Infectious Diseases and Therapy最新文献

Introduction: The molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) impact transmission, clinical presentation, and treatment. Contemporary data on the molecular epidemiology of MRSA causing healthcare-associated (HA) infections in Latin America are scarce. In this study, we aimed to assess the molecular epidemiology, virulence genes, and antimicrobial susceptibility of MRSA bloodstream infections (BSI) isolates from Brazil.

Methods: A multicenter, prospective study in 14 Brazilian hospitals was conducted from August/2022 to August/2023. MRSA isolates recovered from HA-BSIs were sent to a central laboratory for whole-genome sequencing (WGS) and antimicrobial susceptibility testing.

Results: Of 255 S. aureus, 66 (25.9%) were MRSA, and 47 were submitted to WGS. The most frequent clonal complex (CC) was CC5 (n = 34, 72.3%), mostly of sequence types (ST) 105 (19/34; 55.9%) and ST5 (6/34; 17.6%). ST105(CC5)-SCCmecII-t002 was the commonest strain (10/47, 56.2%), detected in three of four studied regions, followed by the ST8(CC8)-SCCmecIV strains with distinct spa types (9/47; 19.2%). Three new MLST alleles were discovered, resulting in new ST designations 10,174, 10,175, and 10,176. Furthermore, the resulting phylogeny revealed three well-defined clades. Twenty-eight virulence genes were detected. All isolates were susceptible to vancomycin, linezolid, and ceftaroline, while susceptibility to daptomycin and delafloxacin was 88.9% and 51.2%, respectively.

Conclusions: The recently reported ST105(CC5)-SCCmecII-t002 clone has disseminated in hospitals from different Brazilian regions, together with other lineages that have been previously associated with community-associated infections, composed a new molecular landscape of MRSA causing HA BSIs in Brazil.

Introduction: Argentina was the first South American country to adopt a single-dose hepatitis A vaccine for 1-year-old children, replacing the standard two-dose regimen in the immunization program in 2005. Here, we assessed the long-term persistence of anti-hepatitis A virus (HAV) antibodies following vaccination.

Methods: A cohort of healthy toddlers from Mendoza, Argentina, who received one (N = 436) or two (N = 108) doses of the inactivated HAV vaccine (Avaxim^® 80U Pediatric), were followed for up to 15 years post-vaccination to assess the persistence of anti-HAV antibodies. Three assays were used to measure anti-HAV antibody concentrations, depending on commercial availability. At year 15 follow-up, 161 and 48 participants who received one and two vaccine doses, respectively, without additional booster, remained in the study. Using all available data, we modeled long-term antibody persistence to project immunity to 40 years after vaccination. Antibody persistence was predicted using a hierarchical model that estimated both participant- and group-specific antibody decay, accounting for assay changes over time and natural boosting from virus exposure.

Results: At year 15, anti-HAV antibody geometric mean concentrations (GMCs) were 73.7 (95% CI 65.0-83.6) mIU/ml and 291.1 (95% CI 226.1-375.0) mIU/ml among those who received one and two vaccine doses, respectively, and all remained seroprotected. Of the four model specifications tested, the log-logistic model with natural boosting provided the best fit to the observed antibody GMCs and seroprotection rates. At 40 years post-vaccination, GMCs were predicted to be 51.8 (95% CI 36.8-75.1) mIU/ml and 134.7 (95% CI 84.5-221.1) mIU/ml after one and two vaccine doses, respectively, with seroprotection rates of 94% (95% CI 89-98) and 93% (95% CI 88-97).

Conclusions: The HAV vaccine, Avaxim^®, administered as one- or two-dose schedule, elicited long-lasting immunity in children, with a single dose sufficient to ensure long-term protection.

Introduction: The optimal duration of antibiotic therapy for Gram-negative bacteremia sourced from urinary tract infections (UTI) remains uncertain. We performed a systematic review and meta-analysis comparing short-course (approximately 7 days) versus prolonged-course (approximately 14 days) antibiotic therapy in this population.

