Antibiotics

19 pages, 2386 KiB

Open AccessArticle

Antimicrobial Susceptibility and Toxin Gene Profiles of Commensal Clostridium perfringens Isolates from Turkeys in Hungarian Poultry Farms (2022–2023)

by Ádám Kerek, Ábel Szabó, Franciska Barnácz, Bence Csirmaz, László Kovács and Ákos Jerzsele

Antibiotics 2025, 14(4), 413; https://doi.org/10.3390/antibiotics14040413 - 17 Apr 2025

Abstract

Background: The global spread of antimicrobial resistance (AMR) remains one of the greatest challenges of our time, necessitating collaboration among professionals in both the animal and public health sectors. One bacterial species that is developing AMR is Clostridium perfringens. It causes serious [...] Read more.

Background: The global spread of antimicrobial resistance (AMR) remains one of the greatest challenges of our time, necessitating collaboration among professionals in both the animal and public health sectors. One bacterial species that is developing AMR is Clostridium perfringens. It causes serious bacterial infections and continues to cause significant economic losses in the poultry industry. Methods: This study aimed to evaluate the antimicrobial susceptibility profiles of commensal C. perfringens strains isolated from large-scale turkey flocks in Hungary using minimum inhibitory concentration (MIC) determination. We complemented our research with polymerase chain reaction (PCR) analysis to detect the major and minor toxin genes that are characteristic of the species and to explore the potential associations between gene presence and antimicrobial resistance profiles. Results: A total of 146 commensal isolates were examined. Sensitivity to penicillin was reduced, with only 44.5% of isolates remaining susceptible, whereas 87.7% of isolates were sensitive to amoxicillin. The PCR results revealed that all isolates carried the alpha major toxin gene, 23.9% harbored the beta major toxin gene, 15.8% the beta2 minor toxin gene, 3.4% the NetB minor toxin gene, and 2.7% the epsilon major toxin gene. No statistically significant associations were observed between the presence of toxin genes and the antimicrobial susceptibility profiles of the isolates; the MIC values showed no correlation with the presence of toxin-producing genes. Conclusions: Clostridium perfringens isolates retained susceptibility to beta-lactam antibiotics, which remain the primary choice for treatment. Regular monitoring can aid in establishing temporal trends. Future studies should include larger sample sizes and employ next-generation sequencing to further investigate multidrug-resistant strains. Full article

(This article belongs to the Special Issue Antibiotics Resistance in Animals and the Environment, 2nd Edition)

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19 pages, 3335 KiB

Open AccessArticle

Synergistic Effect of Bacillus and Chitosan: From Flocculation to Enhanced Antimicrobial Activity

by Selena Dmitrović, Nataša Lukić, Ivana Danilov, Vanja Vlajkov, Jovana Grahovac and Aleksandar Jokić

Antibiotics 2025, 14(4), 412; https://doi.org/10.3390/antibiotics14040412 - 17 Apr 2025

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Abstract

Eco-friendly pest management solutions are acknowledged as a crucial element in shaping the future of agriculture through sustainable practices. Achieving the maximum viable cell concentration while being cost-effective is the main goal of the downstream processing for efficient biomass-based microbial biopesticide production. The [...] Read more.

Eco-friendly pest management solutions are acknowledged as a crucial element in shaping the future of agriculture through sustainable practices. Achieving the maximum viable cell concentration while being cost-effective is the main goal of the downstream processing for efficient biomass-based microbial biopesticide production. The purpose of this study was to determine the effectiveness of chitosan flocculation in recovering bacterial Bacillus sp. BioSol021 biomass from broth cultivated using fruit juice industrial effluent as a medium, with the hypothesis of the synergistic effect of microbial and biopolymer components in phytopathogen suppression. Second-order polynomial models were used to calculate the influence of chitosan concentration and mixing speed on flocculation efficiency, settling velocity, and antibacterial activity against Aspergillus flavus (i.e., the inhibition zone diameter). The response surface approach, followed by desirability function optimization and the genetic algorithm were applied. The optimal values achieved in this study were 97.18%, 0.0369 mm/s, and 74.00 mm for flocculation efficiency, settling velocity, and inhibition zone diameter, respectively. The obtained results suggest that chitosan can be used as a flocculation agent for effective downstream processing, but also has a positive effect on the final product antimicrobial activity. Full article

(This article belongs to the Special Issue Biotechnological Production of Novel Antimicrobials)

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22 pages, 307 KiB

Open AccessArticle

The Impact of the COVID-19 Pandemic on Pediatric Microbial Resistance Patterns and Abandonment Rates in Western Romania—An Interdisciplinary Study

by Dan Dumitru Vulcanescu, Iulia Cristina Bagiu, Tiberiu Liviu Dragomir, Virgiliu Bogdan Sorop, Mircea Diaconu, Octavia Harich, Sonia Aniela Tanasescu, Florin Szasz, Luiza Vlaicu, Cosmin Goian and Florin George Horhat

Antibiotics 2025, 14(4), 411; https://doi.org/10.3390/antibiotics14040411 - 16 Apr 2025

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Abstract

Background: The COVID-19 pandemic in Romania exacerbated pediatric antimicrobial resistance (AMR). Overuse of broad-spectrum antibiotics may be related to increased multidrug-resistant bacteria. The main aim of this study was to assess pediatric AMR trends and phenotypes, while a secondary objective was to investigate [...] Read more.

Background: The COVID-19 pandemic in Romania exacerbated pediatric antimicrobial resistance (AMR). Overuse of broad-spectrum antibiotics may be related to increased multidrug-resistant bacteria. The main aim of this study was to assess pediatric AMR trends and phenotypes, while a secondary objective was to investigate the potential links with hospital abandonment. Methods: This retrospective study from the Children’s Emergency Hospital “Louis Țurcanu”, Timișoara, focused on AMR patterns in 2019 pre-pandemic, 2021 pandemic, and 2023 post-pandemic. The following phenotypes were assessed: MRSA, MRCoNS, VRE, ESBL, CRO, MDR, XDR, and PDR. Results: There were 3530 total patients and 6885 total samples. There were 69.92% of the total samples resistant to at least one antimicrobial class, (72.69% in 2019, 67.05% in 2021, 69.16% in 2023). Specifically, resistance towards penicillins remained high across the entire period (57.45–60.93%), while the following classes presented elevated resistance in the pandemic: cephalosporins (42.91%), combination therapies (40.95%), reserve antibiotics (38.89%), and cyclines (13.83%). As for resistance phenotypes, MRSA and MRCoNS peaked during the pandemic (36.08% and 81.43%, respectively) while VRE remained relatively constant. Overall ESBL declined in 2023 to 14.45%, while overall CRO peaked during the pandemic (8.81%). Overall MDR fell during the pandemic (64.47%), while overall XDR peaked in 2019 (9.87%). No PDR cases were observed. Pediatric abandonment was an increasing concern, with regional cases rising from 5.42% (2019) to 9.83% (2023). Compared to the general population, increased antimicrobial resistance in abandoned patients was observed for fluoroquinolones (50.00%), Aminogycolsides (60.00%), reserve antibiotics (70.00%), cephalosporins (60.00%), and urinary antibiotics (60.00%). Resistance to cephalosporins (OR = 5.17, p = 0.0304) and reserve antibiotics (OR = 5.64, p = 0.0049) were key predictors of abandonment risk. Conclusions: The COVID-19 pandemic influenced resistance trends, with notable peaks in MRSA, MRCoNS, and CRO. Post-pandemic patterns suggest continued escalation of resistance. The association between resistant infections and pediatric abandonment highlights the need for robust antimicrobial stewardship and social intervention policies. Full article

(This article belongs to the Special Issue Antibiotics Use and Stewardship in Hospitals and Outpatient Care Facilities, 2nd Edition)

13 pages, 1280 KiB

Open AccessArticle

Antimicrobial Therapies for Early-Onset Group B Streptococcal Sepsis: Insights from an Italian Multicenter Study

by Valeria Capone, Martina Buttera, Francesca Miselli, Serena Truocchio, Mattia Iaccheri, Cinzia Auriti, Roberta Creti, Lorenza Baroni, Luca Bedetti, Belinda Benenati, Giacomo Biasucci, Jenny Bua, Lidia Decembrino, Luisa Di Luca, Silvia Fanaro, Alessandra Foglianese, Lucia Gambini, Nicola Laforgia, Giuseppe Latorre, Sabrina Loprieno, Gianfranco Maffei, Lucia Marrozzini, Francesca Nanni, Giangiacomo Nicolini, Irene Papa, Barbara Perrone, Giancarlo Piccinini, Maria Rita Pulvirenti, Maria Paola Ronchetti, Enrico Rosati, Daniele Santori, Maria Eleonora Scapillati, Davide Scarponi, Sofia Spinedi, Tzialla Chryssoula, Caterina Vocale, Licia Lugli and Alberto Berardi Show full author list Hide full author list

Antibiotics 2025, 14(4), 410; https://doi.org/10.3390/antibiotics14040410 - 16 Apr 2025

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Abstract

Background: Antimicrobial therapies used for treating group B streptococcus (GBS) early-onset sepsis (EOS) provide insight into clinicians’ adherence to antimicrobial stewardship (AMS) guidelines. Methods: We reviewed antimicrobial therapies given to treat newborns with GBS-EOS. Data were obtained from an Italian surveillance [...] Read more.

