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Comparative Review of Avibactam, Vaborbactam, and Relebactam Against Multidrug-Resistant Superbugs
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Additive Manufacturing, Thermoplastics, CAD, and Reverse Engineering in Orthopedics and Neurosurgery for Infection Prevention and Treatment
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Vancomycin-Resistant E. faecium: Addressing Global and Clinical Challenges
Journal Description
Antibiotics
Antibiotics
is an international, peer-reviewed, open access journal on all aspects of antibiotics, published monthly online by MDPI. The Croatian Pharmacological Society (CPS) is affiliated with Antibiotics and its members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Infectious Diseases) / CiteScore - Q1 (General Pharmacology, Toxicology and Pharmaceutics )
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 15 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.6 (2024);
5-Year Impact Factor:
4.9 (2024)
Latest Articles
Selective Oral Decontamination of the Esophagus to Reduce Microbial Burden in Patients Undergoing Esophagectomy for Esophageal Cancer (SODA)—First Results from a Proof-of-Principle Study
Antibiotics 2025, 14(10), 1033; https://doi.org/10.3390/antibiotics14101033 (registering DOI) - 15 Oct 2025
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Background/Objectives: Postoperative pneumonia and other infectious complications after robotic-assisted minimally invasive esophagectomy still contribute to morbidity and mortality. Selective oral decontamination of the esophagus prior to surgery might reduce the rate of infectious complications. However, its impact on the esophageal microbiota is unknown.
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Background/Objectives: Postoperative pneumonia and other infectious complications after robotic-assisted minimally invasive esophagectomy still contribute to morbidity and mortality. Selective oral decontamination of the esophagus prior to surgery might reduce the rate of infectious complications. However, its impact on the esophageal microbiota is unknown. Therefore, this study aimed to analyze whether selective oral decontamination of the esophagus prior to surgery reduces postoperative pneumonia rates and alters the esophageal microbiome. Methods: We conducted a proof-of-principle study including 22 patients who underwent robotic-assisted minimally invasive esophagectomy. Thirteen patients were treated with 50 mg amphotericin B, 8 mg tobramycin, and 10 mg colistin orally 7 days prior to surgery, intraoperatively, and 5 days postoperatively. The remaining nine patients received standard-of-care treatment (no oral decontamination). The esophageal microbiome was assessed using 16S rRNA gene amplicon libraries which were annotated using the Ribosomal Data Project. The incidence of postoperative (at discharge from hospital or 30 days, whichever was later) infectious complications was assessed. Results: Selective oral decontamination was associated with reduced overall rates of infectious complications (7.7% vs. 55.5%, p = 0.008) and postoperative pneumonia (0% vs. 33.3%, p = 0.007). Alterations in the esophageal microbiome depending on selective oral decontamination were detectable. The microbiomes of patients with infectious complications showed higher abundances of Neisseria and lower abundances of Streptococcus than samples without infectious complications. Conclusions: Selective oral decontamination reduced the rate of postoperative complications, postoperative pneumonia in particular, after robot-assisted esophagectomy. Alterations in the microbiome were also evident following decontamination. Further studies with larger sample sizes are necessary to confirm these data.
Full article
Open AccessArticle
The Effect of Chlorhexidine Mouthwashes on the Microbiota Associated with Peri-Implantitis Lesions: A Pilot Study
by
Félix Pose-Otero, Alexandre Arredondo, Ana Parga, Andrea Muras, Mercedes Gallas, Paz Otero-Casal, José Manuel Pose-Rodríguez and Ana Otero
Antibiotics 2025, 14(10), 1032; https://doi.org/10.3390/antibiotics14101032 (registering DOI) - 15 Oct 2025
Abstract
Background/Objectives: Chlorhexidine (CHX)-based mouthwashes are the most commonly used chemical methods as adjuvants for the treatment of peri-implant diseases, but there is a lack of information on their effect on the peri-implant microbiota. The objective of this study was to evaluate the impact
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Background/Objectives: Chlorhexidine (CHX)-based mouthwashes are the most commonly used chemical methods as adjuvants for the treatment of peri-implant diseases, but there is a lack of information on their effect on the peri-implant microbiota. The objective of this study was to evaluate the impact of short-time (15 days) self-administered 0.05% and 0.12% commercial chlorhexidine mouthwashes on the peri-implant pocket microbiota of patients with peri-implantitis. Methods: In this pilot study, we analyzed the microbial composition of peri-implant lesions in 22 patients before and after a 15-day regimen of thrice-daily use of two commercial chlorhexidine mouthwashes containing 0.05% (n = 11) and 0.12% chlorhexidine (n = 11). Microbial samples were collected using paper points, and the taxonomic composition was determined through sequencing of 16S rRNA gene amplicons using Illumina MiSeq. Results: Although individual responses to chlorhexidine mouthwash treatment varied significantly, neither concentration produced a statistically significant change in the microbial diversity associated with peri-implantitis, suggesting limited treatment penetration into peri-implant lesions. Similarly, changes in the abundance of specific odontopathogens were not statistically significant. Conclusions: We found no significant differences in the effect of mouthwashes with different chlorhexidine concentrations on the peri-implant microbiota in short-period applications. Even though more extensive studies are required, the observed patient-dependent outcomes of both chlorhexidine mouthwashes on the peri-implant microbiota and their limited effect in controlling the abundance of oral pathogens indicate that prescription of chlorhexidine mouthwashes for the treatment of peri-implantitis should be carried out with caution. Novel presentations of chlorhexidine with better penetration capacities should be developed, as they could offer enhanced benefits in managing peri-implant diseases.
