Infectious Diseases and Therapy最新文献

{"title":"Clinical Characteristics of Patients Who Acquired Gram-Negative Bacteria During Ceftazidime-Avibactam Therapy.","authors":"Chien Chuang, Tzu-Chi Kao, Chih-Han Juan, Sheng-Hua Chou, Yu-Chien Ho, Szu-Yu Liu, Yi-Ru Huang, Hsiang-Ling Ho, Yi-Tsung Lin","doi":"10.1007/s40121-025-01126-1","DOIUrl":"10.1007/s40121-025-01126-1","url":null,"abstract":"<p><strong>Introduction: </strong>Ceftazidime-avibactam (CZA) is recommended to treat infections caused by carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa with difficult-to-treat resistance. The selective pressure of CZA results in the isolation of multidrug-resistant Gram-negative bacteria (MDR-GNB), causing superinfection or hospital-wide spread. We aimed to study the clinical characteristics of patients who acquired GNB during CZA treatment.</p><p><strong>Methods: </strong>Adult patients treated with CZA for ≥ 5 days for proven or suspected MDR-GNB were retrospectively enrolled at Taipei Veterans General Hospital between December 2019 and June 2021. GNB acquisition was defined as new GNB species resulting in infection or colonization isolated during the period from 5 days after the initiation of CZA until the end of treatment. Clinical features were compared between patients who acquired GNB from clinical specimen and those who did not. Multivariable analysis was used to explore risk factors for acquisition of GNB and 28-day mortality in patients who acquired GNB.</p><p><strong>Results: </strong>Among 321 patients treated with CZA, 68 GNB were identified in 55 patients (17.1%). Elizabethkingia species (n = 15) was the most common GNB, followed by Acinetobacter species (n = 13) and Burkholderia cenocepacia (n = 11). The presence of diabetes mellitus, and mechanical ventilation were independent risk factors for GNB acquisition. There was a statistically nonsignificant trend toward increased 28-day mortality in patients with GNB acquisition compared to those without (38.2% vs. 27.8%, P = 0.105). Cerebrovascular disease and acquired GNB resulting in infection were associated with 28-day mortality in patients who acquired GNB.</p><p><strong>Conclusions: </strong>Elizabethkingia species, Acinetobacter species, and B. cenocepacia were the major GNB acquired during CZA treatment. A trend toward increased mortality was observed in patients with GNB acquisition during CZA treatment. Further studies on optimal treatments for these patients were warranted.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1027-1042"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763711","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":"Effects of Broad-Spectrum Antimicrobials on Patients with Community-Acquired Pneumonia with Low Risk for Drug-Resistant Pathogens: Historical Cohort Study in Japan.","authors":"Takahiro Takazono, Naoki Hosogaya, Yoshiyuki Saito, Masahiko Takemura, Naoki Iwanaga, Noriho Sakamoto, Junichi Hirayama, Rie Ueno, Hiroshi Mukae","doi":"10.1007/s40121-025-01142-1","DOIUrl":"10.1007/s40121-025-01142-1","url":null,"abstract":"<p><strong>Introduction: </strong>Broad-spectrum antimicrobials are commonly administered for community-acquired pneumonia (CAP); however, unnecessary administration may cause adverse events and poor outcomes. This study aimed to understand the impact of broad-spectrum anti-pseudomonal β-lactam use on clinical outcomes and healthcare resource utilization (HCRU) in inpatients with CAP and a low risk of drug-resistant pathogens (DRPs).</p><p><strong>Methods: </strong>This historical cohort study reviewed Japan's hospital claims database (January to December of 2018) and included inpatients aged ≥ 20 years who received intravenous antimicrobial therapy for CAP. Those with high DRP risk were excluded. According to the initial antimicrobial regimen, patients were divided into broad-spectrum (anti-pseudomonal β-lactam therapy) and narrow-spectrum (non-anti-pseudomonal β-lactam therapy) groups. This study evaluated 30-day hospital mortality as a primary outcome using inverse probability of treatment weighting (IPTW) to adjust for differences between both groups and HCRU as an exploratory analysis.</p><p><strong>Results: </strong>A total of 15,617 patients were analyzed (2627 in the broad-spectrum group and 12,990 in the narrow-spectrum group). In the broad-spectrum group, the 30-day mortality rate was 10.6%, which was higher than that in the narrow-spectrum group (5.3%). Furthermore, it was associated with an increased 30-day mortality compared with the narrow-spectrum group after IPTW (adjusted odds ratio, 1.77; 95% confidence interval, 1.52-2.06; p < 0.001). The mean inpatient cost was USD 6139 and USD 5184 for the broad- and narrow-spectrum groups, respectively.</p><p><strong>Conclusions: </strong>The initial use of anti-pseudomonal β-lactams for CAP with low DRP risk is associated with poor outcomes, including death and high HCRU. Thus, initial antimicrobials should be judiciously selected for CAP management.