Infectious Diseases and Therapy最新文献

{"title":"Detection of Phage's Lytic Activity Against Carbapenemase-Producing Klebsiella pneumoniae Isolates Using a High-Throughput Microbroth Growth Inhibition Assay.","authors":"Paschalis Paranos, Spyros Pournaras, Joseph Meletiadis","doi":"10.1007/s40121-024-01092-0","DOIUrl":"https://doi.org/10.1007/s40121-024-01092-0","url":null,"abstract":"<p><strong>Introduction: </strong>The host range of phages is usually assessed with the agar overlay method. However, this method is both cumbersome and subjective. Therefore, a microbroth assay was developed to assess host range and lytic activity patterns of phages in the agar overlay method against a collection of carbapenemase-producing Klebsiella pneumoniae (CRKP) isolates.</p><p><strong>Methods: </strong>The host range of 11 K. pneumoniae-specific phages against 8 non-repetitive well-characterized CRKP isolates was assessed with the agar overlay method and a microbroth assay by monitoring optical density (OD) at 630 nm for 24 h at different phage concentrations (5 × 10⁹-5 × 10³ PFU/ml) and two bacterial inocula (5 × 10⁶ and 5 × 10⁸ CFU/ml). The lytic activity of phage-bacteria pairs with transparent/semi-transparent (N = 7), turbid (N = 6), and no (N = 6) lysis in overlay agar method was compared statistically with the growth inhibition at 6 and 24 h in the microbroth assay with analysis of variance (ANOVA), receiver operating characteristic curves (ROC) curves and Fisher's exact test. Optimal cutoffs were determined, and sensitivity and specificity were calculated.</p><p><strong>Results: </strong>Statistically significant differences of growth inhibition at 6 and 24 h for phage concentrations ≥ 5 × 10⁸ PFU/ml for both inocula were found between phages with transparent/semi-transparent, turbid, and no lysis. ROC curve analysis indicated an optimal growth inhibition cutoff of ≥ 31% at high phage and bacteria concentrations for detecting phages with lysis and ≥ 61% at high-phage and low-bacteria concentrations for detecting phages with transparent/semi-transparent lysis with sensitivity/specificity 100%/100% and 100%/86%, respectively.</p><p><strong>Conclusions: </strong>The microbroth growth inhibition assay provided fast, reliable, and objective results for K. pneumoniae phage host-range lytic activity differentiating different patterns of lysis in a high-throughput format.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Effectiveness of mRNA-1273.815 Against COVID-19 Hospitalization Among Adults Aged ≥ 18 Years in the United States.","authors":"Amanda Wilson, Neloufar Rahai, Ekkehard Beck, Elisha Beebe, Brian Conroy, Daina Esposito, Priya Govil, Hagit Kopel, Tianyi Lu, James Mansi, Morgan A Marks, Katherine E Mues, Rohan Shah, Michelle Skornicki, Tianyu Sun, Astra Toyip, Mitra Yousefi, David Martin, Andre B Araujo","doi":"10.1007/s40121-024-01091-1","DOIUrl":"https://doi.org/10.1007/s40121-024-01091-1","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is a Consensus Case Definition for Viral Associated Lower Respiratory Tract Disease (LRTD) in Clinical Trials Possible?","authors":"S Elizabeth Williams, Bradford Gessner, Elizabeth Begier, Negar Aliabadi, Kumar Ilangovan, Luis Jodar, Cassandra Hall-Murray, Giovanni Checcucci Lisi, Edward Walsh","doi":"10.1007/s40121-024-01087-x","DOIUrl":"https://doi.org/10.1007/s40121-024-01087-x","url":null,"abstract":"<p><p>Lower respiratory tract illness or disease (LRTI/LRTD) represents a significant source of morbidity and mortality following viral respiratory illnesses, yet a consensus definition for this outcome is lacking. Recent studies of novel vaccines against respiratory syncytial virus (RSV) for older adults used LRTI/LRTD as the primary outcome to assess vaccine efficacy. However, the different vaccine trials have used highly variable criteria to define this outcome, leading to difficulty in comparison of vaccine efficacy results between trials. Here we review the key differences in criteria for case definitions, highlight strategies to best approximate compatibility between definitions, and review vaccine efficacy results among currently US Food and Drug Administration (FDA)-approved vaccines using these strategies. We hope this overview will support the need to develop a consensus definition for LRTI/LRTD to improve future research related to viral respiratory disease.