{"title":"Exploring the Therapeutic Potential of Antibiotics in Hyperglycemia-Induced Macrophage Dysfunctions.","authors":"Montira Yossapol, Piyarat Srinontong, Worapol Aengwanich, Monchaya Panil, Supissara Somsup, Justice Opare Odoi, Jaroon Wandee","doi":"10.3390/antibiotics14020198","DOIUrl":"10.3390/antibiotics14020198","url":null,"abstract":"<p><p><b>Background:</b> Diabetes mellitus exacerbates immune dysfunction, leading to higher susceptibility to infections. This study investigated the effects of antibiotics on macrophage functions under high glucose conditions to mimic a diabetic context. <b>Methods:</b> Using murine macrophage cell line RAW 264.7, the present study evaluated the cytotoxicity, phagocytosis, bactericidal activity, and pro-inflammatory cytokine production after treatment with four antibiotics: oxytetracycline, ciprofloxacin, sulfamethoxazole-trimethoprim, and cefotaxime. <b>Results:</b> All antibiotics demonstrated no cytotoxicity across 1×-8× MIC concentrations. Hyperglycemia significantly impaired macrophage phagocytosis and bactericidal activity while inducing pro-inflammatory mediator markers, <i>IL-1, IL-6, TNF-α,</i> and <i>iNOS</i>. Only ciprofloxacin significantly improved phagocytic achieving levels comparable to the low glucose control. Treatments with ciprofloxacin, sulfamethoxazole-trimethoprim, and cefotaxime significantly enhanced bactericidal activity without altering the pro-inflammatory cytokine profile. <b>Conclusions:</b> These findings underscore the negative effect of high glucose on macrophage functions and suggest that ciprofloxacin may be a potential therapeutic option for diabetes-associated infections.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505844","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}
Antibiotics-BaselPub Date : 2025-02-14DOI: 10.3390/antibiotics14020196
Houda Zaher, José Francisco Quílez Del Moral, Sanae Lemrabet, Neri Koutchala, Bouchaib Bencharki
{"title":"In Vitro Antiviral Activity of a Silydianin-Rich Extract from <i>Silybum marianum</i> Seeds Against Four Strains of Enteroviruses: EV71, Coxsackievirus B2, Coxsackievirus A10, and Poliovirus SL-1 and Its Impact on Improving Delayed Gastric Emptying in Mice.","authors":"Houda Zaher, José Francisco Quílez Del Moral, Sanae Lemrabet, Neri Koutchala, Bouchaib Bencharki","doi":"10.3390/antibiotics14020196","DOIUrl":"10.3390/antibiotics14020196","url":null,"abstract":"<p><strong>Background: </strong>Gastroparesis, a chronic digestive disorder characterized by delayed gastric emptying, often results from diabetes, post-surgical complications, autoimmune diseases, and neurological disorders. In approximately 50% of cases, the cause is idiopathic gastroparesis (IGD). Recent studies suggest a link between chronic enteroviral infection and persistent gastrointestinal symptoms, including delayed gastric emptying. This study investigates the effects of a silydianin-rich extract from <i>Silybum marianum</i> seeds on enteroviral infections in vitro and the mitigation of delayed gastric emptying in mice. Silydianin, a key bioactive compound known for its liver-protective and antioxidant properties, has not been extensively studied for its impact on enteroviral infections and gastroparesis.</p><p><strong>Methods: </strong>NMR spectroscopy (<sup>1</sup>H, <sup>13</sup>C, DEPT 135 and 2D, and HSQC) and HRMS identified silydianin as the primary compound, with minor flavonolignans. This study assessed the cytotoxicity and antiviral activity of the extract at various stages of the viral life cycle, including virucidal activity, cell protection, and post-infection effects, using neutral red assays in RD cells, with results confirmed by real-time PCR. The viruses studied included coxsackievirus B2, coxsackievirus A10, poliovirus SL-1, and enterovirus EV71. The impact on delayed gastric emptying was evaluated in a mouse model using doses of 100 and 200 mg/kg compared to a control group receiving physiological saline.</p><p><strong>Results: </strong>The silydianin-rich extract showed consistent antiviral activity, with the highest selectivity index (SI) for EV71 (4.08) during virucidal activity. It provided moderate cell protection, with EC<sub>50</sub> values ranging from 120.88 to 186.10 µg/mL and SI values from 2.20 to 3.39. Post-infection treatment showed varying efficacy, with coxsackie A10 demonstrating the highest SI (3.90). In vivo, the extract at 200 mg/kg significantly improved gastric emptying to 96.47% and slightly increased gastrointestinal transit from 50.33% to 61.46%.</p><p><strong>Conclusions: </strong>These results suggest that silydianin may be effective for treating enteroviral infections and enhancing intestinal function, making it a promising candidate for gastroparesis treatment and warranting further research.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505985","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}
