Journal Description
Antibiotics
Antibiotics
is an international, peer-reviewed, open access journal on all aspects of antibiotics, published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology & Pharmacy) / CiteScore - Q1 (General Pharmacology, Toxicology and Pharmaceutics)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 13.7 days after submission; acceptance to publication is undertaken in 2.5 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.8 (2022);
5-Year Impact Factor:
4.9 (2022)
Latest Articles
Phylogeny of Transferable Oxazolidinone Resistance Genes and Homologs
Antibiotics 2024, 13(4), 311; https://doi.org/10.3390/antibiotics13040311 (registering DOI) - 28 Mar 2024
Abstract
Oxazolidinone resistance, especially transmissible resistance, is a major public health concern, and the origin of this resistance mechanism is not yet resolved. This study aims to delve into the phylogenetic origin of the transmissible oxazolidinone resistance mechanisms conferring cross-resistance to other drugs of
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Oxazolidinone resistance, especially transmissible resistance, is a major public health concern, and the origin of this resistance mechanism is not yet resolved. This study aims to delve into the phylogenetic origin of the transmissible oxazolidinone resistance mechanisms conferring cross-resistance to other drugs of human and veterinary importance. The amino acid sequences of the five cfr ribosomal methylases and optrA and poxtA were used as queries in searches against 219,549 bacterial proteomes in the NCBI RefSeq database. Hits with > 40% amino acid identity and > 80% query coverage were aligned, and phylogenetic trees were reconstructed. All five cfr genes yielded highly similar trees, with rlmN housekeeping ribosomal methylases located basal to the sister groups of S-adenosyl-methionine-dependent methyltransferases from various Deltaproteobacteria and Actinomycetia, including antibiotic-producing Streptomyces species, and the monophyletic group of cfr genes. The basal branches of the latter contained paenibacilli and other soil bacteria; they then could be split into the clades [cfr(C):cfr(E)] and [[cfr:cfr(B)]:cfr(D)], always with different Bacillaceae in their stems. Lachnospiraceae were encountered in the basal branches of both optrA and poxtA trees. The ultimate origin of the cfr genes is the rlmN housekeeping ribosomal methylases, which evolved into a suicide-avoiding methylase in antibiotic producers; a soil organism (Lachnospiraceae, Paenibacilli) probably acted as a transfer organism into pathogenic bacteria. In the case of optrA, the porcine pathogenic Streptococcus suis was present in all branches, while the proteins closest to poxtA originated from Clostridia.
Full article
(This article belongs to the Special Issue The Evolution of Plasmid-Mediated Antimicrobial Resistance)
Open AccessArticle
Artemisinin May Disrupt Hyphae Formation by Suppressing Biofilm-Related Genes of Candida albicans: In Vitro and In Silico Approaches
by
Esra Sumlu, Merve Aydin, Emine Nedime Korucu, Saliha Alyar and Ahmed Moustapha Nsangou
Antibiotics 2024, 13(4), 310; https://doi.org/10.3390/antibiotics13040310 (registering DOI) - 28 Mar 2024
Abstract
This study aimed to assess the antifungal and antibiofilm efficacy of artemisinin against Candida (C.) species, analyze its impact on gene expression levels within C. albicans biofilms, and investigate the molecular interactions through molecular docking. The antifungal efficacy of artemisinin on a variety
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This study aimed to assess the antifungal and antibiofilm efficacy of artemisinin against Candida (C.) species, analyze its impact on gene expression levels within C. albicans biofilms, and investigate the molecular interactions through molecular docking. The antifungal efficacy of artemisinin on a variety of Candida species, including fluconazole-resistant and -susceptible species, was evaluated by the microdilution method. The effect of artemisinin on C. albicans biofilm formation was investigated by MTT and FESEM. The mRNA expression of the genes related to biofilm was analyzed by qRT-PCR. In addition, molecular docking analysis was used to understand the interaction between artemisinin and C. albicans at the molecular level with RAS1-cAMP-EFG1 and EFG1-regulated genes. Artemisinin showed higher sensitivity against non-albicans Candida strains. Furthermore, artemisinin was strongly inhibitory against C. albicans biofilms at 640 µg/mL. Artemisinin downregulated adhesion-related genes ALS3, HWP1, and ECE1, hyphal development genes UME6 and HGC1, and hyphal CAMP-dependent protein kinase regulators CYR1, RAS1, and EFG1. Furthermore, molecular docking analysis revealed that artemisinin and EFG1 had the highest affinity, followed by UME6. FESEM analysis showed that the fluconazole- and artemisinin-treated groups exhibited a reduced hyphal network, unusual surface bulges, and the formation of pores on the cell surfaces. Our study suggests that artemisinin may have antifungal potential and showed a remarkable antibiofilm activity by significantly suppressing adhesion and hyphal development through interaction with key proteins involved in biofilm formation, such as EFG1.
