Antibiotics

21 pages, 1308 KiB

Open AccessArticle

Mechanisms of Cefiderocol Resistance in Carbapenemase-Producing Enterobacterales: Insights from Comparative Genomics

by Alexander Tristancho-Baró, Ana Isabel López-Calleja, Ana Milagro, Mónica Ariza, Víctor Viñeta, Blanca Fortuño, Concepción López, Miriam Latorre-Millán, Laura Clusa, David Badenas-Alzugaray, Rosa Martínez, Carmen Torres and Antonio Rezusta

Antibiotics 2025, 14(7), 703; https://doi.org/10.3390/antibiotics14070703 (registering DOI) - 12 Jul 2025

Abstract

Background/Objectives: Cefiderocol is a novel siderophore cephalosporin with potent in vitro activity against a broad spectrum of Gram-negative bacteria, including carbapenemase-producing Enterobacterales (CPE). However, the recent emergence of resistance in clinical settings raises important concerns regarding its long-term effectiveness. This study aims [...] Read more.

Background/Objectives: Cefiderocol is a novel siderophore cephalosporin with potent in vitro activity against a broad spectrum of Gram-negative bacteria, including carbapenemase-producing Enterobacterales (CPE). However, the recent emergence of resistance in clinical settings raises important concerns regarding its long-term effectiveness. This study aims to investigate the genomic determinants associated with cefiderocol resistance in CPE isolates of human origin. Methods: Comparative genomic analyses were conducted between cefiderocol-susceptible and -resistant CPE isolates recovered from human clinical and epidemiological samples at a tertiary care hospital. Whole-genome sequencing, variant annotation, structural modelling, and pangenome analysis were performed to characterize resistance mechanisms. Results: A total of 59 isolates (29 resistant and 30 susceptible) were analyzed, predominantly comprising Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae. The most frequent carbapenemase gene among the resistant isolates was bla_NDM, which was also present in a subset of susceptible strains. The resistant isolates exhibited a significantly higher burden of non-synonymous mutations in their siderophore receptor genes, notably within fecR, fecA, fiu, and cirA. Structural modelling predicted deleterious effects for mutations such as fecR:G104S and fecA:A190T. Additionally, porin loss and loop 3 insertions (e.g., GD/TD) in OmpK36, as well as OmpK35 truncations, were more frequent in the resistant isolates, particularly in high-risk clones such as ST395 and ST512. Genes associated with toxin–antitoxin systems (chpB2, pemI) and a hypothetical metalloprotease (group_2577) were uniquely found in the resistant group. Conclusions: Cefiderocol resistance in CPE appears to be multifactorial. NDM-type metallo-β-lactamases and missense mutations in siderophore uptake systems—especially in those encoded by fec, fhu, and cir operons—play a central role. These may be further potentiated by alterations in membrane permeability, such as porin disruption and efflux deregulation. The integration of genomic and structural approaches provides valuable insights into emerging resistance mechanisms and may support the development of diagnostic tools and therapeutic strategies. Full article

(This article belongs to the Special Issue Carbapenem-Resistant Enterobacteriaceae: Epidemiology, Detection and Treatment)

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Graphical abstract

19 pages, 1127 KiB

Open AccessReview

Antibiotic Treatment vs. Non-Antibiotic Treatment in Bovine Clinical Mastitis During Lactation with Mild and Moderate Severity

by Franziska Nankemann, Stefanie Leimbach, Julia Nitz, Anne Tellen, Nicole Wente, Yanchao Zhang, Doris Klocke, Isabel Krebs, Stephanie Müller, Sabrina Teich, Jensine Wilm, Pauline Katthöfer, Jan Kortstegge and Volker Krömker

Antibiotics 2025, 14(7), 702; https://doi.org/10.3390/antibiotics14070702 (registering DOI) - 12 Jul 2025

Abstract

Background/Objectives: This review aimed to compare the efficacy of antibiotic treatment vs. non-antibiotic treatment in mild and moderate clinical mastitis in lactating dairy cows, categorized by the causative pathogen. Methods: The initial systematic review plan, which resulted in only four relevant articles, was [...] Read more.

Background/Objectives: This review aimed to compare the efficacy of antibiotic treatment vs. non-antibiotic treatment in mild and moderate clinical mastitis in lactating dairy cows, categorized by the causative pathogen. Methods: The initial systematic review plan, which resulted in only four relevant articles, was altered due to limited available studies and significant heterogeneity among them. Consequently, five additional articles, closely meeting our criteria with minor differences, were included to ensure comprehensive analysis, resulting in nine included articles. Due to these pragmatic constraints, this review represents a hybrid between a systematic and a narrative review. The outcome of interest was the bacteriological cure (BC). Results: The findings revealed that antibiotic treatment resulted in improved BC rates for cases caused by Streptococci. For cases caused by Escherichia (E.) coli, antibiotic therapy showed no significant improvement in BC rates compared to non-antibiotic treatment, suggesting that antibiotics may be often unnecessary for these cases due to self-limiting tendencies. However, severe E. coli mastitis warrants systemic antibiotic treatment due to potentially life-threatening complications. Klebsiella spp. mastitis showed better cure rates with antibiotic therapy. Conclusions: This study underscores the importance of regular pathogen diagnostics to guide appropriate treatment, advocating for the use of on-farm rapid tests to reduce unnecessary antibiotic use while ensuring effective treatment outcomes. Full article

(This article belongs to the Special Issue Evidence in Antibiotic Mastitis Therapy)

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14 pages, 355 KiB

Open AccessArticle

Distribution and Determinants of Antibiotic Self-Medication: A Cross-Sectional Study in Chinese Residents

by Guo Huang, Pu Ge, Mengyun Sui, He Zhu, Sheng Han and Luwen Shi

Antibiotics 2025, 14(7), 701; https://doi.org/10.3390/antibiotics14070701 (registering DOI) - 12 Jul 2025

Abstract

Antimicrobial resistance (AMR) represents a critical global health threat, with inappropriate antibiotic self-medication (ASM) being a key contributor. China—as the world’s largest antibiotic consumer—faces significant challenges despite regulatory efforts, compounded by limited contemporary data during the COVID-19 pandemic. A nationwide cross-sectional study was [...] Read more.

Antimicrobial resistance (AMR) represents a critical global health threat, with inappropriate antibiotic self-medication (ASM) being a key contributor. China—as the world’s largest antibiotic consumer—faces significant challenges despite regulatory efforts, compounded by limited contemporary data during the COVID-19 pandemic. A nationwide cross-sectional study was conducted using the 2021 China Family Health Index Survey (n = 11,031 participants across 120 cities). Trained investigators administered face-to-face questionnaires assessing ASM practices, decision-making factors, and sociodemographic characteristics. Multivariate logistic regression identified determinants of ASM. Overall, ASM prevalence was 33.7% (n = 3717), with no urban-rural difference (p > 0.05). Physician advice (78.2%), drug safety (67.1%), and efficacy (64.2%) were primary selection criteria; rural residents prioritized drug price and salesperson recommendations more than their urban counterparts (p < 0.01). Key predictors included higher ASM odds among females (OR = 1.30, 95%CI:1.18–1.43), middle-aged adults (46–59 years; OR = 1.20, 95%CI:1.02–1.42), those with health insurance (resident: OR = 1.33; commercial: OR = 1.62), and individuals with drinking histories (OR = 1.20, 95%CI:1.10–1.31). Lower odds were associated with primary education (OR = 0.69, 95%CI:0.58–0.81), unemployment (OR = 0.88, 95%CI:0.79–0.98), and absence of chronic diseases (OR = 0.56, 95%CI:0.47–0.67). One-third of Chinese residents engaged in ASM during the pandemic, driven by intersecting demographic and behavioral factors. Despite converging urban-rural prevalence rates, distinct decision-making drivers necessitate context-specific interventions, including strengthened pharmacy regulation in rural areas, tailored education programs for high-risk groups, and insurance system reforms to disincentivize self-medication. Full article

(This article belongs to the Special Issue Antibiotic Use in the Communities—2nd Edition)

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14 pages, 258 KiB

Open AccessArticle

Evaluation of Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae in an Intensive Care Unit: A Retrospective Study

by Elif Kerimoglu, Tuba Catak and Anil Kilinc

Antibiotics 2025, 14(7), 700; https://doi.org/10.3390/antibiotics14070700 (registering DOI) - 12 Jul 2025

Abstract

Objectives: Carbapenem-resistant Gram-negative bacteria (CR-GNB) infections in intensive care units (ICUs) are increasingly prevalent and associated with high mortality. This study aimed to investigate the distribution of isolated bacteria and determine the factors associated with mortality among ICU patients diagnosed with CR-GNB infections. [...] Read more.