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Achieving Hepatitis C Micro-Elimination in Chinese Injecting Drug Users: A Dynamic Network Modeling Study.","authors":"Ying Chen, Yun Bao, Mengxia Yan, Huajie Jin, Kaijie Yao, Chi Zhang, Wen Li, Bin Wu","doi":"10.1007/s40121-024-01084-0","DOIUrl":"https://doi.org/10.1007/s40121-024-01084-0","url":null,"abstract":"<p><strong>Introduction: </strong>The World Health Organization (WHO) has established objectives for eradicating the hepatitis C virus (HCV). People who inject drugs (PWID), a major driver of HCV transmission, are an essential part of China's hepatitis C elimination program. This study aimed to estimate the requisite screening and antiviral treatment levels to achieve these goals among people who inject drugs in China and identify the most cost-effective strategy.</p><p><strong>Methods: </strong>This study utilized models based on dynamic social networks to simulate HCV transmission and disease progression among people who inject drugs in China, incorporating a cost-effectiveness analysis from a healthcare perspective.</p><p><strong>Results: </strong>To achieve the WHO targets, a minimum screening and treatment rate of 10% is required to meet the mortality goal, while a 25% rate is necessary for the incidence goal. The most cost-effective strategy includes a 25% screening rate and a 95% treatment rate. Compared to no intervention, this approach significantly reduces costs by - $85,873.38 (95% CI  - $94,311.16 to  - $77,435.59) and adds 24.66 (95% CI 23.68 to - 25.64) quality-adjusted life years. The intervention is dominant, with a cost-effectiveness ratio of - $3482.29 (95% CI  - $3982.73 to  - $3020.11) per quality-adjusted life year.</p><p><strong>Conclusion: </strong>Achieving the WHO's hepatitis C virus elimination targets among people who inject drugs in China is feasible and cost-saving.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventing Severe COVID-19 with Tixagevimab-Cilgavimab in Hematological Patients Treated with Anti-CD20 Monoclonal Antibodies: An International Multicenter Study.","authors":"Hovav Azuly, Tali Shafat, Daniel Grupel, Tzvika Porges, Ran Abuhasira, Ana Belkin, Ofir Deri, Yonatan Oster, Shadi Zahran, Ehud Horwitz, Netanel A Horowitz, Hazim Khatib, Marjorie Vieira Batista, Anita Cassoli Cortez, Tal Brosh-Nissimov, Yafit Segman, Linor Ishay, Regev Cohen, Alaa Atamna, Amy Spallone, Roy F Chemaly, Juan Carlos Ramos, Michal Chowers, Evgeny Rogozin, Noga Carmi Oren, Şiran Keske, Orit Wolfovitz Barchad, Lior Nesher","doi":"10.1007/s40121-024-01089-9","DOIUrl":"https://doi.org/10.1007/s40121-024-01089-9","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Dolutegravir/Lamivudine in the Management of Pregnant People Living with HIV-1: A Narrative Review.","authors":"William R Short, Parul Patel, Gustavo Verdier, Ana Puga, Vani Vannappagari, Annemiek de Ruiter, Bryn Jones","doi":"10.1007/s40121-024-01085-z","DOIUrl":"https://doi.org/10.1007/s40121-024-01085-z","url":null,"abstract":"<p><p>Lowering viral load during pregnancy is regarded as the most important method of reducing human immunodeficiency virus 1 (HIV-1) vertical transmission risk, and minimizing fetal exposure to drugs is a guiding principle during pregnancy. Dolutegravir/lamivudine (DTG/3TC) has demonstrated high efficacy, a high barrier to resistance, and a good safety profile in non-pregnant individuals; however, DTG/3TC is not recommended by perinatal HIV treatment