Antibiotics-Basel最新文献

{"title":"Antifungal Agents' Trends of Utilization, Spending, and Prices in the US Medicaid Programs: 2009-2023.","authors":"Abdulrahman A Alsuhibani, Norah A Alobaid, Manar H Alahmadi, Jood S Alqannas, Wejdan S Alfreaj, Rana F Albadrani, Khalid A Alamer, Yasser S Almogbel, Ali Alhomaidan, Jeff J Guo","doi":"10.3390/antibiotics14050518","DOIUrl":"10.3390/antibiotics14050518","url":null,"abstract":"<p><p><b>Background:</b> Fungal infections, particularly among immunocompromised individuals, present significant challenges due to rising incidence rates, treatment costs, and increasing resistance to antifungal agents. This study evaluates trends in antifungal use among Medicaid beneficiaries, focusing on prescribing patterns, costs, and pricing to optimize therapy. <b>Methods:</b> Using the national Medicaid outpatient pharmacy claims data collected by the US Center of Medicare and Medicaid Services, a retrospective drug utilization analysis was conducted for antifungal medications from 2009 to 2023. Antifungal medications were categorized based on therapeutic use. The study examined annual utilization, reimbursement, and pricing trends, along with the market share. <b>Results:</b> Overall Medicaid utilization of superficial fungal infections' (SFIs') medications increased from 3.95 million prescriptions in 2009 to 6.16 million in 2023. Nystatin was the most frequently utilized SFI agent, while fluconazole emerged as the most commonly prescribed agent for invasive fungal infections (IFIs). In 2022, a notable spike occurred in the number of prescriptions for both SFIs and IFIs. Medicaid's total expenditure on SFI medications rose from USD 121.9 million in 2009 to USD 155 million in 2023, while spending on IFI medications fluctuated substantially, peaking at USD 156.8 million in 2022 before declining to USD 80.7 million in 2023. After being introduced to the market, efinaconazole became the most expensive SFI agent over the years. Isavuconazole, the latest approved IFI medication, demonstrated sustained utilization, reimbursement, and price increases. <b>Conclusions:</b> The substantial rise in antifungal utilization and spending underscores the growing financial burden on Medicaid, emphasizing the need for policy interventions to manage costs and generic drug substitution while ensuring equitable access to these essential treatments. However, this study is limited by the lack of clinical outcome data and information on off-label use. Additionally, reimbursement data may not accurately reflect actual drug prices.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial Resistance and Hospital- and Community-Associated Infections.","authors":"Samantha Flores-Treviño","doi":"10.3390/antibiotics14050514","DOIUrl":"10.3390/antibiotics14050514","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) poses a significant global threat to human health, and was estimated to be associated with almost one million deaths in 2019 [...].</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Antimicrobial Efficacy of Copper Complexes: A Review.","authors":"Kwanele Ngece, Vuyolwethu Khwaza, Athandwa M Paca, Blessing A Aderibigbe","doi":"10.3390/antibiotics14050516","DOIUrl":"10.3390/antibiotics14050516","url":null,"abstract":"<p><p>The alarming increase in antimicrobial resistance has intensified the search for novel therapeutic agents capable of combating resistant microbial strains. Copper complexes have emerged as promising antimicrobial agents due to their intrinsic redox activity, ability to disrupt microbial membranes, and interactions with vital biomolecules such as DNA and proteins. This review critically evaluates the antimicrobial potential of copper complexes reported between 2018 and 2025, emphasizing their structural diversity, mechanisms of action, and biological performance against a wide range of bacterial and fungal pathogens. Key findings reveal that Schiff base copper complexes, amino acid derivatives, heterocyclic ligands, and mixed-ligand systems exhibit potent antimicrobial activities, often surpassing standard antibiotics. Mechanistically, copper complexes induce reactive oxygen species (ROS) generation, inhibit enzyme function, cause DNA cleavage, and compromise cell membrane integrity. Furthermore, structure-activity relationship (SAR) analyses indicate that ligand type, coordination geometry, and lipophilicity significantly influence antimicrobial efficacy. Overall, the reviewed studies support the development of copper-based compounds as viable candidates for antimicrobial drug development. This review also identifies current challenges and gaps in knowledge, such as limited in vivo studies and toxicity assessments, which must be addressed to advance these compounds toward clinical application.