Full article
(This article belongs to the Special Issue Biofilm-Associated Oral Diseases: Advances in Diagnosis and Challenges in Treatment)
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Open AccessReview
Green Solutions to a Growing Problem: Harnessing Plants for Antibiotic Removal from the Environment
by
Gaia Cusumano, Giancarlo Angeles Flores, Roberto Venanzoni, Paola Angelini and Gokhan Zengin
Antibiotics 2025, 14(10), 1031; https://doi.org/10.3390/antibiotics14101031 (registering DOI) - 15 Oct 2025
Abstract
Environmental dissemination of antibiotics is a pressing global challenge, driving ecological imbalances and the proliferation of antibiotic resistance genes (ARGs). Conventional treatment technologies often fail to fully eliminate these micropollutants or are cost-prohibitive for widespread use. In this context, phytoremediation—using plants and their
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Environmental dissemination of antibiotics is a pressing global challenge, driving ecological imbalances and the proliferation of antibiotic resistance genes (ARGs). Conventional treatment technologies often fail to fully eliminate these micropollutants or are cost-prohibitive for widespread use. In this context, phytoremediation—using plants and their associated microbiota to remove, transform, or immobilize contaminants—has emerged as an effective and promising, low-impact, and nature-based approach for mitigating antibiotic pollution in aquatic and terrestrial environments. This review provides a comprehensive synthesis of the physiological, biochemical, and ecological mechanisms by which plants interact with antibiotics, including phytoextraction, phytodegradation, rhizodegradation, and phytostabilization. This review prioritizes phytoremediation goals, with attention to high-performing aquatic (e.g., Lemna minor, Eichhornia crassipes, Phragmites australis) and terrestrial plants (e.g., Brassica juncea, Zea mays) and their ability to remediate major classes of antibiotics. This study highlights the role of rhizosphere microbes and engineered systems in phytoremediation, while noting challenges such as variable efficiency, phytotoxicity risks, limited knowledge of by-products, and environmental concerns with antibiotic degradation. Future perspectives include the integration of genetic engineering, microbiome optimization, and smart monitoring technologies to enhance system performance and scalability. Plant-based solutions thus represent a vital component of next-generation remediation strategies aimed at reducing antibiotic burdens in the environment and curbing the rise in antimicrobial resistance.
Full article
(This article belongs to the Special Issue Plant-Based Strategies for the Removal and Degradation of Antibiotics from the Environment)
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Open AccessArticle
Occurrence and Molecular Characterization of Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli in Broilers in Indonesia
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Nur Hidayatullah, Imron Suandy, Montira Intanon, Thomas Alter, Oli Susanti, Ajeng Herpianti, Sani Susanty, Riska Desitania and Nattakarn Awaiwanont
Antibiotics 2025, 14(10), 1030; https://doi.org/10.3390/antibiotics14101030 (registering DOI) - 15 Oct 2025
Abstract
Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-E. coli) are widespread in the food chain, but nationwide surveillance in Indonesian broiler production is limited. This study investigated the occurrence, antimicrobial resistance, phylogenetic diversity, and molecular characteristics of ESBL-E. coli from broilers in Indonesia.
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Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-E. coli) are widespread in the food chain, but nationwide surveillance in Indonesian broiler production is limited. This study investigated the occurrence, antimicrobial resistance, phylogenetic diversity, and molecular characteristics of ESBL-E. coli from broilers in Indonesia. A total of 2182 E. coli isolates from broiler cecal samples across three regions during the period 2018–2020 were analyzed. Antimicrobial susceptibility testing and ESBL phenotyping were performed following the CLSI guidelines. ESBL resistance genes and phylogenetic groups were detected using multiplex/quadruplex PCR. ESBL-E. coli (9.9%) was most frequently observed in the western (15.2%) region, followed by the central (8.0%) and eastern (7.2%) regions. A total of 85 resistance patterns were identified, with 98.5% exhibiting multidrug resistance. The blaCTX-M gene was detected in 97.5% of isolates, predominantly blaCTX-M-1 (97.5%), while blaCTX-M-9 was found in 2.5%. The blaTEM gene was present in 33.0% of ESBL isolates; however, blaSHV and blaOXA-1 were absent. Phylogenetic group A predominated (42.0%), followed by E (22.5%), B1 (20.5%), F (10.5%), C (2.5%), and D (2.0%). This study demonstrates a significant occurrence of ESBL-E. coli in Indonesian broilers with regional variation and blaCTX-M predominance. The high rate of multidrug resistance poses a serious public health concern, emphasizing the urgent need for antimicrobial stewardship and enhanced surveillance programs.
Full article
(This article belongs to the Special Issue Antimicrobial Resistance: Epidemiology and Implications for Veterinary Medicine)
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Open AccessArticle
Environmental Amoxicillin Exposure Induces Cardiotoxicity in Zebrafish Embryos: A Comprehensive Assessment of Heart Function and Molecular Responses
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Azza Naïja, Dalal Mohamed, Somaiya Abdulhakim, Amera Mohamed and Huseyin Cagatay Yalcin
Antibiotics 2025, 14(10), 1029; https://doi.org/10.3390/antibiotics14101029 - 14 Oct 2025
Abstract
Background/Objectives. Environmental pollution poses a significant threat to human health, primarily through the degradation of natural ecosystems. Emerging organic contaminants (EOCs), such as pharmaceuticals like amoxicillin, are especially concerning due to their persistence and potential harm to non-target species. This study evaluates the
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Background/Objectives. Environmental pollution poses a significant threat to human health, primarily through the degradation of natural ecosystems. Emerging organic contaminants (EOCs), such as pharmaceuticals like amoxicillin, are especially concerning due to their persistence and potential harm to non-target species. This study evaluates the cardiotoxic effects of Amoxicillin (AMX) on Zebrafish embryos (Danio rerio), specifically heart function, blood flow, and gene expression linked to cardiogenesis, inflammation, and apoptosis. Methods. Zebrafish embryos were exposed to concentrations of AMX corresponding to environmentally relevant levels, wastewater effluents, as well as acute experimental exposures. Mortality and hatching rates were all assessed, along with heart function and gene expression analysis of key cardiac and inflammatory markers. Results/Conclusions. The findings suggest that higher AMX concentrations have cardiotoxic effects, emphasizing the need for stringent environmental monitoring of antibiotic residuals.
