Antibiotics

13 pages, 602 KB

Open AccessArticle

Prophylactic Antibiotics in Vertebroplasty and Kyphoplasty: A Nationwide Analysis of Infection Rates and Antibiotic Use in South Korea

by Youngjin Kim, Young-Hoon Kim, Sukil Kim, Jun-Seok Lee, Sang-Il Kim, Joonghyun Ahn, So-Young Han and Hyung-Youl Park

Antibiotics 2025, 14(9), 901; https://doi.org/10.3390/antibiotics14090901 - 5 Sep 2025

Abstract

Background/Objectives: Vertebroplasty (VP) and kyphoplasty (KP) are widely performed minimally invasive procedures for osteoporotic vertebral compression fractures and vertebral metastases. Although generally safe, postoperative surgical site infections (SSIs) can lead to severe complications. The true incidence of SSIs and optimal prophylactic antibiotic [...] Read more.

Background/Objectives: Vertebroplasty (VP) and kyphoplasty (KP) are widely performed minimally invasive procedures for osteoporotic vertebral compression fractures and vertebral metastases. Although generally safe, postoperative surgical site infections (SSIs) can lead to severe complications. The true incidence of SSIs and optimal prophylactic antibiotic strategies remains unclear. This study evaluated SSI incidence and the impact of antibiotic timing and type using a nationwide quality assessment (QA) database in South Korea. Methods: We analyzed data from the 7th to 9th QA waves of the Health Insurance Review and Assessment (HIRA) Service, including 23,868 patients who underwent VP or KP. SSI incidence was compared across antibiotic timing groups (preoperative-only, postoperative-only, and combined) and antibiotic types. Multivariate logistic regression identified independent risk factors for SSIs. Results: SSI occurred in 47 patients (0.20% of 23,868 procedures). No infections were observed in the preoperative-only group, compared with 0.36% in the postoperative-only group and 0.19% in the pre- and postoperative group. The lowest incidence (0.16%) was seen with first- or second-generation cephalosporins. Multivariate analysis found no significant difference between the preoperative-only and the combined regimens, nor between first-/second-generation cephalosporins and broad-spectrum antibiotics. However, surgery at a tertiary hospital (aOR: 3.566) and malnutrition (aOR: 2.915) were independently associated with increased SSI risk. Conclusions: This nationwide study, the largest to date on VP and KP, demonstrated that SSIs are rare (0.2%). A single preoperative dose of first- or second-generation cephalosporins was as effective as combined or broader-spectrum regimens. Targeted preventive measures may be warranted for high-risk groups such as patients with malnutrition or those treated in tertiary hospitals. Full article

(This article belongs to the Special Issue Orthopedic Infections: Epidemiology and Antimicrobial Treatment)

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14 pages, 2212 KB

Open AccessArticle

Comparison of Cost Savings of Methods of Prevention of Orthopedic Implant-Associated Infection in Arthroplasty and Closed Fracture Surgery Patients

by Pedro Augusto Maciel Moreira, Thiago de Carvalho Gontijo, Gabriel Costa Colen, Ana Carolina Morganti, Felipe Ismael Ulloa Gómez, Pedro Assis Mourão, Gabrielle Adriane Rodrigues Mota, Braulio R. G. M. Couto, Patrícia Almeida de Vasconcellos Rocha, Laila Gonçalves Machado, Raquel Bandeira da Silva and Mauro José Salles

Antibiotics 2025, 14(9), 900; https://doi.org/10.3390/antibiotics14090900 - 5 Sep 2025

Abstract

Background/Objectives: Surgical site infections (SSIs) are serious complications in orthopedic implant-associated procedures, increasing morbidity, mortality, and hospital costs. The purpose of this study was to evaluate the impact of a structured infection prevention and control (IPC) service on SSI incidence and cost [...] Read more.

Background/Objectives: Surgical site infections (SSIs) are serious complications in orthopedic implant-associated procedures, increasing morbidity, mortality, and hospital costs. The purpose of this study was to evaluate the impact of a structured infection prevention and control (IPC) service on SSI incidence and cost savings across hip arthroplasty (HA), knee arthroplasty (KA), and open reduction and internal fixation (ORIF). Methods: A retrospective analysis included 6930 patients treated between 2019 and 2024, divided into pre-intervention (2019–2022) and post-intervention (2023–2024) cohorts. Preventive methods (PMs) comprised enhanced antibiotic prophylaxis, Staphylococcus aureus screening, chlorhexidine bathing, intraoperative audits, and behavioral interventions. Economic evaluation used literature-based costs, standardized to 2024 US dollars (USD 2024), with sensitivity analyses performed. Results: SSI incidence decreased from 5.6% to 1.1% overall (p < 0.001), with consistent reductions across procedures: ORIF (5.2%→1.0%), HA (9.2%→2.4%), and KA (4.8%→1.2%). In 2023, approximately 31 SSIs and one infection-related death were prevented, avoiding 308 hospital days. Cost savings ranged from USD 209,188 to USD 376,898, with cost saving confirmed in 93% of simulations. Conclusions: Comprehensive infection-prevention protocols, delivered through a structured IPC service, significantly reduced SSIs and generated substantial cost savings. These findings support wider use of these PMs in orthopedic surgery. Full article

(This article belongs to the Special Issue Bone and Joint Infections: The Challenges of Prevention, Diagnosis and Treatment and Opportunities for Future Research)

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18 pages, 1880 KB

Open AccessArticle

Antimicrobial Resistance Profiles of Clinically Relevant Enterobacteriaceae Isolates: A Retrospective Study at a Southern Italian Hospital

by Giorgia Stornelli, Beatrice Marinacci, Valentina Puca, Benedetta Pellegrini, Roberta Zita Marulli, Ivana Cataldo, Francesca Sisto, Vittoria Perrotti, Arianna Pompilio, Mattia Mori, Pamela Di Giovanni and Rossella Grande

Antibiotics 2025, 14(9), 899; https://doi.org/10.3390/antibiotics14090899 - 5 Sep 2025

Abstract

Background: The Enterobacteriaceae family is the most heterogeneous group of Gram-negative bacilli, with both environmental and clinical relevance. Although many of these species are part of the normal intestinal microbiota, species such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis are [...] Read more.

