Infectious Diseases and Therapy最新文献

Introduction: The efficacy and safety of omadacycline have been primarily documented through Phase III clinical trials; however, there are limited data from real-world clinical settings. This study aims to explore the real-world use of omadacycline in China and identify the factors associated with its efficacy.

Methods: We conducted a retrospective review of medical records for patients treated with omadacycline at a single center from March 2022 to March 2024. We analyzed demographic characteristics, laboratory results, antibiotic regimens, and clinical outcomes. Logistic regression was employed to identify risk factors associated with clinical treatment failure or failure of microbial clearance.

Results: A total of 183 patients were included in the final analysis. Clinical success was achieved in 71.0% (130/183) of patients, with a bacterial clearance rate of 61.9% (26/42). Renal impairment was observed in 20.8% (38/183) of patients, with 39.5% (15/38) of these patients receiving nephrotoxic antibiotic treatments. Noteworthy adverse drug reactions were rare during the course of the treatment. Multivariate logistic regression analysis identified several independent factors associated with treatment failure: moderate to severe liver damage (OR: 3.073, 95% CI 1.345-7.021, p = 0.008), admission to the respiratory department (OR: 2.573, 95% CI 1.135-5.834, p = 0.024), and a duration of omadacycline therapy of less than 7 days (OR: 3.762, 95% CI 1.626-8.706, p = 0.002).

Conclusions: Our study demonstrates that omadacycline treatment can achieve favorable clinical success and bacterial clearance, with positive safety and tolerability outcomes. However, high-quality randomized controlled trials are needed to validate these initial findings.

Introduction: Nirmatrelvir/ritonavir (NMV/r) is approved in the United States (US) and more than 70 other countries for the treatment of mild to moderate COVID-19 in nonhospitalized adults at high risk for severe disease. Because ritonavir inhibits several drug metabolizing enzymes, potential drug-drug interactions (DDIs) between ritonavir and concomitant medications are an important consideration for prescribers. Here, we conducted a real-world analysis of data from Pfizer's global safety database regarding adverse events (AEs) reported during use of NMV/r concomitantly with potentially interacting drugs.

Methods: Data were extracted regarding DDI cases occurring from the start of NMV/r authorization through October 31, 2023. Results regarding concomitant treatment, specific AEs, and clinical outcomes are summarized. Overall NMV/r exposure was estimated based on packs of medication dispensed and was used to calculate reporting rates.

Results: Among 19,617,670 patients exposed globally to NMV/r, 966 cases of potential DDIs were reported. Of these, 594 occurred in the US against an estimated US exposure of 14,646,990 patients, representing a reporting rate of 0.004%. Globally and in the United States, 66.8% and 77.3% of cases, respectively, were nonserious. Simvastatin and tacrolimus were the most frequently reported drugs associated with potential DDIs, and the most frequently reported AE regarding a specific event or symptom was dysgeusia (altered sense of taste), an AE known to be associated with NMV/r.

Conclusions: Low reporting rates of DDIs support the potential for NMV/r treatment to be safely managed with careful use of available drug interaction resources to aid in risk mitigation.

Introduction: Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness that is preventable via vaccination. Even with treatment, up to 10-15% of cases are fatal, and many survivors may experience severe long-term sequelae. Building upon the acute-phase findings presented in the Part 1 manuscript for this study, we describe the long-term physical, social, psychological, and economic burden of IMD on US survivors and their caregivers in this Part 2 manuscript.

Methods: This was a novel, non-interventional, mixed-methods study among US survivors and their caregivers using a bespoke survey and qualitative interviews.

Results: Ten adult survivors, one adolescent survivor, and three caregivers participated in this study. Survivors described extensive physical, neurological, and systemic sequelae, including difficulty walking (11/11), repeat secondary infections (9/11), and numbness (6/11), among others, which were echoed by caregivers. Survivors shared that IMD had negatively impacted their long-term quality of life, citing long-term impacts including emotional impacts (11/11), social impacts (10/11), memory (7/11) and attention (5/11) problems, and difficulty with functional (10/11), self-care (7/11), and physical (6/11) activities. Caregivers were also impacted, describing emotional trauma (3/3), sleep problems (2/3), and day-to-day challenges (2/3). Long-term financial challenges related to healthcare resource utilization were substantial, with specialized care and rehabilitation therapy expenses (11/11), insurance challenges (8/11), and high out-of-pocket costs (6/11) for survivors. Productivity losses were also commonly described by survivors (9/11); sequelae hindered ability to attend school (9/11) or work full time (8/11). Caregivers (2/3) described taking leave from their employment, affecting family income.

