Infectious Diseases and Therapy最新文献

Introduction: This study evaluated the effectiveness of Moderna's updated mRNA-1273 vaccine targeting the KP.2 variant, compared to people who did not receive any 2024-2025 COVID-19 vaccine, in preventing COVID-19-associated hospitalizations and medically-attended COVID-19 among adults aged ≥ 18 years in the United States during the 2024-2025 season.

Methods: Data were extracted from linked administrative healthcare claims and electronic health records (EHR) for vaccinations from 23 August 2024 through 23 April 2025 and followed through 30 April 2025. We conducted a retrospective matched cohort study with propensity score weighting to adjust for differences between groups to assess vaccine effectiveness (VE) against COVID-19 outcomes. VE was calculated as 1 minus the hazard ratio (HR) from Cox proportional hazards models.

Results: Overall, 596,248 mRNA-1273 KP.2 vaccine recipients were matched 1:1 to unexposed adults. The mean (standard deviation) age was 63 (17) years, with more than half of the population being 65 years or older. Approximately 70% of individuals had an underlying medical condition making them high-risk for severe outcomes for COVID-19. VE was 52.8% [95% confidence interval (CI) 34.8%, 65.8%] against COVID-19-related hospitalization and 39.4% (35.0%, 43.5%) against medically-attended COVID-19 over a median follow-up of 55 (interquartile range 32-77) days in an interim analysis. The VE was sustained throughout the entire study period and shown to be 45.2% (37.7%, 51.8%) against COVID-19-related hospitalizations and 33.1% (30.6-35.4%) against medically-attended COVID-19 over a median follow-up of 127 (interquartile range 84-173) days.

Conclusion: The mRNA-1273 KP.2 vaccine demonstrated significant incremental effectiveness in preventing hospitalization with COVID-19 and medically-attended COVID-19 in adults during the 2024-2025 season to date. The VE was sustained with longer median follow up time. These findings support ongoing vaccination efforts to mitigate the public health impact of COVID-19.

Introduction: Haemophilus influenzae is a human-specific Gram-negative bacterium responsible for respiratory tract infection, sepsis, and meningitis. The study aimed to investigate the epidemiology, serotype distribution, and mechanisms of beta-lactam resistance among invasive H. influenzae strains isolated in Poland from 2018 to 2023.

Methods: Invasive H. influenzae isolates were received from patients with positive culture results from blood, cerebrospinal fluid (CSF), and pleural fluid. Sample data were obtained from the Polish laboratory surveillance system. For all isolates screening test for beta-lactam resistance was performed and the minimum inhibitory concentrations (MICs) of clinically relevant antibiotics were determined using antibiotic gradient strips. For isolates with inhibition zone P 1U < 12 mm (n = 133), whole genome sequencing (WGS) analysis was performed.

Results: Most strains of H. influenzae were isolated from blood (90.7%). Non-typeable Hinf (NTHi) strains were responsible for most invasive disease in all age groups and accounted for 85.7% (342/399) of all cases. Capsulated isolates constituted 14.3%; among them the most common serotype was type f (Hif; 64.9%), followed by serotypes: e (Hie; 19.3%), b (Hib; 14.0%), and d (Hid; 1.8%). Of the 399 isolates collected between 2018 and 2023, 15.8% and 1.0% were resistant to ampicillin and cefotaxime, respectively. Resistance to meropenem and ciprofloxacin using the meningitis breakpoint was detected in 4.3% and 1.8% strains, respectively. All isolates showed susceptibility to chloramphenicol. Resistance to rifampicin characterized 3.8% of isolates tested. The Cefinase test revealed beta-lactamase production in 8.8% of isolates.

Conclusions: In our study NTHi predominated among invasive cases across all age groups, especially among elderly patients, similarly to other countries. β-Lactam resistance among studies strains has remained stable over the years. Recently, however, resistance to third-generation cephalosporins has emerged. Continuous surveillance and a rational antibiotic policy are essential to address H. influenzae resistance.

