Antibiotics最新文献

{"title":"A Comprehensive Review on Phage Therapy and Phage-Based Drug Development","authors":"Longzhu Cui, Shinya Watanabe, Kazuhiko Miyanaga, Kotaro Kiga, Teppei Sasahara, Yoshifumi Aiba, Xin-Ee Tan, Srivani Veeranarayanan, Kanate Thitiananpakorn, Huong Minh Nguyen, Dhammika Leshan Wannigama","doi":"10.3390/antibiotics13090870","DOIUrl":"https://doi.org/10.3390/antibiotics13090870","url":null,"abstract":"Phage therapy, the use of bacteriophages (phages) to treat bacterial infections, is regaining momentum as a promising weapon against the rising threat of multidrug-resistant (MDR) bacteria. This comprehensive review explores the historical context, the modern resurgence of phage therapy, and phage-facilitated advancements in medical and technological fields. It details the mechanisms of action and applications of phages in treating MDR bacterial infections, particularly those associated with biofilms and intracellular pathogens. The review further highlights innovative uses of phages in vaccine development, cancer therapy, and as gene delivery vectors. Despite its targeted and efficient approach, phage therapy faces challenges related to phage stability, immune response, and regulatory approval. By examining these areas in detail, this review underscores the immense potential and remaining hurdles in integrating phage-based therapies into modern medical practices.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"405 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dosing Evaluation of Ceftazidime–Avibactam in Intensive Care Unit Patients Based on Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling and Simulation","authors":"Hinojal Zazo, Yuridia Aguazul, José M. Lanao","doi":"10.3390/antibiotics13090861","DOIUrl":"https://doi.org/10.3390/antibiotics13090861","url":null,"abstract":"P. aeruginosa is the most common microorganism involved in many ICU-acquired infections. A correct dosage regimen is pivotal to avoiding resistance development, worse outcomes and higher mortality rates. The aim of this study was to perform a pharmacokinetic–pharmacodynamic (PK/PD) evaluation of recommended dosing regimens of ceftazidime–avibactam (CAZ–AVI) in ICU patients with different degrees of renal function for a specific strain of Pseudomonas aeruginosa. A semi-mechanistic PK/PD model has been developed. It allows for the simulation of CAZ–AVI steady-state plasma level curves and the evolution of bacterial growth curves. The percentage of bacterial load reduction and the value of the recommended PK/PD indices have been taken into account to define the success or failure of the regimens. Probabilistic analysis was performed using Monte Carlo simulations of two populations: control and ICU. In both populations, dosing regimens endorsed for patients with CLcr higher than 10 mL/min reach the PK/PD indices recommended, T > MIC > 90% and Cmin/MIC > 1.3. While dosage regimens endorsed for patients with CLcr of 10 mL/min or lower fail (T > MIC < 60% and Cmin/MIC < 0.35). However, proposed dosing regimens based on shortening dosing intervals for these patients would be successful, increasing bacterial load reduction by almost 50% and reaching the proposed PK/PD indices. Therefore, CAZ–AVI dosing strategies based on model-informed precision dosing (MIPD) could directly influence the efficacy of results in ICU patients with renal insufficiency.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistence and Culturability of Escherichia coli under Induced Toxin Expression","authors":"Yousr Dhaouadi, Mohamad Javad Hashemi, Dacheng Ren","doi":"10.3390/antibiotics13090863","DOIUrl":"https://doi.org/10.3390/antibiotics13090863","url":null,"abstract":"Background/Objectives: Bacteria are well known to enter dormancy under stress conditions. However, the mechanisms of different dormancy-related phenotypes are still under debate and many questions remain unanswered. This study aims to better understand the effects of toxin gene expression on the dormancy of Escherichia coli. Methods: The effects of toxin gene expression on growth, persistence, and culturability were characterized. Specifically, we detailed dose- and time-dependent dormancy of E. coli and its susceptibility to ofloxacin via arabinose-induced hipA toxin gene expression under the PBAD promoter. A new plot was developed to better describe the dynamic changes in culturability and persistence. The expression level of hipA was determined using qPCR and cellular activities were monitored using fluorescence imaging and flow cytometry. Results: High-level persister formation and strong tolerance to ofloxacin were observed after high-level hipA induction. The new plot reveals more information than the changes in persistence alone, e.g., reduced culturability of E. coli and thus deeper dormancy under high-level hipA induction. Consistently, controlled hipA induction led to decreased cellular activities at promoter PrrnBP1 and an increase in the non-culturable subpopulation. Conclusions: Overall, this study provides new insights into dormancy induced by toxin gene expression and a more comprehensive view of persistence and culturability. The findings may help develop better control agents against dormant bacterial cells.