Antibiotics

16 pages, 1402 KiB

Open AccessArticle

Prevalence, Antimicrobial Resistance, and Virulence Potential of Staphylococcus aureus in Donkeys from Nigeria

by Onyinye Josephine Okorie-Kanu, Madubuike Umunna Anyanwu, Obichukwu Chisom Nwobi, Regina Yaya Tambe-Ebot, Nkechi Harriet Ikenna-Ezeh, Chukwuemeka Calistus Okolo, Lynda Onyinyechi Obodoechi, Patience Chinasa Ugwu, Ifeyinwa Riona Okosi, Ishmael Festus Jaja and James Wabwire Oguttu

Antibiotics 2025, 14(5), 453; https://doi.org/10.3390/antibiotics14050453 - 29 Apr 2025

Abstract

Background: Animal-associated antimicrobial-resistant staphylococci pose a One Health concern, as they can spread into the environment and cause serious infections. Yet, donkeys in Nigeria have been largely overlooked as potential reservoirs of these pathogens. Aim/Objectives: To isolate Staphylococcus aureus from donkeys in Obollo-Afor, [...] Read more.

Background: Animal-associated antimicrobial-resistant staphylococci pose a One Health concern, as they can spread into the environment and cause serious infections. Yet, donkeys in Nigeria have been largely overlooked as potential reservoirs of these pathogens. Aim/Objectives: To isolate Staphylococcus aureus from donkeys in Obollo-Afor, southeast Nigeria, assess their antimicrobial resistance profiles, and evaluate their virulence potential. Materials and Methods: Staphylococci were isolated from the nasal swabs of 250 donkeys, using mannitol salt agar, confirmed biochemically, with Staphylococcus aureus identified via a latex agglutination test and mass spectrometry. The resistance profiles of the isolates, including in regard to methicillin, inducible clindamycin, and β-lactamase production, were determined using disc diffusion, while vancomycin resistance was assessed through the use of agar dilution. The virulence factors were evaluated phenotypically. Results: Of the 250 samples, 11 (4.4%) contained S. aureus and 239 (95.6%) grew other Staphylococcus species. The resistance rates of the 11 S. aureus isolates to gentamicin, penicillin, tigecycline, cefoxitin, linezolid, and chloramphenicol were 45.5%, 66.7%, 54.5%, 27.3%, 36.4%, and 18.1%, respectively. The phenotypic methicillin-resistant S. aureus prevalence was 1.2%. Additionally, 23.5% of the S. aureus isolates were multidrug resistant, with a mean antibiotic resistance index of 0.25. All the S. aureus isolates exhibited virulence factors like clumping factor expression, catalase, caseinase, lecithinase, and gelatinase activity, while the occurrence of haemagglutinin, biofilm, pellicle, and hemolysin occurred in 27.3%, 54.5%, 36.4%, 72.2%, respectively. Conclusion: Although a small percentage of donkeys in Nigeria may harbor S. aureus, these animals are potentially spreading antimicrobial resistance, including multidrug and methicillin resistance, to humans and the environment. Full article

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

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16 pages, 580 KiB

Open AccessArticle

The Influence of the Seasonal Variability of Candida spp. Bloodstream Infections and Antifungal Treatment: A Mediterranean Pilot Study

by Paola Di Carlo, Nicola Serra, Ornella Collotta, Claudia Colomba, Alberto Firenze, Luigi Aprea, Salvatore Antonino Distefano, Andrea Cortegiani, Giovanni Giammanco, Teresa Maria Assunta Fasciana, Roberta Virruso, Angela Capuano, Consolato M. Sergi and Antonio Cascio

Antibiotics 2025, 14(5), 452; https://doi.org/10.3390/antibiotics14050452 - 29 Apr 2025

Abstract

Background/Objectives: Various factors associated with seasonality, including temperature, humidity, geographical composition, and seasonal fluctuations, can influence the trends of microbes responsible for hospital infections, such as Candida spp. This study evaluates the seasonal variability of Candida spp. bloodstream infections and antifungal resistance [...] Read more.

Background/Objectives: Various factors associated with seasonality, including temperature, humidity, geographical composition, and seasonal fluctuations, can influence the trends of microbes responsible for hospital infections, such as Candida spp. This study evaluates the seasonal variability of Candida spp. bloodstream infections and antifungal resistance in hospitalized patients in Sicily. Methods: We retrospectively analyzed the demographic and epidemiological characteristics of 175 patients with blood cultures positive for Candida spp. Who were hospitalized at University Hospital Paolo Giaccone (A.U.O.P.), University of Palermo, Italy, from 1 January 2022 to 31 December 2024. Data on Candida species and antifungal resistance were also collected from the hospital’s database system to prevent and control hospital infections in A.U.O.P. Results: A total of 175 patients, 57.7% males, with a mean age of 68.3 years, were included in this study. Candida parapsilosis, Candida albicans, and Candida glabrata were more frequent in ICU (54.5%, p = 0.0001), medical (72.5%, p = 0.0003), and surgical settings (24%, p = 0.0161), respectively. C. parapsilosis was more frequent in dead patients (53.2%, p = 0.005). Among the seasons, we observed a significantly higher presence of C. glabrata in Autumn (20%, p = 0.0436). From the analysis of the seasons, C. parapsilosis and C. albicans were more frequent for each season, except in Spring, where the most frequent isolates were C. glabrata (5.1%, p = 0.0237) and C. parapsilosis (9.7%, p < 0.0001). The antifungal with the most resistance to Candida spp. was fluconazole in all seasons. Conclusions: Our study highlights the seasonal trends in Candida spp. and antifungal resistance, emphasizing climate change’s challenges on fungal diseases. These findings may contribute to improving prevention and treatment strategies for candidemia. Full article

(This article belongs to the Special Issue Climate Change and Antibiotic Resistance)

33 pages, 625 KiB

Open AccessReview

Delivery of Outpatient Parenteral Antimicrobial Therapy (OPAT) in an Ever-Changing National Health Service (UK): Benefits, Barriers, and Opportunities

by Oyewole Christopher Durojaiye, Charlotte Fiori and Katharine Cartwright

Antibiotics 2025, 14(5), 451; https://doi.org/10.3390/antibiotics14050451 - 29 Apr 2025

Abstract

Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to manage a broad range of infections, enabling patients to receive intravenous antibiotics safely outside inpatient settings. In this review, we examine the current landscape of OPAT practice across the United Kingdom (UK), assessing its [...] Read more.

Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to manage a broad range of infections, enabling patients to receive intravenous antibiotics safely outside inpatient settings. In this review, we examine the current landscape of OPAT practice across the United Kingdom (UK), assessing its clinical, economic, and operational impact. The benefits of OPAT for patients and the National Health Service (NHS), as well as its associated risks, are discussed. Additionally, we explore the challenges hindering its broader implementation within the UK. Finally, we highlight recent innovations and emerging applications of OPAT relevant to the NHS, underscoring key considerations for its future expansion and emphasising the need for a nationally coordinated strategy to realise its full potential. Full article

19 pages, 2037 KiB

Open AccessArticle

Antimicrobial Susceptibility Profiles of Escherichia coli Isolates from Clinical Cases of Geese in Hungary Between 2022 and 2023

by Ádám Kerek, Ábel Szabó and Ákos Jerzsele

Antibiotics 2025, 14(5), 450; https://doi.org/10.3390/antibiotics14050450 - 29 Apr 2025

Abstract

Background: Antimicrobial resistance (AMR) poses an increasing threat to animal health and food safety. In the poultry sector, particularly in waterfowl farming, the widespread use of antibiotics may contribute to the dissemination of resistant Escherichia coli strains. This study aims to [...] Read more.