Full article
(This article belongs to the Special Issue Antimicrobial and Anti-infective Activity of Natural Products, 2nd Volume)
Open AccessCommunication
Impact of Interfering Substances on the Bactericidal Efficacy of Different Commercially Available Hypochlorous Acid-Based Wound Irrigation Solutions Commonly Found in South-East Asia
by
Jiann Wen Yap, Neni Iffanida Ismail, Cheng Shoou Lee and Ding Yuan Oh
Antibiotics 2024, 13(4), 309; https://doi.org/10.3390/antibiotics13040309 (registering DOI) - 28 Mar 2024
Abstract
The high prevalence of chronic wounds is a growing concern. Recently, hypochlorous acid (HOCl)-based solutions were introduced as an alternative antimicrobial for wound cleansing. In this study, we assessed the in vitro bactericidal activities of seven commercially available wound irrigation products commonly found
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The high prevalence of chronic wounds is a growing concern. Recently, hypochlorous acid (HOCl)-based solutions were introduced as an alternative antimicrobial for wound cleansing. In this study, we assessed the in vitro bactericidal activities of seven commercially available wound irrigation products commonly found in South-East Asia. The evaluation was conducted using quantitative suspension method, EN 13727 in either low or high protein conditions. Under low protein conditions, four out of the five HOCl products achieved bactericidal activity (≥5 log10 reduction factor; RF) within 2–5 min, and only one product achieved 5 log10 RF at 15 s. None of the HOCl achieved 5 log10 RF under high protein, even after 30 min of exposure time. In contrast, protein interference on the antimicrobial activities of polyhexamethylene biguanide-based product is less pronounced (low protein: 60 s vs. high protein: 2 min to attain ≥5 log10 RF). Octenidine dihydrochloride is the only active not affected by protein interference achieving ≥5 log10 RF within 15 s in both low and high protein conditions. These findings warrant the need to screen antimicrobial wound care products, especially HOCl-based products, in high protein condition to better reflect the antimicrobial activities in wound care.
Full article
(This article belongs to the Special Issue Membranes to Fight Drug-Resistant Microbes)
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Open AccessBrief Report
NRX-101 (D-Cycloserine + Lurasidone) Is Active against Drug-Resistant Urinary Pathogens In Vitro
by
Michael T. Sapko, Michael Manyak, Riccardo Panicucci and Jonathan C. Javitt
Antibiotics 2024, 13(4), 308; https://doi.org/10.3390/antibiotics13040308 (registering DOI) - 28 Mar 2024
Abstract
D-Cycloserine (DCS) is a broad-spectrum antibiotic that is currently FDA-approved to treat tuberculosis (TB) disease and urinary tract infection (UTI). Despite numerous reports showing good clinical efficacy, DCS fell out of favor as a UTI treatment because of its propensity to cause side
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D-Cycloserine (DCS) is a broad-spectrum antibiotic that is currently FDA-approved to treat tuberculosis (TB) disease and urinary tract infection (UTI). Despite numerous reports showing good clinical efficacy, DCS fell out of favor as a UTI treatment because of its propensity to cause side effects. NRX-101, a fixed-dose combination of DCS and lurasidone, has been awarded Qualified Infectious Disease Product and Fast Track Designation by the FDA. In this study, we tested NRX-101 against the urinary tract pathogens Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii in cation-adjusted Mueller–Hinton broth (caMHB) and artificial urine media (AUM). Several strains were multidrug resistant. Test compounds were serially diluted in broth/media. Minimum inhibitory concentration (MIC) was defined as the lowest concentration of the test compound at which no bacterial growth was observed. DCS exhibited antibacterial efficacy against all strains tested while lurasidone did not appreciably affect the antibacterial action of DCS in vitro. In AUM, the MICs ranged from 128 to 512 mcg/mL for both DCS and NRX-101. In caMHB, MICs ranged from 8 to 1024 mcg/mL for NRX-101 and 32 to 512 mcg/mL for DCS alone. Our data confirm that DCS has antibacterial activity against reference and drug-resistant urinary pathogens. Furthermore, lurasidone does not interfere with DCS’s antimicrobial action in vitro. These results support the clinical development of NRX-101 as a treatment for complicated urinary tract infections.
Full article
(This article belongs to the Special Issue ‘Non-traditional’ Antimicrobial Approaches to Combat Antimicrobial Resistance)
Open AccessSystematic Review
Brave New World of Artificial Intelligence: Its Use in Antimicrobial Stewardship—A Systematic Review
by
Rafaela Pinto-de-Sá, Bernardo Sousa-Pinto and Sofia Costa-de-Oliveira
Antibiotics 2024, 13(4), 307; https://doi.org/10.3390/antibiotics13040307 (registering DOI) - 28 Mar 2024
Abstract
Antimicrobial resistance (AMR) is a growing public health problem in the One Health dimension. Artificial intelligence (AI) is emerging in healthcare, since it is helpful to deal with large amounts of data and as a prediction tool. This systematic review explores the use
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Antimicrobial resistance (AMR) is a growing public health problem in the One Health dimension. Artificial intelligence (AI) is emerging in healthcare, since it is helpful to deal with large amounts of data and as a prediction tool. This systematic review explores the use of AI in antimicrobial stewardship programs (ASPs) and summarizes the predictive performance of machine learning (ML) algorithms, compared with clinical decisions, in inpatients and outpatients who need antimicrobial prescriptions. This review includes eighteen observational studies from PubMed, Scopus, and Web of Science. The exclusion criteria comprised studies conducted only in vitro, not addressing infectious diseases, or not referencing the use of AI models as predictors. Data such as study type, year of publication, number of patients, study objective, ML algorithms used, features, and predictors were extracted from the included publications. All studies concluded that ML algorithms were useful to assist antimicrobial stewardship teams in multiple tasks such as identifying inappropriate prescribing practices, choosing the appropriate antibiotic therapy, or predicting AMR. The most extracted performance metric was AUC, which ranged from 0.64 to 0.992. Despite the risks and ethical concerns that AI raises, it can play a positive and promising role in ASP.