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1043-1059"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780046","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":"Letter to the Editor Regarding \"Serum Troponin I Assessments in 5- to 30-Year-Olds After BNT162b2 Vaccination\" by Albertson et al. 2024.","authors":"Ivan Pourmir, Adrian Alanis, Niccolò Clemente","doi":"10.1007/s40121-025-01136-z","DOIUrl":"10.1007/s40121-025-01136-z","url":null,"abstract":"","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1133-1136"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795009","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":"Burden and Outcomes of Severe Lower Respiratory Tract Infections with Unknown Etiology: A Retrospective Observational Study on Epidemiological Trends Over an 8-Year Period (2016-2024).","authors":"Giovanni Scaglione, Marta Canuti, Martina Offer, Valentina Breschi, Antonio Piralla, Fausto Baldanti, Gabriele Del Castillo, Francesco Scovenna, Sabrina Buoro, Federica Morani, Danilo Cereda, Alessandra Bandera, Andrea Gori, Marta Colaneri","doi":"10.1007/s40121-025-01148-9","DOIUrl":"10.1007/s40121-025-01148-9","url":null,"abstract":"<p><strong>Introduction: </strong>Severe lower respiratory tract infections often require hospitalization, but a significant proportion lack microbiological diagnosis, leading to challenges in management. This study aimed to compare clinical outcomes of S-LRTIs with unknown versus known bacteria or viral etiology in Lombardy, Italy.</p><p><strong>Methods: </strong>A retrospective study analyzed respiratory infection-related hospitalizations in Lombardy over 8 years (2016-2024) using patient discharge charts. Patients were categorized into four groups: bacterial, viral (non-COVID-19), COVID-19-related, and unknown etiology. Outcomes included length of stay, intensive care unit admissions, and intra-hospital mortality. Temporal, seasonal, and age-specific trends were evaluated.</p><p><strong>Results: </strong>Among 683,741 hospitalizations, 338,211 (49.5%) were of unknown etiology, showing a 12.3% intra-hospital mortality rate (41,627 deaths) and 4.0% intensive care unit admission rate (13,625 admissions). COVID-19-related hospitalizations had the highest intra-hospital mortality rate (22.0%, 36,446 deaths in 165,605 COVID-19-related hospitalizations) and number of intensive care unit admissions (14,725 admissions, 8.9% of COVID-19-related hospitalizations), while viral non-COVID-19 hospitalizations showed the lowest intra-hospital mortality rate (3.2%, 1114 deaths in 34,769 viral-non-COVID-19 hospitalizations) and shortest length of stay (11.9 days). Hospitalizations with unknown etiology were more common in minors (42,190 episodes, 57.6% of total in < 18 years) and elderly (358,534 episodes, 56.2% of total in > 75 years), especially during warm seasons. Post-pandemic years saw increased bacterial and viral hospitalizations alongside a reduced proportion of those without an unknown etiology.</p><p><strong>Conclusions: </strong>Respiratory infection-related hospitalizations with unknown etiology are associated with distinct seasonal and demographic patterns, and poorer outcomes compared to viral non-COVID-19 hospitalizations. COVID-19 reshaped S-LRTI epidemiology and diagnostic approaches, highlighting the need for comprehensive pathogen panels and tailored management strategies, while promoting their expanded use. Future research should integrate detailed clinical data to improve understanding and outcomes of severe respiratory infections, especially in vulnerable populations.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1075-1087"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985630","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":"Healthcare-Associated Infections: The Role of Microbial and Environmental Factors in Infection Control-A Narrative Review.","authors":"Andreea M Sandu, Mariana C Chifiriuc, Corneliu O Vrancianu, Roxana-E Cristian, Cristina F Alistar, Marian Constantin, Mihaela Paun, Alexandru Alistar, Loredana G Popa, Mircea I Popa, Ana C Tantu, Manuela E Sidoroff, Mara M Mihai, Andreea Marcu, George Popescu, Monica M Tantu","doi":"10.1007/s40121-025-01143-0","DOIUrl":"10.1007/s40121-025-01143-0","url":null,"abstract":"<p><p>Healthcare-associated infections (HAIs), previously known as nosocomial infections, represent a significant threat to healthcare systems worldwide, prolonging patient hospital stays and the duration of antimicrobial therapy. One of the most serious consequences of HAIs is the increase in the rate of antibiotic resistance (AR) generated by the prolonged, frequent, and sometimes incorrect use of antibiotics, which leads to the selection of resistant bacteria, making treatment difficult and expensive, with