Antibiotics

26 pages, 4610 KiB

Open AccessArticle

Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from Actinomycetes

by Jianying Han, Xueting Liu, Lixin Zhang, Ronald J. Quinn and Miaomiao Liu

Antibiotics 2025, 14(1), 108; https://doi.org/10.3390/antibiotics14010108 - 20 Jan 2025

Viewed by 613

Abstract

Background: The increasing prevalence of drug-resistant tuberculosis (TB) underscores the urgent need for novel antimicrobial agents. Methods: This study integrates cultivation optimization, nuclear magnetic resonance (NMR) fingerprinting, and principal component analysis (PCA) to explore microbial secondary metabolites as potential anti-TB agents. Results: Using [...] Read more.

Background: The increasing prevalence of drug-resistant tuberculosis (TB) underscores the urgent need for novel antimicrobial agents. Methods: This study integrates cultivation optimization, nuclear magnetic resonance (NMR) fingerprinting, and principal component analysis (PCA) to explore microbial secondary metabolites as potential anti-TB agents. Results: Using the combined approach, 11 bioactive compounds were isolated and identified, all exhibiting anti-Mycobacterium bovis BCG activity. Notable findings include borrelidin, a potent threonyl-tRNA synthetase inhibitor with broad biological activities, and L-O-Lac-L-Val-D-O-Hiv-D-Val, a peptide isolated for the first time from a plant endophyte, demonstrating broad-spectrum antimicrobial activity. Additionally, elaiophylin and polycyclic tetramate macrolactams (PTMs) displayed significant bactericidal effects, with elaiophylin achieving complete BCG inhibition at 72 h and PTMs marking their first reported anti-TB activity. The study also identified bafilomycins as potent scaffolds for anti-TB drug development, showcasing rapid bactericidal activity at low MIC values. Conclusions: These findings emphasize the value of microbial metabolites as a reservoir of bioactive compounds and provide new avenues for developing next-generation anti-TB therapies. Full article

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12 pages, 1182 KiB

Open AccessArticle

Management and Outcome of Invasive Clindamycin-Resistant MRSA Community-Associated Infections in Children

by Amanda E. Macias, Grant Stimes, Sheldon L. Kaplan, Jesus G. Vallejo, Kristina G. Hulten and J. Chase McNeil

Antibiotics 2025, 14(1), 107; https://doi.org/10.3390/antibiotics14010107 - 20 Jan 2025

Viewed by 665

Abstract

Background: Clindamycin resistance among community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) complicates the management of a challenging infection. Little data exist to guide clinicians in the management of invasive clindamycin-resistant CA-MRSA infections in children and studies using oral regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid [...] Read more.

Background: Clindamycin resistance among community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) complicates the management of a challenging infection. Little data exist to guide clinicians in the management of invasive clindamycin-resistant CA-MRSA infections in children and studies using oral regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid for treatment of these infections are limited. We sought to reevaluate antibiotic management among invasive CA-MRSA at a tertiary children’s hospital. Methods: Cases of invasive clindamycin-resistant MRSA infections in children were identified through an ongoing S. aureus surveillance study. Eligible cases were those occurring in otherwise healthy children from 2011–2021. Medical records were reviewed. Results: Thirty-four subjects met inclusion criteria. The most common diagnoses were osteomyelitis (n = 17) and deep abscess (n = 7). The median duration of IV therapy was 11.5 days (IQR 6–42 days) and total therapy (IV + oral) was 32 days (IQR 23–42). Overall, 50% of patients were transitioned to oral therapy. Definitive antibiotics used for treatment included vancomycin (n = 15), TMP/SMX (n = 9), linezolid (n = 7), ceftaroline (n = 2), and doxycycline (n = 1). Cure rates were similar across definitive antibiotic therapies (vancomycin-73.3%; TMP/SMX-88.9%; ceftaroline 50%; linezolid and doxycycline-100%). Three subjects died of MRSA disease; two definitively treated with vancomycin and one with ceftaroline. Conclusions: Vancomycin is the most commonly used agent in the treatment of invasive clindamycin-resistant CA-MRSA in children at our center. However, TMP/SMX and linezolid can be considered as oral options when completing treatment in select cases. Further work is needed to evaluate the optimal management of these infections. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

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24 pages, 5932 KiB

Open AccessArticle

Evaluation of Cinnamon Essential Oil and Its Emulsion on Biofilm-Associated Components of Acinetobacter baumannii Clinical Strains

by Tea Ganić, Ilinka Pećinar, Biljana Nikolić, Dušan Kekić, Nina Tomić, Stefana Cvetković, Stefana Vuletić and Dragana Mitić-Ćulafić

Antibiotics 2025, 14(1), 106; https://doi.org/10.3390/antibiotics14010106 - 19 Jan 2025

Viewed by 850

Abstract

Background/Objectives: Acinetobacter baumannii, one of the most dangerous pathogens, is able to form biofilm structures and aggravate its treatment. For that reason, new antibiofilm agents are in need, and new sources of antibiofilm compounds are being sought from plants and their products. [...] Read more.

Background/Objectives: Acinetobacter baumannii, one of the most dangerous pathogens, is able to form biofilm structures and aggravate its treatment. For that reason, new antibiofilm agents are in need, and new sources of antibiofilm compounds are being sought from plants and their products. Cinnamon essential oil is associated with a wide spectrum of biological activities, but with a further improvement of its physicochemical properties it could provide even better bioavailability. The aim of this work was the evaluation of the antibiofilm properties of cinnamon essential oil and its emulsion. Methods: In order to evaluate the antibiofilm activity, crystal violet assay was performed to determine biofilm biomass. The main components of the biofilm matrix were measured as well as the motile capacity of the tested strains. Gene expression was monitored with RT-qPCR, while treated biofilms were observed with Raman spectroscopy. Results: A particularly strong potential against pre-formed biofilm with a decreased biomass of up to 66% was found. The effect was monitored not only with regard to the whole biofilm biomass, but also on the individual components of the biofilm matrix such as exopolysaccharides, proteins, and eDNA molecules. Protein share drops in treated biofilms demonstrated the most consistency among strains and rose to 75%. The changes in strain motility and gene expressions were investigated after the treatments were carried out. Raman spectroscopy revealed the influence of the studied compounds on chemical bond types and the components present in the biofilm matrix of the tested strains. Conclusions: The results obtained from this research are promising regarding cinnamon essential oil and its emulsion as potential antibiofilm agents, so further investigation of their activity is encouraged for their potential use in biomedical applications. Full article

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13 pages, 263 KiB

Open AccessArticle

Antibiotic Prescription Practice and Resistance Patterns of Bacterial Isolates from a Neonatal Intensive Care Unit: A Retrospective Study from Jordan

by Mariam Alameri, Lobna Gharaibeh, Mervat Alsous, Aseel Yaghi, Asma’a Tanash, Saqr Sa’id and Hanan Sartawi

Antibiotics 2025, 14(1), 105; https://doi.org/10.3390/antibiotics14010105 - 18 Jan 2025

Viewed by 1273

Abstract

Background/Objectives: Neonatal sepsis is a systemic inflammation in neonates caused by bacteria, viruses, or fungi that can progress into severe conditions. In developing countries, neonatal sepsis is a major cause of mortality and a major public health issue with a high prevalence. [...] Read more.

Background/Objectives: Neonatal sepsis is a systemic inflammation in neonates caused by bacteria, viruses, or fungi that can progress into severe conditions. In developing countries, neonatal sepsis is a major cause of mortality and a major public health issue with a high prevalence. This study aims to evaluate the antibiotic prescription practice and resistance patterns of bacterial isolates from the neonatal intensive care unit (NICU) at the largest governmental hospital in Amman, Jordan. Methods: This was a retrospective cross-sectional study. The antibiotic prescription practice and resistance patterns of bacterial isolates from the NICU at Al Basheer Government Hospital in Amman, Jordan, were evaluated. The hospital’s microbiology lab database and medical records were the sources of the retrospective data collection. Results: A total of 266 neonates treated with antibiotics were assessed. The findings showed that most neonates had late-onset sepsis (LOS) (65.4%). The penicillin group of antibiotics (ampicillin) was the most highly prescribed first empiric antibiotic for LOS and early-onset sepsis (EOS) (61.7%). Aminoglycosides (60.9%) were the most prescribed antibiotics as a second empiric treatment for EOS and LOS. The culture results showed that resistance to antibiotics was as follows: 15.4% of the culture samples were resistant to penicillin (Micrococcus and Viridans streptococci), 13.9% were resistant to cefotaxime (Klebsiella pneumoniae and Viridans streptococci), 13.2% were resistant to cefoxitin (Klebsiella pneumoniae and Staphylococcus epidermidis), and 12.4% were resistant to oxacillin (Klebsiella pneumoniae and Staphylococcus epidermidis). Conclusions: This retrospective study sheds light on the antibiotic prescription practice and resistance patterns of bacterial isolates from newborns with sepsis. The results highlight the high rates of antibiotic resistance. These findings underline the urgent need for improved antibiotic stewardship and infection control strategies to prevent resistance from spreading further. Full article

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

28 pages, 11515 KiB

Open AccessArticle

A VersaTile Approach to Reprogram the Specificity of the R2-Type Tailocin Towards Different Serotypes of Escherichia coli and Klebsiella pneumoniae

by Dorien Dams, Célia Pas, Agnieszka Latka, Zuzanna Drulis-Kawa, Lars Fieseler and Yves Briers

Antibiotics 2025, 14(1), 104; https://doi.org/10.3390/antibiotics14010104 - 18 Jan 2025

Viewed by 820

Abstract

Background: Phage tail-like bacteriocins, or tailocins, provide a competitive advantage to producer cells by killing closely related bacteria. Morphologically similar to headless phages, their narrow target specificity is determined by receptor-binding proteins (RBPs). While RBP engineering has been used to alter the target [...] Read more.