Background: The Enterobacteriaceae family is the most heterogeneous group of Gram-negative bacilli, with both environmental and clinical relevance. Although many of these species are part of the normal intestinal microbiota, species such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis are among the most common opportunistic pathogens, frequently responsible for nosocomial infections, including urinary tract infections, bacteraemia, and pneumonia. Based on these concerns, these species are increasingly being studied for their ability to develop antimicrobial resistance, often mediated by extended spectrum β-lactamase or carbapenemase production. The present study aims to analyse the antimicrobial resistance profiles of Enterobacteriaceae isolated from a southern Italian hospital focusing on the species of major clinical importance. Methods: A retrospective analysis was carried out on biological samples collected between 2019 and 2023 at the Microbiology Laboratory of the San Pio Hospital, Vasto (Italy). Eight hundred ninety patients were included, with an average age of 73 years. Bacterial identification was carried out using bacterial culture and biochemical methods, while antimicrobial sensitivity was assessed by using the automated Walk Away System. Results: The most frequently isolated species were Escherichia coli (63.2%), Klebsiella spp. (21.9%), and Proteus spp. (8.8%). All isolates showed resistance to at least one antimicrobial and most to more than four. The highest resistance rates were observed for Cefotaxime (16.0%), followed by Ampicillin (15.6%) and Ciprofloxacin (13.2%). Conclusions: The high prevalence of antimicrobial resistance among clinically relevant Enterobacteriaceae species is a growing clinical challenge. The results of this study, which describe the trend of resistance among Enterobacteriaceae in a local hospital, could help to raise awareness highlighting the urgent need for more advanced diagnostic tools and new therapeutic strategies to treat infections caused by multi-resistant microorganisms. Full article

(This article belongs to the Special Issue Multidrug-Resistant Gram-Negative Bacteria Infections: Current Epidemiology, Prognosis and Treatment Options)

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12 pages, 571 KB

Open AccessArticle

Epidemiological Trends of Carbapenemase-Producing Pseudomonas aeruginosa in a Tertiary Care Hospital in Athens, Greece, During 2020–2023

by Vasiliki Koumaki, Eleni Voudanta, Aikaterini Michelaki, Maria Orfanidou, Eleni Vagiakou, Georgia Vrioni and Athanasios Tsakris

Antibiotics 2025, 14(9), 898; https://doi.org/10.3390/antibiotics14090898 - 5 Sep 2025

Abstract

Background: Infections caused by carbapenemase-producing Pseudomonas aeruginosa (CPPA) isolates have become a worldwide clinical challenge for clinicians due to the limited treatment options. This study provides epidemiological data on CPPA clinical isolates recovered from one of the largest tertiary care hospitals in Athens, [...] Read more.

Background: Infections caused by carbapenemase-producing Pseudomonas aeruginosa (CPPA) isolates have become a worldwide clinical challenge for clinicians due to the limited treatment options. This study provides epidemiological data on CPPA clinical isolates recovered from one of the largest tertiary care hospitals in Athens, Greece, serving a diverse patient population during and after the COVID-19 pandemic. Materials and Methods: The study included all consecutive single-patient CPPA clinical isolates identified from January 2020 to December 2023 in the clinical laboratory. Identification and antimicrobial susceptibility testing were performed using the VITEK-2 automated system. A lateral flow immunoassay and the FilmArray system for blood cultures only were used for the detection of the five most prevalent carbapenemases. Their epidemiological and antimicrobial susceptibility trends were retrospectively analyzed. Results: During the study period, a total of 628 single-patient CPPA were identified among 902 carbapenem-resistant P. aeruginosa clinical isolates. An increasing number of CPPA was revealed during the survey, especially in the post-COVID period (rising from n = 102 in 2020, n = 105 in 2021, and n = 123 in 2022 to n = 298 in 2023; p < 0.05). Regarding the type of carbapenemase, VIM metallo-beta-lactamase was the only carbapenemase identified during the first two years of the study (2020 to 2021). In 2022, VIM- and NDM-producing isolates split almost evenly at proportions of 57% and 43%, respectively. In 2023, NDM-producing isolates seem to have surpassed VIM producers with rates of 54.4% and 45.6%, respectively. As far as antimicrobial resistance profiles, high rates of resistance were observed for most of the antipseudomonal drugs, exceeding 90% across all study years, with little significant variation. However, aztreonam exhibited moderate activity and colistin exhibited excellent activity, remaining the most viable drugs in this setting. Conclusions: Following the COVID-19 pandemic, an increase in CPPA pathogens was identified, while an epidemiological shift was also observed, with the carbapenemase NDM dominating over VIM since 2023. Continuous surveillance is required to track resistance patterns and guide empirical therapy. In this context, new antimicrobials and antimicrobial combinations are also urgently needed. Full article

(This article belongs to the Special Issue Microbial Resistance to Carbapenems: Epidemiology, Detection and Treatment Options)

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14 pages, 1199 KB

Open AccessArticle

Biotransformation of Antibiotics by Coriolopsis gallica: Degradation of Compounds Does Not Always Eliminate Their Toxicity

by Bouthaina Ghariani, Héla Zouari-Mechichi, Abdulrahman H. Alessa, Hussain Alqahtani, Ahmad A. Alsaigh and Tahar Mechichi

Antibiotics 2025, 14(9), 897; https://doi.org/10.3390/antibiotics14090897 - 5 Sep 2025

Abstract

Background/Objectives: Wastewaters containing antibiotics pose risks to human health and soil ecosystems. In this study, the white-rot fungus Coriolopsis gallica (a basidiomycete exhibiting high laccase production) was used for the biotransformation of three antibiotics (50 mg L⁻¹): tetracycline, chloramphenicol, and sulfanilamide. [...] Read more.