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LC-MS/MS Determination of Quorum Sensing Molecules in Plasma from Burn Patients with Septic Shock Sustained by Acinetobacter Baumannii.","authors":"Nicolò Carpenito, Marta Leporati, Alberto Sciarrillo, Anna Pensa, Roberto Gambino, Giovanni Musso, Alberto Mella, Luigi Biancone, Daniela Risso, Filippo Mariano, Domenico Cosseddu","doi":"10.3390/antibiotics14050517","DOIUrl":"10.3390/antibiotics14050517","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Quorum Sensing (QS) refers to the communication mechanism in bacterial cells, which occurs through the production and detection of small signaling molecules to coordinate activities and monitor population size. In Gram-negative bacteria, QS is typically mediated by N-acyl-homoserine lactones (HSLs) and 2-alkyl-4(1H)-quinolone metabolites (AQ). The present study aims to develop and validate an LC-MS/MS method for detecting QS molecules and apply it to the analysis of plasma samples from burn patients with septic shock caused by <i>Acinetobacter baumannii</i>. <b>Methods</b>: The LC-MS/MS method was developed and fully validated for the quantitative, simultaneous determination of five HSLs and four AQ molecules, ultimately derived from the plasma of three patients with septic shock, with samples collected over three consecutive days. <b>Results</b>: The developed method proved to be both specific and selective, demonstrating a good fit and linearity over the entire range of interest. Trueness and accuracy were satisfactory. The method showed excellent intra-assay precision (CV% was lower than 15%) and limits of quantification (LOQ) ranging from 0.02 to 0.79 ng/mL. In the patients' samples, the concentration of 3-OH-C12-HSL peaked at 1.5 ng/mL on the first day, and C7-PQS, C9-PQS, HHQ, and HQNO ranged from 0.5 to 1.5 ng/mL, peaking at 5 ng/mL in one patient on the third day. <b>Conclusions</b>: A method for the simultaneous determination of nine QS molecules by LC-MS/MS was developed and validated. When applied, it showed good performance for the analysis of plasma samples and could be a useful tool for an improvement in the diagnosis, prognosis, or treatment monitoring of infections in burn patients caused by <i>Acinetobacter baumannii</i>.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Activity of Nisin A Against Staphylococci Isolated from Periprosthetic Joint Infection.","authors":"Melissa J Karau, Christina A Koscianski, Andrew D Badley, Nicholas A Bedard, John W Zinckgraf, Robin Patel","doi":"10.3390/antibiotics14050515","DOIUrl":"10.3390/antibiotics14050515","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Staphylococci are the most common causes of periprosthetic joint infection (PJI); new antimicrobials are needed to manage these difficult infections. Nisin A is a lantibiotic peptide derived from <i>Lactococcus lactis</i> that has antimicrobial activity against Gram-positive bacteria, including staphylococci, and is an FDA-approved preservative used in the food and dairy industry. Here, the in vitro nisin A susceptibility of PJI-associated staphylococci was assessed. <b>Methods</b>: The minimum inhibitory concentrations (MICs), minimum biofilm inhibitory concentrations (MBICs), and minimum biofilm bactericidal concentrations (MBBCs) of nisin A were measured by broth microdilution against 106 staphylococcus isolates isolated from PJI. MICs were assessed using 5 × 10⁵ CFU/mL plus nisin A. For MBICs, biofilms were grown on pegged lids for 6 h, followed by 20 h of treatment. For MBBCs, pegged lids were transferred to plates containing media only for 20 h. The results were determined as the lowest concentrations with no visual growth. Two-dimensional MICs with nisin A and vancomycin were assessed for 20 