Background: Phage tail-like bacteriocins, or tailocins, provide a competitive advantage to producer cells by killing closely related bacteria. Morphologically similar to headless phages, their narrow target specificity is determined by receptor-binding proteins (RBPs). While RBP engineering has been used to alter the target range of a selected R2 tailocin from Pseudomonas aeruginosa, the process is labor-intensive, limiting broader application. Methods: We introduce a VersaTile-driven R2 tailocin engineering and screening platform to scale up RBP grafting. Results: This platform achieved three key milestones: (I) engineering R2 tailocins specific to Escherichia coli serogroups O26, O103, O104, O111, O145, O146, and O157; (II) reprogramming R2 tailocins to target, for the first time, the capsule and a new species, specifically the capsular serotype K1 of E. coli and K11 and K63 of Klebsiella pneumoniae; (III) creating the first bivalent tailocin with a branched RBP and cross-species activity, effective against both E. coli K1 and K. pneumoniae K11. Over 90% of engineered tailocins were effective, with clear pathways for further optimization identified. Conclusions: This work lays the groundwork for a scalable platform for the development of engineered tailocins, marking an important step towards making R2 tailocins a practical therapeutic tool for targeted bacterial infections. Full article

(This article belongs to the Section Bacteriophages)

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20 pages, 2352 KiB

Open AccessArticle

Antimicrobial Susceptibility Profiles of Commensal Staphylococcus spp. Isolates from Chickens in Hungarian Poultry Farms Between 2022 and 2023

by Ábel Szabó, Ákos Jerzsele, László Kovács and Ádám Kerek

Antibiotics 2025, 14(1), 103; https://doi.org/10.3390/antibiotics14010103 - 17 Jan 2025

Viewed by 766

Abstract

Background: Antimicrobial resistance is one of the greatest challenges of our time, urging researchers in both veterinary and public health to engage in collaborative efforts, thereby fostering the One Health approach. Infections caused by Staphylococcus species can not only lead to significant diseases [...] Read more.

Background: Antimicrobial resistance is one of the greatest challenges of our time, urging researchers in both veterinary and public health to engage in collaborative efforts, thereby fostering the One Health approach. Infections caused by Staphylococcus species can not only lead to significant diseases in poultry but also pose serious threats to human life, particularly in hospital (nosocomial) infections; therefore, it is crucial to identify their antimicrobial resistance. Methods: Our objective was to assess the susceptibility profile of commensal Staphylococcus aureus strains (n = 227) found in commercial chicken flocks in Hungary through the determination of minimum inhibitory concentration (MIC) values. Results: Based on our findings, resistance to tiamulin (82.8%; 95% CI: 77.4–87.2%) and doxycycline (74.4%; 95% CI: 68.5–79.7%) is the most critical. The 55.1% (95% CI: 48.8–61.3%) resistance rate to enrofloxacin, a critically important antimicrobial, is also concerning. The fact that 58.6% (95% CI: 52.4–64.5%) of the strains were resistant to amoxicillin and 35.7% (95% CI: 29.7–42.1) were resistant to amoxicillin–clavulanic acid suggests that a proportion of the strains produce β-lactamase. Comparing our results with the available human hospital data, it was found that resistance to macrolide antibiotics is similarly high in both cases. Conclusions: Our findings highlight the necessity of conducting regular surveillance studies, which would allow the monitoring of future temporal trends. This information could benefit practitioners making clinical decisions to successfully treat infections. To uncover the underlying causes of multidrug resistance, next-generation sequencing can be employed to elucidate the genetic basis of phenotypic resistance. Full article

(This article belongs to the Special Issue Antibiotics Use in Farms, 2nd Edition)

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19 pages, 887 KiB

Open AccessArticle

The Introduction of the Global Traditional, Complementary, and Integrative Healthcare (TCIH) Research Agenda on Antimicrobial Resistance and Its Added Value to the WHO and the WHO/FAO/UNEP/WOAH 2023 Research Agendas on Antimicrobial Resistance

by Erik W. Baars, Petra Weiermayer, Henrik P. Szőke and Esther T. van der Werf

Antibiotics 2025, 14(1), 102; https://doi.org/10.3390/antibiotics14010102 - 17 Jan 2025

Viewed by 1057

Abstract

Background/Objectives: Given the magnitude and urgency of the global antimicrobial resistance (AMR) problem and the insufficiency of strategies to reduce antimicrobial use, there is a need for novel strategies. Traditional, Complementary, and Integrative Healthcare (TCIH) provides strategies and solutions that contribute to [...] Read more.

Background/Objectives: Given the magnitude and urgency of the global antimicrobial resistance (AMR) problem and the insufficiency of strategies to reduce antimicrobial use, there is a need for novel strategies. Traditional, Complementary, and Integrative Healthcare (TCIH) provides strategies and solutions that contribute to reducing (inappropriate) antimicrobial use, preventing or treating infections in both human and veterinary medicine, and may contribute to promoting the health/resilience of humans and animals and reducing AMR. The aims of this study were to present the core results of a global TCIH research agenda for AMR and its added value to two existing global AMR research agendas published in 2023. Methods: A survey, interviews, and consensus meetings among network members, as an adapted version of the nominal group technique, were executed to develop the global TCIH research agenda. A comparison of the global TCIH research agenda with the two existing global AMR research agendas was performed. The TCIH additions to these two existing global AMR research agendas were determined. Results: The global TCIH research agenda adds to 19 of 40 research priorities of the World Health Organization (WHO) AMR research agenda 2023 and three of the five pillars of the WHO/Food and Agriculture Organization of the United Nations (FAO)/United Nations Environment Programme (UNEP)/World Organisation for Animal Health (WOAH) research agenda 2023. In addition, the TCIH research agenda adds two new research themes with four new research priorities and three new research priorities to already existing themes of the two global AMR research agendas. Conclusions: The global TCIH research agenda fits with and adds to two global AMR research agendas and can be used as an additional strategy to reduce AMR and (inappropriate) use of antibiotics. Full article

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20 pages, 478 KiB

Open AccessArticle

Thromboelastometry-Based Profiling of Haemostatic Alterations in Neonatal Sepsis by Causative Pathogens

by Rozeta Sokou, Eleni A. Gounari, Konstantina A. Tsante, Aikaterini Konstantinidi, Maria Lampridou, Martha Theodoraki, Anastasios G. Kriebardis, Sotirios P. Fortis, Nicoletta Iacovidou and Andreas G. Tsantes

Antibiotics 2025, 14(1), 101; https://doi.org/10.3390/antibiotics14010101 - 17 Jan 2025

Viewed by 731

Abstract

Background: Neonatal sepsis is a serious condition with high mortality, especially in premature and low-birth-weight neonates. This study aims to examine whether the haemostatic profile of neonates with sepsis defers depending on the type of bacteria (Gram-positive or Gram-negative), by using the [...] Read more.