Background/Objectives: Wastewaters containing antibiotics pose risks to human health and soil ecosystems. In this study, the white-rot fungus Coriolopsis gallica (a basidiomycete exhibiting high laccase production) was used for the biotransformation of three antibiotics (50 mg L⁻¹): tetracycline, chloramphenicol, and sulfanilamide. Methods: The biotransformation process was investigated in liquid and solid media using high-performance liquid chromatography (HPLC) and the bacterial growth inhibition agar well diffusion method, respectively. Results: Among the three antibiotics tested, tetracycline showed the highest biotransformation efficiency, achieving a 100% removal rate in the liquid medium and a 100% decrease in the growth inhibition of Escherichia coli in the solid medium. Chloramphenicol and sulfanilamide were partially removed (20% and 16%, respectively) after 12 days of treatment in more than one step without the loss of their antibacterial activities. The presence of these antibiotics in the culture medium of C. gallica enhanced laccase activity, indicating that this ligninolytic enzyme might participate in the biotransformation process. Conclusions: Thus, the results reported in this article extend our knowledge of the catalytic potential of C. gallica and give further perspectives for its application in the biodegradation of antibiotics. To the best of our knowledge, this is the first study wherein C. gallica was used for the treatment of tetracycline, chloramphenicol, and sulfanilamide. Full article

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29 pages, 1619 KB

Open AccessReview

Combined Toxicity of Microplastics and Antimicrobials on Animals: A Review

by Kuok Ho Daniel Tang

Antibiotics 2025, 14(9), 896; https://doi.org/10.3390/antibiotics14090896 - 5 Sep 2025

Abstract

Background/Objectives: Microplastics are ubiquitous pollutants that pose physical toxicity and serve as vectors for antimicrobial agents, altering their bioavailability and toxicity. Unlike previous reviews that focus solely on antibiotics and terrestrial or aquatic ecosystems, this review integrates recent findings on the combined [...] Read more.

Background/Objectives: Microplastics are ubiquitous pollutants that pose physical toxicity and serve as vectors for antimicrobial agents, altering their bioavailability and toxicity. Unlike previous reviews that focus solely on antibiotics and terrestrial or aquatic ecosystems, this review integrates recent findings on the combined impacts of microplastics and antimicrobials on both aquatic and terrestrial animals, highlighting their biological responses. Methods: Recent experimental studies involving aquatic and terrestrial animals published in peer-reviewed journals were reviewed. These studies employed co-exposure designs using microplastics of different sizes, aging conditions, and surface chemistries in combination with antimicrobial compounds. Results: Microplastics combined with antimicrobials cause species-specific and often synergistic toxicity in aquatic organisms, affecting reproduction, immunity, oxidative stress, gene expression, and microbiota, with co-exposure often amplifying adverse physiological and developmental effects. Similarly, co-exposure to microplastics and antimicrobials in rodents, amphibians, birds, and soil invertebrates frequently leads to synergistic toxicity, oxidative stress, disrupted gut microbiota, and enhanced accumulation and bioavailability of pollutants, promoting inflammation, neurotoxicity, metabolic dysfunction, and increased antibiotic resistance gene propagation. Particle size, aging, and antimicrobial type influence toxicity severity. Certain microplastic-antimicrobial combinations can exhibit antagonistic effects, though less frequently reported. Conclusions: The interactions between microplastics and antimicrobials pose heightened risks to the health of organisms and ecological stability. These findings underscore the need to revise current risk assessment protocols to consider pollutant mixtures and microplastics-mediated transport. Future research should focus on environmentally relevant exposures, mechanistic studies using omics tools, and long-term ecological impacts. Integrated regulatory strategies are essential to address the compounded effects of microplastics and chemical contaminants. Full article

(This article belongs to the Special Issue Environmental Fate and Effects of Antibiotics and Antibiotic Resistance Genes, 2nd Edition)

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15 pages, 1307 KB

Open AccessArticle

Impact of Obesity on Serum Concentrations of Vancomycin Administered as Continuous Infusion and on Clinical Outcomes in Critically Ill Patients—A Retrospective Observational Study

by Stefanie Nothofer, Rico Angeli, Manfred Weiss, Christian Dumps, Felix Berger, Josephin Eckert, Felix Girrbach, Nadin Scheidt, Susan Menzel, Mirko Lange, Hermann Wrigge and Philipp Simon

Antibiotics 2025, 14(9), 895; https://doi.org/10.3390/antibiotics14090895 - 4 Sep 2025

Abstract

Background/Objectives: Vancomycin is a commonly used antibiotic in critically ill patients with severe methicillin-resistant Staphylococcus aureus infections. Due to its narrow therapeutic window, under- or overdosing is likely to result in adverse effects, especially in patients with conditions associated with altered pharmacokinetics such [...] Read more.

Background/Objectives: Vancomycin is a commonly used antibiotic in critically ill patients with severe methicillin-resistant Staphylococcus aureus infections. Due to its narrow therapeutic window, under- or overdosing is likely to result in adverse effects, especially in patients with conditions associated with altered pharmacokinetics such as obesity. The objective of this study was to investigate the impact of obesity on serum concentrations of vancomycin in critically ill patients receiving intravenous vancomycin by continuous infusion based on ideal body weight (IBW). Methods: This retrospective observational study performed at the University Hospital of Leipzig, Germany, included all patients admitted to the intensive care unit (ICU) between January 2009 and December 2015 who received guideline-based vancomycin therapy based on IBW. Serum concentrations were obtained through routinely performed therapeutic drug monitoring (TDM). Results: A total of 1066 patients with a median age of 62 years were included in this study. The median (25%; 75% quantile) vancomycin treatment duration was 4 (2; 7) days and the median time to reach target concentrations of 20–25 mg L⁻¹ was 3 (2; 4) days without a significant difference between BMI groups. Overall, only 25.9% of patients were in the therapeutic range of 20–25 mg L⁻¹ in the entire treatment interval. 47.8% of vancomycin concentrations obtained from TDM were below the desired target range with no differences between the BMI groups (p = 0.077). 26.3% of measurements exceeded the target range, with a significant increase in the morbidly obese group (p < 0.001). A higher BMI was associated with an increased ICU, in-hospital, 28- and 90-day mortality in morbidly obese patients (p < 0.05). Age, BMI and high SAPS-II and SOFA scores were significant predictors of an increased risk of death. Conclusions: Our preliminary findings suggest that IBW-based dosing may help reduce the risk of supratherapeutic concentrations in morbidly obese patients. The high rates of sub- and supratherapeutic vancomycin serum concentrations across all patients highlight the need for close TDM and dose adjustments, particularly in morbidly obese patients with the highest rates of supratherapeutic vancomycin serum concentrations and of RRT. Full article

