Antibiotics

27 pages, 2030 KiB

Open AccessReview

Clinical Implications of Helicobacter pylori Antibiotic Resistance in Italy: A Review of the Literature

by Enrico Celestino Nista, Antonio Pellegrino, Lucia Giuli, Marcello Candelli, Tommaso Schepis, Sara Sofia De Lucia, Veronica Ojetti, Francesco Franceschi and Antonio Gasbarrini

Antibiotics 2022, 11(10), 1452; https://doi.org/10.3390/antibiotics11101452 - 21 Oct 2022

Cited by 7 | Viewed by 3158

Abstract

Helicobacter pylori (H. pylori) resistance to antibiotics has increased worldwide in recent decades, especially to clarithromycin. As a result, the World Health Organization (WHO) identified clarithromycin-resistant H. pylori as a “high priority” pathogen in 2017. As international guidelines recommend empirical therapy [...] Read more.

Helicobacter pylori (H. pylori) resistance to antibiotics has increased worldwide in recent decades, especially to clarithromycin. As a result, the World Health Organization (WHO) identified clarithromycin-resistant H. pylori as a “high priority” pathogen in 2017. As international guidelines recommend empirical therapy as first-line treatment, it is crucial to know local resistance rates and history of antibiotic use to determine the most appropriate first-line antibiotic treatment. Italy is one of the European countries with the highest prevalence of H. pylori infection and the highest percentage of antibiotic-resistant H. pylori. The aim of this review is to summarize all data on H. pylori antibiotic resistance in Italy in order to quantify the current rate and determine the most effective therapeutic approach. The study confirms an elevated level of resistance to clarithromycin, metronidazole, and levofloxacin in Italy. In addition, our results show a satisfactory eradication rate for a bismuth-based regimen when used as first- or second-line treatment. Naive patients are also successfully treated with clarithromycin-based quadruple therapies. Considering the good results of bismuth-based therapy as recovery therapy, this argues for the potential use of clarithromycin quadruple therapy as a first-line treatment. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

► Show Figures

Figure 1

30 pages, 1306 KiB

Open AccessReview

Recent Progress in the Discovery and Design of Antimicrobial Peptides Using Traditional Machine Learning and Deep Learning

by Jielu Yan, Jianxiu Cai, Bob Zhang, Yapeng Wang, Derek F. Wong and Shirley W. I. Siu

Antibiotics 2022, 11(10), 1451; https://doi.org/10.3390/antibiotics11101451 - 21 Oct 2022

Cited by 40 | Viewed by 7909

Abstract

Antimicrobial resistance has become a critical global health problem due to the abuse of conventional antibiotics and the rise of multi-drug-resistant microbes. Antimicrobial peptides (AMPs) are a group of natural peptides that show promise as next-generation antibiotics due to their low toxicity to [...] Read more.

Antimicrobial resistance has become a critical global health problem due to the abuse of conventional antibiotics and the rise of multi-drug-resistant microbes. Antimicrobial peptides (AMPs) are a group of natural peptides that show promise as next-generation antibiotics due to their low toxicity to the host, broad spectrum of biological activity, including antibacterial, antifungal, antiviral, and anti-parasitic activities, and great therapeutic potential, such as anticancer, anti-inflammatory, etc. Most importantly, AMPs kill bacteria by damaging cell membranes using multiple mechanisms of action rather than targeting a single molecule or pathway, making it difficult for bacterial drug resistance to develop. However, experimental approaches used to discover and design new AMPs are very expensive and time-consuming. In recent years, there has been considerable interest in using in silico methods, including traditional machine learning (ML) and deep learning (DL) approaches, to drug discovery. While there are a few papers summarizing computational AMP prediction methods, none of them focused on DL methods. In this review, we aim to survey the latest AMP prediction methods achieved by DL approaches. First, the biology background of AMP is introduced, then various feature encoding methods used to represent the features of peptide sequences are presented. We explain the most popular DL techniques and highlight the recent works based on them to classify AMPs and design novel peptide sequences. Finally, we discuss the limitations and challenges of AMP prediction. Full article

(This article belongs to the Special Issue Antimicrobial Peptides - Discovery, Structure, Function, and Application)

► Show Figures

Figure 1

46 pages, 2891 KiB

Open AccessArticle

Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant Staphylococcus aureus

by Steven A. Li, Rebecca J. Zheng, Kenneth Sue, Marie-Lise Bourguet-Kondracki, Azza Troudi, Jean Michel Brunel, Brent R. Copp and Melissa M. Cadelis

Antibiotics 2022, 11(10), 1450; https://doi.org/10.3390/antibiotics11101450 - 21 Oct 2022

Cited by 1 | Viewed by 1757

Abstract

Antibiotics have been the cornerstone of modern medicine saving lives by virtue of being able to cure infectious diseases and to prevent infections in those who are immune compromised. Their intense use has led to a surging increase in the incidence of antibiotic-resistant [...] Read more.

Antibiotics have been the cornerstone of modern medicine saving lives by virtue of being able to cure infectious diseases and to prevent infections in those who are immune compromised. Their intense use has led to a surging increase in the incidence of antibiotic-resistant bacteria resulting in a desperate need for antibiotics with new mechanisms of action. As part of our search for new antimicrobials we have screened an in-house library of compounds and identified two 3-substituted-1H-imidazol-5-yl-1H-indoles as weak growth inhibitors (MIC 16 µg/mL) against methicillin-resistant Staphylococcus aureus (MRSA). An extensive library of analogues was prepared using the Van Leusen three-component reaction, biological evaluation of which led to the identification of two analogues (26 and 32) with favorable anti-MRSA activity (MIC ≤ 0.25 µg/mL) which also lacked cytotoxic or hemolytic properties. The screening campaign also identified two derivatives, a phenethyl-indole-imidazole 57 and a 5-phenyl-1H-imidazole 111 that were non-toxic selective antifungals towards Cryptococcus neoformans. These results have identified 3-substituted-1H-imidazol-5-yl-1H-indoles and 5-phenyl-1H-imidazoles as new structural scaffolds for further investigation as anti-MRSA and anti-C. neoformans agents, respectively. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Drug Discovery)

► Show Figures

Graphical abstract

15 pages, 2146 KiB

Open AccessArticle

An Optimized Workflow for the Discovery of New Antimicrobial Compounds Targeting Bacterial RNA Polymerase Complex Formation

by Alessia Caputo, Sara Sartini, Elisabetta Levati, Ilaria Minato, Gian Marco Elisi, Adriana Di Stasi, Catherine Guillou, Peter G. Goekjian, Pierre Garcia, David Gueyrard, Stéphane Bach, Arnaud Comte, Simone Ottonello, Silvia Rivara and Barbara Montanini

Antibiotics 2022, 11(10), 1449; https://doi.org/10.3390/antibiotics11101449 - 21 Oct 2022

Cited by 4 | Viewed by 2968

Abstract

Bacterial resistance represents a major health problem worldwide and there is an urgent need to develop first-in-class compounds directed against new therapeutic targets. We previously developed a drug-discovery platform to identify new antimicrobials able to disrupt the protein–protein interaction between the β’ subunit [...] Read more.

Bacterial resistance represents a major health problem worldwide and there is an urgent need to develop first-in-class compounds directed against new therapeutic targets. We previously developed a drug-discovery platform to identify new antimicrobials able to disrupt the protein–protein interaction between the β’ subunit and the σ⁷⁰ initiation factor of bacterial RNA polymerase, which is essential for transcription. As a follow-up to such work, we have improved the discovery strategy to make it less time-consuming and more cost-effective. This involves three sequential assays, easily scalable to a high-throughput format, and a subsequent in-depth characterization only limited to hits that passed the three tests. This optimized workflow, applied to the screening of 5360 small molecules from three synthetic and natural compound libraries, led to the identification of six compounds interfering with the β’–σ⁷⁰ interaction, and thus was capable of inhibiting promoter-specific RNA transcription and bacterial growth. Upon supplementation with a permeability adjuvant, the two most potent transcription-inhibiting compounds displayed a strong antibacterial activity against Escherichia coli with minimum inhibitory concentration (MIC) values among the lowest (0.87–1.56 μM) thus far reported for β’–σ PPI inhibitors. The newly identified hit compounds share structural feature similarities with those of a pharmacophore model previously developed from known inhibitors. Full article

(This article belongs to the Special Issue New Antibiotic Compounds: Discovery and Strategies)

► Show Figures

Figure 1

15 pages, 2530 KiB

Open AccessArticle

Improvement of the Antibacterial Activity of Phage Lysin-Derived Peptide P87 through Maximization of Physicochemical Properties and Assessment of Its Therapeutic Potential

by Roberto Vázquez, Antonio Doménech-Sánchez, Susana Ruiz, Julio Sempere, Jose Yuste, Sebastián Albertí and Pedro García

Antibiotics 2022, 11(10), 1448; https://doi.org/10.3390/antibiotics11101448 - 21 Oct 2022

Cited by 5 | Viewed by 2461

Abstract

Phage lysins are a promising alternative to common antibiotic chemotherapy. However, they have been regarded as less effective against Gram-negative pathogens unless engineered, e.g., by fusing them to antimicrobial peptides (AMPs). AMPs themselves pose an alternative to antibiotics. In this work, AMP P87, [...] Read more.