Full article
(This article belongs to the Special Issue Antimicrobial Stewardship in the Digital Age: The Role of Artificial Intelligence and Chatbots in Future Strategies)
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Open AccessArticle
What Is the Rate of Antimicrobial Resistance of a Prosthetic Joint Infection in a Major Orthopaedic Centre?
by
Belgin Coskun, Müge Ayhan, Merve Bozer, Halil Ibrahim Ozaslan, Metin Dogan, Mustafa Citak and Mustafa Akkaya
Antibiotics 2024, 13(4), 306; https://doi.org/10.3390/antibiotics13040306 (registering DOI) - 28 Mar 2024
Abstract
Periprosthetic joint infections (PJIs) are important factors in decreasing the success of hip and knee arthroplasties. It is a necessity to explore the epidemiological data and develop applications for rational antibiotic use, to address future infection control concerns. We aimed to investigate the
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Periprosthetic joint infections (PJIs) are important factors in decreasing the success of hip and knee arthroplasties. It is a necessity to explore the epidemiological data and develop applications for rational antibiotic use, to address future infection control concerns. We aimed to investigate the microorganisms that were responsible and the related antibiograms in 121 patients with PJI, who were managed by two-stage revision surgery. Patients’ data records, demographics, comorbidities, sites of arthroplasty, synovial fluid and deep tissue culture results and antibiotic treatment were summarized on a standardized case report form. There were 43 (35.5%) culture-negative PJI cases and 12 (9.9%) polymicrobial growths. The causative pathogens included Gram-positive (50.4%) and Gram-negative microorganisms (23.1%) and fungi (0.8%). Methicillin resistance was 64.3% for S. aureus and 89.5% for coagulase-negative staphylococcus (CoNS). The extended spectrum beta lactamase (ESBL) rate for Enterobacteriaceae was 68.4%. This study shows that antibiotic resistance is encountered in more than half of the cases, which is valid for all microorganisms most common in PJI. The success of treatment decreases significantly in cases where antibiotic-resistant microorganisms are isolated or in cases where the culture is negative.
Full article
(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)
Open AccessReview
From Polymeric Nanoformulations to Polyphenols—Strategies for Enhancing the Efficacy and Drug Delivery of Gentamicin
by
Ance Bārzdiņa, Aiva Plotniece, Arkadij Sobolev, Karlis Pajuste, Dace Bandere and Agnese Brangule
Antibiotics 2024, 13(4), 305; https://doi.org/10.3390/antibiotics13040305 (registering DOI) - 28 Mar 2024
Abstract
Gentamicin is an essential broad-spectrum aminoglycoside antibiotic that is used in over 40 clinical conditions and has shown activity against a wide range of nosocomial, biofilm-forming, multi-drug resistant bacteria. Nevertheless, the low cellular penetration and serious side effects of gentamicin, as well as
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Gentamicin is an essential broad-spectrum aminoglycoside antibiotic that is used in over 40 clinical conditions and has shown activity against a wide range of nosocomial, biofilm-forming, multi-drug resistant bacteria. Nevertheless, the low cellular penetration and serious side effects of gentamicin, as well as the fear of the development of antibacterial resistance, has led to a search for ways to circumvent these obstacles. This review provides an overview of the chemical and pharmacological properties of gentamicin and offers six different strategies (the isolation of specific types of gentamicin, encapsulation in polymeric nanoparticles, hydrophobization of the gentamicin molecule, and combinations of gentamicin with other antibiotics, polyphenols, and natural products) that aim to enhance the drug delivery and antibacterial activity of gentamicin. In addition, factors influencing the synthesis of gentamicin-loaded polymeric (poly (lactic-co-glycolic acid) (PLGA) and chitosan) nanoparticles and the methods used in drug release studies are discussed. Potential research directions and future perspectives for gentamicin-loaded drug delivery systems are given.