(This article belongs to the Special Issue Epidemiology and Antimicrobial Dosing Regimens in Intensive Care Units)

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12 pages, 265 KB

Open AccessReview

Antibiotics for the Treatment of Patients with Metallo-β-Lactamase (MBL)-Producing Gram-Negative Bacterial Infections

by Matthew E. Falagas, Dimitrios S. Kontogiannis, Dimitrios Ragias and Stylianos A. Kakoullis

Antibiotics 2025, 14(9), 894; https://doi.org/10.3390/antibiotics14090894 - 4 Sep 2025

Abstract

Infections caused by MBL-producing Gram-negative bacterial pathogens have disseminated worldwide and are associated with considerable morbidity and mortality. We evaluated the published clinical evidence on the use of various antibiotics for the treatment of patients with such infections. The available data suggest the [...] Read more.

Infections caused by MBL-producing Gram-negative bacterial pathogens have disseminated worldwide and are associated with considerable morbidity and mortality. We evaluated the published clinical evidence on the use of various antibiotics for the treatment of patients with such infections. The available data suggest the consideration of the new antibiotics cefiderocol and aztreonam-avibactam for the treatment of patients with infections caused by MBL-producing Gram-negative bacterial pathogens. However, their considerable cost and limited availability hinder their use. Also, the combination of ceftazidime-avibactam and aztreonam has been occasionally used, especially when there was an unavailability of aztreonam-avibactam. Additionally, old antibiotics such as colistin and fosfomycin, especially in combination antimicrobial therapy, may be considered for the treatment of patients with such infections. The relevant clinical data on the use of tigecycline and aminoglycosides for infections caused by MBL-producing pathogens are limited. Thus, the evaluation of the published evidence suggests the best treatment options for the treatment of patients with such infections at present. Also, the limited available data highlight the need for dissemination of the already acquired clinical experience and the conduct of new studies examining currently available antibiotics, as well as investigational antimicrobial agents for the treatment of patients with infections caused by MBL-producing Gram-negative bacterial pathogens. Full article

(This article belongs to the Special Issue Gram-Negative Multidrug-Resistant Pathogens and Their Treatment, 2nd Edition)

9 pages, 215 KB

Open AccessCommunication

Rapid Emergence of Cefiderocol Resistance Associated with Mutation of EnvZ Gene in a VIM-Producing ST307 Klebsiella pneumoniae Strain

by Simone Ambretti, Benedetta Secci, Raul Cetatean, Milo Gatti, Pierluigi Viale, Federico Pea and Claudio Foschi

Antibiotics 2025, 14(9), 893; https://doi.org/10.3390/antibiotics14090893 - 4 Sep 2025

Abstract

Infections caused by carbapenem-resistant Enterobacterales (CRE), particularly those harboring metallo-β-lactamases (MBLs) such as VIM, constitute a significant public health threat due to the paucity of effective therapeutic options. Cefiderocol (CFD), a novel siderophore-conjugated cephalosporin, exhibits potent activity against CRE by exploiting bacterial iron [...] Read more.

Infections caused by carbapenem-resistant Enterobacterales (CRE), particularly those harboring metallo-β-lactamases (MBLs) such as VIM, constitute a significant public health threat due to the paucity of effective therapeutic options. Cefiderocol (CFD), a novel siderophore-conjugated cephalosporin, exhibits potent activity against CRE by exploiting bacterial iron uptake systems. Nevertheless, the emergence of CFD resistance has been recently documented. This study aimed to characterize the development of CFD resistance in a VIM-producing Klebsiella pneumoniae isolate during antimicrobial treatment. Antimicrobial susceptibility was assessed by broth microdilution using iron-depleted medium according to EUCAST guidelines. Whole-genome sequencing and comparative genomic analyses focused on mutations in genes related to iron transport and CFD resistance, using Illumina MiSeq. Initial isolates (RS, BA1) were susceptible to CFD (MIC 2 mg/L), whereas the isolate recovered after 9 days of CFD therapy (BA2) was resistant (MIC 8 mg/L). In conclusion, this study illustrates for the first time the rapid emergence of CFD resistance in a VIM-producing ST307 K. pneumoniae isolate linked to a missense variant in envZ gene, arising after a 9-day CFD treatment. Full article

(This article belongs to the Special Issue Epidemiology and Genomics of Antimicrobial Resistance of Difficult-to-Treat Pathogens)

20 pages, 1867 KB

Open AccessArticle

Serratia marcescens Isolates from Bovine Mastitic Milk: Antimicrobial Resistance and Virulence Features

by Guilherme Moreira, Luís Pinho, João R. Mesquita and Eliane Silva

Antibiotics 2025, 14(9), 892; https://doi.org/10.3390/antibiotics14090892 - 3 Sep 2025

Abstract

Background: Bovine mastitis (BM) is a major disease affecting dairy herds (DHs), with Serratia marcescens (S. marcescens) being increasingly implicated as a causative agent. The growing concern over antimicrobial resistance (AMR) extends to BM-associated S. marcescens isolates, where resistance patterns [...] Read more.