direct consequences for the safety of patients and healthcare personnel. Therefore, timely and accurate diagnosis of HAIs is mandatory to develop appropriate infection prevention and control practices (IPC) and new therapeutic strategies. This review aimed to present the prevalence, risk factors, current diagnosis, including artificial intelligence (AI) and machine learning approaches, future perspectives in combating HAIs causative bacteria (phage therapy, microbiome-based interventions, and vaccination), and HAIs surveillance strategies. Also, we discussed the latest findings regarding the relationships of AR with climate change and environmental pollution in the context of the One Health approach. Phage therapy is an emerging option that can offer an alternative to ineffective antibiotic treatments for antibiotic-resistant bacteria causing HAIs. Clinical trials dealing with vaccine development for resistant bacteria have yielded conflicting results. Two promising strategies, fecal microbiota transplantation and probiotic therapy, proved highly effective against recurrent Clostridium difficile infections and have been shown to reduce HAI incidence in hospitalized patients undergoing antibiotic therapy. Artificial intelligence and machine learning systems offer promising predictive capabilities in processing large volumes of clinical, microbiological, and patient data but require robust data integration. Our paper argues that HAIs are still a global challenge, requiring stringent IPC policies, computer vision, and AI-powered tools. Despite promising avenues like integrated One Health approaches, optimized phage therapy, microbiome-based interventions, and targeted vaccine development, several knowledge gaps in clinical efficacy, standardization, and pathogen complexity remain to be answered.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"933-971"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994545","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":"In Vitro Elimination of Highly Multidrug-Resistant Bacteria by the Lactic Acid Bacterial Drug Candidate ILP100.","authors":"Hava Lofton-Tomenius, Yanhong Pang, Anton Pallin, Zhanar Myktybekova, Ninus Lelham, Kristian Riesbeck, Evelina Vågesjö, Stefan Roos, Mia Phillipson","doi":"10.1007/s40121-025-01137-y","DOIUrl":"10.1007/s40121-025-01137-y","url":null,"abstract":"<p><strong>Introduction: </strong>Multidrug resistance (MDR) has been identified in wound bacterial isolates from Ukrainian war victims treated in Ukraine and across Europe. ILP100, a drug candidate for the treatment of skin wounds, is composed of a Limosilactobacillus reuteri expressing human chemokine CXCL12. In this study, the antimicrobial effects of ILP100 were tested on MDR bacteria isolated from wounds of Ukrainian war victims.</p><p><strong>Methods: </strong>ILP100 was co-cultured with one of the wound pathogens (Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus; 12 non-MDR and 12 MDR isolates) in broth media for 12 h with subsequent survival recovery on agar plates. Additionally, agar plates were precoated with ILP100 at clinical doses (3 vs. 24 h, 1 × 10⁷ CFU/cm²) followed by co-culture with pathogens inoculated in soft agar (1 × 10⁴ CFU/cm²). To compare ILP100 with relevant antibiotics, MDR-inoculated soft agar was applied to plates with standardized ILP100 drops and antibiotic-loaded discs, followed by 18-20 h aerobic incubation at 37 °C.</p><p><strong>Results: </strong>Dose-dependent growth inhibition of all pathogens was demonstrated, as 1000:1 and 100:1 (ILP100/isolate) inhibited pathogenic growth up to log 6.4 and log 4.3 CFU/ml, respectively. Potent antimicrobial effects were demonstrated after precoating with ILP100, as pathogen recovery was only demonstrated after 3 h of precoating, only for 10/18 isolates and then only partially. Benchmarking to relevant antibiotic discs resulted in large cleared zones surrounding the ILP100 spots but not the antibiotic discs, demonstrating potent bacterial killing by ILP100-secreted factors. Interestingly, the MDR pathogens were significantly more sensitive to the ILP100 released factors than the non-MDR isolates.</p><p><strong>Conclusion: </strong>ILP100 effectively eliminates MDR wound pathogens, which reveals a promising strategy for the development of new classes of urgently needed antimicrobials.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1119-1131"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752570","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":"Five-Year Immune Persistence of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) and Immunogenicity and Safety of a Booster Dose in Children.","authors":"Federico Martinón-Torres, Robert Simko, Rolf Ebert, Mika Rämet, Céline Zocchetti, Olga Syrkina, Siham Bchir, Isabelle Bertrand-Gerentes","doi":"10.1007/s40121-025-01121-6","DOIUrl":"10.1007/s40121-025-01121-6","url":null,"abstract":"<p><strong>Introduction: </strong>Many countries recommend vaccination against Neisseria meningitidis serogroups A, C, W, and Y in infants and young children to prevent invasive meningococcal disease. We evaluated the immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) booster in children primed with the same meningococcal vaccine 5 years earlier. Immune persistence following priming vaccination was also evaluated, and the study is ongoing to generate 10 years' post-priming data.