Methods: We systematically searched PubMed, Embase, and ClinicalTrials.gov through 26 April 26 2025. Studies were included if they compared 7-day versus 14-day antibiotic therapy in Gram-negative bacteremia with ≥ 65% UTI source or performed a dedicated UTI subgroup analysis. Outcomes assessed included 30- and 90-day mortality and recurrence rates. Recurrence was defined as a repeat episode of Gram-negative bacteremia confirmed by a positive blood culture after completion of therapy, rather than recurrence of urinary tract infection alone. Risk ratios (RR) were pooled using a random-effects model. Noninferiority was assessed using a prespecified margin of RR 1.25, and superiority was assessed with a threshold of RR < 1.00.

Results: In total, six studies (three randomized trials, three observational cohorts) encompassing 4448 patients were included. There were no significant differences between short- and prolonged-course therapy for 30-day mortality (RR 0.97, 95% confident interval (CI) 0.64-1.47; p = 0.90), 30-day recurrence (RR 1.38, 95% CI 0.80-2.37; p = 0.24), 90-day mortality (RR 0.90, 95% CI 0.77-1.06; p = 0.20), or 90-day recurrence (RR 0.68, 95% CI 0.45-1.01; p = 0.06).

Conclusions: Our findings suggest that a 7-day course may be sufficient for most patients with UTI-sourced Gram-negative bacteremia.

Introduction: Routine childhood immunization programs using pneumococcal conjugate vaccines (PCVs) significantly reduce the burden of pneumococcal disease (PD). PCV21, a 21-valent PCV, was recently approved and recommended by the European Commission for use in Norway. The objective of this study was to quantify the health and economic burden of invasive PD (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) attributable to PCV21, PCV20, and PPSV23 serotypes among adults in Norway.

Methods: A published Markov model was adapted to estimate lifetime IPD/NBPP cases, deaths, and direct medical costs (in 2023 Norwegian kroner [NOK]) associated with PCV21, PCV20, and PPSV23 serotypes in Norway. Results were disaggregated by age and risk groups. A one-way sensitivity analysis examined changes in disease costs (± 20%).

Results: The projected number of PD cases and deaths attributable to PCV21 serotypes was substantially higher than those attributable to PCV20 and PPSV23 serotypes. PD cases and deaths attributable to PCV21 serotypes vs. PCV20 and PPSV23 were ~ 41% and ~ 26% higher, respectively, in adults aged 65+ years, ~ 39% and ~ 25% higher in those aged 50-64 years, and ~ 37% and ~ 22% higher in those aged 18-64 years with risk factors. Within each age group, cases and total lifetime costs increased progressively as risk categorization increased. Estimated lifetime direct treatment costs for PD attributable to PCV21 serotypes were higher than those associated with PCV20 or PPSV23, at 3.9 billion NOK, 3.5 billion NOK, and 4.4 billion NOK in adults aged 65+, 50-64, and 18-64 years with risk factors, respectively.

Conclusions: Compared with PCV20 and PPSV23, PCV21 serotypes are associated with a higher health and economic burden in Norway. The inclusion of PCV21 into national vaccine recommendations in Norway can further alleviate the burden associated with PD in adults.

Sexually transmitted infections (STIs) remain a major global health burden, with rising incidence of Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum. Doxycycline post-exposure prophylaxis (DoxyPEP), consisting of a single 200 mg dose within 72 h after condomless sex, has emerged as a promising intervention. Randomized controlled trials demonstrate consistent efficacy in reducing chlamydia and syphilis, while protection against gonorrhea is variable, being strongly influenced by baseline tetracycline resistance and anatomical site. Surveillance data from San Francisco and King County confirm that high-frequency use can drive rapid increases in gonococcal tetracycline resistance. Although no cephalosporin resistance has yet been linked to DoxyPEP, genomic correlations raise concern for co-selection of multidrug-resistant strains, particularly FC428-like clones with mosaic penA alleles. C. trachomatis remains uniformly susceptible, with resistance limited to theoretical horizontal transfer from C. suis. T. pallidum shows no evidence of resistance, supported by genomic constraints and experimental studies. Mycoplasma genitalium demonstrates low intrinsic susceptibility to doxycycline, but no acquired tetracycline resistance has been confirmed. Beyond target pathogens, DoxyPEP alters the functional resistome of the human microbiome, amplifying tetracycline resistance gene expression in gut, skin, and oropharyngeal flora, and selecting for resistant Staphylococcus aureus and commensal Neisseria. These ecological shifts underscore the importance of molecular surveillance to monitor resistance spillover. Overall, DoxyPEP provides substantial benefit in controlling chlamydia and syphilis and conditional utility against gonorrhea in low-resistance settings. Its deployment should be coupled with antimicrobial stewardship, local resistance data, and strengthened genomic surveillance to balance individual protection with population-level risks.