Background: Antimicrobial resistance (AMR) poses an increasing threat to animal health and food safety. In the poultry sector, particularly in waterfowl farming, the widespread use of antibiotics may contribute to the dissemination of resistant Escherichia coli strains. This study aims to map the antibiotic resistance profiles of E. coli isolates from geese in Hungary, determine the prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, and analyze resistance patterns and co-resistance relationships. Methods: E. coli isolates from clinical cases between 2022 and 2023 were examined using minimum inhibitory concentration (MIC) determination. Susceptibility results were evaluated based on the Clinical Laboratory Standard Institute (CLSI) breakpoints. Cluster analysis and principal component analysis (PCA) were applied to identify resistance patterns. Co-resistance relationships were examined through network analysis, while Monte Carlo simulations were used to estimate the expected prevalence of MDR strains. Results: Among the examined isolates, neomycin resistance was particularly high (86.8%), while florfenicol (73.6%) and amoxicillin (65.9%) resistance levels were also significant. The prevalence of MDR strains was 86.8%, and XDR strains accounted for 38.5%. Co-resistance analysis revealed a strong correlation between neomycin and spectinomycin resistance, as well as amoxicillin and doxycycline resistance. Monte Carlo simulations estimated that the expected range of MDR strain prevalence could vary between 80.2% and 92.3%. Conclusions: The high prevalence of MDR and XDR strains highlights the urgent need to reassess antibiotic usage strategies in goose farming. These findings underscore the importance of targeted antibiotic use, continuous microbiological surveillance, and the exploration of alternative therapeutic approaches to mitigate AMR. Full article

(This article belongs to the Special Issue Detection of Bacteria and Antibiotics Surveillance in Livestock)

12 pages, 1201 KiB

Open AccessArticle

Genetic Variation in the blaZ Gene Leading to the BORSA Phenotype in Staphylococcus aureus

by Mia Aarris, Frederik Boëtius Hertz, Karen Leth Nielsen, Alexander Sato, Helle Krogh Johansen, Henrik Westh, Michael Kemp, Svend Ellermann-Eriksen, Anders Løbner-Olesen, Niels Frimodt-Møller and Godefroid Charbon

Antibiotics 2025, 14(5), 449; https://doi.org/10.3390/antibiotics14050449 - 29 Apr 2025

Abstract

Background/Objectives: Staphylococcus aureus is a leading cause of bacteraemia in Danish hospitals. Approximately 70% of clinical S. aureus isolates are penicillin-resistant, which is predominantly due to blaZ-mediated β-lactamase production. Methods: A collection of 489 S. aureus strains derived from bacteraemia were cultured [...] Read more.

Background/Objectives: Staphylococcus aureus is a leading cause of bacteraemia in Danish hospitals. Approximately 70% of clinical S. aureus isolates are penicillin-resistant, which is predominantly due to blaZ-mediated β-lactamase production. Methods: A collection of 489 S. aureus strains derived from bacteraemia were cultured and their genomes sequenced. Results: From this collection, 71% of isolates were methicillin-susceptible S. aureus (MSSA) harbouring blaZ. While most isolates contained the blaZ gene belonging to the well-characterised A, B, C and D variants, three strains (1%) produced a BlaZ protein characterised by having threonine residues on both positions 128 and 216 and, therefore, belonged to neither of the established blaZ variants. We named this variant, variant F. We report that clinical isolates expressing blaZ variant F were resistant to oxacillin. The β-lactamase production phenotype in isolates carrying either of the A, B, C or D variants was only weakly discernible on MIC gradient strip and disk diffusion tests. When the β-lactamases were expressed either from a T7 promoter or from their endogenous promoters in Escherichia coli, variant F was significantly better at degrading ampicillin than variant A. We also showed that variant F conferred oxacillin resistance when expressed in an isogenic S. aureus strain, while variant A did not. Finally, we demonstrated that the F variant threonine 216 played a role in the enzyme’s superior activity. Conclusions: Our findings demonstrate that the new F variant of BlaZ is sufficient to render S. aureus a BORSA strain, which is superior in the degradation of common anti-staphylococcal β-lactam antibiotics, such as benzylpenicillin, cloxacillin, and oxacillin. It is sensitive to β-lactamase inhibitors and rapidly degrades nitrocefin. We provide a genetic explanation for the borderline oxacillin-resistant S. aureus (BORSA) phenotype. Full article

(This article belongs to the Section Genetic and Biochemical Studies of Antibiotic Activity and Resistance)

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21 pages, 1743 KiB

Open AccessArticle

Bacterivorous Ciliate Tetrahymena pyriformis Facilitates vanA Antibiotic Resistance Gene Transfer in Enterococcus faecalis

by Temilola O. Olanrewaju, James S. G. Dooley, Heather M. Coleman, Chris McGonigle and Joerg Arnscheidt

Antibiotics 2025, 14(5), 448; https://doi.org/10.3390/antibiotics14050448 - 28 Apr 2025

Abstract

Background: Wastewater treatment plants (WWTPs) are hotspots for the emergence and spread of antibiotic resistance genes (ARGs). In activated sludge treatment systems, bacterivorous protozoa play a crucial role in biological processes, yet their impact on the horizontal gene transfer in Gram-positive enteric bacteria [...] Read more.

Background: Wastewater treatment plants (WWTPs) are hotspots for the emergence and spread of antibiotic resistance genes (ARGs). In activated sludge treatment systems, bacterivorous protozoa play a crucial role in biological processes, yet their impact on the horizontal gene transfer in Gram-positive enteric bacteria remains largely unexplored. This study investigated whether the ciliate Tetrahymena pyriformis facilitates the transfer of antibiotic resistance genes between Enterococcus faecalis strains. Methods: Conjugation assays were conducted under laboratory conditions using a vanA-carrying donor and a rifampicin-resistant recipient at an initial bacterial concentration of 10⁹ CFU/mL and ciliate density of 10⁵ N/mL. Results: Transconjugant numbers peaked at 2 h when experiments started with recipient bacteria harvested in the exponential growth phase, and at 24 h when bacteria were in the stationary phase. In both cases, vanA gene transfer frequency was highest at 24 h (10⁻⁴–10⁻⁵ CFU/mL), and the presence of energy sources increased gene transfer frequency by one order of magnitude. Conclusions: These findings suggest that ciliate grazing may contribute to vanA gene transfer in WWTP effluents, potentially facilitating its dissemination among permissive bacteria. Given the ecological and public health risks associated with vanA gene persistence in wastewater systems, understanding protozoan-mediated gene transfer is crucial for mitigating the spread of antibiotic resistance in aquatic environments. Full article

(This article belongs to the Special Issue Tracking Reservoirs of Antimicrobial Resistance Genes in Environment)

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13 pages, 991 KiB

Open AccessArticle

The Accuracy of Empirical Antibiotic Treatment for Periprosthetic Joint Infections in Total Shoulder and Knee Arthroplasties

by Katrin Freller, Hannah Punz, Clemens Schopper, Tobias Gotterbarm, Antonio Klasan and Stella Stevoska

Antibiotics 2025, 14(5), 447; https://doi.org/10.3390/antibiotics14050447 - 28 Apr 2025

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Abstract

Introduction: Periprosthetic joint infections (PJIs) remain a major challenge in orthopedic and trauma surgeries. The microbial resistance profiles and the optimal choice of empirical antibiotic therapy in shoulder arthroplasty revision are less well characterized compared to those in knee or hip arthroplasty revision. [...] Read more.

Introduction: Periprosthetic joint infections (PJIs) remain a major challenge in orthopedic and trauma surgeries. The microbial resistance profiles and the optimal choice of empirical antibiotic therapy in shoulder arthroplasty revision are less well characterized compared to those in knee or hip arthroplasty revision. Materials and Methods: This retrospective study constitutes a novel comparative analysis, providing valuable insights into the presence of joint-specific pathogen resistance and the empirical treatment accuracy of shoulder and knee arthroplasties. A review of all the revision cases following primary shoulder and knee arthroplasties conducted between January 2012 and December 2023 was performed. Cases that required revision because of PJIs were identified, and microbial cultures were analyzed to determine the presence of pathogens and their resistance profiles. Results: The most administered postoperative empirical antibiotics were cefuroxime and amoxicillin–sulbactam. A statistically significant difference in the prevalence of anerobic pathogens was observed between total shoulder arthroplasty and knee arthroplasty. Furthermore, a statistically significant difference was observed in the sensitivities of pathogens to metronidazole (p < 0.001) and erythromycin (p = 0.014). Conclusions: This study demonstrates microbiological and antimicrobial resistance differences between PJI TSA and TKA cases. Full article

(This article belongs to the Special Issue Single-Stage Management of Musculo-Skeletal Infections: Local Antibacterial Protection, Antibiotics, and Surgical Treatments)

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24 pages, 4343 KiB

Open AccessArticle

Genomic Insights of Antibiotic-Resistant Escherichia coli Isolated from Intensive Pig Farming in South Africa Using ‘Farm-to-Fork’ Approach

by Shima E. Abdalla, Linda A. Bester, Akebe L. K. Abia, Mushal Allam, Arshad Ismail, Sabiha Y. Essack and Daniel G. Amoako

Antibiotics 2025, 14(5), 446; https://doi.org/10.3390/antibiotics14050446 - 28 Apr 2025

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Abstract

Background/Objectives: Intensive pig farming is a critical component of food security and economic activity in South Africa; however, it also presents a risk of amplifying antimicrobial resistance (AMR). This study provides genomic insights into antibiotic-resistant Escherichia coli (E. coli) circulating [...] Read more.

