Infectious Diseases and Therapy最新文献

Introduction: Difficult-to-treat-resistant (DTR) infections caused by Pseudomonas aeruginosa represent a global public health threat, prioritizing the search and development of new antibiotics for this microorganism.

Methods: We present the real-life experience of the compassionate use of imipenem/cilastatin/relebactam in a descriptive study involving 14 patients with DTR-P. aeruginosa infection and limited treatment options.

Results: The primary source of infection was skin and soft tissue infection, 57.1% (8/14), followed by respiratory infection-pneumonia, 28.6% (4/14). At the onset of infection, 71.4% (10/14) of patients were in the intensive care unit (ICU). All our patients had a Charlson Score of ≥ 3. Septic shock was observed in 64.3% (9/14) of patients. The median treatment duration was 15 days, and no patient experienced an adverse event that required treatment interruption. All-cause 30-day mortality was observed in 42.9% of cases (6/14), while clinical efficacy and microbiological success were observed in 64.3% (9/14).

Conclusions: Imipenem/cilastatin/relebactam may represent a treatment option for patients with DTR-P. aeruginosa infections, which should be validated in prospective clinical trials.

Introduction: Central nervous system adverse events (AE) have been a cause of discontinuation of dolutegravir-containing therapy, especially in combination with abacavir. The main aim of the study was to evaluate whether the switch to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was associated with a reduction in severity and incidence of neuropsychiatric symptoms compared to continued dolutegravir/abacavir/lamivudine (DTG/ABC/3TC).

Methods: DOBINeuro is a randomized trial enrolling people living with HIV (PLWH) treated with DTG/ABC/3TC for > 6 months and with HIV-RNA < 50 cps/ml for > 12 months. At baseline, PLWH are randomized to continue DTG/ABC/3TC or switch to BIC/FTC/TAF. The original sample size was 50 PLWH per arm, but the enrollment was prematurely stopped due to a delayed recruitment process. Neuropsychiatric symptoms were evaluated by the self-report Symptom Checklist (SCL)-90-R and the Mini-International Neuropsychiatric Interview Plus.

Results: A total of 41 PLWH were enrolled and underwent randomization: 20 were randomized to continue DTG/ABC/3TC and 21 to switch to BIC/FTC/TAF. At baseline, clinical and laboratory characteristics were homogeneous in the two arms. Switching from DTG/ABC/3TC to BIC/FTC/TAF in virologically suppressed PLWH was associated with an improvement in sleep disorders but not in any other neuropsychiatric symptom.

Conclusions: Although limited by a low sample size, this study suggests neuropsychiatric tolerability may improve when switching virologically suppressed PLWH from DTG to BIC-based strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are highly infectious respiratory viruses that affect people of all ages and are typically associated with mild symptoms and few complications in immunocompetent individuals. However, the risk of severe outcomes (e.g., hospitalization and death) following infection with these respiratory viruses is higher in certain populations, including older adults and individuals of certain race/ethnic and sociodemographic groups. Additionally, immunocompromising conditions and pre-existing comorbidities, including underlying cardiovascular (e.g., congestive heart failure) and respiratory diseases (e.g., chronic obstructive pulmonary disease), diabetes, chronic kidney disease, and obesity, are key factors that predispose individuals to SARS-CoV-2-, influenza-, and RSV-related severe outcomes. Increased risk for severe outcomes associated with advancing age and comorbidities is compounded by residence in long-term care facilities due to the enhanced spread of respiratory infections in congregate living environments. In this narrative review, risk factors associated with severe outcomes following infection with SARS-CoV-2, influenza, and RSV in adult populations are explored. Additionally, distinct clinical outcomes based on underlying comorbidities following infection are discussed in the context of high-risk populations. Factors unique to each virus that underpin distinct risk profiles are described and suggest the potential for tailored surveillance and healthcare approaches to target and ultimately mitigate SARS-CoV-2-, influenza-, and RSV-associated disease burden in vulnerable populations. Mutual risk factors for severe outcomes are also highlighted; these similarities indicate that cohesive risk reduction strategies may also be feasible, particularly since vaccines are available for each of these respiratory viruses. Ultimately, a more thorough understanding of the risk factors that predispose individuals to develop SARS-CoV-2-, influenza-, and RSV-related severe outcomes may improve risk reduction strategies, inform healthcare policy, and contribute to the expansion and refinement of existing surveillance approaches to ultimately mitigate disease burden in vulnerable populations.