Introduction: There are limited data available on the relationship between chest computed tomography (CT) patterns and clinical severity in adult patients infected with respiratory syncytial virus (RSV). It was hypothesized that specific CT patterns would be associated with distinct clinical outcomes and would correlate with both immune status and viral load.

Methods: We conducted a retrospective, single-center study of adults aged ≥ 18 years with laboratory-confirmed RSV infection and chest CT performed within 7 days of diagnosis. A blinded radiologist reviewed the CT patterns and scored them using the Chest CT Score (CCTS). Clinical severity was defined as World Health Organization (WHO) clinical progression scale ≥ 5 (hospitalized patients requiring oxygen). Multivariable logistic regression was used to identify independent associations between CT features and disease severity.

Results: A total of 113 patients (median age 72 years; 41.6% male) were included from January 2019 to March 2025, of whom 31.9% were immunocompromised. The median CCTS was 6 [25th-75th quartiles, 3-10], with consolidations (55.8%), micronodules (46.0%), mucoid impaction (73.5%), and bronchial wall thickening (65.5%) being the most common chest CT findings. Patients with severe infection (n = 66) had a higher CCTS (7 versus 4; p < 0.001) and were more likely to exhibit consolidations and emphysema. On multivariable analysis, CCTS > 6 (adjusted odds ratio (aOR) 3.66, 95% CI 1.63-8.62), consolidations (aOR 2.87, 95% CI 1.23-6.83), and emphysema (aOR 5.66, 95% CI 1.36-39.15) were independently associated with clinical severity. No significant differences in CT patterns were observed according to immune status, the presence of bacterial co-infection, or elevated versus reduced viral loads.

Conclusion: Higher CCTS, consolidations, and emphysema were found to be independently associated with clinical severity in adults with RSV infection. Standardized CT scoring could help with risk stratification, but this would need to be validated in a prospective study.

Introduction: This study evaluated the impact of "risk stacking" on COVID-19-related hospitalizations, emergency department/urgent care (ED/UC) visits, and outpatient visits among non-immunocompromised individuals aged 18-49 and 50-64 years compared with immunocompromised individuals and those ≥ 65 years.

Methods: Using Optum Clinformatics^® data, adults were assigned to ≥ 1 category based on underlying CDC-categorized high-risk (HR) conditions: HR-Conclusive (from which immunocompromising conditions were separated), HR-Suggestive, Mixed Evidence, No HR Conditions. The impact of multimorbidity quantities and HR categories on COVID-19 healthcare resource utilization (HCRU) was evaluated.

Results: Overall (n = 10,631,427), the most prevalent conditions were hypertension (HTN; 47.4%), obesity/overweight (31.9%), chronic heart disease (CHD; 28.1%), and diabetes (DBT; 20.3%). COVID-19 HCRU was higher for CHD with DBT, CHD with obesity, and HTN with obesity than for immunocompromised individuals and highest among those aged ≥ 65 years. Multimorbidity across multiple HR categories resulted in greater adjusted risk for COVID-19 HCRU for all ages.

Conclusion: Younger adults with multiple non-immunocompromising comorbidities had greater risk of COVID-19-related HCRU than those with immunocompromising conditions or ≥ 65 years without multimorbidity. Stacking HR comorbidities increased the risk of HCRU. Ensuring broad vaccination and treatment recommendations and access is critical to mitigating severe COVID-19 in HR groups of any age.