Introduction: The clinical presentation of critically ill patients with coronavirus disease 2019 (COVID-19) has evolved significantly with the emergence of the Omicron variant. Current intensive care unit (ICU) admissions involve patients with diverse comorbidities and immune statuses, highlighting the need to redefine homogeneous phenotypic subgroups within this population. This study aimed to characterize distinct clinical phenotypes among critically ill patients with COVID-19 and acute respiratory failure.

Methods: This multicenter prospective substudy of the SEVARVIR cohort included adult patients from 39 French ICUs between December 2021 and October 2024 with acute respiratory failure and infected with the Omicron variant. Clustering analysis was conducted using Kohonen's self-organizing maps (SOMs) and validated with ClinTrajan, two unsupervised clustering methods, to identify homogeneous patient phenotypes.

Results: During the study period, 777 patients with Omicron infection were included, and 7 distinct clinical clusters were identified. Clusters 1 and 2 included patients with metabolic and cardiovascular comorbidities. Cluster 3 featured younger, mildly ill patients with isolated chronic respiratory failure, while cluster 4 comprised older male patients with isolated respiratory failure. Cluster 5 included patients with isolated hematologic malignancies, cluster 6 patients with multiorgan failure, and cluster 7 organ transplant recipients, with high severity scores and impaired renal function. ICU management varied substantially across clusters. Patients in clusters 5 and 7 had the highest requirements for organ support, with frequent use of invasive mechanical ventilation, vasopressors (cluster 6), and renal replacement therapy (cluster 7). Dexamethasone and tocilizumab were most commonly prescribed in cluster 4 (91.3% and 30.2%, respectively). Mortality at day 28 varied significantly across clusters, ranging from 13.1% in cluster 3 to 41.1% in cluster 6.

Conclusions: This clustering analysis highlights, for the first time, the clinical heterogeneity of critically ill patients infected with Omicron, identifying seven distinct clusters with varying clinical presentations, management strategies and outcomes. These findings underscore the relevance of a phenotype-driven approach to support personalized treatment strategies and guide future clinical trials.

Trial registration: Clinicaltrials.gov, NCT05162508. A Graphical Abstract is available for this article.

Introduction: SARS-CoV-2, influenza A and B, and respiratory syncytial virus (RSV) are the major seasonal viruses that can cause severe illness. Rapid and accurate diagnosis of these viruses may improve patient management and surveillance efforts. Here, we assessed the diagnostic performance of the STANDARD M10 Flu/RSV/SARS-CoV-2 Fast (M10Fast) real-time polymerase chain reaction assay for near-patient diagnosis of the four viruses.

Methods: This retrospective validation study included 600 nasopharyngeal swab specimens previously tested using the standard-of-care laboratory-based Allplex Respiratory Panels 1-4 and Allplex SARS-CoV-2/FluA/FluB/RSV reference assays. Of these samples, 300 were positive for SARS-CoV-2, influenza A, influenza B, or RSV, while the remaining 300 samples were negative for the four viruses. Positive and negative percent agreements between the M10Fast index and reference tests were the primary endpoints. Additionally, analytical sensitivity of the M10Fast in terms of 95% limit of detection was estimated via serial dilutions of a positive reference material.

Results: Of 600 samples processed in the M10Fast, 590 (98.3%) were fully concordant. Positive percent agreement coefficients were 98.7% for influenza A and 100% for SARS-CoV-2, influenza B, and RSV. Negative percent agreement was 99.2% for influenza A, 99.4% for both SARS-CoV-2 and RSV, and 99.8% for influenza B. Discordant results were characterized by low viral loads with cycle threshold values of 38 or greater. The rate of invalid M10Fast runs was low (1.2%). Limit of detection of the M10Fast varied from 189 copies/mL for RSV to 541 copies/mL for the N gene of SARS-CoV-2.

Conclusions: The M10Fast, developed for near-patient settings, reliably detects SARS-CoV-2, FluA, FluB, and RSV in 36 min and its performance is comparable to standard laboratory-based assays.

Introduction: Infections caused by metallo-β-lactamase-producing Enterobacterales offer limited therapeutic options. Aztreonam-avibactam (ATM-AVI) provides a promising alternative, but its approved intermittent regimen is complex and can lead to substantial drug waste.