Background/Objectives: Intensive pig farming is a critical component of food security and economic activity in South Africa; however, it also presents a risk of amplifying antimicrobial resistance (AMR). This study provides genomic insights into antibiotic-resistant Escherichia coli (E. coli) circulating across the pork production chain, using a ‘farm-to-fork’ approach. Methods: A total of 417 samples were collected from various points along the production continuum, including the farm (n = 144), transport (n = 60), and abattoir (n = 213). E. coli isolates were identified using the Colilert-18 system, and their phenotypic resistance was tested against 20 antibiotics. Thirty-one isolates were selected for further characterization based on their resistance profiles and sampling sources, utilizing whole-genome sequencing and bioinformatic analysis. Results: The isolates exhibited varying resistance to critical antibiotics used in both human and animal health, including ampicillin (31/31, 100%), tetracycline (31/31, 100%), amoxicillin–clavulanate (29/31, 94%), chloramphenicol (25/31, 81%), and sulfamethoxazole–trimethoprim (10/31, 33%). Genetic analysis revealed the presence of resistance genes for β-lactams (bla_EC, bla_TEM), trimethoprim/sulfonamides (dfrA1, dfrA5, dfrA12, sul2, sul3), tetracyclines (tetA, tetB, tetR, tet34), aminoglycosides (aadA, strA, aph variants), and phenicols (catB4, floR, cmlA1), most of which were plasmid-borne. Virulome analysis identified 24 genes, including toxins and adhesion factors. Mobile genetic elements included 24 plasmid replicons, 43 prophages, 19 insertion sequence families, and 7 class 1 integrons. The E. coli isolates belonged to a diverse range of sequence types, demonstrating significant genetic variability. Further phylogenomic analysis revealed eight major clades, with isolate clustering by sequence type alongside South African environmental and clinical E. coli strains, regardless of their sampling source. Conclusions: The genetic complexity observed across the pork production continuum threatens food safety and may impact human health. These findings underscore the need for enhanced AMR monitoring in livestock systems and support the integration of AMR surveillance into food safety policy frameworks. Full article

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

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16 pages, 17861 KiB

Open AccessArticle

The α-Helical Amphipathic Peptide Alleviates Colistin-Induced Nephrotoxicity by Maintaining Mitochondrial Function in Both In Vitro and In Vivo Infection Models

by Min Soo Kook, Heeseung Kim, Yoonhwa Choi, Seong Man Bae, Jaehoon Yu and Yang Soo Kim

Antibiotics 2025, 14(5), 445; https://doi.org/10.3390/antibiotics14050445 - 28 Apr 2025

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Abstract

Background/Objective: Colistin is the primary treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB) infections, but its use is limited by nephrotoxicity, which reduces its effectiveness. There is an urgent need for nephroprotective agents to address this toxicity. This study investigated the potential of CMP3029, [...] Read more.

Background/Objective: Colistin is the primary treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB) infections, but its use is limited by nephrotoxicity, which reduces its effectiveness. There is an urgent need for nephroprotective agents to address this toxicity. This study investigated the potential of CMP3029, an α-helical peptide, to protect against colistin-induced nephrotoxicity. Methods: In vitro, CMP3029 was applied to HK-2 cells before colistin exposure, and cell viability and reactive oxygen species (ROS) levels were measured. In infected mice, CMP3029 was administered before colistin treatment, and urinary kidney injury molecule-1 (KIM-1), cystatin C levels, neutrophil gelatinase-associated lipocalin (NGAL), and renal damage were assessed. Results: CMP3029 preserved cell viability and significantly reduced mitochondrial ROS in HK-2 cells exposed to colistin. CMP3029 lowered urinary biomarkers and mitigated tubular injury in mice, demonstrating significant nephroprotective effects. Conclusions: These findings suggest that CMP3029 mitigates colistin-induced nephrotoxicity. Given the increasing threat of CR-GNB infections, CMP3029 could be a crucial clinical solution for improving patient outcomes in treating colistin-associated nephrotoxicity. Full article

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14 pages, 1892 KiB

Open AccessArticle

In Vivo Antimicrobial Activity of Nisin Z Against S. aureus and Polyurea Pharmadendrimer PURE_G4OEI₄₈ Against P. aeruginosa from Diabetic Foot Infections

by Isa Serrano, Dalila Mil-Homens, Rita F. Pires, Vasco D. B. Bonifácio, Joana F. Guerreiro, Eva Cunha, Sofia S. Costa, Luís Tavares and Manuela Oliveira

Antibiotics 2025, 14(5), 444; https://doi.org/10.3390/antibiotics14050444 - 28 Apr 2025

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Abstract

Background/Objectives: Diabetic foot infections (DFIs) are commonly associated with frequent hospitalizations, limb amputations, and premature death due to the profile of the bacteria infecting foot ulcers. DFIs are generally colonized by a polymicrobial net of bacteria that grows in biofilms, developing an increased [...] Read more.

Background/Objectives: Diabetic foot infections (DFIs) are commonly associated with frequent hospitalizations, limb amputations, and premature death due to the profile of the bacteria infecting foot ulcers. DFIs are generally colonized by a polymicrobial net of bacteria that grows in biofilms, developing an increased antimicrobial resistance to multiple antibiotics. DFI treatment is a hurdle, and the need to develop new therapies that do not promote resistance is urgent. Therefore, the antibacterial efficacy of Nisin Z (antimicrobial peptide), a core–shell polycationic polyurea pharmadendrimer (PURE_G4OEI₄₈) (antimicrobial polymer), and amlodipine (antihypertensive drug) was evaluated against S. aureus and P. aeruginosa isolated from a DFI and previously characterized. Methods: The antibacterial activity was analyzed in vitro by determining the minimal inhibitory concentration (MIC) and in vivo in a Galleria mellonella model by assessing the larvae survival and health index. Results: The results indicate that Nisin Z exhibited antibacterial activity against S. aureus in vivo, allowing larvae full survival, and no antibacterial activity against P. aeruginosa. Nisin Z may have reduced the antibacterial effectiveness of both PURE_G4OEI₄₈ and amlodipine. PURE_G4OEI₄₈ significantly increased the survival of the larvae infected with P. aeruginosa, while amlodipine showed no activity against both bacteria in vivo. Conclusions: These findings suggest that both Nisin Z and PURE_G4OEI₄₈ could potentially be used individually as adjunct treatments for mild DFIs. However, further studies are needed to confirm these findings and assess the potential toxicity and efficacy of PURE_G4OEI₄₈ in more complex models. Full article

(This article belongs to the Special Issue Strategies to Combat Antibiotic Resistance and Microbial Biofilms)

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18 pages, 331 KiB

Open AccessReview

Antimicrobial Resistance in Diverse Ecological Niches—One Health Perspective and Food Safety

by Nedjeljko Karabasil, Milica Mirković, Ivan Vićić, Ivana Perić, Nevena Zlatković, Bojana Luković and Ina Gajić

Antibiotics 2025, 14(5), 443; https://doi.org/10.3390/antibiotics14050443 - 28 Apr 2025

Viewed by 186

Abstract

Antimicrobial resistance (AMR) is a multi-sectoral, systemic, and global issue worldwide. Antimicrobial use (AMU) is a key factor in the selection of resistant bacteria within different ecological niches, from agriculture to food-producing animals to humans. There is a question regarding the extent to [...] Read more.

Antimicrobial resistance (AMR) is a multi-sectoral, systemic, and global issue worldwide. Antimicrobial use (AMU) is a key factor in the selection of resistant bacteria within different ecological niches, from agriculture to food-producing animals to humans. There is a question regarding the extent to which the use of antibiotics in livestock production and the primary food production sector influences the selection and transmission of resistant bacteria and/or resistant genes throughout the food chain and thus contributes to the complexity in the development of AMR in humans. Although the trends in the prevalence of foodborne pathogens have changed over time, the burden of ecological niches with resistance genes, primarily in commensal microorganisms, is of concern. The implementation of the harmonized surveillance of AMU and AMR would provide comprehensive insights into the actual status of resistance and further interventions leading to its reduction. Tracking AMR in different ecological niches by applying advanced genome-based techniques and developing shared AMR data repositories would strengthen the One Health concept. Full article

(This article belongs to the Special Issue Comprehensively Addressing Antimicrobial Resistance, Improving Food Safety and Achieving the One Health Goals: Global Challenges)

19 pages, 16029 KiB

Open AccessArticle

Antibiotic Cocktail Exacerbates Esomeprazole-Induced Intestinal Dysmotility While Ameliorating Gastric Dyspepsia in Mice

by Jing-Hua Wang, Song-Yi Han, Kyungjae Lee, Uijeong Han, Si-Kyung Cho and Hojun Kim

Antibiotics 2025, 14(5), 442; https://doi.org/10.3390/antibiotics14050442 - 27 Apr 2025

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Abstract

Background/Objectives: Esomeprazole, a proton pump inhibitor (PPI), is commonly prescribed for gastric-acid-related disorders but has been associated with impaired gastrointestinal (GI) motility with long-term use. However, the effect of concurrent antibiotic administration on this dysfunction remains unclear. Therefore, this study aimed to investigate [...] Read more.

