk group.

Summary: Despite promising advances in RSV prevention and treatment, immunocompromised patients remain underrepresented in clinical research. Targeted studies are urgently needed to determine optimal strategies for this vulnerable group. Until then, clinicians must rely on limited evidence and institutional protocols to guide care.

Purpose of review: This review explores the impact of community-acquired respiratory virus (CARV) infections on outcomes before proceeding with hematopoietic cell transplantation (HCT) and chimeric-antigen-receptor T-cell (CAR-T) therapy recipients and which conditions should be considered to delay or proceed with cell therapy. It aims to assess current practices, the risks associated with early CARV infections in cell therapy recipients, and potential modifications to reduce complications and improve clinical outcomes if delay is not an option.

Recent findings: Studies have shown that pretransplant CARV infections, particularly those with symptomatic lower respiratory tract disease (LRTD), are linked to increased mortality and prolonged hospitalization after hematopoietic stem cell transplant. The timing of CARV infection regarding the transplant, the type of CARV, and the intensity of immunosuppressive conditioning, among others, are key factors influencing outcomes. Additionally, recent research highlights the potential benefits of delaying transplantation, optimizing immunosuppression, and reducing the duration of neutropenia and lymphopenia to mitigate the risk of severe infections.

Summary: Key challenges include determining the optimal timing for transplant in CARV-positive patients, managing cell procedures, and minimizing risk factors to reduce the development of a severe course resulting in poor outcome. Current practices often prioritize timely transplant/CAR-T procedures but may need to be adjusted to account for CARV infections. Implementing strategies such as reduced-intensity conditioning, enhanced infection prevention measures, and antiviral therapy could significantly impact patient outcomes, particularly in preventing progression to LRTD and reducing the risk for fatal outcome.

Purpose of review: To review the benefits, risks and specific considerations surrounding antibacterial prophylaxis (ABP) in adults with neutropenia, focusing primarily on high-risk patients with hematologic malignancies (HM) and/or hematopoietic cell transplantation (HCT).

Recent findings: There has been an overall reduction in benefit of fluoroquinolone prophylaxis (FQP) observed in recent studies, with a lack of overall mortality benefit and less efficacy in reducing Gram-negative bloodstream infections (BSI) rates, which may be explained by increasing rates of fluoroquinolone resistance (both on center-level and patient-level) and improved early sepsis management. In the context of FQP, epidemiology of BSIs has changed with greater Gram-positive BSIs and resistant Gram-negative BSIs.

Summary: ABP, most frequently FQP, has been introduced since the 1980s with the aim of reducing rates of infection and mortality. While older meta-analyses support its efficacy in reducing episodes of febrile neutropenia (FN), BSI and most importantly mortality, more recent data report lack of benefit on mortality, and negative impacts such as rising antimicrobial resistance, and in the broader literature, safety concerns for FQP. The role of ABP in neutropenia has been increasingly questioned and should be considered at a center-by-center and an individual-patient level.