Objectives: Carbapenem-resistant Gram-negative bacteria (CR-GNB) infections in intensive care units (ICUs) are increasingly prevalent and associated with high mortality. This study aimed to investigate the distribution of isolated bacteria and determine the factors associated with mortality among ICU patients diagnosed with CR-GNB infections. Methods: This retrospective study included 95 patients admitted to the ICU between February 2022 and July 2024 who were diagnosed with CR-GNB infections via culture and initiated on treatment. Thirty-day mortality was defined as the clinical outcome, and patients were divided into two groups: survivors (Group 1, n = 42) and deceased (Group 2, n = 53). Demographic, clinical, laboratory, and microbiological data were analyzed. Results: Advanced age, the presence of malignancy, an elevated Charlson Comorbidity Index (CCI), lower platelet counts, and higher C-reactive protein (CRP) levels were significantly associated with mortality (p < 0.05). Trauma-related admissions were more common among survivors, while sepsis-related admissions predominated among non-survivors. No statistically significant associations were observed between antibiotic regimen type and mortality. Culture-based pathogen distribution revealed A. baumannii as the predominant organism in respiratory samples, while K. pneumoniae was more frequently isolated from bloodstream and urinary specimens. Conclusions: Mortality in ICU patients with CR-GNB infections is influenced by both baseline comorbidities and infection-related inflammatory markers. This study provides region-specific insights from a high-resistance ICU setting and may inform risk stratification, prognostication, and management strategies in critically ill patients with CR-GNB infections. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

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16 pages, 422 KiB

Open AccessArticle

Antimicrobial Peptides SET-M33L and SET-M33L-PEG Are Promising Agents Against Strong Biofilm-Forming P. aeruginosa, Including Multidrug-Resistant Isolates

by Alessio Fontanot, Peter D. Croughs, Clelia Cortese, Adrianus C. J. M. de Bruijn, Chiara Falciani, Alessandro Pini, Isabella Ellinger, Wendy W. J. Unger and John P. Hays

Antibiotics 2025, 14(7), 699; https://doi.org/10.3390/antibiotics14070699 - 11 Jul 2025

Abstract

Background: The antimicrobial peptides (AMPs) SET-M33L and SET-M33L-PEG were investigated against 10 clinical isolates of P. aeruginosa. Methods: Their minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), and minimum biofilm inhibitory concentrations (MBICs) were evaluated against tobramycin, ceftazidime, and polymyxin [...] Read more.

Background: The antimicrobial peptides (AMPs) SET-M33L and SET-M33L-PEG were investigated against 10 clinical isolates of P. aeruginosa. Methods: Their minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), and minimum biofilm inhibitory concentrations (MBICs) were evaluated against tobramycin, ceftazidime, and polymyxin B. Results: MICs and MBCs were 7- to 100-fold lower than tobramycin, and 10- to 300-fold lower than ceftazidime. Fractional inhibitory concentration (FIC) indices showed an additive effect, while fractional bactericidal concentration (FBC) indices showed synergistic effects (FBC < 0.5) for most isolates. Conclusion: SET-M33L and SET-M33L-PEG are promising antimicrobial agents against strong biofilm-forming P. aeruginosa, including MDR isolates. Full article

(This article belongs to the Special Issue Bioactive Peptides and Their Antibiotic Activity)

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12 pages, 1374 KiB

Open AccessArticle

Halicin: A New Approach to Antibacterial Therapy, a Promising Avenue for the Post-Antibiotic Era

by Imane El Belghiti, Omayma Hammani, Fatima Moustaoui, Mohamed Aghrouch, Zohra Lemkhente, Fatima Boubrik and Ahmed Belmouden

Antibiotics 2025, 14(7), 698; https://doi.org/10.3390/antibiotics14070698 - 11 Jul 2025

Abstract

Background: The global spread of antibiotic-resistant bacteria presents a major public health challenge and necessitates the development of innovative antimicrobial agents. Artificial intelligence (AI)-driven drug discovery has recently enabled the repurposing of existing compounds with novel therapeutic potential. Halicin, originally developed as an [...] Read more.

Background: The global spread of antibiotic-resistant bacteria presents a major public health challenge and necessitates the development of innovative antimicrobial agents. Artificial intelligence (AI)-driven drug discovery has recently enabled the repurposing of existing compounds with novel therapeutic potential. Halicin, originally developed as an anti-diabetic molecule, has been identified through AI screening as a promising antibiotic candidate due to its broad-spectrum activity, including efficacy against multidrug-resistant pathogens. Methods: In this study, the antibacterial activity of halicin was evaluated against a range of clinically relevant multidrug-resistant bacterial strains. Bacterial isolates were first characterized using the agar disk diffusion method with a panel of 22 conventional antibiotics to confirm resistance profiles. The minimum inhibitory concentration (MIC) of halicin was then determined for selected isolates, including Escherichia coli ATCC^® 25922™ and Staphylococcus aureus ATCC^® 29213™, using broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Halicin demonstrated notable antibacterial activity, with MIC values of 16 μg/mL and 32 μg/mL against E. coli ATCC^® 25922™ and S. aureus ATCC^® 29213™, respectively. A dose-dependent inhibition of bacterial growth was observed for the majority of tested isolates, except for Pseudomonas aeruginosa, which exhibited intrinsic resistance. This lack of susceptibility is likely related to reduced outer membrane permeability, limiting the intracellular accumulation of halicin. Conclusions: Our findings support the potential of halicin as a novel antimicrobial agent for the treatment of infections caused by antibiotic-resistant bacteria. However, further investigations, including pharmacokinetic, pharmacodynamic, and toxicity studies, are essential to assess its clinical safety and therapeutic applicability. Full article

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32 pages, 2172 KiB

Open AccessReview

Multifaceted Biological Properties of Verbascoside/Acteoside: Antimicrobial, Cytotoxic, Anti-Inflammatory, and Immunomodulatory Effects

by Mirjana Marčetić, Biljana Bufan, Milica Drobac, Jelena Antić Stanković, Nevena Arsenović Ranin, Marina T. Milenković and Dragana D. Božić

Antibiotics 2025, 14(7), 697; https://doi.org/10.3390/antibiotics14070697 - 11 Jul 2025

Abstract

Verbascoside is a polyphenolic compound that belongs to the phenylethanoid glucosides. It occurs in more than 220 plant species. The species with high content of this compound are used in folk medicine, and in modern phytotherapy, mostly based on its recognized anti-inflammatory and [...] Read more.

Verbascoside is a polyphenolic compound that belongs to the phenylethanoid glucosides. It occurs in more than 220 plant species. The species with high content of this compound are used in folk medicine, and in modern phytotherapy, mostly based on its recognized anti-inflammatory and antimicrobial effects. Studies conducted so far confirmed these effects, and also pointed to others (i.e., anti-cancer, neuro-, cardio-, hepato-, and nephro-protective). This review presents data on the chemistry, occurrence, and biosynthesis of verbascoside. Additionally, it focuses on the cytotoxic, antimicrobial, anti-inflammatory, and immunomodulatory effects, as well as the main cellular and molecular mechanisms of its action. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)

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13 pages, 233 KiB

Open AccessArticle

Policy Makers’ Perceptions on Implementation of National Action Plans on Antimicrobial Resistance in South Africa and Eswatini Using Coordination, Accountability, Resourcing, Regulation and Ownership Framework (2018–2019)

by Kholiwe Shabangu, Sabiha Yusuf Essack and Sinegugu Evidence Duma

Antibiotics 2025, 14(7), 696; https://doi.org/10.3390/antibiotics14070696 - 11 Jul 2025

Abstract

Background: Antimicrobial resistance (AMR) is a global threat that affects humans, animals, plants, the environment, societies, and economies—requiring urgent coordinated action. In May 2015, the World Health Assembly (WHA) adopted the Global Action Plan (GAP) on AMR, urging member states to develop [...] Read more.

Background: Antimicrobial resistance (AMR) is a global threat that affects humans, animals, plants, the environment, societies, and economies—requiring urgent coordinated action. In May 2015, the World Health Assembly (WHA) adopted the Global Action Plan (GAP) on AMR, urging member states to develop and implement their own National Action Plans (NAPs) using a One Health approach. Objective: Both South Africa and Eswatini have developed NAPs and are currently in the implementation phase. However, no study has explored policymakers’ perceptions regarding NAP implementation particularly concerning coordination, accountability, resourcing, regulation and ownership. Methods: This qualitative study employed a narrative approach to explore these perceptions in South Africa and Eswatini. A total of 36 key informants were recruited using purposive and snowball sampling methods. Data was collected between November 2018 and March 2019 and transcribed verbatim. Results: Findings revealed that while governance structures for implementing NAPs exist in South Africa and Eswatini, several critical areas require urgent attention. These include limited accountability across One Health sectors, the absence of dedicated national budgets for NAP implementation, poor intra- and inter- ministerial coordination, weak medicine regulation and enforcement, and delayed multisectoral ownership of the NAPs. Conclusions: To address AMR effectively, both countries must allocate dedicated budgets, improve multisectoral integration, and strengthen regulatory frameworks regarding antimicrobial access and use across all One Health sectors. A firm commitment from all sectors is required—not just formal endorsement of the NAPs—to ensure sustainable implementation and ownership. Full article

(This article belongs to the Special Issue A One Health Approach to Antimicrobial Resistance, 2nd Edition)

13 pages, 590 KiB

Open AccessReview

Potential Shifts in the Oral Microbiome Induced by Bariatric Surgery—A Scoping Review

by Zuzanna Ślebioda, Hélène Rangé, Marta Strózik-Wieczorek and Marzena Liliana Wyganowska

Antibiotics 2025, 14(7), 695; https://doi.org/10.3390/antibiotics14070695 - 10 Jul 2025

Abstract

Background: The oral microbiome differs in obese patients compared to normal-weight subjects. Microbiologic shifts very often appear after surgical interventions such as bariatric surgery (BS) and in immunocompromised patients. However, the oral microbiome composition and load in subjects after bariatric surgery are [...] Read more.