Phage lysins are a promising alternative to common antibiotic chemotherapy. However, they have been regarded as less effective against Gram-negative pathogens unless engineered, e.g., by fusing them to antimicrobial peptides (AMPs). AMPs themselves pose an alternative to antibiotics. In this work, AMP P87, previously derived from a phage lysin (Pae87) with a presumed nonenzymatic mode-of-action, was investigated to improve its antibacterial activity. Five modifications were designed to maximize the hydrophobic moment and net charge, producing the modified peptide P88, which was evaluated in terms of bactericidal activity, cytotoxicity, MICs or synergy with antibiotics. P88 had a better bactericidal performance than P87 (an average of 6.0 vs. 1.5 log-killing activity on Pseudomonas aeruginosa strains treated with 10 µM). This did not correlate with a dramatic increase in cytotoxicity as assayed on A549 cell cultures. P88 was active against a range of P. aeruginosa isolates, with no intrinsic resistance factors identified. Synergy with some antibiotics was observed in vitro, in complex media, and in a respiratory infection mouse model. Therefore, P88 can be a new addition to the therapeutic toolbox of alternative antimicrobials against Gram-negative pathogens as a sole therapeutic, a complement to antibiotics, or a part to engineer proteinaceous antimicrobials. Full article

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

► Show Figures

Figure 1

13 pages, 2206 KiB

Open AccessArticle

New Insights into Listeria monocytogenes Antimicrobial Resistance, Virulence Attributes and Their Prospective Correlation

by Mahmoud E. Elsayed, Marwa I. Abd El-Hamid, Attia El-Gedawy, Mahmoud M. Bendary, Reham M. ELTarabili, Majid Alhomrani, Abdulhakeem S. Alamri, Saleh A. Alghamdi, Marwa Arnout, Dalal N. Binjawhar, Mohammad M. Al-Sanea and Amira I. Abousaty

Antibiotics 2022, 11(10), 1447; https://doi.org/10.3390/antibiotics11101447 - 21 Oct 2022

Cited by 9 | Viewed by 3244

Abstract

Listeriosis is one of the most common foodborne diseases caused by Listeria monocytogenes (L. monocytogenes). A poor prognosis has been recorded for the invasive listeriosis, especially neurolisteriosis. In several countries throughout the world, foodborne infections with L. monocytogenes exceeded the legal [...] Read more.

Listeriosis is one of the most common foodborne diseases caused by Listeria monocytogenes (L. monocytogenes). A poor prognosis has been recorded for the invasive listeriosis, especially neurolisteriosis. In several countries throughout the world, foodborne infections with L. monocytogenes exceeded the legal safety limits in animal sourced foods. Therefore, we decided to investigate the variability, virulence and antimicrobial resistance profiles of this pathogen. Both phenotypic and genotypic methods were used for identifying L. monocytogenes isolates and confirming their virulence profiles. The antimicrobial resistances and their correlation analysis with the existence of virulence genes were detected. Additionally, sequencing and phylogenetic analysis based on L. monocytogenes inlA and inlB genes were undertaken. The prevalence rate (11.9%) and the resistance profiles of L. monocytogenes were shocking. The multi-drug resistance (MDR) phenotypes were common among our isolates (64.9%). Fortunately, the resistance phenotypes were always associated with low virulence arrays and the MDR strains possessed low virulence fitness. Herein, the high genotypic and phenotypic diversity of L. monocytogenes isolates and their weak clonality and adaptability highlighted the difficulty in controlling and managing this pathogen. Therefore, it is important to add more restriction guidelines from national authorities on the consumption of ready to eat foods. Full article

(This article belongs to the Special Issue Pathogenic Bacteria: Genomics, Virulence Factors, and Antibiotic Resistance)

► Show Figures

Figure 1

7 pages, 713 KiB

Open AccessPerspective

Beyond Guidelines and Reports on Bacterial Co-/Superinfections in the Context of COVID-19: Why Uniformity Matters

by Johan Van Laethem, Denis Piérard and Sabine D. Allard

Antibiotics 2022, 11(10), 1446; https://doi.org/10.3390/antibiotics11101446 - 20 Oct 2022

Cited by 1 | Viewed by 1639

Abstract

Background: In the period following the declaration of the COVID-19 pandemic, more evidence became available on the epidemiology of bacterial co-/superinfections (bCSs) in hospitalized COVID-19 patients. Various European therapeutic guidelines were published, including guidance on rational antibiotic use. Methods: In this letter to [...] Read more.

Background: In the period following the declaration of the COVID-19 pandemic, more evidence became available on the epidemiology of bacterial co-/superinfections (bCSs) in hospitalized COVID-19 patients. Various European therapeutic guidelines were published, including guidance on rational antibiotic use. Methods: In this letter to the editor, we provide an overview of the largest meta-analyses or prospective studies reporting on bCS rates in COVID-19 patients and discuss why the reader should interpret the results of those reports with care. Moreover, we compare different national and international COVID-19 therapeutic guidelines from countries of the European Union. Specific attention is paid to guidance dedicated to rational antibiotic use. Results: We found a significant heterogeneity in studies reporting on the epidemiology of bCSs in COVID-19 patients. Moreover, European national and international guidelines differ strongly from each other, especially with regard to the content and extent of antibiotic guidance in hospitalized COVID-19 patients. Conclusion: A standardized way of reporting on bCSs and uniform European guidelines on rational antibiotic use in COVID-19 patients are crucial for antimicrobial stewardship teams to halt unnecessary antibiotic use in the COVID-19 setting. Full article

(This article belongs to the Special Issue Antibacterial Therapy in Adults with COVID-19)

► Show Figures

Figure 1

16 pages, 20026 KiB

Open AccessArticle

Lipid Microenvironment Modulates the Pore-Forming Ability of Polymyxin B

by Anastasiia A. Zakharova, Svetlana S. Efimova and Olga S. Ostroumova

Antibiotics 2022, 11(10), 1445; https://doi.org/10.3390/antibiotics11101445 - 20 Oct 2022

Cited by 7 | Viewed by 1800

Abstract

The ability of polymyxin B, an antibiotic used to treat infections caused by multidrug-resistant Gram-negative bacteria as a last-line therapeutic option, to form ion pores in model membranes composed of various phospholipids and lipopolysaccharides was studied. Our data demonstrate that polymyxin B predominantly [...] Read more.