While marked differences exist between influenza virus, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is substantial overlap in the vulnerability of populations most at risk for severe disease following infection, chief among them being advanced age, multiple comorbidities, and immunocompromise. Vaccination is an established and effective preventative strategy to protect against respiratory viral infections (RVIs), reducing morbidity and mortality, minimizing the potential for long-term complications, and mitigating exacerbation of existing health conditions. Despite the demonstrated benefits of immunization throughout the life course and recommendations by health authorities, coverage rates of at-risk populations against vaccine-preventable diseases remain suboptimal and vary considerably by country and demographic strata. The objective of this supplement's concluding article is to discuss the current barriers to vaccination and strategies to enhance coverage against RVIs among adult at-risk populations. Identified barriers include low awareness of the risks of vaccine-preventable diseases, low perceived benefits of vaccination, and doubts regarding vaccine safety, which together contribute to vaccine hesitancy. Additionally, logistical issues related to vaccine supply, access, and costs present further challenges in achieving optimal coverage. Potential strategies to overcome these barriers and improve uptake include strengthening and harmonizing immunization guidelines and improving respiratory disease surveillance systems to appropriately identify needs and direct resources. Co-administration or use of combination vaccines against multiple viruses may be a viable strategy to enhance coverage by simplifying schedules and improving access, together with future utilization of enhanced vaccine platforms to develop novel vaccines. In addition, vaccination-focused healthcare provider training and consumer education are recommended to address vaccine hesitancy. Reaching vaccination targets and expanding coverage in adult at-risk populations are increasingly achievable with the availability of new and updated vaccination strategies for respiratory viruses, but will require collective efforts across providers, policymakers, scientists, health officials, and the general population.

Introduction: In September 2023 the Food and Drug Administration (FDA) approved an updated mRNA COVID-19 vaccine targeting the XBB.1.5 sublineage. This study evaluates the effectiveness of mRNA-1273.815, a 2023-2024 Omicron XBB.1.5-containing mRNA COVID-19 vaccine in preventing COVID-19-related hospitalizations and medically attended COVID-19 in US adults aged ≥ 18 years.

Methods: This observational, matched cohort study used medical and pharmacy claims data from HealthVerity. Adults vaccinated with mRNA-1273.815 between September 12, 2023, and December 31, 2023, were followed through January 26, 2024. Vaccinated individuals were matched with individuals unvaccinated with any 2023-2024 COVID-19 vaccine on demographic and clinical characteristics. The primary and secondary outcomes were COVID-19 hospitalization and medically attended COVID-19, respectively. Inverse probability of treatment weighting and Cox proportional hazards regression were utilized to estimate vaccine effectiveness (VE).

Results: The study included 1,272,161 vaccinated individuals matched 1:1 with unvaccinated individuals, with a maximum follow-up of 128 (median 84) days. The VE against COVID-19 hospitalization was 51% (95% confidence interval [CI]: 48-54%). Subgroup analyses showed a VE of 56% (95% CI 51-61%) among adults ≥ 65 years and 46% (95% CI 39-52%) in immunocompromised adults. For medically attended COVID-19, the VE was 25% (95% CI 24-27%). Time-varying analyses showed that while VE declined over time, VE remained significant.

Conclusion: During the 2023-2024 respiratory season, the mRNA-1273.815 vaccine significantly protected against COVID-19-related hospitalizations and medically attended COVID-19 across diverse adult populations and demonstrated durability of the effect. These results support the continued use of updated COVID-19 vaccines to mitigate severe outcomes and maintain public health safety.

Introduction: Stenotrophomonas maltophilia is an opportunistic pathogen associated with various nosocomial infections and is known for its intrinsic multidrug resistance. This study aims to provide a comprehensive overview of the epidemiology and resistance patterns of S. maltophilia in China from 2014 to 2021.