guidelines for initial therapy in pregnant people living with HIV-1 because of limited data on use of the 2-drug regimen during pregnancy. Efficacy and pharmacokinetic data from pregnant individuals using DTG and/or 3TC are reviewed and used to extrapolate anticipated DTG/3TC efficacy in pregnancy. There are robust data on the use of DTG- and 3TC-containing combination regimens, which are recommended by perinatal HIV treatment guidelines during pregnancy, supporting their well-established efficacy and safety in pregnant people living with HIV-1. Updated data from the Tsepamo and Eswatini surveillance studies (> 14,000 DTG exposures from conception) indicate no increased risk of neural tube defects with DTG. Pharmacokinetic data for DTG and 3TC indicate that exposures in pregnancy are within the therapeutically effective range seen in non-pregnant adults. Two studies evaluated DTG/3TC during pregnancy and both reported high virologic suppression rates [HIV-1 ribonucleic acid (RNA) < 50 copies/mL at delivery: 97% (30/31) overall], no events of vertical transmission, and no new safety signals, consistent with the use of DTG-based 3-drug regimens in pregnancy. The use of DTG/3TC during pregnancy is anticipated to be comparably effective and well tolerated for both parental health and prevention of vertical transmission with fetal exposure to fewer antiretrovirals compared with 3- or 4-drug regimens. These considerations are relevant when evaluating use of DTG/3TC in people living with HIV-1 who are pregnant or considering pregnancy in clinical practice and in perinatal HIV treatment guidelines.Video abstract available for this article. Supplementary file1 (MP4 319,147 KB).</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Retrospective Claims Data Analysis on the Burden of COVID-19-Related Hospitalization in Adults at High Risk for Severe Disease Progression in Germany.","authors":"Timotheus Stremel, Svitlana Schnaidt, Nicole Bihrer, Emma Fröling, Christian Jacob, Agnes Kisser","doi":"10.1007/s40121-024-01088-w","DOIUrl":"https://doi.org/10.1007/s40121-024-01088-w","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness, Safety, and Patterns of Real-World Isavuconazole Use in Europe (2015-2019).","authors":"Dionysios Neofytos, Antonio Pagliuca, Katherine Houghton, Edward Broughton, Maria Lavinea Novis de Figueiredo Valente, Lili Jiang, David A Enoch, Beate Gruener, Raoul Herbrecht, Tobias Lahmer, Olivier Lortholary, Cléa Melenotte, Francesco Giuseppe De Rosa, Carolina Garcia-Vidal, Maria Jimenez, Maria Fernandez, Oliver Cornely","doi":"10.1007/s40121-024-01064-4","DOIUrl":"10.1007/s40121-024-01064-4","url":null,"abstract":"<p><strong>Introduction: </strong>Real-world data from multinational observational studies are required to better understand the role and performance of isavuconazole in real-world practice in Europe.</p><p><strong>Methods: </strong>A retrospective medical record review was conducted at 16 sites in Europe (France, Germany, Italy, Spain, and the United Kingdom). Eligible records were from patients aged ≥ 18 years at the time of isavuconazole initiation and received at least one dose of isavuconazole for suspected or confirmed invasive aspergillosis (IA) or invasive mucormycosis (IM) during the eligibility period (October 15, 2015 to June 30, 2019). Data were descriptively analysed. Success rates, overall survival, and times to these events were descriptively analysed.