Background: The oral microbiome differs in obese patients compared to normal-weight subjects. Microbiologic shifts very often appear after surgical interventions such as bariatric surgery (BS) and in immunocompromised patients. However, the oral microbiome composition and load in subjects after bariatric surgery are unclear. Aim: The aim of this review is to summarize the current state of the art related to the oral microbiome shift induced by bariatric surgery and to discuss its implications on oral cavity health. Methods: Electronic databases: PubMed/Medline, Web of Science, and Cochrane Library were searched for articles published up to March 30, 2025, describing prospective studies focused on changes in the oral microbiota of patients who underwent bariatric surgery. Results: Eight studies measuring the oral microbiome with different approaches—16S ribosomal RNA (16S rRNA) sequencing, polymerase chain reaction (PCR), culture, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI TOF MS)—were included in this review. The following bariatric techniques were used: sleeve gastrectomy, Roux-en-Y gastric bypass, Omega loop gastric bypass, and laparoscopic gastric plication. The follow-up period ranged from 3 to 12 months. The results of microbiologic studies were unequivocal. There was an increment in Streptococcus mutans reported, high levels of Candida species, and increased rates of some periodontitis-associated bacteria (Porphyromonas gingivalis) in the post-bariatric surgery period, though some studies suggested a shift towards non-pathogenic composition of the oral microbiome in prospective observations. Conclusions: The local oral microbial homeostasis becomes strongly impacted by the bariatric surgical treatment itself as well as its consequences in the further post-operative period. Therefore, obese patients undergoing BS require very careful dental observation. Full article

(This article belongs to the Special Issue Periodontal Bacteria and Periodontitis: Infections and Therapy)

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6 pages, 189 KiB

Open AccessEditorial

Combating the Growing Threat of Acinetobacter baumannii Resistance

by Eduarda Kffuri Goncalves, William Frank Penwell and Steven Eugene Fiester

Antibiotics 2025, 14(7), 694; https://doi.org/10.3390/antibiotics14070694 - 9 Jul 2025

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Abstract

Antimicrobial resistance remains one of the most urgent and complex challenges facing global public health in the 21st century [...] Full article

(This article belongs to the Special Issue Antibiotic Resistance in Acinetobacter and Associated Treatment Strategies)

12 pages, 836 KiB

Open AccessArticle

Antimicrobial Resistance Patterns of Staphylococcus aureus Cultured from the Healthy Horses’ Nostrils Sampled in Distant Regions of Brazil

by Mauro M. S. Saraiva, Heitor Leocádio de Souza Rodrigues, Valdinete Pereira Benevides, Candice Maria Cardoso Gomes de Leon, Silvana C. L. Santos, Danilo T. Stipp, Patricia E. N. Givisiez, Rafael F. C. Vieira and Celso J. B. Oliveira

Antibiotics 2025, 14(7), 693; https://doi.org/10.3390/antibiotics14070693 - 9 Jul 2025

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Abstract

Staphylococcus aureus (S. aureus) is a major cause of opportunistic infections in humans and animals, leading to severe systemic diseases. The rise of MDR strains associated with animal carriage poses significant health challenges, underscoring the need to investigate animal-derived S. aureus [...] Read more.

Staphylococcus aureus (S. aureus) is a major cause of opportunistic infections in humans and animals, leading to severe systemic diseases. The rise of MDR strains associated with animal carriage poses significant health challenges, underscoring the need to investigate animal-derived S. aureus. Objectives: This study examined the genotypic relatedness and phenotypic profiles of antimicrobial resistance in S. aureus, previously sampled from nostril swabs of healthy horses from two geographically distant Brazilian states (Northeast and South), separated by over 3700 km. The study also sought to confirm the presence of methicillin-resistant (MRSA) and borderline oxacillin-resistant (BORSA) strains and to characterize the isolates through molecular typing using PCR. Methods: Among 123 screened staphylococci, 21 isolates were confirmed as S. aureus via biochemical tests and PCR targeting species-specific genes (femA, nuc, coa). Results: REP-PCR analysis generated genotypic profiles, revealing four antimicrobial resistance patterns, with MDR observed in ten isolates. Six isolates exhibited cefoxitin resistance, suggesting methicillin resistance, despite the absence of the mecA gene. REP-PCR demonstrated high discriminatory power, grouping the isolates into five major clusters. Conclusions: The genotyping indicated no clustering by geographical origin, highlighting significant genetic diversity among S. aureus strains colonizing horses’ nostrils in Brazil. These findings highlight the widespread and varied nature of S. aureus among horses, contributing to a deeper understanding of its epidemiology and resistance profiles in animals across diverse regions. Ultimately, this genetic diversity can pose a public health risk that the epidemiological surveillance services must investigate. Full article

(This article belongs to the Collection Staphylococcus— Molecular Pathogenesis, Virulence Regulation and Antibiotics Resistance)

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25 pages, 1759 KiB

Open AccessReview

Harnessing the Potential of Antibacterial and Antibiofilm Phytochemicals in the Combat Against Superbugs: A One Health Perspective

by Suma Sarojini, Saranya Jayaram, Sandhya Kalathilparambil Santhosh, Pragyan Priyadarshini, Manikantan Pappuswamy and Balamuralikrishnan Balasubramanian

Antibiotics 2025, 14(7), 692; https://doi.org/10.3390/antibiotics14070692 - 9 Jul 2025

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Abstract

The war between humans and bacteria started centuries ago. With the advent of antibiotics, there was a temporary ceasefire in this war, but the scenario soon started becoming worse with the emergence of drug-resistant strains within years of the deployment of antibiotics in [...] Read more.

The war between humans and bacteria started centuries ago. With the advent of antibiotics, there was a temporary ceasefire in this war, but the scenario soon started becoming worse with the emergence of drug-resistant strains within years of the deployment of antibiotics in the market. With the surge in the misuse of antibiotics, there was a drastic increase in the number of multidrug-resistant (MDR) and extensively drug-resistant bacterial strains, even to antibiotics like Methicillin and vancomycin, aggravating the healthcare scenario. The threat of MDR ESKAPE pathogens is particularly high in nosocomial infections, where biofilms formed by bacteria create a protective barrier that makes them highly resistant to antibiotics, complicating the treatment efforts. Scientists are looking at natural and sustainable solutions, as several studies have projected deaths contributed by drug-resistant bacteria to go beyond 50 million by 2050. Many plant-derived metabolites have shown excellent antibacterial and antibiofilm properties that can be tapped for combating superbugs. The present review explores the current status of various studies on antibacterial plant metabolites like alkaloids and flavonoids and their mechanisms in disrupting biofilms and killing bacteria by way of inhibiting key survival strategies of bacteria like motility, quorum-sensing, reactive oxygen species production, and adhesion. These mechanisms were found to be varied in Gram-positive, Gram-negative, and acid-fast bacteria like Mycobacterium tuberculosis, which will be discussed in detail. The successful tapping of the benefits of such plant-derived chemicals in combination with evolving techniques of nanotechnology and targeted drug delivery can go a long way in achieving the goal of One Health, which advocates the unity of multiple practices for the optimal health of people, animals, and the environment. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens)

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11 pages, 2796 KiB

Open AccessArticle

In Vitro and Ex Vivo Evaluation of Rifampicin Cytotoxicity in Human Skin Models

by Marcel Nani Leite, Natália Aparecida de Paula, Leandra Náira Zambelli Ramalho and Marco Andrey Cipriani Frade

Antibiotics 2025, 14(7), 691; https://doi.org/10.3390/antibiotics14070691 - 8 Jul 2025

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Abstract

Background/Objectives: Drugs for human use require several studies for the assessment of their efficacy and safety. An important property is cytotoxicity, which should be tested in different environments and models in closer proximity to the final use of the drug, with greater [...] Read more.

