Infection最新文献

Background: Cabotegravir (CAB) and rilpivirine (RPV) constitute the first complete non-oral ART regimen for HIV-1 treatment. Due to virologic failure (VF) with resistance in clinical trials, concerns persist regarding broader use in clinical practice. In particular, the role of trough drug concentrations in relation to viremia and VF remains unclear. This study explored the association between CAB and RPV trough concentrations in a retrospective, single-center study.

Methods: We retrospectively analyzed data from the HIV research and clinical care center MVZ München am Goetheplatz, Germany. Inclusion criteria were CAB and RPV long-acting therapy every 8 weeks without additional ART and availability of drug concentrations within 7 days before the next administration. A modified Wilcoxon test assessed differences in concentrations between samples with HIV-1 RNA < 20 vs. ≥20 copies/mL. Odds ratios (ORs) were estimated using generalized estimation equation (GEE) models, and ROC analysis identified potential alternative drug concentration thresholds.

Findings: A total of 737 samples from 185 individuals were included. Median CAB concentrations were 1,480 µg/L (IQR: 1,097-1,955) vs. 1,180 µg/L (879-1,570) for samples with HIV-1 RNA levels < 20 copies/mL vs. ≥ 20 copies/mL, respectively (p = 0.001); for RPV, 77 µg/L (53-107) vs. 63 µg/L (47-87) (p = 0.001). Using ROC-derived thresholds, low concentrations of CAB (< 1,240 µg/L) or RPV (< 76 µg/L) were found in 11.5% and 25.4% of samples, respectively, and associated with ORs of 2.4 (1.5-4.0) and 2.3 (1.4-3.8) for HIV-1 RNA ≥ 20 copies/mL.

Interpretation: Lower CAB and RPV concentrations were associated with viremia, particularly using the ROC-derived thresholds. Among individuals with VF and available drug concentration data, 87.5% had at least one drug below these thresholds. Further research on therapeutic drug monitoring is warranted.

Purpose: Sepsis requires stratification for host-directed therapies through the discovery of adequate biomarkers enabling prediction of outcomes and treatment responses. Adrenomedullin has previously demonstrated potential for prognostic enrichment. This study aimed to assess associations of bioactive adrenomedullin (bio-ADM) levels at ICU admission and sepsis outcomes and to evaluate the potential of bio-ADM as marker to identify subgroups of patients with moderate disease severity that might benefit from hydrocortisone treatment.

Methods: We used data from the HYPRESS trial (NCT00670254) to investigate, if bio-ADM is useful to predict sepsis outcomes (septic shock, 90- and 180-day mortality) and benefit or harm by hydrocortisone treatment. Optimal cut-offs for outcome predictions were determined by Youden's index. Logistic regression was used to assess bio-ADM subgroups and treatment interaction.

Results: Bio-ADM levels differed significantly in patients with or without septic shock within 14 days (p = 0.011). While the area under the ROC curve (AUC) was only 0.603 (CI 0.531-0.676), patient subgrouping using bio-ADM levels showed significantly higher cumulative incidence of septic shock within 14 days in the subgroup of patients with bio-ADM levels ≥ 37 pg/mL (p < 0.001). The odds ratio for the development of septic shock in this group was 4.67 (95% CI 1.53, 20.3, p = 0.016). A bio-ADM cut-off of ≥ 136 pg/mL was predictive for 90-day (OR 8.21, 95% CI 2.46-27.9, p < 0.001) and 180-day mortality (OR 4.87, 95% CI 1.49-16.0, p = 0.008). Hydrocortisone therapy did not reduce the incidence of septic shock (OR 1.59, 95% CI 0.37-8.15, p = 0.54), 90-day (OR 1.53, p = 0.23) or 180-day mortality (OR 1.41, p = 0.25), regardless of bio-ADM stratification (interaction term p = 0.58 for septic shock; p = 0.31 for 90-day mortality; p = 0.51 for 180-day mortality).