Full article
(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)
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Open AccessArticle
Antimicrobial Activity of Bacillus amyloliquefaciens BS4 against Gram-Negative Pathogenic Bacteria
by
Ana Paula Palacios-Rodriguez, Abraham Espinoza-Culupú, Yerson Durán and Tito Sánchez-Rojas
Antibiotics 2024, 13(4), 304; https://doi.org/10.3390/antibiotics13040304 (registering DOI) - 28 Mar 2024
Abstract
Worldwide, bacterial resistance is one of the most severe public health problems. Currently, the failure of antibiotics to counteract superbugs highlights the need to search for new molecules with antimicrobial potential to combat them. The objective of this research was to evaluate the
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Worldwide, bacterial resistance is one of the most severe public health problems. Currently, the failure of antibiotics to counteract superbugs highlights the need to search for new molecules with antimicrobial potential to combat them. The objective of this research was to evaluate the antimicrobial activity of Bacillus amyloliquefaciens BS4 against Gram-negative bacteria. Thirty yeasts and thirty-two Bacillus isolates were tested following the agar well-diffusion method. Four Bacillus sp. strains (BS3, BS4, BS17, and BS21) showed antagonistic activity against E. coli ATCC 25922 using bacterial culture (BC) and the cell-free supernatant (CFS), where the BS4 strain stood out, showing inhibitory values of 20.50 ± 0.70 mm and 19.67 ± 0.58 mm for BC and CFS, respectively. The Bacillus sp. BS4 strain can produce antioxidant, non-hemolytic, and antimicrobial metabolites that exhibit activity against several microorganisms such as Salmonella enterica, Klebsiella pneumoniae, Shigella flexneri, Enterobacter aerogenes, Proteus vulgaris, Yersinia enterocolitica, Serratia marcescens, Aeromonas sp., Pseudomonas aeruginosa, Candida albicans, and Candida tropicalis. According to the characterization of the supernatant, the metabolites could be proteinaceous. The production of these metabolites is influenced by carbon and nitrogen sources. The most suitable medium to produce antimicrobial metabolites was TSB broth. The one-factor-at-a-time method was used to standardize parameters such as pH, agitation, temperature, carbon source, nitrogen source, and salts, resulting in the best conditions of pH 7, 150 rpm, 28 °C, starch (2.5 g/L), tryptone (20 g/L), and magnesium sulfate (0.2 g/L), respectively. Moreover, the co-culture was an excellent strategy to improve antimicrobial activity, achieving maximum antimicrobial activity with an inhibition zone of 21.85 ± 1.03 mm. These findings position the Bacillus amyloliquefaciens BS4 strain as a promising candidate for producing bioactive molecules with potential applications in human health.
Full article
(This article belongs to the Special Issue Antimicrobial and Anti-infective Activity of Natural Products, 2nd Volume)
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Open AccessArticle
2015 versus 2021: Self-Reported Preparedness to Prescribe Antibiotics Prudently among Final Year Medical Students in Sweden
by
Jasmine Al-Nasir, Andrej Belančić, Dora Palčevski, Oliver J. Dyar and on behalf of Student-PREPARE Sweden Working Group
Antibiotics 2024, 13(4), 303; https://doi.org/10.3390/antibiotics13040303 - 27 Mar 2024
Abstract
Cross-sectional surveys have found variations in how prepared medical students feel to prescribe antibiotics responsibly, but insights are lacking on the stability of these outcomes. In a 2015 survey, final-year Swedish medical students reported very high preparedness levels across a comprehensive range of
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Cross-sectional surveys have found variations in how prepared medical students feel to prescribe antibiotics responsibly, but insights are lacking on the stability of these outcomes. In a 2015 survey, final-year Swedish medical students reported very high preparedness levels across a comprehensive range of relevant curriculum topics. We repeated this survey in 2021 to assess the stability of previous findings and to capture the potential impacts of the COVID-19 pandemic. Final-year students in 2015 and 2021 at all seven Swedish medical schools were eligible to participate in an online survey covering curricula topics, teaching methods and COVID-19 impacts (2021). Eligible students received email invitations and reminders from local coordinators. Students from six of seven medical schools participated in both surveys, with response rates of 24.1% (309/1281) in 2021 and 21.3% (239/1124) in 2015. The average global preparedness was 77.0% and 83.2%, respectively (p < 0.001), with lower preparedness levels in 24/27 curriculum topics in 2021. Students at certain universities reported COVID-19 impacts on antibiotic prescribing education (format, duration and perceived quality). Self-reported preparedness levels have fallen slightly but remain high compared with 2015 levels in other European countries. Students consistently reported lower preparedness in specific topics; improvement efforts should consider focusing on these areas, particularly in the context of the ongoing implementation of programmes leading to a full licence upon graduation.
Full article
(This article belongs to the Special Issue Antimicrobial Stewardship and Prescribing Practice)
Open AccessArticle
Characterizing Antibiotic Regimen Modification Behavior, Patient Characteristics, and Outcomes for Patients with Gram-Negative Bacterial Infections, A Retrospective Single-Center Study
by
Jason Yamaki, Mirna Mikhail, Richard Beuttler, Philip Robinson, Emre Yücel and Alexandre H. Watanabe
Antibiotics 2024, 13(4), 302; https://doi.org/10.3390/antibiotics13040302 - 27 Mar 2024
Abstract
Few studies describe the frequency of antibiotic regimen modification behaviors in the acute care setting. We sought to ascertain patient and treatment characteristics, details of regimen modification, and clinical outcomes with antibiotic modifications. This retrospective study included patients admitted to Hoag Memorial Hospital
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Few studies describe the frequency of antibiotic regimen modification behaviors in the acute care setting. We sought to ascertain patient and treatment characteristics, details of regimen modification, and clinical outcomes with antibiotic modifications. This retrospective study included patients admitted to Hoag Memorial Hospital from 1 January 2019–31 March 2021 with a complicated infection caused by a Gram-negative organism resistant to extended-spectrum cephalosporins or with the potential for resistance (AmpC producers). A total of 400 patients were included. The predominant sources were bloodstream (33%), urine (26%), and respiratory (24%), including patients with multiple sources. The most isolated organisms were Pseudomonas spp. and ESBL-producing organisms, 38% and 34%, respectively. A total of 72% of patients had antibiotic regimen modifications to their inpatient antibiotic regimens. In patients where modifications occurred, the number ranged from one to six modifications. The most common reasons for modifications included a lack of patient response (14%), additional history reviewed (9%), and decompensation (7%). No difference in clinical outcomes was observed based on antibiotic modifications. The numerous changes in therapy observed may reflect the limitations in identifying patients with resistant organisms early on in admission. This highlights the need for more novel antibiotics and the importance of identifying patients at risk for resistant organisms.