Background: Neonatal sepsis is a serious condition with high mortality, especially in premature and low-birth-weight neonates. This study aims to examine whether the haemostatic profile of neonates with sepsis defers depending on the type of bacteria (Gram-positive or Gram-negative), by using the method of Rotational Thromboelastometry (ROTEM). Methods: This single-centre prospective cohort study was conducted on 128 neonates with sepsis, including 95 cases caused by Gram-negative pathogens and 33 cases caused by Gram-positive bacteria. All participants were hospitalised in the Neonatal Intensive Care Unit (NICU). ROTEM parameters were compared between neonates with Gram-positive and Gram-negative infections. Results: The ROTEM parameters were found to be significantly different between neonates suffering from Gram-positive versus Gram-negative infections, with Gram-positive pathogens associated with an increased clotting potential compared to Gram-negative pathogens. This is reflected in the higher ROTEM values such as A10, α-angle, and MCF in the EXTEM and INTEM assays. Multivariant analysis showed that Gram-positive infections were linked to increased clot thickness at 10 min (coefficient: 8.9, CI: 2.8–15.0, p = 0.004), higher maximum clot stability (coefficient: 10.4, CI: 4.3–16.6, p = 0.001), and a bigger α-angle (coefficient: 8.0, CI: 2.7–13.2, p = 0.003). Similar findings were observed in the INTEM assay parameters. Conclusions: Neonatal sepsis caused by Gram-positive bacteria leads to a hypercoagulable haemostatic state, whereas neonates with sepsis caused by Gram-negative bacteria exhibit a more hypocoagulable profile and a higher incidence of haemorrhagic episodes. These findings provide valuable insights into the haemostatic disorders associated with sepsis, and may aid in developing an individualised approach for the treatment of those disorders, dependent on and adapted for the specific type of causative organism. Full article

(This article belongs to the Special Issue New Insights into Prevention, Diagnosis, and Treatment of Neonatal Sepsis and Short- and Long-Term Outcomes)

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12 pages, 2231 KiB

Open AccessArticle

Pharmacodynamic Profiling of Amoxicillin: Targeting Multidrug-Resistant Gram-Positive Pathogens Staphylococcus aureus and Staphylococcus pseudintermedius in Canine Clinical Isolates

by Syed Al Jawad Sayem, Ga-Yeong Lee, Muhammad Aleem Abbas, Seung-Chun Park and Seung-Jin Lee

Antibiotics 2025, 14(1), 99; https://doi.org/10.3390/antibiotics14010099 - 16 Jan 2025

Viewed by 827

Abstract

The rising threat of antimicrobial resistance (AMR) is a global concern in both human and veterinary medicine, with multidrug-resistant (MDR) pathogens such as Staphylococcus aureus and Staphylococcus pseudintermedius presenting significant challenges. Background/Objectives: This study evaluates the effectiveness of amoxicillin against these MDR [...] Read more.

The rising threat of antimicrobial resistance (AMR) is a global concern in both human and veterinary medicine, with multidrug-resistant (MDR) pathogens such as Staphylococcus aureus and Staphylococcus pseudintermedius presenting significant challenges. Background/Objectives: This study evaluates the effectiveness of amoxicillin against these MDR pathogens in canine isolates using pharmacokinetic and pharmacodynamic parameters. Methods: Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and mutation prevention concentration (MPC) were assessed. Additionally, time-kill assays and post-antibiotic effect (PAE) assessments were performed. Epidemiological cutoff (ECOFF) values were established for both species to guide therapy. Results: S. aureus had a higher resistance rate (35.89%) than S. pseudintermedius (15.27%), with MIC50 values of 0.50 μg/mL and 0.25 μg/mL, respectively. The MPC analysis revealed that S. pseudintermedius required higher antibiotic concentrations (16.11 μg/mL) to prevent mutations compared to S. aureus (2.20 μg/mL). Time-kill assays indicated that higher amoxicillin dosages caused faster bacterial reduction. The PAE analysis showed extended post-treatment bacterial suppression at elevated doses, particularly against S. aureus. Conclusions: Species-specific amoxicillin dosing strategies are necessary due to differing resistance and susceptibility profiles between S. aureus and S. pseudintermedius. High-dose amoxicillin therapy is recommended to achieve optimal therapeutic outcomes for resistant SA, while slightly adjusted dosing can manage S. pseudintermedius infections. These findings provide essential insights for veterinary antimicrobial stewardship, underscoring the need for tailored therapeutic approaches to minimize AMR development while ensuring effective infection control. Full article

(This article belongs to the Special Issue Rational Use of Antibiotics in Veterinary Medicine)

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18 pages, 3033 KiB

Open AccessArticle

The Prevalence and Risk Factors Associated with the Presence of Antibiotic Residues in Milk from Peri-Urban Dairy Cattle Farms in Kathmandu, Nepal

by Erda E. Rame Hau, Minu Sharma, Bal K. Sharma Khanal, Peter D. Sly, Deirdre Mikkelsen, Nicholas Clark and Ricardo J. Soares Magalhães

Antibiotics 2025, 14(1), 98; https://doi.org/10.3390/antibiotics14010098 - 16 Jan 2025

Viewed by 808

Abstract

Background/Objectives: The presence of antibiotic residues (ARs) in animal products such as milk can be an important driver of antimicrobial resistance in commensal and pathogenic bacteria. Previous studies on ARs in Nepal have demonstrated the presence of ARs in milk samples but without [...] Read more.

Background/Objectives: The presence of antibiotic residues (ARs) in animal products such as milk can be an important driver of antimicrobial resistance in commensal and pathogenic bacteria. Previous studies on ARs in Nepal have demonstrated the presence of ARs in milk samples but without further characterization of the samples for risk factor analysis. This study aimed to quantify the prevalence and risk factors for the presence of ARs in 140 peri-urban dairy farms in Kathmandu, Nepal, included in a cross-sectional survey in 2019 to estimate farm-level AR prevalence. Results: Our results reveal the presence of ARs of sulfamethazine (61%), sulfamethoxazole (53%), ciprofloxacin (46%), and enrofloxacin (42%). Furthermore, of those samples positive for sulfamethazine, sulfamethoxazole, and ciprofloxacin, 81%, 42%, and 42%, respectively, exceeded the maximum residue limit (MRL). While samples taken from farms where staff administered antibiotics were less likely to have single drug residues and multidrug residues (two, three, and four drugs), farms with more workers were more likely to have single residues. Moreover, samples from farms with a higher number of calves and milking cows were more likely to contain single and multiple residues exceeding the MRL, while milk from farms with higher numbers of dry cows and farmers reported by a visiting chemist were less likely to have multidrug residues exceeding the MRL. Methods: High-performance liquid chromatography was conducted on bulk milk samples from farms for an AR analysis, revealing positive results. Additionally, a structured questionnaire and direct farmer interviews were used to collect data on farm biosecurity and farming practices, animal health and hygiene, antibiotic usage (AMU), and attitudes and practices towards antibiotic stewardship. Conclusions: Ultimately, this study provides evidence on the role of modifiable ARs risk factors in the peri-urban milk industry of Kathmandu, which can serve as a foundation for developing improved antimicrobial stewardship guidelines and designing intervention measures to reduce the public health risk posed by ARs in milk sold in Kathmandu, Nepal. Full article

(This article belongs to the Special Issue Research Advances in Antimicrobial Stewardship, Residues and Resistance in Veterinary and Environmental Science)

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16 pages, 1857 KiB

Open AccessArticle

Bacteriocin-Producing Staphylococci and Mammaliicocci Strains for Agro-Food and Public Health Applications with Relevance of Micrococcin P1

by Rosa Fernández-Fernández, Carmen Lozano, Allelen Campaña-Burguet, Carmen González-Azcona, Tamara Álvarez-Gómez, Rocío Fernández-Pérez, Raquel Peña, Myriam Zarazaga, Jaime Carrasco and Carmen Torres

Antibiotics 2025, 14(1), 97; https://doi.org/10.3390/antibiotics14010097 - 16 Jan 2025

Viewed by 861

Abstract

Antimicrobial-producing strains and their bacteriocins hold great promise for the control of bacterial diseases, being an attractive alternative to antibiotics. Thus, the aim of this study was to evaluate the inhibitory activity of 15 bacteriocin-producing staphylococci and mammaliicocci (BP-S/M) strains and their pre-purified [...] Read more.