Background: Antimicrobial therapies used for treating group B streptococcus (GBS) early-onset sepsis (EOS) provide insight into clinicians’ adherence to antimicrobial stewardship (AMS) guidelines. Methods: We reviewed antimicrobial therapies given to treat newborns with GBS-EOS. Data were obtained from an Italian surveillance network (including 35 birthing centers) and were prospectively collected from 1 January 2003 to 31 December 2024. Empiric and definitive therapies were classified as adequate and inadequate. Results: There were 967,054 live births and 200 cases of GBS-EOS, of which 43 (21.5%) were preterm and 157 (78.5%) were full-term; 35 (17.5%) out of 200 showed no signs of illness. Fourteen (7.0%) died (one full-term and thirteen preterm newborns under 34 weeks of gestation). Based on the available information, antibiotics were adequate in 106/137 (77.4%) empiric and 48/119 (40.3%) definitive therapies. The duration of antibiotic courses did not differ between severe (median 10 days, IQR 8.0–14.0) and non-severe cases (median: 10 days; IQR: 10.0–12.5; p = 0.68). Antibiotic treatments lasted ≥ 15 days in 34 (20.1%) out of 169 cases with available information. Conclusions: In this large Italian multicenter study, deviations from international recommendations in antimicrobial therapies for GBS-EOS were critical. Our findings underscore the importance of timely antimicrobial de-escalation and the need to avoid excessively prolonged courses of antimicrobials. Full article

(This article belongs to the Special Issue Neonatal Infections: Epidemiology, Diagnostics and Antibiotic Therapeutics)

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11 pages, 512 KiB

Open AccessArticle

Frequency, Distribution, and Antimicrobial Resistance of Methicillin-Resistant Staphylococci and Mammaliicoccus sciuri Isolated from Dogs and Their Owners in Rio de Janeiro

by Fernanda Cruz Bonnard, Luciana Guimarães, Izabel Mello Teixeira, Sandryelle Mercês Freire, Alessandra Maia, Patrícia Câmara de Castro Abreu Pinto, Thais Veiga Blanchart and Bruno Penna

Antibiotics 2025, 14(4), 409; https://doi.org/10.3390/antibiotics14040409 - 16 Apr 2025

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Abstract

Background: Staphylococcus spp. and Mammaliicoccus sciuri (M. sciuri) are Gram-positive cocci that inhabit mammals’ and birds’ skin and mucous membranes, part of the microbiota. An imbalance in local immunity can increase colonization, resulting in various infections. Inappropriate use of antimicrobials [...] Read more.

Background: Staphylococcus spp. and Mammaliicoccus sciuri (M. sciuri) are Gram-positive cocci that inhabit mammals’ and birds’ skin and mucous membranes, part of the microbiota. An imbalance in local immunity can increase colonization, resulting in various infections. Inappropriate use of antimicrobials leads to Staphylococci and M. sciuri becoming resistant to conventional treatments. The transmission of methicillin-resistant staphylococci and M. sciuri (MRS and MRMs, respectively) between humans and animals is still underreported in Brazil. Objectives: this study aimed to describe the frequency, distribution, resistance pattern, and evaluation of potential sharing of MRS and MRMs in isolates from asymptomatic dogs and their owners in Rio de Janeiro. Methods: Samples from 50 asymptomatic dogs and 34 from their owners were collected. Isolates were identified by mass spectrometry. The mecA gene was confirmed by conventional PCR. Antimicrobial activity of samples that carried the mecA gene was evaluated by disk diffusion method. Results: In this study, MRS and MRMs were analyzed in 50 dogs and their owners (34) by identifying strains carrying the mecA gene. A total of 185 strains were isolated. The mecA gene was found in 33.5% of the isolates. The most prevalent species carrying the mecA gene was S. epidermidis (33.9%). MRMs showed 14.5%. Fourteen dogs had the same strain carrying the mecA gene as their owners. Of these, 50% exhibited the same antimicrobial resistance pattern, determined by the disk diffusion. The highest percentage of resistance observed in the MRS isolated from dogs and the owners was to Erythromycin (51.3% and 56.5%, respectively). Conclusions: The presence of methicillin-resistant staphylococci is worrisome because there is the potential to transfer these strains between dogs and humans. These strains may act as a reservoir of resistance genes. Full article

(This article belongs to the Special Issue Antimicrobial Resistance: Epidemiology and Implications for Veterinary Medicine)

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19 pages, 2157 KiB

Open AccessArticle

Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae in Dogs from Cape Verde and São Tomé and Príncipe: Implications for Public Health

by Raquel Abreu, Alice Matos, Luís Capela, Rita Jorge, Joana F. Guerreiro, Gonçalo Pereira, Eva Cunha, Lélia Chambel, Luis Tavares, Filip Boyen and Manuela Oliveira

Antibiotics 2025, 14(4), 408; https://doi.org/10.3390/antibiotics14040408 - 16 Apr 2025

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Abstract

Antimicrobial resistance is a growing global threat, with surveillance providing essential information to control its spread and support rational treatment strategies. Klebsiella pneumoniae, a member of the Gram-negative Enterobacteriaceae family, frequently develops resistance mechanisms. This study analyzed 195 rectal swabs from companion [...] Read more.

Antimicrobial resistance is a growing global threat, with surveillance providing essential information to control its spread and support rational treatment strategies. Klebsiella pneumoniae, a member of the Gram-negative Enterobacteriaceae family, frequently develops resistance mechanisms. This study analyzed 195 rectal swabs from companion and stray dogs in Santiago and São Nicolau (Cape Verde) and São Tomé and Príncipe, sampled during a neutering and deworming campaign conducted by Veterinary Without Borders Portugal, to detect extended-spectrum β-lactamase (ESBL)-producing bacteria. Samples were enriched and then cultured on ChromID^® ESBL agar, and resulting isolates were identified via MALDI-TOF MS. A total of 35 K. pneumoniae isolates were identified, of which 32 were confirmed as ESBL producers. Antimicrobial susceptibility testing showed 100% resistance to aztreonam, cefotaxime, cefpodoxime, and ceftaroline, and high resistance to cefepime (93.8%), ciprofloxacin (93.8%), and trimethoprim/sulfamethoxazole (90.6%). All isolates were considered multidrug-resistant but remained susceptible to cefoxitin, imipenem, and meropenem. The genes bla_CTX-M, bla_SHV, and bla_TEM were present in 96.9%, 65.6%, and 56.3% of the isolates, respectively. DNA fingerprinting revealed seven clusters, suggesting genetic diversity and strain dissemination across locations. These findings highlight the role of dogs as vectors for antimicrobial resistance dissemination, underscoring the need for continuous surveillance in both veterinary and human medicine. Full article

(This article belongs to the Special Issue Antimicrobial Resistance: Epidemiology and Implications for Veterinary Medicine)

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18 pages, 1248 KiB

Open AccessArticle

Molecular Analysis of Tigecycline Resistance in Carbapenem-Resistant Enterobacterales (CRE) in Mthatha and Surrounding Hospitals

by Luyolo Vumba, Ravesh Singh and Sandeep Vasaikar

Antibiotics 2025, 14(4), 407; https://doi.org/10.3390/antibiotics14040407 - 16 Apr 2025

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Abstract

Background: The emergence of carbapenem-resistant Enterobacterales is prevalent and poses a significant threat to health systems worldwide. This study aimed to conduct a molecular analysis of tigecycline resistance in 100 CRE isolates from Mthatha Hospital and surrounding hospitals. Methods: A retrospective study [...] Read more.

Background: The emergence of carbapenem-resistant Enterobacterales is prevalent and poses a significant threat to health systems worldwide. This study aimed to conduct a molecular analysis of tigecycline resistance in 100 CRE isolates from Mthatha Hospital and surrounding hospitals. Methods: A retrospective study among patients who attended Nelson Mandela Academic Hospital (NMAH) and Mthatha Regional Hospital (MRH), Eastern Cape, South Africa. Enterobacterales isolates were identified using the Vitek2^® system (bioMérieux); an E-test was performed on 100 CRE isolates according to the manufacturer’s instructions. PCR assays for rapid detection of tet(X) and its variants, including tet(X1) and tet(X2), and high-level tigecycline resistance genes tet(X3), tet(X4), and tet(X5) were developed. Results: The results show a notably high prevalence of CRE infections in neonatal, male surgical, and maternal and pediatric wards, predominantly driven by Klebsiella species (53.4%), followed by Enterobacter species (20.5%) and then Escherichia coli (6.7%), and 7.2% of CRE isolates were resistant to tigecycline (E-test). In this study, tet(X) genes were not identified as the primary mechanism of tigecycline resistance. The risk factors associated with tigecycline resistance in CRE include age, pre-exposure to antibiotics, prolonged hospitalization, and undergoing invasive procedures, indicated by strong r = 0.9501. Conclusions: CRE gradually evolves, posing a significant threat to patients of all ages; early detection of carbapenemase production in clinical infections, carriage states, or both is essential to prevent hospital-based outbreaks. Full article

(This article belongs to the Special Issue Antibiotic Use and the Emergence of Antibiotic Resistance in Clinical Settings)

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18 pages, 3595 KiB

Open AccessArticle

Intestinal and Extraintestinal Pathotypes of Escherichia coli Are Prevalent in Food Prepared and Marketed on the Streets from the Central Zone of Mexico and Exhibit a Differential Phenotype of Resistance Against Antibiotics

by Daniela Mora-Coto, Pedro Moreno-Vélez, José Luna-Muñoz, Samadhi Moreno-Campuzano and Miguel Angel Ontiveros-Torres

Antibiotics 2025, 14(4), 406; https://doi.org/10.3390/antibiotics14040406 - 16 Apr 2025

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Abstract

Background/Objectives: Antibiotic resistance is a serious public health problem threatening the treatment of infectious diseases caused by Escherichia coli, the main source of food contamination and responsible for many infectious diseases with high indices of AR profiles. Our objective was to study [...] Read more.