Full article
(This article belongs to the Topic Antimicrobial Agents and Nanomaterials—2nd Edition)
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Open AccessArticle
Epidemiological Evidence Supports the Role of Microbial Interactions in Polymicrobial UTI Infections Revealed by In Vitro Research
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Gabriella Piatti, Alessandro Mannini, Alberto Vitale, Marco Bruzzone, Anna Maria Schito and Marcello Ceppi
Antibiotics 2025, 14(10), 1028; https://doi.org/10.3390/antibiotics14101028 - 14 Oct 2025
Abstract
Background: Molecular techniques for microbial identification have highlighted the relevance of polymicrobial infections in humans, such as those affecting the urinary tract. Although in vitro investigations have demonstrated connections between co-infections and microbial interaction, their role is unclear in clinics, given the
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Background: Molecular techniques for microbial identification have highlighted the relevance of polymicrobial infections in humans, such as those affecting the urinary tract. Although in vitro investigations have demonstrated connections between co-infections and microbial interaction, their role is unclear in clinics, given the overlap with host conditions. Objective: We aimed to separate the roles of organisms and patient conditions in human polymicrobial urinary samples by performing a relevant epidemiological analysis. Methods: We analyzed retrospective results from urine cultures performed during one year in a 1200 beds Italian hospital. Patients were grouped as uncompromised and compromised and positive urine cultures were grouped as monomicrobial and polymicrobial. We assessed associations between single microorganisms and the groups of positive samples and between single microorganisms and the group of patients through a multivariate logistic regression model, adjusting by the confounding effect of seven variables. Results: We enrolled 24,067 urine samples, among which 7208 were positive, 75% monomicrobial and 25% polymicrobial. We found that the polymicrobial samples had a microbial scenario wider than the monomicrobial ones and the organisms most sampled had the highest number of different pairwise associations. Certain organisms shown having absolute numerical advantages in the polymicrobial urine cultures with respect to the monomicrobial ones, independently of host’s conditions. Conclusions: The numerical advantage shown by certain organisms in polymicrobial urine samples over monomicrobial samples supports the hypothesis of microbial synergies favouring the occurrence of certain co-infections.
Full article
(This article belongs to the Special Issue Urinary Tract Infections: Diagnosis, Etiology, Antibiotic Treatment, and Current Trends in Antimicrobial Resistance)
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Antimicrobial Resistance Profile of Staphylococcus pseudintermedius Isolated from Dogs with Otitis Externa and Healthy Dogs: Veterinary and Zoonotic Implications
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Ionela Popa, Ionica Iancu, Vlad Iorgoni, Janos Degi, Alexandru Gligor, Kalman Imre, Emil Tîrziu, Timea Bochiș, Călin Pop, Ana-Maria Plotuna, Paula Nistor, Marius Pentea, Viorel Herman and Ileana Nichita
Antibiotics 2025, 14(10), 1027; https://doi.org/10.3390/antibiotics14101027 - 14 Oct 2025
Abstract
Background/Objectives: Staphylococcus pseudintermedius (S. pseudintermedius) is an opportunistic pathogen frequently isolated from dogs, involved in a wide range of infections, particularly otitis externa. Increasing antimicrobial resistance (AMR), including methicillin-resistant S. pseudintermedius (MRSP), poses significant challenges for veterinary and potentially human
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Background/Objectives: Staphylococcus pseudintermedius (S. pseudintermedius) is an opportunistic pathogen frequently isolated from dogs, involved in a wide range of infections, particularly otitis externa. Increasing antimicrobial resistance (AMR), including methicillin-resistant S. pseudintermedius (MRSP), poses significant challenges for veterinary and potentially human health. This study aimed to assess the prevalence and antimicrobial resistance profiles of S. pseudintermedius in dogs with otitis externa compared to clinically healthy dogs. Methods: Between 2022 and 2025, samples were collected from 400 dogs with otitis externa and 360 healthy dogs in veterinary clinics from Timișoara. Ear swabs were processed by conventional microbiological techniques and confirmed using MALDI-TOF MS. Antimicrobial susceptibility was tested using the VITEK® 2 Compact system, following CLSI VET01, Fifth Edition (2018) standards. Fourteen antimicrobials from 11 classes were evaluated. Results: S. pseudintermedius was isolated in 40% of dogs with otitis externa and in 21.1% of healthy dogs. The highest resistance in both groups was observed to tetracycline (37.5% and 25%, respectively). No resistance was recorded to linezolid, vancomycin, teicoplanin, tigecycline, or fusidic acid. MRSP strains were identified in 1.2% of dogs with otitis, displaying multidrug resistance (MDR). MDR strains were also detected in 8.7% of diseased and 4% of healthy dogs, indicating the potential for subclinical reservoirs. Conclusions: The findings highlight the notable prevalence and AMR of S. pseudintermedius in both symptomatic and asymptomatic dogs. The detection of MRSP and MDR strains emphasizes the need for prudent antibiotic use and continuous AMR surveillance in veterinary medicine to mitigate zoonotic risks and preserve antimicrobial efficacy.
Full article
(This article belongs to the Special Issue Veterinary Microbiology and Antimicrobial Resistance—the One Health Approach)
Open AccessArticle
Peri-Operative Antimicrobial Prophylaxis Modulates CD4+ Lymphocyte Immunophenotype Ex Vivo in High-Risk Patients Undergoing Major Elective Surgery—A Preliminary Observational Study
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Susi Paketci, Jack Williams, Walter Pisciotta, Richard Loye, Alessia V. Waller, Rahila Haque, David Brealey, Mervyn Singer, John Whittle, Ramani Moonesinghe, Nishkantha Arulkumaran, Timothy Arthur Chandos Snow and the University College London Hospitals Critical Care Research Team
Antibiotics 2025, 14(10), 1026; https://doi.org/10.3390/antibiotics14101026 - 14 Oct 2025
Abstract
Background: Post-operative infections are a significant cause of morbidity in patients undergoing major elective surgery. Peri-operative antibiotics are used to reduce the risk of infection. Several antibiotics modulate the host immune response. Objectives: Our objective was to determine the ex vivo
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Background: Post-operative infections are a significant cause of morbidity in patients undergoing major elective surgery. Peri-operative antibiotics are used to reduce the risk of infection. Several antibiotics modulate the host immune response. Objectives: Our objective was to determine the ex vivo immunomodulatory properties of commonly used antibiotics (amoxicillin, cefuroxime, metronidazole, or combined cefuroxime–metronidazole) on monocyte and lymphocyte phenotypes in patients undergoing major elective surgery. Methods: We performed a prospective cohort study of patients aged ≥18 years admitted to the post-anaesthetic care unit following major elective non-cardiac surgery. Peripheral blood mononuclear cells isolated immediately after surgery were incubated with antibiotics with or without a monocyte (heat-killed E coli) or lymphocyte (CD3/CD28 beads) stimulus ex vivo. Immune cell phenotype was characterised using flow cytometry. Results: Twenty-eight patients were included. All antibiotics tested were associated with a reduction in T-cell viability, and changes to monocytes were minimal. Among CD4+ and CD8+ lymphocytes, cefuroxime increased IFN-γ (at low and high doses) and increased CD4+ lymphocyte IL-2 and IL-2R at higher doses. Among CD4+ lymphocytes, at both doses, cefuroxime increased %Th1 population, with a parallel decrease in %Th2, %Th17, IL-17A, FOX-P3, and T-bet. Among the Th1 sub-population, changes were seen at higher cefuroxime doses, including increased viability and PD-1, and a decrease in FAS, IFN-γ and CD28, and IL-7R expression. Conclusions: The choice of antibiotics directly impacts immune function following major surgery, with cefuroxime associated with ex vivo immunomodulatory effects on CD4+ lymphocytes. The functional implications on the development of subsequent post-operative infectious complications and long-term cancer-free survival require further investigation.