Background/Objectives: Esomeprazole, a proton pump inhibitor (PPI), is commonly prescribed for gastric-acid-related disorders but has been associated with impaired gastrointestinal (GI) motility with long-term use. However, the effect of concurrent antibiotic administration on this dysfunction remains unclear. Therefore, this study aimed to investigate the effects of antibiotics on esomeprazole-induced GI motility dysfunction and explore the underlying mechanisms in a mouse model. Methods: Male C57BL/6 mice were orally administered esomeprazole (160 mg/kg) five times per week for 4 weeks. Three days before initiating esomeprazole treatment, a broad-spectrum antibiotic cocktail (ABX) consisting of ampicillin (1 g/kg), neomycin (1 g/kg), metronidazole (1 g/kg), and vancomycin (0.5 g/kg) was provided in drinking water and maintained throughout the experimental period. Mosapride (3 mg/kg), a prokinetic agent, was used as a positive control. Results: Neither esomeprazole alone nor in combination with ABX affected body weight or food intake. Compared to normal controls, esomeprazole treatment significantly delayed both intestinal transit and gastric emptying. However, ABX co-administration further pronounced intestinal transit time and improved gastric motility. The potential mechanisms may involve interactions among gastric H⁺/K⁺-ATPase, CYP3A11, gastrointestinal hormones (secretin and motilin), and the gut microbiome. Conclusions: Long-term esomeprazole use can impair both gastric and intestinal motility, and ABX co-treatment further exacerbates intestinal transit delay while paradoxically enhancing gastric emptying. These findings highlight the critical role of the gut microbiota in esomeprazole-induced GI motility dysfunction and suggest that antibiotic use should be approached with caution, particularly when combined with PPI therapy. Full article

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14 pages, 3522 KiB

Open AccessArticle

Thermoplastic Zinc-Infused Polymer for Chairside Socket Seal Abutments Enhances Antimicrobial and Tissue-Integrative Properties

by Wannes Van Holm, Katleen Vandamme, Jill Hadisurya, Ferda Pamuk, Naiera Zayed, Merve Kübra Aktan, Annabel Braem, Andy Temmerman and Wim Teughels

Antibiotics 2025, 14(5), 441; https://doi.org/10.3390/antibiotics14050441 - 27 Apr 2025

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Abstract

Background/Objectives: The essential trace element zinc (Zn) has a pivotal role in wound healing and can show antibacterial activity, but its application in oral implant materials is underexplored. Customized healing abutments can modulate the peri-implant tissue health when appropriate bioactive materials promoting [...] Read more.

Background/Objectives: The essential trace element zinc (Zn) has a pivotal role in wound healing and can show antibacterial activity, but its application in oral implant materials is underexplored. Customized healing abutments can modulate the peri-implant tissue health when appropriate bioactive materials promoting mucosal healing are used. The present study investigated a novel Zn-containing polymer for its potential in soft-tissue engineering applications. Methods: Four traditional materials—titanium, glass ionomer, a composite, and the novel Zn-containing polymer—were tested in vitro for bacterial growth using a multispecies oral bacterial model compared to hydroxyapatite. The biocompatibility of the materials was also evaluated by evaluating the adhesion, proliferation, and cytotoxicity of human oral keratinocytes (HOK-18A) onto these materials, compared to tissue culture plastic. Results: The Zn-containing polymer exhibited a significantly lower biofilm formation compared to conventional materials as it was composed of less pathogenic bacteria. The Zn-containing material also demonstrated a superior biocompatibility towards HOK-18A, approximating the adhesion and proliferation of the keratinocytes to optimal tissue culture conditions. Moreover, these properties did not seem to degrade and were maintained over a period of 31 days. The cytotoxicity assessment revealed no significant reduction in metabolic activity for any material. Conclusions: This study highlights the potential of the novel Zn-containing polymer in soft-tissue engineering, owing to its antimicrobial and biocompatible assets. These properties, combined with the ease of chairside modeling, position the material as a promising alternative for creating customized healing abutments. Further research is needed to explore its mechanism of wound healing modulation and its clinical performance. Full article

(This article belongs to the Special Issue Biofilm-Associated Oral Diseases: Advances in Diagnosis and Challenges in Treatment)

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14 pages, 1185 KiB

Open AccessArticle

A Cross-Sectional Study Assessing Antibiotic Resistance Awareness Among University Students in Samborondón, Greater Guayaquil, Ecuador

by Norka Michelle Mora Pincay, José Luis Villegas, César Marcelo Larrea-Álvarez, Daniela Beatriz Briones Caiminagua, Lilibeth Torres-Elizalde, Miroslava Anna Šefcová and Marco Larrea-Álvarez

Antibiotics 2025, 14(5), 440; https://doi.org/10.3390/antibiotics14050440 - 27 Apr 2025

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Abstract

Background/Objectives: Education on antibiotic use has the potential to positively shape the practices and perspectives of future professionals. Assessing awareness levels of antibiotic resistance among university students is, therefore, critical, as they represent a vital demographic capable of influencing public health outcomes, especially [...] Read more.

Background/Objectives: Education on antibiotic use has the potential to positively shape the practices and perspectives of future professionals. Assessing awareness levels of antibiotic resistance among university students is, therefore, critical, as they represent a vital demographic capable of influencing public health outcomes, especially in low- and middle-income countries. Methods: This cross-sectional study employed the World Health Organization’s Antibiotic Resistance: Multi-Country Public Awareness Survey, which examines demographics, antibiotic use, knowledge, perspectives, and sources of information. A total of 922 surveys were collected from students across various disciplines at two universities in Greater Guayaquil. Results: Most participants reported obtaining antibiotics through healthcare professionals, adhering to proper usage instructions, and purchasing them primarily from pharmacies. However, only 56% of the responses were correct, with many students incorrectly associating antibiotic use with conditions where they are typically ineffective. Despite these gaps, the students expressed positive attitudes toward proposed measures to address antibiotic resistance. While the participants demonstrated familiarity with terms related to antibiotic resistance and identified doctors and educators as their main sources of information, educational campaigns were not widely recognized as important. Conclusions: These findings evidence knowledge gaps among an essential group, suggesting the need for targeted health programs, preventive strategies, and educational initiatives to combat misinformation regarding antimicrobial resistance. Full article

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

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13 pages, 384 KiB

Open AccessSystematic Review

Effectiveness of Bacillus clausii (O/C, N/R, SIN, T) in the Prevention of Antibiotic-Associated Diarrhea and Gastrointestinal Symptoms: A Systematic Review

by Ana Teresa Abreu, Rodrigo Vázquez Frías, Christian Boggio Marzet, Juan Pablo Stefanolo, Alejandro Concha Mejía, Luis Bustos Fernández, Oscar Laudanno, Dimas Rosa, Maria Claudia Cruz Serrano, Karen Cárdenas and Julio Zuluaga

Antibiotics 2025, 14(5), 439; https://doi.org/10.3390/antibiotics14050439 - 27 Apr 2025

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Abstract

Background: Dysbiosis and antibiotic-associated diarrhea (AAD) are significant concerns in clinical settings. Probiotics, such as Bacillus clausii (O/C, N/R, SIN, T), a spore-forming bacterium resistant to gastrointestinal conditions and most commonly used antibiotics, emerge as a promising approach. We aim to assess [...] Read more.

Background: Dysbiosis and antibiotic-associated diarrhea (AAD) are significant concerns in clinical settings. Probiotics, such as Bacillus clausii (O/C, N/R, SIN, T), a spore-forming bacterium resistant to gastrointestinal conditions and most commonly used antibiotics, emerge as a promising approach. We aim to assess the role of B. clausii in preventing AAD in children and adults during antibiotic therapy. Materials and methods: A systematic literature search was conducted across multiple databases, including MEDLINE, EMBASE, Cochrane Library, LILACS, and SciELO, up to May 2024. Studies were included if they involved B. clausii (O/C, N/R, SIN, T) administration during antibiotic treatment and reported AAD-related outcomes. Results: A total of four studies were included in the review. The studies comprised two randomized controlled trials (RCTs), one meta-analysis of RCTs, and one expert consensus. The primary outcome was the effectiveness of B. clausii (O/C, N/R, SIN, T) in reducing the incidence of diarrhea. Results showed a significant reduction in the risk of AAD and gastrointestinal symptoms in patients receiving it at a dosage of 4 × 10⁹ CFU/day for children and 6 × 10⁹ CFU/day for adolescents and adults for up to 14 days. Conclusions: B. clausii (O/C, N/R, SIN, T) appears to be an effective probiotic for preventing AAD in adults and children. It significantly improves gastrointestinal symptoms associated with antibiotic treatment, including diarrhea, nausea, and epigastric pain. Future studies are recommended to further elucidate its effectiveness in diverse populations, especially in low- and middle-income countries. Full article

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12 pages, 870 KiB

Open AccessArticle

Navigating Vancomycin and Acute Kidney Injury: AUC- vs. Trough-Guided Monitoring in Initial and Steady-State Therapy

by Astrid Marovič, Tomaž Vovk and Maja Petre

Antibiotics 2025, 14(5), 438; https://doi.org/10.3390/antibiotics14050438 - 27 Apr 2025

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Abstract

Background/Objectives: Vancomycin, a glycopeptide antibiotic used for gram-positive infections, is associated with acute kidney injury (AKI). Therapeutic drug monitoring (TDM) is recommended to minimize this risk while ensuring therapeutic efficacy. This study evaluated whether AUC-guided monitoring improved patient safety compared to traditional [...] Read more.