Background/Objectives: Drugs for human use require several studies for the assessment of their efficacy and safety. An important property is cytotoxicity, which should be tested in different environments and models in closer proximity to the final use of the drug, with greater reliability. Thus, we proposed to evaluate the toxicity of rifampicin, the only bactericidal drug in the anti-leprosy multidrug therapy, using skin cells and skin explant cultures. Methods: Cell viability was tested by the MTT method using primary keratinocytes and fibroblasts and immortalized skin cells (HaCaT and 3T3) at 24, 48, and 72 h of treatment. For the skin explant, we used the TTC assay to determine viability (24, 48, 72, and 96 h), hematoxylin and eosin staining to analyze the structure and architecture of the tissue, and TUNEL to assess apoptotic cells at 3, 6, 12, 24, 48, 72, and 96 h. Results: Regarding the toxicity of primary and immortalized cells, viability was above 70% up to a concentration of 50 μg/mL at 24, 48, and 72 h, and at the concentration of 200 μg/mL, all cells showed greater sensitivity, especially at 72 h. Tissue viability analysis revealed a high percentage (above 96%) of viable tissue at the concentrations of 100, 150, and 200 μg/mL at the time points studied. Histological analysis showed that tissue architecture was maintained, with no apoptotic cells being observed. Conclusions: Thus, our results showed the importance of evaluating drug toxicity using different cell types, with the ex vivo skin model proving to be an alternative to animal use. Full article

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2 pages, 365 KiB

Open AccessCorrection

Correction: Alshawwa et al. In Situ Biosynthesis of Reduced Alpha Hematite (α-Fe₂O₃) Nanoparticles by Stevia Rebaudiana L. Leaf Extract: Insights into Antioxidant, Antimicrobial, and Anticancer Properties. Antibiotics 2022, 11, 1252

by Samar Zuhair Alshawwa, Eman J. Mohammed, Nada Hashim, Mohamed Sharaf, Samy Selim, Hayaa M. Alhuthali, Hind A. Alzahrani, Alsayed E. Mekky and Mohamed G. Elharrif

Antibiotics 2025, 14(7), 690; https://doi.org/10.3390/antibiotics14070690 - 8 Jul 2025

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Abstract

In the original publication [...] Full article

23 pages, 3213 KiB

Open AccessArticle

Multidrug Resistance and Virulence Traits of Salmonella enterica Isolated from Cattle: Genotypic and Phenotypic Insights

by Nada A. Fahmy, Sumin Karna, Angel Bhusal, Ajran Kabir, Erdal Erol and Yosra A. Helmy

Antibiotics 2025, 14(7), 689; https://doi.org/10.3390/antibiotics14070689 - 8 Jul 2025

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Abstract

Background/Objective: Non-typhoidal Salmonella is a leading cause of foodborne illness worldwide and presents a significant One Health concern due to zoonotic transmission. Although antibiotic therapy remains a standard approach for treating salmonellosis in severe cases in animals, the widespread misuse of antibiotics has [...] Read more.

Background/Objective: Non-typhoidal Salmonella is a leading cause of foodborne illness worldwide and presents a significant One Health concern due to zoonotic transmission. Although antibiotic therapy remains a standard approach for treating salmonellosis in severe cases in animals, the widespread misuse of antibiotics has contributed to the emergence of multidrug-resistant (MDR) Salmonella strains. This study provides insights into the genotypic and phenotypic characteristics among Salmonella isolates from necropsied cattle. Methods: A total of 1008 samples were collected from necropsied cattle. Salmonella enterica subspecies were identified by MALDI-TOF MS and subsequently confirmed by serotyping. The biofilm-forming ability of the isolated bacteria was assessed using a crystal violet assay. The motility of the isolates was assessed on soft agar plates. Additionally, the antimicrobial resistance genes (ARGs) and virulence genes were investigated. Antimicrobial resistance patterns were investigated against 19 antibiotics representing 9 different classes. Results:Salmonella species were isolated and identified in 27 necropsied cattle. Salmonella Dublin was the most prevalent serotype (29.6%). Additionally, all the isolates were biofilm producers at different levels of intensity, and 96.3% of the isolates exhibited both swarming and swimming motility. Furthermore, virulence genes, including invA, hilA, fimA, and csgA, were detected in all the isolates. The highest resistance was observed to macrolides (azithromycin and clindamycin) (100%), followed by imipenem (92.6%), and chloramphenicol (85.2%). All isolates were multidrug-resistant, with a multiple antibiotic resistance (MAR) index ranging between 0.32 and 0.74. The aminoglycoside resistance gene aac(6′)-Ib was detected in all the isolates (100%), whereas the distribution of other antimicrobial resistance genes (ARGs) varied among the isolates. Conclusions: The increasing prevalence of MDR Salmonella poses a significant public health risk. These resistant strains can reduce the effectiveness of standard treatments and elevate outbreak risks. Strengthening surveillance and regulating antibiotic use in livestock are essential to mitigating these threats. Full article

(This article belongs to the Special Issue Genomic Characterization of Antimicrobial Resistance and Evolution Mechanism of Bacteria)

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6 pages, 184 KiB

Open AccessBrief Report

Assessing Clinical Outcomes of Metronidazole for Intra-Abdominal Infections When Dosed Every 12 h Versus Every 8 h in a Multi-Center Health System

by Sarah Galante, Ramya Castillo, Todd Price, MaiCuc Tran and Stefanie Stramel-Stafford

Antibiotics 2025, 14(7), 688; https://doi.org/10.3390/antibiotics14070688 - 8 Jul 2025

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Abstract

Background: Metronidazole is the preferred anaerobic agent for empiric treatment of intra-abdominal infections (IAI). Although dosed every 8 h (q8hr), blood concentrations exceed the in vitro minimum inhibitory concentration (MIC) for anaerobic organisms at 12 h (q12hr). A drug shortage of intravenous [...] Read more.

Background: Metronidazole is the preferred anaerobic agent for empiric treatment of intra-abdominal infections (IAI). Although dosed every 8 h (q8hr), blood concentrations exceed the in vitro minimum inhibitory concentration (MIC) for anaerobic organisms at 12 h (q12hr). A drug shortage of intravenous (IV) metronidazole prompted the conversion to every 12 h dosing in qualifying patients treated for IAI. Objective: To determine efficacy outcomes of metronidazole dosed every 12 h versus every 8 h in patients treated for IAI. Methods: This was a multi-center, retrospective, cohort study of 201 patients from January to July 2021 (q8hr) and January to November 2023 (q12hr) at five hospitals through the greater Houston area. Included patients were adults with a diagnosis of IAI confirmed by radiographic evidence and a white blood count (WBC) > 12,000 cells/µL and/or temperature > 100.4 °F at the time of diagnosis. The primary outcome was clinical cure of IAI, defined as resolution of signs/symptoms of IAI and normalization of WBC or temperature. Results: A total of 201 patients were included, 103 patients in the q8hr group and 98 patients in the q12hr group. Clinical cure of IAI occurred in 72 patients (69.9%) in the q8hr group and 62 patients (63.2%) in the q12hr group (p = 0.318). The median duration of therapy days was similar for both groups (4.0 [4.0–6.0] vs. 4.0 [3.0–6.0] (p = 0.509)). The frequency of clinical failure was higher in the q12hr group (8.7% vs. 21.4%; p = 0.01). Seven patients in the q8hr group and fourteen patients in the q12hr group required escalation of antibiotics due to the need for broader-spectrum antimicrobial therapy by clinical failure definition. Conclusions: There was no difference in clinical cure of IAI with an extended dosing interval. Clinical failure and escalation in antibiotics was higher in the q12h group due to the need for broader-spectrum gram-negative coverage and not related to the need for anaerobic coverage. Findings suggest that every 12 h dosing has similar outcomes. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

11 pages, 392 KiB

Open AccessArticle

Should Microhematuria Be Incorporated into the 2023 Duke-International Society for Cardiovascular Infectious Diseases Minor Immunological Criteria?

by Jean Regina, Louis Stavart, Benoit Guery, Georgios Tzimas, Pierre Monney, Lars Niclauss, Matthias Kirsch, Dela Golshayan and Matthaios Papadimitriou-Olivgeris

Antibiotics 2025, 14(7), 687; https://doi.org/10.3390/antibiotics14070687 - 7 Jul 2025

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Abstract

Background/Objectives: Microhematuria is common in patients with infective endocarditis (IE). The present study aims to assess whether the addition of microhematuria in the 2023 Duke-International Society for Cardiovascular Infectious Diseases (ISCVID) minor immunological criteria could enhance its diagnostic performance. Methods: This [...] Read more.