Background/Objectives: Antibiotic resistance is a serious public health problem threatening the treatment of infectious diseases caused by Escherichia coli, the main source of food contamination and responsible for many infectious diseases with high indices of AR profiles. Our objective was to study the presence of Escherichia coli in foods that are distributed and prepared on the street, characterizing its sensitivity profile and resistance to antibiotic drugs commonly prescribed in this geographical area. Methods: Standard procedures were performed to identify and isolate E. coli colonies from food samples collected during a three-year study. Susceptibility assays were conducted to determine the antibiotic resistance profile, and Colony PCR assays were performed to determine the pathogenic and antibiotic resistance genes. Results: A total of 189 food samples were collected, and 100% of the samples were positive for E. coli, with higher percentages of contamination for vegetables and fruits. ETEC (lt) and UPEC (vat, cnf1, hylA) genes were identified in 100% of the samples and DAEC (afa) in 27%. E. coli exhibited high percentages of resistance against ampicillin and amoxicillin/clavulanic acid (100%) and cephalexin (45%). The most effective antibiotics were tetracycline, TMP-SMX, polymyxin, and quinolones. The AR genes tetA, sul1, catA1, strA, qnrS, and floR were identified among the samples. Conclusions: Food prepared and marketed on the streets seriously threatens human health. Ampicillin and amoxicillin/clavulanic acid should not be used to treat infections caused by the multidrug-resistant ETEC and UPEC identified in this area. To our knowledge, this is the first study that explores the status of AR in this geographical area. Full article

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12 pages, 949 KiB

Open AccessArticle

Impact of the COVID-19 Pandemic on Antibiotic Prescriptions at the University Clinical Dentistry Center of Kosovo

by Agon Hoti, Ivana Sutej and Arianit Jakupi

Antibiotics 2025, 14(4), 405; https://doi.org/10.3390/antibiotics14040405 - 15 Apr 2025

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Abstract

Background: The COVID-19 pandemic led to significant disruptions in healthcare services worldwide, including dental care, resulting in increased reliance on antibiotics as a substitute for in-person dental interventions. Aim: This study aimed to examine the prescription of different classes of antibiotics at the [...] Read more.

Background: The COVID-19 pandemic led to significant disruptions in healthcare services worldwide, including dental care, resulting in increased reliance on antibiotics as a substitute for in-person dental interventions. Aim: This study aimed to examine the prescription of different classes of antibiotics at the University Dental Clinical Center of Kosovo during the COVID-19 pandemic and compare it with prescription trends from the pre-pandemic period. Methodology: This study analyzed antibiotic prescription patterns at the University Dental Clinical Center of Kosovo (UCDCK) from 2019 to 2022, focusing on dental patients. Data were collected using a standardized form and a review of electronic health records. Descriptive statistics were used to examine trends, which were compared to data from other countries facing similar healthcare disruptions. The data is organized into quartiles, allowing for a comprehensive understanding of the distribution and trends in antibiotic usage over the four-year period. Results: The study revealed a significant increase in the prescription of broad-spectrum antibiotics, including amoxicillin, clavulanic acid, clindamycin, and metronidazole, during the pandemic period. Data collected from the university dentistry center showed that the highest frequency of antibiotic prescriptions occurred in 2021 (27.6%), while the lowest was in 2022 (22.8%). Metronidazole (39.4%) and amoxicillin with clavulanic acid (38.5%) were the most frequently prescribed antibiotics, together accounting for the majority of prescriptions. Amoxicillin alone represented 18.2%, with other antibiotics prescribed at significantly lower rates. These findings highlight the reliance on these antibiotics for dental treatments and underscore the importance of monitoring prescription trends to optimize usage and minimize resistance risks. Conclusions: The study highlights the impact of the COVID-19 pandemic on dental antibiotic prescription practices in Kosovo, revealing a concerning increase in broad-spectrum antibiotic use. This underscores the need for improved antibiotic stewardship in dental settings, particularly during public health crises, to prevent the exacerbation of antimicrobial resistance. Ensuring continued access to routine dental care and developing robust protocols for antibiotic prescription during emergencies are essential to mitigate the long-term public health impacts of increased antibiotic use. Full article

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28 pages, 723 KiB

Open AccessReview

Novel Antibacterial Approaches and Therapeutic Strategies

by Gustavo A. Niño-Vega, Jorge A. Ortiz-Ramírez and Everardo López-Romero

Antibiotics 2025, 14(4), 404; https://doi.org/10.3390/antibiotics14040404 - 15 Apr 2025

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Abstract

The increase in multidrug-resistant organisms worldwide is a major public health threat driven by antibiotic overuse, horizontal gene transfer (HGT), environmental drivers, and deficient infection control in hospitals. In this article, we discuss these factors and summarize the new drugs and treatment strategies [...] Read more.

The increase in multidrug-resistant organisms worldwide is a major public health threat driven by antibiotic overuse, horizontal gene transfer (HGT), environmental drivers, and deficient infection control in hospitals. In this article, we discuss these factors and summarize the new drugs and treatment strategies suggested to combat the increasing challenges of multidrug-resistant (MDR) bacteria. New treatments recently developed involve targeting key processes involved in bacterial growth, such as riboswitches and proteolysis, and combination therapies to improve efficacy and minimize adverse effects. It also tackles the challenges of the Gram-negative bacterial outer membrane, stressing that novel strategies are needed to evade permeability barriers, efflux pumps, and resistance mechanisms. Other approaches, including phage therapy, AMPs, and AI in drug discovery, are also discussed as potential alternatives. Finally, this review points out the urgency for continued research and development (R&D), industry–academic partnerships, and financial engines to ensure that MDR microbes do not exceed the value of antibacterial therapies. Full article

(This article belongs to the Special Issue Evaluation of Emerging Antimicrobials)

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12 pages, 1013 KiB

Open AccessArticle

Potential Inhibitory Effect of the Peptide Melittin Purified from Apis mellifera Venom on CTX-M-Type Extended-Spectrum β-Lactamases of Escherichia coli

by Sheril Ramos-Alcántara, María Alejandra Cornejo Napan, Giovanni Lopez Campana and Jesus Tamariz Ortiz

Antibiotics 2025, 14(4), 403; https://doi.org/10.3390/antibiotics14040403 - 14 Apr 2025

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Abstract

Background. Extended-spectrum β-lactamases (ESBLs) hydrolyze nearly all β-lactam antibiotics, affecting one of the most important groups of antimicrobials used in Gram-negative infections. Among them, CTX-M is the most widespread type of ESBL. This study aimed to evaluate the hydrolytic activity of CTX-M-type ESBLs [...] Read more.

Background. Extended-spectrum β-lactamases (ESBLs) hydrolyze nearly all β-lactam antibiotics, affecting one of the most important groups of antimicrobials used in Gram-negative infections. Among them, CTX-M is the most widespread type of ESBL. This study aimed to evaluate the hydrolytic activity of CTX-M-type ESBLs following exposure to the antimicrobial peptide Melittin. Methods. Melittin was purified from Apis mellifera venom through ultrafiltration and characterized by SDS-PAGE. The minimum inhibitory concentration (MIC) of Melittin against ESBL-producing E. coli was determined by the broth microdilution method. The inhibition of ESBL’s hydrolytic activity following exposure to sub-MIC doses of Melittin was quantified using a kinetic assay based on hydrolyzed nitrocefin. Additionally, the effect of Melittin on the expression of the bla_CTX-M gene was evaluated via RT-PCR. Results. The peptide fraction of Apitoxin smaller than 10 kDa exhibited a protein band corresponding to Melittin, devoid of higher molecular weight proteins. The MIC of Melittin ranged from 50 to 80 µg/mL. Exposure to Melittin at sub-MIC doses significantly inhibited ESBL hydrolytic activity, reducing it by up to 67%. However, the transcription of the bla_CTX-M gene in the presence of Melittin revealed no significant changes. Conclusions. Melittin is able to inhibit ESBL’s hydrolytic activity but not bla_CTX-M transcription possibly indicating an effect at the translational or post-translational level. Full article

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

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28 pages, 1436 KiB

Open AccessArticle

Repurposing High-Throughput Screening Reveals Unconventional Drugs with Antimicrobial and Antibiofilm Potential Against Methicillin-Resistant Staphylococcus aureus from a Cystic Fibrosis Patient

by Arianna Pompilio, Veronica Lupetti, Valentina Puca and Giovanni Di Bonaventura

Antibiotics 2025, 14(4), 402; https://doi.org/10.3390/antibiotics14040402 - 14 Apr 2025

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Abstract

Background/Objectives: Antibiotic therapy faces challenges from rising acquired and biofilm-related antibiotic resistance rates. High resistance levels to commonly used antibiotics have been observed in methicillin-resistant Staphylococcus aureus (MRSA) strains among cystic fibrosis (CF) patients, indicating an urgent need for new antibacterial agents. This study [...] Read more.

