International Journal of Infectious Diseases最新文献

Background: Effective care for bacterial infections requires both new antibiotics (ABx) to address antimicrobial resistance (AMR) and appropriate diagnostics (Dx) to guide their use. Diagnostics are essential to identify pathogens, determine susceptibility, and support targeted prescribing, including ruling out unnecessary antibiotic use. However, diagnostics are undervalued in the current market, limiting their availability and integration with antibiotic development.

Aim: To examine the interplay between antibiotics and diagnostics and assess the potential value of coordinated development and partnerships.

Methods: This paper analyses the antibiotic and diagnostic development landscape, focusing on market dynamics, regulatory frameworks, and collaboration models involving ABx developers, Dx developers, clinicians, and public-sector stakeholders.

Results: Antibiotics and diagnostics are rarely developed or introduced in parallel, and available diagnostics often fail to deliver treatment-focused or point-of-care-relevant results. This misalignment hampers the effective deployment of new antibiotics and weakens stewardship. Cross-technology partnerships can improve trial efficiency, enhance market valuation, and support more targeted antibiotic use. Key barriers include fragmented incentives, regulatory misalignment, and financial constraints.

Conclusion: Better alignment between antibiotic and diagnostic development is critical to maximise clinical impact and support resistance monitoring. Public-sector support could help enable effective partnerships and improve patient outcomes.

Objectives: Despite the availability of rapid tuberculosis (TB) nucleic acid amplification (NAA) testing, prevention of TB transmission within healthcare facilities remains a challenge due to ongoing difficulties in promptly isolating infectious TB cases upon hospitalization.

Methods: We reviewed all hospitalized sputum culture-positive TB patients who were not immediately placed in airborne isolation before anti-TB treatment at a high caseload medical center in Taiwan during 2016-2019, and applied root cause analysis to systematically identify structural barriers to prompt isolation.

Results: Among 235 cases, 95 (40.4%) had non-suggestive chest radiography (CXR) findings (Category 1), 62 (26.4%) had suggestive findings but sputum testing was delayed (≥3 days; Category 2), and 78 (33.2%) had timely sputum testing but delayed positive results (Category 3,). In Category 1, 52.6% later developed typical CXR findings. In Category 2, 72.6% had misread CXRs and 27.4% had delayed review. In Category 3 (65.4% had sputum result turnaround time >3 days), TB-NAA test was not done in 24 (30.8%) patients (1 smear-positive and 23 smear-negative). Of the 13 false-negative TB-NAA cases, only one had repeat NAA testing.

Conclusions: Prompt isolation requires clinical alertness, accurate CXR interpretations, frontline TB-NAA, and repeat testing when suspicion persists despite negative results.

Objective: The aim of this study is to guide other investigators in designing and implementing an appropriate pediatric outpatient parenteral antimicrobial therapy program in healthcare settings.

Methods: A systematic review of studies that included a description of outpatient parenteral antimicrobial therapy in children was conducted. A register of the review protocol was carried out in PROSPERO (registration number: CRD420251054490), which followed PRISMA guidelines. The literature search was performed in four healthcare databases (PubMed, EMBASE, Cochrane Library and CINAHL) with no publication date or language restrictions.

Results: A total of 1,764 articles were identified, of which only 37 met the inclusion criteria. Most outpatient parenteral antimicrobial therapy programs were home-based and mainly involved pediatricians and nurses. In terms of clinical results, most programs demonstrated a hospital readmission rate of 0-10% and full antimicrobial therapy completion. In regard to safety, catheter-related infections and neutropenia were the most common complications identified.

Conclusion: Home-based therapy treatment appears to be the most frequently implemented model, associated with reduced healthcare costs and high patient and caregiver satisfaction. This systematic review advances current knowledge by synthesising available evidence on paediatric OPAT program organisation, clinical outcomes, and safety, and by identifying key gaps to inform future program development and standardisation.

Background: Bacterial meningitis remains a major cause of neurological morbidity and mortality, particularly in low- and middle-income countries. To better characterise the aetiology, clinical features, and prognostic determinants, we conducted a seven-year investigation of adult bacterial meningitis cases admitted to a large tertiary hospital in northern Vietnam.

Methods: A retrospective-prospective observational cohort study was conducted between 2018 and 2024, including adults diagnosed with bacterial meningitis. Clinical characteristics, cerebrospinal fluid (CSF) parameters, culture results, and targeted in-house PCR findings were analysed. Outcomes were assessed using Glasgow Outcome Scale (GOS), with unfavourable outcomes defined as GOS 1-4. Multivariate logistic regression identified independent predictors of mortality and unfavourable outcomes.