Conclusions: The humanistic burden of IMD on survivors and their caregivers is substantial and persistent. A comprehensive approach, including preventative measures (e.g., vaccination) and long-term medical, psychological, and financial support for those affected, is needed to mitigate the burden of IMD. A video abstract is available with this article. Video abstract (MP4 1,17,430 kb).

Invasive meningococcal disease (IMD) is associated with high morbidity and mortality and predominantly caused by five Neisseria meningitidis serogroups (A/B/C/W/Y). Polysaccharide conjugate vaccines induce T-cell-dependent immune responses, are immunogenic in infants and adults, and reduce carriage, and vaccination of age groups associated with high-carriage can provide indirect protection in the unvaccinated (herd immunity). Successful vaccination programs must be tailored to local epidemiology, which varies geographically, temporally, and by age and serogroup. Serogroup A IMD once predominated globally, but has largely disappeared following mass vaccination programs. Serogroup B was a predominant cause of IMD in many global regions from 2010 to 2018, typically affecting younger age groups. Spread of serogroup C clonal complex-11 IMD in the 1990s prompted implementation of MenC vaccine programs in many countries, resulting in declines in prevalence. Serogroup C still caused > 20% of global IMD through the mid-2010s. Serogroup W became a significant contributor to global IMD after Hajj pilgrimage outbreaks in 2000; subsequent increases of endemic disease and outbreaks were reported pre-pandemic in many regions. Serogroup Y emerged in the 1990s as a significant cause of IMD throughout various regions and prevalence had increased or stabilized from 2010 to 2018. Serogroup X is uncommon outside the African meningitis belt, and its prevalence has declined since before the COVID-19 pandemic. Global IMD declines during the pandemic were followed by resurgences generally caused by serogroups that were prevalent pre-pandemic and affecting mainly unvaccinated age groups (particularly adolescents/young adults). Recent IMD epidemiology underscores the importance of vaccinating at-risk age groups against regionally prevalent serogroups; for example, the anti-serogroup X component of the recently prequalified MenACWXY vaccine is likely to provide limited protection outside the African meningitis belt. In other regions, comprehensive vaccination against MenB and MenACWY, which could be streamlined by the recently approved MenABCWY vaccine, seems more appropriate.

Introduction: Infective endocarditis (IE) due to methicillin-resistant Staphylococcus aureus (MRSA) is characterized by frequent treatment failure to first-line agents and high mortality, necessitating use of alternative management strategies. Ceftaroline fosamil (CPT) is a cephalosporin antibiotic with activity against MRSA but without regulatory approval for the indication of IE. This study describes clinical experience with CPT-based regimens utilized in MRSA-IE.

Methods: This is a retrospective, observational, descriptive analysis of patients from two major urban medical centers in Detroit, Michigan from 2011 to 2023. Included adult patients (≥ 18 years) had ≥ 1 positive blood culture for MRSA, met definitive clinical criteria for IE, and received CPT for ≥ 72 h. The primary outcome was treatment failure, defined as a composite of 30-day all-cause mortality from index culture or failure to improve or resolve infectious signs/symptoms after CPT initiation.

Results: Seventy patients were included. The median (interquartile range [IQR]) age was 51 (34-63) years and 45.7% were male. Persons with injection drug use (PWID) made up 55.7% of the cohort and right-sided IE was the most prevalent subtype (50.0%). CPT was frequently employed second-line or later, often in combination with vancomycin (10.0%) or daptomycin (72.9%). Overall, 31.4% experienced treatment failure and 30-day all-cause mortality occurred in 15.7%.

Conclusions: These findings illustrate the challenges posed by MRSA-IE, including frequent treatment failures, and highlight the utilization of CPT as salvage therapy. Comparative studies are needed to more clearly define its role in MRSA-IE.

Introduction: The United States Advisory Committee on Immunization Practices (ACIP) and the Centers for Disease Control (CDC) recommend COVID-19 vaccines for all immunocompromised individuals. Certain disease groups are at increased risk of comorbidity and death for which disease-specific recommendations should be considered. The objective of the Delphi panel of experts was to summarize expert consensus on COVID-19 vaccinations for patients with rheumatologic disease, renal disease, hematologic malignancy and solid organ transplant (SOT) in the US.