Background/Objectives: Antibiotic therapy faces challenges from rising acquired and biofilm-related antibiotic resistance rates. High resistance levels to commonly used antibiotics have been observed in methicillin-resistant Staphylococcus aureus (MRSA) strains among cystic fibrosis (CF) patients, indicating an urgent need for new antibacterial agents. This study aimed to identify potential novel therapeutics with antibacterial and antibiofilm activities against an MRSA CF strain by screening, for the first time, the Drug Repurposing Compound Library (MedChem Express). Methods/Results: Among the 3386 compounds, a high-throughput screening-based spectrophotometric approach identified 2439 (72%), 654 (19.3%), and 426 (12.6%) drugs active against planktonic cells, biofilm formation, and preformed biofilm, respectively, although to different extents. The most active hits were 193 (5.7%), against planktonic cells, causing a 100% growth inhibition; 5 (0.14%), with excellent activity against biofilm formation (i.e., reduction ≥ 90%); and 4, showing high activity (i.e., 60% ≤ biofilm reduction < 90%) against preformed biofilms. The potential hits belonged to several primary research areas, with “cancer” being the most prevalent. After performing a literature review to identify other, already published biological properties that could be relevant to the CF lung environment (i.e., activity against other CF pathogens, and anti-inflammatory and anti-virulence potential), the most interesting hits were the following: 5-(N,N-Hexamethylene)-amiloride (diuretic), Toremifene (anticancer), Zafirlukast (antiasthmatic), Fenretide (anticancer), and Montelukast (antiasthmatic) against planktonic S. aureus cells; Hemin against biofilm formation; and Heparin, Clemastine (antihistaminic), and Bromfenac (nonsteroidal anti-inflammatory) against established biofilms. Conclusions: These findings warrant further in vitro and in vivo studies to confirm the potential of repurposing these compounds for managing lung infections caused by S. aureus in CF patients. Full article

(This article belongs to the Special Issue Strategies to Counteract Mono- and Polymicrobial Biofilm-Related Infections)

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9 pages, 700 KiB

Open AccessArticle

Intravenous Fosfomycin for Difficult-to-Treat Infections: A Real-Life Multicentric Study in Italy

by Verena Zerbato, Gianfranco Sanson, Lisa Fusaro, Valentina Gerussi, Sara Sincovich, Fabiana Dellai, Giovanni Del Fabro, Nicholas Geremia, Cristina Maurel, Donatella Giacomazzi, Chiara Biasinutto, Filippo Giorgio Di Girolamo, Gianfranco Scrivo, Venera Costantino, Manuela Di Santolo, Marina Busetti, Lory Saveria Crocè, Simone Giuliano, Massimo Crapis, George Zhanel, Carlo Tascini, Roberto Luzzati and Stefano Di Bella Show full author list Hide full author list

Antibiotics 2025, 14(4), 401; https://doi.org/10.3390/antibiotics14040401 - 14 Apr 2025

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Abstract

Background: Fosfomycin, an old antibiotic attracting renewed interest, offers a broad spectrum of activity and unique synergy with other agents. While widely used in severe infections, real-world data on intravenous fosfomycin remain limited. Objectives: This study aimed to describe the clinical and microbiological [...] Read more.

Background: Fosfomycin, an old antibiotic attracting renewed interest, offers a broad spectrum of activity and unique synergy with other agents. While widely used in severe infections, real-world data on intravenous fosfomycin remain limited. Objectives: This study aimed to describe the clinical and microbiological characteristics of patients treated with intravenous fosfomycin and to analyze its administration modalities in a real-world setting. Methods: A multicenter retrospective cohort study was conducted across five Italian hospitals. Adult patients receiving intravenous fosfomycin between January 2020 and December 2023 were included. Results: We enrolled 393 patients. The median age was 69 years, with most patients (45%) admitted to Critical Care Units. Pneumonia (34%), bloodstream infections (22%), and urinary tract infections (21%) were the most common indications. Gram-negative bacteria, particularly E. coli and P. aeruginosa, were the predominant pathogens. Fosfomycin was used as empirical therapy in 55% of cases and was combined with other agents in almost all cases (99%). The most frequent partners were piperacillin/tazobactam (21%) and new beta-lactam/beta-lactamase inhibitor combinations (18%). The median treatment duration was seven days, with most subjects (65%) receiving a fosfomycin dosage regimen of 16 g/day. Minimum inhibitory concentrations (MICs) values for fosfomycin were available for 61 isolates (15%), with 78.7% (48/61) showing MIC ≤ 32 mg/L. C. difficile infection occurred in only 2% of patients. Mortality rates at 30, 60, and 90 days were 21.6%, 26.7%, and 29.3%, respectively. Conclusions: This study provides valuable insights into the real-world use of intravenous fosfomycin. Full article

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

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11 pages, 869 KiB

Open AccessArticle

Evaluating Vancomycin Monotherapy and Dual Therapy with Nifuroxazide for Medium–Severe Clostridioides Difficile Infection

by Jasna Rahimić, Ervin Alibegović, Lana Lekić, Marijana Marković Boras, Amina Džidić-Krivić, Esma Karahmet Farhat and Emina Karahmet Sher

Antibiotics 2025, 14(4), 400; https://doi.org/10.3390/antibiotics14040400 - 14 Apr 2025

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Abstract

Background: All currently used therapeutic protocols and drugs for Clostridioides difficile infection (CDI) treatment do not have a satisfying success and usually cost a lot. Objectives: To compare the efficacy of vancomycin monotherapy vs modified dual therapy with vancomycin + nifuroxazide as a [...] Read more.

Background: All currently used therapeutic protocols and drugs for Clostridioides difficile infection (CDI) treatment do not have a satisfying success and usually cost a lot. Objectives: To compare the efficacy of vancomycin monotherapy vs modified dual therapy with vancomycin + nifuroxazide as a therapeutic protocol for a medium–severe form of CDI. In addition, the effects of a modified therapeutic protocol with standard monotherapy on the number of stools and stool consistency in a medium–severe CDI will be compared. Materials and Methods: A prospective, randomized, controlled clinical trial that included 60 patients divided into two groups was conducted. One group of patients was treated with vancomycin monotherapy. The other group was treated with the modified therapeutic protocol (vancomycin + nifuroxazide). Results: The modified therapy with vancomycin + nifuroxazide demonstrated enhanced pharmacological efficacy in the management of CDI compared to the standard vancomycin monotherapy. Patients treated with dual therapy reported a significantly lower number of stools in first, second and third control; first control (4.47 ± 2.20 compared to 5.70 ± 1.91 in vancomycin group (p = 0.024)), second control (2.37 ± 0.85 compared to 3.13 ± 0.90 in vancomycin group (p = 0.001)), and third control (1.53 ± 0.51 compared to 1.80 ± 0.61 in vancomycin group (p = 0.035)). Also, the first and third controls noted significant improvements in stool consistency, measured as a decrease in the number of completely watery stools (p = 0.011 and p < 0.001, respectively). Conclusions: Nifuroxazide and vancomycin have demonstrated accelerated improvement in patient status and hold promise as a novel dual therapeutic regimen for managing patients diagnosed with a medium–severe form of CDI. Full article

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

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33 pages, 3548 KiB

Open AccessArticle

Analysis of ESAC-Net/EARS-Net Data from 29 EEA Countries for Spatiotemporal Associations Between Antimicrobial Use and Resistance—Implications for Antimicrobial Stewardship?

by James C. McSorley

Antibiotics 2025, 14(4), 399; https://doi.org/10.3390/antibiotics14040399 - 13 Apr 2025

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Abstract

Background/Objectives: Antimicrobial resistance is one of the foremost global health concerns of today, and it could offset much of the progress accrued in healthcare over the last century. Excessive antibiotic use accelerates this problem, but it is recognised that specific agents differ in [...] Read more.