Conclusions: Whereas bio-ADM levels are associated with sepsis outcomes, our data do not indicate usefulness of the marker to identify patients potentially benefitting from hydrocortisone therapy.

Introduction: Invasive fungal diseases (IFD) present serious risks to solid organ transplant recipients, particularly in the first 180 days post-transplant. Existing European and US guidelines offer limited evidence, prompting a shift away from universal prophylaxis due to adverse effects, drug-interactions, and costs. This study investigates antifungal prophylaxis practices in transplant centers to guide IFD management.

Methods: From May 2023 to May 2024, tertiary care institutions completed an online survey on antifungal prophylaxis post-transplant. Data included transplant volumes, IFD incidence by pathogen, and prophylactic strategies.

Results: Responses from 64 centers in 32 countries, mainly in Europe, highlighted kidney and liver as the most common transplants. Prophylaxis was universal in lung transplants and common in liver, bowel, and heart transplants, often triggered by reintervention or Candida spp. colonization. Preferred agents included liposomal amphotericin B and fluconazole.

Conclusions: This global survey reveals substantial variation in antifungal prophylaxis practices among solid organ transplant centers, driven by a lack of standardized, evidence-based guidelines. Our findings underscore the urgent need for harmonized recommendations that reflect evolving fungal epidemiology, improved diagnostics, and new antifungal agents.

Purpose: This study aimed to assess the associations between serum concentrations of copper, zinc and selenium, and pneumonia death risk.

Methods: Study included 2088 men from the Kuopio Ischaemic Heart Disease Risk Factor Study aged 42-60 years. Pneumonia deaths were collected by computer linkage to the national Causes of Death Register. Cox proportional hazards regression models, adjusted for multiple variables, were used for analysis.

Results: During a mean follow-up of 21.7 years (SD 7.5 years), 139 pneumonia deaths occurred. The multivariable-adjusted hazard ratio for pneumonia death in the highest serum copper-to-zinc-ratio and copper concentration tertiles were 1.75 (95% CI: 1.13-2.71) and 1.64 (95% CI: 1.08-2.50), respectively. Serum zinc concentration showed a statistically significant association with pneumonia death, with the lowest risk observed in the second tertile and no further decrease in risk in the highest tertile. Serum copper-to-selenium ratio nor selenium concentrations were associated with pneumonia death risk.

Conclusions: Our findings suggest that a higher serum copper-to-zinc-ratio and higher serum copper concentration are associated with increased risk of pneumonia death, while a higher serum zinc concentration is linked to a decreased risk of pneumonia death in middle-aged and older men.

Purpose: Rabies is a fatal zoonotic disease, and India accounts for 35% of global rabies-related deaths. In 2018, the World Health Organization (WHO) revised its guidelines for pre-exposure prophylaxis (PrEP) from a 3-dose to a cost-saving 2-dose intradermal (ID) regimen. This study evaluates the immunogenicity and safety of this regimen in pediatric populations, including children exposed to immunosuppressant therapy.

Methods: This single-center, prospective, comparative follow-up study was conducted at a tertiary care hospital. Participants (5-18 years) were enrolled into two groups: (1) children with no known immunodeficiency (n = 31) and (2) children on immunosuppressant therapy (n = 10). All received Vero cell culture rabies vaccine (RABIVAX-S^®) intradermally at two sites on days 0 and 7. Serum anti-rabies virus glycoprotein antibody titres were assessed on days 28, 90, and 180 using an ELISA-based assay. Booster doses were administered to those with insufficient titers (≤ 0.5 EU/ml).

Results: By day 28, both groups achieved a 100% seroconversion rate (SCR). Geometric mean titers (GMT) were 2.168 EU/ml and 1.547 EU/ml in the no-known-immunodeficiency and immunosuppressant therapy groups, respectively. At day 90, SCRs were 90% and 70%, with GMTs of 1.358 EU/ml and 0.962 EU/ml, respectively. Booster doses restored titers in all participants with insufficient levels. Pain at the injection site was the only solicited adverse effect.