Antibiotics-BaselPub Date : 2025-02-14DOI: 10.3390/antibiotics14020199
Fahmida Chowdhury, Saju Bhuiya, Mohammad Abdul Aleem, Tanzir Ahmed Shuvo, Gazi Md Salahuddin Mamun, Probir Kumar Ghosh, Lubaba Shahrin, Samin Yasar Khan, Md Ariful Islam, Mahmudur Rahman
{"title":"Decade-Long Trends in Antibiotic Prescriptions According to WHO AWaRe Classification Among Severe Acute Respiratory Infection Patients at Tertiary Hospitals in Bangladesh (2011-2020).","authors":"Fahmida Chowdhury, Saju Bhuiya, Mohammad Abdul Aleem, Tanzir Ahmed Shuvo, Gazi Md Salahuddin Mamun, Probir Kumar Ghosh, Lubaba Shahrin, Samin Yasar Khan, Md Ariful Islam, Mahmudur Rahman","doi":"10.3390/antibiotics14020199","DOIUrl":"10.3390/antibiotics14020199","url":null,"abstract":"<p><p><b>Background:</b> To aid in the development of antimicrobial stewardship programs (ASPs), we analyzed the patterns and trends in antibiotic prescriptions for patients with severe acute respiratory infection (SARI), utilizing the WHO's AWaRe classification. <b>Methods:</b> We analyzed data from hospital-based influenza surveillance from January 2011 to December 2020 across nine Bangladeshi tertiary-level hospitals. Surveillance physicians collected WHO-defined SARI patient data, including demographics, clinical characteristics, and antibiotic prescriptions. Descriptive statistics and parametric and non-parametric tests were used for the analysis. <b>Results:</b> Of 21,566 SARI patients [median age 20 years (IQR: 1.33-45), 66% male], 91% were prescribed at least one antibiotic. A total of 25,133 antibiotics were prescribed, of which 47.0% were third-generation cephalosporins, 16.5% were macrolides, and 11.1% were beta-lactam/beta-lactamase inhibitors. According to the AWaRe classification, 28.7% were in the Access group, while 71.3% were in the Watch group, and none were from the Reserve group. A downward trend in Access group (30.4% to 25.1%; <i>p</i> = 0.010) and an upward trend in Watch group antibiotic prescription (69.6% to 74.9%; <i>p</i> = 0.010) were observed. We identified that patients aged < 5 years (aOR: 1.80; 95% CI: 1.44-2.25), who were treated in government hospitals (aOR: 1.45; 95% CI: 1.35-1.57), patients with the presence of lung diseases (aOR: 1.56; 95% CI: 1.35-1.80) had an increased likelihood of being prescribed Watch group antibiotics. <b>Conclusions</b>: This study reveals a concerning pattern of antibiotic overuse among SARI patients in Bangladesh, with a growing trend over the past decade towards increased Watch group antibiotic prescriptions. Only one-third of the prescribed antibiotics were from the Access group, falling short of the two-thirds threshold recommended by the WHO. Effective ASPs are crucial to optimize antibiotic prescriptions and mitigate the risk of antimicrobial resistance.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505915","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}
Antibiotics-BaselPub Date : 2025-02-14DOI: 10.3390/antibiotics14020200
László Kovács, Ábel Szabó, Franciska Barnácz, Bence Csirmaz, Ákos Jerzsele, Ádám Kerek
{"title":"Antimicrobial Susceptibility Profiles of Commensal <i>Staphylococcus</i> spp. Isolates from Turkeys in Hungarian Poultry Farms Between 2022 and 2023.","authors":"László Kovács, Ábel Szabó, Franciska Barnácz, Bence Csirmaz, Ákos Jerzsele, Ádám Kerek","doi":"10.3390/antibiotics14020200","DOIUrl":"10.3390/antibiotics14020200","url":null,"abstract":"<p><p><b>Background:</b> The poultry industry is one of the most rapidly growing sectors, producing the highest amount of animal-derived protein per unit time while also being the second-largest consumer of antibiotics. The widespread and accelerating spread of antimicrobial resistance (AMR) underscores the necessity of regular monitoring studies. Periodic assessments, especially focusing