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15 pages, 1264 KB  
Article
First Report of fusF Gene in Staphylococcus kloosii from Virgin Tropical Soil: Expanding the Ecological Reservoirs of Fusidic Acid Resistance
by Muhammad Haziq Ruzaini Abdullah, Mohd Huzairi Mohd Zainudin, Musheer A. Aljaberi, Noor Azira Binti Abdul Mutalib, Hui-min Neoh and Rukman Awang Hamat
Microorganisms 2026, 14(1), 197; https://doi.org/10.3390/microorganisms14010197 - 15 Jan 2026
Viewed by 165
Abstract
Fusidic acid resistance in Staphylococcus spp. has historically been confined to Staphylococcus ureilyticus, with limited data on its environmental distribution. This study presents the first detection of the fusidic acid resistance gene fusF in Staphylococcus kloosii recovered from virgin soil at Kampung [...] Read more.
Fusidic acid resistance in Staphylococcus spp. has historically been confined to Staphylococcus ureilyticus, with limited data on its environmental distribution. This study presents the first detection of the fusidic acid resistance gene fusF in Staphylococcus kloosii recovered from virgin soil at Kampung Batu 16, Dusun Tua, Hulu Langat, Malaysia. A total of ten Staphylococcus isolates were identified using the VITEK®2 system with high confidence (97–99%), comprising seven S. kloosii and three S. ureilyticus. Sequencing of representative isolates further corroborated the species identification. All isolates displayed phenotypic resistance to fusidic acid, while all S. ureilyticus (3/3) exhibited multi-drug resistant (MDR) traits and S. kloosii (7/7) exhibited non-MDR traits. PCR and sequencing confirmed the presence of fusF gene in S. ureilyticus (3/3) and S. kloosii (3/7). In addition, fusB and fusC genes were not detected in both species. The phylogenetic analysis (Maximum Likelihood, Tamura–Nei model) revealed high sequence conservation and clustering between fusF-positive S. kloosii and S. ureilyticus soil isolates, suggesting recent horizontal gene transfer between these two related species. The first detection of fusF gene in S. kloosii from virgin soil signifies the expansion of the ecological and host range beyond S. ureilyticus, establishes virgin soil as a potential antimicrobial resistance (AMR) reservoir, and underscores the One Health risks of resistance dissemination from environmental staphylococci. This baseline study highlights the importance of early AMR surveillance in tropical environments prior to agricultural development. Full article
(This article belongs to the Special Issue Genomics Approaches in Microbial Ecology)
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26 pages, 398 KB  
Review
Nitric Oxide-Releasing Gels in the Context of Antimicrobial Stewardship, Biofilm Management, and Wound-Repair Biology
by Simon J. L. Teskey, Lisa Khoma, Michelle Lorbes and Chris C. Miller
Antibiotics 2026, 15(1), 54; https://doi.org/10.3390/antibiotics15010054 - 4 Jan 2026
Viewed by 257
Abstract
Topical antibiotics have long been used for the prevention and treatment of superficial skin and soft tissue infections; however, increasing evidence indicates that their clinical value is undermined by rising antimicrobial resistance, high rates of allergic sensitization, inadequate activity against biofilms, and a [...] Read more.
Topical antibiotics have long been used for the prevention and treatment of superficial skin and soft tissue infections; however, increasing evidence indicates that their clinical value is undermined by rising antimicrobial resistance, high rates of allergic sensitization, inadequate activity against biofilms, and a lack of wound-healing properties. Agents such as bacitracin, neomycin, polymyxin B, mupirocin, and fusidic acid act through narrow, target-specific mechanisms that facilitate resistance selection and provide limited benefit in chronic or polymicrobial wound environments. Contemporary antimicrobial stewardship frameworks therefore discourage routine use of topical antibiotics and increasingly favor non-antibiotic antiseptics with broad-spectrum activity and low resistance risk, including silver, iodine, polyhexamethylene biguanide, octenidine, and medical-grade honey. These modalities, however, primarily serve to reduce microbial burden and do not directly address the underlying biological impairments that prevent healing. Nitric oxide-releasing gels (NORGs) represent a novel class of topical antimicrobials that combine multi-target bactericidal activity with physiologic pro-healing effects. Nitric oxide exerts potent antimicrobial and antibiofilm effects via oxidative and nitrosative stress, disruption of metabolic pathways, inhibition of DNA replication, and interference with quorum sensing. Simultaneously, nitric oxide enhances angiogenesis, modulates inflammation, improves microvascular perfusion, and promotes fibroblast and keratinocyte function. Preclinical models and early-phase clinical studies demonstrate broad-spectrum efficacy—including activity against multidrug-resistant organisms—with favorable tolerability and minimal risk of resistance development. Although the current evidence base remains preliminary, NORGs offer a promising antimicrobial platform with the potential to reduce reliance on topical antibiotics while simultaneously addressing key barriers to wound healing. Larger randomized controlled trials, direct comparisons with established advanced dressings, and robust pharmacoeconomic evaluations are needed to define their optimal role within stewardship-aligned wound-care practice. Full article
20 pages, 2519 KB  
Article
Antibiotic Resistance Patterns of Bacteria Isolated from Canine Skin and Ear Infections in Serbia
by Isidora Prošić, Branislav Vejnović, Dušan Mišić, Andrea Radalj, Aleksandar Nikšić, Ksenija Aksentijević, Marina Radojičić, Vladimir Gajdov, Milica Ilić, Natalija Milčić Matić and Dejan Krnjaić
Antibiotics 2026, 15(1), 21; https://doi.org/10.3390/antibiotics15010021 - 23 Dec 2025
Viewed by 406
Abstract
Background: Canine skin and ear infections are common in small-animal practice and increasingly complicated by multidrug resistance (MDR), yet data from Serbia are limited. This study aimed to describe the bacterial etiology and antimicrobial resistance patterns in canine otitis externa and pyoderma. [...] Read more.