Antimicrobial-producing strains and their bacteriocins hold great promise for the control of bacterial diseases, being an attractive alternative to antibiotics. Thus, the aim of this study was to evaluate the inhibitory activity of 15 bacteriocin-producing staphylococci and mammaliicocci (BP-S/M) strains and their pre-purified extracts with butanol (BT) against a collection of 27 harmful or zoonotic strains (including Gram-positive/-negative bacteria and molds) with relevance in the public health and agro-food fields. These indicators (excluding Gram-negative strains) were grouped into seven categories based on their potential application areas: dairy livestock mastitis, avian pathogen zoonoses, swine zoonoses, food safety, aquaculture, wine making, and mushroom cultivation. In addition, cross-immunity assays between the BP-S/M strains were carried out to identify potential strain combinations to enhance their activity against pathogens. Finally, the hemolytic and gelatinase activities were tested in the BP-S/M strains. A strong inhibitory capacity of the BP-S/M strains was verified against relevant Gram-positive indicators, such as methicillin-resistant Staphylococcus aureus, Listeria monocytogenes, and Clostridium perfringens, among others, while no activity was detected against Gram-negative ones. Interestingly, several BT extracts inhibited the two mold indicators included in this study as representants of mushroom pathogens. The Micrococcin P1 producer Staphylococcus hominis C5835 (>60% of indicators were intensively inhibited by all the methods) can be proposed as a potential candidate for the control of bacterial diseases in the aforementioned categories alone or in combination with other BP-S/M strains (mainly with Staphylococcus warneri X2969). In this regard, five potential combinations of BP-S/M strains that enhanced their activity against specific pathogens were detected. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: New Strategies to Overcome Antibiotic Resistance)

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16 pages, 1074 KiB

Open AccessReview

Bicarbonate Within: A Hidden Modulator of Antibiotic Susceptibility

by Selvi C. Ersoy, Warren E. Rose and Richard A. Proctor

Antibiotics 2025, 14(1), 96; https://doi.org/10.3390/antibiotics14010096 - 16 Jan 2025

Viewed by 812

Abstract

Since its standardization, clinical antimicrobial susceptibility testing (AST) has relied upon a standard medium, Mueller-Hinton Broth/Agar (MHB/A), to determine antibiotic resistance. However, this microbiologic medium bears little resemblance to the host milieu, calling into question the physiological relevance of resistance phenotypes it reveals. [...] Read more.

Since its standardization, clinical antimicrobial susceptibility testing (AST) has relied upon a standard medium, Mueller-Hinton Broth/Agar (MHB/A), to determine antibiotic resistance. However, this microbiologic medium bears little resemblance to the host milieu, calling into question the physiological relevance of resistance phenotypes it reveals. Recent studies investigating antimicrobial susceptibility in mammalian cell culture media, a more host-mimicking environment, demonstrate that exposure to host factors significantly alters susceptibility profiles. One such factor is bicarbonate, an abundant ion in the mammalian bloodstream/tissues. Importantly, bicarbonate sensitizes methicillin-resistant Staphylococcus aureus (MRSA) to early-generation β-lactams used for the treatment of methicillin-susceptible S. aureus (MSSA). This “NaHCO₃-responsive” phenotype is widespread among US MRSA USA300/CC8 bloodstream and skin and soft tissue infection isolates. Translationally, β-lactam therapy has proven effective against NaHCO₃-responsive MRSA in both ex vivo simulated endocarditis vegetation (SEV) and in vivo rabbit infective endocarditis (IE) models. Mechanistically, bicarbonate appears to influence mecA expression and PBP2a production/localization, as well as key elements for PBP2a functionality, including the PBP2a chaperone PrsA, components of functional membrane microdomains (FMMs), and wall teichoic acid (WTA) synthesis. The NaHCO₃-responsive phenotype highlights the critical role of host factors in shaping antibiotic susceptibility, emphasizing the need to incorporate more physiological conditions into AST protocols. Full article

(This article belongs to the Special Issue Staphylococcal Biology and Pathogenesis)

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20 pages, 781 KiB

Open AccessReview

Oral Antibacterial Drug Prescribing in Primary Care Out-of-Hours Services: A Scoping Review

by Sarah Khalid Al Hussain, Rhian Deslandes, Deborah Edwards and Karen Louise Hodson

Antibiotics 2025, 14(1), 100; https://doi.org/10.3390/antibiotics14010100 - 16 Jan 2025

Viewed by 735

Abstract

Background/Objectives: The rapid spread of antimicrobial resistance (AMR) presents a critical threat to global health. Primary care plays a significant role in this crisis, with oral antibacterial drugs among the most prescribed medications. Antibacterial prescribing rates are often high and complicated in out-of-hours [...] Read more.

Background/Objectives: The rapid spread of antimicrobial resistance (AMR) presents a critical threat to global health. Primary care plays a significant role in this crisis, with oral antibacterial drugs among the most prescribed medications. Antibacterial prescribing rates are often high and complicated in out-of-hours (OOH) services, including weekdays outside regular hours, weekends, and holidays, potentially exacerbating AMR. This review aims to identify the existing literature on oral antibacterial drug prescribing within primary care OOH services. Methods: This review followed established frameworks, adhered to PRISMA-ScR guidelines, and the protocol was registered on Open Science Framework. Seven databases were searched from 2017 to May 2022. Data were summarised, tabulated, and presented narratively to explore themes and patterns that aligned with the review objectives. Results: The search identified 28 studies from nine high-income countries, mainly the UK (n = 6) and Belgium (n = 5). Most were quantitative studies (n = 23). Key areas identified included common oral antibacterial prescriptions, prescribing trends, presentations and conditions managed in OOH services, factors and predictors associated with prescribing, prescribing appropriateness, the impact of interventions on prescribing, prescribing in the context of COVID-19, patient satisfaction and expectations, and the challenges encountered, such as factors influencing prescribing behaviour and decision making, safety netting, and communication. Conclusions: This review highlights key areas around oral antibacterial prescribing in primary care OOH services. Despite the numerous articles identified covering various areas within OOH services, the variability in OOH services approaches across countries and studies complicates the comparison of practice. Further research is needed to better understand practices in these settings. Full article

(This article belongs to the Special Issue Knowledge, Attitudes and Practices of Antimicrobial Resistance and Stewardship in Primary Care Setting: From Understanding to Informing Interventions)

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20 pages, 5735 KiB

Open AccessArticle

Antimicrobial Resistance Genes in Clinical Escherichia coli Strains from Livestock and Poultry in Shandong Province, China During 2015–2020

by Miaoli Wang, Shaopeng Wu, Yao Wang, Feng Chen, Zhangqi Shen and Zouran Lan

Antibiotics 2025, 14(1), 95; https://doi.org/10.3390/antibiotics14010095 - 15 Jan 2025

Viewed by 883

Abstract

Antimicrobial resistant (AMR) Escherichia coli (E. coli) isolated from animals may lead to antibiotic treatment failure and economic losses to farmers. The co-existence of antimicrobial resistant genes (ARGs) in the same isolate presents a major challenge for the prevention and control [...] Read more.

Antimicrobial resistant (AMR) Escherichia coli (E. coli) isolated from animals may lead to antibiotic treatment failure and economic losses to farmers. The co-existence of antimicrobial resistant genes (ARGs) in the same isolate presents a major challenge for the prevention and control of infection in multidrug-resistant (MDR) Gram-negative organisms. There have been a lot of studies on the antibiotic resistance of E. coli in livestock and poultry, but few of them have focused on clinical pathogens. Objective: The aim of this study was to explore the genetic characteristics, co-occurrence, and correlations between ARGs of E. coli isolated from the pathological tissues of livestock and poultry in Shandong Province, East China during 2015–2020. Methods: A total of 158 E. coli strains were collected and subjected to antimicrobial susceptibility testing and sequencing by whole-genome Next Generation Sequencing (NGS). Results: MDR strains accounted for 46.20% of the 158 E. coli strains with the highest resistant rate of ciprofloxacin (71.52%). In addition, strains with bla_NDM-5/mcr-1.1 and mcr-1.1/mcr-3.24 were found in chickens, while three strains with Tet(X4) were found in pigs. In addition, the most common serotypes detected were the O serotype (76/158) and H serotype (36/158). Moreover, seventy-one STs were found and the most common STs were ST10 (6.33%), ST155 (6.33%), and ST101 (5.69%). The genetic environment analysis of the phylogroups revealed that E. coli belonging to phylogroup B1, phylogroup A, and phylogroup C constituted 39.87%, 27.85%, and 15.19%, respectively. Through the correlation analysis, mcr genes were observed to have certain relationships with ARGS such as bla_TEM, floR, catA/B, and oqx. Conclusions: This study demonstrates the high prevalence and gene diversity of MDR E. coli isolated from a clinic in Shandong Province, East China. We predicted the transmission risk of animal-borne Tet(X4)-bearing and mcr-harboring E. coli to public health and provided insight into the relationship of co-existence or co-transfer between mcr with ARGS. These relationships present a great challenge for the infection control of MDR Gram-negative organisms. Full article

(This article belongs to the Special Issue Molecular Characterization and Antimicrobial Resistance of Pathogens Isolated from Animals)

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15 pages, 1484 KiB

Open AccessStudy Protocol

Sources and Transmission Routes of Carbapenem-Resistant Pseudomonas aeruginosa: Study Design and Methodology of the SAMPAN Study

by Anneloes van Veen, Selvi N. Shahab, Amber Rijfkogel, Anne F. Voor in ’t holt, Corné H. W. Klaassen, Margreet C. Vos, Yulia Rosa Saharman, Anis Karuniawati, Silvia Zelli, Desy De Lorenzis, Giulia Menchinelli, Giulia De Angelis, Maurizio Sanguinetti, Merel Kemper, Anniek E. E. de Jong, Sima Mohammadi, Valentine Renaud, Irena Kukavica-Ibrulj, Marianne Potvin, Guillaume Q. Nguyen, Jeff Gauthier, Roger C. Levesque, Heike Schmitt and Juliëtte A. Severin Show full author list Hide full author list

Antibiotics 2025, 14(1), 94; https://doi.org/10.3390/antibiotics14010094 - 15 Jan 2025

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Abstract

Background/Objectives: The global spread of carbapenem-resistant Pseudomonas aeruginosa (CRPA) warrants collaborative action. Guidance should come from integrated One Health surveillance; however, a surveillance strategy is currently unavailable due to insufficient knowledge on the sources and transmission routes of CRPA. The aim of [...] Read more.