The ability of polymyxin B, an antibiotic used to treat infections caused by multidrug-resistant Gram-negative bacteria as a last-line therapeutic option, to form ion pores in model membranes composed of various phospholipids and lipopolysaccharides was studied. Our data demonstrate that polymyxin B predominantly interacts with negatively charged lipids. Susceptibility decreases as follows: Kdo₂-Lipid A >> DOPG ≈ DOPS >> DPhPG ≈ TOCL ≈ Lipid A. The dimer and hexamer of polymyxin B are involved in the pore formation in DOPG(DOPS)- and Kdo₂-Lipid A-enriched bilayers, respectively. The pore-forming ability of polymyxin B significantly depends on the shape of membrane lipids, which indicates that the antibiotic produces toroidal lipopeptide-lipid pores. Small amphiphilic molecules diminishing the membrane dipole potential and inducing positive curvature stress were shown to be agonists of pore formation by polymyxin B and might be used to develop innovative lipopeptide-based formulations. Full article

(This article belongs to the Special Issue Mechanisms of Antimicrobial Peptides on Pathogens, 2nd Edition)

► Show Figures

Figure 1

9 pages, 1500 KiB

Open AccessCommunication

Genome Mining Discovery of a New Benzazepine Alkaloid Pseudofisnin A from the Marine Fungus Neosartorya pseudofischeri F27-1

by Xiao-Xin Xue, Lin Chen and Man-Cheng Tang

Antibiotics 2022, 11(10), 1444; https://doi.org/10.3390/antibiotics11101444 - 20 Oct 2022

Cited by 4 | Viewed by 1870

Abstract

l-Kynurenine (Kyn) is an intermediate in the kynurenine pathway and is also found to be a building block or biosynthetic precursor to bioactive natural products. Recent studies revealed that l-Kyn can be incorporated via nonribosomal peptide synthetase (NRPS) biosynthetic routes to [...] Read more.

l-Kynurenine (Kyn) is an intermediate in the kynurenine pathway and is also found to be a building block or biosynthetic precursor to bioactive natural products. Recent studies revealed that l-Kyn can be incorporated via nonribosomal peptide synthetase (NRPS) biosynthetic routes to generate 1-benzazepine-containing compounds, while 1-benzazepine is a pharmaceutically important scaffold that is rarely found in natural products. Using a core biosynthetic enzyme-guided genome-mining approach, we discovered a biosynthetic gene cluster from Neosartorya pseudofischeri and identified that it encodes for the biosynthesis of pseudofisnins, novel 1-benzazepine-containing compounds. The biosynthetic pathway of pseudofisnins was elucidated through in vivo and in vitro experiments. The methyltransferase PseC from the pathway was biochemically characterized to be an iterative methyltransferase that catalyzes off-NRPS line di-methylation on an amine group. Full article

(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)

► Show Figures

Figure 1

20 pages, 20675 KiB

Open AccessArticle

Emergence of a Novel Lineage and Wide Spread of a bla_CTX-M-15/IncHI2/ST1 Plasmid among Nosocomial Enterobacter in Guadeloupe

by Matthieu Pot, Yann Reynaud, David Couvin, Alexis Dereeper, Séverine Ferdinand, Sylvaine Bastian, Tania Foucan, Jean-David Pommier, Marc Valette, Antoine Talarmin, Stéphanie Guyomard-Rabenirina and Sébastien Breurec

Antibiotics 2022, 11(10), 1443; https://doi.org/10.3390/antibiotics11101443 - 20 Oct 2022

Cited by 4 | Viewed by 2794

Abstract

Between April 2018 and August 2019, a total of 135 strains of Enterobacter cloacae complex (ECC) were randomly collected at the University Hospital Center of Guadeloupe to investigate the structure and diversity of the local bacterial population. These nosocomial isolates were initially identified [...] Read more.

Between April 2018 and August 2019, a total of 135 strains of Enterobacter cloacae complex (ECC) were randomly collected at the University Hospital Center of Guadeloupe to investigate the structure and diversity of the local bacterial population. These nosocomial isolates were initially identified genetically by the hsp60 typing method, which revealed the clinical relevance of E. xiangfangensis (n = 69). Overall, 57/94 of the third cephalosporin-resistant strains were characterized as extended-spectrum-β-lactamase (ESBL) producers, and their whole-genome was sequenced using Illumina technology to determine the clonal relatedness and diffusion of resistance genes. We found limited genetic diversity among sequence types (STs). ST114 (n = 13), ST1503 (n = 9), ST53 (n = 5) and ST113 (n = 4), which belong to three different Enterobacter species, were the most prevalent among the 57 ESBL producers. The bla_CTXM-15 gene was the most prevalent ESBL determinant (56/57) and was in most cases associated with IncHI2/ST1 plasmid replicon carriage (36/57). To fully characterize this predominant bla_CTXM-15/IncHI2/ST1 plasmid, four isolates from different lineages were also sequenced using Oxford Nanopore sequencing technology to generate long-reads. Hybrid sequence analyses confirmed the circulation of a well-conserved plasmid among ECC members. In addition, the novel ST1503 and its associated species (ECC taxon 4) were analyzed, in view of its high prevalence in nosocomial infections. These genetic observations confirmed the overall incidence of nosocomial ESBL Enterobacteriaceae infections acquired in this hospital during the study period, which was clearly higher in Guadeloupe (1.59/1000 hospitalization days) than in mainland France (0.52/1,000 hospitalization days). This project revealed issues and future challenges for the management and surveillance of nosocomial and multidrug-resistant Enterobacter in the Caribbean. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Healthcare Associated Infections)

► Show Figures

Figure 1

22 pages, 4546 KiB

Open AccessArticle

An Investigation into the Re-Emergence of Disease Following Cessation of Antibiotic Treatment in Balb/c Mice Infected with Inhalational Burkholderia pseudomallei

by Thomas R. Laws, Kay B. Barnes, Dominic C. Jenner, Alejandro Núñez, Mark I. Richards, Joanne E. Thwaite, Andreas Vente, David Rushton, Michelle Nelson and Sarah V. Harding

Antibiotics 2022, 11(10), 1442; https://doi.org/10.3390/antibiotics11101442 - 20 Oct 2022

Cited by 1 | Viewed by 2031

Abstract

Burkholderia pseudomallei is the causative agent of melioidosis, a multifaceted disease. A proportion of the mortality and morbidity reported as a result of infection with this organism may be due to the premature cessation of antibiotic therapy typically lasting for several months. The [...] Read more.

Burkholderia pseudomallei is the causative agent of melioidosis, a multifaceted disease. A proportion of the mortality and morbidity reported as a result of infection with this organism may be due to the premature cessation of antibiotic therapy typically lasting for several months. The progression of re-emergent disease was characterised in Balb/c mice following cessation of a 14 day treatment course of co-trimoxazole or finafloxacin, delivered at a human equivalent dose. Mice were culled weekly and the infection characterised in terms of bacterial load in tissues, weight loss, clinical signs of infection, cytokine levels and immunological cell counts. Following cessation of treatment, the infection re-established in some animals. Finafloxacin prevented the re-establishment of the infection for longer than co-trimoxazole, and it is apparent based on the protection offered, the development of clinical signs of disease, bodyweight loss and bacterial load, that finafloxacin was more effective at controlling infection when compared to co-trimoxazole. Full article

(This article belongs to the Special Issue Animal Models of Biodefence Pathogens: Exploring Treatment)

► Show Figures

Figure 1

20 pages, 1862 KiB

Open AccessArticle

Detection of Acquired Antibiotic Resistance Genes in Domestic Pig (Sus scrofa) and Common Carp (Cyprinus carpio) Intestinal Samples by Metagenomics Analyses in Hungary

by Balázs Libisch, Sahabi Abdulkadir, Tibor Keresztény, Péter P. Papp, Ferenc Olasz, Hedvig Fébel, Zsuzsanna J. Sándor, Geertrui Rasschaert, Ellen Lambrecht, Marc Heyndrickx, András Szabó, Melinda Kovács and Katalin Posta

Antibiotics 2022, 11(10), 1441; https://doi.org/10.3390/antibiotics11101441 - 20 Oct 2022

Cited by 5 | Viewed by 3089

Abstract

The aim of this study was metagenomics analyses of acquired antibiotic-resistance genes (ARGs) in the intestinal microbiome of two important food-animal species in Hungary from a One Health perspective. Intestinal content samples were collected from 12 domestic pigs (Sus scrofa) and [...] Read more.