Methods: A two-stage Delphi panel method was employed, starting with qualitative interviews with key opinion leaders (KOLs) in the four disease areas (n = 4 KOLs, n = 16 total) followed by three rounds of iterative revision of disease-specific COVID-19 vaccine recommendations. Final consensus was rated after the third round. Statements addressed primary and booster dosing (e.g., number and frequency) and other considerations such as vaccine type or heterologous messenger ribonucleic acid (mRNA) vaccination. Following the Delphi Panel, an online survey was conducted to assess physician agreement within the disease areas (n = 50 each, n = 200 total) with the consensus statements.

Results: Moderate to strong consensus was achieved for all primary series vaccination statements across disease groups, except one in hematology. Similarly, moderate to strong consensus was achieved for all booster series statements in all disease areas. However, statements on antibody titer measurements for re-vaccination considerations and higher dosages for immunocompromised patients did not reach agreement. Overall, approximately 62%-96% of physicians strongly agreed with the primary and booster vaccine recommendations. However, low agreement (29%-69%) was found among physicians for time interval between disease-specific treatment and vaccination, recommendations for mRNA vaccines, heterologous mRNA vaccination, antibody titer measurement and higher vaccine dosage for immunocompromised groups.

Conclusion: Consensus was achieved for disease-specific COVID-19 vaccine recommendations concerning primary and booster series vaccines and was generally well accepted by practicing physicians.

Introduction: Lower respiratory tract illness (LRTI) caused by respiratory syncytial virus (RSV) is common among young children in Argentina. Use of the currently available prophylactic agent is limited to children aged ≤ 2 years with selected high-risk conditions, and thus the majority of infants remain unprotected. We estimated the value-based price (VBP) of a novel RSVpreF vaccine for use among pregnant people for prevention of RSV-LRTI among infants during the first year of life.

Methods: Clinical outcomes and economic costs of RSV-LRTI during infancy and expected impact of RSVpreF vaccination during pregnancy were projected using a population-based Markov-type cohort model. Model results-estimated on the basis of gestational age at birth, disease/fatality rates, and mother's vaccination status-include total numbers of RSV-LRTI cases, RSV-LRTI-related deaths, and associated costs. Base case analyses (RSVpreF vs. no vaccine) were conducted from the healthcare system perspective. Probabilistic sensitivity analyses (PSA; 1000 replications) were also conducted. Willingness-to-pay (WTP) was $10,636 per quality-adjusted life-year (QALY; i.e., 1 × 2021 gross domestic product [GDP] per capita) in base case analyses and PSA. Costs are reported in USD, estimated on the basis of the June 22, 2023 exchange rate.

Results: Use of RSVpreF among 342,110 pregnant persons provided protection to 330,079 infants at birth. In total, RSVpreF prevented 3915 RSV hospitalizations, 6399 RSV cases requiring emergency department care, 6182 RSV cases requiring a physician office visit, and 67 disease-related deaths. Direct costs were projected to be reduced by $5.0 million. With 2061 QALYs gained and vaccine administration cost of $1.4 million, the VBP of RSVpreF was estimated to be $74.46 per dose. In PSA, mean VBP was $75.02 (95% confidence interval 54.24-97.30).

Conclusions: RSVpreF among pregnant persons would significantly reduce the clinical and economic burden of RSV-LRTI among infants in Argentina and would be considered a cost-effective intervention up to a price of approximately $75.

The spread of carbapenemase-producing gram-negative pathogens, especially those producing metallo-β-lactamases (MBLs), has become a major health concern. MBLs are molecularly the most diverse carbapenemases, produced by a wide spectrum of gram-negative organisms, including the Enterobacterales, Pseudomonas spp., Acinetobacter baumannii, and Stenotrophomonas maltophilia, and can hydrolyze most β-lactams using metal ion cofactors in their active sites. Over the years, the prevalence of MBL-carrying isolates has increased globally, particularly in Asia. MBL infections are associated with adverse clinical outcomes including longer length of hospital stay, ICU admission, and increased mortality across the globe. The optimal treatment for MBL infections not only depends on the pathogen but also on the underlying resistance mechanisms. Currently, there are only few drugs or drug combinations that can efficiently offset MBL-mediated resistance, which makes the treatment of MBL infections challenging. The rising concern of MBLs along with the limited treatment options has led to the need and development of drugs that are specifically targeted towards MBLs. This review discusses the prevalence of MBLs, their clinical impact, and the current treatment options for MBL infections and their limitations. Furthermore, this review will discuss agents currently in the pipeline for treatment of MBL infections.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare systems globally. The lack of quality guidelines on the management of COVID-19 in rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients has resulted in a wide variation in clinical practice.