Background: Canine skin and ear infections are common in small-animal practice and increasingly complicated by multidrug resistance (MDR), yet data from Serbia are limited. This study aimed to describe the bacterial etiology and antimicrobial resistance patterns in canine otitis externa and pyoderma. Methods: We retrospectively reviewed laboratory records from the Clinical Bacteriology and Mycology Laboratory, Faculty of Veterinary Medicine, University of Belgrade (January 2017–August 2024). A total of 422 non-invasive swabs from clinically ill dogs were included (ears: n = 210; skin: n = 212). Bacterial identification used conventional methods and commercial systems, and disk-diffusion susceptibility testing followed CLSI/EUCAST guidance. Methicillin resistance in staphylococci was assessed by cefoxitin/oxacillin screening; MRSA was confirmed by PCR and PBP2a detection. Resistance trends were compared between 2017–2020 and 2021–2024. Results: The leading pathogens were Staphylococcus pseudintermedius (ears 48.1%; skin 79.7%) and Pseudomonas aeruginosa (ears 29.1%; skin 7.6%). Staphylococci showed high resistance to macrolides, clindamycin, tetracycline, and first-line β-lactams (amoxicillin–clavulanate, cephalexin), with the highest susceptibilities to amikacin, florfenicol, and rifampicin. P. aeruginosa remained most susceptible to amikacin, polymyxin B, and imipenem. Between the two periods, S. pseudintermedius resistance increased to amikacin, fusidic acid, and cephalexin, while resistance to florfenicol decreased. P. aeruginosa resistance to imipenem increased. The prevalence of methicillin-resistant S. pseudintermedius (MRSP) was 27.4% (74/270). MDR S. pseudintermedius and MDR P. aeruginosa were identified in 38.5% and 53.3% of isolates, respectively. One isolate of each species was resistant to all tested drugs. Conclusions: These findings confirm high levels of antimicrobial resistance in major canine skin and ear pathogens and emphasize the need for susceptibility-based therapy, rational antimicrobial use, and ongoing surveillance in small-animal practice. Full article
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15 pages, 1226 KB  
Article
Culture-Based Wastewater Surveillance for the Detection and Monitoring of Antimicrobial Resistance in Staphylococcal Species
by Douha Shouqair, Rashed Alghafri, Mohammed Naji, Abdulla Albastaki, Rania Nassar, Lobna Mohamed, Bisola Aloba, Bayan S. Awad, Fatima Al Dhaheri, Dean Everett, Ihab Habib, Mahmood Almashadani, Ahmed A. Shibl, Jorge Rodríguez, Danesh Moradigaravand, Stefan Monecke, Ralf Ehricht, Mushtaq Khan, Richard Goering and Abiola Senok
Vet. Sci. 2026, 13(1), 14; https://doi.org/10.3390/vetsci13010014 - 23 Dec 2025
Viewed by 566
Abstract
Wastewater-based surveillance (WBS) is valuable for monitoring antimicrobial resistance (AMR). Staphylococci are key targets, as wastewater can facilitate gene transfer and resistance emergence. Data on WBS for population-level AMR in the Arabian-Gulf remain limited. This study assessed Staphylococcus diversity and resistance in Dubai [...] Read more.