Background/Objectives: Vancomycin, a glycopeptide antibiotic used for gram-positive infections, is associated with acute kidney injury (AKI). Therapeutic drug monitoring (TDM) is recommended to minimize this risk while ensuring therapeutic efficacy. This study evaluated whether AUC-guided monitoring improved patient safety compared to traditional trough-guided monitoring. Methods: A retrospective observational cohort study was conducted at the University Medical Centre Maribor, Slovenia, involving patients receiving intravenous vancomycin. One cohort was managed using trough-guided monitoring (n = 85), while the other was monitored using the AUC-guided approach (n = 139). The primary outcome was AKI incidence, and secondary outcomes included renal replacement therapy and mortality. Risk factors for AKI were identified, and pharmacokinetic parameters were evaluated at vancomycin therapy initiation and steady state. Results: The incidence of AKI was 20% in the trough-guided group and 18% in the AUC-guided group (p = 0.727). Secondary outcomes were similar in both cohorts. Risk factors for AKI included older age (OR 1.04; p = 0.042), higher steady-state AUC (OR 1.01; p < 0.001), longer duration of concomitant nephrotoxic therapy (OR 1.06; p = 0.019), and concomitant use of loop diuretics (OR 2.46; p = 0.045). Steady-state AUC values and trough levels (AUC_0–24ss, AUC_24–48ss, AUC_0–48ss, and C_min48ss) were significantly lower in the AUC-guided group, which was further reflected in the lower percentage of patients exceeding the AUC > 600 mg·h/L threshold at steady state. Conclusions: Although AKI incidence was lower in the AUC-guided group, the difference did not reach statistical significance. However, lower AUC values and trough levels in the AUC-guided group at steady state suggest a trend toward reduced vancomycin exposure and toxicity. Full article

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18 pages, 3321 KiB

Open AccessArticle

Anti-Staphylococcus aureus Activity and Structural Characterization of Rationally Designed Peptides

by Lorenza Artesani, Mariana Gallo, Laura Giovati, Francesca Maria Bisignano, Elena Ferrari, Lara M. Castronovo, Stefania Conti, Francesco Santoro, Thelma A. Pertinhez and Tecla Ciociola

Antibiotics 2025, 14(5), 437; https://doi.org/10.3390/antibiotics14050437 - 26 Apr 2025

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Abstract

Background/Objectives: Microbial infections represent a significant threat to public health due to the emergence and spread of antimicrobial resistance. Adjunctive and alternative therapeutic strategies are explored to tackle this issue, including the use of natural or synthetic antimicrobial peptides. Previous research showed [...] Read more.

Background/Objectives: Microbial infections represent a significant threat to public health due to the emergence and spread of antimicrobial resistance. Adjunctive and alternative therapeutic strategies are explored to tackle this issue, including the use of natural or synthetic antimicrobial peptides. Previous research showed that antibody-derived peptides possess antimicrobial, antiviral, and immunomodulatory properties. This study aimed to characterize newly designed antibody-derived peptides and evaluate their effectiveness against representative strains of Staphylococcus aureus, including drug-resistant isolates. Methods: Colony-forming unit assays and confocal microscopy studies were performed to evaluate peptide activity against planktonic microbial cells. Cytotoxicity tests were performed on THP-1 human monocytic cells. Circular dichroism (CD) and nuclear magnetic resonance (NMR) were employed for the conformational characterization of peptides. Results: The half-maximal effective concentrations of the peptides against bacterial reference strains and drug-resistant isolates ranged from 0.17 to 18.05 µM, while cytotoxic effects were not observed against mammalian cells. A killing kinetics analysis and observation by confocal microscopy of the interaction between peptides and bacteria suggested a mechanism of action involving membrane perturbation. CD studies showed that all peptides predominantly exhibit a random coil arrangement in aqueous solution. NMR spectroscopy revealed that the most active peptide adopts a helical conformation in the presence of membrane mimetics. Conclusions: The structural characterization and evaluation of the newly designed peptides’ antimicrobial activity may lead to the selection of a candidate to be further studied to develop an alternative treatment against microbial infections caused by drug-resistant strains. Full article

(This article belongs to the Section Antimicrobial Peptides)

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23 pages, 2021 KiB

Open AccessReview

A Scoping Review Unveiling Antimicrobial Resistance Patterns in the Environment of Dairy Farms Across Asia

by Yuvaneswary Veloo, Syahidiah Syed Abu Thahir, Zunita Zakaria, Salina Abdul Rahman, Rozaihan Mansor and Sakshaleni Rajendiran

Antibiotics 2025, 14(5), 436; https://doi.org/10.3390/antibiotics14050436 - 26 Apr 2025

Viewed by 149

Abstract

Antimicrobial resistance (AMR) poses a significant “One Health” challenge in the farming industry attributed to antimicrobial misuse and overuse, affecting the health of humans, animals, and the environment. Recognizing the crucial role of the environment in facilitating the transmission of AMR is imperative [...] Read more.

Antimicrobial resistance (AMR) poses a significant “One Health” challenge in the farming industry attributed to antimicrobial misuse and overuse, affecting the health of humans, animals, and the environment. Recognizing the crucial role of the environment in facilitating the transmission of AMR is imperative for addressing this global health issue. Despite its urgency, there remains a notable gap in understanding resistance levels in the environment. This scoping review aims to consolidate and summarize available evidence of AMR prevalence and resistance genes in dairy farm settings. This study was conducted following the PRISMA Extension checklist to retrieve relevant studies conducted in Asian countries between 2013 and 2023. An electronic literature search involving PubMed, ScienceDirect, Embase, and Scopus resulted in a total of 1126 unique articles that were identified. After a full-text eligibility assessment, 39 studies were included in this review. The findings indicate that AMR studies in dairy farm environments have primarily focused on selective bacteria, especially Escherichia coli and other bacteria such as Staphylococcus aureus, Klebsiella spp., and Salmonella spp. Antimicrobial resistance patterns were reported across 24 studies involving 78 antimicrobials, which predominantly consisted of gentamicin (70.8%), ampicillin (58.3%), and tetracycline (58.3%). This review emphasizes the current state of AMR in the environmental aspects of dairy farms across Asia, highlighting significant gaps in regional coverage and bacterial species studied. It highlights the need for broader surveillance, integration with antimicrobial stewardship, and cross-sector collaboration to address AMR through a One Health approach. Full article

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

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13 pages, 1484 KiB

Open AccessArticle

Distribution, Antibiotic Resistance, and Virulence Factors of Vibrio parahaemolyticus in the Southern Coastal Waters of Republic of Korea

by Hyunwoo Zin, Intae Ham, Soonbum Shin, Hongsik Yu, Tae-Jin Choi, Kwangsoo Ha and Jong Soo Mok

Antibiotics 2025, 14(5), 435; https://doi.org/10.3390/antibiotics14050435 - 26 Apr 2025

Viewed by 116

Abstract

Background/Objectives: Vibrio parahaemolyticus is a marine bacterium and a major cause of food poisoning worldwide, primarily associated with gastric illnesses such as gastroenteritis. This study aimed to investigate the distribution, antibiotic resistance, and virulence genes of V. parahaemolyticus present in shellfish and [...] Read more.

Background/Objectives: Vibrio parahaemolyticus is a marine bacterium and a major cause of food poisoning worldwide, primarily associated with gastric illnesses such as gastroenteritis. This study aimed to investigate the distribution, antibiotic resistance, and virulence genes of V. parahaemolyticus present in shellfish and seawater of the southern coast of Korea, a major shellfish harvesting area. Methods: Shellfish and seawater samples were collected monthly in 2023 from 24 coastal sites in Korea. V. parahaemolyticus was isolated and identified using the MPN method, biochemical tests, MALDI-TOF mass spectrometry, and 16S rRNA sequencing. Antimicrobial susceptibility was tested for 673 isolates using the Sensititre MIC system, and virulence genes (tdh and trh) were detected by PCR. Results:V. parahaemolyticus had a detection rate of 18.2–58.3% in shellfish and 8.3–50% in seawater samples. Among the isolates, 97.9% and 97.3% were resistant to ampicillin and colistin, respectively, while 8.3% showed resistance to four or more antibiotics. The virulence genes tdh and trh were detected in 0.45% and 3.34% of shellfish samples and 1.23% and 4.46% of seawater samples, respectively. Conclusions: These findings will help implement appropriate precautionary measures to prevent potential human health risks arising from exposure to multidrug-resistant or pathogenic V. parahaemolyticus. Full article

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17 pages, 3733 KiB

Open AccessArticle

Impact of Parenteral Ceftiofur on Developmental Dynamics of Early Life Fecal Microbiota and Antibiotic Resistome in Neonatal Lambs

by Mohamed Donia, Nasr-Eldin Aref, Mohamed Zeineldin, Ameer Megahed, Benjamin Blair, James Lowe and Brian Aldridge

Antibiotics 2025, 14(5), 434; https://doi.org/10.3390/antibiotics14050434 - 25 Apr 2025

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Abstract

Background: Early gut microbiome development is critical for neonatal health, and its dysbiosis may impact long-term animal productivity. This study examined the effects of parenteral Ceftiofur Crystalline Free Acid (CCFA) on the composition and diversity of the neonatal lamb fecal microbiome. The emergence [...] Read more.