Background: Bovine mastitis (BM) is a major disease affecting dairy herds (DHs), with Serratia marcescens (S. marcescens) being increasingly implicated as a causative agent. The growing concern over antimicrobial resistance (AMR) extends to BM-associated S. marcescens isolates, where resistance patterns are emerging. Methods: Here, four BM Gram-negative isolates were investigated: 1-DH1, 2-DH1, 3-DH2, and 4-DH3. Phenotypic characterization was performed using the Neg-Urine-Combo98 panel on a MicroScan WalkAway Plus system. Whole-genome sequencing (WGS) was performed to characterize and identify AMR and virulence factors (VF) genes and plasmids in isolates 1-DH1, 3-DH2, and 4-DH3, and phylogenomic analyses were conducted for a visual comparison of the genomes. Results: Phenotypically, isolates 1-DH1, 2-DH1, and 4-DH3 were identified as S. marcescens, and 3-DH2 as Serratia odorifera (confirmed as S. marcescens by WGS). A 28.00% (n = 25) prevalence of phenotypic AMR for isolates 1-DH1, 2-DH1, and 4-DH3 against Aug-E, AM, To, Cfx, Crm, Cl, and Fd was shown, and 24.00% (n = 25) for isolate 3-DH2 against Aug-E, AM, To, Crm, Cl, and Fd. The AMR genes AAC(6′)-Ic, aac(6′)-Ic_1, aac(6′)-Ial, H-NS, SRT-2, oqxB, oqxB_1, oqxB25, mexI, CRP, and blaSST-1, and flgH, fliP, fliM, and fliG VF genes were identified in the whole genome of the S. marcescens sequenced isolates 1-DH1, 2-DH1, and 4-DH3. In addition, a phylogenomic analysis of these three isolates revealed that WGS genomes are more closely related to S. marcescens prevenient from environmental sources. Conclusions: This study reports, for the first time, AMR resistance to tobramycin, cefuroxime, colistin, and nitrofurantoin in BM S. marcescens isolates. Genomic analysis revealed the presence of multiple AMR and VF genes, further highlighting the pathogenic potential of these isolates. Phylogenomic analysis revealed that the genome of the three BM S. marcescens isolates is more closely related to environmental S. marcescens strains. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Virulence in Bacterial Isolates: A Genomic Perspective from Human and Animal Sources)

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22 pages, 1985 KB

Open AccessArticle

Selective Antimicrobial Chitosan Films Incorporating Green-Synthesized Silver and Copper Oxide Nanoparticles for Acne Treatment

by Roberta Albino dos Reis, Carolina C. de Freitas, Leonardo Longuini da Silva, Laura Pierobão Monteiro, Gerson Nakazato, Mathilde Champeau, Ricardo A. Galdino da Silva and Amedea Barozzi Seabra

Antibiotics 2025, 14(9), 891; https://doi.org/10.3390/antibiotics14090891 - 3 Sep 2025

Abstract

Background/Objectives: Chitosan-based films incorporating green-synthesized silver nanoparticles AgNPs) or copper oxide nanoparticles (CuONPs) were developed to compare their selective antimicrobial action for topical applications. While AgNPs are known for broad-spectrum activity, this study hypothesized that CuONPs would exhibit superior, targeted efficacy against the [...] Read more.

Background/Objectives: Chitosan-based films incorporating green-synthesized silver nanoparticles AgNPs) or copper oxide nanoparticles (CuONPs) were developed to compare their selective antimicrobial action for topical applications. While AgNPs are known for broad-spectrum activity, this study hypothesized that CuONPs would exhibit superior, targeted efficacy against the acne-associated bacterium Cutibacterium acnes. Methods: Nanoparticles were synthesized using Camellia sinensis extract and characterized. Antimicrobial activity was evaluated using Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays. Chitosan films containing AgNPs or CuONPs were further tested for selective antimicrobial activity and fibroblast cytocompatibility. Results: AgNPs showed strong activity against Escherichia coli and Staphylococcus aureus (MIC = 15 µg/mL) but were less effective against C. acnes (MIC = 125 µg/mL). In contrast, CuONPs demonstrated selective efficacy against C. acnes (MIC = 62 µg/mL; MBC = 125 µg/mL). When incorporated into chitosan films, AgNPs@CHI inhibited E. coli (35 mm halo) and S. aureus (30 mm), whereas CuONPs@CHI were selectively effective against C. acnes (45 mm). All films preserved fibroblast viability above the 70% ISO 10993-5 threshold. Conclusions: CuONPs@CHI films validated selective anti-C. acnes performance, highlighting their promise for targeted anti-acne therapies, while AgNPs@CHI films served as effective broad-spectrum antimicrobial barriers.revealed that AgNPs were potent against Escherichia coli and Staphylococcus aureus (MIC = 15 µg/mL) but less effective against C. acnes (MIC = 125 µg/mL). Conversely, CuONPs demonstrated a marked selective advantage against C. acnes (MIC = 62 µg/mL; MBC = 125 µg/mL). When incorporated into chitosan films, AgNPs@CHI films inhibited E. coli (35 mm halo) and S. aureus (30 mm), whereas CuONPs@CHI films were selectively effective only against C. acnes (45 mm), confirming the targeted performance. All films maintained fibroblast viability above the 70% ISO 10993-5 cytotoxicity threshold. These findings validate the selective action of CuONPs@CHI films, positioning them as a promising biomaterial for targeted anti-acne therapies, while AgNPs@CHI films serve as effective broad-spectrum antimicrobial barriers. Full article

(This article belongs to the Special Issue Nanoparticles as Antibacterial/Antibiofilm Agents)

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17 pages, 422 KB

Open AccessReview

Gut Microbiome and Intestinal Colonization with Multidrug-Resistant Strains of Enterobacterales: An Interplay Between Microbial Communities

by Béla Kocsis, Dóra Szabó and László Sipos

Antibiotics 2025, 14(9), 890; https://doi.org/10.3390/antibiotics14090890 - 3 Sep 2025

Abstract

Background: The intestinal tract is a host to a high number of diverse bacteria, and the presence of multidrug-resistant (MDR) Enterobacterales strains acts as a reservoir and a source of infection. The interactions between the intestinal microbiome and colonizer Enterobacterales strains influence [...] Read more.