The aim of this study was metagenomics analyses of acquired antibiotic-resistance genes (ARGs) in the intestinal microbiome of two important food-animal species in Hungary from a One Health perspective. Intestinal content samples were collected from 12 domestic pigs (Sus scrofa) and from a common carp (Cyprinus carpio). Shotgun metagenomic sequencing of DNA purified from the intestinal samples was performed on the Illumina platform. The ResFinder database was applied for detecting acquired ARGs in the assembled metagenomic contigs. Altogether, 59 acquired ARG types were identified, 51 genes from domestic pig and 12 genes from the carp intestinal microbiome. ARG types belonged to the antibiotic classes aminoglycosides (27.1%), tetracyclines (25.4%), β-lactams (16.9%), and others. Of the identified ARGs, tet(E), a bla_OXA-_48-like β-lactamase gene, as well as cphA4, ampS, aadA2, qnrS2, and sul1, were identified only in carp but not in swine samples. Several of the detected acquired ARGs have not yet been described from food animals in Hungary. The tet(Q), tet(W), tet(O), and mef(A) genes detected in the intestinal microbiome of domestic pigs had also been identified from free-living wild boars in Hungary, suggesting a possible relationship between the occurrence of acquired ARGs in domestic and wild animal populations. Full article

(This article belongs to the Special Issue Antimicrobial Compounds and Antimicrobial Resistance: The Big Challenge of the One Health Approach)

► Show Figures

Figure 1

11 pages, 744 KiB

Open AccessArticle

Combination Regimens with Colistin Sulfate versus Colistin Sulfate Monotherapy in the Treatment of Infections Caused by Carbapenem-Resistant Gram-Negative Bacilli

by Min Hao, Yang Yang, Yan Guo, Shi Wu, Fupin Hu and Xiaohua Qin

Antibiotics 2022, 11(10), 1440; https://doi.org/10.3390/antibiotics11101440 - 19 Oct 2022

Cited by 14 | Viewed by 2610

Abstract

Carbapenem-resistant organisms (CRO) have become a global concern because of the limited antibiotic treatment options for CRO infections. Colistin sulfate is a type of polymyxin approved for the treatment of CRO in China. To date, studies on polymyxin have mainly focused on in [...] Read more.

Carbapenem-resistant organisms (CRO) have become a global concern because of the limited antibiotic treatment options for CRO infections. Colistin sulfate is a type of polymyxin approved for the treatment of CRO in China. To date, studies on polymyxin have mainly focused on in vitro antibacterial activity or pharmacokinetics/pharmacodynamics, and few have evaluated its clinical efficacy. We aimed to compare the clinical efficacy and safety of colistin sulfate monotherapy and its combination with other antimicrobials in the treatment of carbapenem-resistant Gram-negative bacilli (CR-GNB) infections in adults. This retrospective study included adult patients with CR-GNB infections treated with colistin sulfate by intravenous drip between January and June 2020. The patients were divided into two groups, according to the administration of colistin sulfate alone or in combination with other antibiotics. Group-wise demographic data, comorbidities, clinical efficacy, prognosis, and adverse events were analyzed and compared. In total, 26 patients in the colistin sulfate monotherapy group and 54 patients in the combined therapy group were recruited. The clinical efficacy in the combined therapy group (94.4%) was significantly higher than that in the colistin monotherapy group (73.1%) (p = 0.007); however, the 28-day mortality and length of hospital stay were not significantly different between groups. The incidence of adverse events (including elevated aminotransferase, bilirubin, serum creatinine, and decreased platelet) was not significantly different between the groups. Combination therapies with colistin sulfate are recommended for the treatment of CR-GNB infections, over colistin sulfate alone. Full article

► Show Figures

Figure 1

13 pages, 3327 KiB

Open AccessArticle

Emergence of Cfr-Mediated Linezolid Resistance among Livestock-Associated Methicillin-Resistant Staphylococcus aureus (LA-MRSA) from Healthy Pigs in Portugal

by Célia Leão, Lurdes Clemente, Maria Cara d’Anjo, Teresa Albuquerque and Ana Amaro

Antibiotics 2022, 11(10), 1439; https://doi.org/10.3390/antibiotics11101439 - 19 Oct 2022

Cited by 13 | Viewed by 2281

Abstract

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) ST398 is mainly found in Europe and North America, colonizing the nasal cavity of pigs. This study characterized the MRSA isolates recovered from pig nasal swabs (n = 171) by evaluating the antimicrobial susceptibility profile by broth [...] Read more.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) ST398 is mainly found in Europe and North America, colonizing the nasal cavity of pigs. This study characterized the MRSA isolates recovered from pig nasal swabs (n = 171) by evaluating the antimicrobial susceptibility profile by broth microdilution and characterizing the genetic lineages by spa-typing. Three linezolid-resistant isolates were subjected to Whole-Genome Sequencing (WGS). All strains harbored the mecA gene and were resistant to tetracycline and susceptible to vancomycin. A high frequency of multidrug resistance (97.6%) was evidenced, with 55 different multidrug resistance profiles identified. The MRSA strains were found to belong to 17 spa-types, three being novel. The linezolid-resistant strains appeared to belong to the ST398 type, spa-type t011, and SCCmec_type_Vc and to harbor the cfr, fexA, blaZ, mecA, tetM, and tetK genes. The cfr gene was predicted to be carried in the plasmid, flanked by ISSau9 and the transposon TnpR. MRSA from Portuguese fattening pigs present a high diversity of genetic lineages. The presence of cfr-positive LA-MRSA may represent a risk of transmission to humans, mainly to those in contact with livestock. Full article

(This article belongs to the Special Issue Molecular Evolution and Pathogenicity of Methicillin-Resistant Staphylococcus aureus)

► Show Figures

Figure 1

12 pages, 1915 KiB

Open AccessArticle

Epidemiology of Nocardia Species at a Tertiary Hospital in Southern Taiwan, 2012 to 2020: MLSA Phylogeny and Antimicrobial Susceptibility

by Shu-Fang Kuo, Fang-Ju Chen, I-Chia Lan, Chun-Chih Chien and Chen-Hsiang Lee

Antibiotics 2022, 11(10), 1438; https://doi.org/10.3390/antibiotics11101438 - 19 Oct 2022

Cited by 1 | Viewed by 2086

Abstract

The identification and antimicrobial susceptibility of Nocardia spp. are essential for guiding antibiotic treatment. We investigated the species distribution and evaluated the antimicrobial susceptibility of Nocardia species collected in southern Taiwan from 2012 to 2020. A total of 77 Nocardia isolates were collected [...] Read more.

The identification and antimicrobial susceptibility of Nocardia spp. are essential for guiding antibiotic treatment. We investigated the species distribution and evaluated the antimicrobial susceptibility of Nocardia species collected in southern Taiwan from 2012 to 2020. A total of 77 Nocardia isolates were collected and identified to the species level using multi-locus sequence analysis (MLSA). The susceptibilities to 15 antibiotics for Nocardia isolates were determined by the broth microdilution method, and the MIC₅₀ and MIC₉₀ for each antibiotic against different species were analyzed. N. cyriacigeorgica was the leading isolate, accounting for 32.5% of all Nocardia isolates, and the prevalence of Nocardia isolates decreased in summer. All of the isolates were susceptible to trimethoprim/sulfamethoxazole, amikacin, and linezolid, whereas 90.9% were non-susceptible to cefepime and imipenem. The phylogenic tree by MLSA showed that the similarity between N. beijingensis and N. asiatica was as high as 99%, 73% between N. niigatensis and N. crassostreae, and 86% between N. cerradoensis and N. cyriacigeorgica. While trimethoprim/sulfamethoxazole, amikacin, and linezolid remained fully active against all of the Nocardia isolates tested, 90.9% of the isolates were non-susceptible to cefepime and imipenem. Full article

(This article belongs to the Special Issue Epidemiology of Pathogens and Antimicrobial Resistance)

► Show Figures

Figure 1

24 pages, 974 KiB

Open AccessArticle

Limosilactobacillus fermentum Strain 3872: Antibacterial and Immunoregulatory Properties and Synergy with Prebiotics against Socially Significant Antibiotic-Resistant Infections of Animals and Humans

by Vyacheslav M. Abramov, Igor V. Kosarev, Andrey V. Machulin, Tatiana V. Priputnevich, Irina O. Chikileva, Evgenia I. Deryusheva, Tatiana N. Abashina, Almira D. Donetskova, Alexander N. Panin, Vyacheslav G. Melnikov, Nataliya E. Suzina, Ilia N. Nikonov, Marina V. Selina, Valentin S. Khlebnikov, Vadim K. Sakulin, Raisa N. Vasilenko, Vladimir A. Samoilenko, Vladimir N. Uversky and Andrey V. Karlyshev

Antibiotics 2022, 11(10), 1437; https://doi.org/10.3390/antibiotics11101437 - 19 Oct 2022

Cited by 5 | Viewed by 3064

Abstract

Limosilactobacillus fermentum strain 3872 (LF3872) was originally isolated from the breast milk of a healthy woman during lactation and the breastfeeding of a child. The high-quality genome sequencing of LF3872 was performed, and a gene encoding a unique bacteriocin was discovered. It was [...] Read more.