on commensal strains, can serve as indicators of emerging resistance patterns. <b>Methods:</b> This study assesses the antimicrobial susceptibility profiles of putative commensal <i>Staphylococcus</i> strains (<i>n</i> = 166) isolated from large-scale turkey flocks in Hungary using minimal inhibitory concentration (MIC) determination. The isolated strains were tested against antibiotics of veterinary and public health importance. The results were analyzed using the Kruskal-Wallis test and the Mann-Whitney <i>U</i> test, as well as <i>t</i>-tests. Additionally, correlation analysis and principal component analysis were performed. <b>Results:</b> Our findings revealed the highest resistance rates to tiamulin (90.4%), doxycycline (79.5%), and enrofloxacin (68.7%). <b>Conclusions:</b> These results reflect the extensive antibiotic use in the poultry sector, which contributes to the widespread presence of antimicrobial resistance. As regular monitoring and the identification of trends can aid in mitigating the spread of resistance, these findings should be complemented by data on antibiotic usage at the surveyed farms in further studies. The observed resistance rate of 18.1% to vancomycin is particularly concerning from a public health perspective, given that comparative human data show only a 0.05% resistance rate. Additionally, for multidrug-resistant strains, next-generation sequencing should be utilized to elucidate the genetic mechanisms underlying resistance, particularly in strains exhibiting high levels of resistance to vancomycin, which is of critical importance in human medicine, as well as to the critically important enrofloxacin and the widely used doxycycline and tiamulin. However, the limitations of the study should also be acknowledged, including the relatively small sample size, which is significantly lower than that of available human data, as well as the spatial distribution of the samples.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505832","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}
Antibiotics-BaselPub Date : 2025-02-14DOI: 10.3390/antibiotics14020202
Stephan Schmid, Katharina Zimmermann, Chiara Koch, Patricia Mester, Georgios Athanasoulas, Jonas Buttenschoen, Daniel Fleischmann, Sophie Schlosser-Hupf, Vlad Pavel, Tobias Schilling, Martina Müller, Alexander Kratzer
{"title":"Interprofessional Therapeutic Drug Monitoring of Piperacillin/Tazobactam Enhances Care for Patients with Acute-on-Chronic Liver Failure in the ICU: A Retrospective Observational Pilot Study.","authors":"Stephan Schmid, Katharina Zimmermann, Chiara Koch, Patricia Mester, Georgios Athanasoulas, Jonas Buttenschoen, Daniel Fleischmann, Sophie Schlosser-Hupf, Vlad Pavel, Tobias Schilling, Martina Müller, Alexander Kratzer","doi":"10.3390/antibiotics14020202","DOIUrl":"10.3390/antibiotics14020202","url":null,"abstract":"<p><p><b>Background:</b> Acute-on-chronic liver failure (ACLF) is a severe, rapidly progressing syndrome in patients with liver cirrhosis, often triggered by bacterial infections. Piperacillin/Tazobactam is a key antibiotic in this setting, and therapeutic drug monitoring (TDM) helps optimize its dosing. This study evaluates the impact of an interprofessional TDM strategy for Piperacillin/Tazobactam in ACLF patients in the ICU. <b>Methods:</b> This retrospective ICU study evaluated an interprofessional TDM approach for optimizing Piperacillin/Tazobactam dosing in critically ill ACLF patients. The team, consisting of physicians, clinical pharmacists, and staff nurses, engaged in shared decision making, collaboratively interpreting TDM results and adjusting the dosing accordingly. This study included 26 patients with ACLF who underwent initial TDM and 7 who received follow-up TDM. Piperacillin/Tazobactam dosing was modified based on TDM recommendations, with serum concentrations measured weekly. Adherence to and the implementation of interprofessional dosing recommendations were systematically analyzed to assess the impact of this approach. <b>Results:</b> The initial TDM showed that 30.8% of patients had Piperacillin/Tazobactam levels within the target range, while 53.8% were above and 15.4% below. The interprofessional team recommended dose reductions in seven patients, increases in three, and no change in eleven, with five requiring antibiotic modifications. At the first follow-up TDM, 20.0% reached target levels, while 80.0% remained above, with no subtherapeutic cases. The team recommended one further dose reduction and maintained dosing in four patients. All recommendations were fully implemented, demonstrating strong adherence to the collaborative protocol. <b>Conclusions:</b> The interprofessional TDM strategy optimized Piperacillin/Tazobactam dosing in ACLF patients with full adherence to the recommendations. This collaborative approach improves outcomes and supports global efforts to curb antibiotic resistance.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505934","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}