Background/Objectives: The global spread of carbapenem-resistant Pseudomonas aeruginosa (CRPA) warrants collaborative action. Guidance should come from integrated One Health surveillance; however, a surveillance strategy is currently unavailable due to insufficient knowledge on the sources and transmission routes of CRPA. The aim of the SAMPAN study (“A Smart Surveillance Strategy for Carbapenem-resistant Pseudomonas aeruginosa”) is to develop a globally applicable surveillance strategy. Methods: First, an international cross-sectional study will be conducted to investigate CRPA in clinical and environmental settings in Rotterdam (The Netherlands), Rome (Italy), and Jakarta (Indonesia). Screening cultures and risk factor questionnaires will be taken from healthy individuals and patients upon hospital admission. Clinical CRPA isolates will also be included. Additionally, samples will be taken twice from wet hospital environments and monthly from the hospitals’ (drinking) water system, hospital and municipal wastewater treatment plants, and receiving rivers. Whole-genome sequencing will be performed to characterize CRPA isolates and determine the genetic relatedness among the isolates from different reservoirs. Findings from the cross-sectional study, combined with expert elicitation using a Delphi method, will serve as the input for the surveillance strategy. Conclusions: The SAMPAN study will provide a broader understanding of the sources and transmission routes of CRPA. Therewith, the development of a globally applicable smart surveillance strategy will be made possible, delivering information that is needed to guide actions against the spread of CRPA. Full article

(This article belongs to the Section The Global Need for Effective Antibiotics)

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22 pages, 2441 KiB

Open AccessArticle

Chemical Characterization and Antimicrobial Activity of Essential Oils and Nanoemulsions of Eugenia uniflora and Psidium guajava

by Rebeca Dias dos Santos, Breno Noronha Matos, Daniel Oliveira Freire, Franklyn Santos da Silva, Bruno Alcântara do Prado, Karolina Oliveira Gomes, Marta Oliveira de Araújo, Carla Azevedo Bilac, Letícia Fernandes Silva Rodrigues, Izabel Cristina Rodrigues da Silva, Lívia Cristina Lira de Sá Barreto, Claudio Augusto Gomes da Camara, Marcilio Martins de Moraes, Guilherme Martins Gelfuso and Daniela Castilho Orsi

Antibiotics 2025, 14(1), 93; https://doi.org/10.3390/antibiotics14010093 - 14 Jan 2025

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Abstract

Background/Objectives: This study aimed to develop gel nanoemulsions (NEs) of Brazilian essential oils (EOs) from Eugenia uniflora and Psidium guajava, as well as to perform chemical characterization and investigate the antimicrobial activity of the EOs and NEs. Results/Conclusions: The main chemical [...] Read more.

Background/Objectives: This study aimed to develop gel nanoemulsions (NEs) of Brazilian essential oils (EOs) from Eugenia uniflora and Psidium guajava, as well as to perform chemical characterization and investigate the antimicrobial activity of the EOs and NEs. Results/Conclusions: The main chemical compounds of E. uniflora EO were curzerene (34.80%) and germacrene B (11.92%), while those of P. guajava EO were β-caryophyllene (25.92%), β-selinene (22.64%), and γ-selinene (19.13%). The NEs of E. uniflora and P. guajava had droplet sizes of 105.30 and 99.50 nm and polydispersity index (PDI) values of 0.32 and 0.43, respectively. The NEs remained stable for 30 days of storage at 25 °C, with droplet sizes of 104.7 and 103.8 nm, PDI values below 0.50, and no phase separation. The NE of E. uniflora exhibited inhibition zones ranging from 8.41 to 15.13 mm against the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Additionally, the NE of E. uniflora showed the largest inhibition zones against Candida albicans (20.97 mm) and Candida krusei (15.20 mm), along with low minimum inhibitory concentration (MIC) values (0.54–1.22 mg/mL) and minimal bactericidal concentration (MBC) values (4.84–11.02 mg/mL) against these pathogenic yeasts. The NE of P. guajava demonstrated low MIC (1.26 mg/mL) and MBC (11.35 mg/mL) values for C. krusei. The time–growth inhibition assay also suggests the effectiveness of the NE against the tested pathogens S. aureus and E. coli, highlighting its potential as a novel alternative therapeutic agent. Full article

(This article belongs to the Section Novel Antimicrobial Agents)

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18 pages, 1214 KiB

Open AccessReview

PK/PD-Guided Strategies for Appropriate Antibiotic Use in the Era of Antimicrobial Resistance

by Tetsushu Onita, Noriyuki Ishihara and Takahisa Yano

Antibiotics 2025, 14(1), 92; https://doi.org/10.3390/antibiotics14010092 - 14 Jan 2025

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Abstract

Antimicrobial resistance (AMR) poses a critical global health threat, necessitating the optimal use of existing antibiotics. Pharmacokinetic/pharmacodynamic (PK/PD) principles provide a scientific framework for optimizing antimicrobial therapy, particularly to respond to evolving resistance patterns. This review examines PK/PD strategies for antimicrobial dosing optimization, [...] Read more.

Antimicrobial resistance (AMR) poses a critical global health threat, necessitating the optimal use of existing antibiotics. Pharmacokinetic/pharmacodynamic (PK/PD) principles provide a scientific framework for optimizing antimicrobial therapy, particularly to respond to evolving resistance patterns. This review examines PK/PD strategies for antimicrobial dosing optimization, focusing on three key aspects. First, we discuss the importance of drug concentration management for enhancing efficacy while preventing toxicity, considering various patient populations, including pediatric and elderly patients with their unique physiological characteristics. Second, we analyze different PK modeling approaches: the classic top-down approach exemplified by population PK analysis, the bottom-up approach represented by physiologically based PK modeling, and hybrid models combining both approaches for enhanced predictive performance. Third, we explore clinical applications, including nomogram-based dosing strategies, Bayesian estimation, and emerging artificial intelligence applications, for real-time dose optimization. Critical challenges in implementing PK/PD simulation are addressed, particularly the selection of appropriate PK models, the optimization of PK/PD indices, and considerations concerning antimicrobial concentrations at infection sites. Understanding these principles and challenges is crucial for optimizing antimicrobial therapy and combating AMR through improved dosing strategies. Full article

(This article belongs to the Special Issue PK/PD Models for Optimizing Antibiotic Use and Avoiding Drug-Drug Interaction)

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13 pages, 2367 KiB

Open AccessArticle

Evaluation of Antimicrobial Performance of Calcium Dihydroxide (Ca(OH)₂) Coating on Ti for Potential Metallic Orthopedic Implant Applications

by Harald Holeczek, Michael de Wild, Jasmine Ruegg, Philipp Gruner, Walter Moser and Olivier Braissant

Antibiotics 2025, 14(1), 91; https://doi.org/10.3390/antibiotics14010091 - 14 Jan 2025

Viewed by 762

Abstract

Background/Objectives: Orthopedic implant infections are rare but represent a significant problem for patients, surgeons, and the healthcare systems. This is because these infections cause severe and persistent pain and, in some cases, may require revision of the implant, among other things. Thus, there [...] Read more.