Limosilactobacillus fermentum strain 3872 (LF3872) was originally isolated from the breast milk of a healthy woman during lactation and the breastfeeding of a child. The high-quality genome sequencing of LF3872 was performed, and a gene encoding a unique bacteriocin was discovered. It was established that the bacteriocin produced by LF3872 (BLF3872) belongs to the family of cell-wall-degrading proteins that cause cell lysis. The antibacterial properties of LF3872 were studied using test cultures of antibiotic-resistant Gram-positive and Gram-negative pathogens. Gram-positive pathogens (Staphylococcus aureus strain 8325-4 and S. aureus strain IIE CI-SA 1246) were highly sensitive to the bacteriolytic action of LF3872. Gram-negative pathogens (Escherichia coli, Salmonella strains, and Campylobacter jejuni strains) were more resistant to the bacteriolytic action of LF3872 compared to Gram-positive pathogens. LF3872 is a strong co-aggregator of Gram-negative pathogens. The cell-free culture supernatant of LF3872 (CSLF3872) induced cell damage in the Gram-positive and Gram-negative test cultures and ATP leakage. In the in vitro experiments, it was found that LF3872 and Actigen prebiotic (Alltech Inc., Nicholasville, KY, USA) exhibited synergistic anti-adhesive activity against Gram-negative pathogens. LF3872 has immunoregulatory properties: it inhibited the lipopolysaccharide-induced production of proinflammatory cytokines IL-8, IL-1β, and TNF-α in a monolayer of Caco-2 cells; inhibited the production of IL-12 and stimulated the production of IL-10 in immature human dendritic cells; and stimulated the production of TGF-β, IFN-γ, and IgA in the immunocompetent cells of intestinal Peyer’s patches (PPs) in mice. These results indicate the possibility of creating a synbiotic based on LF3872 and a prebiotic derived from Saccharomyces cerevisiae cell wall components. Such innovative drugs and biologically active additives are necessary for the implementation of a strategy to reduce the spread of antibiotic-resistant strains of socially significant animal and human infections. Full article

► Show Figures

Figure 1

16 pages, 3897 KiB

Open AccessArticle

High-Throughput Transcriptomic Profiling Reveals the Inhibitory Effect of Hydroquinine on Virulence Factors in Pseudomonas aeruginosa

by Nontaporn Rattanachak, Sattaporn Weawsiangsang, Krai Daowtak, Yordhathai Thongsri, Sukunya Ross, Gareth Ross, Nungruthai Nilsri, Robert A. Baldock, Sutatip Pongcharoen, Touchkanin Jongjitvimol and Jirapas Jongjitwimol

Antibiotics 2022, 11(10), 1436; https://doi.org/10.3390/antibiotics11101436 - 19 Oct 2022

Cited by 3 | Viewed by 4896

Abstract

Hydroquinine is an organic alkaloid compound that exhibits antimicrobial activity against several bacterial strains including strains of both drug-sensitive and multidrug-resistant P. aeruginosa. Despite this, the effects of hydroquinine on virulence factors in P. aeruginosa have not yet been characterized. We [...] Read more.

Hydroquinine is an organic alkaloid compound that exhibits antimicrobial activity against several bacterial strains including strains of both drug-sensitive and multidrug-resistant P. aeruginosa. Despite this, the effects of hydroquinine on virulence factors in P. aeruginosa have not yet been characterized. We therefore aimed to uncover the mechanism of P. aeruginosa hydroquinine-sensitivity using high-throughput transcriptomic analysis. We further confirmed whether hydroquinine inhibits specific virulence factors using RT-qPCR and phenotypic analysis. At half the minimum inhibitory concentration (MIC) of hydroquinine (1.250 mg/mL), 254 genes were differentially expressed (97 downregulated and 157 upregulated). We found that flagellar-related genes were downregulated by between −2.93 and −2.18 Log₂-fold change. These genes were consistent with the analysis of gene ontology and KEGG pathway. Further validation by RT-qPCR showed that hydroquinine significantly suppressed expression of the flagellar-related genes. By analyzing cellular phenotypes, P. aeruginosa treated with ½MIC of hydroquinine exhibited inhibition of motility (30–54% reduction) and pyocyanin production (~25–27% reduction) and impaired biofilm formation (~57–87% reduction). These findings suggest that hydroquinine possesses anti-virulence factors, through diminishing flagellar, pyocyanin and biofilm formation. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Antimicrobial Resistance, and Virulence Genes in Drug-Resistant Bacteria)

► Show Figures

Figure 1

11 pages, 1786 KiB

Open AccessArticle

Early Years of Carbapenem-Resistant Enterobacterales Epidemic in Abu Dhabi

by Tibor Pál, Aqdas B. Butt, Akela Ghazawi, Jens Thomsen, Tahir A. Rizvi and Ágnes Sonnevend

Antibiotics 2022, 11(10), 1435; https://doi.org/10.3390/antibiotics11101435 - 19 Oct 2022

Cited by 4 | Viewed by 1829

Abstract

Recent studies showed that the current endemic of carbapenem-resistant Enterobacterales (CRE) in the Emirate of Abu Dhabi is dominated by highly resistant Klebsiella pneumoniae clones ST14, ST231, and CC147, respectively. In the absence of continuous, molecular typing-based surveillance, it remained unknown whether they [...] Read more.

Recent studies showed that the current endemic of carbapenem-resistant Enterobacterales (CRE) in the Emirate of Abu Dhabi is dominated by highly resistant Klebsiella pneumoniae clones ST14, ST231, and CC147, respectively. In the absence of continuous, molecular typing-based surveillance, it remained unknown whether they lately emerged and rapidly became dominant, or they had been present from the early years of the endemic. Therefore, antibiotic resistance, the presence of carbapenemase and 16S methylase genes, and the sequence types of CRE strains collected between 2009 and 2015 were compared with those collected between 2018 and 2019. It was found that members of these three clones, particularly those of the most prevalent ST14, started dominating already in the very early years of the CRE outbreak. Furthermore, while severely impacting the overall antibiotic resistance patterns, the effect of these clones was not exclusive: for example, increasing trends of colistin or decreasing rates of tigecycline resistance were also observed among nonclonal isolates. The gradually increasing prevalence of few major, currently dominating clones raises the possibility that timely, systematic, molecular typing-based surveillance could have provided tools to public health authorities for an early interference with the escalation of the local CRE epidemic. Full article

(This article belongs to the Special Issue Mechanism of Carbapenem Resistance in Enterobacteriaceae, Acinetobacter and Pseudomonas aeruginosa)

► Show Figures

Figure 1

13 pages, 436 KiB

Open AccessArticle

Antimicrobial Resistance Policy Protagonists and Processes—A Qualitative Study of Policy Advocacy and Implementation

by Olivia S. K. Chan, Wendy W. T. Lam, Keiji Fukuda, Hein Min Tun, Norio Ohmagari, Jasper Littmann, Xu Dong Zhou, Yonghong Xiao, Ping Liu and Didier Wernli

Antibiotics 2022, 11(10), 1434; https://doi.org/10.3390/antibiotics11101434 - 18 Oct 2022

Cited by 4 | Viewed by 2123

Abstract

Antimicrobial resistance (AMR) fundamentally weakens societal foundations economically and in health care. The development of well-considered policies against AMR is important. However, in many places, AMR policy implementation remains elusive. This study aims to identify enablers and deterrents as well as processes and [...] Read more.

