Antibiotics

46 pages, 2500 KiB

Open AccessArticle

Genome-Wide Analysis of Escherichia coli Isolated from Dairy Animals Identifies Virulence Factors and Genes Enriched in Multidrug-Resistant Strains

by Bradd J. Haley, Seon Woo Kim, Serajus Salaheen, Ernest Hovingh and Jo Ann S. Van Kessel

Antibiotics 2023, 12(10), 1559; https://doi.org/10.3390/antibiotics12101559 - 23 Oct 2023

Cited by 7 | Viewed by 2982

Abstract

The gastrointestinal tracts of dairy calves and cows are reservoirs of antimicrobial-resistant bacteria (ARB), which are present regardless of previous antimicrobial therapy. Young calves harbor a greater abundance of resistant bacteria than older cows, but the factors driving this high abundance are unknown. [...] Read more.

The gastrointestinal tracts of dairy calves and cows are reservoirs of antimicrobial-resistant bacteria (ARB), which are present regardless of previous antimicrobial therapy. Young calves harbor a greater abundance of resistant bacteria than older cows, but the factors driving this high abundance are unknown. Here, we aimed to fully characterize the genomes of multidrug-resistant (MDR) and antimicrobial-susceptible Escherichia coli strains isolated from pre-weaned calves, post-weaned calves, dry cows, and lactating cows and to identify the accessory genes that are associated with the MDR genotype to discover genetic targets that can be exploited to mitigate antimicrobial resistance in dairy farms. Results indicated that both susceptible and resistant E. coli isolates recovered from animals on commercial dairy operations were highly diverse and encoded a large pool of virulence factors. In total, 838 transferrable antimicrobial resistance genes (ARGs) were detected, with genes conferring resistance to aminoglycosides being the most common. Multiple sequence types (STs) associated with mild to severe human gastrointestinal and extraintestinal infections were identified. A Fisher’s Exact Test identified 619 genes (ARGs and non-ARGs) that were significantly enriched in MDR isolates and 147 genes that were significantly enriched in susceptible isolates. Significantly enriched genes in MDR isolates included the iron scavenging aerobactin synthesis and receptor genes (iucABCD-iutA) and the sitABCD system, as well as the P fimbriae pap genes, myo-inositol catabolism (iolABCDEG-iatA), and ascorbate transport genes (ulaABC). The results of this study demonstrate a highly diverse population of E. coli in commercial dairy operations, some of which encode virulence genes responsible for severe human infections and resistance to antibiotics of human health significance. Further, the enriched accessory genes in MDR isolates (aerobactin, sit, P fimbriae, and myo-inositol catabolism and ascorbate transport genes) represent potential targets for reducing colonization of antimicrobial-resistant bacteria in the calf gut. Full article

(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)

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15 pages, 828 KiB

Open AccessArticle

Development and Validation of a Gas Chromatography–Mass Spectrometry Method for the Analysis of the Novel Plant-Based Substance with Antimicrobial Activity

by Viktor A. Filatov, Egor A. Ilin, Olesya Yu. Kulyak and Elena I. Kalenikova

Antibiotics 2023, 12(10), 1558; https://doi.org/10.3390/antibiotics12101558 - 22 Oct 2023

Cited by 2 | Viewed by 2282

Abstract

The research into new pharmaceutical substances based on essential oils, individual biologically active phytochemicals, and plant extracts is a priority in field of pharmaceutical sciences. A novel multicomponent substance based on Melaleuca alternifolia (M. alternifolia) leaf oil (TTO), 1,8-cineole (eucalyptol), and [...] Read more.

The research into new pharmaceutical substances based on essential oils, individual biologically active phytochemicals, and plant extracts is a priority in field of pharmaceutical sciences. A novel multicomponent substance based on Melaleuca alternifolia (M. alternifolia) leaf oil (TTO), 1,8-cineole (eucalyptol), and (-)-α-bisabolol with potent synergetic antimicrobial activity was investigated and suggested for the treatment of seborrheic dermatitis (SD) and dandruff. The objective of this research was to establish and validate a specific, accurate, and precise gas chromatography–mass spectrometry (GC–MS) method for further quantitative and qualitative analysis in order to ensure quality control. The main parameters of validation were suitability, specificity, linearity, accuracy, and intermediate precision according to the European Pharmacopoeia (XI edition), Russian Pharmacopoeia (XIV edition), and some parameters of ICH requirements. The peaks of fifteen chemical phytoconstituents were identified in the test sample solution with the prevalence of (−)-α-bisabolol (27.67%), 1,8-cineole (25.63%), and terpinen-4-ol (16.98%). These phytochemicals in the novel substance were chosen for standardization and validation of the GC–MS method. The chosen chromatographic conditions were confirmed for testing of the plant-based substance in a suitability test. It was established that the GC–MS method provides a significant separation, symmetry of peaks and resolution between phytochemicals. The calibration curves of each phytochemical had good linearity (R² > 0.999) in five concentrations. In the same concertation range, the accuracy of terpinen-4-ol, 1,8-cineol, and (−)-α-bisabolol determination using the method of additives was 98.3–101.60%; the relative standard deviation (RSD) ranged from 0.89% to 1.51% and corresponded to requirements. The intraday and interday precision was ≤2.56%. Thus, the GC–MS method was validated to be specific, sensitive, linear, accurate, and precise. This GC–MS method could be recommended as a routine analytic technique for multicomponent plant-based substances-enriched terpenes. Full article

(This article belongs to the Special Issue Essential Oil and Plant Extracts: Chemical Composition and Antimicrobial Activity)

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25 pages, 723 KiB

Open AccessReview

Antimicrobial Stewardship in the Hospital Setting: A Narrative Review

by Helen Giamarellou, Lamprini Galani, Theodoros Karavasilis, Konstantinos Ioannidis and Ilias Karaiskos

Antibiotics 2023, 12(10), 1557; https://doi.org/10.3390/antibiotics12101557 - 21 Oct 2023

Cited by 12 | Viewed by 5434

Abstract

The increasing global threat of antibiotic resistance, which has resulted in countless fatalities due to untreatable infections, underscores the urgent need for a strategic action plan. The acknowledgment that humanity is perilously approaching the “End of the Miracle Drugs” due to the unjustifiable [...] Read more.

The increasing global threat of antibiotic resistance, which has resulted in countless fatalities due to untreatable infections, underscores the urgent need for a strategic action plan. The acknowledgment that humanity is perilously approaching the “End of the Miracle Drugs” due to the unjustifiable overuse and misuse of antibiotics has prompted a critical reassessment of their usage. In response, numerous relevant medical societies have initiated a concerted effort to combat resistance by implementing antibiotic stewardship programs within healthcare institutions, grounded in evidence-based guidelines and designed to guide antibiotic utilization. Crucial to this initiative is the establishment of multidisciplinary teams within each hospital, led by a dedicated Infectious Diseases physician. This team includes clinical pharmacists, clinical microbiologists, hospital epidemiologists, infection control experts, and specialized nurses who receive intensive training in the field. These teams have evidence-supported strategies aiming to mitigate resistance, such as conducting prospective audits and providing feedback, including the innovative ‘Handshake Stewardship’ approach, implementing formulary restrictions and preauthorization protocols, disseminating educational materials, promoting antibiotic de-escalation practices, employing rapid diagnostic techniques, and enhancing infection prevention and control measures. While initial outcomes have demonstrated success in reducing resistance rates, ongoing research is imperative to explore novel stewardship interventions. Full article

(This article belongs to the Special Issue Antibiotic Resistant Pathogens in Hospital)

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24 pages, 3081 KiB

Open AccessArticle

Antarctic Marine Bacteria as a Source of Anti-Biofilm Molecules to Combat ESKAPE Pathogens

by Marco Artini, Rosanna Papa, Gianluca Vrenna, Marika Trecca, Irene Paris, Caterina D’Angelo, Maria Luisa Tutino, Ermenegilda Parrilli and Laura Selan

Antibiotics 2023, 12(10), 1556; https://doi.org/10.3390/antibiotics12101556 - 21 Oct 2023

Cited by 4 | Viewed by 1979

Abstract

The ESKAPE pathogens, including bacteria such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, pose a global health threat due to their ability to resist antimicrobial drugs and evade the immune system. [...] Read more.