Wastewater-based surveillance (WBS) is valuable for monitoring antimicrobial resistance (AMR). Staphylococci are key targets, as wastewater can facilitate gene transfer and resistance emergence. Data on WBS for population-level AMR in the Arabian-Gulf remain limited. This study assessed Staphylococcus diversity and resistance in Dubai wastewater. Samples were collected over eight months from nine community sites, two hospital nodes, and two wastewater treatment plants (WWTPs) and were analysed by culture-based method. Ninety-six Staphylococcus isolates were recovered from community, hospital, and WWTP influent, with no growth in effluent. Most isolates (n/N = 88/96) were coagulase-negative Staphylococcus (CoNS), spanning 15 species, dominated by S. saprophyticus, S. cohnii and S. sciuri. The only coagulase-positive Staphylococcus was S. aureus (n = 8) and the only species detected across all wastewater sources. Resistance was highest to benzylpenicillin (88%) and fusidic acid (82%), whereas all isolates remained susceptible to glycopeptides, tigecycline, and linezolid. Fusidic acid resistance was higher in community-wastewater isolates, whereas β-lactam resistance predominated in hospital-wastewater isolates. Sixty percent of CoNS were multidrug-resistant; methicillin resistance occurred in 37.5% of CoNS and 50% of S. aureus. Wastewater is a reservoir of diverse multidrug-resistant staphylococci, underscoring One Health relevance reflecting the potential for circulation between humans, animals, and the shared environment. WBS can support population-level AMR monitoring to inform public health and veterinary interventions. Full article
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10 pages, 223 KB  
Case Report
Salmonellosis Outbreak in a Rottweiler Kennel Associated with Raw Meat-Based Diets
by Betina Boneva-Marutsova, Plamen Marutsov, Marie-Louise Geisler and Georgi Zhelev
Animals 2025, 15(21), 3196; https://doi.org/10.3390/ani15213196 - 3 Nov 2025
Cited by 1 | Viewed by 635
Abstract
This case describes an outbreak of salmonellosis caused by Salmonella enterica subspecies enterica serotype Agona in a Rottweiler breeding kennel, associated with raw meat-based diet (RMBD) of unlicensed origin. The report presents the clinical, epidemiological, and microbiological characteristics of the outbreak, as well [...] Read more.
This case describes an outbreak of salmonellosis caused by Salmonella enterica subspecies enterica serotype Agona in a Rottweiler breeding kennel, associated with raw meat-based diet (RMBD) of unlicensed origin. The report presents the clinical, epidemiological, and microbiological characteristics of the outbreak, as well as the control and preventive measures undertaken. Methods: Samples of faeces, vomit, raw food, and environmental surfaces were collected and examined. The isolated pathogen was identified using bacteriological culture, biochemical testing, MALDI-TOF mass spectrometry, and serotyping according to the White–Kauffmann–Le Minor scheme. Antimicrobial susceptibility was determined by the broth microdilution method in accordance with standards of Clinical and Laboratory Standards Institute (CLSI). Results: Clinical signs included vomiting, diarrhoea, lethargy, and dehydration without fever, with disease exacerbation observed in post-partum animals. Extensive carriage and faecal shedding of S. Agona were detected in affected dogs, along with widespread contamination of food and the kennel environment. The isolate was susceptible to some antimicrobial agents but resistant to cephalexin, aminoglycosides, lincosamides, macrolides, and fusidic acid, and showed intermediate susceptibility to polymyxin B. Following discontinuation of raw meat feeding, targeted antimicrobial therapy, and environmental disinfection, all dogs recovered, and subsequent tests for Salmonella spp., were negative. All human contacts also tested negative. Conclusions: This represents the first documented outbreak of S. Agona infection in dogs in Bulgaria linked to a RMBD. The findings emphasise the importance of feed safety, biosecurity, and traceability of feed sources in kennels, as well as the potential zoonotic risk associated with raw feeding practices. The diagnostic and therapeutic measures implemented in this case provide an effective model for managing similar epidemiological events within the One Health framework. Full article
(This article belongs to the Section Veterinary Clinical Studies)
8 pages, 979 KB  
Case Report
First Report of Multidrug-Resistant Staphylococcus sciuri Isolated from the Urinary Bladder of a Domestic Rabbit in Romania: A Case Study
by Bogdan Florea, Doru Morar, Cristina Văduva, Florin Simiz, Simina Velescu, Corina Kracunovic, Vlad Iorgoni, Paula Nistor, Janos Degi, Ionica Iancu, Viorel Herman, Alexandra Pocinoc and Eugenia Dumitrescu
Antibiotics 2025, 14(11), 1089; https://doi.org/10.3390/antibiotics14111089 - 29 Oct 2025
Viewed by 802
Abstract
Background/ObjectivesStaphylococcus sciuri, traditionally regarded as a commensal organism in animals and the environment, is increasingly recognized as a potential opportunistic pathogen with zoonotic significance. Its genomic reservoir of methicillin resistance homologues further raises concern regarding its role in antimicrobial resistance [...] Read more.