Antimicrobial resistance (AMR) fundamentally weakens societal foundations economically and in health care. The development of well-considered policies against AMR is important. However, in many places, AMR policy implementation remains elusive. This study aims to identify enablers and deterrents as well as processes and conditions in AMR policy advocacy. It also aims to identify AMR implementation conditions where AMR national policies are adopted and, to a certain extent, formulated and implemented. This study adopts qualitative research methodology and applies the Grounded Theory Framework to identify thematic findings from interviews conducted in China, Japan, Norway, the United Kingdom (UK), and the United States of America (US). It was identified that AMR policy protagonists are critical to filtering AMR issues and identifying policies “fit to prioritize” and “fit to implement”. They have helped move policy prioritization needles in the UK and the US and engaged in diplomatic efforts in the UK. In these cases, no clientelism was considered. In the US, protagonists who talked to the right decision-makers in the right office at the right time both moved AMR issues from individuals to institutional agenda and from social norms to policy agenda. To conclude, there are three thematic policy conditions that are significant to AMR policy advocacy and implementation: committed personal championship, institutionalization of policies, and social norms facilitate AMR policy advocacy and implementation. Full article

(This article belongs to the Special Issue One Health: Opportunities and Challenges of Antibiotic Resistance and Stewardship)

► Show Figures

Figure 1

7 pages, 1073 KiB

Open AccessBrief Report

The Effect of the COVID-19 Pandemic on Outpatient Antibiotic Prescription Rates in Children and Adolescents—A Claims-Based Study in Germany

by Manas K. Akmatov, Claudia Kohring, Lotte Dammertz, Joachim Heuer, Maike Below, Jörg Bätzing and Jakob Holstiege

Antibiotics 2022, 11(10), 1433; https://doi.org/10.3390/antibiotics11101433 - 18 Oct 2022

Cited by 4 | Viewed by 1887

Abstract

The aim of the study was to examine whether the COVID-19 pandemic had any effect on antibiotic prescription rates in children in Germany. Using the nationwide outpatient prescription data from the Statutory Health Insurance from 2010 to 2021, changes in the monthly prescriptions [...] Read more.

The aim of the study was to examine whether the COVID-19 pandemic had any effect on antibiotic prescription rates in children in Germany. Using the nationwide outpatient prescription data from the Statutory Health Insurance from 2010 to 2021, changes in the monthly prescriptions of systemic antibiotics dispensed to children aged 0–14 years were examined (n = 9,688,483 in 2021). Interrupted time series analysis was used to assess the effect of mitigation measures against SARS-COV-2, introduced in March and November 2020, on antibiotic prescription rates. In the pre-pandemic period, the antibiotic prescription rates displayed a linear decrease from 2010 to 2019 (mean annual decrease, –6%). In 2020, an immediate effect of mitigation measures on prescription rates was observed; in particular, the rate decreased steeply in April (RR 0.24, 95% CI: 0.14–0.41) and November 2020 (0.44, 0.27–0.73). The decrease was observed in all ages and for all antibiotic subgroups. However, this effect was temporary. Regionally, prescription rates were highly correlated between 2019 and 2020/2021. Substantial reductions in antibiotic prescription rates following the mitigation measures may indicate limited access to medical care, changes in care-seeking behavior and/or a decrease of respiratory infections. Despite an all-time low of antibiotic use, regional variations remained high and strongly correlated with pre-pandemic levels. Full article

(This article belongs to the Special Issue Antimicrobial Use across Different Healthcare Settings, Countries and Specific Populations)

► Show Figures

Figure 1

19 pages, 972 KiB

Open AccessReview

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis

by Johnny Zakhour, Sima L. Sharara, Joya-Rita Hindy, Sara F. Haddad and Souha S. Kanj

Antibiotics 2022, 11(10), 1432; https://doi.org/10.3390/antibiotics11101432 - 18 Oct 2022

Cited by 20 | Viewed by 16811

Abstract

Pseudomonas aeruginosa is a pathogen often encountered in a healthcare setting. It has consistently ranked among the most frequent pathogens seen in nosocomial infections, particularly bloodstream and respiratory tract infections. Aside from having intrinsic resistance to many antibiotics, it rapidly acquires resistance to [...] Read more.

Pseudomonas aeruginosa is a pathogen often encountered in a healthcare setting. It has consistently ranked among the most frequent pathogens seen in nosocomial infections, particularly bloodstream and respiratory tract infections. Aside from having intrinsic resistance to many antibiotics, it rapidly acquires resistance to novel agents. Given the high mortality of pseudomonal infections generally, and pseudomonal sepsis particularly, and with the rise of resistant strains, treatment can be very challenging for the clinician. In this paper, we will review the latest evidence for the optimal treatment of P. aeruginosa sepsis caused by susceptible as well as multidrug-resistant strains including the difficult to treat pathogens. We will also discuss the mode of drug infusion, indications for combination therapy, along with the proper dosing and duration of treatment for various conditions with a brief discussion of the use of non-antimicrobial agents. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jean-Francois Timsit—Outstanding Contributions in the Fields of Hospital-Acquired Infections and Optimization of Anti-infective Treatments)

► Show Figures

Scheme 1

15 pages, 1613 KiB

Open AccessReview

Antibiotic Resistance to Mycobacterium tuberculosis and Potential Use of Natural and Biological Products as Alternative Anti-Mycobacterial Agents

by Roberto Arrigoni, Andrea Ballini, Skender Topi, Lucrezia Bottalico, Emilio Jirillo and Luigi Santacroce

Antibiotics 2022, 11(10), 1431; https://doi.org/10.3390/antibiotics11101431 - 18 Oct 2022

Cited by 17 | Viewed by 4439

Abstract

Background: Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). TB treatment is based on the administration of three major antibiotics: isoniazid, rifampicin, and pyrazinamide. However, multi-drug resistant (MDR) Mtb strains are increasing around the world, thus, [...] Read more.

Background: Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). TB treatment is based on the administration of three major antibiotics: isoniazid, rifampicin, and pyrazinamide. However, multi-drug resistant (MDR) Mtb strains are increasing around the world, thus, allowing TB to spread around the world. The stringent response is demonstrated by Mtb strains in order to survive under hostile circumstances, even including exposure to antibiotics. The stringent response is mediated by alarmones, which regulate bacterial replication, transcription and translation. Moreover, the Mtb cell wall contributes to the mechanism of antibiotic resistance along with efflux pump activation and biofilm formation. Immunity over the course of TB is managed by M1-macrophages and M2-macrophages, which regulate the immune response against Mtb infection, with the former exerting inflammatory reactions and the latter promoting an anti-inflammatory profile. T helper 1 cells via secretion of interferon (IFN)-gamma, play a protective role in the course of TB, while T regulatory cells secreting interleukin 10, are anti-inflammatory. Alternative therapeutic options against TB require further discussion. In view of the increasing number of MDR Mtb strains, attempts to replace antibiotics with natural and biological products have been object of intensive investigation. Therefore, in this review the anti-Mtb effects exerted by probiotics, polyphenols, antimicrobial peptides and IFN-gamma will be discussed. All the above cited compounds are endowed either with direct antibacterial activity or with anti-inflammatory and immunomodulating characteristics. Full article

(This article belongs to the Special Issue Antibiotics in Health and Diseases)

► Show Figures

Figure 1

13 pages, 1055 KiB

Open AccessArticle

Ciprofloxacin Concentrations 1/1000th the MIC Can Select for Antimicrobial Resistance in N. gonorrhoeae—Important Implications for Maximum Residue Limits in Food

by Natalia González, Saïd Abdellati, Irith De Baetselier, Jolein Gyonne Elise Laumen, Christophe Van Dijck, Tessa de Block, Sheeba Santhini Manoharan-Basil and Chris Kenyon

Antibiotics 2022, 11(10), 1430; https://doi.org/10.3390/antibiotics11101430 - 18 Oct 2022

Cited by 6 | Viewed by 2510

Abstract

Background: Concentrations of fluoroquinolones up to 200-fold lower than the minimal inhibitory concentration (MIC) have been shown to be able to select for antimicrobial resistance in E. coli and Salmonella spp. (the minimum selection concentration—MSC). We hypothesized that the low concentrations of quinolones [...] Read more.