Background: Early gut microbiome development is critical for neonatal health, and its dysbiosis may impact long-term animal productivity. This study examined the effects of parenteral Ceftiofur Crystalline Free Acid (CCFA) on the composition and diversity of the neonatal lamb fecal microbiome. The emergence of antimicrobial resistance genes associated with CCFA exposure was also investigated. Results: There were distinct microbial populations in the CCFA-treated lambs compared to the control group at each time point, with a highly significant decrease in alpha and beta diversity. The CCFA treatment showed a reduction in several key microbial taxa during nursing, but these differences were diminished by day 56. Unlike the control group, CCFA-treated lambs had core microbes potentially carrying multiple antibiotic resistance genes, including those for beta-lactam, fosfomycin, methicillin, and multidrug resistance. Methods: Twenty-four healthy neonatal lambs were randomly assigned to CCFA-treated (n = 12) and control (n = 12) groups. Fecal samples were collected on days 0, 7, 14, 28, and 56. Genomic DNA was extracted and sequenced using the Illumina MiSeq platform. Microbial composition was analyzed using the MG-RAST pipeline with the RefSeq database. Conclusions: Despite temporary reductions in critical bacterial populations during nursing, the early sheep fecal microbiome demonstrated resilience by repopulating after CCFA antibiotic disruption. While this highlights microbiota stability after short-course antibiotic exposure, the transient disturbance underscores potential risks to early gut health. Importantly, persistent CCFA resistance poses environmental dissemination risks, emphasizing the need for cautious antibiotic use in livestock to mitigate ecological impacts. Full article

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14 pages, 270 KiB

Open AccessArticle

A One Health Approach Metagenomic Study on Antimicrobial Resistance Traits of Canine Saliva

by Adrienn Gréta Tóth, Darinka Lilla Tóth, Laura Remport, Imre Tóth, Tibor Németh, Attila Dubecz, Árpád V. Patai, Zsombor Wagenhoffer, László Makrai and Norbert Solymosi

Antibiotics 2025, 14(5), 433; https://doi.org/10.3390/antibiotics14050433 - 25 Apr 2025

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Abstract

Background: According to the One Health concept, the physical proximity between pets and their owners facilitates the interspecies spread of bacteria including those that may harbor numerous antimicrobial resistance genes (ARGs). Methods: A shotgun sequencing metagenomic data-based bacteriome and resistome study of 1830 [...] Read more.

Background: According to the One Health concept, the physical proximity between pets and their owners facilitates the interspecies spread of bacteria including those that may harbor numerous antimicrobial resistance genes (ARGs). Methods: A shotgun sequencing metagenomic data-based bacteriome and resistome study of 1830 canine saliva samples was conducted considering the subsets of ARGs with higher public health risk, ESKAPE pathogen relatedness (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species), and survey results on the physical and behavioral characteristics of the participating dogs. Results: A total of 318 ARG types achieved sufficiently high detection rates. These ARGs can affect 31 antibiotic drug classes through various resistance mechanisms. ARGs against tetracyclines, cephalosporins, and, interestingly, peptides appeared in the highest number of samples. Other Critically Important Antimicrobials (CIAs, WHO), such as aminoglycosides, fluoroquinolones, or macrolides, were among the drug classes most frequently affected by ARGs of higher public health risk and ESKAPE pathogen-related ARGs of higher public health risk. Several characteristics, including coat color, sterilization status, size, activity, or aggressiveness, were associated with statistically significant differences in ARG occurrence rates (p < 0.0500). Conclusions: Although the oral microbiome of pet owners is unknown, the One Health and public health implications of the close human–pet bonds and the factors potentially underlying the increase in salivary ARG numbers should be considered, particularly in light of the presence of ARGs affecting critically important drugs for human medicine. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and One Health: New Solutions for an Old Problem?)

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20 pages, 5562 KiB

Open AccessArticle

Antifungal and Antibiofilm Activities of 2-Aminobenzoic Acid Derivatives Against a Clinical Ocular Candida albicans Isolate for Biomedical Applications

by Francesco Petrillo, Angela Maione, Marisa Spampinato, Lea Di Massa, Marco Guida, Armando Zarrelli, Emilia Galdiero and Luigi Longobardo

Antibiotics 2025, 14(5), 432; https://doi.org/10.3390/antibiotics14050432 - 25 Apr 2025

Viewed by 161

Abstract

Ocular fungal infections are slow-progressing conditions that primarily affect the cornea but can also involve the entire eyeball. Candida albicans is one of the most involved species. Both diagnosing and treating these infections require prompt and effective action. However, the currently available treatment [...] Read more.

Ocular fungal infections are slow-progressing conditions that primarily affect the cornea but can also involve the entire eyeball. Candida albicans is one of the most involved species. Both diagnosing and treating these infections require prompt and effective action. However, the currently available treatment options mainly rely on azoles and polyenes, which are known for their poor penetration into ocular tissue and associated toxicity. Moreover, conventional antifungals are usually ineffective when tested against biofilm-associated infections, mainly due to the metabolically inactive state of dormant cells embedded in the extracellular biofilm matrix. Here, analysis of the in vitro antifungal activity of four 2-aminobenzoic acid derivatives synthesized using a green method and their combination with Fluconazole (FLC) showed efficacy against the FLC-resistant clinical isolate of C. albicans under both planktonic and biofilm formation conditions. Results showed that compounds 1 and 2 exhibited the best antifungal activity in the checkerboard association test, presenting a synergistic effect towards antifungal action. The downregulation of HWP, ERG11, and ASL3 genes during biofilm inhibition suggested a reduced capacity of the four compounds for hyphal growth and adhesion, as well as a decrease in pathogenicity due to the downregulation of some SAP genes. In vitro and in vivo toxicity profiles indicated that these compounds exhibited low toxicity, as well as the absence of genotoxic effects. Therefore, green-synthetized 2-aminobenzoic acid derivatives may have potential as antifungal agents for the inhibition of C. albicans growth and biofilm formation. Full article

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18 pages, 2812 KiB

Open AccessArticle

Repurposing of Furin Inhibitors to Reduce Pathogenic E. coli- and Shigella flexneri-Induced Cytotoxicity, Oxidative Stress and Inflammation in Mammalian Epithelial Cells

by Isabella Rumer, Lilla Tóth, Annelie Wohlert, András Adorján, Ákos Jerzsele, Roman W. Lange, Torsten Steinmetzer and Erzsébet Gere-Pászti

Antibiotics 2025, 14(5), 431; https://doi.org/10.3390/antibiotics14050431 - 24 Apr 2025

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Abstract

Background/Objectives: Enterobacteriaceae, including pathogenic Shigella (S.) flexneri and Escherichia (E.) coli, cause severe gastrointestinal infections through toxins like Shiga and Shiga-like toxins. Antibiotic use is often discouraged due to its potential to increase toxin effects or contribute to [...] Read more.