Antibiotics-BaselPub Date : 2025-02-14DOI: 10.3390/antibiotics14020201
Bruno T S Luz, João S Rebelo, Francisca Monteiro, Francisco Dionisio
{"title":"What Is the Impact of Antibiotic Resistance Determinants on the Bacterial Death Rate?","authors":"Bruno T S Luz, João S Rebelo, Francisca Monteiro, Francisco Dionisio","doi":"10.3390/antibiotics14020201","DOIUrl":"10.3390/antibiotics14020201","url":null,"abstract":"<p><p><b>Objectives:</b> Antibiotic-resistant bacteria are widespread, with resistance arising from chromosomal mutations and resistance genes located in the chromosome or in mobile genetic elements. While resistance determinants often reduce bacterial growth rates, their influence on bacterial death under bactericidal antibiotics remains poorly understood. When bacteria are exposed to bactericidal antibiotics to which they are susceptible, they typically undergo a two-phase decline: a fast initial exponentially decaying phase, followed by a persistent slow-decaying phase. This study examined how resistance determinants affect death rates during both phases. <b>Methods:</b> We analyzed the death rates of ampicillin-exposed <i>Escherichia coli</i> populations of strains sensitive to ampicillin but resistant to nalidixic acid, rifampicin, or both, and bacteria carrying the conjugative plasmids RN3 or R702. <b>Results:</b> Single mutants resistant to nalidixic acid or rifampicin decayed faster than sensitive cells during the early phase, whereas the double-resistant mutant exhibited prolonged survival. These contrasting impacts suggest epistatic interactions between both chromosomal mutations. Persistent-phase death rates for chromosomal mutants did not differ significantly from wild-type cells. In contrast, plasmid-carrying bacteria displayed distinct dynamics: R702 plasmid-bearing cells showed higher persistent-phase death rates than plasmid-free cells, while RN3 plasmid-bearing cells exhibited lower rates. <b>Conclusions:</b> Bactericidal antibiotics may kill bacteria resistant to other antibiotics more effectively than wild-type cells. Moreover, epistasis may occur when different resistance determinants occur in the same cell, impacting the bactericidal potential of the antibiotic of choice. These results have significant implications for optimizing bacterial eradication protocols in clinical settings, as well as in animal health and industrial food safety management.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506122","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}
Antibiotics-BaselPub Date : 2025-02-14DOI: 10.3390/antibiotics14020197
Laura Cristina Nocua-Báez, Patricia Reyes, Jorge Alberto Cortes
{"title":"Effect of Inadequate Treatment in Adult Patients with Community-Acquired Acute Pyelonephritis Due to Enterobacterales Under Empirical Management with Cefazolin.","authors":"Laura Cristina Nocua-Báez, Patricia Reyes, Jorge Alberto Cortes","doi":"10.3390/antibiotics14020197","DOIUrl":"10.3390/antibiotics14020197","url":null,"abstract":"<p><p><b>Background/Objectives</b>: First-generation cephalosporins are used in some countries, primarily in Latin America and other low-resource regions, as a first-line or alternative empirical treatment for patients with acute pyelonephritis (AP). This study aimed to evaluate the impact of inappropriate empirical therapy with cefazolin on the clinical outcomes of adult patients with community-acquired AP caused by resistant Enterobacterales, requiring hospitalization in two tertiary hospitals in Bogotá. <b>Methods</b>: This retrospective cohort study included hospitalized patients with community-acquired AP caused by Enterobacterales who received initial treatment with cefazolin at two tertiary-level institutions