Background: Concentrations of fluoroquinolones up to 200-fold lower than the minimal inhibitory concentration (MIC) have been shown to be able to select for antimicrobial resistance in E. coli and Salmonella spp. (the minimum selection concentration—MSC). We hypothesized that the low concentrations of quinolones found in meat may play a role in the genesis of quinolone resistance in Neisseria gonorrhoeae. We aimed to (i) establish the ciprofloxacin MSC for N. gonorrhoeae and (ii) assess if, at the ecological level, the prevalence of gonococcal ciprofloxacin resistance is associated with the concentration of quinolones used in food animal production, which is an important determinant of long-term low-dose exposure to ciprofloxacin in humans. Methods: (i) To assess if subinhibitory ciprofloxacin concentrations could select for de novo generated resistant mutants, a susceptible WHO-P N. gonorrhoeae isolate was serially passaged at 1, 1:10, 1:100 and 1:1000 of the ciprofloxacin MIC of WHO-P (0.004 mg/L) on GC agar plates. (ii) Spearman’s correlation was used to assess the association between the prevalence of ciprofloxacin resistance in N. gonorrhoeae and quinolone use for animals and quinolone consumption by humans. Results: Ciprofloxacin concentrations as low as 0.004 µg/L (1/1000 of the MIC of WHO-P) were able to select for ciprofloxacin resistance. The prevalence of ciprofloxacin resistance in N. gonorrhoeae was positively associated with quinolone use for food animals (ρ = 0.47; p = 0.004; N = 34). Conclusion: Further individual level research is required to assess if low doses of ciprofloxacin from ingested foodstuffs are able to select for ciprofloxacin resistance in bacteria colonizing humans and other species. Full article

(This article belongs to the Special Issue Research of Antimicrobial Resistance in the Food Chain)

► Show Figures

Figure 1

29 pages, 497 KiB

Open AccessArticle

Physicochemical Profile, Antioxidant and Antimicrobial Activities of Honeys Produced in Minas Gerais (Brazil)

by Vanessa de A. Royo, Dario A. de Oliveira, Pedro Henrique F. Veloso, Verônica de M. Sacramento, Ellen L. A. Olimpio, Luciano F. de Souza, Nathália da C. Pires, Carlos Henrique G. Martins, Mariana B. Santiago, Tânia Maria de A. Alves, Thaís M. Acácio, Afrânio F. de Melo Junior, Murilo M. Brandão and Elytania V. Menezes

Antibiotics 2022, 11(10), 1429; https://doi.org/10.3390/antibiotics11101429 - 18 Oct 2022

Cited by 2 | Viewed by 3051

Abstract

Honeys can be classified as polyfloral or monofloral and have been extensively studied due to an increased interest in their consumption. There is concern with the correct identification of their flowering, the use of analyses that guarantee their physicochemical quality and the quantification [...] Read more.

Honeys can be classified as polyfloral or monofloral and have been extensively studied due to an increased interest in their consumption. There is concern with the correct identification of their flowering, the use of analyses that guarantee their physicochemical quality and the quantification of some compounds such as phenolics, to determine their antioxidant and antimicrobial action. This study aims at botanical identification, physicochemical analyses, and the determination of total polyphenols, chromatographic profile and antiradical and antimicrobial activity of honey from different regions of Minas Gerais. Seven different samples were analyzed for the presence of pollen, and color determination. The physicochemical analyses performed were total acidity, moisture, HMF, reducing sugar, and apparent sucrose. The compound profile was determined by UHPLC/MS, the determination of total phenolics and antiradical activity (DPPH method) were performed by spectrophotometry, and minimum inhibitory and bacterial concentrations were determined for cariogenic bacteria. All honey samples met the quality standards required by international legislation, twenty compounds were detected as the main ones, the polyfloral honey was the only honey that inhibited all of the bacteria tested. Sample M6 (Coffee) was the one with the highest amount of total polyphenols, while the lowest was M4 (Cipó-uva). Regarding the antioxidant activity, M5 (Velame) had the best result and M4 (Cipó-uva) was the one that least inhibited oxidation. Of the polyfloral honeys, there was not as high a concentration of phenolic compounds as in the others. Coffee, Aroeira, Velame and Polyfloral have the best anti-radical actions. Betônica, Aroeira, Cipó-uva and Pequi inhibited only some bacteria. The best bacterial inhibition results are from Polyfloral. Full article

(This article belongs to the Special Issue Antioxidant and Antibacterial Properties of Honey)

14 pages, 1728 KiB

Open AccessArticle

Phytogenic Blend Improves Intestinal Health and Reduces Obesity, Diabetes, Cholesterol and Cancers: A Path toward Customised Supplementation

by Sung J. Yu, Yadav S. Bajagai, Friedrich Petranyi, Sara de las Heras-Saldana, Thi Thu Hao Van and Dragana Stanley

Antibiotics 2022, 11(10), 1428; https://doi.org/10.3390/antibiotics11101428 - 18 Oct 2022

Cited by 1 | Viewed by 2207

Abstract

Poultry production is among the most challenging industries for pathogen control. High animal density and abundance of faecal material demand strict biosecurity measures and continual vigilance in monitoring animal health parameters. Despite this vigilance, dealing with disease outbreaks is a part of farmers’ [...] Read more.

Poultry production is among the most challenging industries for pathogen control. High animal density and abundance of faecal material demand strict biosecurity measures and continual vigilance in monitoring animal health parameters. Despite this vigilance, dealing with disease outbreaks is a part of farmers’ routines. Phytogenic feed additives comprised of herbs, spices, essential oils, and oleoresins have potent antimicrobial and anti-inflammatory actions. Related studies are gaining substantial interest in human and animal health worldwide. In this study, a commercial blend phytogenic feed additive was supplemented to layers in an industrial free-range production system with 20,000 birds in both control and treatment groups. At the end of the trial, the ileum tissue was sampled for RNAseq transcriptomic analysis to study the host reaction to the supplement. Phytogenic supplement significantly inhibited four cholesterol-related pathways and reduced the Arteriosclerosis disease category towards improved cardiovascular health. The supplemented birds exhibited reduced disease susceptibility for 26 cancer categories with p-values in the range from 5.23 × 10⁻⁴ to 1.02 × 10⁻²⁵. Major metabolic shifts in Lipid metabolism in combination with Carbohydrate metabolism have resulted in a decrease in the Obesity category, altering the ratio of fat and carbohydrate metabolism toward lower fat storage. Full article

(This article belongs to the Special Issue Advances in the Discovery of Novel Antimicrobial Agents in Nature and Their Applications)

► Show Figures

Figure 1

13 pages, 1592 KiB

Open AccessArticle

Highly Sensitive Determination of Antibiotic Residues in Aquatic Products by High-Performance Liquid Chromatography–Tandem Mass Spectrometry

by Hongli Ye, Siman Li, Yinfeng Xi, Yongfu Shi, Xiaorui Shang and Dongmei Huang

Antibiotics 2022, 11(10), 1427; https://doi.org/10.3390/antibiotics11101427 - 17 Oct 2022

Cited by 12 | Viewed by 2646

Abstract

Antibiotic drug residues are crucial to ensure food safety and minimize risk to human health. Herein, a sensitive high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was developed and validated for the determination of antibiotic residues (mainly amphenicols) consisting of chloramphenicol (CAP), thiamphenicol (TAP), [...] Read more.

Antibiotic drug residues are crucial to ensure food safety and minimize risk to human health. Herein, a sensitive high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was developed and validated for the determination of antibiotic residues (mainly amphenicols) consisting of chloramphenicol (CAP), thiamphenicol (TAP), florfenicol (FF), and florfenicol amine (FFA) in aquatic products. Amphenicols were well separated on a Kinetex F5 (100 mm × 3.0 mm, 2.6 µm) chromatographic column with the mobile phases of 1 mM ammonium acetate aqueous solution and methanol solution and measured after positive and negative electrospray ionizations using four internal standards. To our knowledge, it was the first time to report the good performance of F5 column and four internal standards for the determination of amphenicols. The established method featured a good linear relationship between chromatographic peak area ratios and the concentrations of amphenicols (R² > 0.992), a wide and low detection matrix-based range of 0.01–5 μg/L, a low detection limit of 0.01 μg/kg, etc. The spiked assays evidenced the accuracy and reliability of the developed method with the recoveries between 84.0 and 105%, the intraday relative standard deviations (RSDs) over the range of 0.769–13.7%, and the interday RSDs over the range of 0.582–13.3%. Finally, the proposed method was applied to investigate amphenicol residues in various aquatic products, including fish, shrimp, crab, shellfish, and other aquatic species. Full article

► Show Figures

Figure 1

14 pages, 2669 KiB

Open AccessArticle

CcpA Regulates Staphylococcus aureus Biofilm Formation through Direct Repression of Staphylokinase Expression

by Mingxia Zheng, Keting Zhu, Huagang Peng, Weilong Shang, Yan Zhao, Shuguang Lu, Xiancai Rao, Ming Li, Renjie Zhou and Gang Li

Antibiotics 2022, 11(10), 1426; https://doi.org/10.3390/antibiotics11101426 - 17 Oct 2022

Cited by 6 | Viewed by 2620

Abstract

Staphylococcus aureus represents a notorious opportunistic pathogen causing various infections in biofilm nature, imposing remarkable therapeutic challenges worldwide. The catabolite control protein A (CcpA), a major regulator of carbon catabolite repression (CCR), has been recognized to modulate S. aureus biofilm formation, while the [...] Read more.