Background/Objectives: Microhematuria is common in patients with infective endocarditis (IE). The present study aims to assess whether the addition of microhematuria in the 2023 Duke-International Society for Cardiovascular Infectious Diseases (ISCVID) minor immunological criteria could enhance its diagnostic performance. Methods: This retrospective study was conducted at the Lausanne University Hospital, Switzerland (2014–2024). All patients with suspected IE and urinalysis within 24 h from presentation were included. The Endocarditis Team classified episodes as IE or non-IE. Microhematuria was defined as >5 red blood cells per high power field (HPF). Results: Among 801 episodes with suspected IE, 263 (33%) were diagnosed with IE. Microhematuria (>5/HPF) was present in 462 (58%) episodes, with no difference between episodes with and without confirmed IE (61% versus 56%; p = 0.223). Based on the 2023 ISCVID-Duke, minor immunological criteria were present in 42 episodes (5%). By adding microhematuria, 473 (59%) episodes met the minor immunological criteria. Sensitivity of the clinical criteria of the 2023 ISCVID-Duke version without and with hematuria was calculated at 75% (69–80%) and 86% (81–90%), respectively. Specificity was at 52% (48–57%) and 40% (36–45%), respectively. Among episodes with suspected IE, microhematuria was associated with female sex, enterococcal bacteremia, sepsis or septic shock, acute kidney injury, non-cerebral embolic events, and bone and joint infection. Conclusions: Microhematuria was frequent among patients with suspected IE, but it was not associated with the diagnosis of IE. The addition of microhematuria in the 2023 ISCVID-Duke minor immunological criteria did not enhance the overall performance of the criteria. Full article

(This article belongs to the Special Issue Advances in Infective Endocarditis Research: From Bench to Bedside)

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15 pages, 1325 KiB

Open AccessArticle

Comparative Effects of Intermittent vs. Constant Ceftiofur Hydrochloride Exposure on Staphylococcus aureus In Vitro

by Junli Wang, Chongyang Li, Fanxi Guo and Zugong Yu

Antibiotics 2025, 14(7), 686; https://doi.org/10.3390/antibiotics14070686 - 6 Jul 2025

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Abstract

Background/Objectives: Ceftiofur hydrochloride (CEF) is a third-generation cephalosporin widely used in cattle to treat various disease. The recommended dosage was 1.1 to 2.2 mg/kg BW for 3 to 5 consecutive days by intramuscular or subcutaneous injection. Incomplete treatment, overuse, or misuse, often observed [...] Read more.

Background/Objectives: Ceftiofur hydrochloride (CEF) is a third-generation cephalosporin widely used in cattle to treat various disease. The recommended dosage was 1.1 to 2.2 mg/kg BW for 3 to 5 consecutive days by intramuscular or subcutaneous injection. Incomplete treatment, overuse, or misuse, often observed in clinical practice, are major contributors to resistance development. This study aims to explore how different concentrations, durations, and dosing frequencies affect susceptibility and bactericidal efficacy of Staphylococcus aureus to optimize CEF dosage regimens. Methods: First, CEF was intermittently administered at 1/2 × minimum inhibitory concentration (MIC), 2 × MIC, 6 × MIC, and 100 × MIC for 30 cycles. Second, CEF was continuously administered for 48, 72, 96, 120, 144, and 168 h. Bacterial susceptibility, regrowth, survival rate, and the emergence of persisters or tolerant phenotypes were assessed. Genetic mutations were identified by whole-genome resequencing. Membrane permeability, integrity, and efflux pump activity were analyzed to elucidate the mechanism of CEF. Results: After 30 cycles, the MIC increased eight-fold in the 2 × MIC group. No significant MIC increase was found in other groups, but a progression from susceptibility to persistence and then to tolerance was observed in the 100 × MIC intermittent group. The survival rate increased both in the 2 × MIC and 100 × MIC groups. With continuous exposure to ≥6 × MIC over 120 h, strains were completely eradicated without MIC increase. Resistance-associated single-nucleotide polymorphism (SNP) mutations were detected only in strains of the 2 × MIC and 100 × MIC intermittent groups. CEF altered the membrane hydrophobicity, damaging membrane integrity after 30 cycles. Conclusions: These findings suggest that high-dose, prolonged exposure is more effective for eliminating Staphylococcus aureus and avoiding resistance, whereas intermittent dosing may promote persistence, tolerance, and resistance evolution. Full article

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17 pages, 1703 KiB

Open AccessArticle

Canine Pyoderma and Otitis Externa: A Retrospective Analysis of Multidrug-Resistant Bacterial Carriage in Hong Kong

by Wing Yu Chan, Stefan Hobi, Andrew Ferguson and Ibrahim Elsohaby

Antibiotics 2025, 14(7), 685; https://doi.org/10.3390/antibiotics14070685 - 6 Jul 2025

Viewed by 291

Abstract

Background: Canine pyoderma and otitis externa are prevalent bacterial skin infections in veterinary practice, frequently complicated by the emergence of multidrug-resistant (MDR) pathogens. Objectives: To investigate the frequency, antimicrobial resistance (AMR) profiles, and frequency of MDR bacterial isolates from dogs with pyoderma [...] Read more.

Background: Canine pyoderma and otitis externa are prevalent bacterial skin infections in veterinary practice, frequently complicated by the emergence of multidrug-resistant (MDR) pathogens. Objectives: To investigate the frequency, antimicrobial resistance (AMR) profiles, and frequency of MDR bacterial isolates from dogs with pyoderma or otitis externa in Hong Kong. Methods: A retrospective study of bacterial isolates from 215 clinical samples collected from dogs presenting with pyoderma (n = 63) or otitis externa (n = 152) at veterinary clinics across Hong Kong between 2018 and 2022. Bacterial isolates were identified and subjected to antimicrobial susceptibility testing against 13 antimicrobial classes. Results: Staphylococcus spp., particularly S. pseudintermedius, were the most commonly isolated species, followed by Pseudomonas spp. and Proteus spp. High resistance rates were observed for orbifloxacin (61.3% in pyoderma; 76.7% in otitis externa), doxycycline (59.3%; 69.2%), clindamycin (62%; 68.9%), and enrofloxacin (50%; 55.5%). Most isolates were sensitive to ofloxacin, ticarcillin–clavulanate, tobramycin, ciprofloxacin, cefpodoxime, cefuroxime, and cefixime. MDR was detected in 67.5% of pyoderma and 66.8% of otitis externa isolates. Gram-negative bacteria exhibited significantly higher MDR rates than Gram-positive isolates. The multiple antibiotic resistance (MAR) index averaged 0.41 for pyoderma and 0.52 for otitis externa isolates. We found no significant associations between MDR and non-modifiable risk factors (i.e., age, sex, breed, and reproductive status). Conclusions: These findings highlight the critical need for prudent antimicrobial use and continuous surveillance of AMR trends in companion animals. A higher focus should be placed on topical antiseptic therapy, with oral antibiotics used only in exceptional cases and after susceptibility testing. From a One Health perspective, the potential transmission of MDR bacteria between companion animals and humans underscores the importance of a coordinated approach to antimicrobial stewardship across both veterinary and human medicine. Full article

(This article belongs to the Special Issue Companion Animals: Antimicrobial Resistance in Bacterial and Fungal Pathogens Associated with Skin and Ear Infections)

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21 pages, 3409 KiB

Open AccessArticle

Mapping the AMR Infection Landscape in Bihar: Implications for Strengthening Policy and Clinical Practice

by Vinay Modgil, Sundeep Sahay, Neelam Taneja, Burhanuddin Qayyumi, Ravikant Singh, Arunima Mukherjee, Bibekananda Bhoi and Gitika Arora

Antibiotics 2025, 14(7), 684; https://doi.org/10.3390/antibiotics14070684 - 5 Jul 2025

Viewed by 599

Abstract

Background: Antimicrobial resistance (AMR) poses a significant threat to public health, especially in low- and middle-income countries (LMICs), where surveillance infrastructure is underdeveloped. Bihar, India’s third most populous state and one of its least-resourced states, has remained largely absent from national AMR monitoring [...] Read more.