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Physiologically Based Pharmacokinetic Model to Delineate the Impact of Aging and Renal Impairment on Ceftazidime Clearance","authors":"Khaled Abduljalil, Iain Gardner, Masoud Jamei","doi":"10.3390/antibiotics13090862","DOIUrl":"https://doi.org/10.3390/antibiotics13090862","url":null,"abstract":"The impact of physiological changes during aging on drug disposition has not always been thoroughly assessed in clinical studies. This has left an open question such as how and to what extent patho- and physiological changes in renal function can affect pharmacokinetics in the geriatric population. The objective of this work was to use a physiologically based pharmacokinetic (PBPK) model to quantify the impact of aging and renal impairment (RI) separately and together on ceftazidime pharmacokinetics (PK). The predicted plasma concentrations and PK parameters from the PBPK model were compared to the observed data in individuals of different ages with or without RI (16 independent studies were investigated in this analysis). Apart from clearance in one study, the predicted ceftazidime PK parameters of young adults, elderly, and in individuals with different levels of renal function were within 2-fold of the observed data, and the observed concentrations fell within the 5th–95th prediction interval from the PBPK model simulations. The PBPK model predicted a 1.2-, 1.5-, and 1.8-fold increase in the plasma exposure (AUC) ratio in individuals aged 40, 60, and 70 years old, respectively, with normal renal function for their age compared to 20-year-old individuals with normal renal function. The impact of RI on ceftazidime was predicted to be less marked in older individuals (a 1.04-, 1.43-, and 2.55-fold change in mild, moderate, or severe RI compared to a healthy age-matched control) than in younger individuals (where a 1.47-, 2.03-, and 3.50-fold increase was predicted in mild, moderate, or severe RI compared to a healthy age-matched control). Utilization of the applied population-based PBPK approach allows delineation of the effects of age from renal disease and can better inform future study design and dosing recommendations in clinical study of elderly patients depending on their age and renal function.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focusing on the Basic Principles of Dialysis to Optimize Antibiotic Therapy during Renal Replacement Therapy in Critically Ill Patients","authors":"Filippo Mariano, Alberto Mella, Luigi Biancone","doi":"10.3390/antibiotics13090864","DOIUrl":"https://doi.org/10.3390/antibiotics13090864","url":null,"abstract":"Bacterial infections frequently occur in patients in the ICU undergoing renal dialysis using extracorporeal procedures (KRT) that can be applied for different time periods, such as Prolonged Intermittent Renal Replacement Therapy (PIRRT) or Continuous Kidney Replacement Therapy (CKRT) [...]","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[18F]FDG PET/CT Imaging Is Associated with Lower In-Hospital Mortality in Patients with Pyogenic Spondylodiscitis—A Registry-Based Analysis of 29,362 Cases","authors":"Siegmund Lang, Nike Walter, Stefanie Heidemanns, Constantin Lapa, Melanie Schindler, Jonas Krueckel, Nils Ole Schmidt, Dirk Hellwig, Volker Alt, Markus Rupp","doi":"10.3390/antibiotics13090860","DOIUrl":"https://doi.org/10.3390/antibiotics13090860","url":null,"abstract":"Background: While MRI is the primary diagnostic tool for the diagnosis of spondylodiscitis, the role of [18F]-fluorodeoxyglucose ([18F]FDG) PET/CT is gaining prominence. This study aimed to determine the frequency of [18F]FDG PET/CT usage and its impact on the in-hospital mortality rate in patients with spondylodiscitis, particularly in the geriatric population. Methods: We conducted a Germany-wide cross-sectional study from 2019 to 2021 using an open-access, Germany-wide database, analyzing cases