Results: Of 232 screened patients, 150 met inclusion criteria. Pathogens were identified in 62 (41%) cases. Streptococcus suis was the predominant pathogen (n=26), followed by Streptococcus pneumoniae (n=10). CSF culture yielded growth in 35% of cases, while PCR detected six additional culture-negative infections. Overall mortality was 5%, and 10% of patients experienced unfavourable outcomes. Independent predictors included alcoholism (unfavourable outcome OR 13.8, 95% CI 2.1-100; mortality OR 16.5, 95% CI 1.9-165), focal neurological deficits (unfavourable outcome OR 41.4, 95% CI 9.2-250; mortality OR 12.8, 95% CI 1.7-123), and altered mental status (OR 8.6, 95% CI 1.5-86).

Conclusions: S. suis remains the leading cause of adult bacterial meningitis in northern Vietnam. Targeted interventions addressing high-risk groups, particularly individuals with alcoholism or neurological deficits at presentation, could improve clinical outcomes.

Background: Varicella-zoster virus (VZV) encephalitis typically presents with lymphocytic pleocytosis and mild-to-moderate elevation of cerebrospinal fluid (CSF) protein. Markedly elevated CSF protein concentrations and high viral loads are uncommon, particularly in immunocompetent individuals, and their clinical implications remain poorly defined.

Case presentation: We reported a 67-year-old immunocompetent woman with VZV encephalitis who exhibited an extremely elevated CSF protein level (12.31 g/L) and a high CSF VZV viral load detected in CSF by next-generation sequencing. Neuroimaging revealed multifocal encephalitic lesions complicated by cerebral infarction and hemorrhage. The patient received standard antiviral and supportive management, with gradual clinical stabilization and marked improvement in CSF parameters. However, she developed delayed-onset hydrocephalus during the follow-up and underwent ventriculoperitoneal shunting, after which sustained neurological recovery was achieved.

Conclusions: This case broadens the spectrum of recognized CSF abnormalities in VZV encephalitis and underscores delayed hydrocephalus as a clinically important complication, even following apparent clinical and biochemical improvement. Prolonged surveillance may therefore be warranted in patients with severe VZV-related central nervous system infection.

Objective: This study aimed to determine the accuracy of metagenomic next-generation sequencing (mNGS) in diagnosing non-tuberculous mycobacteria (NTM) osteoarticular infection (OAI) and compare it with mycobacteria growth indicator tube (MGIT) culture.

Methods: This study was conducted on 193 patients with suspected NTM OAI treated from January 2019 to July 2022 at the Beijing Chest Hospital, Capital Medical University, Yantai Qishan Hospital or The Fourth People's Hospital of Nanning who had mNGS assay and MGIT culture results. Clinical comprehensive diagnosis was taken as the "gold standard". We investigated the diagnostic sensitivity, specificity, predictive value, and likelihood ratio of these tests.

Results: Of the 193 patients, 26 (13.47%) were diagnosed with NTM OAI, and 167 (86.53%) had non-NTM OAI. Compared to the MGIT culture results, mNGS showed higher sensitivity (100.0% vs. 7.7%), specificity (99.4% vs. 80.2%), positive predictive value (96.3% vs. 5.7%), negative predictive value (100.0% vs. 84.8%), positive likelihood ratio (167.000 vs. 0.389) and negative likelihood ratio (0.000 vs. 1.150). The area under the curve of the mNGS assay was 0.997 (95% confidence interval, 0.990-1.000).

Conclusions: The mNGS assay had greater diagnostic accuracy than the MGIT culture in patients with suspected NTM OAI.

Objectives: Fecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection (rCDI). However, the detection of Blastocystis spp. in potential donors remains controversial and often leads to donor exclusion, despite uncertain pathogenicity. This review aims to critically evaluate the available evidence on Blastocystis spp. transmission through FMT, its clinical impact, and the implications of current donor screening strategies.

Methods: A narrative review of the literature was performed using PubMed, Embase, and Web of Science. Studies reporting Blastocystis spp. detection in FMT donors or recipients, transmission events, clinical outcomes, diagnostic methods, and microbiome associations were included and analyzed.

Results: Across published reports, 34 FMT recipients were exposed to Blastocystis spp.-positive donor material. Transmission was limited to common subtypes (ST1-ST3), was transient, and was not associated with adverse clinical outcomes or reduced efficacy of FMT for rCDI. No cases of symptomatic infection were reported. Frozen stool preparations appeared to abolish parasite viability. Molecular screening methods markedly increased detection rates compared with microscopy, frequently identifying low-burden colonization of uncertain clinical relevance. Available data suggest that Blastocystis spp. carriage may coexist with a healthy microbiome and does not negatively impact FMT outcomes.

Conclusions: Current evidence indicates that Blastocystis spp. transmission through FMT in immunocompetent adults is clinically benign. Routine donor exclusion based solely on Blastocystis spp. detection may therefore be overly restrictive. A risk-based approach incorporating parasite burden, subtype, host factors, and processing methods may better balance patient safety with donor availability, supporting more sustainable FMT programs.