Methods: We describe a case of mastoiditis with a retrotympanic abscess due to OXA-48- and NDM-1-producing Klebsiella pneumoniae, managed with continuous infusion (CI) of ATM-AVI after a full-vial loading dose, supported by therapeutic drug monitoring (TDM) and whole-genome sequencing (EPISEQ CS V2.0, bioMérieux).

Results: A 35-year-old man previously treated abroad for meningitis and brain abscesses presented with residual deep-seated infection caused by OXA-48- and NDM-1-producing K. pneumoniae. After initial treatment with ceftazidime-avibactam plus aztreonam, therapy was switched to ATM-AVI using a full-vial loading dose followed by CI. TDM demonstrated sustained plasma levels of both drugs, and the patient improved without adverse events.

Conclusion: CI of ATM-AVI following a high loading dose was feasible, safe, and allowed optimized pharmacokinetic/pharmacodynamic (PK/PD) exposure while preventing drug wastage. Larger studies are warranted to determine the clinical utility of CI ATM-AVI across different MIC ranges.

Introduction: Extraintestinal pathogenic Escherichia coli can infect normally sterile body sites, causing invasive E. coli disease (IED). The IED burden is often underestimated. Here, we provide more insights into the real-world epidemiology of IED in the United States from 2002 to 2022.

Methods: In this retrospective cohort study, a narrow and a broad algorithm composed of coded diagnoses combined with laboratory data (microbiology culture) were first validated against the gold-standard IED case definition. The algorithms were selected to identify IED cases among adults in the Kaiser Permanente Northwest database. IED incidence rates (IRs) and case fatality rates (CFRs) were calculated and stratified by period, age, and sex. The risk of IED in the population with pre-defined comorbidities, including urinary tract infections (UTIs), was assessed using incidence rate ratios.

Results: A source population of 1,163,319 and 1,169,224 persons was identified by the narrow and broad algorithms, respectively. In these populations, 5832 (narrow algorithm) and 10,490 (broad algorithm) IED cases were identified, corresponding to an IED IR of 80.9 (95% confidence interval [CI]: 78.8-83.0) and 145.8 (143.0-148.6) cases per 100,000 person-years, respectively. The IR was higher among females than males and increased with age and over time. All-cause mortality among cases at 30 days after IED diagnosis was 7.6% (95% CI: 6.9-8.3%) and 7.2% (6.7-7.7%) based on the narrow and broad algorithms, respectively, and CFRs increased with age to 13.1% (both algorithms) among ≥ 80-year-olds. Having a history of UTIs was confirmed as an independent risk factor, multiplying the risk of IED by more than five compared to the population without a history of UTIs.

Conclusions: These observations demonstrate that IED is a substantial and growing global health concern that disproportionally affects older adults.

Introduction: Although Cutibacterium acnes is considered a typical pathogen of postoperative central nervous system (CNS) infections, data on its role as a pathogen, remain limited. This study aimed to address this knowledge gap.

Methods: A case-case-control study of adults with monomicrobial Cutibacterium acnes infections (CaIs) following nonspine neurosurgical procedures (2016-2024) (Cases I). These were individually matched (1:1:1) by age, year, and procedure type to individuals who did not develop infection (controls) and to individuals with aerobic bacterial infections (abIs; cases II). Multivariable conditional logistic regression models were implemented to assess clinical correlates for infection by either bacterial group, clinical presentation, and outcomes differences.

Results: Cutibacterium acnes isolation predominantly reflected contamination (131/213, 62%), and ultimately 32 (15%) CaIs cases were included. Smoking (adjusted odds ratio [aOR] 3.25, 95% confidence interval [CI] 1.06-9.97) was the only independent risk factor identified for CaIs. In contrast, nonelective procedure was identified as an independent risk factor for abIs (aOR 6.0, 95% CI 1.34-26.81, p = 0.019). CaIs commonly involved empyema (84% [27/32] versus 53% [17/32] with abIs, p = 0.014). Individuals with CaIs tended to follow a relatively indolent clinical course, were less likely to present with fever (aOR 0.15, 95% CI 0.04-0.68), and had favorable outcomes. When compared with CaIs, patients with abIs were less likely to achieve clinical cure at 90 days (aOR 0.02, 95% CI 0.001-0.41).