Background/Objectives: Enterobacteriaceae, including pathogenic Shigella (S.) flexneri and Escherichia (E.) coli, cause severe gastrointestinal infections through toxins like Shiga and Shiga-like toxins. Antibiotic use is often discouraged due to its potential to increase toxin effects or contribute to the development of resistance. The host protease furin is capable of activating several viral glycoproteins and bacterial toxins, thus enhancing pathogen infectivity. Methods: To assess the therapeutic potential of furin inhibitors, cultured epithelial cell models (IPEC-J2 and MDCK) were used. The effects of MI-1851 and MI-2415 were evaluated after short-term (2 h) and long-term (6 h) exposure to S. flexneri, enterohemorrhagic E. coli (EHEC), and enteropathogenic E. coli (EPEC). Cytotoxicity was determined using the CCK-8 assay, and the inflammatory response was assessed by measuring interleukin (IL)-6 and IL-8 levels. Additionally, extracellular hydrogen peroxide production was monitored in IPEC-J2 cells to evaluate the potential alterations in redox status. Results: Infections with EHEC, EPEC, and S. flexneri significantly reduced the viability of epithelial cells after 6 h of incubation. Furin inhibitors MI-1851 and MI-2415 decreased cytotoxicity and compensated for IL-6 and IL-8 overproduction in cells during infection with EHEC and S. flexneri, but not in cells exposed to EPEC. In addition, they alleviated oxidative stress, particularly during S. flexneri addition. Conclusions: The development of new antimicrobial drugs that act via alternative mechanisms and effectively manage life-threatening enterobacterial infections is of key importance. Targeting furin with inhibitors MI-1851 and MI-2415, thus blocking toxin activation, could prevent the development of antimicrobial resistance, reduce the need for antibiotics and enhance overall treatment outcomes. Full article

(This article belongs to the Special Issue Discovery and Synthesis of Antimicrobial Compounds Against Multidrug Resistance)

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21 pages, 3968 KiB

Open AccessArticle

Antifungal Peptides SmAP_α1–21 and SmAP_γ27–44 Designed from Different Loops of DefSm2-D Have Distinct Modes of Action

by Micaela Iturralde, Juan Pablo Bracho, Jessica A. Valdivia-Pérez, Fanny Guzmán, Ismael Malbrán, Sabina María Maté, María Laura Fanani and Sandra Vairo Cavalli

Antibiotics 2025, 14(5), 430; https://doi.org/10.3390/antibiotics14050430 - 24 Apr 2025

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Abstract

Background: The use of antimicrobial peptides (AMPs) as biotechnological tools is an area of growing interest in the research that seeks to improve crop defense. SmAP_α1–21 and SmAP_γ27–44 were previously reported to inhibit Fusarium graminearum, permeabilize the plasma membrane and [...] Read more.

Background: The use of antimicrobial peptides (AMPs) as biotechnological tools is an area of growing interest in the research that seeks to improve crop defense. SmAP_α1–21 and SmAP_γ27–44 were previously reported to inhibit Fusarium graminearum, permeabilize the plasma membrane and induce cytoplasmic disorganization. To exert its activity, SmAP_α1–21 initially enters through the basal and apical cells of F. graminearum conidia and then displays a general but non-homogeneous distribution in the cytoplasm of all conidial cells, in contrast. Methods: We analyzed, focusing on membrane interaction, the mode of action of SmAP_γ27–44, a peptide based on the γ-core of defensins DefSm2-D and DefSm3, and SmAP_α1–21, based on the α-core of DefSm2-D. Additionally, we compared the behavior of SmAP_α1–21 with that of SmAP3_α1–21 based on DefSm3 but with no activity against F. graminearum. Results: In this study, we showed that SmAP_γ27–44 enters the cells with discrete intracellular localization. Furthermore, both peptides disrupted the plasma membrane, but with different modes of action. When large unilamellar liposomes (LUVs) containing phosphatidic acid and ergosterol were used as a filamentous fungal plasma membrane model, SmAP_γ27–44 strongly induced aggregation concomitantly with the solubilization of the liposomes and showed the maximal insertion of its tryptophan moiety into the membrane’s hydrophobic interior. In comparison, SmAP_α1–21 showed a high effect on the ζ potential of anionic vesicles, vesicle aggregation capacity after reaching a concentration threshold, and moderate transfer of tryptophan to the membrane. SmAP3_α1–21, on the other hand, showed poor superficial adsorption to liposomes. Conclusions: In view of our results, a cell penetration peptide-like effect was pictured for the γ-core defensin-derived peptide and a classical AMP action was observed for the α-core defensin-derived one. Full article

(This article belongs to the Section Antimicrobial Peptides)

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24 pages, 4838 KiB

Open AccessArticle

Genetically Modified Mesenchymal Stromal/Stem Cells as a Delivery Platform for SE-33, a Cathelicidin LL-37 Analogue: Preclinical Pharmacokinetics and Tissue Distribution in C57BL/6 Mice

by Vagif Ali oglu Gasanov, Dmitry Alexandrovich Kashirskikh, Victoria Alexandrovna Khotina, Arthur Anatolievich Lee, Sofya Yurievna Nikitochkina, Daria Mikhailovna Kuzmina, Irina Vasilievna Mukhina, Ekaterina Andreevna Vorotelyak and Andrey Valentinovich Vasiliev

Antibiotics 2025, 14(5), 429; https://doi.org/10.3390/antibiotics14050429 - 24 Apr 2025

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Abstract

Background: The genetic modification of mesenchymal stromal/stem cells (MSCs) to express antimicrobial peptides may provide a promising strategy for developing advanced cell-based therapies for bacterial infections, including those caused or complicated by antibiotic-resistant bacteria. We have previously demonstrated that genetically modified Wharton’s jelly-derived [...] Read more.

Background: The genetic modification of mesenchymal stromal/stem cells (MSCs) to express antimicrobial peptides may provide a promising strategy for developing advanced cell-based therapies for bacterial infections, including those caused or complicated by antibiotic-resistant bacteria. We have previously demonstrated that genetically modified Wharton’s jelly-derived MSCs expressing an antimicrobial peptide SE-33 (WJ-MSC-SE33) effectively reduce bacterial load, inflammation, and mortality in a mouse model of Staphylococcus aureus-induced pneumonia compared with native WJ-MSCs. The present study aimed to evaluate the pharmacokinetics and tissue distribution of the SE-33 peptide expressed by WJ-MSC-SE33 following administration to animals. Methods: WJ-MSC-SE33 were administered to C57BL/6 mice at therapeutic and excess doses. The biodistribution and pharmacokinetics of the SE-33 peptide were analyzed in serum, lungs, liver, and spleen using chromatographic methods after single and repeated administrations. Results: The SE-33 peptide exhibited dose-dependent pharmacokinetics. The highest levels of SE-33 peptide were detected in the liver and lungs, with persistence in tissues for up to 48 h at medium and high doses of administered WJ-MSC-SE33. A repeated administration of WJ-MSC-SE33 increased SE-33 levels in target organs. Conclusions: The SE-33 peptide expressed by genetically modified WJ-MSCs demonstrated predictable pharmacokinetics and effective biodistribution. These findings, together with the previously established safety profile of WJ-MSC-SE33, support its potential as a promising cell-based therapy for bacterial infections, particularly those associated with antibiotic resistance. Full article

(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics of Antibacterial and Antivirulence Drugs, 2nd Edition)

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29 pages, 2491 KiB

Open AccessArticle

Clinical and Epidemiological Characteristics of Pediatric Pertussis Cases: A Retrospective Study from Southeast Romania

by Cristina Maria Mihai, Ancuta Lupu, Tatiana Chisnoiu, Adriana Luminita Balasa, Ginel Baciu, Silvia Fotea, Vasile Valeriu Lupu, Violeta Popovici, Simona Claudia Cambrea, Mircea Grigorian, Felicia Suciu, Florin-Daniel Enache, Anna Sora and Ramona Mihaela Stoicescu

Antibiotics 2025, 14(5), 428; https://doi.org/10.3390/antibiotics14050428 - 23 Apr 2025

Viewed by 233

Abstract

Background/Objectives: Pertussis remains a significant cause of respiratory illness in children, particularly in regions with suboptimal vaccination coverage. This retrospective study analyzes the clinical presentations, co-infections, treatment, and outcomes of pediatric patients diagnosed with Bordetella pertussis at the Constanța County Clinical Emergency Hospital [...] Read more.

Background/Objectives: Pertussis remains a significant cause of respiratory illness in children, particularly in regions with suboptimal vaccination coverage. This retrospective study analyzes the clinical presentations, co-infections, treatment, and outcomes of pediatric patients diagnosed with Bordetella pertussis at the Constanța County Clinical Emergency Hospital “St. Apostle Andrew” between 1 January and 30 September 2024. Methods: Thirty-eight children, predominantly under the age of 3 years (81.58%), were included. Demographic data, clinical features, coinfecting pathogens, antimicrobial regimens, and hospital outcomes were reviewed. Results: Only 7 out of 38 children (18.42%) had received pertussis vaccination, and none benefited from maternal immunization. The highest incidence occurred in infants under 1 year (44.74%). Intensive care was required in 18.42% of cases, and macrolides were the most frequently used antibiotics (68.42%). Co-detection of respiratory pathogens—particularly Streptococcus pneumoniae, enteroviruses, and human rhinoviruses—was common. Severe cases often exhibited hyperleukocytosis, which was associated with complications such as heart failure. Conclusions: These findings underscore the need for timely recognition and management of pertussis and its complications. Although macrolides remain the first-line therapy, adjunctive treatments like leukoreduction may be considered in critical cases. The persistence of pertussis despite vaccination efforts highlights the challenges posed by waning immunity and diagnostic limitations, reinforcing the need for strengthened public health strategies. Full article

(This article belongs to the Special Issue Epidemiology, Clinical Microbiology and Antimicrobial Therapy: A Shared Effort against Infectious Diseases)

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17 pages, 1861 KiB

Open AccessReview

Overcoming Pseudomonas aeruginosa in Chronic Suppurative Lung Disease: Prevalence, Treatment Challenges, and the Promise of Bacteriophage Therapy

by Jagdev Singh, Melinda Solomon, Jonathan Iredell and Hiran Selvadurai

Antibiotics 2025, 14(5), 427; https://doi.org/10.3390/antibiotics14050427 - 23 Apr 2025

Viewed by 295

Abstract

Pseudomonas aeruginosa, a multidrug-resistant pathogen, significantly impacts patients with chronic respiratory conditions like cystic fibrosis (CF) and non-CF chronic suppurative lung disease (CSLD), contributing to progressive lung damage and poor clinical outcomes. This bacterium thrives in the airway environments of individuals with [...] Read more.