Background/ObjectivesStaphylococcus sciuri, traditionally regarded as a commensal organism in animals and the environment, is increasingly recognized as a potential opportunistic pathogen with zoonotic significance. Its genomic reservoir of methicillin resistance homologues further raises concern regarding its role in antimicrobial resistance dissemination. This study describes the first documented case of S. sciuri isolated from the urinary bladder of a domestic rabbit (Oryctolagus cuniculus) in Romania, emphasizing its clinical relevance and antimicrobial profile. Methods: A seven-year-old intact female rabbit presenting with apathy, dysuria, and hematuria underwent clinical evaluation, ultrasonography, and cystocentesis. The aspirated intravesical content was subjected to bacterial culture, MALDI-TOF MS identification, and antimicrobial susceptibility testing via the VITEK 2 system. Results: Pure colonies of Gram-positive cocci were identified as S. sciuri with high confidence. Antimicrobial susceptibility testing revealed susceptibility to β-lactams, aminoglycosides, glycopeptides, linezolid, rifampicin, fusidic acid, tigecycline, and trimethoprim-sulfamethoxazole, while resistance was observed against fluoroquinolones, macrolides, lincosamides, and tetracycline, indicating a multidrug-resistant phenotype. Treatment with trimethoprim-sulfamethoxazole combined with ultrasound-guided bladder lavage and supportive therapy resulted in complete clinical recovery within 10 days. Conclusions: This case highlights the pathogenic potential of S. sciuri in domestic rabbits and its capacity to exhibit multidrug resistance. The findings underscore the necessity of including rabbits in antimicrobial resistance surveillance programs and reinforce the importance of culture and sensitivity testing in guiding the therapeutic management of exotic companion animals. Full article
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13 pages, 307 KB  
Article
Antimicrobial Resistance Profile of Staphylococcus pseudintermedius Isolated from Dogs with Otitis Externa and Healthy Dogs: Veterinary and Zoonotic Implications
by Ionela Popa, Ionica Iancu, Vlad Iorgoni, Janos Degi, Alexandru Gligor, Kalman Imre, Emil Tîrziu, Timea Bochiș, Călin Pop, Ana-Maria Plotuna, Paula Nistor, Marius Pentea, Viorel Herman and Ileana Nichita
Antibiotics 2025, 14(10), 1027; https://doi.org/10.3390/antibiotics14101027 - 14 Oct 2025
Viewed by 919
Abstract
Background/Objectives: Staphylococcus pseudintermedius (S. pseudintermedius) is an opportunistic pathogen frequently isolated from dogs, involved in a wide range of infections, particularly otitis externa. Increasing antimicrobial resistance (AMR), including methicillin-resistant S. pseudintermedius (MRSP), poses significant challenges for veterinary and potentially human [...] Read more.
Background/Objectives: Staphylococcus pseudintermedius (S. pseudintermedius) is an opportunistic pathogen frequently isolated from dogs, involved in a wide range of infections, particularly otitis externa. Increasing antimicrobial resistance (AMR), including methicillin-resistant S. pseudintermedius (MRSP), poses significant challenges for veterinary and potentially human health. This study aimed to assess the prevalence and antimicrobial resistance profiles of S. pseudintermedius in dogs with otitis externa compared to clinically healthy dogs. Methods: Between 2022 and 2025, samples were collected from 400 dogs with otitis externa and 360 healthy dogs in veterinary clinics from Timișoara. Ear swabs were processed by conventional microbiological techniques and confirmed using MALDI-TOF MS. Antimicrobial susceptibility was tested using the VITEK® 2 Compact system, following CLSI VET01, Fifth Edition (2018) standards. Fourteen antimicrobials from 11 classes were evaluated. Results: S. pseudintermedius was isolated in 40% of dogs with otitis externa and in 21.1% of healthy dogs. The highest resistance in both groups was observed to tetracycline (37.5% and 25%, respectively). No resistance was recorded to linezolid, vancomycin, teicoplanin, tigecycline, or fusidic acid. MRSP strains were identified in 1.2% of dogs with otitis, displaying multidrug resistance (MDR). MDR strains were also detected in 8.7% of diseased and 4% of healthy dogs, indicating the potential for subclinical reservoirs. Conclusions: The findings highlight the notable prevalence and AMR of S. pseudintermedius in both symptomatic and asymptomatic dogs. The detection of MRSP and MDR strains emphasizes the need for prudent antibiotic use and continuous AMR surveillance in veterinary medicine to mitigate zoonotic risks and preserve antimicrobial efficacy. Full article
11 pages, 894 KB  
Article
Multidrug-Resistant Staphylococcus haemolyticus ST42 Carrying ΨSCCmec57395-like SCCmec and Resistant Islands with Type I aj1–LP–fusB Structure Emerges in Taiwan Hospitals
by Cheng-Mao Ho, Lee-Chung Lin, Yu-Hsiang Ou, Kai-Hsiang Lin and Jang-Jih Lu
Antibiotics 2025, 14(10), 1015; https://doi.org/10.3390/antibiotics14101015 - 13 Oct 2025
Viewed by 826
Abstract
Background/Objectives: Staphylococcus haemolyticus is a common commensal bacterium that has emerged as an important nosocomial pathogen. Its multi-antibiotics resistance presents substantial therapeutic challenges in healthcare settings worldwide. Despite its growing clinical relevance, most investigations into antimicrobial resistance determinants have been focused on [...] Read more.