Conclusions: Although no modifiable risk factors were identified, CaIs frequently caused empyema, were less likely to present with fever, and were associated with a favorable prognosis.

Introduction: Respiratory syncytial virus (RSV) can cause severe outcomes in hospitalized older adults and those with underlying comorbidities, but little is known regarding such outcomes stratified by age and comorbidity status. This study aimed to describe the intensive care unit (ICU) stay and receipt of mechanical ventilation (MV) among adults with RSV-related hospitalizations by age and risk group.

Methods: A retrospective cohort study was conducted using Optum Market Clarity Database to identify RSV-related hospitalizations among adults aged ≥ 18 years. ICU admission, length of ICU stays, and MV use were summarized by age and risk group. Patients with at least one predefined underlying condition were defined as high-risk, while low-risk adults lacked any of these conditions.

Results: A total of 13,734 RSV-related hospitalizations were identified, including 11,838 unique patients. Of these, 10.2% were low-risk and 89.8% were high-risk. ICU admissions occurred in 31.2% of RSV-related hospitalizations (high-risk, 32.1%; low-risk, 22.6%). High-risk younger adults had higher percentage of ICU admissions (18-49 years, 31.1%; 50-59 years, 34.8%) than older adults at low-risk (60-74 years, 27.8%; ≥ 75 years, 21.6%). Mean length of ICU stay was 4.5 days (high-risk, 4.6 days; low-risk, 2.8 days). Younger adults at high-risk had longer ICU stays (18-49 years, 5.9 days; 50-59 years, 5.4 days) compared to older adults at low-risk (60-74 years, 4.2 days; ≥ 75 years, 1.8 days). MV was used in 6.2% of RSV-related hospitalizations (high-risk, 6.6%; low-risk, 2.6%). ICU stays for those receiving MV were more than twice as long as ICU stays overall (mean 10.6 days).

Conclusions: During RSV-related hospitalizations, adults at high-risk experienced more critical care outcomes compared to low-risk adults. Within risk status, results were similar with increasing age. However, younger adults at high-risk had more severe outcomes compared to older adults without such comorbidities, highlighting the importance of disease prevention in this group.

Introduction: Patients with human papillomavirus-related gynaecological diseases (HPV-RGD) are at risk of synchronous HPV infections in other regions, including the anal canal. The primary objective of this work was to examine the prevalence of anal HPV in patients treated for HPV-RGD. Secondary objectives were to test HPV type distribution and the risk of anal infection depending on the HPV-RGD localization.

Methods: A prospective study was conducted with two groups: the research group, histologically confirmed HPV-RGD, and the control group, gynaecological diseases not related to HPV (all human immunodeficiency virus (HIV) negative). The swabs for HPV genotyping and liquid cytology (Anyplex II HPV HR Detection test) were collected from the anal canal (both groups) and the area of gynaecological disease (research group).

Results: The prevalence of anal HPV infection in the research group (n = 130) was significantly higher than in the control group (n = 100) (64.62% vs. 11%, p < 0.05). All patients with vulva cancer (n = 7) and vaginal precancer (n = 6) exhibited anal HPV infection (p < 0.05). The risk of anal infection in patients with cervical cancer and precancer was 64% and 61.9%, respectively (both p < 0.05). The most common HPV types detected in the anus were 16 (53.6% of all anal HPV-positives), followed by 31 (17.9%) and 51 (14.3%). In 84.5% of cases, the same HPV type was present in the anus and gynaecological organ.

Conclusions: Patients with HPV-RGD, HIV-negative, are at risk for synchronous anal HPV infection, with type 16 being the most common. Further research is warranted to define the clinical significance of this finding and the introduction of anal cancer screening among patients with HPV-RGD.

Trial registration: ClinicalTrials.gov identifier, NCT06574087.