Full article
(This article belongs to the Special Issue Antimicrobial Resistance and Hospital- and Community-Associated Infections)
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Open AccessArticle
Attitudes, Beliefs, and Behaviors of Topical Antibiotic Prescribing among Primary Care Providers in Saudi Arabia: A Cross-Sectional Study
by
Baneen A. AlBeladi, Sara A. Alhubail, Riam A. Alsaqer, Ali N. Al-Nasser, Amira S. Radwan and Haytham A. Wali
Antibiotics 2024, 13(4), 301; https://doi.org/10.3390/antibiotics13040301 - 27 Mar 2024
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Background: The World Health Organization (WHO) estimates that 20–50% of antibiotics are misused in society. In addition to the development of antimicrobial resistance, topical antibiotics have been associated with adverse effects such as allergic contact dermatitis (ACD) and inadequate wound healing. This study
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Background: The World Health Organization (WHO) estimates that 20–50% of antibiotics are misused in society. In addition to the development of antimicrobial resistance, topical antibiotics have been associated with adverse effects such as allergic contact dermatitis (ACD) and inadequate wound healing. This study investigated the appropriateness of topical antibiotic prescriptions among primary care providers in Saudi Arabia. Methods: A cross-sectional survey was conducted among Saudi Arabian primary care providers (physicians (general, family, and internal medicine)) employed in governmental and non-governmental healthcare facilities (primary care centers and outpatient clinics). Results: In total, 222 participants were included in the analysis. A total of 73% agreed that inappropriate topical antibiotic use puts patients at risk, and 43% reported antibiotic resistance in daily practice. Many respondents lacked knowledge of the proper indications for topical antibiotics, and 66.2% attributed this to a lack of updated knowledge, while 45% blamed inadequate supervision. Conclusion: Antibiotic prescription patterns deviated from the standards recommended by WHO. This calls for continuous review at all levels of healthcare, providing more physician education and ensuring that antibiotic therapy guidelines are easily accessible and effectively used to avoid the negative consequences of inappropriate antibiotic prescription.
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Open AccessArticle
Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities
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Attilio Di Maio, Hamza Olleik, Elise Courvoisier-Dezord, Sophie Guillier, Fabienne Neulat-Ripoll, Romain Haudecoeur, Jean-Michel Bolla, Magali Casanova, Jean-François Cavalier, Stéphane Canaan, Valérie Pique, Yolande Charmasson, Elias Baydoun, Akram Hijazi, Josette Perrier, Marc Maresca and Maxime Robin
Antibiotics 2024, 13(4), 300; https://doi.org/10.3390/antibiotics13040300 - 26 Mar 2024
Abstract
The development of new and effective antimicrobial compounds is urgent due to the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules, but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new
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The development of new and effective antimicrobial compounds is urgent due to the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules, but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new aurone derivatives bearing acetamido and amino groups at the position 5 of the A ring and managing various monosubstitutions at the B ring. A series of 31 new aurone derivatives were first evaluated for their antimicrobial activity with five derivatives being the most active (compounds 10, 12, 15, 16, and 20). The evaluation of their cytotoxicity on human cells and of their therapeutic index (TI) showed that compounds 10 and 20 had the highest TI. Finally, screening against a large panel of pathogens confirmed that compounds 10 and 20 possess large spectrum antimicrobial activity, including on bioweapon BSL3 strains, with MIC values as low as 0.78 µM. These results demonstrate that 5-acetamidoaurones are far more active and safer compared with 5-aminoaurones, and that benzyloxy and isopropyl substitutions at the B ring are the most promising strategy in the exploration of new antimicrobial aurones.
Full article
(This article belongs to the Special Issue Rise of Antibiotic Resistance: Mechanisms Involved and Solutions to Tackle It)
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Open AccessArticle
Peptidome Profiling of Bubalus bubalis Urine and Assessment of Its Antimicrobial Activity against Mastitis-Causing Pathogens
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Rohit Kumar, Nikunj Tyagi, Anju Nagpal, Jai Kumar Kaushik, Ashok Kumar Mohanty and Sudarshan Kumar
Antibiotics 2024, 13(4), 299; https://doi.org/10.3390/antibiotics13040299 - 26 Mar 2024
Abstract
Urinary proteins have been studied quite exhaustively in the past, however, the small sized peptides have remained neglected for a long time in dairy cattle. These peptides are the products of systemic protein turnover, which are excreted out of the body and hence
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Urinary proteins have been studied quite exhaustively in the past, however, the small sized peptides have remained neglected for a long time in dairy cattle. These peptides are the products of systemic protein turnover, which are excreted out of the body and hence can serve as an important biomarker for various pathophysiologies. These peptides in other species of bovine have been reported to possess several bioactive properties. To investigate the urinary peptides in buffalo and simultaneously their bioactivities, we generated a peptidome profile from the urine of Murrah Buffaloes (n = 10). Urine samples were processed using <10 kDa MWCO filter and filtrate obtained was used for peptide extraction using Solid Phase Extraction (SPE). The nLC-MS/MS of the aqueous phase from ten animals resulted in the identification of 8165 peptides originating from 6041 parent proteins. We further analyzed these peptide sequences to identify bioactive peptides and classify them into anti-cancerous, anti-hypertensive, anti-microbial, and anti-inflammatory groups with a special emphasis on antimicrobial properties. With this in mind, we simultaneously conducted experiments to evaluate the antimicrobial properties of urinary aqueous extract on three pathogenic bacterial strains: S. aureus, E. coli, and S. agalactiae. The urinary peptides observed in the study are the result of the activity of possibly 76 proteases. The GO of these proteases showed the significant enrichment of the antibacterial peptide production. The total urinary peptide showed antimicrobial activity against the aforementioned pathogenic bacterial strains with no significant inhibitory effects against a buffalo mammary epithelial cell line. Just like our previous study in cows, the present study suggests the prime role of the antimicrobial peptides in the maintenance of the sterility of the urinary tract in buffalo by virtue of their amino acid composition.