Background/Objectives: Staphylococcus haemolyticus is a common commensal bacterium that has emerged as an important nosocomial pathogen. Its multi-antibiotics resistance presents substantial therapeutic challenges in healthcare settings worldwide. Despite its growing clinical relevance, most investigations into antimicrobial resistance determinants have been focused on Staphylococcus aureus or Staphylococcus epidermidis, leaving S. haemolyticus comparatively understudied. This study aimed to elucidate the genetic basis of multi-drug resistance by characterizing mobile genetic elements associated with predominant S. haemolyticus clones circulating in Taiwan. Methods: From 2010 to 2017, 140 clinical targeted isolates of S. haemolyticus were obtained from individual patients. Two representative strains, SH53 (ST3) and SH51 (ST42), were sequenced using the PacBioTM platform. The structural organization of SCCmec cassettes and phage-associated resistance islands in the remaining 138 isolates was analyzed by polymerase chain reaction (PCR) using specifically designed primers. Results: Of the 140 isolates, 92 (65.7%) were ST42 and 48 (34.3%) were ST3. PCR analysis showed that over two-thirds harbored heavy metal resistance genes. cadD, cadX, arsC, arsB, and arsR occurred in 90.2% of ST42 isolates, with copA in 71.7%. In ST3, these five genes were present in 89.6%, and copA in 64.6%. Fusidic acid (FA) resistance was more frequent in ST42 (46.7%) than ST3 (22.9%) (p = 0.015). Only one ST42 isolate carried fusC. The remaining 52 FA-resistant isolates contained a type I aj1–leader peptide (LP)–fusB structure downstream of smpB, except for a single ST42 isolate with the type IV structure. Conclusions: MDR ST42 S. haemolyticus carrying SCCmec cassettes with heavy metal resistance genes and phage-related islands carrying type I aj1–leader peptide (LP)–fusB structures may represent emerging opportunistic pathogens in Taiwan. Continued longitudinal surveillance is warranted to track the evolution of resistance-associated mobile elements under selective antimicrobial pressure. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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15 pages, 1767 KB  
Article
Antibacterial Activity of Fusidic Acid-Loaded Electrospun Polylactide Fiber Fleeces Against Periodontopathogenic Species
by Bernd W. Sigusch, Markus Reise, Stefan Kranz, Julius Beck, Kerstin Wagner, André Guellmar and Markus Heyder
Pharmaceutics 2025, 17(7), 821; https://doi.org/10.3390/pharmaceutics17070821 - 24 Jun 2025
Viewed by 879
Abstract
Background/Objectives: The effect of fusidic acid on oral bacteria, especially on Gram- negative periodontopathogenic species, has not yet been investigated. This in vitro study aimed to analyze the antibacterial effect of fusidic acid alone and as an active component in electrospun poly(L-lactide-co-D/L-lactide) fiber [...] Read more.