Background/Objectives: Orthopedic implant infections are rare but represent a significant problem for patients, surgeons, and the healthcare systems. This is because these infections cause severe and persistent pain and, in some cases, may require revision of the implant, among other things. Thus, there is strong interest in the use of antimicrobial coatings on orthopedic implants. Here, we investigate electrochemically deposited Ca(OH)₂ antimicrobial coating for its potential to be used on metallic orthopedic implants. Methods: A triphenyl tetrazolim chloride (TTC) assay and isothermal microcalorimetry (IMC) were used to determine the reduction in microbial activity on three sets of Ti parts (discs and screws): uncoated, coated with hydroxyapatite (HA), and coated with Ca(OH)₂. Results: Using the TTC assay, a ~70% reduction in the growth of bacteria on Ca(OH)₂-coated discs was found, and using IMC, bacterial growth on these discs showed a decreased rate and an increased lag phase up to 25 h. Each of these sets of results was statistically superior to the corresponding results obtained using the other sets of parts. Conclusions: The present results suggest that the Ca(OH)₂ coating may have potential for use on metallic orthopedic implants. Full article

(This article belongs to the Special Issue Development and Biomedical Application of Antibacterial Coatings)

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19 pages, 1226 KiB

Open AccessReview

Antibiotic Residues in Animal Products from Some African Countries and Their Possible Impact on Human Health

by Oluwaseun Mary Oladeji, Liziwe Lizbeth Mugivhisa and Joshua Oluwole Olowoyo

Antibiotics 2025, 14(1), 90; https://doi.org/10.3390/antibiotics14010090 - 14 Jan 2025

Viewed by 762

Abstract

This review investigates the levels of antibiotic residues in animal products, types of antibiotics, and their possible impact on human health in Africa. The literature search involved the use of a systematic survey using data that were published from Africa from 2015 to [...] Read more.

This review investigates the levels of antibiotic residues in animal products, types of antibiotics, and their possible impact on human health in Africa. The literature search involved the use of a systematic survey using data that were published from Africa from 2015 to 2024. The search terms used the Boolean operators with keywords such as antibiotics, antibiotic residues, antibiotics in animal products in Africa, and impact on human health. Only research conducted in Africa was used in the present study. The findings showed that the most prevalent groups of antibiotic residues were aminoglycoside, macrolides, β-lactams, fluoroquinolones, tetracyclines sulfonamides, and phenicols. Tetracycline showed the most prevalent antibiotic residue with 43% mostly from East Africa, followed by sulfonamides at 19%, and β-lactams at 16%; most of the antibiotic residue levels were higher than the World Health Organization permissible limit. Noncompliance with withdrawal periods and maximum residue limits for antibiotics used in food-producing animals may lead to negative outcomes such as allergic reactions, teratogenicity, carcinogenicity, microbiome alterations, and, most notably, antibiotic resistance. As a result, there is a need for constant monitoring of antibiotic residues in animal products in addition to the consideration of alternatives to antibiotics in order to avoid their health implications. Full article

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18 pages, 2817 KiB

Open AccessArticle

Antimicrobial Residues in Poultry Litter: Assessing the Association of Antimicrobial Persistence with Resistant Escherichia coli Strains

by Paula Cortés, Ekaterina Pokrant, Karina Yévenes, Aldo Maddaleno, Andrés Flores, María Belén Vargas, Lina Trincado, Matías Maturana, Lisette Lapierre and Javiera Cornejo

Antibiotics 2025, 14(1), 89; https://doi.org/10.3390/antibiotics14010089 - 14 Jan 2025

Viewed by 700

Abstract

Objective: We set out to evaluate the persistence of sulfachloropyridazine, oxytetracycline, and enrofloxacin in broiler chicken litter following therapeutic oral treatment and its association with the isolation of Escherichia coli resistant to these antimicrobials. Methods: Forty broiler chickens were raised under [...] Read more.

Objective: We set out to evaluate the persistence of sulfachloropyridazine, oxytetracycline, and enrofloxacin in broiler chicken litter following therapeutic oral treatment and its association with the isolation of Escherichia coli resistant to these antimicrobials. Methods: Forty broiler chickens were raised under controlled conditions and divided into three experimental groups, each treated with a different antimicrobial, in addition to an untreated/control group. Litter samples were collected post treatment, analyzed by UPLC-MS/MS, and processed for the isolation of E. coli. The antimicrobial susceptibility of E. coli was assessed using the Kirby–Bauer disk diffusion method. Results: Chemical analysis detected concentrations of antimicrobials throughout post treatment, reaching maxima of 42,910.14 μg kg⁻¹, 92,712 μg kg⁻¹, and 9567 μg kg⁻¹ for sulfachloropyridazine, oxytetracycline plus 4-epi-oxytetracycline, and enrofloxacin plus ciprofloxacin, respectively. It was estimated that the concentrations of sulfachloropyridazine, oxytetracycline, and enrofloxacin would persist in broiler litter for 61, 244, and 514 days, respectively. A very strong association was observed between the presence of antimicrobial residues and the antimicrobial resistance of E. coli (p-value < 0.0001, and Cramer’s coefficient of 0.47), and an independence between the level of residue concentration and susceptibility (p-value 0.5262). Conclusions: The persistence of antimicrobial residues contributes to the selection of resistant bacteria, regardless of persistent antimicrobial concentrations. These findings highlight the need for stricter regulations on poultry litter management, including residue thresholds and resistance monitoring, to minimize environmental and public health risks. Proper treatment of poultry litter is essential to ensure its sustainable and safe re-use in agricultural systems. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in One Health Perspective: New Insights in Human, Animal, and Environment Interlace, 2nd Edition)

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18 pages, 3541 KiB

Open AccessArticle

Antimicrobial Potential of Secalonic Acids from Arctic-Derived Penicillium chrysogenum INA 01369

by Yulia A. Roshka, Natalia N. Markelova, Sofia D. Mashkova, Kseniya V. Malysheva, Marina L. Georgieva, Igor B. Levshin, Vladimir I. Polshakov, Alexander M. Arutyunian, Alexey S. Vasilchenko and Vera S. Sadykova

Antibiotics 2025, 14(1), 88; https://doi.org/10.3390/antibiotics14010088 - 14 Jan 2025

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Abstract

In this study, two compounds have been isolated from the Arctic-derived fungus Penicillium chrysogenum INA 13460. Structural elucidation, performed using 2D NMR and HR-ESIMS data, has identified the compounds as stereoisomers of secalonic acids, dimeric tetrahydroxanthones. The absolute configurations of these stereoisomers have [...] Read more.

In this study, two compounds have been isolated from the Arctic-derived fungus Penicillium chrysogenum INA 13460. Structural elucidation, performed using 2D NMR and HR-ESIMS data, has identified the compounds as stereoisomers of secalonic acids, dimeric tetrahydroxanthones. The absolute configurations of these stereoisomers have been determined through conformational NMR analysis and circular dichroism spectroscopy. The antimicrobial activity of secalonic acids D and F has been evaluated against a diverse range of microorganisms, including Gram-positive multidrug-resistant Staphylococcus aureus, Gram-negative Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, the phytopathogen Pectobacterium carotovorum VKM-B1247, and the fungi Fusarium oxysporum VKPM F 890, Aspergillus fumigatus VKM F-37, and A. niger ATCC 16404. Genomic and chemical analyses further support P. chrysogenum INA 13460 as a promising natural source for antimicrobial drug discovery and biological control applications. Full article

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

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10 pages, 2388 KiB

Open AccessCommunication

The Appearance of Antiphage Antibodies in Sera of Patients Treated with Phages

by Marzanna Łusiak-Szelachowska, Beata Weber-Dąbrowska, Maciej Żaczek, Ryszard Międzybrodzki and Andrzej Górski

Antibiotics 2025, 14(1), 87; https://doi.org/10.3390/antibiotics14010087 - 14 Jan 2025

Viewed by 471

Abstract

Background: Bacteriophages are neutralized by the sera of patients undergoing phage therapy (PT), particularly during local or concomitant local and oral phage administration in bone infections, soft tissue infections, or upper respiratory tract infections. Methods: The antiphage activity of the sera (AAS) [...] Read more.