with ICD-10 codes M46.2-, M46.3-, and M46.4- (‘Osteomyelitis of vertebrae’, ‘Infection of intervertebral disc (pyogenic)’, and ‘Discitis unspecified’). Diagnostic modalities were compared for their association with in-hospital mortality, with a focus on [18F]FDG PET/CT. Results: In total, 29,362 hospital admissions from 2019 to 2021 were analyzed. Of these, 60.1% were male and 39.9% were female, and 71.8% of the patients were aged 65 years and above. The overall in-hospital mortality rate was 6.5% for the entire cohort and 8.2% for the geriatric subgroup (p < 0.001). Contrast-enhanced (ce) MRI (48.1%) and native CT (39.4%) of the spine were the most frequently conducted diagnostic modalities. [18F]FDG PET/CT was performed in 2.7% of cases. CeCT was associated with increased in-hospital mortality (OR = 2.03, 95% CI: 1.90–2.17, p < 0.001). Cases with documented [18F]FDG PET/CT showed a lower frequency of in-hospital deaths (OR = 0.58, 95% CI: 0.18–0.50; p = 0.002). This finding was more pronounced in patients aged 65 and above (OR = 0.42, 95% CI: 0.27–0.65, p = 0.001). Conclusions: Despite its infrequent use, [18F]FDG PET/CT was associated with a lower in-hospital mortality rate in patients with spondylodiscitis, particularly in the geriatric cohort. This study is limited by only considering data on hospitalized patients and relying on the assumption of error-free coding. Further research is needed to optimize diagnostic approaches for spondylodiscitis.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping Worldwide Antibiotic Use in Dental Practices: A Scoping Review","authors":"Fatemeh Soleymani, Carlos Pérez-Albacete Martínez, Mehrdad Makiabadi, José Eduardo Maté Sánchez de Val","doi":"10.3390/antibiotics13090859","DOIUrl":"https://doi.org/10.3390/antibiotics13090859","url":null,"abstract":"Antibiotic resistance is a critical issue today, necessitating the monitoring of antibiotic usage across various sectors. To determine the defined daily doses (DDDs) of antibiotics prescribed by dentists globally, a comprehensive search was conducted in PubMed, ProQuest, ScienceDirect, Web of Science, Scopus, and EBSCOhost, resulting in the inclusion of 15 documents in this scoping review. The DDD per 1000 inhabitants per day (DID) for oral antibiotics prescribed by dentists for the studied countries was generally below 2.11, with the exception of South Korea, which had a DDD per 1000 patients per day (DPD) of less than 6.97. Most countries, except Croatia and Belgium, demonstrated a decreasing trend in DID before the COVID-19 pandemic, but restrictions during the pandemic led to an increase in these numbers. Penicillin-derived antibiotics were the most commonly prescribed antibiotic among dentists in most countries. This study highlights significant gaps and missing data regarding antibiotics prescribed by dentists worldwide. However, it also indicates that the publication of guidelines, education, and evaluation of antibiotic use can lead to more controlled and appropriate prescriptions among dental professionals.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Tolerability of ShigActive™, a Shigella spp. Targeting Bacteriophage Preparation, in a Phase 1 Randomized, Double-Blind, Controlled Clinical Trial","authors":"Wilbur H. Chen, Joelle Woolston, Silvia Grant-Beurmann, Courtney K. Robinson, Garima Bansal, Joseph Nkeze, Jasnehta Permala-Booth, Claire M. Fraser, Sharon M. Tennant, Mallory C. Shriver, Marcela F. Pasetti, Yuanyuan Liang, Karen L. Kotloff, Alexander Sulakvelidze, Jennifer A. Schwartz","doi":"10.3390/antibiotics13090858","DOIUrl":"https://doi.org/10.3390/antibiotics13090858","url":null,"abstract":"Bacterial diseases of the gastrointestinal (GI) tract continue to be a major worldwide cause of human morbidity and mortality. Among various enteric pathogens, Shigella spp. are some of the most common and deadly bacterial pathogens. They are responsible for ~125 million worldwide cases of shigellosis, and ~14,000 deaths annually, the majority in children under the age of 5 and occurring in developing countries. Preventing and treating shigellosis with conventional drugs (e.g., vaccines and antibiotics) has proven to be very difficult. Here, we assessed the safety and tolerability of ShigActive™, a lytic bacteriophage preparation targeting Shigella spp., in a randomized, placebo-controlled, double-blind Phase 1 clinical trial. Ten participants randomized 4:1 received ShigActive™ or placebo co-administered with sodium bicarbonate orally three times daily for 7 days. Solicited and unsolicited adverse events (AEs) were observed for 29 days. Fifty percent of the subjects receiving ShigActive™ reported mild GI-related symptoms, while one participant experienced moderate fatigue. No serious or medically attended AEs occurred through day 90. Additionally, no significant differences in GI-associated inflammatory mediators or fecal microbiome changes were observed between placebo- and ShigActive™-treated subjects, or from a participants’ baseline value. The results of this first-in-human (FIH) randomized, controlled Phase 1 trial of ShigActive™ demonstrate that it is safe and well tolerated when orally administered with no significant differences compared to placebo controls.