Full article
(This article belongs to the Special Issue Bioactive Peptides and Their Antibiotic Activity)
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Open AccessFeature PaperArticle
Detection of Vancomycin Resistance among Methicillin-Resistant Staphylococcus aureus Strains Recovered from Children with Invasive Diseases in a Reference Pediatric Hospital
by
Lorena Pardo, María Inés Mota, Andrés Parnizari, Adriana Varela, Gabriela Algorta and Gustavo Varela
Antibiotics 2024, 13(4), 298; https://doi.org/10.3390/antibiotics13040298 - 26 Mar 2024
Abstract
Vancomycin is the cornerstone intreating methicillin-resistant Staphylococcus aureus (MRSA) infections. However, therapeutic failures can occur when MRSA strains with decreased susceptibility to glycopeptides (DSG) are involved. The aim of this study was to detect and characterize DSG in MRSA recovered from children with
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Vancomycin is the cornerstone intreating methicillin-resistant Staphylococcus aureus (MRSA) infections. However, therapeutic failures can occur when MRSA strains with decreased susceptibility to glycopeptides (DSG) are involved. The aim of this study was to detect and characterize DSG in MRSA recovered from children with invasive diseases at a reference pediatric hospital between 2009 and 2019. Fifty-two MRSA strains were screened using agar plates with vancomycin 3 and 4 mg/L (BHI-3 and BHI-4); the VITEK2 system; and standard and macro E-tests. Suspicious hVISA were studied by population analysis profiling–area under the curve (PAP-AUC), and wall thickness was analyzed by transmission electron microscopy. Neither VRSA nor VISA were detected in this set. As only three strains met the hVISA criteria, the PAP-AUC study included 12 additional MRSA strains that grew one colony on BHI-4 plates or showed minimum inhibitory concentrations of vancomycin and/or teicoplanin ≥ 1.5 mg/L. One strain was confirmed as hVISA by PAP-AUC. The wall thickness was greater than the vancomycin-susceptible control strain; it belonged to ST30 and carried SCCmec IV. As expected, a low frequency of hVISA was found (1.9%). The only hVISA confirmed by PAP-AUC was not detected by the screening methods, highlighting the challenge that its detection represents for microbiology laboratories.
Full article
(This article belongs to the Special Issue ESKAPE Pathogen Infection and Antibiotic Resistance)
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Open AccessArticle
Restraining Staphylococcus aureus Virulence Factors and Quorum Sensing through Lactic Acid Bacteria Supernatant Extracts
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Myriam Anabel Díaz, Esteban Gabriel Vega-Hissi, María Amparo Blázquez, María Rosa Alberto and Mario Eduardo Arena
Antibiotics 2024, 13(4), 297; https://doi.org/10.3390/antibiotics13040297 - 25 Mar 2024
Abstract
The escalating prevalence of antibiotic-resistant bacteria poses a grave threat to human health, necessitating the exploration of novel alternatives to conventional antibiotics. This study investigated the impact of extracts derived from the supernatant of four lactic acid bacteria strains on factors contributing to
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The escalating prevalence of antibiotic-resistant bacteria poses a grave threat to human health, necessitating the exploration of novel alternatives to conventional antibiotics. This study investigated the impact of extracts derived from the supernatant of four lactic acid bacteria strains on factors contributing to the pathogenicity of three Staphylococcus aureus strains. The study evaluated the influence of lactic acid bacteria supernatant extracts on the growth, biofilm biomass formation, biofilm metabolic activity, and biofilm integrity of the S. aureus strains. Additionally, the impact on virulence factors (hemolysin and coagulase) was examined. Gas chromatography coupled with mass spectrometry was used to identify the bioactive compounds in the extracts, while molecular docking analyses explored potential interactions. Predominantly, the extracts contain eight 2,5-diketopiperazines, which are cyclic forms of peptides. The extracts demonstrated inhibitory effects on biofilm formation, the ability to disrupt mature biofilms, and reduce the biofilm cell metabolic activity of the S. aureus strains. Furthermore, they exhibited the ability to inhibit α-hemolysin production and reduce coagulase activity. An in silico docking analysis reveals promising interactions between 2,5-diketopiperazines and key proteins (SarA and AgrA) in S. aureus, confirming their antivirulence and antibiofilm activities. These findings suggest that 2,5-diketopiperazines could serve as a promising lead compound in the fight against antibiotic-resistant S. aureus.