isolates. Fractional inhibitory concentrations (FICs) were calculated to determine synergistic, additive, antagonistic, or indifferent interactions. <b>Results</b>: The MIC that inhibited 90% of <i>S. aureus</i> and <i>S. epidermidis</i> was 4 µg/mL, apart from for the MRSA subset (8 µg/mL). The MBIC that inhibited 90% of isolates was 4 µg/mL. The MBBCs ranged from 4 to 256 µg/mL. When tested together, nisin A and vancomycin yielded an FIC between 1.25 and 1.5, indicative of indifference, except for one isolate each of MRSA and MSSA, for which an additive effect (FIC of 1) was observed. <b>Conclusions</b>: Nisin A showed inhibitory activity against staphylococci that cause PJI.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conventional Antimicrobial and Medicinal Plants from a Traditional Medicine Market in South Africa: An Interactive Antimicrobial and Toxicity Study.","authors":"Zelna Booth, Sabiha Essack, Sandy van Vuuren","doi":"10.3390/antibiotics14050512","DOIUrl":"10.3390/antibiotics14050512","url":null,"abstract":"<p><strong>Background: </strong>The World Health Organization (WHO) has proposed the use of integrative medicine to achieve extended healthcare coverage in developing countries facing high morbidity. Traditional remedies are frequently employed to prevent and treat infections among South Africans; however, the ways in which they interact with conventional antimicrobials are largely unknown. Therefore, this study aimed to explore the interactions between commonly traded medicinal plants at a traditional medicine market in KwaZulu-Natal (KZN), South Africa, and conventional antibiotics and antifungals.</p><p><strong>Methods: </strong>To determine the interactive antimicrobial profiles for plant/conventional antimicrobial combinations, minimum inhibitory concentration (MIC) assays were performed against ESKAPE pathogens and the yeasts <i>Candida albicans</i> and <i>Candida glabrata</i>. Calculated fractional inhibitory concentration (ΣFIC) values were used to identify synergism or antagonism, with synergistic interactions further tested in vitro for toxicity.</p><p><strong>Results: </strong>A total of 952 combinations were tested, of which 5.8% and 54.6% of the plant/antibiotic combinations were synergistic and antagonistic, respectively; additionally, 1.7% and 58.6% of the plant/antifungal combinations showed synergism or antagonism, respectively. The most toxic plant/antibiotic combination was <i>Artemisia afra</i> with doxycycline (71.1% mortality). The most toxic plant/antifungal combination was <i>Acorus calamus</i> with fluconazole (78.8% mortality).</p><p><strong>Conclusions: </strong>When medicinal plants acquired from a traditional medicine market in South Africa are used in combination with conventional antibiotics and antifungals, more than half of the combinations exhibit antagonism, which is concerning.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One Health at Risk: Plasmid-Mediated Spread of <i>mcr-1</i> Across Clinical, Agricultural, and Environmental Ecosystems.","authors":"Abdelaziz Touati, Nasir Adam Ibrahim, Assia Mairi, Hassina Kirat, Nosiba S Basher, Takfarinas Idres","doi":"10.3390/antibiotics14050506","DOIUrl":"10.3390/antibiotics14050506","url":null,"abstract":"<p><p>The global dissemination of plasmid-mediated <i>mcr</i> genes, which confer resistance to the last-resort antibiotic colistin, represents a critical public health challenge driven by the interplay of clinical, agricultural, and environmental factors. This review examines the genetic and ecological dynamics of <i>mcr</i>-bearing plasmids, focusing on their role in disseminating colistin resistance across diverse bacterial hosts and ecosystems. Key plasmid families demonstrate distinct evolutionary strategies, including IncI2, IncHI2, and IncX4. IncI2 plasmids favor stability in livestock and clinical settings. IncHI2 plasmids, on the other hand, leverage transposons to co-select for multidrug resistance, while IncX4 plasmids achieve global dissemination through streamlined, conjugation-efficient architectures. The pervasive spread of <i>mcr</i> genes is exacerbated by their integration into chromosomes via mobile genetic elements and co-selection with resistance to other antibiotic classes, amplifying multidrug-resistant phenotypes. Environmental reservoirs, food chains, and anthropogenic practices further facilitate cross-niche transmission, underscoring the interconnectedness of resistance under the One Health framework. Addressing this crisis requires coordinated strategies, including reducing colistin misuse in agriculture, enhancing surveillance of high-risk plasmid types, and fostering international collaboration to preserve antimicrobial efficacy and mitigate the threat of untreatable infections.