The ESKAPE pathogens, including bacteria such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, pose a global health threat due to their ability to resist antimicrobial drugs and evade the immune system. These pathogens are responsible for hospital-acquired infections, especially in intensive care units, and contribute to the growing problem of multi-drug resistance. In this study, researchers focused on exploring the potential of Antarctic marine bacteria as a source of anti-biofilm molecules to combat ESKAPE pathogens. Four Antarctic bacterial strains were selected, and their cell-free supernatants were tested against 60 clinical ESKAPE isolates. The results showed that the supernatants did not exhibit antimicrobial activity but effectively prevented biofilm formation and dispersed mature biofilms. This research highlights the promising potential of Antarctic bacteria in producing compounds that can counteract biofilms formed by clinically significant bacterial species. These findings contribute to the development of new strategies for preventing and controlling infections caused by ESKAPE pathogens. Full article

(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Biofilm Infections)

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12 pages, 1379 KiB

Open AccessArticle

Bacteremia Prevention during Periodontal Treatment—An In Vivo Feasibility Study

by Patrick Jansen, Georg Conrads, Johannes-Simon Wenzler, Felix Krause and Andreas Braun

Antibiotics 2023, 12(10), 1555; https://doi.org/10.3390/antibiotics12101555 - 20 Oct 2023

Viewed by 2240

Abstract

The link between periodontitis and systemic diseases has increasingly become a focus of research in recent years. In this context, it is reasonable—especially in vulnerable patient groups—to minimize bacteremia during periodontal treatment. The aim of the present in vivo feasibility study was to [...] Read more.

The link between periodontitis and systemic diseases has increasingly become a focus of research in recent years. In this context, it is reasonable—especially in vulnerable patient groups—to minimize bacteremia during periodontal treatment. The aim of the present in vivo feasibility study was to investigate the possibility of laser-based bacteremia prevention. Patients with stage III, grade B generalized periodontitis were therefore treated in a split-mouth design either with prior 445 nm laser irradiation before nonsurgical periodontal therapy or without. During the treatments, clinical (periodontal measures, pain sensation, and body temperature), microbiological (sulcus samples and blood cultures before, 25 min after the start, and 10 min after the end of treatment), and immunological parameters (CRP, IL-6, and TNF-α) were obtained. It was shown that periodontal treatment-related bacteremia was detectable in both patients with the study design used. The species isolated were Schaalia georgiae, Granulicatella adiacens, and Parvimonas micra. The immunological parameters increased only slightly and occasionally. In the laser-assisted treatments, all blood cultures remained negative, demonstrating treatment-related bacteremia prevention. Within the limitations of this feasibility study, it can be concluded that prior laser disinfection can reduce bacteremia risk during periodontal therapy. Follow-up studies with larger patient numbers are needed to further investigate this effect, using the study design presented here. Full article

(This article belongs to the Special Issue Antibacterial Treatment in Periodontal and Endodontic Therapy, 2nd Edition)

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17 pages, 3306 KiB

Open AccessArticle

Comparison of Oral Microbial Composition and Determinants Encoding Antimicrobial Resistance in Dogs and Their Owners

by Laura Šakarnytė, Rita Šiugždinienė, Judita Žymantienė and Modestas Ruzauskas

Antibiotics 2023, 12(10), 1554; https://doi.org/10.3390/antibiotics12101554 - 20 Oct 2023

Cited by 4 | Viewed by 1933

Abstract

Consolidated studies on animal, human, and environmental health have become very important for understanding emerging zoonotic diseases and the spread of antimicrobial resistance (AMR). The aim of this study was to analyse the oral microbiomes of healthy dogs and their owners, including determinants [...] Read more.

Consolidated studies on animal, human, and environmental health have become very important for understanding emerging zoonotic diseases and the spread of antimicrobial resistance (AMR). The aim of this study was to analyse the oral microbiomes of healthy dogs and their owners, including determinants of AMR. Shotgun metagenomic sequencing detected 299 bacterial species in pets and their owners, from which 70 species were carried by dogs and 229 species by humans. Results demonstrated a unique microbial composition of dogs and their owners. At an order level, Bacteroidales were the most prevalent oral microbiota of dogs with significantly lower prevalence in their owners where Actinomycetales and Lactobacillales predominated. Porphyromonas and Corynebacterium were the most prevalent genera in dogs, whereas Streptococcus and Actinomyces were in animal owners. The resistances to macrolides, tetracyclines, lincosamides and Cfx family A class broad-spectrum β-lactamase were detected in both animal and human microbiomes. Resistance determinants to amphenicols, aminoglycosides, sulphonamides, and quaternary ammonium compounds were detected exceptionally in dogs. In conclusion, the study demonstrated different bacterial composition in oral microbiomes of healthy dogs without clinical signs of periodontal disease and their owners. Due to the low numbers of the samples tested, further investigations with an increased number of samples should be performed. Full article

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21 pages, 7932 KiB

Open AccessArticle

Artemisia brevifolia Wall. Ex DC Enhances Cefixime Susceptibility by Reforming Antimicrobial Resistance

by Aroosa Zafar, Yusra Wasti, Muhammad Majid, Durdana Muntaqua, Simona Gabriela Bungau and Ihsan ul Haq

Antibiotics 2023, 12(10), 1553; https://doi.org/10.3390/antibiotics12101553 - 20 Oct 2023

Cited by 2 | Viewed by 2449

Abstract

(1) Background: A possible solution to antimicrobial resistance (AMR) is synergism with plants like Artemisia brevifolia Wall. ex DC. (2) Methods: Phytochemical quantification of extracts (n-hexane (NH), ethyl acetate (EA), methanol (M), and aqueous (Aq)) was performed using RP-HPLC and chromogenic assays. Extracts [...] Read more.

(1) Background: A possible solution to antimicrobial resistance (AMR) is synergism with plants like Artemisia brevifolia Wall. ex DC. (2) Methods: Phytochemical quantification of extracts (n-hexane (NH), ethyl acetate (EA), methanol (M), and aqueous (Aq)) was performed using RP-HPLC and chromogenic assays. Extracts were screened against resistant clinical isolates via disc diffusion, broth dilution, the checkerboard method, time–kill, and protein quantification assays. (3) Results: M extract had the maximum phenolic (15.98 ± 0.1 μg GAE/mgE) and flavonoid contents (9.93 ± 0.5 μg QE/mgE). RP-HPLC displayed the maximum polyphenols in the M extract. Secondary metabolite determination showed M extract to have the highest glycosides, alkaloids, and tannins. Preliminary resistance profiling indicated that selected isolates were resistant to cefixime (MIC 20–40 µg/mL). Extracts showed moderate antibacterial activity (MIC 60–100 µg/mL). The checkerboard method revealed a total synergy between EA extract and cefixime with 10-fold reductions in cefixime dose against resistant P. aeruginosa and MRSA. Moreover, A. brevifolia extracts potentiated the antibacterial effect of cefixime after 6 and 9 h. The synergistic combination was non- to slightly hemolytic and could inhibit bacterial protein in addition to cefixime disrupting the cell wall, thus making it difficult for bacteria to survive. (4) Conclusion: A. brevifolia in combination with cefixime has the potential to inhibit AMR. Full article

(This article belongs to the Special Issue Antibacterial Resistance and Novel Therapeutic Strategies)

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18 pages, 1794 KiB

Open AccessArticle

Efficacy of Chlorhexidine after Oral Surgery Procedures on Wound Healing: Systematic Review and Meta-Analysis

by María de Nuria Romero-Olid, Elena Bucataru, Pablo Ramos-García and Miguel Ángel González-Moles

Antibiotics 2023, 12(10), 1552; https://doi.org/10.3390/antibiotics12101552 - 20 Oct 2023

Cited by 2 | Viewed by 2648

Abstract

Our objective was to evaluate qualitatively and quantitatively, through a systematic review and meta-analysis, available evidence on the efficacy of chlorhexidine (CHX) when applied after oral surgery on wound healing and related clinical parameters. MEDLINE/PubMed, Embase, CENTRAL, Web of Science, and Scopus were [...] Read more.