Full article
(This article belongs to the Special Issue Antimicrobial Resistance and Antimicrobial Activity of Natural Products and Derivatives)
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Open AccessArticle
Comparative Impact of an Optimized PK/PD Target Attainment of Piperacillin-Tazobactam vs. Meropenem on the Trend over Time of SOFA Score and Inflammatory Biomarkers in Critically Ill Patients Receiving Continuous Infusion Monotherapy for Treating Documented Gram-Negative BSIs and/or VAP
by
Milo Gatti, Matteo Rinaldi, Tommaso Tonetti, Antonio Siniscalchi, Pierluigi Viale and Federico Pea
Antibiotics 2024, 13(4), 296; https://doi.org/10.3390/antibiotics13040296 - 25 Mar 2024
Abstract
(1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over
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(1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over time of both Sequential Organ Failure Assessment (SOFA) score and inflammatory biomarkers in critically ill patients receiving continuous infusion (CI) monotherapy with piperacillin-tazobactam or meropenem for treating documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP). (2) Methods: We performed a retrospective observational study comparing critically ill patients receiving targeted treatment with CI meropenem monotherapy for documented Gram-negative BSIs or VAP with a historical cohort of critical patients receiving CI piperacillin-tazobactam monotherapy. Patients included in the two groups were admitted to the general and post-transplant intensive care unit in the period July 2021–September 2023 and fulfilled the same inclusion criteria. The delta values of the SOFA score between the baseline of meropenem or piperacillin-tazobactam treatment and those at 48-h (delta 48-h SOFA score) or at 7-days (delta 7-days SOFA) were selected as primary outcomes. Delta 48-h and 7-days C-reactive protein (CRP) and procalcitonin (PCT), microbiological eradication, resistance occurrence, clinical cure, multi-drug resistant colonization at 90-day, ICU, and 30-day mortality rate were selected as secondary outcomes. Univariate analysis comparing primary and secondary outcomes between critically ill patients receiving CI monotherapy with piperacillin-tazobactam vs. meropenem was carried out. (3) Results: Overall, 32 critically ill patients receiving CI meropenem monotherapy were compared with a historical cohort of 43 cases receiving CI piperacillin-tazobactam monotherapy. No significant differences in terms of demographics and clinical features emerged at baseline between the two groups. Optimal PK/PD target was attained in 83.7% and 100.0% of patients receiving piperacillin-tazobactam and meropenem, respectively. No significant differences were observed between groups in terms of median values of delta 48-h SOFA (0 points vs. 1 point; p = 0.89) and median delta 7-days SOFA (2 points vs. 1 point; p = 0.43). Similarly, no significant differences were found between patients receiving piperacillin-tazobactam vs. meropenem for any of the secondary outcomes. (4) Conclusion: Our findings may support the contention that in critically ill patients with documented Gram-negative BSIs and/or VAP, the decreases in the SOFA score and in the inflammatory biomarkers serum levels achievable with CI piperacillin-tazobactam monotherapy at 48-h and at 7-days may be of similar extent and as effective as to those achievable with CI meropenem monotherapy provided that optimization on real-time by means of a TDM-based expert clinical pharmacological advice program is granted.
Full article
(This article belongs to the Special Issue Antibacterial Resistance and Infection Control in ICU)
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Open AccessReview
The Importance of Carbapenemase-Producing Enterobacterales in African Countries: Evolution and Current Burden
by
Edgar-Costin Chelaru, Andrei-Alexandru Muntean, Mihai-Octav Hogea, Mădălina-Maria Muntean, Mircea-Ioan Popa and Gabriela-Loredana Popa
Antibiotics 2024, 13(4), 295; https://doi.org/10.3390/antibiotics13040295 - 24 Mar 2024
Abstract
Antimicrobial resistance (AMR) is a worldwide healthcare problem. Multidrug-resistant organisms (MDROs) can spread quickly owing to their resistance mechanisms. Although colonized individuals are crucial for MDRO dissemination, colonizing microbes can lead to symptomatic infections in carriers. Carbapenemase-producing Enterobacterales (CPE) are among the most
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Antimicrobial resistance (AMR) is a worldwide healthcare problem. Multidrug-resistant organisms (MDROs) can spread quickly owing to their resistance mechanisms. Although colonized individuals are crucial for MDRO dissemination, colonizing microbes can lead to symptomatic infections in carriers. Carbapenemase-producing Enterobacterales (CPE) are among the most important MDROs involved in colonizations and infections with severe outcomes. This review aimed to track down the first reports of CPE in Africa, describe their dissemination throughout African countries and summarize the current status of CRE and CPE data, highlighting current knowledge and limitations of reported data. Two database queries were undertaken using Medical Subject Headings (MeSH), employing relevant keywords to identify articles that had as their topics beta-lactamases, carbapenemases and carbapenem resistance pertaining to Africa or African regions and countries. The first information on CPE could be traced back to the mid-2000s, but data for many African countries were established after 2015–2018. Information is presented chronologically for each country. Although no clear conclusions could be drawn for some countries, it was observed that CPE infections and colonizations are present in most African countries and that carbapenem-resistance levels are rising. The most common CPE involved are Klebsiella pneumoniae and Escherichia coli, and the most prevalent carbapenemases are NDM-type and OXA-48-type enzymes. Prophylactic measures, such as screening, are required to combat this phenomenon.