Background: The intestinal tract is a host to a high number of diverse bacteria, and the presence of multidrug-resistant (MDR) Enterobacterales strains acts as a reservoir and a source of infection. The interactions between the intestinal microbiome and colonizer Enterobacterales strains influence long-lasting colonization. Aims: In this narrative review, we summarize available data about the intestinal colonization of MDR Enterobacterales strains and correlations between colonization and the intestinal microbiome. Results: Several endogenous and exogenous factors influence the intestinal colonization of MDR Enterobacterales strains. On the gut microbiome level, the intestinal microbial community is composed of the Lachnospiraceae family (e.g., Lachnoclostridium, Agathobacter, Roseburia, Tyzzerella), which indicates a protective role against colonizer MDR Enterobacterales strains; by contrast, a high abundance of Enterobacterales correlates with the colonization of MDR Enterobacterales strains. In specific patient groups, striking differences in microbiome composition can be detected. Among hematopoietic stem-cell-transplanted patients colonized by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, a greater abundance of Bifidobacterium, Blautia, Clostridium, Coprococcus, L-Ruminococcus, Mogibacteriaceae, Peptostreptococceae and Oscillospira was observed compared to patients not colonized by ESBL-producing strains, who had a greater abundance of Actinomycetales. In liver transplant patients, a reduction in the alpha-diversity of the intestinal microbiome in fecal samples correlates with the carriage of MDR Enterobacterales. Conclusions: Intestinal colonization with MDR Enterobacterales is a multifactorial process that involves the MDR strain (e.g., its plasmids, fimbria), host and mucosal factors (e.g., IgA and defensin) and exogenous factors (e.g., use of antibiotics, hospitalization). On the gut microbiome level, the Lachnospiraceae family is dominant among intestines not colonized by MDR strains, but a high abundance of Enterobacterales was correlated with colonization with MDR Enterobacterales strains. Full article

(This article belongs to the Special Issue The Role of the Gut Microbiome in Antibiotic Resistance and Therapy: Mechanisms and Implications)

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16 pages, 2039 KB

Open AccessArticle

Machine Learning Models to Establish the Risk of Being a Carrier of Multidrug-Resistant Bacteria upon Admission to the ICU

by Sulamita Carvalho-Brugger, Mar Miralbés Torner, Gabriel Jiménez Jiménez, Montserrat Vallverdú Vidal, Begoña Balsera Garrido, Xavier Nuvials Casals, Mercedes Palomar Martínez and Javier Trujillano Cabello

Antibiotics 2025, 14(9), 889; https://doi.org/10.3390/antibiotics14090889 - 3 Sep 2025

Abstract

Objectives: To establish the risk of being a carrier of multidrug-resistant bacteria (MDR) upon ICU admission, according to the risk factors (RFs) from the Spanish “Resistencia Zero” (RZ) project checklist, using machine learning methodology. Methods: A retrospective cohort study, conducted with a consecutive [...] Read more.

Objectives: To establish the risk of being a carrier of multidrug-resistant bacteria (MDR) upon ICU admission, according to the risk factors (RFs) from the Spanish “Resistencia Zero” (RZ) project checklist, using machine learning methodology. Methods: A retrospective cohort study, conducted with a consecutive sample of patients admitted to the ICU between 2014 and 2016. The study analyzed the RZ RFs for MDR, as well as other pathological variables and comorbidities. The study group was randomly divided into a development group (70%) and a validation group (30%). Several machine learning models were used: binary logistic regression, CHAID-type decision tree, and the XGBOOST methodology (version 2.1.0) with SHAP analysis. Results: Data from 2459 patients were analyzed, of whom 210 (8.2%) were carriers of MDR. The risk grew with the accumulation of RF. Binary logistic regression identified colonization or previous infection by MDR, prior antibiotic treatment, living in a nursing home, recent hospitalization, and renal failure as the most influential factors. The CHAID tree detected MDR in 56% of patients with previous colonization or infection, a figure that increased to almost 74% if they had also received antibiotic therapy. The XGBOOST model determined that variables related to antibiotic treatment were the most important. Conclusions: The RZ RFs have limitations in predicting MDR upon ICU admission, and machine learning models offer certain advantages. Not all RFs have the same importance, but their accumulation increases the risk. There is a group of patients with no identifiable RFs, which complicates decisions on preventive isolation. Full article

(This article belongs to the Special Issue Preventing Antimicrobial Resistance in Hospitals: Infection Control and Antibiotic Use)

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16 pages, 1067 KB

Open AccessArticle

Antibiotic Consumption at the Community Level: The Potential of a Single Health Policy Instrument to Assist Appropriate Use—Insights from Bulgaria

by Desislava Vankova, Nadia Veleva, Petya Boncheva, Katerina Kondova, Zhaneta Radkova and Silviya Mihaylova

Antibiotics 2025, 14(9), 888; https://doi.org/10.3390/antibiotics14090888 - 3 Sep 2025

Abstract

Background: Antimicrobial resistance (AMR) is accelerated by inappropriate antibiotic use in community settings. While most EU countries have achieved a statistically significant reduction in antibiotic consumption, Bulgaria has shown the opposite trend. The aim of this study is to investigate the implementation of [...] Read more.

Background: Antimicrobial resistance (AMR) is accelerated by inappropriate antibiotic use in community settings. While most EU countries have achieved a statistically significant reduction in antibiotic consumption, Bulgaria has shown the opposite trend. The aim of this study is to investigate the implementation of mandatory electronic prescriptions (e-Rx) for antibiotics in Bulgarian primary care and to analyse community-level sales trends (2022–Q1 2025) in the context of related policy changes. Methods: The study applied a content analysis approach to publicly available policy documents and antibiotic sales and prescription data (IQVIA Bulgaria, NHIS). Participatory approaches facilitated the contextual interpretation of the data. The Health Policy Triangle framework guided the analysis of e-Rx implementation across four dimensions: content, context, process, and key actors involved in the e-Rx policy rollout. Trends in sales were assessed before and after the policy’s full enforcement in April 2024. Results: Sales data from IQVIA Bulgaria show a steady ≈10% decline in outpatient antibiotic sales from 2022 to 2024, with over 1.1 million fewer packages dispensed. Although the estimated annual and quarterly declines in community sales did not reach statistical significance in the short term, the consistent downward trajectory remains noteworthy. Conclusions: Mandatory e-Rx has shown early potential as a policy instrument to reduce antibiotic overuse in Bulgaria. It is expected to contribute to the reduction in AMR and to support the implementation of integrated national One Health policies. Full article