Pseudomonas aeruginosa, a multidrug-resistant pathogen, significantly impacts patients with chronic respiratory conditions like cystic fibrosis (CF) and non-CF chronic suppurative lung disease (CSLD), contributing to progressive lung damage and poor clinical outcomes. This bacterium thrives in the airway environments of individuals with impaired mucociliary clearance, leading to persistent infections and increased morbidity and mortality. Despite advancements in management of these conditions, treatment failure remains common, emphasising the need for alternative or adjunctive treatment strategies. Bacteriophage therapy, an emerging approach utilising viruses that specifically target bacteria, offers a potential solution to combat P. aeruginosa infections resistant to conventional antibiotics. This review examines the prevalence and disease burden of P. aeruginosa in CF and CSLD, explores the mechanisms behind antibiotic resistance, the promising role of bacteriophage therapy and clinical trials in this sphere. Full article

(This article belongs to the Section Bacteriophages)

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16 pages, 248 KiB

Open AccessArticle

Rapid Syndromic Testing: A Key Strategy for Antibiotic Stewardship in ICU Patients with Pneumonia

by Silvana Vulpie, Monica Licker, Oana Izmendi, Delia Muntean, Diana Lungeanu, Beatrice Sarah Zembrod, Iasmina Maria Hancu, Ovidiu Bedreag, Dorel Sandesc, Romanita Jumanca and Luminita Mirela Baditoiu

Antibiotics 2025, 14(5), 426; https://doi.org/10.3390/antibiotics14050426 - 23 Apr 2025

Viewed by 172

Abstract

Background/Objectives: According to the European Centre for Disease Prevention and Control, improved antimicrobial stewardship programs (ASPs) combined with rapid diagnostic tests could potentially prevent thousands of deaths caused by multidrug-resistant organisms annually. This study aimed to compare the results obtained using the Unyvero [...] Read more.

Background/Objectives: According to the European Centre for Disease Prevention and Control, improved antimicrobial stewardship programs (ASPs) combined with rapid diagnostic tests could potentially prevent thousands of deaths caused by multidrug-resistant organisms annually. This study aimed to compare the results obtained using the Unyvero system/hospital-acquired pneumonia (HPN) panel with those obtained using classic microbiological diagnostic methods to evaluate the potential of introducing this rapid diagnostic test into routine diagnosis and improving local ASPs. Methods: A single-center, observational, cross-sectional, analytical study was performed; it included patients admitted to the intensive care unit (ICU) with the presumptive diagnosis of community- or hospital-acquired pneumonia. One hundred non-repetitive endotracheal aspirates were collected and subjected to analysis using both methods. The concordance between the results obtained via the standard-of-care (SoC) culture and Unyvero was analyzed. Results: Of the results generated using Unyvero/HPN, 51% were fully concordant with those obtained via culture, 48% were partially concordant, and only 1% represented failure. It was also more efficient in identifying multiple organisms in a single sample than the SoC culture (1.32 versus 1.1 per sample). The three most common isolates identified via both methods were Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The most common resistance markers identified with Unyvero were sul1 (41%), tem and ndm (25%), and kpc, imp, vim, and gyrA87 (2% of results). Conclusions: Unyvero/HPN, if associated with appropriate diagnostic stewardship, could be used to manage critically ill patients to ensure an appropriate ASP. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Epidemiological Study of Clinically Relevant Pathogens)

8 pages, 699 KiB

Open AccessBrief Report

Suitability of Piperacillin–Tazobactam for Treating Dogs Infected with Extended-Spectrum β-Lactamase-Producing Enterobacterales: Pharmacokinetic and Pharmacodynamic Analysis

by Kazuki Harada, Hyo Harada, Yuka Kanao and Mizuki Kusumoto

Antibiotics 2025, 14(5), 425; https://doi.org/10.3390/antibiotics14050425 - 23 Apr 2025

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Abstract

Background/Objectives: Piperacillin–tazobactam (TZP) is a potential alternative to carbapenems for the treatment of dogs infected with extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), but its efficacy remains unestablished. In this study, pharmacokinetic–pharmacodynamic (PK/PD) analysis was performed to estimate the clinical efficacy of TZP against ESBL-E [...] Read more.

Background/Objectives: Piperacillin–tazobactam (TZP) is a potential alternative to carbapenems for the treatment of dogs infected with extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), but its efficacy remains unestablished. In this study, pharmacokinetic–pharmacodynamic (PK/PD) analysis was performed to estimate the clinical efficacy of TZP against ESBL-E infections in dogs. Methods: We determined the minimum inhibitory concentrations (MICs) of TZP in canine ESBL-E isolates, including Escherichia coli (n = 62), Klebsiella pneumoniae (n = 89), and Enterobacter cloacae (n = 31), using agar dilution. Monte Carlo Simulation (MCS) was performed to estimate the probability of target attainment (PTA) based on the PK/PD characteristics of TZP. Results: The MICs that can inhibit the growth of 90% of the isolates for the three bacterial species were determined as 16/4 µg/mL. MCS analysis revealed that the piperacillin PK/PD cutoff values (highest MICs with a PTA ≥90%) were ≤0.031, ≤0.5, and ≤2 μg/mL at a bolus dose of 50 mg/kg TZP (44.4 mg/kg piperacillin) every 12, 8, and 6 h (q12h, q8h, and q6h), respectively. The cumulative fractions of response were ≤90% based on the MIC distribution of ESBL-producing E. coli, K. pneumoniae, and E. cloacae isolates from dogs: 1.60, 0.48, and 0.15% at q12h; 32.56, 14.57, and 9.65% at q8h; and 74.51, 45.85, and 43.92% at q6h, respectively. Conclusions: We believe that TZP is not recommended for the treatment of canine ESBL-E infections, except for cases with a lower MIC than the PK/PD cutoff values determined in this study. Full article

(This article belongs to the Special Issue Antibiotic and Antiparasitic Resistance in Veterinary Clinical Settings)

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11 pages, 1183 KiB

Open AccessArticle

Metabolic Stress Induced by Quercetin Enhances Dormancy and Persistence in Staphylococcus aureus

by Dae-Youn Kim and Tae-Jong Kim

Antibiotics 2025, 14(5), 424; https://doi.org/10.3390/antibiotics14050424 - 22 Apr 2025

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Abstract

Background/Objectives: The persistence of Staphylococcus aureus poses a significant challenge in clinical treatments because of its ability to withstand antibiotic therapy. This study assessed the role of quercetin in promoting bacterial dormancy and persistence through ATP depletion and revealed its potential impact [...] Read more.

Background/Objectives: The persistence of Staphylococcus aureus poses a significant challenge in clinical treatments because of its ability to withstand antibiotic therapy. This study assessed the role of quercetin in promoting bacterial dormancy and persistence through ATP depletion and revealed its potential impact on antibiotic tolerance. Methods: To assess the effects of quercetin on bacterial metabolism and persistence, S. aureus cultures were treated with quercetin, and intracellular ATP levels were then measured. The effect of quercetin on persister cell formation was assessed using antibiotic exposure assays, including pre-treatment and post-treatment strategies. Results: Quercetin treatment significantly depleted intracellular ATP levels in a dose-dependent manner, suggesting the presence of metabolic stress. This ATP depletion correlated with increased persister cell formation across multiple antibiotic treatments, indicating that quercetin-induced dormancy enhances bacterial persistence. Notably, quercetin pre-treatment further increased persister cell counts, while delayed quercetin administration increased persister cell survival, highlighting the influence of the timing of metabolic stress on persistence outcomes. Conclusions: Quercetin promotes bacterial persistence by inducing ATP depletion and metabolic dormancy. Although quercetin’s bactericidal properties may initially impair bacterial growth, its potential to enhance persistence underscores the complexity of its effects. Further research is necessary to determine optimal strategies for harnessing the antimicrobial properties of quercetin while minimizing its persistence-promoting effects. Full article

(This article belongs to the Special Issue Antimicrobial and Anti-Infective Activity of Natural Products, 2nd Edition)

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Antibiotics, Volume 14, Issue 5 (May 2025) – 32 articles

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