Background: Antimicrobial resistance (AMR) poses a significant threat to public health, especially in low- and middle-income countries (LMICs), where surveillance infrastructure is underdeveloped. Bihar, India’s third most populous state and one of its least-resourced states, has remained largely absent from national AMR monitoring initiatives. Methods: This study aimed to characterize the AMR infection landscape across five public tertiary care hospitals in Bihar over three years (2022–2024) and to assess the feasibility of integrating digital workflows for real-time microbiological reporting. Standardized antimicrobial susceptibility testing (AST) was performed on >48,000 urine, pus, and blood samples using CLSI guidelines. Facility-level data were digitized into an open-source AMR reporting system, enabling automated antibiogram generation. Results: The findings revealed substantial resistance: high resistance to beta-lactams, carbapenems, and fluoroquinolones across pathogens. For instance, E. coli sensitivity to nitrofurantoin varied from 86.5% at NMCH (Patna) to 44.7% at JLNMCH (Bhagalpur), while cephalosporin sensitivity in Klebsiella spp. dropped below 2% in several hospitals. MRSA prevalence exceeded 65% in two facilities, far above the national average of 47.8%. Digital integration led to a four-fold increase in culture testing in all facilities and improved data completeness and turnaround times. Spatial analysis and microbiology laboratory assessment revealed significant geographic disparities in diagnostic access, with facilities in remote districts facing delays of over four hours for basic testing. Conclusions: Our study is the first study from India to create such a broad, facility-associated AMR picture over time at a state level. Policy implications include the need for a state-level AMR surveillance dashboard, alignment of procurement with facility-specific resistance patterns, and routine stewardship audits. Clinically, this study demonstrates the utility of localized antibiograms for guiding empirical therapy in resource-limited settings. This study provides a scalable framework for embedding AMR surveillance into routine health system workflows in LMICs. Full article

(This article belongs to the Special Issue Antibiotic Stewardship Implementation Strategies)

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14 pages, 1012 KiB

Open AccessArticle

Outcomes of Implementing a Multidimensional Antimicrobial Stewardship Program in a Medical Ward in a Third-Level University Hospital in Northern Italy

by Maria Mazzitelli, Daniele Mengato, Gianmaria Barbato, Sara Lo Menzo, Fabio Dalla Valle, Margherita Boschetto, Paola Stano, Cristina Contessa, Daniele Donà, Vincenzo Scaglione, Giacomo Berti, Elisabetta Mariavittoria Giunco, Tiziano Martello, Francesca Venturini, Ignazio Castagliuolo, Michele Tessarin, Paolo Simioni and Annamaria Cattelan

Antibiotics 2025, 14(7), 683; https://doi.org/10.3390/antibiotics14070683 - 5 Jul 2025

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Abstract

Background/Objectives: Antimicrobial stewardship programs (ASPs) optimize antimicrobial use, improving outcomes and reducing resistance. This study assessed the impact of a ward-specific ASP. Methods: A pre/post quasi-experimental study was conducted in an internal medicine ward at a tertiary hospital in Padua, Italy. [...] Read more.

Background/Objectives: Antimicrobial stewardship programs (ASPs) optimize antimicrobial use, improving outcomes and reducing resistance. This study assessed the impact of a ward-specific ASP. Methods: A pre/post quasi-experimental study was conducted in an internal medicine ward at a tertiary hospital in Padua, Italy. During the intervention year (September 2023–August 2024), a multidisciplinary team (infectious disease consultants, pharmacists, microbiologists, nurses, and hygienists) held bi-weekly ward-based audits, reviewing antimicrobial prescriptions and performing bedside assessments. Therapy adjustments followed guidelines and local epidemiology. Educational sessions and infection prevention and control (IPC) protocols were also reinforced. Outcomes were compared to the previous year, considering patient characteristics. The primary outcome was antimicrobial consumption (DDD/100 patient days, DDD/100PD); secondary outcomes included cost savings, length of stay (LOS), and mortality. Results: Fifty audits assessed 1074 patients and 1401 antimicrobial treatments. Patient characteristics were similar. Antibiotic suspension or de-escalation occurred in 37.9% and 22% of patients, respectively. AWARE ACCESS class use increased (+17.5%), while carbapenem (−54.4%) and fluoroquinolone (−42.0%) use significantly declined (p < 0.05). IPC and microbiological culture guidance were provided in 12.1% of cases. Antimicrobial consumption dropped from 107.7 to 84.4 DDD/100PD (p < 0.05). No significant changes in LOS or mortality were observed. Antimicrobial costs fell by 48.8% (with EUR 57,100 saved). Conclusions: ASP reduced antimicrobial consumption, improved prescription quality, and cut costs without compromising patient outcomes. Multidisciplinary collaboration, audits, and education proved essential. Future studies should assess long-term resistance trends and integrate rapid diagnostics for enhanced stewardship. Full article

(This article belongs to the Special Issue Antibiotic Stewardship Implementation Strategies)

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15 pages, 695 KiB

Open AccessArticle

In Vitro Susceptibility to Imipenem/Relebactam and Comparators in a Multicentre Collection of Mycobacterium abscessus Complex Isolates

by Alejandro Seoane-Estévez, Pablo Aja-Macaya, Andrea Garcia-Pose, Paula López-Roa, Alba Ruedas-López, Verónica Gonzalez-Galán, Jaime Esteban, Jorge Arca-Suárez, Martín Pampín, Alejandro Beceiro, Marina Oviaño, Germán Bou and on behalf of the GEIM-SEIMC Study Group

Antibiotics 2025, 14(7), 682; https://doi.org/10.3390/antibiotics14070682 - 5 Jul 2025

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Abstract

Background and Objectives: Infections caused by non-tuberculous mycobacteria (NTM), including Mycobacterium abscessus complex (MABc), are increasing globally and are notoriously difficult to treat due to the intrinsic resistance of these bacteria to many common antibiotics. The aims of this study were to demonstrate [...] Read more.

Background and Objectives: Infections caused by non-tuberculous mycobacteria (NTM), including Mycobacterium abscessus complex (MABc), are increasing globally and are notoriously difficult to treat due to the intrinsic resistance of these bacteria to many common antibiotics. The aims of this study were to demonstrate the in vitro activity of imipenem/relebactam against MABc clinical isolates and to determine any in vitro synergism between imipenem/relebactam and other antimicrobials. Methods: A nationwide collection of 175 MABc clinical respiratory isolates obtained from 24 hospitals in Spain (August 2022–April 2023) was studied. Fifteen different antimicrobial agents were comprised, including imipenem/relebactam. MICs were determined according to CLSI criteria, and the synergism studies were performed with the selected clinical isolates. Results: Of the 175 isolates obtained, 110 were identified as M. abscessus subsp. abscessus (62.9%), 51 as M. abscessus subsp. massiliense (29.1%), and 14 as M. abscessus subsp. bolleti (8%). The antibiotics yielding the highest susceptibility rates were tigecycline, eravacycline, and omadacycline (100%); followed by imipenem/relebactam and clofazimine (97.6%); and finally amikacin (94.6%). Only four isolates were resistant to imipenem/relebactam, three of which were further characterized by WGS, revealing MABc mutations in Bla_Mab as well as D,D- and L,D-transpeptidades and mspA porin, which may play an important role in reduced susceptibility to imipenem/relebactam, even though none were previously described or associated with resistance to β-lactams. Conclusions: Our data demonstrate that relebactam improved the anti-MABc activity of imipenem, representing a β-lactam for the treatment of MABc infections. Furthermore, imipenem/relebactam demonstrated in vitro synergism with other anti-MABc treatments, thus supporting its use as part of dual regimens. Full article

(This article belongs to the Section Novel Antimicrobial Agents)

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10 pages, 429 KiB

Open AccessArticle

Clinical Outcomes of Escherichia coli Acute Bacterial Prostatitis: A Comparative Study of Oral Sequential Therapy with β-Lactam Versus Quinolone Antibiotics

by Laura Gisbert, Beatriz Dietl, Mariona Xercavins, Aina Mateu, María López, Ana Martínez-Urrea, Lucía Boix-Palop and Esther Calbo

Antibiotics 2025, 14(7), 681; https://doi.org/10.3390/antibiotics14070681 - 5 Jul 2025

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Abstract

Background/Objectives: Optimal management of acute bacterial prostatitis (ABP) remains uncertain, but the use of antibiotics with good prostatic tissue penetration is critical to prevent recurrence and chronic progression. This study aimed to describe clinical characteristics and outcomes of ABP due to Escherichia coli [...] Read more.

Background/Objectives: Optimal management of acute bacterial prostatitis (ABP) remains uncertain, but the use of antibiotics with good prostatic tissue penetration is critical to prevent recurrence and chronic progression. This study aimed to describe clinical characteristics and outcomes of ABP due to Escherichia coli (ABP-E.coli), compare effectiveness of sequential high-dose cefuroxime (ABP-CXM) versus ciprofloxacin (ABP-CIP), and identify risk factors for clinical failure. Methods: We conducted a retrospective study including men >18 years diagnosed with ABP-E. coli between January 2010 and November 2023 at a 400-bed hospital. Patients received oral cefuroxime (500 mg/8 h) or oral ciprofloxacin (500 mg/12 h). Outcomes over 90 days included clinical cure, recurrence and reinfection. Definitions: Clinical cure—resolution of symptoms without recurrences; recurrence—new ABP episode with the same E. coli strain; reinfection—ABP involving different microorganism or E. coli strain; clinical failure—lack of cure, recurrence, or reinfection. Results: Among 326 episodes (158 ABP-CXM, 168 ABP-CIP), ABP-CXM patients were younger (median 63.5 vs. 67.5 years, p = 0.005) and had fewer comorbidities. Clinical cure was higher in ABP-CIP (96.9% vs. 85.7%, p < 0.001). Recurrence occurred only in ABP-CXM (6.96% vs. 0%, p < 0.001), while reinfection and mortality were similar. Multivariable analysis showed ciprofloxacin was protective against clinical failure (OR: 0.16, 95% CI: 0.06–0.42, p < 0.001), while prior urinary tract infection (UTI) increased failure risk (OR: 2.87, 95% CI: 1.3–6.3). Conclusions: Ciprofloxacin was more effective than cefuroxime in treating ABP-E. coli. Patients with recent UTIs may need closer monitoring or alternative therapies. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