(This article belongs to the Special Issue Managing Appropriate Antibiotic Prescribing and Use in Primary Care)

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16 pages, 306 KB

Open AccessArticle

Honey Compounds Exhibit Antibacterial Effects Against Aggregatibacter actinomycetemcomitans JP2

by Abdelhadi Hbibi, Amine Ezzahi, Ferhat Ozturk, Niels A. J. Cremers, Jalal Kasouati, Ahmed Moussaif, Anders Johansson, Mimoun Zouhdi, Babacar Touré and Itto Maroui

Antibiotics 2025, 14(9), 887; https://doi.org/10.3390/antibiotics14090887 - 3 Sep 2025

Abstract

Background: Aggregatibacter actinomycetemcomitans JP2 genotype is a virulent pathogen linked to severe periodontitis and systemic diseases. Honey and royal jelly (RJ) have demonstrated bioactive properties against this microorganism. This study aims to assess the bioactive properties of honeys and RJ against this [...] Read more.

Background: Aggregatibacter actinomycetemcomitans JP2 genotype is a virulent pathogen linked to severe periodontitis and systemic diseases. Honey and royal jelly (RJ) have demonstrated bioactive properties against this microorganism. This study aims to assess the bioactive properties of honeys and RJ against this key periodontal pathogen and to preliminarily identify key compounds with antibacterial potential. Methods: The antibacterial activity of honeys and commercial products (manuka, L-Mesitran^® as a medical-grade honey-based formulation (MGHF), and Honix^® RJ) against A. actinomycetemcomitans JP2 was evaluated using the agar well diffusion method and microdilution assays. Extensive physicochemical characterization (e.g., hydrogen peroxide level, total phenolic content, and total flavonoid content) was conducted to correlate the bioactive compounds with the antimicrobial activity. Results: All tested samples exhibited varying antibacterial potency, with inhibition zones ranging from 21 to 37 mm. The MICs ranged from 40.7 to 104.3 mg/mL. MGHF, RJ, and multifloral honeys showed the lowest MICs. The pH of six out of eight samples could not induce enamel decalcification while the pH of three samples may not influence cementum demineralization. Vitamin C, zinc, magnesium, and potassium were present in measurable quantities, and were not associated with significant antibacterial activity. MGHF showed the highest hydrogen peroxide activity and TFC values. TFC and H₂O₂ content were statistically correlated with lower MIC values. Conclusions: Honey and RJ showed antibacterial activity against A. actinomycetemcomitans JP2, partly attributed to their content of hydrogen peroxide and flavonoids. Clinical trials are needed to confirm the potential role of honey, RJ, and their bioactive compounds in managing periodontitis. Full article

(This article belongs to the Section Novel Antimicrobial Agents)

18 pages, 3564 KB

Open AccessArticle

Antimicrobial and Cytoprotective Effects of Tea Extracts Against Escherichia coli-Producing Colibactin Toxin Infections

by Wipawadee Teppabut, Yingmanee Tragoolpua and Thida Kaewkod

Antibiotics 2025, 14(9), 886; https://doi.org/10.3390/antibiotics14090886 - 2 Sep 2025

Abstract

Background/Objectives: Camellia sinensis (L.) Kuntze or tea contains bioactive compounds such as catechin and caffeine, known for their antimicrobial and health-promoting properties. Colibactin-producing Escherichia coli are linked to genotoxicity in colon epithelial cells, potentially contributing to colorectal disease. This study aimed to [...] Read more.

Background/Objectives: Camellia sinensis (L.) Kuntze or tea contains bioactive compounds such as catechin and caffeine, known for their antimicrobial and health-promoting properties. Colibactin-producing Escherichia coli are linked to genotoxicity in colon epithelial cells, potentially contributing to colorectal disease. This study aimed to evaluate the inhibitory effects of tea extracts (green, oolong, and black) and the phytochemicals catechin and caffeine on E. coli pathogenesis mediated by colibactin toxins, including transient infections, DNA damage, and cell cycle alterations in Caco-2 colon cells. Methods: Tea extracts were analyzed by HPLC for phytochemical content. Their antimicrobial activity against colibactin-producing E. coli (ATCC 25922) was assessed. Caco-2 cells were infected with the bacteria and treated with tea extracts or compounds. Cell viability was measured by MTT assay, DNA damage was measured by alkaline comet assay, and the expression of CDK-1, CDK-2, and Ki-67 genes was measurd by qRT-PCR. Results: Tea extracts and catechin inhibited colibactin-producing E. coli and significantly protected Caco-2 cells. Oolong tea showed the highest protection (90.78 ± 2.76%), with others maintaining viability above 80%. DNA damage was markedly reduced, and cell cycle regulation improved. All extracts upregulated CDK-1 and downregulated CDK-2, aiding in cell cycle restoration. Ki-67 expression indicated enhanced cell proliferation during infection. Conclusions: This study highlights new findings showing that tea extracts, including green, oolong, and black tea, as well as the tea compounds catechin and caffeine, can protect against DNA damage and help maintain the normal cell cycle of colon cells infected with E. coli-producing colibactin toxin. These results support their potential role in preventing and mitigating infections caused by such E. coli strains while promoting colon cell health. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Extracts from Plants, 2nd Edition)

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14 pages, 1323 KB

Open AccessArticle

Utilization of a Multi-Tissue Extracellular Matrix in Complex Wound Care in Gaza: A Case Series

by Bilal Irfan, Adam Hamawy, Ruba Musallam, Rahaf Abudagga, Sameer Khan, Nour Alshaer, Mohammed Tabash, Abdullah Ghali, Khaled Saleh and Mohammed Tahir

Antibiotics 2025, 14(9), 885; https://doi.org/10.3390/antibiotics14090885 - 2 Sep 2025

Abstract

Purpose: This case series examines the feasibility and outcomes of using a multi-tissue extracellular matrix (ECM) powder as an adjunct to standard wound care in a conflict zone. Primary objectives were granulation by day 7, wound closure, and minimizing early complications among patients [...] Read more.