Methods: Data were extracted from the China Antimicrobial Resistance Surveillance System (CARSS) and the Blood Bacterial Resistance Investigation Collaborative System (BRICS), encompassing 1412 medical institutions across 31 provinces in China. We analyzed the prevalence of S. maltophilia in clinical isolates, focusing on specific patient populations and departments, as well as resistance profiles to recommended first-line antibiotics, including sulfamethoxazole-trimethoprim, levofloxacin, and minocycline.

Results: A total of 514,768 S. maltophilia strains were analyzed. The overall prevalence of S. maltophilia among all clinical bacterial isolates remained stable at approximately 2.1%, with higher rates observed in intensive care units and elderly patients. Resistance rates to sulfamethoxazole-trimethoprim decreased from 9.8% in 2014 to 7.5% in 2021. In contrast, resistance to levofloxacin showed a slight upward trend, increasing from 8.5% in 2014 to 9.5% in 2021. Meanwhile, minocycline resistance remained low, fluctuating marginally from 2.7% in 2014 to 1.7% in 2021.

Conclusions: This study highlights the stable prevalence of S. maltophilia in clinical settings in China and the overall low resistance rates to recommended first-line antibiotics. However, alarmingly high resistance rates were observed in specific specimen types, particularly in blood cultures, suggesting that minocycline may be the only reliable therapeutic option among the six tested antibiotics for treating such infections in China. Continuous surveillance and effective infection control measures are essential to manage S. maltophilia infections, particularly in vulnerable populations. Future research should focus on measuring the true burden of these infections and monitoring the susceptibility of the newly introduced antibiotics, such as cefiderocol.

Introduction: Despite the ongoing efforts to refine treatment durations and methods for patients with chronic pulmonary aspergillosis, the clinical use of antifungal agents remains unclear. This study aimed to describe the treatment practices, trajectories, and prognoses of newly diagnosed patients with chronic pulmonary aspergillosis.

Methods: Data from a longitudinal database from hospitals in Japan was used. The target population included patients who started antifungal treatment following their initial diagnosis of pulmonary aspergillosis, pulmonary aspergilloma, or chronic necrotizing pulmonary aspergillosis between October 2015 and September 2017. We described patient characteristics and treatment practices.

Results: Of the 680 patients analyzed, 253 (37.2%), 231 (34.0%), 155 (22.8%), 31 (4.6%), and 10 (1.5%) patients received the initial treatment with voriconazole, itraconazole, micafungin, caspofungin, and liposomal amphotericin B, respectively. Over 50% of the patients initially treated with micafungin or caspofungin switched to azoles within a month. Of the patients treated with antifungal agents, only 46.8% continued treatment for 6 months, indicating a lower retention rate. The overall mortality rate at 1 year was 24.7%. The median treatment duration of initial treatment until switching was 83 days (interquartile range [IQR], 159) for voriconazole and 162 days (IQR, 310) for itraconazole, indicating a significant variation in treatment duration. Notably, 15.7% (76/484) of the patients underwent a treatment switch between voriconazole and itraconazole in the initial azole treatment group.

Conclusions: Our findings highlight the challenges associated with sustaining long-term antifungal treatment.

Introduction: Individuals at increased risk of severe coronavirus disease 2019 (COVID-19) progression have a higher probability of being hospitalized. Nirmatrelvir/ritonavir (NMV/r) is an antiviral drug aiming to prevent severe disease courses. Our study aimed to assess the resource utilization and costs of adults hospitalized for COVID-19 at high risk for severe disease progression.

Methods: A retrospective study was conducted using German claims data. The presence of high-risk criteria was determined through recorded diagnoses, operations, procedures, and prescriptions. Individuals at high risk for severe COVID-19 progression, primarily hospitalized for COVID-19, required a recorded diagnosis for COVID-19 and additionally a diagnosis of sepsis, pulmonary embolism, acute respiratory failure, pneumonia, or a remdesivir prescription. Patients were grouped by eligibility for NMV/r treatment (eligible, eligible with restrictions, and not eligible). The outcomes of interest were reported for the timeframe of the last dominant virus variant available in the database, i.e., Delta (June 21, 2021 to December 31, 2021).