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"357 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Autologous Platelet Concentrates as a Local Antibiotic Delivery System: A Systematic Scoping Review","authors":"Roberta Gasparro, Federica Di Spirito, Maria Domenica Campana, Gilberto Sammartino, Alessandro E. di Lauro","doi":"10.3390/antibiotics13090856","DOIUrl":"https://doi.org/10.3390/antibiotics13090856","url":null,"abstract":"Objectives: Ongoing research has begun to develop innovative approaches to deliver local antibiotics while minimizing systemic side effects, antimicrobial resistance, and limited tissue penetration. Autologous platelet concentrates (APCs) offer promise in delivering antibiotics directly to infection sites. Despite the interest, a comprehensive evaluation of their effectiveness is lacking. Therefore, this systematic scoping review aims to collect and appraise studies regarding the efficacy of APCs in delivering antibiotics. Methods: A systematic electronic search of PubMed, Scopus, and Web of Science, using a combination of keywords, was conducted up to February 2024. Articles addressing the use of APCs as a local antibiotic delivery system were included. Results: A total of 13 articles, including 10 in vitro studies, 1 in vitro and clinical study, 1 ex vivo study, and 1 clinical study, were selected. Antibiotic loading capacity and release was confirmed in all studies using doxycycline, gentamicin, linezolid, vancomycin, metronidazole, and penicillin. In addition, the antibacterial effect was obtained mainly against E. coli., P. aeruginosa, S. mitis, H. influenzae, S. pneumoniae, and S. aureus. Conclusions: The incorporation of antibiotics into APCs has been proven to facilitate the effective release of antimicrobial agents at optimal concentrations, potentially reducing the incidence of post-operative infections, substituting, or augmenting systemic antibiotic treatment while retaining APCs’ inherent healing properties.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient Absorbance-Based Assay for Rapid Antibiotic Susceptibility Testing of Enterobacterales","authors":"Carolina Axelsson, Bo Nilson, Ann-Sofi Rehnstam-Holm","doi":"10.3390/antibiotics13090852","DOIUrl":"https://doi.org/10.3390/antibiotics13090852","url":null,"abstract":"It is increasingly important to rapidly receive information on the antimicrobial susceptibility of bacteria due to the rise in antimicrobial resistance worldwide. However, traditional phenotypic methods are time-consuming. Thus, the objective of this study was to develop a rapid assay that can detect antibiotic-resistant bacterial isolates phenotypically in less than 2 h. The microplate assay used in this study is based on absorbance measurements of previously pure bacterial isolates grown in liquid media with and without antibiotics. Absorbance was measured at the beginning of the assay and after 90 min of incubation at 37 °C. Susceptibility was calculated for bacterial isolates that, in the absence of antibiotics, exhibited more than a 50% growth increase by comparing the absorbance value of the culture in the presence of an antibiotic at 90 min with its initial value. Here, we show that it is possible to phenotypically screen the antibiotic susceptibility of Enterobacterales and Acinetobacter spp. isolates to three different antibiotics in 90 min. The test demonstrated an accuracy of 98.8%, sensitivity of 97.6%, and specificity of 99.6%. The false susceptibility rates were 0.2% and false resistance rates were 1.0%. This rapid and simple absorbance test has proven suitable for the screening of antibiotic susceptibility for a large number of strains with high accuracy and sensitivity. This method can be performed without specialized and costly materials and/or equipment, which makes it highly suitable for laboratories with limited resources.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}