Conclusions: The 2-dose ID PrEP regimen is immunogenic and safe in pediatric populations, including immunosuppressed children. It offers a cost-effective alternative in rabies-endemic regions, enhancing compliance and accessibility.

Trial registration: Prospectively registered with the Clinical Trials Registry India with Trial Registration No. CTRI/2022/10/046777.

Purpose: Diagnosing extrapulmonary tuberculosis (EPTB) - including pleural, peritoneal, pericardial, meningeal forms - remains challenging due to the insufficient sensitivity of smear microscopy (SM), mycobacteriological culture, and nucleic acid amplification test (NAAT). The Adenosine Deaminase (ADA) assay has potential as a diagnostic tool for EPTB, but its performance in high-income countries is poorly documented. This study aimed to evaluate the diagnostic performance of ADA for microbiologically confirmed EPTB in such a setting.

Methods: We retrospectively analyzed data from all patients undergoing ADA testing in our hospital network in Paris area between May 2014 and April 2024. Microbiological confirmation (positive SM, culture, or NAAT) from the same sample site served as the reference standard.

Results: Among 363 ADA assays (352 patients), 69% were pleural fluid, 18% peritoneal, < 1% pericardial, 11% CSF. For pleural fluid, ADA at a threshold of 30 U/L demonstrated 92% sensitivity (CI 80-98%), 75% specificity (CI 68-81%), 47% PPV (CI 37-57%), and 97% NPV (CI 94-99%). For peritoneal fluid, sensitivity, specificity, PPV, and NPV were 77% (CI 46-95%), 81% (CI 69-91%), 50% (CI 27-73%), and 94% (CI 82-99%), respectively. Raising the ADA threshold to 60 U/L improved specificity to 92% in pleural fluid (CI 87-95%) and 85% in peritoneal fluid (CI 73-93%). Combining ADA with other biomarkers showed no added diagnostic value.

Conclusion: ADA testing is a rapid and practical tool for EPTB diagnosis. In pleural and peritoneal fluids, a threshold < 30 U/L effectively excludes EPTB, while a threshold > 60 U/L supports initiating treatment pending culture results.

Purpose: Melioidosis is a serious infection caused by Burkholderia pseudomallei, a bacterium found in soil, water, and plants in tropical and subtropical regions. The infection can present with a range of clinical symptoms and may be fatal without appropriate treatment.

Case presentation: We present four confirmed cases of melioidosis in patients with a history as tourists travelling to endemic areas. These cases illustrate the diverse clinical manifestations of the infection, ranging from respiratory tract involvement to multiple organ abscesses, as well as the therapeutic approaches employed.

Conclusion: Melioidosis is a severe infection with variable clinical presentations, including fever, night sweats, weight loss, dyspnoea, and abscess formation at different sites. The broad spectrum of symptoms complicates diagnosis. Therefore, melioidosis should be considered in returning travellers from endemic regions presenting with compatible clinical features. Prolonged antibiotic treatment is essential for effective infection control.

Background: Community-acquired pneumonia (CAP) causes significant morbidity and mortality, but Swiss data are limited. We analyzed the Swiss CAPNETZ cohort to describe patient characteristics, pathogens, diagnostics, and outcomes.

Methods: Adults with CAP were prospectively enrolled between 2010 and 2022 at two tertiary hospitals. Data on demographics, comorbidities, microbiology, and outcomes were collected. Mortality was assessed at 28 and 180 days.

Results: Among 478 patients, 97.7% were hospitalized (median 7 days), and 76.4% had ≥ 1 comorbidity. ICU admission occurred in 7.3%. Overall mortality was 2.9% at 28 days and 5.5% at 180 days, increasing during the COVID-19 pandemic (28-day: 5.7%; 180-day: 10.9%). Higher mortality was observed in older, immunosuppressed, and oncologic patients. The etiological pathogens were detected in 38.3%, and molecular testing of sputum and bronchioalveolar lavage (BAL) enhances pathogen detection rates. Bacterial monoinfections predominated (20.2%), followed by viral (7.4%) and mixed infections (9.5%). Leading pathogens were Streptococcus pneumoniae (35.0%) and Haemophilus influenzae (16.1%). In immunocompromised patients, H. influenzae predominated.