Background/Objectives: The effect of fusidic acid on oral bacteria, especially on Gram- negative periodontopathogenic species, has not yet been investigated. This in vitro study aimed to analyze the antibacterial effect of fusidic acid alone and as an active component in electrospun poly(L-lactide-co-D/L-lactide) fiber fleeces. Methods: Minimal inhibitory concentrations (MIC) of fusidic acid and metronidazole (control) were determined for various oral bacteria. Eluates were collected from electrospun poly(L-lactide-co-D/L-lactide) fiber fleeces loaded with 10 and 20 wt% fusidic acid over a period of 28 d. Antibacterial activity was analyzed by means of a microdilution assay. Cytotoxicity was observed toward human gingival fibroblasts (HGFs). Results: All tested Gram-positive and Gram-negative oral bacteria were susceptible to fusidic acid. The lowest MIC was observed for Porphyromonas gingivalis (MIC < 0.062 µg/mL). Compared to the antibacterial activity of metronidazole, that of Porphyromonas gingivalis was suppressed by significant lower fusidic acid concentrations (p < 0.01). The eluates obtained from electrospun poly(L-lactide-co-D/L-lactide) fiber fleeces inhibited the growth of P. gingivalis, S. aureus, A. viscosus, and A. neslundii over a course of 28 days. The largest inhibition zones were detected for Porphyromonas gingivalis in case of the 20 wt% concentrations. The eluates were not cytotoxic toward HGFs. Conclusions: It was shown that fusidic acid has significant antibacterial potential. The results of the present investigation suggest that fusidic acid alone or delivered by electrospun fiber fleeces might be attractive for controlling oral pathogenic bacteria. Full article
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13 pages, 274 KB  
Article
Microbiological Quality and Safety of Fresh Pork Meat with Special Reference to Methicillin-Resistant S. aureus and Other Staphylococci
by Alba Martinez-Laorden, Celia Arraiz-Fernandez, Gonzalo Ibañez-Torija and Elena Gonzalez-Fandos
Vet. Sci. 2025, 12(6), 568; https://doi.org/10.3390/vetsci12060568 - 10 Jun 2025
Cited by 1 | Viewed by 2546
Abstract
Nowadays, there is a great concern about the prevalence of multidrug-resistant bacteria in meat, especially Staphylococcus aureus resistant to methicillin (MRSA). The aim of this work was to evaluate the microbiological quality of fresh pork meat and the presence and resistance of S. [...] Read more.
Nowadays, there is a great concern about the prevalence of multidrug-resistant bacteria in meat, especially Staphylococcus aureus resistant to methicillin (MRSA). The aim of this work was to evaluate the microbiological quality of fresh pork meat and the presence and resistance of S. aureus and other Staphylococcus spp., Mammaliicoccus spp., and Macrococcus spp. to methicillin and other antibiotics. A total of 39 fresh pork meat samples were analyzed. MRSA was isolated from one sample, being resistant to eight antimicrobial families, including aminoglycosides, β-lactams, lincosamides, macrolides, sulfonamides, tetracycline, and others such as fusidic acid, and mupirocin. Also, other multidrug-resistant strains with resistance to 5 or 6 antimicrobial families were isolated including Staphylococcus succinus, Mammaliicoccus sciuri, and Macrococcus caseolyticus. Additional measures should be taken to control MRSA in pork meat. Full article
22 pages, 2291 KB  
Article
Novel Crown Ether-Functionalized Fusidic Acid Butyl Ester: Synthesis, Biological Evaluation, In Silico ADMET, and Molecular Docking Studies
by Hira Sultan, Nuzhat Arshad and Mehreen Lateef
Molecules 2025, 30(9), 2033; https://doi.org/10.3390/molecules30092033 - 2 May 2025
Viewed by 1261
Abstract
Crown ethers have gained importance in the field of medicine because of their resemblance to natural ionophores like valinomycin. With the goal of developing new pharmacologically important crown ethers, a novel series of crown ethers linked with Fusidic acid butyl ester 10a [...] Read more.
