Infection最新文献

Purpose: Doxycycline is frequently prescribed during pregnancy, yet evidence on fetal safety is inconsistent and often excludes non-live births. We assessed whether exposure during the first or third trimester is associated with major congenital malformations or late-pregnancy adverse outcomes in a population-based cohort that also included stillbirths and terminations.

Methods: Using data from Clalit Health Services Southern district, we identified 265,686 pregnancies in women aged 15-45 years (from 1998 to 2017). Pharmacy records classified doxycycline dispensation in the first trimester (≤ 13 weeks) or third trimester (≥ 27 weeks). Crude and adjusted negative-binomial models estimated relative risks (RRs) for total and organ-specific major congenital malformations diagnosed up to age 1 year and for perinatal mortality, preterm birth, low/very-low birthweight, and low Apgar scores. Sensitivity analyses explored dose-response relations and propensity-score-matched cohorts.

Results: Among 2,696 first-trimester exposures, major malformations occurred in 7.7% versus 7.0% of 262,990 unexposed pregnancies (SMD = 0.03, p = 0.17). No association with major malformations was observed in both crude (Crude Relative Risk (RR) = 1.10; 95% CI 0.96-1.27) and adjusted (Adjusted RR = 1.07; 95% CI 0.93-1.23) analyses, nor by organ-specific sub-groups. Third-trimester exposure (n = 112) was linked to a higher risk of very-low birthweight, while other late-pregnancy outcomes were comparable to unexposed pregnancies.

Conclusion: First-trimester doxycycline use was not associated with increased major congenital malformation risk, and most late-pregnancy outcomes were unaffected. These findings support the relative safety of doxycycline when clinically indicated during pregnancy.

Purpose: Measles outbreaks have occurred across England since mid-2023. We estimated measles and rubella antibody seroprevalence among individuals in 2018 in English regions outside London, and estimated the effective reproduction number (Re) for measles to predict the potential for outbreaks.

Methods: Using validated enzyme-linked immunosorbent assays, anti-Measles and anti-Rubella IgG antibodies were measured in residual sera from 3758 1-30-year-olds born after introduction of measles-mumps-rubella vaccination who submitted samples to clinical laboratories outside London. The measles Re was calculated using seronegatives defined by the manufacturer's cutoff, mixture modelling, and vaccination coverage data.

Results: Using the manufacturer's cutoffs, the overall proportion seronegative to measles was 9.2% (95% confidence interval 8.3-10.1), and 10.3% (9.4-11.3) had equivocal results. The respective estimates for rubella were lower at 5.2% (4.6-6.0) and 5.4% (4.7-6.1). For both viruses, equivocal proportions increased with age, consistent with antibody waning. Mixture modelling for measles identified a common seronegative distribution across age groups, with lower proportions seronegative than using the manufacturer's cutoff. Re for measles using the manufacturer's seronegative cutoff (~ 150 mille international units/mL) was 1.00, versus 0.38 and 0.51 using the mixture model and vaccination coverage, respectively.

Conclusions: Re for measles estimated from seroepidemiology using an antibody cut-off similar to that considered a correlate of protection for measles was a more accurate predictor of recent measles resurgences outside London than those estimated using mixture modelling of seronegatives or coverage data. Seroepidemiological studies are a useful adjunct to coverage data in monitoring population immunity and in predicting the potential for measles outbreaks.

Background: Livestock-MRSA (methicillin-resistant Staphylococcus aureus) can cause infections in persons without known contact to livestock, but the route of transmission is unclear. We investigated whether the risk of livestock-MRSA infection among persons with no known contact to livestock is associated with the number of pig farms near the home, and whether this association is affected by the upwind/downwind location of the farms.

Methods: Register-based case-control study of 518 persons from Denmark with clinical infections with livestock-MRSA in 2016-2021 and no known exposure to livestock, and 4,944 matched controls. Distances and angles from home addresses to all pig farms within a distance of 25 km were calculated, and compared with the mean wind direction in the area.

Results: The mean number of pig farms within 13,127 m of the home address was 3.3 [0.3; 6.3] higher for cases (60.5) than controls (57.1), with a larger difference for farms upwind than downwind. The primary analysis showed that the livestock-MRSA exposure from a downwind farm was 59% [40%; 178%] of the exposure from an upwind farm, but the difference disappeared after confounder adjustment. In a post-hoc analysis, cases were surrounded by more pig farms at 50 - 6,250 m from the home address, and in the interval 1,250-6,250 m the difference was only seen in the upwind directions.