Our objective was to evaluate qualitatively and quantitatively, through a systematic review and meta-analysis, available evidence on the efficacy of chlorhexidine (CHX) when applied after oral surgery on wound healing and related clinical parameters. MEDLINE/PubMed, Embase, CENTRAL, Web of Science, and Scopus were searched for studies published before January 2023. The quality of the methodology used in primary-level studies was assessed using the RoB2 tool; meta-analyses were performed jointly with heterogeneity and small-study effect analyses. Thirty-three studies and 4766 cases were included. The results point out that the application of CHX was significantly more effective, compared to controls where CHX was not employed, providing better wound healing after oral surgery (RR = 0.66, 95% CI = 0.55–0.80, p < 0.001). Stratified meta-analyses confirmed the higher efficacy of 0.20% CHX gel vs. other vehicles and concentrations (p < 0.001, respectively). Likewise, the addition of chitosan to CHX significantly increased the efficacy of surgical wound healing (p < 0.001). The use of CHX has also been significantly beneficial in the prevention of alveolar osteitis after any type of dental extraction (RR = 0.46, 95% CI = 0.39–0.53, p < 0.001) and has also been effective when applied as a gel for a reduction in pain after the surgical extraction of third molars (MD = −0.97, 95% CI = −1.26 to −0.68, p < 0.001). In conclusion, this systematic review and meta-analysis demonstrate on the basis of evidence that the application of CHX exerts a beneficial effect on wound healing after oral surgical procedures, significantly decreasing the patient’s risk of developing surgical complications and/or poor wound healing. This benefit was greater when CHX was used at 0.20% in gel form with the addition of chitosan. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Dental Biomaterials)

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15 pages, 850 KiB

Open AccessArticle

Molecular Typing and Resistance Profile of Acinetobacter baumannii Isolates during the COVID-19 Pandemic: Findings from the “EPIRADIOCLINF” Project

by Antonella Agodi, Arturo Montineri, Rosa Manuele, Paola Noto, Giuseppe Carpinteri, Giacomo Castiglione, Patrizia Grassi, Antonio Lazzara, Anna Rita Mattaliano, Giuseppa Granvillano, Claudia La Mastra, Maria Clara La Rosa, Andrea Maugeri and Martina Barchitta

Antibiotics 2023, 12(10), 1551; https://doi.org/10.3390/antibiotics12101551 - 19 Oct 2023

Viewed by 1788

Abstract

Due to the COVID-19 pandemic, there has been a shift in focus towards controlling the spread of SARS-CoV-2, which has resulted in the neglect of traditional programs aimed at preventing healthcare-associated infections and combating antimicrobial resistance. The present work aims to characterize the [...] Read more.

Due to the COVID-19 pandemic, there has been a shift in focus towards controlling the spread of SARS-CoV-2, which has resulted in the neglect of traditional programs aimed at preventing healthcare-associated infections and combating antimicrobial resistance. The present work aims to characterize the colonization or infection with Acinetobacter baumannii of COVID-19 patients and to identify any clonality between different isolates. Specifically, data and resistance profiles of A. baumannii isolates were prospectively collected from patients recruited by the EPIRADIOCLINF project. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were used for molecular typing. Overall, we analyzed 64 isolates of A. baumannii from 48 COVID-19 patients. According to our analysis, we have identified the spread of a clonally related isolate, referred to as B. The PFGE pattern B includes four subtypes: B1 (consisting of 37 strains), B2 (11), B3 (5), and B4 (2). Furthermore, in the isolates that were examined using MLST, the most observed sequence type was ST/281. In terms of resistance profiles, 59 out of the total isolates (92.2%) were found to be resistant to gentamicin, carbapenems, ciprofloxacin, and tobramycin. The isolation and identification of A. baumannii from COVID-19 patients, along with the high levels of transmission observed within the hospital setting, highlight the urgent need for the implementation of effective prevention and containment strategies. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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15 pages, 2532 KiB

Open AccessArticle

Itraconazole Loaded Biosurfactin Micelles with Enhanced Antifungal Activity: Fabrication, Evaluation and Molecular Simulation

by Faisal Usman, Mudassir Farooq, Tanveer A. Wani, Hassan Ahmad, Ibrahim Javed, Mazhar Iqbal, Fatima Akbar Sheikh, Farhan Siddique, Seema Zargar and Saleh Sheikh

Antibiotics 2023, 12(10), 1550; https://doi.org/10.3390/antibiotics12101550 - 19 Oct 2023

Cited by 5 | Viewed by 2275

Abstract

Itraconazole (ITZ) is a broad-spectrum antifungal for superficial subcutaneous and systemic fungal infections. This study aimed to enhance the antifungal activity of ITZ using surfactin A (SA), a cyclic lipopeptide produced by the SA-producing Bacillus strain NH-100, possessing strong antifungal activity. SA was [...] Read more.

Itraconazole (ITZ) is a broad-spectrum antifungal for superficial subcutaneous and systemic fungal infections. This study aimed to enhance the antifungal activity of ITZ using surfactin A (SA), a cyclic lipopeptide produced by the SA-producing Bacillus strain NH-100, possessing strong antifungal activity. SA was extracted, and ITZ-loaded SA micelles formulations were prepared via a single-pot rinsing method and characterized by particle size, zeta potential, and infrared spectroscopy. In vitro dissolution at pH 1.2, as well as hemolysis studies, was also carried out. The fabricated formulations were stable and non-spherical in shape, with an average size of about 179 nm, and FTIR spectra depicted no chemical interaction among formulation components. ITZ-loaded micelles showed decreased hemolysis activity in comparison to pure ITZ. The drug released followed the Korsmeyer–Peppas model, having R² 0.98 with the diffusion release mechanism. In an acidic buffer, drug release of all prepared formulations was in the range of 73–89% in 2 h. The molecular simulation showed the outstanding binding and stability profile of the ITZ-SA complex. The aromatic ring of the ITZ mediates a π-alkyl contact with a side chain in the SA. It can be concluded that ITZ-loaded micelles, owing to significant enhanced antifungal activity up to 6-fold due to the synergistic effect of SA, can be a promising drug delivery platform for delivery of poorly soluble ITZ. Full article

(This article belongs to the Special Issue Discovery and Development of Novel Therapeutic Agents in Infectious Diseases Treatment)

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14 pages, 1205 KiB

Open AccessArticle

Comprehensive Analysis of Virulence Determinants and Genomic Islands of bla_NDM-1-Producing Enterobacter hormaechei Clinical Isolates from Greece

by Angeliki Mavroidi, Konstantina Gartzonika, Nick Spanakis, Elisavet Froukala, Christos Kittas, Georgia Vrioni and Athanasios Tsakris

Antibiotics 2023, 12(10), 1549; https://doi.org/10.3390/antibiotics12101549 - 18 Oct 2023

Cited by 1 | Viewed by 1888

Abstract

Nosocomial outbreaks of multidrug-resistant (MDR) Enterobacter cloacae complex (ECC) are often reported worldwide, mostly associated with a small number of multilocus-sequence types of E. hormaechei and E. cloacae strains. In Europe, the largest clonal outbreak of bla_NDM-1-producing ECC has been recently [...] Read more.

Nosocomial outbreaks of multidrug-resistant (MDR) Enterobacter cloacae complex (ECC) are often reported worldwide, mostly associated with a small number of multilocus-sequence types of E. hormaechei and E. cloacae strains. In Europe, the largest clonal outbreak of bla_NDM-1-producing ECC has been recently reported, involving an ST182 E. hormaechei strain in a Greek teaching hospital. In the current study, we aimed to further investigate the genetic make-up of two representative outbreak isolates. Comparative genomics of whole genome sequences (WGS) was performed, including whole genome-based taxonomic analysis and in silico prediction of virulence determinants of the bacterial cell surface, plasmids, antibiotic resistance genes and virulence factors present on genomic islands. The enterobacterial common antigen and the colanic antigen of the cell surface were identified in both isolates, being similar to the gene clusters of the E. hormaechei ATCC 49162 and E. cloacae ATCC 13047 type strains, whereas the two strains possessed different gene clusters encoding lipopolysaccharide O-antigens. Other virulence factors of the bacterial cell surface, such as flagella, fimbriae and pili, were also predicted to be encoded by gene clusters similar to those found in Enterobacter spp. and other Enterobacterales. Secretion systems and toxin–antitoxin systems, which also contribute to pathogenicity, were identified. Both isolates harboured resistance genes to multiple antimicrobial classes, including β-lactams, aminoglycosides, quinolones, chloramphenicol, trimethoprim, sulfonamides and fosfomycin; they carried bla_TEM-1, bla_OXA-1, bla_NDM-1, and one of them also carried bla_CTXM-14, bla_CTXM-15 and bla_LAP-2 plasmidic alleles. Our comprehensive analysis of the WGS assemblies revealed that bla_NDM-1-producing outbreak isolates possess components of the bacterial cell surface as well as genomic islands, harbouring resistance genes to several antimicrobial classes and various virulence factors. Differences in the plasmids carrying β-lactamase genes between the two strains have also shown diverse modes of acquisition and an ongoing evolution of these mobile elements. Full article

(This article belongs to the Special Issue Antimicrobial Resistance Genes: Spread and Evolution)

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17 pages, 1308 KiB

Open AccessArticle

Time-Kill Analysis of Canine Skin Pathogens: A Comparison of Pradofloxacin and Marbofloxacin

by Stefano Azzariti, Andrew Mead, Pierre-Louis Toutain, Ross Bond and Ludovic Pelligand

Antibiotics 2023, 12(10), 1548; https://doi.org/10.3390/antibiotics12101548 - 17 Oct 2023

Viewed by 1737

Abstract

Time-kill curves (TKCs) are more informative compared with the use of minimum inhibitory concentration (MIC) as they allow the capture of bacterial growth and the development of drug killing rates over time, which allows to compute key pharmacodynamic (PD) parameters. Our study aimed, [...] Read more.