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Antibacterial Potency of Cymbopogon Essential Oils: Liposome Encapsulation and Phytochemical Insights.","authors":"Abdirahman Elmi, Fatouma M Abdoul-Latif, Andréea Pasc, Arnaud Risler, Stéphanie Philippot, Ricardo Gil-Ortiz, Dominique Laurain-Mattar, Rosella Spina","doi":"10.3390/antibiotics14050510","DOIUrl":"10.3390/antibiotics14050510","url":null,"abstract":"<p><p><b>Background</b>: Antimicrobial resistance (AMR) represents a critical global health challenge, requiring innovative strategies to combat resistant bacterial strains. <i>Cymbopogon</i> essential oils (EOs) are promising natural antimicrobial agents. <b>Methods</b>: The EO of <i>Cymbopogon commutatus</i> was extracted by hydrodistillation from fresh aerial parts and compared to commercial EOs from <i>C. citratus</i>, <i>C. nardus</i>, and <i>C. winterianus</i>. Antibacterial activity was evaluated against seven bacterial strains (two Gram-positive and five Gram-negative). Both water-soluble fractions and liposome-encapsulated formulations were tested. Liposomes were prepared using soybean lecithin, and their stability was assessed by dynamic light scattering (DLS). The chemical composition of the pure EOs, water-soluble fractions and non-water-soluble fractions was analyzed by gas chromatography-mass spectrometry (GC-MS). <b>Results</b>: Liposome encapsulation improved EO solubility in aqueous media and significantly enhanced antibacterial efficacy, reducing minimum inhibitory concentration (MIC) values compared to the water-soluble fractions (MICs ≥ 25%). Among the tested formulations, the liposome containing <i>C. citratus</i> EO exhibited the strongest inhibitory effect against <i>Staphylococcus aureus</i> (MIC: 0.04%) followed by liposomes with <i>C. nardus</i> and <i>C. commutatus</i> (MIC: 0.08%). Against <i>Enterococcus faecalis</i>, the most effective formulation was the liposome containing <i>C. winterianus</i> EO (MIC: 0.02%), followed by <i>C. citratus</i> (MIC: 0.08%). The liposome formulated with <i>C. winterianus</i> maintained its particle size over 72 h without phase separation. GC-MS analysis revealed distinct phytochemical profiles: <i>C. commutatus</i> EO was rich in piperitone (73.9%) and <i>C. citratus</i> was rich in (Z)-(3,3-Dimethyl)-cyclohexylideneacetaldehyde (39.9%) and citral (32.5%), while <i>C. nardus</i> and <i>C. winterianus</i> were dominated by geraniol (21.5%) and citronellal (30.8%), respectively. Notably, piperitone, the major compound in <i>C. commutatus</i> EO, exhibited strong antibacterial activity against <i>S. aureus</i> (MIC of <0.04%). <b>Conclusions</b>: These findings support the potential of liposome-encapsulated <i>Cymbopogon</i> EOs as an effective and sustainable strategy to address AMR. This study provides a foundation for the development of plant-based antimicrobial formulations with improved efficacy.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Determinants of Health and Antibiotic Consumption.","authors":"Yuliya Semenova, Kamila Akhmetova, Daniil Semenov, Larissa Makalkina, Vladimir Surov, Lyudmila Pivina, Assiya Turgambayeva, Tatiana Belikhina, Saule Maukayeva, Maya Goremykina, Praveen Kumar","doi":"10.3390/antibiotics14050513","DOIUrl":"10.3390/antibiotics14050513","url":null,"abstract":"<p><p><b>Background/Objectives</b>: This study aims to analyze antibiotic consumption trends from 2014 to 2023 in Kazakhstan, Kyrgyzstan, Tajikistan, and Russia; forecast future trends up to 2030; and identify key social and economic factors influencing antibiotic use. <b>Methods</b>: Data on antibiotic consumption were obtained from the World Health Organization Regional Office for Europe Antimicrobial Consumption Network. Social and economic indicators were