Full article
(This article belongs to the Special Issue Antimicrobial Stewardship in Surgical Infection)
Open AccessArticle
Looking for ESKAPE Bacteria: Occurrence and Phenotypic Antimicrobial Resistance Profiles in Wild Birds from Northern and Central Italy Sites
by
Guido Grilli, Maria Cristina Rapi, Laura Musa, Giacomo Di Giacinto, Fabrizio Passamonti, Stefano Raimondi, Oriana Cianca and Maria Pia Franciosini
Antibiotics 2025, 14(10), 1025; https://doi.org/10.3390/antibiotics14101025 - 14 Oct 2025
Abstract
Background/Objectives: Antimicrobial resistance is a critical global health challenge. Among resistant pathogens, the group of bacteria collectively referred to as ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) is of particular
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Background/Objectives: Antimicrobial resistance is a critical global health challenge. Among resistant pathogens, the group of bacteria collectively referred to as ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) is of particular concern due to their ability to evade multiple classes of antimicrobials. This study aimed to investigate the occurrence and resistance patterns of ESKAPE bacteria in wild birds from Northern and Central Italy sites, and to assess the presence of other bacteria of public health relevance. Methods: Cloacal swabs were collected from 141 wild birds. Samples were processed on selective and differential media, and bacterial identification was performed using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Antimicrobial susceptibility was evaluated through Minimum Inhibitory Concentration assays and interpreted according to international guidelines. Results: Thirty-seven isolates belonging to the ESKAPE group were identified: E. faecium (n = 10), K. pneumoniae (n = 9), P. aeruginosa (n = 8), Enterobacter spp. (n = 7), S. aureus (n = 2), and A. baumannii (n = 1). Multidrug-resistant isolates were observed among K. pneumoniae and Enterobacter hormaechei. Escherichia coli, although not included in the ESKAPE group, was frequently detected and often co-isolated with clinically relevant bacteria, highlighting its potential role as a reservoir of resistance genes. Conclusions: Wild birds can harbor resistant bacteria of clinical importance, including multidrug-resistant ESKAPE species. Their presence in avian populations underscores the role of wildlife in the environmental dissemination of antimicrobial resistance, with implications for both animal and human health.
Full article
(This article belongs to the Special Issue Epidemiology, Drug Resistance, and Virulence in Zoonotic Pathogens)
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Open AccessArticle
Ampicillin- and Multidrug-Resistant Escherichia coli and Enterococcus spp. in Costa Rican Wastewater and Surface Water
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Eleanor A. Brodrick, Adriana González-Fernández, Andrew M. Kramer and Valerie J. Harwood
Antibiotics 2025, 14(10), 1024; https://doi.org/10.3390/antibiotics14101024 - 14 Oct 2025
Abstract
Antibiotic-resistant bacteria (ARB) such as Escherichia coli and Enterococcus released into surface waters have strong potential to impact human health. We assessed the prevalence of antibiotic-resistant bacteria (ARB) and multidrug-resistant (MDR) bacteria in undisinfected wastewater effluent in a tropical estuary that receives the
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Antibiotic-resistant bacteria (ARB) such as Escherichia coli and Enterococcus released into surface waters have strong potential to impact human health. We assessed the prevalence of antibiotic-resistant bacteria (ARB) and multidrug-resistant (MDR) bacteria in undisinfected wastewater effluent in a tropical estuary that receives the discharge from a major wastewater treatment plant (WWTP) in Costa Rica. Methods: We quantified culturable ampicillin-resistant (ampR) and (MDR) E. coli and Enterococcus in wastewater influent from hospital and residential sources, effluent, and estuarine receiving waters of the secondary-treated effluent of a WWTP. AmpR isolates confirmed to species or genus were tested for resistance against six additional antibiotic classes. Results: The proportion of ampR E. coli (18%) was significantly greater than that of ampR enterococci (4%) but neither differed among sites. AmpR E. coli concentrations were significantly different by site (estuary, 3.9 log10 CFU/100 mL vs. untreated residential wastewater, 6.4 log10 CFU/100 mL), but ampR enterococci concentrations were consistent among sites. MDR E. coli and Enterococcus were most prevalent in hospital wastewater (57% and 45% of ampR isolates, respectively), but were found at all sites. MDR E. coli and Enterococcus isolates resistant to five antibiotics were isolated from the estuary, and gentamicin-resistant Enterococcus were isolated only from effluent. Conclusions: Undisinfected effluent is a source of ARB and MDR opportunistic pathogens in the tropical estuary and has the potential to impact the health of beachgoers. Our findings highlight the importance of rigorous treatment of wastewater effluent, including disinfection, as a contribution to efforts to achieve effective stewardship of antibiotics.