in Colombia (January 2013-2020). Inappropriate treatment was defined as a resistant isolate to cefazolin in the urine culture. Outcomes assessed included hospital stay, hospital mortality, and recurrence. <b>Results</b>: A total of 1031 patients were admitted, among whom 218 (21.1%) received inappropriate treatment. The mean length of stay was 4.8 (5.1) days, 996 (96.6%) survived to discharge, and 113 (11.0%) were admitted for a recurrence of AP. Inappropriate treatment had no impact on hospital stay (RRA 0.98, 95% CI 0.84-1.15) or hospital mortality (OR 1.02, 95% CI 0.47-2.19), although it was associated with a greater risk of admission because of recurrence (OR 3.7, 95% CI 2.4-5.8). <b>Conclusions</b>: We found that inadequate empirical treatment with cefazolin in adult patients with community-acquired acute pyelonephritis does not appear to change the length of hospital stay or in-hospital mortality in patients but is associated with an increased risk of readmission due to recurrence; this might favor the use of empirical narrow-spectrum antibiotics but with strategies that allow monitoring or early detection of microbiological non-eradication to prevent recurrence.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505981","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":"Multidose Dalbavancin Population Pharmacokinetic Analysis for Prolonged Target Attainment in Patients Requiring Long-Term Treatment.","authors":"Giammarco Baiardi, Michela Cameran Caviglia, Silvia Boni, Antonello Di Paolo, Valeria Marini, Giuliana Cangemi, Alessia Cafaro, Emanuele Pontali, Francesca Mattioli","doi":"10.3390/antibiotics14020190","DOIUrl":"10.3390/antibiotics14020190","url":null,"abstract":"<p><p><b>Introduction:</b> Dalbavancin (DAL) is a long-acting lipoglycopeptide active against Gram-positive bacteria, including multidrug-resistant isolates. A growing body of evidence supports its efficacy in various difficult-to-treat infections. DAL shows time-dependent bactericidal activity <i>in vitro</i> at free drug concentrations equal to 4×MIC values. However, the optimal dosing scheme for achieving the PK/PD target in multidose treatment has not been fully established. <b>Methods:</b> Pharmacokinetic analysis was based on a nonlinear mixed effects modelling approach performed in NONMEM v7.5/Pirana, while R was used for data management and graphical summaries. Final model parameters were used to simulate the plasma disposition of DAL by Monte Carlo simulations to determine the multidose DAL regimen associated with a 90% target attainment of 100% <i>f</i>T > 4×MIC. <b>Results:</b> A two-compartmental model with first-order elimination and allometric-scaled bodyweight best described DAL disposition in patients with CLcr > 30 mL/min. Monte Carlo simulations showed that two 1500 mg DAL doses 7 days apart granted an optimal PTA > 90% of 100% <i>f</i>T > 4×MIC up to 5, 4, and 3 weeks in patients weighting from 40-80 kg, 80-120 kg and 120-200 kg, respectively. An additional third 1500 mg dose at the above time points by weight bands may extend the optimal PTA up to 9, 7, and 6 weeks of total treatment. <b>Conclusions:</b> Two 1500 mg DAL doses administered 7 days apart could be a valuable starting strategy for patients of all weight classes with CLcr > 30 mL/min. In patients requiring long-term DAL treatment, the optimal timing of additional administrations should be guided by routine TDM or empirically through patients' total body weight when TDM is unavailable.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506031","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}
Antibiotics-BaselPub Date : 2025-02-13DOI: 10.3390/antibiotics14020192
Ali Heydari, Nick D Kim, Patrick J Biggs, Jacqui Horswell, Gerty J H P Gielen, Alma Siggins, Collette Bromhead, Juan Carlos Meza-Alvarado, Barry R Palmer