Tuberculosis (TB) continues to represent a significant global public health concern, with China being a country that bears the burden of a high incidence of TB cases on a global scale. Although linezolid (LZD) has been recommended for treating drug-resistant tuberculosis (DR-TB), its intolerability and adverse events, such as myelosuppression, neurotoxicity, etc., have limited its long-term usage in anti-TB treatment. Contezolid (CZD), a new generation of oxazolidinone drug, shows comparable or superior antibacterial activity to LZD, with lower risks of myelosuppressive toxicity, neurotoxicity, and lactic acidosis. Its unique metabolic pathway and favorable pharmacokinetic profile render it a promising alternative to LZD for TB treatment. Recent years have seen mounting evidence of the potential of CZD in treating TB. In this paper, the development history, the mode of action, resistance mechanisms, and research progress on CZD for TB treatment are reviewed, aiming to enhance understanding of its role in anti-TB therapy and to provide valuable references for clinical use and future research.

Introduction: The COVID-19 pandemic and associated non-pharmaceutical interventions (NPIs) markedly reduced the circulation of respiratory pathogens. In late 2023, a resurgence of Mycoplasma pneumoniae (MP) infections, including macrolide-resistant strains (MRMP), was documented worldwide. This study aimed to determine MRMP prevalence and epidemiological characteristics in Southern Italy during the post-pandemic period.

Methods: Between January 2023 and May 2025, 5362 respiratory specimens were tested for M. pneumoniae and other respiratory pathogens using multiplex real-time polymerase chain reaction (PCR). Macrolide resistance-associated mutations in the 23S rRNA gene were identified through PCR amplification and Sanger sequencing. Data were stratified by age group and clinical setting.

Results: MP prevalence peaked at 15.8% in May 2025. Of 305 positive cases, the median age was 10 years, 52.1% were male, and 86.9% were hospitalized. Coinfections occurred in 23.3% of cases, particularly among children < 5 years. Macrolide resistance was detected in 7.5% of MP-positive samples, predominantly the A2063G mutation (96%), with the highest prevalence in patients aged 10-14 years (12.6%). No resistance was identified in ICU patients.

Conclusion: The post-pandemic resurgence of M. pneumoniae in Southern Italy, coupled with sustained macrolide resistance, underscores the need for continuous molecular surveillance and targeted antimicrobial stewardship to optimize therapy and prevent further resistance spread.

Introduction: Adults with certain comorbidities, including metabolic and cardiopulmonary diseases, are at increased risk of severe respiratory syncytial virus (RSV) disease. We evaluated the cost-effectiveness of adjuvanted RSVPreF3 vaccination in adults in the USA aged 50-59 years at increased risk of severe RSV.

Methods: A Markov model with a 5-year time horizon estimated health and cost outcomes associated with adjuvanted RSVPreF3 vaccination in 3,259,715 adults aged 50-59 years with chronic obstructive pulmonary disease (COPD) from a societal perspective, compared with no vaccination. Inputs related to epidemiology, vaccine efficacy, and demographics came from published literature and public sources; assumptions, when needed, relied on expert consultation. A 46.2% vaccine uptake was assumed, on the basis of influenza vaccination. We reported incremental public health impact, costs, quality-adjusted life years (QALYs) lost, and incremental cost-effectiveness ratios. Scenario analyses investigated outcomes in adults aged 50-59 years with heart failure (HF), coronary artery disease (CAD), diabetes, or asthma.

Results: Over a 5-year time horizon, one-time adjuvanted RSVPreF3 vaccination of 1,505,989 adults aged 50-59 years with COPD was projected to prevent 163,181 RSV acute respiratory illness cases, 126,565 lower respiratory tract disease cases, 11,609 RSV-related hospitalizations, 4117 emergency department visits, 816 deaths, and 12,144 QALY losses, compared with no vaccination. Adjuvanted RSVPreF3 vaccination was a cost-saving strategy (i.e., dominant) versus no vaccination in US adults aged 50-59 years with the modeled comorbidities, reducing societal costs and improving health outcomes in each scenario.

Conclusions: In US adults aged 50-59 years at increased risk of severe RSV, a single dose of adjuvanted RSVPreF3 vaccination was projected to improve public health outcomes at a lower societal cost compared with no vaccination. Efforts are needed to ensure access to vaccination for populations at increased risk of severe RSV disease.