Time-kill curves (TKCs) are more informative compared with the use of minimum inhibitory concentration (MIC) as they allow the capture of bacterial growth and the development of drug killing rates over time, which allows to compute key pharmacodynamic (PD) parameters. Our study aimed, using a semi-mechanistic mathematical model, to estimate the best pharmacokinetic/pharmacodynamic (PK/PD) indices (ƒAUC/MIC or %ƒT > MIC) for the prediction of clinical efficacy of veterinary FQs in Staphylococcus pseudintermedius, Staphylococcus aureus, and Escherichia coli collected from canine pyoderma cases with a focus on the comparison between marbofloxacin and pradofloxacin. Eight TCKs for each bacterial species (4 susceptible and 4 resistant) were analysed in duplicate. The best PK/PD index was ƒAUC_24h/MIC in both staphylococci and E. coli. For staphylococci, values of 25–40 h were necessary to achieve a bactericidal effect, whereas the calculated values (25–35 h) for E. coli were lower than those predicting a positive clinical outcome (100–120 h) in murine models. Pradofloxacin showed a higher potency (lower EC₅₀) in comparison with marbofloxacin. However, no difference in terms of a maximal possible pharmacological killing rate (E_max) was observed. Taking into account in vivo exposure at the recommended dosage regimen (3 and 2 mg/kg for pradofloxacin and marbofloxacin, respectively), the overall killing rates (K_drug) computed were also similar in most instances. Full article

(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics of Antibacterial and Antivirulence Drugs)

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15 pages, 2317 KiB

Open AccessArticle

Secondary and Co-Infections in Hospitalized COVID-19 Patients: A Multicenter Cross-Sectional Study in Malaysia

by Siti Roszilawati Ramli, Fashihah Sherina Abdul Hadi, Nur Asyura Nor Amdan, Insyirah Husna Kamaradin, Noraliza Zabari, Saraswathiy Maniam, Nur Suffia Sulaiman, Sumarni Ghazali, Zamtira Seman, Rohaidah Hashim and Norazah Ahmad

Antibiotics 2023, 12(10), 1547; https://doi.org/10.3390/antibiotics12101547 - 16 Oct 2023

Viewed by 1711

Abstract

Bacterial and fungal secondary and co-infections are commonly identified with viral respiratory infections. This study was undertaken to determine the incidence and factors associated with bacterial and fungal infections in patients with COVID-19 as well as antibiotics prescription patterns within the first and [...] Read more.

Bacterial and fungal secondary and co-infections are commonly identified with viral respiratory infections. This study was undertaken to determine the incidence and factors associated with bacterial and fungal infections in patients with COVID-19 as well as antibiotics prescription patterns within the first and second waves of the outbreak in Malaysia. Clinical records of 3532 COVID-19 patients admitted to hospitals in Malaysia between 4 February and 4 August 2020 were analyzed. Co-morbidities, clinical features, investigations, treatment, and complications were captured using the REDCap database. Culture and sensitivity test results were retrieved from the WHONET database. Univariate and multivariate regression analyses were used to identify associated determinants. A total of 161 types of bacterial and fungal infections were found in 81 patients, i.e., 2.3%. The most common bacterial cultures were Gram-negative, i.e., Pseudomonas aeruginosa (15.3%) and Klebsiella pneumoniae (13.9%). The most common fungal isolate was Candida albicans (41.2%). Augmentin, ceftriaxone, tazocin, meropenem, and azithromycin were the five most frequently prescribed antibiotics. The latter four were classified under the “Watch” category in the WHO AwaRe list. Our data showed that bacterial and fungal secondary and co-infections were frequently found in severely ill COVID-19 patients and were associated with a higher mortality rate. Full article

(This article belongs to the Special Issue Antimicrobial Use and Stewardship during the COVID-19 Era, 2nd Edition)

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16 pages, 3152 KiB

Open AccessArticle

Enhancing Medical Students’ Confidence and Knowledge in Antibiotic Prescription and Administration through Virtual Education: A Quasi-Experimental Study

by Israa Abdullah Malli, Mohamud Salaad Mohamud and Sami Al-Nasser

Antibiotics 2023, 12(10), 1546; https://doi.org/10.3390/antibiotics12101546 - 16 Oct 2023

Cited by 1 | Viewed by 1541

Abstract

Background: Antibiotic resistance is a worldwide health concern that necessitates antibiotic stewardship. Medical students significantly impact future healthcare practices; thus, their trust in antibiotic prescription and administration is crucial. This research aims to assess medical students’ levels of confidence and knowledge in these [...] Read more.

Background: Antibiotic resistance is a worldwide health concern that necessitates antibiotic stewardship. Medical students significantly impact future healthcare practices; thus, their trust in antibiotic prescription and administration is crucial. This research aims to assess medical students’ levels of confidence and knowledge in these areas before and after exposure to virtual antibiotic stewardship education. Methods: A one-group pretest-posttest design was conducted with medical students from King Saud bin Abdulaziz University for Health Sciences in Jeddah, Saudi Arabia. Participants were enrolled in the WHO-online antibiotic stewardship course. Results: The group’s baseline confidence and background knowledge were reported to be lower than what was offered after introducing the virtual course. The McNemar–Bowker test showed a significant difference in students’ confidence in pre-course and post-course scores (Z = 20, p < 0.002); the matched paired t-test revealed a significant difference in students’ knowledge scores (M = 7.66 verses M = 5.36, Z = 3.54, p = 0.001). In the sample, 70% of the students were unfamiliar with antibiotic stewardship; thus, the analysis revealed a significant difference in their familiarity before and after enrolling in the online course (30 vs. 100, p < 0.001). Conclusion: Medical students experience low confidence in the safe practice of the antibiotic stewardship program. The WHO-online antibiotic stewardship course is considered a valuable resource that can be used in a formative medical curriculum. Thus, educators and the academic curriculum must promote practical strategies to minimize antibiotic stewardship literacy and increase antibiotic prescribing and administration quality. Introducing antibiotic stewardship across the medical curriculum and establishing educational courses are some strategies that can be undertaken to ensure that future doctors are well-educated in the principles and practices of the appropriate use of antibiotic stewardship. Full article

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

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25 pages, 5034 KiB

Open AccessArticle

Consumer Preferences and Attitudes towards Antibiotic Use in Food Animals

by Katherine E. Adam and Ann Bruce

Antibiotics 2023, 12(10), 1545; https://doi.org/10.3390/antibiotics12101545 - 16 Oct 2023

Cited by 3 | Viewed by 2316

Abstract

Antimicrobial resistance (AMR) is one of the major challenges faced by society, with the real threat of the failure of many medical procedures. Antibiotics are also used in livestock production and provide a potential pathway to increasing AMR. The central challenge involves ensuring [...] Read more.

Antimicrobial resistance (AMR) is one of the major challenges faced by society, with the real threat of the failure of many medical procedures. Antibiotics are also used in livestock production and provide a potential pathway to increasing AMR. The central challenge involves ensuring animal health and welfare while securing the long-term effectiveness of antibiotics. This paper reports the results of a survey of 5693 respondents from the customer panels of four major UK supermarkets regarding preferences and attitudes towards antibiotic use in food animals, and their perspectives on how the balance between animal welfare and human benefit can be achieved. The results of these surveys are consistent with those from other countries that found that consumers generally have limited knowledge about antibiotic use in agriculture and AMR, with around 50% responding “don’t know” to many questions. There was agreement about the benefits of antibiotics outweighing harm, with 40% agreeing that, overall, the use of antibiotics to treat disease in farm animals delivers more benefit than harm. However, 44% neither agreed nor disagreed, indicating a high level of uncertainty and a situation that is potentially unstable. The seriousness of the AMR challenge is such that continued action for the more discriminating use of antibiotics must continue. Full article

(This article belongs to the Special Issue Epidemiology, Impact and Mitigation of Antimicrobial Resistance in Veterinary Medicine, 2nd Edition)

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12 pages, 855 KiB

Open AccessArticle

Molecular Characterisation of Antimicrobial Resistance in E. coli Isolates from Piglets in the West Region of Romania

by Bianca Cornelia Lungu, Ioan Hutu and Paul Andrew Barrow

Antibiotics 2023, 12(10), 1544; https://doi.org/10.3390/antibiotics12101544 - 15 Oct 2023

Cited by 2 | Viewed by 2254 | Correction

Abstract

Antibiotics are widely used for prophylaxis and therapy, reducing morbidity and mortality produced by bacterial pathogensin pigs, including infections caused by Escherichia coli. The aim of this study was to characterise antibiotic resistance phenotypes and genotypes in E. coli isolates in pigs [...] Read more.