Conclusion: The risk of livestock-MRSA infection among persons without known livestock contact was influenced by the number of and distance to pig farms. In an exploratory post-hoc analysis, but not the main analysis, the risk was also influenced by mean wind direction.

Background: Sepsis therapy is still limited to treatment of the underlying infection and supportive measures. To date, various sepsis subtypes were proposed, but therapeutic options addressing the molecular changes of sepsis were not identified. With the aim of a future individualized therapy, we used machine learning (ML) to identify clinical phenotypes and their temporal development in a prospective, multicenter sepsis cohort and characterized them using plasma proteomics.

Methods: Routine clinical data and blood samples were collected from 384 patients. Sepsis phenotypes were identified based on clinical measurements and plasma samples from 301 patients were analyzed using mass spectrometry. The obtained data were evaluated in relation to the phenotypes, and supervised ML models were developed enabling prospective phenotype classification.

Results: Three sepsis phenotypes were identified. Cluster C was characterized by the highest disease severity and multi-organ failure with leading liver failure. Cluster B showed relevant organ failure, with renal damage being particularly prominent in comparison to cluster A. Time course analysis showed a strong association of cluster C with mortality, while patients in cluster B were likely to change the cluster until day 4. The plasma proteome reflected the clinical features of the phenotypes and showed gradual consumption of complement and coagulation factors with increasing sepsis severity. Supervised ML models allowed the assignment of patients based on only seven widely available features (alanine transaminase (ALT), aspartate transaminase (AST), base excess (BE), international normalized ratio of thrombin time (INR), diastolic arterial blood pressure, systolic arterial blood pressure (BPdia, BPsys) and activated partial thromboplastin time (aPTT)).

Conclusions: The identified clinical phenotypes reflected varying degrees of sepsis severity and were mirrored in the plasma proteome. Proteomic profiling offered novel insights into the molecular mechanisms underlying sepsis and enabled a deeper characterization of the identified phenotypes.

Purpose: Increasing travel, climate change, spread of antimicrobial resistance and pandemics increased the need for well-trained infectious diseases (ID) specialists and qualified ID specialist training for protecting public health all over the world. In this study, we aimed to provide a comprehensive overview of ID specialty training programs for standardization and quality improvement in a large geographical area.

Methods: We conducted a cross-sectional study among national respondents of 29 countries [Central Asia (Azerbaijan, Uzbekistan, the Kyrgyz Republic, Kazakhstan), the Middle East (Iran, Saudi Arabia, Jordan, Iraq, Oman, the United Arab Emirates, Qatar, Lebanon), Southeast Europe (Albania, Greece, Kosovo, Slovenia, Bosnia and Herzegovina, Serbia, the Republic of North Macedonia, Croatia), Eastern Europe (Russia, Moldova, Romania, Bulgaria), South Asia (India, Pakistan, Afghanistan), Southeast Asia (Malaysia), Türkiye] to evaluate the structure and components of ID training programs.

Results: In this study, structural variability in ID training programs was notable. 65.5% of the countries offered independent specialty program, 59% of the countries reported a required exam for entry into the ID specialization. Nearly all of the countries had a formal training curriculum; written exams were the most common used assessment method.

Conclusion: This study provides a comprehensive overview of ID specialty training across diverse regions, highlighting major structural differences in curricula, training duration, and national standards. Its broad geographic scope and contributions from actively engaged ID educators offer a unique global perspective. The findings underscore the urgent need for harmonized training frameworks, the strengthening of national curricula, and the promotion of international collaboration and inclusive strategies, all essential for developing a skilled, competent and resilient global ID workforce.

Purpose: Respiratory tract infections are among the most common reasons for consultations in primary health care (PHC) settings. In this review, we aim to provide an overview of diagnostic tests for selected respiratory pathogens useful in PHC.

Methods: We performed a PubMed search on diagnostic tests for influenza virus, respiratory syncytial virus (RSV), Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), Streptococcus pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae and Bordetella pertussis. We then selected and summarized clinical trials, meta-analyses and systematic reviews published between May 1994 and April 2025 relevant to PHC.