{"title":"Antibiotic and Heavy Metal Resistance in Bacteria from Contaminated Agricultural Soil: Insights from a New Zealand Airstrip.","authors":"Ali Heydari, Nick D Kim, Patrick J Biggs, Jacqui Horswell, Gerty J H P Gielen, Alma Siggins, Collette Bromhead, Juan Carlos Meza-Alvarado, Barry R Palmer","doi":"10.3390/antibiotics14020192","DOIUrl":"10.3390/antibiotics14020192","url":null,"abstract":"<p><strong>Background/objectives: </strong>Agricultural soils accumulate inorganic contaminants from the application of phosphate fertilisers. An airstrip located at Belmont Regional Park (BRP), near Wellington, New Zealand, has been found to have a gradient of cadmium contamination due to spillage of superphosphate fertiliser.</p><p><strong>Methods: </strong>Soil samples from the BRP airstrip with a gradient of cadmium contamination, were used as a novel source to explore bacterial communities' resistance to heavy metals (HMs) and any co-selected antibiotic (Ab) resistance.</p><p><strong>Results: </strong>Differences between BRP soil samples with higher levels of HMs compared to those with lower HM concentrations showed significantly more bacterial isolates resistant to both HMs (40.6% versus 63.1% resistant to 0.01 mM CdCl<sub>2</sub>, <i>p</i> < 0.05) and Abs (23.4% versus 37.8% resistant to 20 μg/mL tetracycline, <i>p</i> < 0.05) in soils with higher initial levels of HMs (1.14 versus 7.20 mg kg<sup>-1</sup> Cd). Terminal restriction fragment length polymorphism (TRFLP) and 16S rDNA next-generation sequencing profiling investigated changes in HM-induced bacterial communities. Significant differences were observed among the bacterial community structures in the selected BRP soil samples. Conjugative transfer of cadmium resistance from 23-38% of cadmium-resistant isolates to a characterised recipient bacterial strain in vitro suggested many of these genes were carried by mobile genetic elements. Transconjugants were also resistant to zinc, mercury, and Abs. Higher levels of HMs in soil correlated with increased resistance to HMs, Abs, and elevated levels of HMs thus disturbed the bacterial community structure in BRP soil significantly.</p><p><strong>Conclusions: </strong>These findings suggest that HM contamination of agricultural soil can select for Ab resistance in soil bacteria with potential risks to human and animal health.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504831","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}
Antibiotics-BaselPub Date : 2025-02-13DOI: 10.3390/antibiotics14020191
Yi Li, Andrew D Berti, Wessam Abdelhady, Yan Q Xiong
{"title":"Prophage ϕSA169 Enhances Vancomycin Persistence in Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA).","authors":"Yi Li, Andrew D Berti, Wessam Abdelhady, Yan Q Xiong","doi":"10.3390/antibiotics14020191","DOIUrl":"10.3390/antibiotics14020191","url":null,"abstract":"<p><p><b>Background:</b> Persistent methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) endovascular infections present a significant clinical therapeutic challenge. Prophages are increasingly recognized as important genetic factors influencing the pathogenicity of <i>S. aureus</i>, yet their role in antibiotic persistence in MRSA remains underexplored. Our previous work demonstrated that prophage ϕSA169 promotes vancomycin (VAN) persistence in an experimental model of endocarditis caused by MRSA strains with a clonal complex (CC) 45 genetic background. However, it is unknown whether this persistence-promoting effect of ϕSA169 extends to other clinically relevant MRSA lineages. This study aims to elucidate the role of ϕSA169 in influencing VAN persistence across diverse MRSA genetic backgrounds. <b>Methods:</b> A pilot analysis of clinical data suggested that patients infected by MRSA containing ϕSA169-like prophage appear to have worse clinical outcomes. Thus, we lysogenized representative clinical resolving bacteremia (RB) MRSA strains with ϕSA169 and evaluated phenotypes closely associated with VAN persistence, including VAN susceptibility, biofilm formation, and the efficacy of VAN treatment in an experimental infective endocarditis (IE) model. Each ϕSA169 lysogenic strain was compared to its isogenic MRSA parental counterpart. <b>Results:</b> ϕSA169 lysogeny significantly promotes biofilm formation and enhances survival to VAN exposure under human-mimicking conditions for RB strains from CC5 and CC30. ϕSA169 lysogeny significantly reduces VAN effectiveness in the IE model due to RB lysogen from CC5 despite no detectable impact on VAN MICs. <b>Conclusions:</b> These results indicate that ϕSA169 promotes VAN persistence across clonal backgrounds, likely through biofilm formation and VAN tolerance. Targeting prophage could provide new strategies to combat persistent MRSA infections.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505321","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}