Antibiotics are widely used for prophylaxis and therapy, reducing morbidity and mortality produced by bacterial pathogensin pigs, including infections caused by Escherichia coli. The aim of this study was to characterise antibiotic resistance phenotypes and genotypes in E. coli isolates in pigs in West Romanian grower farms. Differential phenotypic susceptibility profiles and the contribution of resistance genes to phenotypic expression of susceptibility or resistance were evaluated. A total of 76 E. coli isolates were identified and confirmed by the MicroScan Walk Away System. The occurrence of four resistance genes, ampC, blaZ, blaTEM and tetK in strains resistant to 13 antibiotics was assessed. Of the E. coli isolates, 0% showed resistance to meropenem, 3.9% to tigecycline and 10.5% to piperacillin/tazobactam, whereas, in contrast, 100% were resistant to ampicillin and mezlocillin, 76.31% to piperacillin and 59.3% to tetracycline. The prevalence of resistance genes in resistant isolates detected by q-PCR analysis was 97.0% for ampC, 96% for blaZ, 32.9% for blaTEM and 58.8% for tetK. Penetrance (the proportion of individuals carrying a particular variant of a gene that also expresses an associated trait) was 50% for ampC (32% for amoxicillin/clavulanate, 62% for cefazolin, 32% for cefepime, 100% for cefotaxime, 56% for cefuroxime and 99% for ampicillin), 65% for blaZ (32% for amoxicillin/clavulanate and 99% for ampicillin), 51% for blaTEM (81% for piperacillin) and 44% for the tetK gene (83% for tetracycline). The result of phenotypic antibiotic resistance testing may indicate the presence of plasmid-borne resistance, with a diagnostic odds ratio of a positive phenotypic resistance for tetK being 4.52. As a management decision, the maximum penetrance admitted for using a specific antibiotic for E. coli infections in pigs is recommended to be less than 20%. Full article

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21 pages, 2144 KiB

Open AccessReview

Inorganic Nanoparticles: Tools to Emphasize the Janus Face of Amphotericin B

by Ariane Boudier, Nour Mammari, Emmanuel Lamouroux and Raphaël E. Duval

Antibiotics 2023, 12(10), 1543; https://doi.org/10.3390/antibiotics12101543 - 15 Oct 2023

Viewed by 1615

Abstract

Amphotericin B is the oldest antifungal molecule which is still currently widely used in clinical practice, in particular for the treatment of invasive diseases, even though it is not devoid of side effects (particularly nephrotoxicity). Recently, its redox properties (i.e., both prooxidant and [...] Read more.

Amphotericin B is the oldest antifungal molecule which is still currently widely used in clinical practice, in particular for the treatment of invasive diseases, even though it is not devoid of side effects (particularly nephrotoxicity). Recently, its redox properties (i.e., both prooxidant and antioxidant) have been highlighted in the literature as mechanisms involved in both its activity and its toxicity. Interestingly, similar properties can be described for inorganic nanoparticles. In the first part of the present review, the redox properties of Amphotericin B and inorganic nanoparticles are discussed. Then, in the second part, inorganic nanoparticles as carriers of the drug are described. A special emphasis is given to their combined redox properties acting either as a prooxidant or as an antioxidant and their connection to the activity against pathogens (i.e., fungi, parasites, and yeasts) and to their toxicity. In a majority of the published studies, inorganic nanoparticles carrying Amphotericin B are described as having a synergistic activity directly related to the rupture of the redox homeostasis of the pathogen. Due to the unique properties of inorganic nanoparticles (e.g., magnetism, intrinsic anti-infectious properties, stimuli-triggered responses, etc.), these nanomaterials may represent a new generation of medicine that can synergistically enhance the antimicrobial properties of Amphotericin B. Full article

(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)

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11 pages, 1357 KiB

Open AccessArticle

Extended Versus Intermittent Meropenem Infusion in the Treatment of Nosocomial Pneumonia: A Retrospective Single-Center Study

by Dong-gon Hyun, Jarim Seo, Su Yeon Lee, Jee Hwan Ahn, Sang-Bum Hong, Chae-Man Lim, Younsuck Koh and Jin Won Huh

Antibiotics 2023, 12(10), 1542; https://doi.org/10.3390/antibiotics12101542 - 15 Oct 2023

Cited by 1 | Viewed by 2830

Abstract

The efficacy of extended meropenem infusions in patients with nosocomial pneumonia is not well defined. Therefore, we compared the clinical outcomes of extended versus intermittent meropenem infusions in the treatment of nosocomial pneumonia. We performed a retrospective analysis of extended versus intermittent meropenem [...] Read more.

The efficacy of extended meropenem infusions in patients with nosocomial pneumonia is not well defined. Therefore, we compared the clinical outcomes of extended versus intermittent meropenem infusions in the treatment of nosocomial pneumonia. We performed a retrospective analysis of extended versus intermittent meropenem infusions in adult patients who had been treated for nosocomial pneumonia at a medical ICU between 1 May 2018 and 30 April 2020. The primary outcome was mortality at 14 days. Overall, 64 patients who underwent an extended infusion and 97 with an intermittent infusion were included in this study. At 14 days, 10 (15.6%) patients in the extended group and 22 (22.7%) in the intermittent group had died (adjusted hazard ratio (HR), 0.55; 95% confidence interval (CI): 0.23–1.31; p = 0.174). In the subgroup analysis, significant differences in mortality at day 14 were observed in patients following empirical treatment with meropenem (adjusted HR, 0.17; 95% CI: 0.03–0.96; p = 0.045) and in Gram-negative pathogens identified by blood or sputum cultures (adjusted HR, 0.01; 95% CI: 0.01–0.83; p = 0.033). Extended infusion of meropenem compared with intermittent infusion as a treatment option for nosocomial pneumonia may have a potential advantage in specific populations. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Therapy in Intensive Care Unit)

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23 pages, 2589 KiB

Open AccessArticle

Molecular Epidemiologic and Geo-Spatial Characterization of Staphylococcus aureus Cultured from Skin and Soft Tissue Infections from United States-Born and Immigrant Patients Living in New York City

by Lilly Cheng Immergluck, Xiting Lin, Ruijin Geng, Mike Edelson, Fatima Ali, Chaohua Li, TJ Lin, Chamanara Khalida, Nancy Piper-Jenks, Maria Pardos de la Gandara, Herminia de Lencastre, Alexander Tomasz, Teresa H. Evering, Rhonda G. Kost, Roger Vaughan and Jonathan N. Tobin

Antibiotics 2023, 12(10), 1541; https://doi.org/10.3390/antibiotics12101541 - 14 Oct 2023

Viewed by 2081

Abstract

(1) Background: With increasing international travel and mass population displacement due to war, famine, climate change, and immigration, pathogens, such as Staphylococcus aureus (S. aureus), can also spread across borders. Methicillin-resistant S. aureus (MRSA) most commonly causes skin and soft tissue [...] Read more.