</p><p><strong>Methods: </strong>Healthy children, vaccinated with MenACYW-TT 5 years earlier as toddlers, were enrolled. Participants were randomized to receive MenACYW-TT booster (group 1) or no booster (group 2), stratified by country and meningococcal serogroup C (MenC) vaccination status (primed at age ≤ 1 year vs. naive). Antibodies against each serogroup were measured by serum bactericidal assay using human complement (hSBA). Seroresponse sufficiency at 30 days post-booster was demonstrated if the lower limit of the one-sided 97.5% confidence interval (CI) of the seroresponse rate (proportion of participants with post-vaccination titers ≥ 1:16 when baseline titers were < 1:8 or with a ≥ fourfold increase when baseline titers were ≥ 1:8) was > 75% for each serogroup. Seroprotection rates (proportion with hSBA titers ≥ 1:8) and geometric mean titers (GMTs) for each serogroup were also assessed.</p><p><strong>Results: </strong>A total of 209 participants were enrolled across 26 sites in Finland, Germany, Hungary, and Spain (group 1, n = 93; group 2, n = 116). Five years post-priming, GMTs, and seroprotection rates were higher than those observed before priming vaccination in both groups, indicating long-term persistence. Booster seroresponse rates in group 1 for all serogroups ranged from 93.2% to 98.9%, with seroresponse sufficiency demonstrated (lower limit of one-sided 97.5% CIs for the seroresponse rates ranging from 85.7% to 93.8%). Seroprotection rates and GMTs post-booster increased across all serogroups, with nearly all participants seroprotected, suggesting adequate booster response. Seroresponse was comparable between MenC-primed and MenC-naive participants. No new safety concerns were identified.</p><p><strong>Conclusions: </strong>MenACYW-TT provides long-term immune persistence and a robust immune response when administered as a booster in children primed 5 years earlier.</p><p><strong>Trial registrations: </strong>Clinicaltrials.gov, NCT04936685; EudraCT: 2021-000104-38; WHO: U1111-1255-4941. Graphical abstract available for this article.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"991-1010"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763712","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":"Indirect Comparison of PCV20 Immunogenicity with PCV10 in Pediatric 3 + 1 and 2 + 1 Schedules.","authors":"Eileen M Dunne, Valda A Struwig, Wing Lowe, Claire H Wilson, Johnna E Perdrizet, Noor Tamimi, Kyla Hayford, Luis Jodar, Bradford D Gessner, Christian Theilacker","doi":"10.1007/s40121-025-01151-0","DOIUrl":"10.1007/s40121-025-01151-0","url":null,"abstract":"<p><strong>Introduction: </strong>The 20-valent pneumococcal conjugate vaccine (PCV20) was licensed for prevention of pneumococcal disease in infants and children on the basis of immunogenicity compared with PCV13. We aimed to evaluate PCV20 immunogenicity compared with PCV10 (Synflorix; PhiD-CV) because both vaccines demonstrated lower immunogenicity than PCV13. Nevertheless, PCV10 was highly effective against vaccine-serotype pneumococcal disease in post-licensure studies. Since no study has directly compared PCV20 versus PCV10, we conducted an indirect comparison.</p><p><strong>Methods: </strong>We conducted indirect comparisons for PCV20 versus PCV10 using data from published randomized control trials that directly compared these vaccines with PCV13 in 3 + 1 or 2 + 1 schedules. Serotype-specific immunoglobulin (Ig)G concentrations and opsonophagocytic activity (OPA) were assessed post-booster dose and post-primary series. First, geometric mean ratios (GMRs) were obtained for shared serotypes for each direct comparison against PCV13; we conducted a meta-analysis to generate pooled GMRs if data from multiple trials were available. Next, we indirectly compared relative GMRs of PCV20 versus PCV10 using PCV13 as the common comparator. In this descriptive analysis, GMRs > 1 favored PCV20 and GMR < 1 favored PCV10.</p><p><strong>Results: </strong>Meta-analyses of PCV10 versus PCV13 data found that PCV10 was less immunogenic for most of the ten shared serotypes. When indirectly compared via PCV13, the relative immunogenicity of PCV20 versus PCV10 varied by serotype. Overall, IgG responses for the ten shared serotypes were similar for both 3 + 1 and 2 + 1 schedules, both post-primary series and post-booster dose. GMRs for both IgG and OPA were close to the line of equivalence, or spread between favoring PCV20 or PCV10.