Full article
Open AccessArticle
Bacteriophages Biocontrol of Kiwifruit Bacterial Canker Caused by Pseudomonas syringae pv. actinidiae (Psa) in Two Seasons Under Field Conditions
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Paulina Sanhueza, Natalia Riquelme, Marcela Leon, Javiera Gaete Morales, Camila Prince, M. Fernanda Flores, Carolina Yañez, Italo F. Cuneo, Roberto Bastías and Ximena Besoain
Antibiotics 2025, 14(10), 1023; https://doi.org/10.3390/antibiotics14101023 - 14 Oct 2025
Abstract
Background: Since 2008, the kiwifruit industry has been significantly impacted by Pseudomonas syringae pv. actinidiae (Psa), the agent responsible for bacterial canker in kiwifruit. Existing treatments, such as copper-based compounds and antibiotics, have faced challenges related to resistance and soil contamination. Phage therapy
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Background: Since 2008, the kiwifruit industry has been significantly impacted by Pseudomonas syringae pv. actinidiae (Psa), the agent responsible for bacterial canker in kiwifruit. Existing treatments, such as copper-based compounds and antibiotics, have faced challenges related to resistance and soil contamination. Phage therapy is a promising and safe alternative for controlling this pathogen. This study aimed to evaluate the use of a mixture of four isolated and characterized bacteriophages as potential biocontrol agents against Psa. Methods: Trials were conducted at two locations in Chile, where Psa presence was reported during the 2019/2020 and 2020/2021 seasons, with a focus on the spring stages. Different formulations were tested each season to evaluate possible improvements in effectiveness. Pseudomonas spp. isolates obtained from epiphyte populations were characterized using morphological, biochemical (LOPAT), and molecular techniques. Results: Field trials demonstrated that the phage mixture effectively reduced the damage associated with Psa on kiwi leaves, resulting in a decrease in the Pseudomonas spp. bacterial load (42.9% for Peumo and 25% for Linares) at both locations during the first season trials. This decrease is associated with a reduction in the incidence and severity of the disease in kiwi plants in the Peumo orchard. In both seasons, bacteriophages reduce Psa symptoms in treated kiwi plants compared to untreated controls, at least at one location and evaluation. In both orchards during the first season, bacteriophages also outperformed copper- and antibiotic-based treatments used by farmers. Bacteriophage therapy is eco-friendly and safe for both applicators and consumers.
Full article
(This article belongs to the Special Issue Bacteriophage Therapy a Renaissance Weapon Recent Developments and Application, 2nd Edition)
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Open AccessSystematic Review
Mangrove Ecosystems as Reservoirs of Antibiotic Resistance Genes: A Narrative Review
by
Monthon Lertcanawanichakul, Phuangthip Bhoopong and Phusit Horpet
Antibiotics 2025, 14(10), 1022; https://doi.org/10.3390/antibiotics14101022 - 14 Oct 2025
Abstract
Background: Mangrove ecosystems are critical coastal environments providing ecological services and acting as buffers between terrestrial and marine systems. Rising antibiotic use in aquaculture and coastal agriculture has led to the dissemination of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in
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Background: Mangrove ecosystems are critical coastal environments providing ecological services and acting as buffers between terrestrial and marine systems. Rising antibiotic use in aquaculture and coastal agriculture has led to the dissemination of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in these habitats. Aim: This narrative review aims to synthesize current knowledge on the prevalence, diversity, and environmental drivers of ARGs in mangrove ecosystems, highlighting their role as reservoirs and the potential for horizontal gene transfer. Methods: Studies published up to September 2024 were identified through PubMed, Scopus, Web of Science, and Google Scholar. Inclusion criteria focused on ARGs and ARB in mangrove sediments, water, and associated biota. Data on ARG prevalence, microbial community composition, detection methods, and environmental factors were extracted and narratively synthesized. Results: Seventeen studies from Asia, South America, and Africa were included. ARGs conferring resistance to tetracyclines, sulfonamides, β-lactams, and multidrug resistance were found to be widespread, particularly near aquaculture and urban-influenced areas. Metagenomic analyses revealed diverse resistomes with frequent mobile genetic elements, indicating high potential for horizontal gene transfer. Environmental factors, including sediment type, organic matter, and salinity, influenced ARG abundance and distribution. Conclusions: Mangrove ecosystems act as both reservoirs and natural buffers for ARGs. Sustainable aquaculture practices, continuous environmental monitoring, and integrated One Health approaches are essential to mitigate ARG dissemination in these sensitive coastal habitats.
Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Aquaculture: Balancing Health and Sustainability)
Open AccessArticle
ISApl4, a New IS1595 Family Insertion Sequence Forming a Novel Pseudo-Compound Transposon That Confers Antimicrobial Multidrug Resistance in Actinobacillus pleuropneumoniae
by
Janine T. Bossé, Yanwen Li, Marc Stegger, Liza Miriam Cohen, Øystein Angen, Søren Overballe-Petersen, Dennis Hanke, Stefan Schwarz, Paul R. Langford and Henrike Krüger-Haker
Antibiotics 2025, 14(10), 1021; https://doi.org/10.3390/antibiotics14101021 - 14 Oct 2025
Abstract
Background/Objectives: Actinobacillus pleuropneumoniae is an important respiratory tract pathogen of swine worldwide. Insertion sequences (ISs) play a major role in the transfer of antimicrobial resistance (AMR) among various porcine respiratory tract pathogens. In this study, three A. pleuropneumoniae genomes were investigated for the
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Background/Objectives: Actinobacillus pleuropneumoniae is an important respiratory tract pathogen of swine worldwide. Insertion sequences (ISs) play a major role in the transfer of antimicrobial resistance (AMR) among various porcine respiratory tract pathogens. In this study, three A. pleuropneumoniae genomes were investigated for the presence of a novel IS. Methods: Analysis of the draft genomes of three A. pleuropneumoniae serovar 8 isolates (AP_1, AP_120, AP_123) suggested the presence of a novel IS. A closed whole-genome sequence was generated for strain AP_123 by hybrid assembly of Oxford Nanopore MinION long-reads and Illumina MiSeq short-reads, followed by sequence analysis using standard online tools. Transfer was tested by natural transformation. Antimicrobial susceptibility testing was conducted by broth microdilution following Clinical and Laboratory Standards Institute standards. Results: A novel IS, designated ISApl4, was detected in all three genomes. ISApl4 is 712 bp in size and has a transposase gene (tnp) of 654 bp. Moreover, it has perfect terminal 14-bp inverted repeats and produces 8-bp direct repeats at its integration site. This IS was found in 39 copies in the AP_123 genome, two of which formed the 5,765-bp pseudo-compound transposon Tn7560. This transposon carries four AMR genes: sul2 (sulfonamide resistance), strA-strB (streptomycin resistance), and tet(Y) (tetracycline resistance). RT-PCR confirmed tnp gene expression and horizontal transfer of Tn7560 into A. pleuropneumoniae MIDG2331. Conclusions: This study identified the novel ISApl4 in porcine A. pleuropneumoniae and its association with the novel pseudo-compound transposon Tn7560, which proved to be an active element capable of disseminating multidrug resistance amongst A. pleuropneumoniae.