(1) Background: With increasing international travel and mass population displacement due to war, famine, climate change, and immigration, pathogens, such as Staphylococcus aureus (S. aureus), can also spread across borders. Methicillin-resistant S. aureus (MRSA) most commonly causes skin and soft tissue infections (SSTIs), as well as more invasive infections. One clonal strain, S. aureus USA300, originating in the United States, has spread worldwide. We hypothesized that S. aureus USA300 would still be the leading clonal strain among US-born compared to non-US-born residents, even though risk factors for SSTIs may be similar in these two populations (2) Methods: In this study, 421 participants presenting with SSTIs were enrolled from six community health centers (CHCs) in New York City. The prevalence, risk factors, and molecular characteristics for MRSA and specifically clonal strain USA300 were examined in relation to the patients’ self-identified country of birth. (3) Results: Patients born in the US were more likely to have S. aureus SSTIs identified as MRSA USA300. While being male and sharing hygiene products with others were also significant risks for MRSA SSTI, we found exposure to animals, such as owning a pet or working at an animal facility, was specifically associated with risk for SSTIs caused by MRSA USA300. Latin American USA300 variant (LV USA300) was most common in participants born in Latin America. Spatial analysis showed that MRSA USA300 SSTI cases were more clustered together compared to other clonal types either from MRSA or methicillin-sensitive S. aureus (MSSA) SSTI cases. (4) Conclusions: Immigrants with S. aureus infections have unique risk factors and S. aureus molecular characteristics that may differ from US-born patients. Hence, it is important to identify birthplace in MRSA surveillance and monitoring. Spatial analysis may also capture additional information for surveillance that other methods do not. Full article

(This article belongs to the Special Issue Staphylococcus aureus Skin and Soft Tissue Infections Pathogenesis and Therapeutic Approaches)

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28 pages, 464 KiB

Open AccessArticle

A Narrative Review of Antibiotic Prescribing Practices in Primary Care Settings in South Africa and Potential Ways Forward to Reduce Antimicrobial Resistance

by Audrey Chigome, Nishana Ramdas, Phumzile Skosana, Aislinn Cook, Natalie Schellack, Stephen Campbell, Giulia Lorenzetti, Zikria Saleem, Brian Godman and Johanna C. Meyer

Antibiotics 2023, 12(10), 1540; https://doi.org/10.3390/antibiotics12101540 - 14 Oct 2023

Cited by 9 | Viewed by 3091

Abstract

There are concerns with the current prescribing of antibiotics in both the private and public primary care settings in South Africa. These concerns need to be addressed going forward to reduce rising antimicrobial resistance (AMR) rates in South Africa. Concerns include adherence to [...] Read more.

There are concerns with the current prescribing of antibiotics in both the private and public primary care settings in South Africa. These concerns need to be addressed going forward to reduce rising antimicrobial resistance (AMR) rates in South Africa. Concerns include adherence to current prescribing guidelines. Consequently, there is a need to comprehensively summarise current antibiotic utilization patterns from published studies as well as potential activities to improve prescribing, including indicators and antimicrobial stewardship programs (ASPs). Published studies showed that there was an appreciable prescribing of antibiotics for patients with acute respiratory infections, i.e., 52.9% to 78% or more across the sectors. However, this was not universal, with appreciable adherence to prescribing guidelines in community health centres. Encouragingly, the majority of antibiotics prescribed, albeit often inappropriately, were from the ‘Access’ group of antibiotics in the AWaRe (Access/Watch/Reserve) classification rather than ‘Watch’ antibiotics to limit AMR. Inappropriate prescribing of antibiotics in primary care is not helped by concerns with current knowledge regarding antibiotics, AMR and ASPs among prescribers and patients in primary care. This needs to be addressed going forward. However, studies have shown it is crucial for prescribers to use a language that patients understand when discussing key aspects to enhance appropriate antibiotic use. Recommended activities for the future include improved education for all groups as well as regularly monitoring prescribing against agreed-upon guidelines and indicators. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Clinical Infection and Antibiotic Stewardship)

11 pages, 1317 KiB

Open AccessArticle

Inhibition of Acinetobacter baumannii Biofilm Formation by Terpenes from Oregano (Lippia graveolens) Essential Oil

by Melvin Roberto Tapia-Rodriguez, Ernesto Uriel Cantu-Soto, Francisco Javier Vazquez-Armenta, Ariadna Thalia Bernal-Mercado and Jesus Fernando Ayala-Zavala

Antibiotics 2023, 12(10), 1539; https://doi.org/10.3390/antibiotics12101539 - 14 Oct 2023

Cited by 9 | Viewed by 2164

Abstract

Acinetobacter baumannii is a nosocomial pathogen known for its ability to form biofilms, leading to persistent infections and antibiotic resistance. The limited effective antibiotics have encouraged the development of innovative strategies such as using essential oils and their constituents. This study evaluated the [...] Read more.

Acinetobacter baumannii is a nosocomial pathogen known for its ability to form biofilms, leading to persistent infections and antibiotic resistance. The limited effective antibiotics have encouraged the development of innovative strategies such as using essential oils and their constituents. This study evaluated the efficacy of oregano (Lippia graveolens) essential oil (OEO) and its terpene compounds, carvacrol and thymol, in inhibiting A. baumannii biofilms. These treatments showed a minimum inhibitory concentration of 0.6, 0.3, and 2.5 mg/mL and a minimum bactericidal concentration of 1.2, 0.6, and 5 mg/mL, respectively. Sub-inhibitory doses of each treatment and the OEO significantly reduced biofilm biomass and the covered area of A. baumannii biofilms as measured by fluorescence microscopy. Carvacrol at 0.15 mg/mL exhibited the most potent efficacy, achieving a remarkable 95% reduction. Sub-inhibitory concentrations of carvacrol significantly reduced the biofilm formation of A. baumannii in stainless steel surfaces by up to 1.15 log CFU/cm² compared to untreated bacteria. The OEO and thymol exhibited reductions of 0.6 log CFU/cm² and 0.4 log CFU/cm², respectively, without affecting cell viability. Moreover, the terpenes inhibited twitching motility, a crucial step in biofilm establishment, with carvacrol exhibiting the highest inhibition, followed by OEO and thymol. The study provides valuable insights into the potential of terpenes as effective agents against A. baumannii biofilms, offering promising avenues for developing novel strategies to prevent persistent infections and overcome antibiotic resistance. Full article

(This article belongs to the Section Plant-Derived Antibiotics)

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17 pages, 1019 KiB

Open AccessEditor’s ChoiceArticle

Antimicrobial Susceptibility to 27 Drugs and the Molecular Mechanisms of Macrolide, Tetracycline, and Quinolone Resistance in Gemella sp.

by Michiko Furugaito, Yuko Arai, Yutaka Uzawa, Toshinori Kamisako, Kohei Ogura, Shigefumi Okamoto and Ken Kikuchi

Antibiotics 2023, 12(10), 1538; https://doi.org/10.3390/antibiotics12101538 - 14 Oct 2023

Cited by 3 | Viewed by 2922 | Correction

Abstract

Gemella is a catalase-negative, facultative anaerobic, Gram-positive coccus that is commensal in humans but can become opportunistic and cause severe infectious diseases, such as infective endocarditis. Few studies have tested the antimicrobial susceptibility of Gemella. We tested its antimicrobial susceptibility to 27 [...] Read more.

Gemella is a catalase-negative, facultative anaerobic, Gram-positive coccus that is commensal in humans but can become opportunistic and cause severe infectious diseases, such as infective endocarditis. Few studies have tested the antimicrobial susceptibility of Gemella. We tested its antimicrobial susceptibility to 27 drugs and defined the resistant genes using PCR in 58 Gemella strains, including 52 clinical isolates and six type strains. The type strains and clinical isolates included 22 G. morbillorum, 18 G. haemolysans (GH) group (genetically indistinguishable from G. haemolysans and G. parahaemolysans), 13 G. taiwanensis, three G. sanguinis, and two G. bergeri. No strain was resistant to beta-lactams and vancomycin. In total, 6/22 (27.3%) G. morbillorum strains were erythromycin- and clindamycin-resistant ermB-positive, whereas 4/18 (22.2%) in the GH group, 7/13 (53.8%) G. taiwanensis, and 1/3 (33.3%) of the G. sanguinis strains were erythromycin-non-susceptible mefE- or mefA-positive and clindamycin-susceptible. The MIC₉₀ of minocycline and the ratios of tetM-positive strains varied across the different species—G. morbillorum: 2 µg/mL and 27.3% (6/22); GH group: 8 µg/mL and 27.8% (5/18); G. taiwanensis: 8 µg/mL and 46.2% (6/13), respectively. Levofloxacin resistance was significantly higher in G. taiwanensis (9/13 69.2%) than in G. morbillorum (2/22 9.1%). Levofloxacin resistance was associated with a substitution at serine 83 for leucine, phenylalanine, or tyrosine in GyrA. The mechanisms of resistance to erythromycin and clindamycin differed across Gemella species. In addition, the rate of susceptibility to levofloxacin differed across Gemella sp., and the quinolone resistance mechanism was caused by mutations in GyrA alone. Full article

(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)

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12 pages, 2066 KiB

Open AccessArticle

The Economic Value of Antimicrobial Use in Livestock Production

by Jamal L. Roskam, Alfons G. J. M. Oude Lansink and Helmut W. Saatkamp

Antibiotics 2023, 12(10), 1537; https://doi.org/10.3390/antibiotics12101537 - 13 Oct 2023

Viewed by 1659

Abstract

(1) Introduction: Antimicrobial agents have played an important role in improving the productivity of worldwide livestock production by reducing the impact of livestock diseases. However, a major drawback of antimicrobial use is the emergence of antimicrobial-resistant pathogens in food-producing animals. To reduce the [...] Read more.