Background/Objectives: Antimicrobial resistance is one of the foremost global health concerns of today, and it could offset much of the progress accrued in healthcare over the last century. Excessive antibiotic use accelerates this problem, but it is recognised that specific agents differ in their capacity to promote resistance, a concept recently promoted by the World Health Organisation in the form of its Access, Watch, Reserve (AWaRe) schema. Which, if any, agents should be construed as having a high proclivity for selection of resistance has been contested. The European Antimicrobial Resistance Surveillance Network (EARS-NET) and European Surveillance of Antimicrobial Consumption Network (ESAC-NET) curate population level data over time and throughout the European Economic Area (EEA). EARS-NET monitors resistance to antimicrobials amongst invasive isolates of sentinel pathogens whereas ESAC-NET tracks usage of systemic antimicrobials. Together, data from these networks were interrogated to delineate correlations between antimicrobial consumption and resistance. Methods: Using univariate and multivariate regression analyses, spatiotemporal associations between the use of specific antimicrobial classes and 14 key resistance phenotypes in five sentinel pathogens were assessed methodically for 29 EEA countries. Results: Use of second and third generation cephalosporins, extended spectrum penicillin/β-lactamase inhibitor combinations, carbapenems, fluoroquinolones, nitroimidazoles and macrolides strongly correlated with key resistance phenotypes, as did overall antimicrobial consumption. Conclusions: The data obtained mostly support the WHO AWaRe schema with critical caveats. They have the potential to inform antimicrobial stewardship initiatives in the EEA, highlighting obstacles and shortcomings which may be modified in future to minimise positive selection for problematic resistance. Full article

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

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14 pages, 496 KiB

Open AccessArticle

Prevalence, Antimicrobial Resistance Patterns, and Emerging Carbapenemase-Producing Enterococcus Species from Different Sources in Lagos, Nigeria

by Wasiu Olawale Salami, Samuel Oluwasegun Ajoseh, Aminat Olajumoke Lawal-Sanni, Ashraf A. Abd El Tawab, Heinrich Neubauer, Gamal Wareth and Kabiru Olusegun Akinyemi

Antibiotics 2025, 14(4), 398; https://doi.org/10.3390/antibiotics14040398 - 12 Apr 2025

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Abstract

Background: Enterococcus species present significant health risks due to their widespread presence in humans, animals, and the environment. This study examined the patterns of antimicrobial resistance (AMR) and the presence of carbapenemase-producing Enterococcus species from various sources. Methods: Between November 2023 [...] Read more.

Background: Enterococcus species present significant health risks due to their widespread presence in humans, animals, and the environment. This study examined the patterns of antimicrobial resistance (AMR) and the presence of carbapenemase-producing Enterococcus species from various sources. Methods: Between November 2023 and February 2024, 500 samples were collected in Lagos State, including 350 clinical human samples, 50 environmental samples, and 100 animal samples. The samples were processed, and Enterococcus isolates were identified and subjected to antimicrobial susceptibility tests (AST) by standard methods. Furthermore, carbapenemase (bla_KPC and oxa-48) and virulence genes (gelE) were detected by real-time polymerase chain reaction (RT-PCR) methods using specific primers. Results: The overall prevalence of Enterococcus isolates was 4.6% (23/500), including 18 E. faecalis and 5 E. faecium. The source prevalence was 24% (12/50) from the environmental samples, 5% (5/100) from animal sources, and 1.7% (6/350) from the clinical samples. All Enterococcus isolates were 100% resistant to ciprofloxacin, erythromycin, imipenem, vancomycin, and ampicillin. However, 91% were susceptible to gentamicin. Six (6) distinct resistance profiles were observed, with the pattern AMP-ERY-TGC-CIP-TS-VA-CHL-AUG-MEM-IMI being the most frequent in 12 E. faecalis (4 isolates from humans, 2 from animals, and 6 from the environment). Notably, 39.1% (9/23) of multiple-drug resistant Enterococcus isolates harbored the gelE virulence gene, including seven E. faecalis (five environmental and two human) and two E. faecium from animal sources. The E. faecalis strains HB003 and HB050, from human bacteremia cases carrying gelE, were the first in Nigeria to produce bla_KPC and oxa-48 carbapenemase genes. Conclusions: This study revealed the emergence of carbapenemase-producing Enterococcus species in our environment. A one-health approach and further molecular studies are essential to mitigate the spread and understand the transmission dynamics. Full article

(This article belongs to the Special Issue Livestock Antibiotic Use and Resistance)

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8 pages, 854 KiB

Open AccessArticle

Co-Colonization of Non-difficile Clostridial Species in Antibiotic-Associated Diarrhea Caused by Clostridioides difficile

by Daniel Salas-Treviño, Samantha Flores-Treviño, Carlos Cisneros-Rendón, Cristian Valdemar Domínguez-Rivera and Adrián Camacho-Ortiz

Antibiotics 2025, 14(4), 397; https://doi.org/10.3390/antibiotics14040397 - 11 Apr 2025

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Abstract

Background/Objectives: Antibiotic-associated diarrhea (AAD) is a public health problem that develops in the hospital setting. The most common causative agent of AAD is Clostridioides difficile infection (CDI), although other non-difficile Clostridia (NDC) might also be present. NDC include members of the [...] Read more.

Background/Objectives: Antibiotic-associated diarrhea (AAD) is a public health problem that develops in the hospital setting. The most common causative agent of AAD is Clostridioides difficile infection (CDI), although other non-difficile Clostridia (NDC) might also be present. NDC include members of the RIC group such as Clostridium ramosum [T. ramosa], Clostridium innocuum and Clostridium clostridioforme [E. clostridioformis]. The co-colonization of NDC and CDI in patients with AAD has not been fully analyzed. Methods: We compared clinical and laboratory data of patients with C. difficile infection (CDI) plus NDC against patients with only CDI. This study was a retrospective, case–control study. Hospitalized confirmed CDI cases were analyzed. CDI detection was performed using a 2-step diagnostic algorithm, including glutamate dehydrogenase (GDH) with toxin A/toxin B assays and molecular detection of the tpi gene. Stool samples were cultured and colonies morphologically compatible with any Clostridia were identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Fisher’s exact test and odds ratio (OR) were calculated to determine the degree of correlation between the variables and the study groups. Results: In the CDI + NDC group (n = 7), positive culture was observed for C. ramosum [T. ramosa] (n = 3), C. innocuum (n = 3), and C. butyricum (n = 1). According to our results, CDI + NDC patients received more days of antibiotic therapy, took more days to reduce diarrhea, had a significant increase in the number of days to suppress diarrhea, and previous hospitalizations were more frequently reported. Conclusions: In conclusion, the positive culture of NDC species such as C. innocuum or C. ramosum in patients with AAD caused by CDI correlates with treatment extension and/or failure. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Hospital- and Community-Associated Infections)

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23 pages, 3042 KiB

Open AccessArticle

Methylglyoxal Alone or Combined with Light-Emitting Diodes/Complex Electromagnetic Fields Represent an Effective Response to Microbial Chronic Wound Infections

by Firas Diban, Paola Di Fermo, Silvia Di Lodovico, Morena Petrini, Serena Pilato, Antonella Fontana, Morena Pinti, Mara Di Giulio, Emilio Lence, Concepción González-Bello, Luigina Cellini and Simonetta D’Ercole

Antibiotics 2025, 14(4), 396; https://doi.org/10.3390/antibiotics14040396 - 10 Apr 2025

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Abstract

Background: antimicrobial resistance represents a critical issue leading to delayed wound healing; hence, it is necessary to develop novel strategies to address this phenomenon. Objectives: this study aimed to explore the antimicrobial/anti-virulence action of Methylglyoxal-MGO alone or combined with novel technologies such as [...] Read more.

Background: antimicrobial resistance represents a critical issue leading to delayed wound healing; hence, it is necessary to develop novel strategies to address this phenomenon. Objectives: this study aimed to explore the antimicrobial/anti-virulence action of Methylglyoxal-MGO alone or combined with novel technologies such as Light-Emitting Diodes-LED and Complex Magnetic Fields-CMFs against resistant clinical strains isolated from chronic wounds. Methods: characterized planktonic Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans isolates were used. Antimicrobial activity was evaluated by measuring optical density, Colony Forming Units-CFU, and synergy between MGO/LED or CMFs. Cellular membrane permeability by propidium iodide fluorescence and fluidity by Laurdan generalized polarization measurements were performed. P. aeruginosa motility was tested using the soft agar method. A docking study was performed to evaluate the possible interaction between MGO and urease in P. aeruginosa. Results: single/combined treatments showed significant antimicrobial activity. Major CFU reduction was detected after CMFs/MGO+CMFs application on C. albicans. Treatments exhibited significant changes in membrane permeability and fluidity. The treatments decreased P. aeruginosa motility with a major reduction after LED application. Docking analysis showed that MGO could bind with P. aeruginosa urease leading to defective folding and functional alterations. Conclusions: the results suggest that these treatments could represent promising and green therapeutic solutions against resistant isolates from chronic wounds. Full article

(This article belongs to the Special Issue Honey: Antimicrobial and Anti-infective Function)

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25 pages, 4512 KiB

Open AccessArticle

Efficient Removal of Tetracyclines and Their Metabolites from Wastewater Using Purified Stevensite: Adsorption Capacity, Reusability, and Antibiotic Decontamination

by Noelia García-Criado, Laura Martín-Pozo, Julia Martín, Juan Luis Santos, Irene Aparicio and Esteban Alonso

Antibiotics 2025, 14(4), 395; https://doi.org/10.3390/antibiotics14040395 - 10 Apr 2025

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Abstract

Background/Objectives: The persistence of tetracycline residues in aquatic environments poses substantial risks to ecosystems and public health, emphasizing the need for effective removal strategies. This study examines the use of purified stevensite (ST), a natural clay mineral, as an efficient and cost-effective adsorbent [...] Read more.