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14 pages, 706 KiB

Open AccessArticle

First-Line Prescriptions and Effectiveness of Helicobacter pylori Eradication Treatment in Ireland over a 10-Year Period: Data from the European Registry on Helicobacter pylori Management (Hp-EuReg)

by Sinéad M. Smith, Olga P. Nyssen, Rebecca FitzGerald, Thomas J. Butler, Deirdre McNamara, Asghar Qasim, Conor Costigan, Anna Cano-Catalá, Pablo Parra, Leticia Moreira, Francis Megraud, Colm O’Morain and Javier P. Gisbert

Antibiotics 2025, 14(7), 680; https://doi.org/10.3390/antibiotics14070680 - 5 Jul 2025

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Abstract

Background: Local audits of Helicobacter pylori (H. pylori) prescriptions and outcomes are necessary to assess guideline awareness among clinicians and treatment effectiveness. Aims: The aims were to investigate first-line prescriptions and effectiveness over a 10-year period in Ireland and evaluate the [...] Read more.

Background: Local audits of Helicobacter pylori (H. pylori) prescriptions and outcomes are necessary to assess guideline awareness among clinicians and treatment effectiveness. Aims: The aims were to investigate first-line prescriptions and effectiveness over a 10-year period in Ireland and evaluate the influence of the 2017 Irish consensus guidelines on these trends. Methods: Data were collected at e-CRF AEG-REDCap from the European Registry on H. pylori management (Hp-EuReg) and quality reviewed from 2013 to 2022. All treatment-naïve cases were assessed for effectiveness by modified intention-to-treat (mITT) analysis. Multivariate analysis was also performed. Results: Data from 1000 patients (mean age 50 ± 15 years; 54% female) were analyzed. Clarithromycin (C) and amoxicillin (A) triple therapy represented 88% of treatments, followed by sequential C, A, and metronidazole (M) therapy (4.3%) and triple C + M (2.7%). Bismuth quadruple therapy was prescribed in 1.7% of cases. Treatment durations of 14, 10, and 7 days accounted for 87%, 4.5%, and 8.5% of prescriptions, respectively. High-, standard-, and low-dose proton pump inhibitors (PPIs; 80 mg, 40 mg, and 20 mg omeprazole equivalent b.i.d.) were used in 86%, 0.9%, and 13% of cases, respectively. The overall eradication rate was 80%, while it was 81% for triple C + A. Good compliance and high-dose PPI were associated with higher overall mITT eradication rates (OR 4.5 and OR 1.9, respectively) and triple C + A eradication rates (OR 4.2 and OR 1.9, respectively). Overall eradication rates increased from 74% pre-2017 to 82% (p < 0.05) by the end of 2022. Similarly, the triple C + A eradication rates increased from 76% to 83% (p < 0.05). Conclusions: While first-line treatment effectiveness improved in clinical practice over time, cure rates remain below 90%. Alternative first-line strategies are required in Ireland. Full article

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19 pages, 1038 KiB

Open AccessArticle

Microbial Profile and Antibiotic Resistance Patterns in Bile Aspirates from Patients with Acute Cholangitis: A Multicenter International Study

by Matei-Alexandru Cozma, Mihnea-Alexandru Găman, Camelia Cristina Diaconu, Arthur Berger, Frank Zerbib and Radu Bogdan Mateescu

Antibiotics 2025, 14(7), 679; https://doi.org/10.3390/antibiotics14070679 - 4 Jul 2025

Viewed by 256

Abstract

Objectives: Significant differences in antibiotic resistance (AR) rates and multi-drug resistant (MDR) bacteria incidence exist in patients with acute cholangitis (AC) from different countries or regions. We aim to characterize and compare the microbial spectrum and AR patterns in patients with AC from [...] Read more.

Objectives: Significant differences in antibiotic resistance (AR) rates and multi-drug resistant (MDR) bacteria incidence exist in patients with acute cholangitis (AC) from different countries or regions. We aim to characterize and compare the microbial spectrum and AR patterns in patients with AC from two tertiary centers in Europe. Methods: We conducted a prospective, observational, multicentric study including patients diagnosed with AC and a positive bile culture, admitted to the Colentina Clinical Hospital (CCH), Bucharest, Romania, and the Haut-Lévêque Hospital (HLH), Bordeaux, France, between April 2022 and October 2023. Results: We included a total of 144 patients from the CCH with 190 positive bile cultures (31 patients had up to five episodes of AC during the study period) and 241 identified microbial strains, and 62 patients from the HLH with 67 positive bile cultures (5 patients had two episodes of AC) and 194 identified microbial strains. The most frequently isolated bacteria were Escherichia coli (30.70%) and Pseudomonas spp. (27.80%) in the CCH group, and Enterococcus faecalis (15.46%) and Escherichia coli (22/11.34%) in the HLH group. Furthermore, 51 (21.16%) of the strains identified in the CCH group and 15 (7.21%) in the HLH group were MDR, such as extended-spectrum beta-lactamase-producing Enterobacteriaceae or carbapenemase-producing Enterobacterales. The resistance rates for common antibiotics were 13.69% in the CCH group vs. 8.76% in the HLH group for ceftriaxone, 9.54% vs. 2.06% for meropenem, 16.59% vs. 6.70% for piperacillin/tazobactam, and 25.31% vs. 7.73% for levofloxacin. Conclusions: This comparative study shows significant differences between these countries in terms of the AR rates and MDR bacteria prevalence, highlighting the role of bile cultures as a safe and cost-effective method for guiding antibiotic treatment, thereby reducing the AR rates and complications. Full article

(This article belongs to the Special Issue Epidemiological Data on Antibiotic Resistance)

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18 pages, 3219 KiB

Open AccessArticle

Mobilome of Environmental Isolates of Clostridioides difficile

by Khald Blau and Claudia Gallert

Antibiotics 2025, 14(7), 678; https://doi.org/10.3390/antibiotics14070678 - 4 Jul 2025

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Abstract

Background/Objectives: Clostridioides difficile is a “One Health” pathogen and a cause of antibiotics-associated diarrhea and pseudomembranous colitis. Mobile genetic elements (MGEs) have been documented in the genomes of clinical C. difficile strains; however, the presence of MGEs in environmental strains remains poorly characterized. [...] Read more.

Background/Objectives: Clostridioides difficile is a “One Health” pathogen and a cause of antibiotics-associated diarrhea and pseudomembranous colitis. Mobile genetic elements (MGEs) have been documented in the genomes of clinical C. difficile strains; however, the presence of MGEs in environmental strains remains poorly characterized. Thus, the present study was conducted with the objective of identifying the prevalence of MGEs, including mobilizable transposons (MTns), conjugative transposons (CTns), plasmids, and insertion sequences, in whole genome sequences (WGSs) of environmental C. difficile isolates. Methods: The analysis of MGEs was conducted using 166 WGSs obtained from C. difficile strains isolated from various environmental sources contaminated with feces. The MGEs were identified using bioinformatic tools. Results: A total of 48.2% (80/166) of the studied genomes were identified to harbor nine transposons, including Tn916, Tn6194-like, Tn5397, Tn6215, Tn4001, Tn6073, Tn6110, Tn6107, or Tn5801-like. The majority of MTns and CTns could be found within C. difficile sequence types ST11, ST3, and ST35. The results demonstrated close genetic relatedness among the studied genomes, the array of antimicrobial resistance (AMR) genes, such as tetM, ermB, and aac(6′)-aph(2″), and the presence of CTns. Furthermore, the analysis revealed that 24.7% (41/166) of the genome sequences of isolates were associated with various predominant plasmid groups, including pCD6, pCD-ECE4-6, pCD-WTSI1-4, pCDBI1, and pCd1_3, which belonged to 16 different sequence types. Furthermore, several plasmids were identified as harboring the prophage phiCDHM19. Conclusions: The results of the current study suggest that the identified plasmids are abundant and may encode functions that are relevant to C. difficile physiology. The genomes of C. difficile strains examined contain closely related CTns, suggesting that horizontal transfer of AMR is important in this species or other bacterial species. Further research is required to ascertain the effect of these genetic elements and their transferability on the biology of C. difficile. Full article

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29 pages, 512 KiB

Open AccessReview

Antimicrobial and Antioxidant Activity of Essential Oils from Selected Pinus Species from Bosnia and Herzegovina

by Snježana Mirković, Milica Martinović, Vanja M. Tadić, Ivana Nešić, Aleksandra Stolić Jovanović and Ana Žugić

Antibiotics 2025, 14(7), 677; https://doi.org/10.3390/antibiotics14070677 - 3 Jul 2025

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Abstract

Essential oils are lipophilic secondary metabolites produced in various parts of aromatic plants and stored in specialized secretory structures. They play a vital role in plant defense, offering protection against microorganisms and herbivores. These oils are known for a wide range of biological [...] Read more.