Results: Of approximately 3.7 million individuals continuously observable in the database, about 60% were identified as being at high risk for severe COVID-19 progression. Among high-risk individuals, 2938 patients were primarily hospitalized for COVID-19 between June 21, 2021, and December 31, 2021, two-thirds of which were suitable for NMV/r treatment (half without restrictions). Advanced age (86.3%) and cardiovascular conditions (83.9%) were the most prevalent of the predefined risk factors. Identified patients stayed, on average, 11.3 days in hospital, with inpatient mortality of 18.9%. These COVID-19-related hospitalizations resulted in mean healthcare costs of €8728.

Conclusions: This study reflects the economic burden of hospitalized adult individuals with COVID-19 at high risk for severe disease progression from payer's perspective in Germany. Our findings highlight the need to prevent severe disease courses and associated hospitalizations to relieve healthcare systems regarding costs and resource allocation.

Introduction: Despite the declining public health emergency status, COVID-19 still poses significant risks, especially for immunocompromised individuals. We aimed to evaluate the effectiveness of tixagevimab-cilgavimab (T-C) prophylaxis in preventing severe COVID-19 in patients with hematologic malignancies (HM) treated with anti-CD20 therapy during the early Omicron variant phase of the pandemic.

Methods: The European Society of Clinical Microbiology and Infectious Diseases Study Group for Respiratory Viruses (ESGREV) conducted a multicenter retrospective cohort study involving 15 centers from 5 countries. The study included 749 patients with HM treated with anti-CD20 between February 15 and June 30, 2022, comparing 215 who received T-C prophylaxis to 534 who did not.

Results: The study revealed a significant reduction in the risk of COVID-19 among patients who received T-C prophylaxis compared to those who did not (11.2% vs 23.4%, p < 0.001), with hazard ratio (HR) of 0.40 (95% CI 0.26-0.63), adjusted for age, sex, vaccination status, baseline HM malignancy and type of anti-CD-20. We also demonstrated a reduction for severe-critical diseases within all study populations, 1.4% vs 5.2%, p = 0.017, HR 0.26 (95% CI 0.08-0.84).

Conclusion: T-C prophylaxis effectively prevented COVID-19 and severe-critical COVID-19 in patients with HM treated with anti-CD20 monoclonal antibodies during the early Omicron variant phase of the pandemic. Even though T-C is ineffective against current variants, these findings highlight the importance of additional protective measures and the continued development of monoclonal antibodies to protect immunocompromised individuals to mitigate the impact of COVID-19 and other respiratory viral diseases.

Influenza virus, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are acute respiratory infections (ARIs) that can cause substantial morbidity and mortality among at-risk individuals, including older adults. In this narrative review, we summarize themes identified in the literature regarding the epidemiology, seasonality, immunity after infection, clinical presentation, and transmission for these ARIs, along with the impact of the COVID-19 pandemic on seasonal patterns of influenza and RSV infections, with consideration of data specific to older adults when available. As the older adult population increases globally, it is of paramount importance to fully characterize the true disease burden of ARIs in order to develop appropriate mitigation strategies to minimize their impact in vulnerable populations. Challenges associated with characterizing the burden of these diseases include the shared symptomology and clinical presentation of influenza virus, RSV, and SARS-CoV-2, which complicate accurate diagnosis and highlight the need for improved testing and surveillance practices. To this end, multiple regional, national, and global virologic and disease surveillance systems have been established to provide accurate knowledge of viral epidemiology, support appropriate preparedness and response to potential outbreaks, and help inform prevention strategies to reduce disease severity and transmission. Beyond the burden of acute illness, long-term health consequences can also result from influenza virus, RSV, and SARS-CoV-2 infection. These include cardiovascular and pulmonary complications, worsening of existing chronic conditions, increased frailty, and reduced life expectancy. ARIs among older adults can also place a substantial financial burden on society and healthcare systems. Collectively, the existing data indicate that influenza virus, RSV, and SARS-CoV-2 infections in older adults present a substantial global health challenge, underscoring the need for interventions to improve health outcomes and reduce the disease burden of respiratory illnesses.Graphical abstract and video abstract available for this article.