Full article
(This article belongs to the Special Issue Antibiotic Therapy in Respiratory Tract Infections (RTIs))
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Open AccessArticle
Correlation Between Antimicrobial Consumption and Resistance in Klebsiella pneumoniae During the COVID-19 Pandemic Using Dynamic Regression Models: A Quasi-Experimental Epidemiological Time-Series Study
by
Paul Laffont-Lozes, Florian Salipante, Paul Loubet, Catherine Dunyach-Remy, Jean-Philippe Lavigne, Albert Sotto and Romaric Larcher
Antibiotics 2025, 14(10), 1020; https://doi.org/10.3390/antibiotics14101020 - 14 Oct 2025
Abstract
Background/Objectives: The COVID-19 pandemic has been reported to impact antimicrobial consumption (AMC) and antimicrobial resistance (AMR) worldwide. We aimed to assess this correlation in Klebsiella pneumoniae before and during the COVID-19 pandemic and to estimate the burden of each antibiotic. Methods:
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Background/Objectives: The COVID-19 pandemic has been reported to impact antimicrobial consumption (AMC) and antimicrobial resistance (AMR) worldwide. We aimed to assess this correlation in Klebsiella pneumoniae before and during the COVID-19 pandemic and to estimate the burden of each antibiotic. Methods: We collected data on AMC of penicillins and beta-lactamase inhibitors (PBIs), anti-pseudomonal activity penicillins and beta-lactamase inhibitors (AAPBIs), cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and AMR in K. pneumoniae strains. The correlation between AMC and AMR was studied using dynamic regression models. Results: Overall, AMC of AAPBIs and fourth-generation cephalosporin increased, while fluoroquinolone consumption and AMR in the 2862 K. pneumoniae strains analyzed decreased. However, during the first year of the pandemic, we reported an increase in AMC and AMR. We found that 46% to 48% of the increase in cephalosporin, AAPBI, and fluoroquinolone resistance was explained by increased cephalosporin and fluoroquinolone consumption, 55% of the increase in PBI resistance was explained by increased PBI, cephalosporin, and fluoroquinolone consumption, and 58% of the increase in aminoglycoside resistance was explained by increased aminoglycoside consumption. Conclusions: During the COVID-19 pandemic, the increase in AMR in K. pneumoniae was correlated with the increase in AMC of several antibiotics, mainly cephalosporins and especially fluoroquinolones.
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(This article belongs to the Special Issue Multi-Drug Resistant Gram-Negative Infections: Molecular Epidemiology, Microbiological Diagnosis, and Antimicrobial Treatment, 2nd Edition)
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Open AccessArticle
Antimicrobial: Antibiofilm, Anti-Quorum Sensing and Cytotoxic Activities of Dorystoechas hastata Boiss & Heldr. ex Bentham Essential Oil
by
Timur Hakan Barak, Basar Karaca, Huseyin Servi, Simge Kara Ertekin, Tuğba Buse Şentürk, Muhittin Dinc, Hatice Ustuner and Mujde Eryilmaz
Antibiotics 2025, 14(10), 1019; https://doi.org/10.3390/antibiotics14101019 - 14 Oct 2025
Abstract
Background/Objectives: The aim of the present study was to evaluate the antimicrobial, antibiofilm, anti-quorum sensing, and cytotoxic activities of the essential oils extracted from the leaves of Dorystoechas hastata Boiss & Helder. ex Bentham (Lamiaceae) (DHL-EO) as well as to determine the chemical
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Background/Objectives: The aim of the present study was to evaluate the antimicrobial, antibiofilm, anti-quorum sensing, and cytotoxic activities of the essential oils extracted from the leaves of Dorystoechas hastata Boiss & Helder. ex Bentham (Lamiaceae) (DHL-EO) as well as to determine the chemical composition of the essential oils obtained from both the leaves and roots. Methods: The essential oils of the root and leaf were extracted by the hydrodistillation method. The chemical composition of the two oils was determined by Gas Chromatography–Mass Spectrometry (GC-MS). The antimicrobial activity of DHL-EO was determined against Gram-positive, Gram-negative bacteria, and various Candida species using the broth microdilution method. Pseudomonas aeruginosa PAO1 and Chromobacterium violaceum ATCC 12472 were used for antibiofilm and anti-quorum sensing activities, respectively. The cytotoxic activity of the DHL-EO was examined by MTT assay. Results: Eucalyptol (21.3%), 2-bornanone (17.0%), and α-pinene (10.3%) were the main compounds of the DHL-EO. The root essential oil (DHR-EO) had trans-ferruginol (19.2%), guaiol (14.1%), and ar-abietatriene (14.0%) as the main components. The DHL-EO displayed weak and moderate antimicrobial activity. The DHL-EO showed moderate antibacterial activity against Staphylococcus aureus ATCC 29213 (methicillin-susceptible, MSSA) and S. aureus ATCC 43300 (methicillin-resistant, MRSA), with a MIC value of 12.5 mg/mL. The DHL-EO exhibited the strongest antifungal activity against Candida parapsilosis RSKK 994, with a MIC value of 0.78 mg/mL. It also demonstrated antifungal activity against C. parapsilosis ATCC 22019 and Candida krusei RSKK 3016, with MIC values of 3.12 mg/mL. The DHL-EO showed antibiofilm activity in a concentration-dependent manner, particularly at higher concentrations, and inhibited violacein production in a dose-dependent manner, with anti-quorum sensing activity. The DHL-EO displayed moderate cytotoxic activity against MCF-7 (IC50: 110.3 μg/mL) and A549 (IC50: 120.4 μg/mL) cell lines. Conclusions: The chemical composition of DHL-EO and DHR-EO showed qualitative and quantitative differences from each other in the present study. The essential oil of the leaves showed moderate cytotoxic and antibacterial activities.
