Clinical Infectious Diseases最新文献

Background: Chlamydia trachomatis (CT) is the most commonly reported bacterial sexually transmitted infection in the United States and is routinely detected using nucleic acid amplification tests (NAATs). However, its obligate intracellular life cycle creates challenges for culture, viability determination, and antimicrobial susceptibility testing (AST). Despite these challenges, culture remains important for select applications, including strain typing, test-of-cure, sexual assault investigations, and resistance monitoring.

Methods: We conducted a systematic literature search across 5 electronic databases using defined terms to identify studies on CT culture methods, viability assays, and molecular or phenotypic approaches for antimicrobial resistance detection. Twenty-nine manuscripts met inclusion criteria and were synthesized narratively.

Results: Our review found limited progress in CT culture techniques over the past decade. While several methods show promise for viability assessment and resistance detection, standardization and widespread implementation remain lacking. Phenotypic AST is restricted to specialized laboratories, and validated genotypic assays are not widely available. These gaps hinder accurate assessment of treatment failure and resistance trends.

Conclusions: The need for CT culture in routine clinical practice is declining, but culture continues to play a role in research, surveillance, and select clinical scenarios. Significant gaps in current technology include the inability to distinguish viable from nonviable organisms and lack of standardized AST protocols and genotypic resistance assays. Future research should prioritize development of clinical viability assays, consensus AST methods, and integrated genomic approaches to improve diagnostics and strengthen surveillance.

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most commonly reported sexually transmitted infections (STIs) in the United States, and their accurate diagnosis is critical for preventing serious health outcomes. Nucleic acid amplification tests (NAATs) are still considered the gold standard for the laboratory diagnosis of chlamydia and gonorrhea due to their high sensitivity and specificity. Since the 2014 CDC laboratory recommendations, several key improvements to FDA-cleared NAATs have been made including expanded specimen types, technology, and process improvements.

Methods: We conducted a systematic literature search and a narrative review focused on the performance of laboratory-based molecular diagnostics for CT and NG. This systematic review evaluated 145 studies to assess current diagnostic performance, focusing on six key areas: FDA-cleared diagnostic NAATs, self-collected specimens, pooling strategies, time to negativity, confirmatory/repeat testing, and LGV diagnostics.

Results: Many assays now include claims for clinician-collected extragenital specimens and self-collected vaginal swabs with high sensitivity (>90%) and specificity (>98%), and the recent FDA authorization of the first self-collection kit for nonclinical settings represents a major milestone in STI care access. However, no NAATs currently have claims for patient-collected extragenital specimens, despite strong evidence of comparable performance and high patient acceptability. Newer versions of assays incorporate dual targets for both CT and NG to enhance positive predictive value and reduce diagnostic escape. While no FDA-cleared assays exist for LGV differentiation, several laboratory-developed tests show promise.

Conclusions: Future directions include expanding FDA clearance for self-collected extragenital specimens and developing viability assays to better distinguish active infection from residual nucleic acids. Together, these advances underscore the progress in CT/NG testing and highlight opportunities to further improve diagnostic reach and clinical relevance.

Background: Neisseria gonorrhoeae (GC) rapidly develops antimicrobial resistance, complicating treatment and surveillance. Although interest in resistance-guided therapy is increasing, most infections are treated empirically. Culture-based antimicrobial susceptibility testing (AST) remains essential but is limited by the fastidious nature of GC. Molecular AST shows promise but is constrained by incomplete validation of resistance determinants.

Methods: We conducted a systematic review of phenotypic and molecular AST methods for GC using predefined search strategies across Medline, Embase, Cochrane, CINAHL, and Scopus (2009-2024). Of 3136 unique manuscripts identified, 80 met inclusion criteria. Data extraction captured test methods, performance characteristics, and reported strengths and limitations.

Results: Agar dilution remains the gold standard for GC AST, though its labor-intensive workflow limits routine use. Disk diffusion, gradient diffusion, and broth microdilution offer feasible alternatives but show method- and drug-dependent variability compared with agar dilution, influenced by media and manufacturer differences. Molecular assays reliably predict ciprofloxacin susceptibility via the gyrA S91F mutation, whereas predictive accuracy for other antibiotics is limited due to multigenic resistance mechanisms. Next-generation sequencing expands detection of resistance determinants but is not yet practical for rapid clinical decision-making.

Conclusions: Culture-based AST remains the most reliable approach for detecting GC resistance. Molecular methods have targeted utility, primarily for ciprofloxacin, and require broader validation. Standardizing alternative phenotypic methods, improving molecular marker characterization, and strengthening surveillance capacity will be essential to support resistance-guided therapy.

Background: Point-of-care tests (POCTs) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae offer the potential for rapid diagnosis and treatment, improving patient outcomes and reducing disease transmission. We sought to compile evidence on the accuracy and clinical utility of molecular-based POCTs and near-POCTs for the detection of C. trachomatis and N. gonorrhoeae.