Background: Bacteriophages are neutralized by the sera of patients undergoing phage therapy (PT), particularly during local or concomitant local and oral phage administration in bone infections, soft tissue infections, or upper respiratory tract infections. Methods: The antiphage activity of the sera (AAS) level of 27 patients with bacterial infections such as bone infections, soft tissue infections, or upper respiratory tract infections undergoing PT was performed using the plate phage neutralization test. Results: Our preliminary results suggest that high levels of antiphage antibodies appear late in the treatment period, at the earliest in the 3rd–8th week of PT. Patients with bone infections treated locally with the S. aureus phage Staph_1N and patients with upper respiratory tract infections administered locally and orally with the S. aureus phage Staph_A5L had elevated levels of antiphage antibodies in sera during PT. In parallel to these results, it has been shown that a strong antiphage humoral response does not prevent a positive outcome of phage treatment. Conclusions: The earliest time point at which high levels of antiphage antibodies in sera appear during local and oral PT is day 21 of therapy. We noticed that the high level of antiphage antibodies in sera occurring during local or both local and oral PT was correlated with the type of infection and phage type. Full article

(This article belongs to the Special Issue Bacteriophages and Phage-Derived Enzymes as Antibacterial Agents)

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15 pages, 2949 KiB

Open AccessArticle

Antibacterial Efficacy Comparison of Electrolytic and Reductive Silver Nanoparticles Against Propionibacterium acnes

by Suparno Suparno, Rita Prasetyowati, Khafidh Nur Aziz, Anggarwati Rahma, Eka Sentia Ayu Lestari, Siti Chaerani Nabiilah and Deby Grace

Antibiotics 2025, 14(1), 86; https://doi.org/10.3390/antibiotics14010086 - 14 Jan 2025

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Abstract

Background: The aim of this study was to develop an electrolysis system to produce silver nanoparticles free from toxic gases, as the most common reduction and electrolysis techniques produce nitrogen dioxide (NO₂) as a byproduct, which is harmful to human health. [...] Read more.

Background: The aim of this study was to develop an electrolysis system to produce silver nanoparticles free from toxic gases, as the most common reduction and electrolysis techniques produce nitrogen dioxide (NO₂) as a byproduct, which is harmful to human health. The new electrolysis system used two identical silver plate electrodes, replacing silver and carbon rods, and used water as the electrolyte instead of silver nitrate (AgNO₃) solution since AgNO₃ is the source of NO₂. Methods: The electrolytic silver nanoparticles (ESNs) produced by the new system were characterized and compared with reductive silver nanoparticles (RSNs). Using UV–Visible spectrophotometry, absorption peaks were found at 425 nm (ESN) and 437 nm (RSN). Using dynamic light scattering, the particle diameters were measured at 40.3 nm and 39.9 nm for ESNs at concentrations of 10 ppm and 30 ppm, respectively, and 74.0 nm and 74.6 nm for RSNs at concentrations of 10 ppm and 30 ppm, respectively. Antibacterial activity against Propionibacterium acnes (P. acnes) was assessed using the Kirby–Bauer method. Results: It was found that the efficacy of ESNs and RSNs was relatively lower than that of 5% chloramphenicol because it was measured in different concentration units (ESNs and RSNs in ppm and chloramphenicol in %). Using the calibration curve, the efficacy of 5% chloramphenicol was comparable to that of 0.005% ESN. It was also found that P. acnes developed a strong resistance to chloramphenicol and showed no resistance to ESNs. Conclusions: This finding underlines the tremendous potential of ESNs as a future antibiotic raw material. Full article

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19 pages, 1575 KiB

Open AccessReview

The Evolution of Antimicrobial Resistance in Acinetobacter baumannii and New Strategies to Fight It

by Viola Camilla Scoffone, Gabriele Trespidi, Giulia Barbieri, Arooba Arshad, Aygun Israyilova and Silvia Buroni

Antibiotics 2025, 14(1), 85; https://doi.org/10.3390/antibiotics14010085 - 14 Jan 2025

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Abstract

Acinetobacter baumannii is considered one of the prioritized ESKAPE microorganisms for the research and development of novel treatments by the World Health Organization, especially because of its remarkable persistence and drug resistance. In this review, we describe how this can be acquired by [...] Read more.

Acinetobacter baumannii is considered one of the prioritized ESKAPE microorganisms for the research and development of novel treatments by the World Health Organization, especially because of its remarkable persistence and drug resistance. In this review, we describe how this can be acquired by the enzymatic degradation of antibiotics, target site modification, altered membrane permeability, multidrug efflux pumps, and their ability to form biofilms. Also, the evolution of drug resistance in A. baumannii, which is mainly driven by mobile genetic elements, is reported, with particular reference to plasmid-associated resistance, resistance islands, and insertion sequences. Finally, an overview of existing, new, and alternative therapies is provided. Full article

(This article belongs to the Special Issue Antimicrobial Resistance Evolution and New Strategies to Fight It)

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2 pages, 135 KiB

Open AccessRetraction

RETRACTED: Kanan et al. Empowering Low- and Middle-Income Countries to Combat AMR by Minimal Use of Antibiotics: A Way Forward. Antibiotics 2023, 12, 1504

by Mohammed Kanan, Maali Ramadan, Hanan Haif, Bashayr Abdullah, Jawaher Mubarak, Waad Ahmad, Shahad Mari, Samaher Hassan, Rawan Eid, Mohammed Hasan, Mohammed Qahl, Atheer Assiri, Munirah Sultan, Faisal Alrumaih and Areej Alenzi

Antibiotics 2025, 14(1), 84; https://doi.org/10.3390/antibiotics14010084 - 14 Jan 2025

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Abstract

The journal retracts the article “Empowering Low- and Middle-Income Countries to Combat AMR by Minimal Use of Antibiotics: A Way Forward” [...] Full article

14 pages, 2941 KiB

Open AccessArticle

High Antimicrobial Susceptibility of Cloacal Enterococci and Escherichia coli from Free-Living Dalmatian and Great White Pelicans with Detection of Cefotaximase CTX-M-15 Producing Escherichia coli ST69

by Teresa Cardona-Cabrera, Sandra Martínez-Álvarez, Carmen González-Azcona, Carlos Javier Gijón-García, Olga Alexandrou, Giorgos Catsadorakis, Panagiotis Azmanis, Carmen Torres and Ursula Höfle

Antibiotics 2025, 14(1), 83; https://doi.org/10.3390/antibiotics14010083 - 14 Jan 2025

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Abstract

Background/Objectives: In 2022, an outbreak of H5N1 highly pathogenic avian influenza (HPAI) killed 60% of the largest breeding colony of Dalmatian pelicans (DPs) in the world at Mikri Prespa Lake (Greece), prompting a multidisciplinary study on HPAI and other pathogens. This study determines [...] Read more.

Background/Objectives: In 2022, an outbreak of H5N1 highly pathogenic avian influenza (HPAI) killed 60% of the largest breeding colony of Dalmatian pelicans (DPs) in the world at Mikri Prespa Lake (Greece), prompting a multidisciplinary study on HPAI and other pathogens. This study determines the antimicrobial resistance rates of cloacal enterococci and Escherichia coli in DPs. Methods: Fifty-two blood and cloacal swab samples were collected from 31 nestlings (20 DP/11 great white pelicans) hatched after the H5N1 outbreak at the Prespa colony and 21 subadult/adult DPs captured at a spring migration stopover. The swabs were inoculated in non-selective and chromogenic-selective media. Identification was performed using MALDI-TOF, and antimicrobial susceptibility was tested. The genetic content was characterized using PCR and sequencing, and the clonality of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli isolates was characterized using Multilocus Sequence Typing. Results: Twenty-eight non-repetitive E. coli and 45 enterococci isolates were recovered in non-selective media; most of them were susceptible to all antibiotics tested (85.7% E. coli/91.1% enterococci). Three of the fifty-two samples (6%, all adults) contained ESBL-E. coli isolates (detected in chromogenic ESBL plates), all carrying the bla_CTX-M-15 gene and belonging to the lineage ST69. Conclusions: Despite the susceptibility of most fecal E. coli and enterococci isolates to all antibiotics tested, the finding that E. coli of lineage ST69 carry bla_CTX-M-15 is of concern. This high-risk clone needs further investigation to elucidate its primary sources and address the growing threat of antimicrobial resistance from an integrated “One Health” perspective. Furthermore, it is imperative to study the potential impacts of ESBL-E. coli on the endangered DP further. Full article

(This article belongs to the Special Issue Distribution, Sources and Risks of Bacteria and Their Antimicrobial Resistance Genes in the Environment)

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12 pages, 449 KiB

Open AccessArticle

Antibacterial and Antifungal Activities of Linear and Cyclic Peptides Containing Arginine, Tryptophan, and Diphenylalanine

by David Salehi, Eman H. M. Mohammed, Naiera M. Helmy and Keykavous Parang

Antibiotics 2025, 14(1), 82; https://doi.org/10.3390/antibiotics14010082 - 13 Jan 2025

Viewed by 877

Abstract

Background. We have previously reported peptides composed of sequential arginine (R) residues paired with tryptophan (W) or 3,3-diphenyl-L-alanine residues (Dip), such as cyclic peptides [R₄W₄] and [R₄(Dip)₃], as antibacterial agents. Results. Herein, we report antibacterial [...] Read more.