Essential oils are lipophilic secondary metabolites produced in various parts of aromatic plants and stored in specialized secretory structures. They play a vital role in plant defense, offering protection against microorganisms and herbivores. These oils are known for a wide range of biological activities, including antibacterial, anti-inflammatory, antitumor, analgesic, antioxidant, and immunomodulatory effects. Given the increasing interest in natural alternatives to synthetic drugs, this review explored the therapeutic relevance of Pinus-derived essential oils as promising candidates in modern phytotherapy. Species of the genus Pinus have been widely investigated for their phytochemical composition and biological potential, with a focus on their medicinal and pharmaceutical applications. This review aimed to assess the biological properties of Pinus species commonly used in traditional medicine. In this paper, thorough insight into the chemical composition, as well as into the antimicrobial and antioxidant activities of essential oils obtained from the different parts of Pinus species, was given. Although recognized for their antimicrobial activity against a wide range of bacterial strains, including both Gram-positive and Gram-negative bacteria, the practical application of Pinus essential oils is often limited by their physicochemical instability and volatility. Therefore, this review highlighted the advances in formulation strategies, particularly encapsulation techniques, as the possible direction of future research concerning essential oils. Full article

(This article belongs to the Special Issue Antimicrobial and Antioxidant Efficacy of Essential Oils)

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8 pages, 278 KiB

Open AccessArticle

Antibiotic Prescription in Dentistry: Trends, Patient Demographics, and Drug Preferences in Germany

by Lisa Lotta Cirkel, Jens Martin Herrmann, Claudia Ringel, Bernd Wöstmann and Karel Kostev

Antibiotics 2025, 14(7), 676; https://doi.org/10.3390/antibiotics14070676 - 3 Jul 2025

Viewed by 190

Abstract

Background and objectives: ABs are widely used in dental practice in the treatment of odontogenic infections and as systemic prophylaxis in high-risk patients. However, AB overuse contributes to antimicrobial resistance (AMR), which is a major global concern. This study examined dental AB prescribing [...] Read more.

Background and objectives: ABs are widely used in dental practice in the treatment of odontogenic infections and as systemic prophylaxis in high-risk patients. However, AB overuse contributes to antimicrobial resistance (AMR), which is a major global concern. This study examined dental AB prescribing trends in Germany in 2024, focusing on the share of overall AB prescriptions, patient demographics, and commonly used agents. Methods: This retrospective cross-sectional study used data from the IQVIA Longitudinal Prescription Database (LRx), covering approximately 80% of prescriptions reimbursed by statutory health insurance funds in Germany. Patients with at least one AB prescription (ATC code: J01) issued by a dentist in 2024 were analyzed. Descriptive statistics covered age, sex, and prescribed substances. Results: In 2024, German dentists prescribed ABs to 2,325,500 patients, accounting for 13.9% of all patients in the database who received AB prescriptions. Dentists were the second-largest group of AB prescribers, surpassed only by general physicians. Amoxicillin (54.2%) was most frequently prescribed, followed by amoxicillin with clavulanic acid (24.5%) and clindamycin (21.0%). Dental patients receiving AB prescriptions were older (mean age: 49.8 years) than the general antibiotic patient population (44.7 years). Interestingly, dental AB prescriptions increased during the COVID-19 pandemic, in contrast to the sharp overall decline in AB prescriptions. Between 2015 and 2019, the proportion of dental antibiotic prescriptions showed a moderate upward tendency, followed by a marked increase during the COVID-19 pandemic and a subsequent decline. In contrast, the number of patients receiving antibiotic prescriptions from other medical disciplines decreased over the same period. One particularly notable finding was the extended use of clindamycin, a reserve AB with known side effects and resistance risks, in dentistry. Conclusions: Dentists are responsible for a significant share of AB prescriptions in Germany. The rise in dental AB prescriptions, particularly the frequent prescription of clindamycin, underscores the need for interventions such as updated clinical guidelines and awareness campaigns concerning AB-related risks and their mitigation directed at dentists. These could focus on microbial culture and sensitivity testing and patient adherence education and control for targeted AB interventions. Emphasizing preventive and alternative anti-infective treatment strategies in dentistry may also help to contain AMR. Full article

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

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9 pages, 457 KiB

Open AccessCommunication

Antimicrobial Susceptibility Testing of the Combination of Aztreonam and Avibactam in NDM-Producing Enterobacterales: A Comparative Evaluation Using the CLSI and EUCAST Methods

by Linda Mei-Wah Chan, Doris Yui Ling Lok, River Chun Wai Wong, Alfred Lok-Hang Lee, Ingrid Yu-Ying Cheung, Christopher Koon-Chi Lai and Viola C. Y. Chow

Antibiotics 2025, 14(7), 675; https://doi.org/10.3390/antibiotics14070675 - 3 Jul 2025

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Abstract

Background: The combination of aztreonam (ATM) and avibactam (AVI) presents an important therapeutic option for carbapenem-resistant Enterobacterales, particularly the NDM-producing Enterobacterales. In 2024, both the CLSI and EUCAST published their methods in antimicrobial susceptibility testing for this combination of agents. [...] Read more.

Background: The combination of aztreonam (ATM) and avibactam (AVI) presents an important therapeutic option for carbapenem-resistant Enterobacterales, particularly the NDM-producing Enterobacterales. In 2024, both the CLSI and EUCAST published their methods in antimicrobial susceptibility testing for this combination of agents. Materials and Methods: Forty carbapenem-resistant Enterobacterales isolates, including Escherichia coli (n = 35), Enterobacter cloacae complex (n = 2), Klebsiella pneumoniae complex (n = 2), and Citrobacter freundii complex (n = 1) were included in this study. All isolates harbored the NDM carbapenemase except one, which had no known detected carbapenemases. Four antimicrobial susceptibility testing methods of the combination of ATM and AVI were evaluated on these isolates, including the CLSI broth disk elution (BDE) method, the disk diffusion (DD) method of aztreonam–avibactam (AZA) following the EUCAST breakpoints, the MIC test strip (MTS) method of AZA following the EUCAST breakpoints, and the gradient strip stacking (SS) method. BDE was used as the standard of comparison. Results: Using BDE as the standard of comparison, the AZA DD, AZA MTS, and SS methods had 100% categorical agreement (CA), 0% very major error (VME), and 0% major error (ME). The essential agreement (EA) between the AZA MTS and SS method was 57.5%. Conclusions: The AZA DD, AZA MTS, and the SS methods showed complete concordance with the BDE method. However, the MICs obtained from the AZA MTS and SS were not comparable. Full article

(This article belongs to the Special Issue Present and Future of Antibiotic Treatment for Carbapenem-Resistant Enterobacteriaceae)

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14 pages, 428 KiB

Open AccessReview

Potential Future Applications of Postbiotics in the Context of Ensuring Food Safety and Human Health Improvement

by Zorica Tomičić, Ljubiša Šarić and Ružica Tomičić

Antibiotics 2025, 14(7), 674; https://doi.org/10.3390/antibiotics14070674 - 3 Jul 2025

Viewed by 301

Abstract

Postbiotics are defined as non-viable metabolites or compounds produced by probiotic microorganisms with significant impact on human health. The growing interest in postbiotics is supported by numerous studies due to their additional benefits over probiotics that show positive outcomes for specific conditions, as [...] Read more.

Postbiotics are defined as non-viable metabolites or compounds produced by probiotic microorganisms with significant impact on human health. The growing interest in postbiotics is supported by numerous studies due to their additional benefits over probiotics that show positive outcomes for specific conditions, as well as their application as biopreservatives in the food industry. Their potential in functional foods and therapeutic applications is increasingly recognized as they exhibit stability, safety, and diverse biological activities. As for their most important biological roles, postbiotics have been shown to have effective anti-inflammatory, antimicrobial, antioxidant, and anticancer properties, in addition to reducing food allergies. The application of postbiotics in functional foods contributes to improving intestinal health and reducing the risk of foodborne diseases. The concept of postbiotics is relatively new in the food industry. They offer a promising alternative to conventional food preservatives due to their ability to inhibit pathogenic bacteria and extend shelf life. Considering the diversity of postbiotic compounds and their significant biological activities, this review presents and discusses the mechanisms of action and future trends in their application in the food industry and their impact on human health. Increasing research and development in the production and formulation of postbiotics will play a key role in the upward trajectory of the market. Full article

(This article belongs to the Special Issue Bioactive Natural Products in Antimicrobial Resistance Management)

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Antibiotics, Volume 14, Issue 7 (July 2025) – 80 articles

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