Methods: Using a Delphi process, a panel of 16 key opinion leaders developed clinical practice statements regarding vaccine recommendations in areas where standards are absent or limited. Agreement among practicing physicians with consensus statements was also assessed via an online physician survey. The strength of the consensus was determined by the following rating system: a strong rating was defined as all four key opinion leaders (KOLs) rating the statement ≥ 8, a moderate rating was defined as three out of four KOLs rating the statement ≥ 8, and no consensus was defined as less than three out of four KOLs provided a rating of ≤ 8. Specialists voted on agreement with each consensus statement for their disease area using the same ten-point scoring system.

Results: Key opinion leaders in rheumatology, nephrology, and hematology achieved consensuses for all nine statements pertaining to the primary and booster series with transplant physicians reaching consensus on eight of nine statements. Experts agreed that COVID-19 vaccines are safe, effective, and well tolerated by patients with rheumatological conditions, renal disease, hematologic malignancy, and recipients of solid organ transplants. The Delphi process yielded strong to moderate suggestions for the use of COVID-19 messenger ribonucleic acid (mRNA) vaccines and the necessity of the COVID-19 booster for the immunocompromised population. The expert panel had mixed feelings concerning the measurement of antibody titers, higher-dose mRNA vaccines, and the development of disease-specific COVID-19 guidance.

Conclusions: These results confirmed the necessity of COVID-19 vaccines and boosters in immunocompromised patients with rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients. Statements where consensus was not achieved were due to absent or limited evidence.

Introduction: We aimed to describe the risk profile of RSV infections among children aged ≤ 24 months in Valladolid from January 2010 to August 2022 and to compare them with influenza and COVID-19 controls.

Methods: We conducted a retrospective cohort study of all laboratory-confirmed RSV, influenza, and COVID-19 infections. We analyzed risk factors for RSV hospitalization and severity (length-of-stay ≥ 8 days, intensive-care-unit admission, in-hospital death or readmission < 30 days) and compared severity between hospitalized RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models.

Results: We included 1507 patients with RSV (1274 inpatient), 32 with influenza, and 52 COVID-19 controls. Hospitalized RSV (mean age 5.3 months) and COVID-19 (4 months) were younger than influenza (9.1 months) patients. Sixteen percent of patients had RSV within the first month of life. Most infants did not have comorbidities (74% RSV, 56% influenza, and 69% COVID-19). Forty-one percent of patients with RSV and influenza were coinfected vs. 27% COVID-19 (p = 0.04). Among RSV, hospitalization risk factors were prematurity (adjusted OR 3.11 [95% CI 1.66, 4.44]) and coinfection (2.03 [1.45, 2.85]). Risks for higher severity were maternal smoking (1.89 [1.07, 3.33]), prematurity (2.31 [1.59, 3.34]), chronic lung disease (2.20 [1.06, 4.58]), neurodevelopmental condition (4.28 [2.10, 8.73]), and coinfection (2.67 [2.09, 3.40]). Breastfeeding was protective against hospitalization (0.87 [0.80, 0.95]) and severity (0.81 [0.74, 0.88]), while complete vaccination schedule was protective against severity (0.51 [0.27, 0.97]). RSV had 2.47 (1.03, 5.96) higher risk of experiencing any severe outcome compared to influenza and did not show significant differences vs. COVID-19.

Conclusions: RSV hospitalizations were more frequent and severe than influenza, while severity was comparable to the early pandemic COVID-19. Currently, both influenza and COVID-19 vaccines are included in the maternal and childhood Spanish immunization schedule between the ages of 6 and 59 months. RSV monoclonal antibody is recommended for ≤ 6 months but a third of patients were aged 6-24 months. Maternal RSV vaccination can protect their children directly from birth and indirectly through breastfeeding.