Objectives: This study aimed to determine the proportion of patients admitted "for" and "with" COVID-19 and to compare their characteristics.

Methods: This was a retrospective cohort study using data from the cluster-wide COVID-19 registry from January 2020 to December 2022. Characteristics of admissions 'for' and 'with' COVID-19 were compared using the Wilcoxon rank-sum test or the Chi-square test, as appropriate.

Results: Of 28,538 COVID-19-related admissions, 9,539 (33.4%) were classified as 'for' COVID-19 and 18,999 (66.6%) as 'with' COVID-19. Compared to patients admitted 'with' COVID-19, those admitted 'for' COVID-19 were significantly older (median (IQR): 71 (54 - 82) vs. 34 (4 - 60) years, p < 2.2 × 10⁻¹⁶), tended to be male (59.0% vs. 51.7%, p < 2.2 × 10⁻¹⁶) and had more comorbidities (proportion with ≥3 comorbidities: 41.7% vs. 15.1%, p < 2.2 × 10⁻¹⁶). Admissions 'for' COVID-19 were also associated with poorer outcomes compared to admissions 'with COVID-19, with higher Intensive Care Unit (ICU) admission (5.1% vs. 0.9%, p < 2.2 × 10⁻¹⁶) and mortality rates (6.1% vs. 0.7%, p < 2.2 × 10⁻¹⁶).

Conclusion: Our findings also highlighted the demographic and clinical differences between the two groups, emphasizing the importance of distinguishing between admission types when evaluating disease burden and allocating healthcare resources.

Background & aim: Paradoxical reactions (PR) in HIV-negative tuberculosis is not well understood. This study aimed to determine incidence, clinical and immunological predictors of paradoxical reactions.

Methods: Patients with tuberculous lymphadenitis (TBLN) on anti-tuberculous therapy (ATT) were monitored for PR. Clinical, histopathological, microbiological, and immunological parameters of PR (n=10) and no PR (n=66) groups were analysed at baseline, 2 months and 6 months. Peripheral blood mononuclear cells from paradoxical reaction (n=9) and no paradoxical reaction (n=13) patients were stimulated with TB-ESAT peptide, and mRNA expressions of cytokines (IL-4, IL-10, IL-12, TNF-α, IFN-γ) and transcription factors (T-bet, GATA-3) were quantified.

Results: PR incidence was 5.7% (4/70); six patients presented with PR at baseline. The mean paradoxical reaction onset was 3.25 months. Absence of necrosis at baseline was protective (OR: 0.069; p=0.039). IL-10 mRNA at 2 months and IL-12 mRNA at 6 months increased in the PR compared to no PR group (p=0.05). In PR group, only baseline T-bet mRNA correlated with IFN-γ (r=0.79, p<0.01) but TNF-α correlated at baseline and 2 months (r=0.97, p<0.000; r=0.86, p<0.002). In no PR, T-bet mRNA correlated with IFN-γ and TNF-α at all time points (p<0.05), while GATA-3 mRNA correlated with IL-4 and IL-10 at 2 and 6 months (p<0.05).

Conclusion: Differential Th1/Th2 regulation driven by transcriptional factors alters cytokine expression, influencing paradoxical reaction. Further transcriptomic/proteomic studies are needed to elucidate immune mechanisms.

Background: Faecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridioides difficile infection (CDI); its use is increasingly being investigated for other indications. Although regional surveys and national registries have provided insight into local practices, a comprehensive global overview of FMT access, implementation and governance is lacking.

Methods: A survey regarding key aspects related to FMT use was disseminated electronically to members of the World Gastroenterology Organisation, European FMT Network, and International Society of Infectious Diseases. Responses were analysed both descriptively and using appropriate statistical methods.

Findings: 80 responses were obtained from 55 countries. FMT was available in significantly more Tier 1/2, than Tier 3/4, nations (24/28 vs 8/27; p<0.001). In countries lacking access to FMT reasons included: lack of expertise/infrastructure; financial constraints; regulatory uncertainty; and perceived lack of clinical need. Most countries using FMT employed both upper and lower gastrointestinal administration routes; 18/32 (56%) used capsulised FMT. Almost all countries with access to FMT used it to treat CDI, albeit with different thresholds for the number of CDI episodes prior to use. There were many non-CDI indications for FMT in current use. Payment for stool donation was reported by 10 countries.

Interpretation: This is the first global overview of FMT availability and governance, highlighting substantial international inequities and considerable heterogeneity in regulation, clinical use, donor screening, and cost. Standardisation of practice and targeted support for lower income countries is needed to ensure equitable access and to promote safe, high-quality delivery as FMT and microbiome-based therapeutics continue to evolve.