Full article
(This article belongs to the Special Issue Essential Oils as Natural Antimicrobials: Extraction, Characterization, and Synergistic Applications)
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Open AccessArticle
Trends in Pseudomonas aeruginosa In Vitro Susceptibility to Ceftolozane/Tazobactam in Latin America: SMART Surveillance Program, 2016–2024
by
Mark G. Wise, James A. Karlowsky, Thales J. Polis, Fakhar Siddiqui, Katherine Young, Mary R. Motyl and Daniel F. Sahm
Antibiotics 2025, 14(10), 1018; https://doi.org/10.3390/antibiotics14101018 - 14 Oct 2025
Abstract
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Objectives: To describe annual trends in the susceptibility of clinical isolates of Pseudomonas aeruginosa from Latin America to ceftolozane/tazobactam. Methods: The Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program collected 10,188 P. aeruginosa isolates from 57 unique clinical sites in
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Objectives: To describe annual trends in the susceptibility of clinical isolates of Pseudomonas aeruginosa from Latin America to ceftolozane/tazobactam. Methods: The Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program collected 10,188 P. aeruginosa isolates from 57 unique clinical sites in 12 Latin American countries from 2016 to 2024. MICs were determined by reference broth microdilution testing and interpreted using 2025 CLSI M100 breakpoints. Results: Overall, 86.3% of clinical isolates of P. aeruginosa collected in Latin America were susceptible to ceftolozane/tazobactam, including 45.5% of multidrug-resistant (MDR) isolates. From 2016 to 2024, annual percent susceptible values for ceftolozane/tazobactam ranged from 84.9% (2016, n = 779) to 89.2% (2023, n = 1144), with a statistically significant linear trend for increasing susceptibility (p = 0.024; Cochran–Armitage test for trend). However, limiting analysis solely to the 14 clinical sites, from six countries, that participated in each of the nine years (n = 4565) indicated that the annual percent susceptible values for ceftolozane/tazobactam remained unchanged from 2016 (82.6%) to 2024 (83.9%) (p = 0.367; percent susceptible value range, 82.6 to 89.1%). Every year, from 2016 to 2024, all P. aeruginosa isolates from pediatric patients (<18 years of age) were consistently more susceptible to ceftolozane/tazobactam than those from adult patients (90.3 to 95.0%/year versus 83.3 to 88.6%/year, respectively). Significant variation (p < 0.05) in annual ceftolozane/tazobactam percent susceptible values was not observed for isolates from blood, intra-abdominal, and respiratory tract sources, while isolates from urine showed a trend of increasing ceftolozane/tazobactam susceptibility from 73.1% (2018, n = 145) to 90.6% (2023, n = 117) (p < 0.0001). Among individual countries that participated each year, P. aeruginosa isolates from all except Guatemala displayed stable or increasing rates of susceptibility to ceftolozane/tazobactam. Conclusions: Since it was first tested by the SMART program in 2016, and for 8 years thereafter, the in vitro activity of ceftolozane/tazobactam has remained consistent against clinical isolates of P. aeruginosa from the Latin American region (overall, 86.3% susceptible), with limited resistance development restricted to specific clinical sites.
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Open AccessCase Report
Staphylococcal Scalded Skin Syndrome (SSSS) in a Preterm Infant: Clinical Presentation and Role of Next-Generation Sequencing in Toxin Gene Identification—A Case Report
by
Giovanni Lorenzin, Maddalena Carlin, Claudio Scarparo, Mariachiara Cardellini, Francesca Tota and Aldo Naselli
Antibiotics 2025, 14(10), 1017; https://doi.org/10.3390/antibiotics14101017 - 13 Oct 2025
Abstract
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Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated dermatosis caused by exfoliative toxin–producing Staphylococcus aureus strains, with neonates and preterm infants being particularly vulnerable due to immature immunity and reduced toxin clearance. We report the case of a male preterm infant, born
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Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated dermatosis caused by exfoliative toxin–producing Staphylococcus aureus strains, with neonates and preterm infants being particularly vulnerable due to immature immunity and reduced toxin clearance. We report the case of a male preterm infant, born at 24 weeks of gestation, who presented at the age of one month with fever and later developed widespread erythema, flaccid bullae, and periorificial desquamation. Methicillin-sensitive S. aureus (MSSA) was isolated from blood, catheter, and auricular swabs. Whole-genome sequencing revealed sequence type ST121 carrying both eta and etb genes, confirming the dual-toxin profile associated with severe disease. The infant improved with targeted intravenous oxacillin following catheter removal. A subsequent nasal swab identified a methicillin-resistant S. aureus (MRSA) ST30 strain lacking exfoliative toxins, consistent with asymptomatic colonization. This case underscores the importance of integrating advanced molecular diagnostics such as next-generation sequencing into the management of neonatal SSSS, enabling precise identification of virulence factors and resistance genes. Literature also highlights the global epidemiology of SSSS, diversity of S. aureus toxin genes, and value of genomic surveillance in neonatal care; our case aligns with reports of ST121 strains carrying both ETA and ETB, where the dual-toxin profile drives rapid onset, extensive skin disease, and good outcomes with prompt therapy.
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Open AccessArticle
Influence of Florfenicol Treatments on Marine-Sediment Microbiomes: A Metagenomic Study of Bacterial Communities in Proximity to Salmon Aquaculture in Southern Chile
by
Sergio Lynch, Pamela Thomson, Rodrigo Santibañez and Ruben Avendaño-Herrera
Antibiotics 2025, 14(10), 1016; https://doi.org/10.3390/antibiotics14101016 - 13 Oct 2025
Abstract
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Background/Objectives: Metagenomic analyses are an important tool for understanding ecological effects, particularly in sites exposed to antimicrobial treatments. Marine sediments host diverse microbial communities and may serve as reservoirs for microbial resistance. Although it is known that antimicrobials can alter microbial composition,
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Background/Objectives: Metagenomic analyses are an important tool for understanding ecological effects, particularly in sites exposed to antimicrobial treatments. Marine sediments host diverse microbial communities and may serve as reservoirs for microbial resistance. Although it is known that antimicrobials can alter microbial composition, specific impacts on sediments surrounding salmon farms remain poorly understood. This study analyzed bacterial community structure in marine sediments subjected to florfenicol treatment from salmon farms in the Los Lagos Region of southern Chile. Methods: Sediment samples were collected and examined through DNA extraction and PCR amplification of the 16S rRNA gene (V3-V4 region). Sequences were analyzed using a bioinformatics pipeline, and amplicon sequence variants (ASVs) were taxonomically classified with a Naïve Bayesian classifier. The resulting ASV abundance were then used to predict metabolic functions and pathways via PICRUSt2, referencing the MetaCyc database. Results: Significant differences in bacterial phyla were observed between the control farm and two farms treated with florfenicol (17 mg kg−1 body weight per day) for 33 and 20 days, respectively. Farm 1 showed notable differences in phyla such as Bacteroidota, Bdellovibrionota, Crenarchaeota, Deferrisomatota, Desulfobacterota, Fibrobacterota, Firmicutes, and Fusobacteriota, while Farm 2 exhibited differences in the phyla Bdellovibrionota, Calditrichota, Crenarchaeota, Deferrisomatota, Desulfobacterota, Fusobacteriota, Nanoarchaeota, and Nitrospirota. Shannon Index analysis revealed a reduction in alpha diversity in the treated farms. Comparative analysis between the control and the treated farms showed pronounced shifts in the relative abundance of several bacterial phyla, including statistically significant differences in Chloroflexi and Firmicutes. Predicted functional pathways revealed a notable enrichment of L-methionine biosynthesis III in Farm 2, suggesting a shift in sulfur metabolism potentially driven by antimicrobial treatment. Additionally, increased activity in fatty acid oxidation pathways indicates a higher microbial potential for lipid degradation at this site. Conclusions: These findings highlight the considerable influence of florfenicol on sediment microbial communities and reinforce the need for sustainable management strategies to minimize ecological disruption and the spread of antimicrobial resistance.