Conclusion: Overall mortality of CAP stays high. S. pneumoniae remains the most common pathogen overall, while H. influenzae is the most frequent pathogen in immunocompromised patients. Molecular testing of sputum and BAL improves pathogen detection.

Objectives: There is a lack of systematic data on cerebrospinal fluid (CSF) findings in the different clinical manifestations of tick-borne encephalitis (TBE) and according to the duration of neurological involvement. This study aims to evaluate and compare routine CSF parameters in TBE patients presenting with meningitis, meningoencephalitis, or meningoencephalomyelitis, and to assess temporal changes in CSF during the first 10 days after the onset of neurological symptoms.

Methods: We analysed 15 CSF parameters in 717 consecutive adult patients hospitalized for TBE at the Department of Infectious Diseases, University Medical Centre Ljubljana, Slovenia. Among these patients, 230 (32%) had meningitis, 446 (62%) meningoencephalitis, and 41 (6%) meningoencephalomyelitis.

Results: CSF findings differed significantly among the three clinical presentations. Leukocyte count, neutrophil proportion, protein levels, immunoglobulin concentrations (IgM, IgG, IgA), and intrathecal synthesis quotients were highest in meningoencephalomyelitis and lowest in meningitis. These differences remained largely significant after adjusting for confounding factors. CSF abnormalities were detectable from day one of neurological symptoms, peaked around days 4-5, and then stabilized or showed mild improvement. Neutrophils predominated during the first two days, followed by a predominance of lymphocytes and monocytes from day 3 onward. This pattern was consistent in meningitis and meningoencephalitis but less pronounced in meningoencephalomyelitis.

Conclusions: Clinical manifestations of TBE exhibit distinct CSF profiles. Abnormalities are most pronounced in meningoencephalomyelitis and least in meningitis. These alterations appear early, peak within the first days, and then stabilize or improve, although this pattern is less predictable in meningoencephalomyelitis.

Purpose: With waning immunity and vaccine hesitancy, the COVID-19 pandemic continues to pose risks. A live microbial consortium (OL-1) with bacteria containing potentially cross-reactive antigens (CRAGs) stimulates anti-SARS-CoV-2 immune responses in vitro/vivo. We evaluated OL-1's efficacy in enhancing anti-SARS-CoV-2 immunity in unvaccinated, previously infected adults.

Methods: We conducted a pilot, parallel-group, triple-blind randomized controlled trial in 2021-2022 involving 52 generally healthy adults ages 18-60, unvaccinated against COVID-19, with SARS-CoV-2 infection ≥ 4 months prior. Participants received 21 days of either standard-dose OL-1, high-dose OL-1, or placebo. The primary outcome was change in plasma anti-SARS-CoV-2 IgG titers from baseline to Day 21. Secondary efficacy outcomes included changes through Day 42, interferon gamma (IFNg) release from stimulated peripheral blood mononuclear cells, and new SARS-CoV-2 infections. Safety was assessed through adverse events.

Results: Significant increases in plasma IgG levels were observed by Day 42 in the standard-dose OL-1 group (n = 17) compared to placebo (n = 18) (p = 0.02). No significant changes were observed in the high-dose group (n = 17). Marginal increases in IFNg release were observed in standard-dose recipients after stimulation with CD4+-specific CRAG and SARS-CoV-2 peptides and TLR7 ligands; only changes post-TLR7 ligand stimulation were significant. No new SARS-CoV-2 infections were detected. The most common adverse events overall were mild gastrointestinal symptoms; headaches were more frequent in OL-1 recipients.

Conclusion: The live microbial consortium OL-1 was well-tolerated and associated with slightly increased anti-SARS-CoV-2 IgG levels in previously infected, unvaccinated adults at standard, but not high, dosage. Further research should confirm these findings and their clinical implications in larger populations. This study was registered on ClinicalTrials.gov (NCT04847349) on April 14, 2021.