Background/Objectives: The persistence of tetracycline residues in aquatic environments poses substantial risks to ecosystems and public health, emphasizing the need for effective removal strategies. This study examines the use of purified stevensite (ST), a natural clay mineral, as an efficient and cost-effective adsorbent for removing tetracycline antibiotics from contaminated water. Methods: Batch experiments were conducted to assess the adsorption kinetics, isotherms, and influence of environmental factors. Material characterization studies were performed before and after tetracycline adsorption. Results: ST demonstrated optimal removal efficiency at an acidic pH, achieving over 99% elimination of both tetracyclines and their metabolites at an adsorbent dose of 2 g L⁻¹ and antibiotic concentration of 5 mg L⁻¹. Equilibrium was reached within 30 min. Regeneration experiments confirmed that ST retained over 90% of its adsorption capacity after five adsorption–desorption cycles. Surface characterization revealed that ST’s large surface area, high cation exchange capacity, and potential for hydrogen bonding may explain its high adsorption capabilities. The material was tested on real samples of tap water, surface water, and wastewater, demonstrating an effective removal rate over 99%. Conclusions: With its high efficiency, low cost and favourable reusability, purified ST is a promising option for large-scale wastewater treatment, contributing to safer water resources and improved environmental protection. Full article

(This article belongs to the Special Issue Antibiotics in the Environment: Sources, Fate, and Mitigation Strategies)

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39 pages, 6950 KiB

Open AccessReview

Emerging Trends in Antimicrobial Resistance in Polar Aquatic Ecosystems

by Melissa Bisaccia, Francesca Berini, Flavia Marinelli and Elisa Binda

Antibiotics 2025, 14(4), 394; https://doi.org/10.3390/antibiotics14040394 - 10 Apr 2025

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Abstract

The global spread of antimicrobial resistance (AMR) threatens to plummet society back to the pre-antibiotic era through a resurgence of common everyday infections’ morbidity. Thus, studies investigating antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in urban, agricultural, and clinical settings, as well [...] Read more.

The global spread of antimicrobial resistance (AMR) threatens to plummet society back to the pre-antibiotic era through a resurgence of common everyday infections’ morbidity. Thus, studies investigating antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in urban, agricultural, and clinical settings, as well as in extreme environments, have become increasingly relevant in the One Health perspective. Since the Antarctic and Arctic regions are considered amongst the few remaining pristine environments on Earth, the characterization of their native resistome appears to be of the utmost importance to understand whether and how it is evolving as a result of anthropogenic activities and climate change. In the present review, we report on the phenotypic (e.g., disk diffusion test) and genotypic (e.g., PCR, metagenomics) approaches used to study AMR in the aquatic environment of polar regions, as water represents one of AMR main dissemination routes in nature. Their advantages and limits are described, and the emerging trends resulting from the analysis of ARB and ARGs diffusion in polar waters discussed. The resistome detected in these extreme environments appears to be mostly comparable to those from more anthropized areas, with the predominance of tetracycline, β-lactam, and sulfonamide resistance (and related ARGs). Indeed, AMR is, in all cases, more consistently highlighted in sites impacted by human and wildlife activities with respect to more pristine ones. Surprisingly, aminoglycoside and fluroquinolone determinants seem to have an even higher incidence in the Antarctic and Arctic aquatic environment compared to that from other areas of the world, corroborating the need for a more thorough AMR surveillance in these regions. Full article

(This article belongs to the Special Issue Antibiotic Resistance: The Role of Aquatic Environments)

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13 pages, 737 KiB

Open AccessArticle

Influence of N-Acetyl-L-Cysteine on the Pharmacokinetics and Antibacterial Activity of Marbofloxacin in Chickens

by Albena Roydeva, Nikolina Rusenova and Aneliya Milanova

Antibiotics 2025, 14(4), 393; https://doi.org/10.3390/antibiotics14040393 - 10 Apr 2025

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Abstract

Background/Objectives: Marbofloxacin, a second-generation fluoroquinolone, is used to control economically significant poultry diseases caused by pathogenic bacteria such as Staphylococcus aureus and Escherichia coli. Although synergistic antimicrobial activity between fluoroquinolones and N-acetyl-L-cysteine (NAC) has been observed in vitro, data on their [...] Read more.

Background/Objectives: Marbofloxacin, a second-generation fluoroquinolone, is used to control economically significant poultry diseases caused by pathogenic bacteria such as Staphylococcus aureus and Escherichia coli. Although synergistic antimicrobial activity between fluoroquinolones and N-acetyl-L-cysteine (NAC) has been observed in vitro, data on their pharmacokinetic interactions in vivo remain limited. This study aimed to evaluate the effect of NAC on the oral pharmacokinetics of marbofloxacin in broiler chickens and its antibacterial activity against E. coli ATCC 25922 and S. aureus ATCC 25923, assessing the potential benefits of their combined administration. Methods: The pharmacokinetics of marbofloxacin was evaluated in broilers (5 mg/kg dose) after a single intravenous (n = 12) or single oral (n = 12) administration into the crop. The protocol for the co-administration of marbofloxacin and NAC (400 mg/kg via feed) was as follows: on the first day, the poultry (n = 12) received a single oral dose of marbofloxacin via the crop and over the next four days the fluoroquinolone drug was administered via their drinking water. The plasma levels of the drugs were determined using LC-MS/MS analyses, and minimum inhibitory concentrations were determined using the microbroth dilution method. Results: NAC significantly reduced the bioavailability of marbofloxacin after a single oral administration into the crop and decreased the elimination rate constant following the administration of both drugs. At a concentration of 20 μg/mL, NAC led to a 3.8-fold reduction in the MIC of marbofloxacin against E. coli ATCC 25922 and a 2-fold decrease at concentrations between 1 μg/mL and 6 μg/mL, while no change was observed in marbofloxacin’s effect on S. aureus ATCC 25923. Conclusions: Oral co-administration of NAC and marbofloxacin reduced the fluoroquinolone’s bioavailability by two-fold while enhancing its antibacterial activity against E. coli ATCC 25922. Full article

(This article belongs to the Special Issue Antibiotic Resistance and the Responsible Use of Antibiotics in Human and Veterinary Medicine)

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14 pages, 1100 KiB

Open AccessArticle

Development of a Bloodstream Infection Surveillance Programme at a Resource-Limited South African Neonatal Unit

by Frances Ashton, Adrie Bekker, Magdalena Aucamp, Kessendri Reddy, Andrew Whitelaw and Angela Dramowski

Antibiotics 2025, 14(4), 392; https://doi.org/10.3390/antibiotics14040392 - 10 Apr 2025

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Abstract

Background: Data from African neonatal units conducting bloodstream infection (BSI) surveillance is limited. Methods: Prospective clinical and laboratory surveillance of incident BSI episodes was conducted among in-patients at the 132-bed neonatal service at Tygerberg Hospital, Cape Town, South Africa (2017–2021), describing [...] Read more.

Background: Data from African neonatal units conducting bloodstream infection (BSI) surveillance is limited. Methods: Prospective clinical and laboratory surveillance of incident BSI episodes was conducted among in-patients at the 132-bed neonatal service at Tygerberg Hospital, Cape Town, South Africa (2017–2021), describing patient demographics, BSI rates, pathogen profiles, and empiric antibiotic concordance rates. Results: In total, 842 BSI episodes were identified in 740 neonates; most were preterm (661/740; 89.3%) and of low birth weight (640/740; 86.5%). The early onset BSI rate (<3 days of life) was 2.9/1000 live births, with S. agalactiae, K. pneumoniae, and E. coli predominating. Over time, ampicillin plus gentamicin coverage rates for early onset BSI pathogens declined from 93.8% to 63.6%. The healthcare-associated BSI rate (onset >3 days of life) was 3.4/1000 in-patient days, with K. pneumoniae, S. aureus, and S. marcescens predominating. Antibiotic coverage rates for healthcare-associated BSIs improved over time, from 72.2% to 89.2% (piperacillin plus amikacin) and from 68.1% to 84.6% (meropenem). Nearly one-third of BSI episodes were fatal (244/842; 29.0%), with two-thirds of these deaths considered BSI-attributable. Gram-negative BSIs increased mortality (OR 2.88; 95% CI 1.93–4.32) compared to Gram-positive BSIs (p < 0.001). Discordant empiric antibiotic therapy (OR 1.55; 95% CI 1.10–2.17) increased the risk of death compared to concordant therapy (p = 0.012). Conclusions: Neonatal BSI surveillance demonstrated that Gram-negative pathogens remain important causes of early onset and healthcare-associated BSIs in this resource-limited neonatal service. Declining coverage rates for empiric antibiotics prescribed for early onset BSI highlight the need for a change in treatment guidelines to minimise discordant therapy. Full article

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18 pages, 2983 KiB

Open AccessReview

Infective Spondylitis in Adults: A Journey Through Diagnosis, Management, and Future Directions

by Woo-Seok Jung, Sung-Ryul Choi, Ji-Won Kwon, Kyung-Soo Suk, Hak-Sun Kim, Seong-Hwan Moon, Si-Young Park, Jae-Won Shin and Byung-Ho Lee

Antibiotics 2025, 14(4), 391; https://doi.org/10.3390/antibiotics14040391 - 9 Apr 2025

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Abstract

Infective spondylitis is a rare but potentially devastating spinal infection that requires timely diagnosis and appropriate treatment to prevent severe complications, including neurological deficits and spinal deformity. Despite advancements in diagnostic imaging, microbiological techniques, and antimicrobial therapies, clinical challenges persist because of the [...] Read more.