(1) Introduction: Antimicrobial agents have played an important role in improving the productivity of worldwide livestock production by reducing the impact of livestock diseases. However, a major drawback of antimicrobial use is the emergence of antimicrobial-resistant pathogens in food-producing animals. To reduce the use of antimicrobials, it is important to know the economic value of the use of antimicrobials and factors that determine that economic value. (2) Results: A theoretical framework was developed to assess the economic value of antimicrobial use. Three situations were distinguished: firstly, a baseline model for a farm with a conventional production system; secondly, an extension of the baseline model that includes the impact of production system improvements; and thirdly, an extension of the baseline model that includes the impacts of risk and risk attitude. This framework shows that the economic value of antimicrobial use is negatively affected by the price of productive inputs and damage-abatement inputs, and positively affected by the output price, the input–output combination, the damage abatement effect, risk aversion and variance in profit. (3) Conclusions: The theoretical framework presented in this study shows that there are several factors that (can) affect the economic value of antimicrobial use. The knowledge about the effect of these factors can be utilized to affect the economic value of antimicrobials and, consequently, affect antimicrobial use. Full article

(This article belongs to the Special Issue Epidemiology, Impact and Mitigation of Antimicrobial Resistance in Veterinary Medicine, 2nd Edition)

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9 pages, 483 KiB

Open AccessArticle

The Association of Procalcitonin and C-Reactive Protein with Bacterial Infections Acquired during Intensive Care Unit Stay in COVID-19 Critically Ill Patients

by Simone Campani, Marta Talamonti, Lorenzo Dall’Ara, Irene Coloretti, Ilenia Gatto, Emanuela Biagioni, Martina Tosi, Marianna Meschiari, Roberto Tonelli, Enrico Clini, Andrea Cossarizza, Giovanni Guaraldi, Cristina Mussini, Mario Sarti, Tommaso Trenti and Massimo Girardis

Antibiotics 2023, 12(10), 1536; https://doi.org/10.3390/antibiotics12101536 - 12 Oct 2023

Cited by 1 | Viewed by 1831

Abstract

In COVID-19 patients, procalcitonin (PCT) and C-reactive protein (CRP) performance in identifying bacterial infections remains unclear. Our study aimed to evaluate the association of PCT and CRP with secondary infections acquired during ICU stay in critically ill COVID-19 patients. This observational study included [...] Read more.

In COVID-19 patients, procalcitonin (PCT) and C-reactive protein (CRP) performance in identifying bacterial infections remains unclear. Our study aimed to evaluate the association of PCT and CRP with secondary infections acquired during ICU stay in critically ill COVID-19 patients. This observational study included adult patients admitted to three COVID-19 intensive care units (ICUs) from February 2020 to May 2022 with respiratory failure caused by SARS-CoV-2 infection and ICU stay ≥ 11 days. The values of PCT and CRP collected on the day of infection diagnosis were compared to those collected on day 11 after ICU admission, the median time for infection occurrence, in patients without secondary infection. The receiver operating characteristic curve (ROC) and multivariate logistic model were used to assess PCT and CRP association with secondary infections. Two hundred and seventy-nine patients were included, of whom 169 (60.6%) developed secondary infection after ICU admission. The PCT and CRP values observed on the day of the infection diagnosis were larger (p < 0.001) than those observed on day 11 after ICU admission in patients without secondary infections. The ROC analysis calculated an AUC of 0.744 (95%CI 0.685–0.803) and 0.754 (95%CI 0.695–0.812) for PCT and CRP, respectively. Multivariate logistic models showed that PCT ≥ 0.16 ng/mL and CRP ≥ 1.35 mg/dL were associated (p < 0.001) with infections acquired during ICU stay. Our results indicated that in COVID-19 patients, PCT and CRP values were associated with infections acquired during the ICU stay and can be used to support, together with clinical signs, rather than predict or rule out, the diagnosis of these infections. Full article

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

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22 pages, 1216 KiB

Open AccessArticle

Ligilactobacillus salivarius 7247 Strain: Probiotic Properties and Anti-Salmonella Effect with Prebiotics

by Vyacheslav M. Abramov, Igor V. Kosarev, Andrey V. Machulin, Evgenia I. Deryusheva, Tatiana V. Priputnevich, Alexander N. Panin, Irina O. Chikileva, Tatiana N. Abashina, Ashot M. Manoyan, Anna A. Ahmetzyanova, Olga E. Ivanova, Tigran T. Papazyan, Ilia N. Nikonov, Nataliya E. Suzina, Vyacheslav G. Melnikov, Valentin S. Khlebnikov, Vadim K. Sakulin, Vladimir A. Samoilenko, Alexey B. Gordeev, Gennady T. Sukhikh and Vladimir N. Uversky Show full author list Hide full author list

Antibiotics 2023, 12(10), 1535; https://doi.org/10.3390/antibiotics12101535 - 12 Oct 2023

Cited by 4 | Viewed by 2204

Abstract

The Ligilactobacillus salivarius 7247 (LS7247) strain, originally isolated from a healthy woman’s intestines and reproductive system, has been studied for its probiotic potential, particularly against Salmonella Enteritidis (SE) and Salmonella Typhimurium (ST) as well as its potential use in synbiotics. LS7247 showed high [...] Read more.

The Ligilactobacillus salivarius 7247 (LS7247) strain, originally isolated from a healthy woman’s intestines and reproductive system, has been studied for its probiotic potential, particularly against Salmonella Enteritidis (SE) and Salmonella Typhimurium (ST) as well as its potential use in synbiotics. LS7247 showed high tolerance to gastric and intestinal stress and effectively adhered to human and animal enterocyte monolayers, essential for realizing its probiotic properties. LS7247 showed high anti-Salmonella activity. Additionally, the cell-free culture supernatant (CFS) of LS7247 exhibited anti-Salmonella activity, with a partial reduction upon neutralization with NaOH (p < 0.05), suggesting the presence of anti-Salmonella factors such as lactic acid (LA) and bacteriocins. LS7247 produced a high concentration of LA, reaching 124.0 ± 2.5 mM after 48 h of cultivation. Unique gene clusters in the genome of LS7247 contribute to the production of Enterolysin A and metalloendopeptidase. Notably, LS7247 carries a plasmid with a gene cluster identical to human intestinal strain L. salivarius UCC118, responsible for class IIb bacteriocin synthesis, and a gene cluster identical to porcine strain L. salivarius P1ACE3, responsible for nisin S synthesis. Co-cultivation of LS7247 with SE and ST pathogens reduced their viability by 1.0–1.5 log, attributed to cell wall damage and ATP leakage caused by the CFS. For the first time, the CFS of LS7247 has been shown to inhibit adhesion of SE and ST to human and animal enterocytes (p < 0.01). The combination of Actigen prebiotic and the CFS of LS7247 demonstrated a significant combined effect in inhibiting the adhesion of SE and ST to human and animal enterocytes (p < 0.001). These findings highlight the potential of using the LS7247 as a preventive strategy and employing probiotics and synbiotics to combat the prevalence of salmonellosis in animals and humans caused by multidrug resistant (MDR) strains of SE and ST pathogens. Full article

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14 pages, 4654 KiB

Open AccessArticle

Aerosol Inhalation Delivery of Ag Nanoparticles in Mice: Pharmacokinetics and Antibacterial Action

by Sergey V. Valiulin, Andrei A. Onischuk, Alexandra P. Pyryaeva, Sergey V. An’kov, Anatoly M. Baklanov, Nikolay N. Shkil, Ekaterina V. Nefedova, Kirill S. Ershov, Tatyana G. Tolstikova and Galina G. Dultseva

Antibiotics 2023, 12(10), 1534; https://doi.org/10.3390/antibiotics12101534 - 12 Oct 2023

Viewed by 1424

Abstract

The aerosol inhalation delivery of composite particles consisting of Ag nanoparticles enveloped by polyvinylpyrrolidone was investigated in experiments with mice. An ultrasonic nebulizing system was created for the generation of aerosols with a mean diameter and mass concentration of 700 ± 50 nm [...] Read more.