</p><p><strong>Conclusions: </strong>The comparable immunogenicity of PCV20 versus PCV10 in 2 + 1 and 3 + 1 schedules suggests that PCV20 will have similar effectiveness for the ten serotypes included in both vaccines, including for direct protection during infancy and toddler age, while also expanding serotype coverage. Effectiveness for PCV20 needs to be confirmed in post-marketing studies.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1103-1117"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006909","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":"From Clinical Trials to Real-World Experiences: Evidence About Cefiderocol Use and Potential Role in Empirical Therapy.","authors":"Alessandro Russo, Francesca Serapide","doi":"10.1007/s40121-025-01147-w","DOIUrl":"10.1007/s40121-025-01147-w","url":null,"abstract":"<p><p>Cefiderocol is a novel siderophore cephalosporin that has gained attention for its potent activity against multidrug-resistant (MDR) Gram-negative pathogens, making it a valuable addition to the antimicrobial armamentarium. Its efficacy in treating complicated urinary tract infections (cUTIs) and nosocomial pneumonia has been well-established, although challenges remain regarding its role in Acinetobacter baumannii infections and the possible emergence of resistance. The decision to use cefiderocol as a monotherapy or in combination should be guided by pathogen susceptibility, clinical severity, and local epidemiology. Then, the potential to serve as an effective empirical therapy, careful stewardship, and further research are essential to maximize its therapeutic benefits and ensure its long-term efficacy. This review explores the efficacy of cefiderocol, resistance development, heteroresistance, its use as monotherapy or in combination therapy, and its role in empirical treatment regimens. We discuss data about clinical trials and real-world evidence to assess the future role of cefiderocol in antibiotic regimens.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"897-909"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019360","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":"Clinical Pharmacokinetics and Safety of Orally Administered VH4011499, a New HIV-1 Capsid Inhibitor, in Adults Without HIV.","authors":"Nilay Thakkar, Rulan Griesel, Amy Pierce, Veronica Bainbridge, Bronagh Shepherd, Konstantinos Angelis, Andrew Tomlinson, Yash Gandhi, Darin Brimhall, Brian Spears, Daijha Anderson, Emma Pinnick, Carolina Acuipil, Cynthia McCoig, Mark Baker, Paul Benn","doi":"10.1007/s40121-025-01129-y","DOIUrl":"10.1007/s40121-025-01129-y","url":null,"abstract":"<p><strong>Introduction: </strong>This first-time-in-human study describes the pharmacokinetics, drug-drug interaction potential, and safety of VH4011499 (VH-499), a new HIV-1 capsid inhibitor.</p><p><strong>Methods: </strong>This double-blind, randomized, placebo-controlled, phase 1 study evaluated VH-499 in adults without HIV administered orally as single ascending doses as powder-in-bottle (PiB; part 1) and tablet (part 3) formulations and as multiple ascending doses as PiB formulation dosed once daily for 14 days (part 2). Midazolam was used to evaluate the effect of VH-499 on cytochrome P450 3A (CYP3A) activity (part 2).</p><p><strong>Results: </strong>Overall, 73 participants were included (VH-499, n = 56; placebo, n = 17). VH-499 plasma exposures were less than dose-proportional, with median time to maximum observed concentration of 8.0-12.0 h for the PiB formulation and 24.0 h for the tablet formulation. Geometric mean terminal half-life was 51.2-66.5 h (2-3 days). The tablet formulation resulted in 45-63% lower exposures compared with PiB. Concomitant midazolam administration after single and multiple VH-499 doses did not lead to clinically significant changes in midazolam or 1-hydroxymidazolam exposures; therefore, VH-499 is not expected to inhibit or induce CYP3A4. VH-499 was well tolerated. Adverse event (AE) frequency was comparable between placebo and VH-499 groups. VH-499-related AEs were predominantly grade 1. No serious AEs across VH-499 groups, AEs leading to withdrawal from drug/study, or deaths occurred. There were no trends in vital signs, electrocardiograms, or laboratory hematology parameters and no clinically relevant changes in chemistry parameters.</p><p><strong>Conclusion: </strong>First-time-in-human data further characterize the pharmacokinetics of orally administered VH-499 and provide support for development of VH-499 as part of a complete long-acting regimen for HIV-1 treatment and prevention.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov, NCT05393271.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1011-1025"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763659","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}