</p><p><strong>Results: </strong>Data were abstracted from 218 patients (201, IA; 17, IM) who received isavuconazole as monotherapy (initiated as infusion, 52%; oral, 46%). Isavuconazole was initiated as primary therapy in 92 patients (42.2%) and salvage therapy in 121 patients (55.5%) (unknown for five patients). Mean (standard deviation) age was 56.8 (15.6) years, 66% were men and 62% had at least three comorbidities, most frequently haematologic malignancy (62%). Estimated clinical response rate at week 24 was 54.5% (95% confidence interval [CI], 38.2-66.5%) for primary treatment and 73.5% (95% CI, 62.7-81.1%) for salvage therapy. Overall, 45 patients (21%) experienced at least one adverse event (AE). Serious AEs were experienced by 37 patients (17%), with seven related to isavuconazole; five patients (2.3%) discontinued isavuconazole monotherapy due to the serious AE. A total of 137 patients (63%) died, with 17 deaths (12.4%) related to their invasive fungal infection, 11 of whom initiated isavuconazole as salvage therapy.</p><p><strong>Conclusions: </strong>This study adds to the growing body of evidence that whether used as first-line therapy or after the failure of other antifungal therapies, isavuconazole appears to have a promising clinical response and a good safety profile as an antifungal agent in patients with varied underlying conditions.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2527-2543"},"PeriodicalIF":4.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics of Vancomycin in Intensive Care Patients with the Time-Varying Status of Temporary Mechanical Circulatory Support or Continuous Renal Replacement Therapy.","authors":"Meng-Ta Tsai, Wei-Chun Wang, Jun-Neng Roan, Chwan-Yau Luo, Chen-Hsi Chou","doi":"10.1007/s40121-024-01071-5","DOIUrl":"10.1007/s40121-024-01071-5","url":null,"abstract":"<p><strong>Introduction: </strong>This study characterized the population pharmacokinetics (PK) of vancomycin in patients treated with and without continuous renal replacement therapy (CRRT) or temporary mechanical circulatory support (tMCS), including extracorporeal membrane oxygenation or extracorporeal ventricular assist device.</p><p><strong>Methods: </strong>Critically ill adults with and without tMCS or CRRT prescribed vancomycin were enrolled for population PK modeling. Monte Carlo simulation provided dosing recommendations based on the probability of target attainment (PTA), achieving a 24-h area under curve (AUC24h) of 400-600 mg*h/L.</p><p><strong>Results: </strong>Twenty-five patients with 184 plasma samples were analyzed. The median age was 61.0 years. The final model was a two-compartment PK model. CRRT, serum creatinine, and body weight were significant predictors of clearance. CRRT was a covariate on the central volume of distribution. tMCS significantly decreased the intercompartmental clearance. The simulated mean trough levels at the 48th hour were lower in the tMCS group (13.4 versus 14.2 mg/dL in non-tMCS, p < 0.001) in a 70-kg subject with a creatinine of 1 mg/dL and a daily dose of 20 mg/kg, but the PTA was similar (61.8% versus 62.2%). A reduction of maintenance dose from 30 to 10 mg/kg/day with loading dose from 25 to 15 mg/kg is recommended while serum creatinine progresses from 0.5 to 4.0 mg/dL. For CRRT, the optimal regimen consists of 20-25 mg/kg loading and maintenance of 15 mg/kg/day.</p><p><strong>Conclusions: </strong>The dosing strategy of vancomycin can be based on body weight or renal function, regardless of tMCS. Intercompartmental clearance decreases under tMCS, which can mislead a dosing adjustment based on trough level.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2617-2635"},"PeriodicalIF":4.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous Versus Oral Omadacycline or Linezolid for Acute Bacterial Skin and Skin Infections: A post hoc Analysis of the OASIS Trials.","authors":"George D Rodriguez, Nathan Warren, Roman Yashayev, Surya Chitra, Maria Amodio-Groton, Kelly Wright","doi":"10.1007/s40121-024-01057-3","DOIUrl":"10.1007/s40121-024-01057-3","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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]).</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov, NCT02378480 and NCT02877927.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2637-2648"},"PeriodicalIF":4.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}