Full article
(This article belongs to the Special Issue Epidemiology and Mechanism of Bacterial Resistance to Antibiotics)
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Open AccessReview
Bacteriophage Therapy in Companion and Farm Animals
by
Laura Bianchessi, Giulia De Bernardi, Martina Vigorelli, Paola Dall’Ara and Lauretta Turin
Antibiotics 2024, 13(4), 294; https://doi.org/10.3390/antibiotics13040294 - 23 Mar 2024
Abstract
Bacteriophages, which are viruses with restricted tropism for bacteria, have been employed for over a century as antimicrobial agents; they have been largely abandoned in Western countries but are constantly used in Eastern European countries with the advent of antibiotics. In recent decades,
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Bacteriophages, which are viruses with restricted tropism for bacteria, have been employed for over a century as antimicrobial agents; they have been largely abandoned in Western countries but are constantly used in Eastern European countries with the advent of antibiotics. In recent decades, the growing spread of multidrug-resistant bacteria, which pose a serious threat to worldwide public health, imposed an urgent demand for alternative therapeutic approaches to antibiotics in animal and human fields. Based on this requirement, numerous studies have been published on developing and testing bacteriophage-based therapy. Overall, the literature largely supports the potential of this perspective but also highlights the need for additional research as the current standards are inadequate to receive approval from regulatory authorities. This review aims to update and critically revise the current knowledge on the application of bacteriophages to treat bacterial-derived infectious diseases in animals in order to provide topical perspectives and innovative advances.
Full article
(This article belongs to the Special Issue Alternative Approaches to Treating Antimicrobial Resistant Infections—3rd Volume)
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Appropriate Duration of Antimicrobial Treatment for Prosthetic Joint Infections: A Narrative Review
by
Jaime Lora-Tamayo, Mikel Mancheño-Losa, María Ángeles Meléndez-Carmona, Pilar Hernández-Jiménez, Natividad Benito and Oscar Murillo
Antibiotics 2024, 13(4), 293; https://doi.org/10.3390/antibiotics13040293 - 23 Mar 2024
Abstract
Prosthetic joint infections are considered difficult to treat they needing aggressive surgery and long antimicrobial treatments. However, the exact duration of these therapies has been established empirically. In the last years, several studies have explored the possibility of reducing the length of treatment
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Prosthetic joint infections are considered difficult to treat they needing aggressive surgery and long antimicrobial treatments. However, the exact duration of these therapies has been established empirically. In the last years, several studies have explored the possibility of reducing the length of treatment in this setting, with conflicting results. In this narrative review, we critically appraise the published evidence, considering the different surgical approaches (implant retention [DAIR] and one-step and two-step exchange procedures) separately. In patients managed with DAIR, usually treated for at least 12 weeks, a large, randomized trial failed to show that 6 weeks were non-inferior. However, another randomized clinical trial supports the use of 8 weeks, as long as the surgical conditions are favorable and antibiotics with good antibiofilm activity can be administered. In patients managed with a two-step exchange procedure, usually treated during 6 weeks, a randomized clinical trial showed the efficacy of a 4-week course of antimicrobials. Also, the use of local antibiotics may allow the use of even shorter treatments. Finally, in the case of one-step exchange procedures, there is a trend towards reducing the length of therapy, and the largest randomized clinical trial supports the use of 6 weeks of therapy.
Full article
(This article belongs to the Special Issue Antimicrobial Therapeutics for Bone and Periprosthetic Joint Infection)
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Open AccessArticle
Knowledge, Attitudes, and Practices of Rural Communities Regarding Antimicrobial Resistance and Climate Change in Adadle District, Somali Region, Ethiopia: A Mixed-Methods Study
by
Abdifatah Muktar Muhummed, Ashenafi Alemu, Yahya Osman Maidane, Rea Tschopp, Jan Hattendorf, Pascale Vonaesch, Jakob Zinsstag and Guéladio Cissé
Antibiotics 2024, 13(4), 292; https://doi.org/10.3390/antibiotics13040292 - 22 Mar 2024
Abstract
There is an urgent need for interventions in addressing the rapid and disproportionate impact of antimicrobial resistance (AMR) and climate change (CC) on low- and middle-income countries. Within this context, it is important to understand indigenous knowledge in rural communities, which are highly
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There is an urgent need for interventions in addressing the rapid and disproportionate impact of antimicrobial resistance (AMR) and climate change (CC) on low- and middle-income countries. Within this context, it is important to understand indigenous knowledge in rural communities, which are highly affected. This study examined knowledge, attitude, and practices (KAP) regarding AMR and CC in the Adadle district, Somali region, Ethiopia, utilizing mixed methods, including 362 surveys and 12 focus group discussions among rural communities. Findings showed that 39% and 63% of participants were familiar with AMR and CC, respectively. Of those surveyed, 57% attributed AMR to inappropriate antimicrobial use in animals and humans, while CC was often associated with Allah/God. Multivariable analysis indicated that males exhibited superior knowledge and a positive attitude towards AMR and CC. Additionally, individuals aged 26–35 and 36–45 years showed heightened awareness of AMR and CC, respectively. Moreover, participants who were government employees, pastoralists, and business owners showed better knowledge on CC compared to family caretaker. Religious education and households with more than six members were linked to lower AMR knowledge. This study underlines a greater awareness of CC than AMR and highlights gender-based disparities, recommending integrated educational AMR programs targeting different demographics through a One Health lens, actively involving females, and incorporating local beliefs and practices.
Full article
(This article belongs to the Special Issue Antibiotic Resistance and Antimicrobial Use in Elderly Patients)
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