Results: Diagnostic tests are useful if the test result will guide subsequent clinical management. Polymerase chain reaction (PCR) tests have high diagnostic accuracy but are not always available in PHC. Accurate rapid antigen detections tests (RADTs) are required to have a sensitivity of at least 80% and a specificity of at least 97% and are available for influenza virus, RSV and SARS-CoV-2 as are urinary antigen tests for Streptococcus pneumoniae and Legionella pneumophila. In contrast, due to the lack of appropriate RADTs, infections with Mycoplasma pneumoniae or Bordetella pertussis typically require PCR tests.

Conclusion: From a clinical perspective, the differentiation between viral and bacterial infections and the accurate identification of the specific causative agent may guide medical interventions including antimicrobial therapy. From a diagnostic perspective, adequate microbiologic sampling and careful interpretation of laboratory test results in a clinical context are central requirements.

Purpose: Drug-induced liver injury (DILI) is a relevant adverse event of tuberculosis treatment (TBT) especially in sub-Saharan Africa, but data remains limited. Genetic hepatic transport proteins polymorphisms (HTPP) are potential contributors. This study aimed to assess frequency and timing of DILI, identify risk factors, and explore the association of HTPP with DILI risk in Ethiopian TBT-patients.

Methods: In this prospective study, 424 confirmed tuberculosis patients in Ethiopian were recruited before initiation of TBT. Liver function tests were conducted during the first 8 weeks of treatment. Baseline evaluations included sociodemographic-, lifestyle- and clinical data including testing for viral co-infections, and HTPP as well as liver stiffness measurement by transient elastography (TE). Multivariable logistic regression, Cox proportional hazards models, and Fine and Gray competing risks analyses were employed for statistical analysis.

Results: Cumulative DILI incidence was 16.0% with 4.2% classified as severe occurring most commonly within the first two weeks. Urban residence (OR 2.00, 95% CI 1.03-3.84; HR 1.80, 95% CI 1.00-3.22) was associated with increased DILI risk. In the competing risks model, urban residence (sHR 6.26, p = 0.010) and pathologic TE (sHR 5.23, p = 0.005) predicted severe DILI. The investigated HTPPs were not significantly associated with DILI.

Conclusion: DILI is a common early complication of TBT in Ethiopian patients. Assessment of sociodemographic factors and TE before TBT may help identify high-risk individuals and offers a pragmatic approach for DILI management in resource-limited settings.

Purpose: Infective endocarditis (IE) has been associated with severe outcomes when complicated by diabetes mellitus (DM). We aimed to report characteristics, microbial etiology, and mortality for patients with IE stratified by DM from a nationwide cohort.

Methods: We used Danish registries, and patients with first-time IE (2010-2020) were stratified by DM. We computed inverse Kaplan-Meier estimates for one-year mortality from admission. We computed multivariable adjusted Cox regression for the adjusted one-year mortality from admission and discharge.

Results: We identified 6,211 patients with first-time IE; 1,503 (24.2%) with DM (26.1% Type 1 DM, 68.1% male, median age 72.7 years); 4,708 (75.8%) did not have DM (67.0% male, median age 72.4 years). Patients with IE and DM had a higher proportion of chronic kidney disease (35.9% vs. 11.1%). The most predominant microorganism was Staphylococcus aureus (S. aureus) for patient with IE and DM (36.5%), and Streptococcus species (spp.) for those without DM (29.4%). Patients with IE and DM were associated with an increased one-year mortality from admission (41.1% [95% CI: 38.5%-43.6%] vs. 31.0% [95% CI: 29.6%-32.3%]). The adjusted mortality estimates were higher for patients with IE and DM compared to those without DM one year from admission (HR = 1.15 [95% CI: 1.04-1.27]), and one year from discharge (HR = 1.26 [95% CI: 1.09-1.46]).

Conclusion: Patients with IE and DM were associated with a higher burden of kidney disease, S. aureus as the predominant microorganism, and increased one-year mortality both from admission and discharge. These findings call for improved management of IE in patients with DM.

We present a case report of an 8-year-old African origin, Italian born girl, fully immunized for Diphtheria, with multiple ulcers caused by Corynebacterium diphtheria. The clinical event was preceded by a recent trip to Burkina Faso in a rural area. The atypical presentation with ulcers spread to the entire body and particularly to one leg, led to a bacterial swab, from whose culture the pathogen emerged. The girl was initially empirically treated with amoxicillin/clavulanate and then azithromycin. Cutaneous forms are the most common of all forms and have a relevant spreading role. This case is of particular concern in the context of a rising number of cases in Europe, and it's peculiar since it doesn't regard immigrants and refugees, whereas it regards a fully immunized child who traveled from an endemical country.