The aerosol inhalation delivery of composite particles consisting of Ag nanoparticles enveloped by polyvinylpyrrolidone was investigated in experiments with mice. An ultrasonic nebulizing system was created for the generation of aerosols with a mean diameter and mass concentration of 700 ± 50 nm and 65 ± 5 mg/m³, respectively. The mass fraction of Ag in the composite particles was α = 0.061. The aerosol delivery was performed in a whole-body chamber with an exposition time of 20 min. Pharmacokinetic measurements were taken and the silver concentrations in the blood and lungs of the mice were measured as a function of time after exposition by means of electrothermal (graphite furnace) atomic absorption spectrometry. The inhalation dose and other pharmacokinetic parameters were determined. The antibacterial effect of aerosolized silver was assessed for mice infected with Klebsiella pneumoniae 82 and Staphylococcus aureus ATCC 25953. The survival rate of the infected mice after the aerosol exposure demonstrated the high antibacterial efficiency of Ag nanoparticles after inhalation delivery. Full article

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9 pages, 1031 KiB

Open AccessPerspective

The Role of Biofilms in Contact Lens Associated Fungal Keratitis

by Jipan Yi, Yao Sun, Chenghong Zeng, Xenia Kostoulias and Yue Qu

Antibiotics 2023, 12(10), 1533; https://doi.org/10.3390/antibiotics12101533 - 12 Oct 2023

Cited by 3 | Viewed by 2303

Abstract

Biofilm formation is an important microbial strategy for fungal pathogens, such as Fusarium, Aspergillus, and Candida, to establish keratitis in patients wearing soft contact lenses. Despite the well-documented 2006 outbreak of Fusarium keratitis that eventually led to the withdrawal of [...] Read more.

Biofilm formation is an important microbial strategy for fungal pathogens, such as Fusarium, Aspergillus, and Candida, to establish keratitis in patients wearing soft contact lenses. Despite the well-documented 2006 outbreak of Fusarium keratitis that eventually led to the withdrawal of the Bausch & Lomb multipurpose lens care solution ReNu with MoistureLoc (“MoistureLoc”) from the global market, contact lens care systems and solutions currently available on the market do not specifically target fungal biofilms. This is partially due to the lack of recognition and understanding of important roles that fungal biofilms play in contact lens associated fungal keratitis (CLAFK). This review aims to reemphasize the link between fungal biofilms and CLAFK, and deepen our comprehension of its importance in pathogenesis and persistence of this medical device-related infection. Full article

(This article belongs to the Collection Antimicrobial Resistance and Anti-Biofilms)

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18 pages, 3389 KiB

Open AccessEditor’s ChoiceArticle

Modified CLEC3A-Derived Antimicrobial Peptides Lead to Enhanced Antimicrobial Activity against Drug-Resistant Bacteria

by Denise Meinberger, Marco G. Drexelius, Joshua Grabeck, Gabriele Hermes, Annika Roth, Dzemal Elezagic, Ines Neundorf, Thomas Streichert and Andreas R. Klatt

Antibiotics 2023, 12(10), 1532; https://doi.org/10.3390/antibiotics12101532 - 11 Oct 2023

Cited by 3 | Viewed by 1945

Abstract

Antimicrobial peptides (AMPs) represent a promising alternative to conventional antibiotics. Sequence changes can significantly improve the therapeutic properties of antimicrobial peptides. In our study, we apply different sequence modifications to enhance the performance of the CLEC3A-derived AMPs HT-16 and HT-47. We truncated their [...] Read more.

Antimicrobial peptides (AMPs) represent a promising alternative to conventional antibiotics. Sequence changes can significantly improve the therapeutic properties of antimicrobial peptides. In our study, we apply different sequence modifications to enhance the performance of the CLEC3A-derived AMPs HT-16 and HT-47. We truncated their sequences, inserting a triple-glycine linker, adding an N-terminal tryptophan residue, and generating a D-amino acid variant, resulting in the generation of seven new peptides. We investigated their antimicrobial activity against gram-positive and gram-negative bacteria, their cytotoxicity to murine cells, and the biostability of the modified peptides in serum. We identified a novel antimicrobial peptide, WRK-30, with enhanced antimicrobial potency against S. aureus and MRSA. Additionally, WRK-30 was less cytotoxic to eukaryotic cells, allowing its application in higher concentrations in an in vivo setting. In conclusion, we identified a novel CLEC3A-derived antimicrobial peptide WRK-30 with significantly improved therapeutic properties and the potential to widen the repertoire of conventional antibiotics. Full article

(This article belongs to the Special Issue Design, Modification and Application of Antimicrobial Peptides)

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13 pages, 298 KiB

Open AccessArticle

Rational Drug and Antibiotic Use Status, E-Health Literacy in Syrian Immigrants and Related Factors: A Cross-Sectional Study

by Mehmet Sait Değer, Mehmet Akif Sezerol and Muhammed Atak

Antibiotics 2023, 12(10), 1531; https://doi.org/10.3390/antibiotics12101531 - 11 Oct 2023

Cited by 4 | Viewed by 1848

Abstract

Rational drug use is a pivotal concept linked with morbidity and mortality. Immigration plays a significant role as a determinant affecting individuals’ health-related attitudes, behaviors, and the pursuit of health services. Within this context, the study was initiated to assess the factors influencing [...] Read more.

Rational drug use is a pivotal concept linked with morbidity and mortality. Immigration plays a significant role as a determinant affecting individuals’ health-related attitudes, behaviors, and the pursuit of health services. Within this context, the study was initiated to assess the factors influencing health literacy and rational drug use among Syrian immigrants in Istanbul. A cross-sectional study was undertaken on 542 Syrian adults utilizing a three-part questionnaire encompassing sociodemographics, rational drug use, and the e-health literacy scale (eHEALS). With an average age of 39.19 ± 13.10 years, a majority of participants believed medications should solely be doctor-prescribed (97%) and opposed keeping antibiotics at home (93.7%). Yet, 62.5% thought excessive herbal medicine use was harmless. The mean eHEALS score stood at 20.57 ± 7.26, and factors like age, marital status, income, and duration of stay in Turkey influenced e-health literacy. Associations were seen between low e-health literacy and being female, being older, having a lower education level, and regular medication use. Syrian immigrants displayed proper knowledge concerning antibiotics yet exhibited gaps in their understanding of general drug usage, treatment adherence, and herbal medicines. Approximately 80.3% had limited health literacy, pointing to the need for targeted interventions for enhanced health and societal assimilation. Full article

(This article belongs to the Special Issue Feature Papers in Antibiotic Use in the Communities)

11 pages, 1553 KiB

Open AccessArticle

Streptococcus pyogenes Lineage ST62/emm87: The International Spread of This Potentially Invasive Lineage

by Caroline Lopes Martini, Deborah Nascimento Santos Silva, Alice Slotfeldt Viana, Paul Joseph Planet, Agnes Marie Sá Figueiredo and Bernadete Teixeira Ferreira-Carvalho

Antibiotics 2023, 12(10), 1530; https://doi.org/10.3390/antibiotics12101530 - 11 Oct 2023

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Abstract

Streptococcus pyogenes is known to be associated with a variety of infections, from pharyngitis to necrotizing fasciitis (flesh-eating disease). S. pyogenes of the ST62/emm87 lineage is recognized as one of the most frequently isolated lineages of invasive infections caused by this [...] Read more.

Streptococcus pyogenes is known to be associated with a variety of infections, from pharyngitis to necrotizing fasciitis (flesh-eating disease). S. pyogenes of the ST62/emm87 lineage is recognized as one of the most frequently isolated lineages of invasive infections caused by this bacterium, which may be involved in hospital outbreaks and cluster infections. Despite this, comparative genomic and phylogenomic studies have not yet been carried out for this lineage. Thus, its virulence and antimicrobial susceptibility profiles are mostly unknown, as are the genetic relationships and evolutionary traits involving this lineage. Previously, a strain of S. pyogenes ST62/emm87 (37–97) was characterized in our lab for its ability to generate antibiotic-persistent cells, and therapeutic failure in severe invasive infections caused by this bacterial species is well-reported in the scientific literature. In this work, we analyzed genomic and phylogenomic characteristics and evaluated the virulence and resistance profiles of ST62/emm87 S. pyogenes from Brazil and international sources. Here we show that strains that form this lineage (ST62/emm87) are internationally spread, involved in invasive outbreaks, and share important virulence profiles with the most common emm types of S. pyogenes, such as emm1, emm3, emm12, and emm69, which are associated with most invasive infections caused by this bacterial species in the USA and Europe. Accordingly, the continued increase of ST62/emm87 in severe S. pyogenes diseases should not be underestimated. Full article

(This article belongs to the Special Issue Streptococcus: Biology, Pathogenesis, Epidemiology and Evolution)

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Antibiotics, Volume 12, Issue 10 (October 2023) – 85 articles

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