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Open AccessArticle
Multidrug-Resistant Staphylococcus haemolyticus ST42 Carrying ΨSCCmec57395-like SCCmec and Resistant Islands with Type I aj1–LP–fusB Structure Emerges in Taiwan Hospitals
by
Cheng-Mao Ho, Lee-Chung Lin, Yu-Hsiang Ou, Kai-Hsiang Lin and Jang-Jih Lu
Antibiotics 2025, 14(10), 1015; https://doi.org/10.3390/antibiotics14101015 - 13 Oct 2025
Abstract
Background/Objectives: Staphylococcus haemolyticus is a common commensal bacterium that has emerged as an important nosocomial pathogen. Its multi-antibiotics resistance presents substantial therapeutic challenges in healthcare settings worldwide. Despite its growing clinical relevance, most investigations into antimicrobial resistance determinants have been focused on
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Background/Objectives: Staphylococcus haemolyticus is a common commensal bacterium that has emerged as an important nosocomial pathogen. Its multi-antibiotics resistance presents substantial therapeutic challenges in healthcare settings worldwide. Despite its growing clinical relevance, most investigations into antimicrobial resistance determinants have been focused on Staphylococcus aureus or Staphylococcus epidermidis, leaving S. haemolyticus comparatively understudied. This study aimed to elucidate the genetic basis of multi-drug resistance by characterizing mobile genetic elements associated with predominant S. haemolyticus clones circulating in Taiwan. Methods: From 2010 to 2017, 140 clinical targeted isolates of S. haemolyticus were obtained from individual patients. Two representative strains, SH53 (ST3) and SH51 (ST42), were sequenced using the PacBioTM platform. The structural organization of SCCmec cassettes and phage-associated resistance islands in the remaining 138 isolates was analyzed by polymerase chain reaction (PCR) using specifically designed primers. Results: Of the 140 isolates, 92 (65.7%) were ST42 and 48 (34.3%) were ST3. PCR analysis showed that over two-thirds harbored heavy metal resistance genes. cadD, cadX, arsC, arsB, and arsR occurred in 90.2% of ST42 isolates, with copA in 71.7%. In ST3, these five genes were present in 89.6%, and copA in 64.6%. Fusidic acid (FA) resistance was more frequent in ST42 (46.7%) than ST3 (22.9%) (p = 0.015). Only one ST42 isolate carried fusC. The remaining 52 FA-resistant isolates contained a type I aj1–leader peptide (LP)–fusB structure downstream of smpB, except for a single ST42 isolate with the type IV structure. Conclusions: MDR ST42 S. haemolyticus carrying SCCmec cassettes with heavy metal resistance genes and phage-related islands carrying type I aj1–leader peptide (LP)–fusB structures may represent emerging opportunistic pathogens in Taiwan. Continued longitudinal surveillance is warranted to track the evolution of resistance-associated mobile elements under selective antimicrobial pressure.
Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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Open AccessArticle
Isolation of Dual-Active Drugs with Anticancer and Antibacterial Activities That Target Both Tubulin and FtsZ
by
Yanting Wang, Xufang Wang, Chunmeng Yao, Yaliang Zhang, Lantian Liu, Yan Cao and Bin Lu
Antibiotics 2025, 14(10), 1014; https://doi.org/10.3390/antibiotics14101014 - 13 Oct 2025
Abstract
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Background: Cancer patients experience a high incidence of concomitant infections due to the effects of chemotherapy drugs and their suppressed immune function. Infection has become a major cause and an accelerating factor of cancer-related deaths. The combined use of anticancer drugs and
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Background: Cancer patients experience a high incidence of concomitant infections due to the effects of chemotherapy drugs and their suppressed immune function. Infection has become a major cause and an accelerating factor of cancer-related deaths. The combined use of anticancer drugs and antibiotics can produce adverse effects, necessitating the urgent search for dual-active drugs that are effective against both cancer and bacteria. Since tubulin has a homologous protein filamenting temperature-sensitive mutant Z (FtsZ) in bacteria, tubulin inhibitors have the potential to emerge as dual-active drugs against both cancer and bacteria. Methods: A comprehensive screening of a tubulin inhibitor library, encompassing 196 compounds, was conducted to evaluate their various activities. Results: Compounds 6, 23, 33, 56, 60, and 71 exhibited both anticancer and antibacterial activities in vitro, and 23, 33, 56, and 60 displayed varying degrees of FtsZ inhibitory activity. Particularly, compound 23 stood out as the most potent, exhibiting not only the strongest anticancer activity with IC50 values of 12, 20, and 10 nM against A549, MCF-7 and Hela cells, respectively, but also the most exceptional antibacterial activity with minimum inhibitory concentration (MIC) values of 8, 8, 64, and 32 μM against Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa), respectively. Furthermore, compound 23 possessed the superior FtsZ inhibitory activity, facilitating polymerization. This was evident in the remarkably elongated cell morphology of Bacillus subtilis treated with compound 23. To gain a deeper understanding of the underlying mechanisms, molecular docking studies were conducted, revealing the interaction mode between compound 23 and both tubulin and FtsZ, further elucidating its multifaceted biological activities. Conclusions: The dual-active drugs obtained in this study provide a new solution to the problem of bacterial infection in cancer patients. The revealed FtsZ as the antibacterial target provides an important theoretical basis for further optimization of such drugs.
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