Methods: We performed a systematic literature search of 5 electronic databases from January 2009 to January 2024 to understand the performance characteristics and implementation considerations associated with Food and Drug Administration-cleared POCTs and near-POCTs. Results were described in a narrative format.

Results: From 3743 identified studies, 64 met our inclusion criteria. As of 2025, there are 4 Food and Drug Administration-cleared POCTs/near-POCTs for detecting C. trachomatis and N. gonorrhoeae, 3 of which are waived by the Clinical Laboratory Improvement Amendments and suitable for use during a patient visit. Evidence suggests that POCTs are most beneficial in symptomatic patients within acute care settings, where they can prevent loss to follow-up and reduce the need for empiric antibiotic treatment.

Conclusions: While some POCTs for C. trachomatis and N. gonorrhoeae have achieved regulatory clearance, challenges remain, including the need to expand specimen type clearance to include extragenital specimens, to further improve turnaround times, and to decrease cost for adoption. There is need to optimize the use of POCTs in acute care settings to manage sexually transmitted infections.

Background: Neisseria gonorrhoeae (GC) culture remains critical for gonorrhea treatment and surveillance, as antimicrobial susceptibility testing currently depends on culture-based methods. Here we aim to describe how GC culture and identification methods have changed since they were last described by the US Centers for Disease Control and Prevention.

Methods: We performed a systematic literature search to address the questions, "Have culture methods for GC changed since they were last described in 2009," "What biochemical tests can be used for the identification of GC," "What is the utility of MALDI-TOF for detecting GC," and "When should GC culture be performed?" Using defined search terms across 5 electronic databases, we identified 4926 papers published between 2009 and 2024, of which 51 met inclusion criteria for narrative review.

Results: GC culture conditions have remained largely unchanged, but there has been continued improvement in preanalytical processing products and procedures. Patient-collected specimens, including urine, demonstrate equivalent culture yield compared with clinician-collected specimens, offering opportunities to enhance GC surveillance. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has emerged as a reliable, rapid, cost-effective, and accurate method of GC identification, offering numerous advantages over traditional biochemical methods for GC identification.

Conclusions: Although the evidence suggests that GC cultures from urogenital specimens of symptomatic patients yield the highest recovery rates, the potential for antimicrobial-resistant GC in the pharynx underscores the importance of culturing all anatomical sites of exposure. Maintaining GC culture capacity remains critically important for surveillance and antimicrobial susceptibility testing of GC.

This supplement review article discusses recent advancements in Chlamydia trachomatis and Neisseria gonorrhoeae detection methods, addressing key questions related to laboratory-based molecular methods, point-of-care testing, culture, and resistance detection. Each manuscript in this supplement summarizes available test methods and their performance characteristics. Additionally, current challenges and research gaps are described. Emerging technologies, such as molecular point-of-care tests and self-collection kits, are highlighted for their potential to improve accessibility, accuracy, and patient-centered care.

Among 667 CAR-T recipients, the 2-year cumulative incidence of RSV was 7%, with 29% of diagnosed cases progressing to LRTI. Older age and lymphopenia were associated with severity. Most infections (74%) occurred beyond day +100 (median 8 months). No RSV-attributable deaths occurred. Clinical vigilance is warranted, especially during RSV season.

Background: To investigate the clinical characteristics and outcome of patients with herpes simplex type 1 (HSV-1) encephalitis.

Methods: Nationwide, prospective, population-based cohort study using the Danish Study Group for Infections of the Brain database to identify all adults hospitalized with microbiologically confirmed HSV-1 encephalitis from 2015-2023 in Denmark. Modified Poisson regression was used to estimate relative risks (RR) with 95% confidence intervals (CI) for 6-month mortality by time to acyclovir after admission and adjusted for age, sex, immunocompromise, altered mental status, and imaging abnormalities. Analysis was repeated post-hoc using time after lumbar puncture as reference.

Results: Overall, 154 patients with confirmed HSV-1 encephalitis were included yielding a mean annual incidence of 0.36/100.000. Frequent symptoms at admission included a history of fever 101/128 (79%) and confusion 99/154 (78%). The median times from admission to lumbar puncture and acyclovir treatment were 21 hours (interquartile range [IQR] 6-70) and 24 hours (IQR 7-74), respectively. The adjusted RR for 6-month mortality was 1.15 (95% CI 0.39-3.41) for acyclovir initiation >6 hours after admission and 1.06 (95% CI: 1.004-1.13) for each day of delay after admission. The adjusted RR of 6-month mortality was 1.85 (95% CI: 1.01-3.45) for delayed acyclovir treatment of >6 hours since lumbar puncture. Anti N-Methyl-D-aspartate receptor encephalitis was diagnosed in 9/154 (6%) of patients after HSV-1 encephalitis.

Conclusion: Early recognition of HSV-1 encephalitis remains challenging, and the condition is associated with high mortality. Delayed acyclovir treatment, especially following lumbar puncture, was associated with increased risks of fatal outcome.