Purpose: This case series examines the feasibility and outcomes of using a multi-tissue extracellular matrix (ECM) powder as an adjunct to standard wound care in a conflict zone. Primary objectives were granulation by day 7, wound closure, and minimizing early complications among patients with complex ballistic and blast injuries in Gaza during the 2024 Israeli military offensive. Methods: A retrospective observational study was conducted at the European Gaza Hospital from April to June 2024. Fifteen patients with high-energy soft tissue injuries who received ECM powder (XCellistem™) after surgical debridement were included. Data were extracted from operative reports, wound documentation, and clinical follow-up. Outcomes included granulation by day 7, wound closure method, and complications such as infection or dehiscence. Results: All 15 patients (median age 28; 14 male) sustained severe trauma, with 80% having exposed bone or tendon. ECM was applied directly to wound beds and often co-applied with vancomycin. Granulation tissue was observed in 12 patients by day 7, and 13 achieved wound closure via grafting, flap coverage, or secondary intention. No adverse reactions to ECM were reported. Conclusions: Multi-tissue ECM powder seems feasible and safe under austere conditions and appeared to support wound healing in severely injured patients. Its shelf stability, ease of use, and regenerative potential make it a promising adjunct for surgical care in resource-constrained conflict zones. Full article

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12 pages, 703 KB

Open AccessArticle

Risk Factor Analysis of CRE Infections at Different Anatomical Sites in ICU Patients

by Guoxing Tang, Huijuan Song, Liyan Mao, Shaozhen Yan, Lei Tian, Cui Jian, Zhongju Chen, Ziyong Sun and Yue Wang

Antibiotics 2025, 14(9), 884; https://doi.org/10.3390/antibiotics14090884 - 1 Sep 2025

Abstract

Objectives: This study aimed to identify differences in risk factors for carbapenem-resistant Enterobacteriaceae (CRE) infections across different anatomical sites and to explore risk factors associated with mortality in CRE-infected patients. Methods: Patients who underwent CRE screening and were subsequently diagnosed with [...] Read more.

Objectives: This study aimed to identify differences in risk factors for carbapenem-resistant Enterobacteriaceae (CRE) infections across different anatomical sites and to explore risk factors associated with mortality in CRE-infected patients. Methods: Patients who underwent CRE screening and were subsequently diagnosed with CRE infections were included and categorized by infection site: respiratory tract (RTI), urinary tract (UTI), and bloodstream (BSI). Forty ICU patients without CRE infection were randomly selected as controls. Statistical comparisons were performed using the Mann–Whitney U or Chi-square test, as appropriate. Potential risk factors were evaluated via univariate and multivariate analyses, and a predictive model was constructed, with its performance assessed using ROC curve analysis. Results: CRE colonization was identified as a common independent risk factor across all three groups (RTI, UTI, and BSI). Infection-site-specific analyses revealed independent risk factors: RTI was associated with mechanical ventilation, UTI with trauma, and BSI with gastrointestinal injury. Predictive models for RTI, UTI, and BSI demonstrated good discrimination, with ROC AUCs of 0.94, 0.94, and 0.95, respectively. In the analysis of Survived versus Deceased patients, the BSI group had the highest mortality, though the difference was not statistically significant. Deceased patients exhibited significantly higher PCT levels than Survived patients (p = 0.005). Prior use of carbapenems and antifungal agents, as well as Ln(PCT), were independently associated with mortality in CRE-infected patients. Conclusions: Risk factors for CRE infections vary across anatomical sites, with CRE colonization, mechanical ventilation, trauma, and gastrointestinal injury playing key roles. Overuse of antibiotics and elevated inflammatory responses are associated with increased mortality. These findings provide evidence for early identification of high-risk patients and optimization of individualized treatment strategies. Full article

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22 pages, 5608 KB

Open AccessArticle

1,5-Diarylidene-4-Piperidones as Promising Antifungal Candidates Against Cryptococcus neoformans

by Elise Courvoisier-Dezord, Hugo Ragusa, Axelle Grandé, Louise Denudt, Yolande Charmasson, Frédéric Dumur, Didier Siri, Marc Maresca and Malek Nechab

Antibiotics 2025, 14(9), 883; https://doi.org/10.3390/antibiotics14090883 - 1 Sep 2025

Abstract

Background/Objectives: The present study investigates the antifungal potential of 1,5-diarylidene-4-piperidones. Methods: These compounds were synthesized via Claisen–Schmidt condensation, and their antifungal efficacy was tested against Cryptococcus neoformans, a yeast recently qualified as a critical priority pathogen by the World Health Organization, through [...] Read more.

Background/Objectives: The present study investigates the antifungal potential of 1,5-diarylidene-4-piperidones. Methods: These compounds were synthesized via Claisen–Schmidt condensation, and their antifungal efficacy was tested against Cryptococcus neoformans, a yeast recently qualified as a critical priority pathogen by the World Health Organization, through determination of their minimum inhibitory concentration (MIC). We designed and synthesized a series of piperidones to explore structure–activity relationships. Results: Systematic modification of the substituent pattern revealed that tetrabutoxy groups exhibited potent activity (MIC of 7.8 µM), surpassing standard antifungals like fluconazole. The selectivity index (SI) values confirmed their safety profile across various human cells. Docking analysis demonstrated that these compounds target sterol 14-demethylase, suggesting potential inhibition of ergosterol synthesis as a mechanism of action. Interestingly, the compounds also demonstrated broad-spectrum activity against other pathogenic yeasts and fungi, including Candida and Aspergillus species, and against fluconazole-resistant strains. Conclusions: These findings underscore the potential of 1,5-diarylidene-4-piperidones as promising antifungal candidates with a favorable safety profile. Full article

(This article belongs to the Special Issue Challenges and Strategies for the Antibiotic Resistance Crisis)

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