Crown ethers have gained importance in the field of medicine because of their resemblance to natural ionophores like valinomycin. With the goal of developing new pharmacologically important crown ethers, a novel series of crown ethers linked with Fusidic acid butyl ester 10ad were synthesized and characterized by means of their 1H NMR, 13C NMR DEPT-135, FT-IR, and mass spectrometry. In vitro antioxidant and α-glucosidase inhibition activities of all crown ethers along with the precursor Fusidic acid butyl ester were examined and compared to the standard butylated hydroxyanisole and acarbose, respectively. Compounds (FABE-16-crown-4) 10b and (FABE-19-crown-5) 10c showed high antioxidant potential with the IC50 = 22.5 ± 0.2 μM and 32.1 ± 0.3 μM, respectively, when compared to the standard BHA (IC50 = 44.2 ± 0.34 μM). To understand the binding mode of the compounds, molecular docking investigations were performed using human antioxidant protein, peroxiredoxin 5. Molecular docking studies revealed higher docking scores (−6.5 and −6.7 kcal/mol) for the highly active compounds 10c and 10b, respectively, than standard BHA (−5.3 kcal/mol). Synthesized crown ethers exhibited moderate α-glucosidase inhibition with (IC50 = 23.5 ± 0.2 to 76.5 ± 0.1 μM) when compared to acarbose as standard (IC50 = 5.2 ± 0.8 μM). The in silico ADMET predictions indicated that the prepared compounds obeyed (bRO5) and Veber’s rule for the acceptance as orally administered drugs and indicated that all the prepared crown ethers exhibited calculated values of drug likeness parameters in acceptable ranges that showed good potential of these molecules for further drug development investigations. Full article
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24 pages, 16546 KB  
Article
Multi-Modal Design, Synthesis, and Biological Evaluation of Novel Fusidic Acid Derivatives
by Luqi Wang, Zhiyuan Geng, Yuhang Liu, Linhui Cao, Yao Liu, Hourui Zhang, Yi Bi and Jing Lu
Molecules 2025, 30(9), 1983; https://doi.org/10.3390/molecules30091983 - 29 Apr 2025
Viewed by 1064
Abstract
Fusidic acid (FA), a tetracyclic triterpenoid, has been approved to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. However, there are few reports about FA derivatives with high efficacy superior to FA, manifesting the difficulty of discovering the derivatives based on experience-based drug design. In [...] Read more.
Fusidic acid (FA), a tetracyclic triterpenoid, has been approved to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. However, there are few reports about FA derivatives with high efficacy superior to FA, manifesting the difficulty of discovering the derivatives based on experience-based drug design. In this study, we employed a stepwise method to discover novel FA derivatives. First, molecular dynamics (MD) simulations were performed to identify the molecular mechanism of FA against elongation factor G (EF-G) and drug resistance. Then, we utilized a scaffold decorator to design novel FA derivatives at the 3- and 21-positions of FA. The ligand-based and structure-based screening models, including Chemprop and RTMScore, were employed to identify promising hits from the generated set. Ten generated FA derivatives with high efficacy in the Chemprop and RTMScore models were synthesized for in vitro testing. Compounds 4 and 10 demonstrated a 2-fold increase in potency against MRSA strains compared to FA. This study highlights the significant impact of AI-based methods on the design of novel FA derivatives with drug efficacy, which provides a new approach for drug discovery. Full article
(This article belongs to the Special Issue Advances in Antibacterial Molecules)
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25 pages, 2478 KB  
Article
Off-Label Use of Antibiotics in Small Animal Medicine—A Germany-Wide Anonymous Online Survey
by Marie Tarillion, Robert Hertzsch and Angelika Richter
Antibiotics 2025, 14(4), 419; https://doi.org/10.3390/antibiotics14040419 - 21 Apr 2025
Cited by 1 | Viewed by 1442
Abstract
Background/Objectives: Since 28 January 2022, veterinary medicinal products (VMPs) must be used in accordance with the conditions of the marketing authorisation (Regulation (EU) 2019/6, Article 106). This entails further restrictions on therapeutic freedom, for example, with regard to dose deviations. Off-label use is [...] Read more.
Background/Objectives: Since 28 January 2022, veterinary medicinal products (VMPs) must be used in accordance with the conditions of the marketing authorisation (Regulation (EU) 2019/6, Article 106). This entails further restrictions on therapeutic freedom, for example, with regard to dose deviations. Off-label use is any use of a product that deviates from the Summary of Product Characteristics (SPCs). To date, there are no data available on the type and extent of off-label use on the basis of which the feasibility of the new regulation in Germany can be assessed. Methods: Therefore, a Germany-wide anonymous online survey was conducted as a quantitative cross-sectional study comprising 196 questions according to off-label use in dogs and cats. Results: In quantitative terms, the survey was representative of 358 participants but limited due to the demographic characteristics of the participants. A total of 91.3% (326/357) veterinarians stated that they had used antibiotics off-label. Fusidic acid, chloramphenicol, tylosin, and florfenicol were most frequently reclassified with regard to animal species. Authorised drugs for cats and dogs such as amoxicillin/clavulanic acid, doxycycline, metronidazole, and fluoroquinolones, like enrofloxacin and marbofloxacin, were also used off-label, often with regard to indication and treatment duration. Conclusions: Although there are comparatively many antibacterial preparations available for cats and dogs, off-label use is common practice. In many cases, special circumstances of the individual case justify the off-label use of authorised preparations for cats and dogs. The survey results indicate that some dose revisions are recommended. Guidance for specific indications in cats and dogs could contribute to greater legal certainty in small animal practice with regard to the justification of off-label use. Full article
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15 pages, 278 KB  
Article
Clinical Features and Antibiotic Susceptibility of Staphylococcus aureus-Infected Dermatoses
by Dimitra Koumaki, Sofia Maraki, Georgios Evangelou, Vasiliki Koumaki, Stamatios Gregoriou, Stamatoula Kouloumvakou, Danae Petrou, Evangelia Rovithi, Kyriaki Zografaki, Aikaterini Doxastaki, Petros Ioannou, Ioanna Gkiaouraki, Antonios Rogdakis, Viktoria Eirini Mavromanolaki and Konstantinos Krasagakis
J. Clin. Med. 2025, 14(4), 1084; https://doi.org/10.3390/jcm14041084 - 8 Feb 2025
Cited by 2 | Viewed by 3091
Abstract
Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) poses significant treatment challenges, particularly in community settings. Limited data are available on S. aureus-associated infected dermatoses (ID) in outpatient dermatology clinics. This study examines the clinical characteristics, microbiological profiles, resistance patterns, and treatment outcomes of dermatoses [...] Read more.
Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) poses significant treatment challenges, particularly in community settings. Limited data are available on S. aureus-associated infected dermatoses (ID) in outpatient dermatology clinics. This study examines the clinical characteristics, microbiological profiles, resistance patterns, and treatment outcomes of dermatoses caused by S. aureus. Methods: Between January 2023 and January 2025, consecutive patients with confirmed S. aureus-associated SD were recruited in a dermatology clinic in Heraklion, Greece. Demographic, clinical, and treatment data were collected. Skin swabs underwent bacterial culture and antimicrobial susceptibility testing following CLSI guidelines. Statistical analyses evaluated associations between clinical and microbiological findings. Results: Sixty-eight patients were included, 54.4% of whom were male, with a mean age of 46.7 years (± SD 25.1). MRSA was identified in 22.1% of cases and was significantly associated with female gender (p = 0.014). The most common diagnoses were eczema (35.3%) and folliculitis (19.1%). Oxacillin-resistant patients were more likely to receive systemic therapy (p = 0.039). Resistance rates were highest for benzylpenicillin (81.8%), levofloxacin (54.9%), and erythromycin (39.4%). Resistance rates for fusidic acid, clindamycin, mupirocin, and tetracycline were 38.2%, 20.6%, 16.9%, and 10.3%, respectively. Other pathogens, including Pseudomonas aeruginosa and Escherichia coli, were isolated in 27.9% of cases. Conclusions: This study highlights the high prevalence of MRSA in outpatient dermatology settings, emphasizing the need for local antimicrobial resistance surveillance to guide treatment strategies and improve outcomes in superinfected dermatoses. Full article
(This article belongs to the Section Dermatology)
18 pages, 4028 KB  
Article
Exploration of the Fusidic Acid Structure Activity Space for Antibiotic Activity
by Yoon-Suk Kang, Simone C. Silva, Kenneth Smith, Krissty Sumida, Yuhan Wang, Lucius Chiaraviglio, Ramachandra Reddy Donthiri, Alhanouf Z. Aljahdali, James E. Kirby and George A. O’Doherty
Molecules 2025, 30(3), 465; https://doi.org/10.3390/molecules30030465 - 21 Jan 2025
Viewed by 2692
Abstract
Fusidic acid is a translation inhibitor with activity against major Gram-positive bacterial pathogens such as S. aureus. However, its activity against Gram-negatives is poor based on an inability to access its cytoplasmic target in these organisms. Opportunities for functionalization of the fusidic [...] Read more.
Fusidic acid is a translation inhibitor with activity against major Gram-positive bacterial pathogens such as S. aureus. However, its activity against Gram-negatives is poor based on an inability to access its cytoplasmic target in these organisms. Opportunities for functionalization of the fusidic acid scaffold to enhance activity against Gram-negative pathogens have not been explored. Using an activity-guided synthetic strategy, the tolerance of the tetracyclic natural product to derivatization at the A- and C-rings and its carboxylic acid side chain was explored with the goal of enhancing its activity spectrum and pharmacological properties. All side-chain carboxylic acid esters were inactive. Oxidation of the C-ring alcohol and oxime were not tolerated either. A number of esters of the A-ring alcohol retained modest activity against Gram-positive bacteria and were informative for future activity-guided studies. For the A-ring esters, differences in antibacterial activity relative to inhibitory activity in a ribosome in vitro translation assay suggested the possibility of a pro-druglike effect for the fusidic acid pyrazine-2-carboxylate. This study furthers the understanding of the activity of the fusidic acid scaffold against Gram-positive bacteria. These results suggest promise for future modification of the A-ring alcohol of fusidic acid in the advancement of its antibiotic properties. Full article
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