Infectious Diseases and Therapy最新文献

Introduction: Appropriate oral antibiotic therapy for the treatment of acute bacterial skin and skin structure infections (ABSSSI) is a challenge, as current oral treatment guidelines do not fully cover the most common skin pathogens. Both linezolid and omadacycline are available as intravenous or bioequivalent oral formulations.

Materials and methods: This post hoc analysis of the OASIS-1 (ClinicalTrials.gov identifier NCT02378480) and OASIS-2 (ClinicalTrials.gov identifier NCT02877927) phase 3 trials assessed safety and clinical efficacy of intravenous (IV)-start versus oral (PO)-start therapy in patients treated with omadacycline or linezolid for ABSSSI. In OASIS-1, patients were randomized to IV omadacycline or linezolid, with optional switch to oral therapy, while patients in OASIS-2 received oral omadacycline or linezolid. Treatment was provided for 7-14 days in both studies. The primary endpoint was an early clinical response (ECR) at 48 to 72 h, defined as survival and ≥ 20% reduction in lesion size, without rescue antibacterial therapy.

Results: A total of 645 IV-start inpatients and 735 PO-start outpatients were assessed. Median age was 47 years for the IV-start group and 44 years for the PO-start group. Most patients had solely gram-positive infections (97% in each group; ECR [85.2% IV-start and 85.0% PO-start]), and the incidence of treatment-emergent adverse events (AEs) was similar between the groups. The most frequent AEs observed were nausea (11.2% [IV-start] versus 18.9% [PO-start]) and subcutaneous abscess (5.6% [IV-start] versus 1.9% [PO-start]). Discontinuation due to AEs was infrequent in both groups (2% [IV-start] versus 1.2% [PO-start]).

Conclusion: Oral therapy is equally efficacious to IV therapy when omadacycline or linezolid is used to treat ABSSSIs. These data strengthen the evidence for oral omadacycline as a therapeutic option for ABSSSI, particularly for patients who have experienced treatment failure because of the limitations of other therapies.

Trial registration: Clinicaltrials.gov, NCT02378480 and NCT02877927.

Introduction: Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness with a 10-15% mortality rate. Even with timely treatment, survivors may experience acute and long-term health complications. While meningococcal vaccines are recommended for adolescents and young adults in the USA, vaccination coverage remains uneven across serotypes. This study investigated the physical, social, psychological, and economic burden of IMD on survivors and their caregivers in the USA during the acute phase (Part 1, presented in this manuscript) and the long-term phase (Part 2, presented in a separate manuscript) of IMD.

Methods: This study implemented a non-interventional, mixed-methods approach using a bespoke survey and qualitative interviews (designed on the basis of a preliminary conceptual model of IMD) with US survivors and their caregivers.

Results: A total of 11 survivors (1 adolescent, 10 adults) and 3 caregivers participated in the study. Survivors contracted IMD during infancy (n = 2), childhood (n = 3), or adulthood (n = 6), and often described leading healthy lives pre-IMD. At IMD onset, interactions with the healthcare system impacted participants' experiences; confusion and care delays were common, and procedures were often invasive (e.g., amputations). Survivors commonly experienced symptoms including skin rash (7/11), fever (6/11), and unconsciousness (6/11), consistent with caregivers' reports. Survivors able to report on the short-term impacts of IMD (n = 9) described functional limitations (9/9), emotional impacts (6/9) such as fear and trauma, and school (6/9), work (4/9), and financial (5/9) challenges. Caregivers also experienced emotional impacts (3/3) and family (2/3), work (3/3), and financial (3/3) impacts during the acute phase.

Conclusions: IMD places a significant humanistic burden on survivors and their caregivers during the acute phase. Results from Part 1 of this study indicate a need for increased disease awareness and healthcare provider education, expeditious diagnosis, and improved access to prevention methods such as available meningococcal vaccines. A video abstract is available with this article. Video abstract (MP4 1,24,432 kb).

Introduction: Given the recent approval and recommendation of V116, a 21-valent pneumococcal conjugate vaccine (PCV), in the United States (US), we evaluated the cost-effectiveness of using V116 versus the 20-valent PCV (PCV20) or the 15-valent PCV (PCV15) in series with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) among adults aged ≥ 65 years in the US who had never received a PCV previously.

Methods: A static multi-cohort state-transition Markov model was developed to estimate the lifetime incremental clinical and economic impact of V116 vs. PCV20 or PCV15 + PPSV23 from the societal perspective. All model inputs were based on published literature and publicly available databases and/or reports. Model outcomes included undiscounted clinical cases: invasive pneumococcal disease (IPD), inpatient and outpatient non-bacteremic pneumococcal pneumonia (NBPP), post-meningitis sequelae (PMS), deaths from IPD and inpatient NBPP, discounted quality-adjusted life years (QALYs) as well as the discounted total cost (in 2023 USD), which consisted of vaccine acquisition and administration costs, direct and indirect costs associated with the disease, and travel costs for vaccination. The final summary measure was the incremental cost-effectiveness ratio (ICER), reported as $/QALY gained. Three percent was used for the annual discounting rate.

Results: Based on the inputs and assumptions used, the results indicated that the V116 strategy prevented 27,766 and 32,387 disease cases/deaths and saved $239 million and $1.8 billion in total costs when compared to the PCV20 and PCV15 + PPSV23 strategies, respectively, in vaccine-naïve adults aged ≥ 65 years. The estimated ICERs were cost saving in both regimens (i.e., V116 vs. PCV20 or vs. PCV15 + PPSV23). The scenario analysis and deterministic and probabilistic sensitivity analyses also demonstrated the robustness of the qualitative results.

Conclusions: These results demonstrated that using V116 in adults aged ≥ 65 years in the US can prevent a substantial number of PD cases and deaths while remaining highly favorable economically over a wide range of inputs and scenarios.

Antiretroviral therapy has evolved significantly over the last 20-30 years, from requiring multiple tablets multiple times per day to single-tablet regimens and most recently, in 2021, long-acting injectable antiretrovirals. These long-acting antiretrovirals have expanded the treatment options for individuals with HIV who may have difficulty adhering to daily oral medications, difficulty taking oral medications, and/or individuals with multidrug-resistant HIV. This article reviews the currently available long-acting injectable antiretrovirals, including cabotegravir/rilpivirine, lenacapavir, and ibalizumab. The available data supporting these agents and current place in therapy will be discussed. Data supporting the use of additional long-acting injectable agents, broadly neutralizing antibodies, currently in the pipeline will be reviewed as well.

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.