Background. We have previously reported peptides composed of sequential arginine (R) residues paired with tryptophan (W) or 3,3-diphenyl-L-alanine residues (Dip), such as cyclic peptides [R₄W₄] and [R₄(Dip)₃], as antibacterial agents. Results. Herein, we report antibacterial and antifungal activities of five linear peptides, namely ((DipR)₄(WR)), ((DipR)₃(WR)₂), ((DipR)₂(WR)₃), ((DipR)(WR)₄), and (DipR)₄R, and five cyclic peptides [(DipR)₄(WR)], [(DipR)₃(WR)₂], [(DipR)₂(WR)₃], [(DipR)(WR)₄], and [DipR]₅, containing alternate positively charged R and hydrophobic W and Dip residues against fungal, Gram-positive, and Gram-negative bacterial pathogens. The minimum inhibitory concentrations (MICs) of all peptides were determined by the micro-broth dilution method against Methicillin-Resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus subtilis. Fungal organisms were Candida albicans, Candida parapsilosis, and Aspergillus fumigatus. [DipR]₅ and ((DipR)₂(WR)₃) showed MIC values of 0.39–25 µM and 0.78–12.5 µM against Gram-positive and Gram-negative bacteria strains, respectively. The highest activity was observed against S. pneumoniae with MIC values of 0.39–0.78 µM among tested compounds. [DipR]₅ demonstrated MIC values of 6.6 µM against C. parapsilosis and 1.6 µM against A. fumigatus, whereas fluconazole showed MIC values of 3.3 µM and >209 µM, respectively. Conclusions. These findings highlight the potential of these peptides as broad-spectrum antimicrobial agents. Full article

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14 pages, 2585 KiB

Open AccessArticle

Characterization of Clostridium perfringens Phage Endolysin PlyDolk21

by Suyoung Seo, Bokyung Son and Minsuk Kong

Antibiotics 2025, 14(1), 81; https://doi.org/10.3390/antibiotics14010081 - 13 Jan 2025

Viewed by 762

Abstract

Background: Clostridium perfringens is a significant cause of food poisoning. Broad-spectrum antibiotics, commonly used to control C. perfringens, are becoming less effective due to the rise of antibiotic-resistant strains, necessitating alternative control strategies. Methods: A C. perfringens-infecting bacteriophage, Dolk21, and [...] Read more.

Background: Clostridium perfringens is a significant cause of food poisoning. Broad-spectrum antibiotics, commonly used to control C. perfringens, are becoming less effective due to the rise of antibiotic-resistant strains, necessitating alternative control strategies. Methods: A C. perfringens-infecting bacteriophage, Dolk21, and its endolysin, PlyDolk21, were isolated and characterized. The lytic activity of PlyDolk21 was assessed in comparison to its catalytic domain alone. Both PlyDolk21 and its cell wall binding domain (CBD) were evaluated in beef and milk for their antimicrobial activity and cell wall binding activity, respectively. Results: While phage Dolk21 was specific to certain C. perfringens strains, PlyDolk21 exhibited lytic activity against all C. perfringens strains tested. The full-length PlyDolk21 showed stronger lytic activity compared to its catalytic domain alone. PlyDolk21_CBD successfully bound to C. perfringens in vitro and in foods. Additionally, PlyDolk21 effectively reduced the viable cell counts of C. perfringens by 3-log in beef soup and milk samples. Conclusions: This study demonstrates that PlyDolk21 and its CBD hold potential as a biocontrol and detection agent targeting C. perfringens in various food matrices. Full article

(This article belongs to the Special Issue Beyond Phages: Exploring Endolysins as Key Players in the Future of Antibacterial Therapeutics)

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25 pages, 5527 KiB

Open AccessArticle

Molecular Epidemiological Characteristics of Staphylococcus pseudintermedius, Staphylococcus coagulans, and Coagulase-Negative Staphylococci Cultured from Clinical Canine Skin and Ear Samples in Queensland

by Sara Horsman, Julian Zaugg, Erika Meler, Deirdre Mikkelsen, Ricardo J. Soares Magalhães and Justine S. Gibson

Antibiotics 2025, 14(1), 80; https://doi.org/10.3390/antibiotics14010080 - 13 Jan 2025

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Abstract

Background/Objectives: Infections in dogs caused by methicillin-resistant staphylococci (MRS) present limited treatment options. This study’s objective was to investigate the molecular epidemiology of Staphylococcus spp. cultured exclusively from clinical canine skin and ear samples in Queensland, Australia, using whole-genome sequencing (WGS). Methods: Forty-two [...] Read more.

Background/Objectives: Infections in dogs caused by methicillin-resistant staphylococci (MRS) present limited treatment options. This study’s objective was to investigate the molecular epidemiology of Staphylococcus spp. cultured exclusively from clinical canine skin and ear samples in Queensland, Australia, using whole-genome sequencing (WGS). Methods: Forty-two Staphylococcus spp. isolated from clinical canine skin and ear samples, from an unknown number of dogs, were sourced from two veterinary diagnostic laboratories between January 2022 and May 2023. These isolates underwent matrix-assisted laser desorption ionisation– time of flight bacterial identification, minimum inhibitory concentration testing using Sensititre^TM plates and WGS. Phylogenetic trees and core genome multilocus sequence typing (cgMLST) minimum spanning trees (MSTs) were constructed. Results: The isolates included methicillin-resistant and -sensitive S. pseudintermedius (MRSP: 57.1%, 24/42; and MSSP: 19.1%, 8/42), methicillin-resistant and -sensitive S. coagulans (MRSC: 14.3%, 6/42; and MSSC: 2.4%, 1/42) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS: 7.1%, 3/42). Thirty-nine isolates were included after WGS, where all MRS harboured the mecA gene. Eighteen sequence types (STs) were identified, including three novel MRSP and six novel MSSP STs. MRSP ST496-V-VII (23%; 9/39) and MRSP ST749-IV-(IVg) (12.8%; 5/39) were commonly isolated. Phylogenetic analysis of single nucleotide polymorphisms showed that MRSP, MRSC and MSSC were similar to globally isolated staphylococci from canine skin and ear infections. Using cgMLST MSTs, MRSP isolates were not closely related to global strains. Conclusions: Our findings revealed a genotypically diverse geographical distribution and phylogenetic relatedness of staphylococci cultured from clinical canine skin and ear samples across Queensland. This highlights the importance of ongoing surveillance to aid in evidence-based treatment decisions and antimicrobial stewardship. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Infections in Animals)

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10 pages, 478 KiB

Open AccessArticle

A Longer Duration of Intravenous Antibiotic Treatment for Patients with Early Periprosthetic Joint Infections Is Not Associated with a Lower Failure Rate

by Janneke Meijer, Alex Soriano, Wierd Zijlstra, Bas ten Have, Saad Tarabichi, Paul Jutte, Javad Parvizi and Marjan Wouthuyzen-Bakker

Antibiotics 2025, 14(1), 79; https://doi.org/10.3390/antibiotics14010079 - 13 Jan 2025

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Abstract

Background: In recent years, many studies have demonstrated the efficacy of an early switch to oral antibiotics after surgical treatment in orthopedic-related infections. However, large analyses on periprosthetic joint infections (PJIs) are lacking. Material and Methods: We conducted a retrospective observational multicenter study [...] Read more.

Background: In recent years, many studies have demonstrated the efficacy of an early switch to oral antibiotics after surgical treatment in orthopedic-related infections. However, large analyses on periprosthetic joint infections (PJIs) are lacking. Material and Methods: We conducted a retrospective observational multicenter study in patients diagnosed with an early post-operative PJI, defined as one occurring <3 months after the index arthroplasty and treated with debridement, antibiotics, and implant retention (DAIR). Patients from Europe and the USA were included. We took advantage of the fact that an early oral antibiotic switch is routine practice in Europe as opposed to a long duration of intravenous (IV) antibiotic treatment in the USA. Failure was defined as the clinical need for (i) a second unintended DAIR procedure, (ii) implant removal, (iii) suppressive antibiotic treatment, or (iii) PJI-related death, all within one year after DAIR. Results: A total of 668 patients were included. A total of 277 received IV antibiotics for <14 days, 232 between 14 and 27 days, and 159 for >27 days. The overall 1-year failure rate within the 3 groups was 41.5%, 44.4%, and 42.1%, respectively (p = 0.80). This observation remained when excluding patients who failed during IV therapy. A longer duration of IV therapy seemed beneficial for those patients with a high pre-operative C-reactive protein level and lack of modular component exchange. Conclusions: In early post-operative PJIs, a longer duration of IV therapy is not associated with a lower failure rate but may be continued until a sufficient bacterial load reduction has been achieved. Full article

(This article belongs to the Special Issue Antimicrobial Therapeutics for Bone and Periprosthetic Joint Infection)

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Antibiotics, Volume 14, Issue 1 (January 2025) – 108 articles

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