Infective spondylitis is a rare but potentially devastating spinal infection that requires timely diagnosis and appropriate treatment to prevent severe complications, including neurological deficits and spinal deformity. Despite advancements in diagnostic imaging, microbiological techniques, and antimicrobial therapies, clinical challenges persist because of the disease’s insidious onset, varied etiologies, and increasing antimicrobial resistance. This review article provides a comprehensive analysis of the current literature on the epidemiology, pathophysiology, diagnostic approaches, and treatment strategies for infective spondylitis. Full article

(This article belongs to the Special Issue Advances in the Field of Biofilm-Associated Musculoskeletal Infections)

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14 pages, 1330 KiB

Open AccessArticle

A Laboratory Protocol for Routine Therapeutic Drug Monitoring of Beta-Lactams Antimicrobials in Horses and Dogs

by Anisa Bardhi, Aliai Lanci, Aurora Mannini, Carolina Castagnetti and Andrea Barbarossa

Antibiotics 2025, 14(4), 390; https://doi.org/10.3390/antibiotics14040390 - 9 Apr 2025

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Abstract

Background: Although antibiotic resistance is a well-known issue in veterinary medicine, studies proposing real-time therapeutic monitoring (TDM) are lacking. The objective of the present study was to develop a simple and rapid protocol for the real-time therapeutic monitoring of antibiotics in horses and [...] Read more.

Background: Although antibiotic resistance is a well-known issue in veterinary medicine, studies proposing real-time therapeutic monitoring (TDM) are lacking. The objective of the present study was to develop a simple and rapid protocol for the real-time therapeutic monitoring of antibiotics in horses and dogs. Methods: A reliable TDM protocol should encompass guidelines for the definition of plasma/serum collection time points, sample management by the clinical staff, transportation to the laboratory, and the availability of robust and swift analytical technologies. Ampicillin and sulbactam were quantified using liquid chromatography–tandem mass spectrometry (LC-MS/MS) in the plasma or serum of animals treated with ampicillin alone or combined with sulbactam. Results: The method was successfully applied to samples collected from animals hospitalized in our veterinary hospital and proved helpful in understanding the pharmacokinetics of this antibiotic in critically ill patients. Conclusions: Combined with minimum inhibitory concentration (MIC) data, this approach enables PK/PD evaluations to support the development of personalized therapeutic strategies and optimized dosing regimens for animals. Full article

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

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14 pages, 4380 KiB

Open AccessArticle

Antimicrobial Activity of Pediococcus pentosaceus PMY2 Against Multidrug-Resistant Pathogens

by Gyeong-Seon Yi, Xiangji Jin, Qiwen Zheng, Trang Thi Minh Nguyen, Su-Jin Yang and Tae-Hoo Yi

Antibiotics 2025, 14(4), 389; https://doi.org/10.3390/antibiotics14040389 - 8 Apr 2025

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Abstract

Background/Objectives: Multidrug-resistant (MDR) pathogens pose a critical challenge in infection treatment. Pediococcus pentosaceus (P. pentosaceus) is known for its antimicrobial activity; however, studies on its effects against MDR pathogens remain limited. This study aimed to evaluate the antimicrobial and biological [...] Read more.

Background/Objectives: Multidrug-resistant (MDR) pathogens pose a critical challenge in infection treatment. Pediococcus pentosaceus (P. pentosaceus) is known for its antimicrobial activity; however, studies on its effects against MDR pathogens remain limited. This study aimed to evaluate the antimicrobial and biological activities of P. pentosaceus PMY2, isolated from fermented porcine colostrum yogurt, against MDR pathogens, including Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli). Methods: The antimicrobial, anti-inflammatory, and cytotoxic effects of P. pentosaceus PMY2 were evaluated in vitro. In addition, IL-6 and TNF-α levels were analyzed using an ELISA kit. Results: The MIC value against S. aureus KCTC 3881 and MRSA (CCARM 3089) was 0.31 mg/mL, while the MBC values were 0.63 mg/mL and 2.5 mg/mL, respectively. At MIC, biofilm formation was inhibited by 62.2% in S. aureus KCTC 3881 and by 51.5% in MRSA. CFS exhibited low cytotoxicity in RAW 264.7 macrophages and significantly reduced NO production, IL-6, and TNF-α levels, indicating strong anti-inflammatory effects. Conclusions: These findings suggest that P. pentosaceus PMY2 exhibited excellent antimicrobial and anti-inflammatory activity against MDR pathogens, demonstrating its potential as a natural antimicrobial agent. These results indicate that PMY2 CFS could be a promising candidate for addressing antibiotic resistance issues. Full article

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

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13 pages, 933 KiB

Open AccessArticle

Real-Life Cefiderocol Use in Bone and Joint Infection: A French National Cohort

by Ava Diarra, Maxime Degrendel, Isabelle Eberl, Tristan Ferry, Karim Jaffal, Lelia Escaut, Antoine Asquier Khati, Nicolas Taar, Johan Courjon, Laurène Deconinck, Benjamin Lefevre, Aurélie Baldolli, Messaline Bermejo, Alexandre Bleibtreu, Vincent Dacquet, Victoire de Lastours, Pierre Gazeau, Romaric Larcher, Pierre Patoz, Olivier Robineau, Nicolas Rouzic, Naomi Sayre, Diana Isabela Costescu Strachinaru, Benjamin Valentin, Heidi Wille and Eric Senneville Show full author list Hide full author list

Antibiotics 2025, 14(4), 388; https://doi.org/10.3390/antibiotics14040388 - 8 Apr 2025

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Abstract

Background: Cefiderocol (CFD) is a novel siderophore cephalosporin developed for the treatment of infections involving multidrug-resistant (MDR) Gram-negative bacilli (GNB) infections (1–3). For bone and joint infections (BJIs), the use of CFD is currently neither part of its market authorization nor recommended, [...] Read more.

Background: Cefiderocol (CFD) is a novel siderophore cephalosporin developed for the treatment of infections involving multidrug-resistant (MDR) Gram-negative bacilli (GNB) infections (1–3). For bone and joint infections (BJIs), the use of CFD is currently neither part of its market authorization nor recommended, and has not yet been assessed by large-scale studies. Objectives: To fill the scarcity of data regarding the use of CFD in BJIs, we aimed to describe patients’ and infection characteristics along with the outcomes of the infection. Methods: We conducted a retrospective observational multicenter study in 22 French centers from January 2019 to December 2023. Results: From January 2019 to December 2023, 45 patients were included. Patients were mainly males (73%) with a median age of 62 years (interquartile range [IQR] 29), and a median Charlson comorbidity index of 3. Implant-related infections (20) were the most prominent, accounting for 44% of the cases. Carbapenemase-producing GNB were involved in 74% of the cases (n = 17/23), among which Pseudomonas aeruginosa accounted for 38% of these cases. Most patients received 6 g of CFD per day. CFD was used in combination with an antibiotic in 40 out of 45 cases (89%). The median duration of CFD treatment was 34 days. Seven patients (16%) experienced side effects, mainly gastro-intestinal disorders, including three (7%) who induced treatment cessation. Infection control included surgery in 37 (82%) patients. Failures and deaths occurred, respectively, in 22 (49%) and 10 (22%) cases. Conclusions: Our results suggest that CFD may be an alternative in MDR-GNB infections with limited therapeutic options. Full article

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

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14 pages, 250 KiB

Open AccessReview

Antibiotic Considerations in the Treatment of Maternal Sepsis

by Sarah E. White, R. Phillips Heine and Talla M. Widelock

Antibiotics 2025, 14(4), 387; https://doi.org/10.3390/antibiotics14040387 - 7 Apr 2025

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Abstract

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains the third leading cause of maternal mortality globally. Pregnancy-associated physiological adaptations predispose pregnant individuals to infection, impair maternal response to infection, affect antibiotic pharmacokinetics and metabolism, and complicate diagnosing [...] Read more.