sourced from the World Bank DataBank. Of the 86 factors initially considered, 35 were included in the analyses. The forecast modeling of antibiotic consumption trends until 2030 and linear regression analysis to assess associations between antibiotic consumption and its predictors were conducted via SPSS. <b>Results</b>: The lowest antibiotic consumption rates were observed in Kazakhstan and Russia, whereas Kyrgyzstan and Tajikistan presented higher rates. The projected antibiotic consumption rates are expected to decline only in Kazakhstan, with other countries remaining stable. Birth and death rates, as well as under-five mortality rates, were significant determinants of antibiotic consumption in Kazakhstan and Tajikistan. In Russia, per capita GDP was a key determinant, whereas in Kazakhstan, inflation in consumer prices played a significant role. Additionally, cereal production was significantly associated with antibiotic consumption in Kazakhstan. In Kyrgyzstan and Russia, measles immunization rates were important determinants, whereas in Kyrgyzstan, access to clean fuels and technologies for cooking was significantly associated with antibiotic consumption. <b>Conclusions</b>: The findings of this study provide valuable insights for strengthening antimicrobial stewardship programs by addressing key social and economic determinants of antibiotic use.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Dose Ceftriaxone in Elderly Patients with Enterococcal Infective Endocarditis: Population Pharmacokinetics of Free Ceftriaxone and Dose Optimization.","authors":"Beatriz Fernández Rubio, Fernando Docobo Pérez, Laura Herrera Hidalgo, Luis Eduardo López-Cortés, Rafael Luque Márquez, José Manuel Lomas Cabezas, Luis Fernando López-Cortés, Marta Mejías Trueba, Ana Belén Guisado Gil, Alicia Gutiérrez Valencia, Arístides de Alarcón González, María Victoria Gil Navarro","doi":"10.3390/antibiotics14050508","DOIUrl":"10.3390/antibiotics14050508","url":null,"abstract":"<p><p><b>Background:</b> Ampicillin plus ceftriaxone (AC) is a first-line treatment for <i>Enterococcus faecalis</i> infective endocarditis (IE). Its administration in outpatient parenteral antibiotic treatment (OPAT) programs is challenging. The design of a ceftriaxone regimen suitable for OPAT requires deep knowledge of ceftriaxone pharmacokinetics (PK). <b>Objective:</b> We aim to explore ceftriaxone PK in elderly patients and propose dose regimens adapted to OPAT to maintain synergistic concentrations (Cs) with ampicillin against <i>E. faecalis</i>. <b>Methods:</b> We conducted a prospective observational pharmacokinetic study on patients (>55 years old) affected by <i>E. faecalis</i> IE. Ceftriaxone free concentration was measured at three time-points: before the administration (C_min) and two and four hours after ceftriaxone administration (C₂ and C₄). Both structural and covariate population pharmacokinetic models were built. Monte Carlo simulations of six ceftriaxone dosages were performed and the probability of target attainment (PTA) of an optimal Cs range was analyzed. The pharmacokinetic/pharmacodynamic index (PK/PD) to predict efficacy was defined as maintaining free ceftriaxone concentrations superior to the Cs at 50-100% of the dosing interval (fT ≥ Cs ≥ 50-100% of the dosing interval). Ceftriaxone dosing regimens were considered optimal if at least 90% of the simulated population was able to achieve the defined PK/PD targets. <b>Results:</b> Twenty-four episodes from 16 patients were included. Mean free ceftriaxone concentration pre-dose, +2 h, and +4 h were C_min = 7.8 ± 6.5 mg/L, C₂ = 34 ± 26.5 mg/L, and C₄ = 22.7 ± 19.7 mg/L, respectively. A two-compartment model with first-order absorption and elimination best described the data. Ceftriaxone one-hour infusions only achieved the minimum PK/PD target when the 2 g/12 h regimen was tested. On the other hand, ceftriaxone continuous infusion maintained a Cs above the PK/PD target for 100% of the dosing interval using ceftriaxone 4-6 g regimens. <b>Conclusions:</b> Our findings suggest that the optimal ceftriaxone exposure may be achieved using high-dose continuous infusions to ensure an ampicillin-killing effect when treating <i>E. faecalis</i> IE.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}