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains the third leading cause of maternal mortality globally. Pregnancy-associated physiological adaptations predispose pregnant individuals to infection, impair maternal response to infection, affect antibiotic pharmacokinetics and metabolism, and complicate diagnosing infections and sepsis. Therefore, it is tantamount that clinicians readily recognize maternal sepsis and understand antibiotic regimens and treatment principles to avoid adverse maternal outcomes. In this article, we present an overview of the diagnosis and management of maternal sepsis and the physiological changes in pregnancy that alter antibiotic pharmacokinetics. Common microorganisms implicated in maternal sepsis are discussed with an emphasis on E. coli and Group A Streptococcus due to their prevalence and morbidity in the pregnant population. Lastly, we provide an overview of commonly used antibiotics and dosage recommendations in the treatment of maternal infection and sepsis. Full article

(This article belongs to the Special Issue Sepsis Management and Antibiotic Therapy)

10 pages, 1379 KiB

Open AccessArticle

Efficacy of Ceftobiprole and Daptomycin at Bone Concentrations Against Methicillin-Resistant Staphylococcus aureus Biofilm: Results of a Dynamic In Vitro PK/PD Model

by Mikel Mancheño-Losa, María Ángeles Meléndez-Carmona, Carlos Lumbreras and Jaime Lora-Tamayo

Antibiotics 2025, 14(4), 386; https://doi.org/10.3390/antibiotics14040386 - 5 Apr 2025

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Abstract

Background: The presence of biofilms and low antimicrobial concentrations in bone tissue make prosthetic joint infections (PJI) difficult to treat. Ceftobiprole (CTO) has a potential role in MRSA PJI. This study evaluated the efficacy of ceftobiprole and daptomycin (DAP) alone and in [...] Read more.

Background: The presence of biofilms and low antimicrobial concentrations in bone tissue make prosthetic joint infections (PJI) difficult to treat. Ceftobiprole (CTO) has a potential role in MRSA PJI. This study evaluated the efficacy of ceftobiprole and daptomycin (DAP) alone and in combination against MRSA biofilms at expected bone tissue concentrations. We assessed whether CTO-DAP outperformed DAP combined with a non-anti-MRSA beta-lactam (cefazolin [CZO]). Methods: A dynamic in vitro PK/PD biofilm model (CDC biofilm reactor) was used to simulate concentrations expected in cortical bone at a standard dosing of DAP (10 mg/kg/24 h), CTO (500 mg/8 h), and CZO (2 g/8 h), and assess performance against a 48-h MRSA biofilm from two clinical isolates that cause PJI (MRSA-1811 and MRSA-1733). Time–kill curves using the log change method (Δlog₁₀ CFU/cm²) assessed antimicrobial efficacy over 56 h. Resistance emergence was monitored. Results: Although both monotherapies were active, neither reached bactericidal levels nor was one superior to the other (Δlog₁₀ CFU/cm² CTO vs. DAP: −1.44 ± 0.25 vs. −1.50 ± 0.01 [p = 0.686] and −1.55 ± 0.74 vs. −0.56 ± 0.36 [p = 0.108] for MRSA-1811 and MRSA-1733, respectively). Only in the MRSA-1811 isolate did the CTO-DAP combination improve the activity of each monotherapy, without achieving a synergistic effect (Δlog₁₀ CFU/cm²: CTO-DAP −2.087 ± 0.048 vs. CTO −1.436 ± 0.249 [p = 0.013] and vs. DAP −1.503 ± 0.011 [p = 0.006]). No combination therapy (CTO-DAP vs. DAP-CZO) outperformed the other in either strain. No resistant bacterial subpopulations appeared with any antibiotic regimen. Conclusions: At clinically relevant concentrations, ceftobiprole and daptomycin showed similar activity against MRSA biofilms. The CTO-DAP combination showed comparable efficacy to DAP-CZO. Full article

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

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21 pages, 7272 KiB

Open AccessArticle

Structure–Activity Study of the Antimicrobial Lipopeptide Humimycin A and Screening Against Multidrug-Resistant Staphylococcus aureus

by Md Ramim Tanver Rahman, Louis-David Guay, Ismail Fliss and Eric Biron

Antibiotics 2025, 14(4), 385; https://doi.org/10.3390/antibiotics14040385 - 5 Apr 2025

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Abstract

Background: The emergence of multidrug-resistant (MDR) Staphylococcus aureus presents a critical global health challenge due to treatment failures and high mortality rates. Faced with this growing threat, new antimicrobials with original modes of action are urgently needed, and antimicrobial peptides proved to be [...] Read more.

Background: The emergence of multidrug-resistant (MDR) Staphylococcus aureus presents a critical global health challenge due to treatment failures and high mortality rates. Faced with this growing threat, new antimicrobials with original modes of action are urgently needed, and antimicrobial peptides proved to be promising alternatives. Objectives: The aim of this study is to explore the structure–function relationship of the lipopeptide humimycin A, compare the spectrum of activity of the synthetic analogs against a panel of S. aureus isolates, and investigate their binding to the humimycin target, the lipid II flippase MurJ. Methods: Humimycin A and 15 analogs were produced by solid-phase peptide synthesis, and their antimicrobial activity was evaluated by agar diffusion and microtitration assays against 19 S. aureus isolates from bovine mastitis and other pathogens. Results: Among the synthesized peptides, four humimycin analogs exhibited activity against methicillin-sensitive and methicillin-resistant S. aureus, as well as several isolates in the panel, including MDR S. aureus, with minimal inhibitory concentration values ranging from 0.5 to 256 µg/mL. Results from the structure–activity relationship study showed that the β-hydroxymyristoyl lipid chain and C-terminal carboxylic acid are essential for antimicrobial efficacy. In presence of human erythrocytes, the active humimycin analogs exhibited moderate hemolytic activity, suggesting selectivity indexes ranging from 3 to 27 against the more sensitive S. aureus strains. Critical micelle concentration measurements elucidated micelle formation and proved to not be essential for the antibacterial activity. Molecular docking and 100 ns simulations with the lipid II flippase MurJ (PDB: 5T77) provided favorable binding energy. Conclusions: The findings underscore the potential of humimycin analogs as antimicrobials for preventing and treating MDR S. aureus infections in veterinary, animal husbandry, and human medicine. Full article

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

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20 pages, 2184 KiB

Open AccessArticle

Phenolic-Rich Wine Pomace Extracts as Antioxidant and Antipathogenic Agents Against Pseudomonas aeruginosa

by Carolina María Viola, Mariana Elizabeth Danilovich, Romina Torres-Carro, Manuela M. Moreira, Francisca Rodrigues, Elena Cartagena, María Rosa Alberto, María Amparo Blázquez and Mario Eduardo Arena

Antibiotics 2025, 14(4), 384; https://doi.org/10.3390/antibiotics14040384 - 5 Apr 2025

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Abstract

Background/Objectives: Wine pomace is a rich source of bioactive phenolic compounds with potential health benefits. This study aimed to evaluate the antipathogenic and antioxidant properties of ethanol and ethyl acetate extracts from wine pomace of three grape varietals (Tannat, Bonarda, and Malbec) to [...] Read more.

Background/Objectives: Wine pomace is a rich source of bioactive phenolic compounds with potential health benefits. This study aimed to evaluate the antipathogenic and antioxidant properties of ethanol and ethyl acetate extracts from wine pomace of three grape varietals (Tannat, Bonarda, and Malbec) to explore their potential as natural alternatives for mitigating bacterial virulence in Pseudomonas aeruginosa. Methods: Successive exhaustion extractions were performed using solvents of increasing polarity (ethyl acetate and ethanol). The phenolic content was quantified, and the antioxidant activity was evaluated using standard assays. The antipathogenic activity against P. aeruginosa was assessed by measuring biofilm formation, elastase and protease activity, pyocyanin production, and swarming motility. Quorum sensing (QS) inhibition was tested using a violacein production assay in Chromobacterium violaceum. Results: Ethanol was more effective at extracting phenolic compounds, with Tannat exhibiting the highest total phenolic content (162.5 µg GAE/mg). HPLC-DAD analysis identified 16 phenolic acids, 18 flavonoids, and 3 stilbenes across the extracts. The ethanol extracts showed strong antioxidant activity (phosphomolybdenum reducing capacity 67–128 μg AAE/mg, ABTS^•+ scavenging 37–71 µg/mL, Fe³⁺ reducing power 31–68 µg/mL) and inhibited biofilm formation (up to 61%), elastase (up to 41%), and protease (up to 46%) activities in P. aeruginosa. The extracts also reduced pyocyanin production (up to 78%) and swarming motility (up to 68%), suggesting interference with QS. Moreover, the extracts inhibited violacein production in C. violaceum, confirming QS inhibition (up to 26%). Conclusions: Among the extracts, ethanol-extracted Tannat pomace showed the most substantial antipathogenic and antioxidant activities. The results add value to wine pomace by suggesting its use as natural extracts rich in phenolic compounds, capable of controlling the bacterial virulence of Pseudomonas aeruginosa without promoting the development of resistance. Full article

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Antibiotics, Volume 14, Issue 4 (April 2025) – 86 articles

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