Staphylococcus aureus represents a notorious opportunistic pathogen causing various infections in biofilm nature, imposing remarkable therapeutic challenges worldwide. The catabolite control protein A (CcpA), a major regulator of carbon catabolite repression (CCR), has been recognized to modulate S. aureus biofilm formation, while the underlying mechanism remains to be fully elucidated. In this study, the reduced biofilm was firstly determined in the ccpA deletion mutant of S. aureus clinical isolate XN108 using both crystal violet staining and confocal laser scanning microscopy. RNA-seq analysis suggested that sak-encoding staphylokinase (Sak) was significantly upregulated in the mutant ∆ccpA, which was further confirmed by RT-qPCR. Consistently, the induced Sak production correlated the elevated promoter activity of sak and increased secretion in the supernatants, as demonstrated by Psak-lacZ reporter fusion expression and chromogenic detection, respectively. Notably, electrophoretic mobility shift assays showed that purified recombinant protein CcpA binds directly to the promoter region of sak, suggesting the direct negative control of sak expression by CcpA. Double isogenic deletion of ccpA and sak restored biofilm formation for mutant ∆ccpA, which could be diminished by trans-complemented sak. Furthermore, the exogenous addition of recombinant Sak inhibited biofilm formation for XN108 in a dose-dependent manner. Together, this study delineates a novel model of CcpA-controlled S. aureus biofilm through direct inhibition of sak expression, highlighting the multifaceted roles and multiple networks regulated by CcpA. Full article

(This article belongs to the Special Issue Bacterial Biofilms: From Regulation to Strategies to Study and Fight Them)

► Show Figures

Figure 1

14 pages, 3791 KiB

Open AccessArticle

Thermoplastic Starch Composites Reinforced with Functionalized POSS: Fabrication, Characterization, and Evolution of Mechanical, Thermal and Biological Activities

by Raja Venkatesan, Ramkumar Vanaraj, Krishnapandi Alagumalai, Shakila Parveen Asrafali, Chaitany Jayprakash Raorane, Vinit Raj and Seong-Cheol Kim

Antibiotics 2022, 11(10), 1425; https://doi.org/10.3390/antibiotics11101425 - 17 Oct 2022

Cited by 12 | Viewed by 2186

Abstract

Rapid advancements in materials that offer the appropriate mechanical strength, barrier, and antimicrobial activity for food packaging are still confronted with significant challenges. In this study, a modest, environmentally friendly method was used to synthesize functionalized octakis(3-chloropropyl)octasilsesquioxane [fn-POSS] nanofiller. Composite films compared to [...] Read more.

Rapid advancements in materials that offer the appropriate mechanical strength, barrier, and antimicrobial activity for food packaging are still confronted with significant challenges. In this study, a modest, environmentally friendly method was used to synthesize functionalized octakis(3-chloropropyl)octasilsesquioxane [fn-POSS] nanofiller. Composite films compared to the neat thermoplastic starch (TS) film, show improved thermal and mechanical properties. Tensile strength results improved from 7.8 MPa to 28.1 MPa (TS + 5.0 wt.% fn-POSS) with fn-POSS loading (neat TS). The barrier characteristics of TS/fn-POSS composites were increased by fn-POSS by offering penetrant molecules with a twisting pathway. Also, the rates of O₂ and H₂O transmission were decreased by 50.0 cc/m²/day and 48.1 g/m²/day in TS/fn-POSS composites. Based on an examination of its antimicrobial activity, the fn-POSS blended TS (TSP-5.0) film exhibits a favorable zone of inhibition against the bacterial pathogenic Staphylococcus aureus and Escherichia coli. The TS/fn-POSS (TSP-5.0) film lost 78.4% of its weight after 28 days in natural soil. New plastic materials used for packaging, especially food packaging, are typically not biodegradable, so the TS composite with 5.0 wt.% fn-POSS is therefore of definite interest. The incorporation of fn-POSS with TS composites can improve their characteristics, boost the use of nanoparticles in food packaging, and promote studies on biodegradable composites. Full article

(This article belongs to the Special Issue Nanocarriers Strategies against Microorganisms and Their Associated Biofilm Infections)

► Show Figures

Figure 1

15 pages, 1332 KiB

Open AccessArticle

A Meta-Analysis to Estimate Prevalence of Resistance to Tetracyclines and Third Generation Cephalosporins in Enterobacteriaceae Isolated from Food Crops

by Ariel A. Brunn, Manon Roustit, Zaharat Kadri-Alabi, Luca Guardabassi and Jeff Waage

Antibiotics 2022, 11(10), 1424; https://doi.org/10.3390/antibiotics11101424 - 17 Oct 2022

Cited by 1 | Viewed by 2360

Abstract

Application of human and animal waste to fields and water sources and on-farm antimicrobial usage are documented contributors to the occurrence of antimicrobial resistance (AMR) in agricultural domains. This meta-analysis aimed to determine the prevalence of resistance to tetracycline (TET) and third generation [...] Read more.

Application of human and animal waste to fields and water sources and on-farm antimicrobial usage are documented contributors to the occurrence of antimicrobial resistance (AMR) in agricultural domains. This meta-analysis aimed to determine the prevalence of resistance to tetracycline (TET) and third generation cephalosporins (3GC) in Enterobacteriaceae isolated from food crops. TET was selected in view of its wide use in agriculture, whereas 3GC were selected because of the public health concerns of reported resistance to these critically important antibiotics in the environment. Forty-two studies from all six world regions published between 2010 and 2022 met the eligibility criteria. A random effects model estimated that 4.63% (95% CI: 2.57%, 7.18%; p-value: <0.0001) and 3.75% (95%CI: 2.13%, 5.74%; p-value: <0.0001) of surveyed food crops harboured Enterobacteriaceae resistant to TET and 3GC, respectively. No significant differences were observed between pre- and post-harvest stages of the value chain. 3GC resistance prevalence estimates in food crops were highest for the African region (6.59%; 95% CI: 2.41%, 12.40%; p-value: <0.0001) and lowest for Europe (1.84%; 95% CI: 0.00%, 6.02%; p-value: <0.0001). Considering the rare use of 3GC in agriculture, these results support its inclusion for AMR surveillance in food crops. Integrating food crops into One Health AMR surveillance using harmonized sampling methods could confirm trends highlighted here. Full article

(This article belongs to the Special Issue One Health: Opportunities and Challenges of Antibiotic Resistance and Stewardship)

► Show Figures

Figure 1

20 pages, 707 KiB

Open AccessArticle

Determinants of the Empiric Use of Antibiotics by General Practitioners in South Africa: Observational, Analytic, Cross-Sectional Study

by Sinenhlanhla Pearl Guma, Brian Godman, Stephen M. Campbell and Ozayr Mahomed

Antibiotics 2022, 11(10), 1423; https://doi.org/10.3390/antibiotics11101423 - 17 Oct 2022

Cited by 16 | Viewed by 3267

Abstract

The overuse of antibiotics is the main driver of antimicrobial resistance (AMR). However, there has been limited surveillance data on AMR and antibiotic prescribing at a primary healthcare level in South Africa. An observational, analytic, cross-sectional study was undertaken to assess key factors [...] Read more.

The overuse of antibiotics is the main driver of antimicrobial resistance (AMR). However, there has been limited surveillance data on AMR and antibiotic prescribing at a primary healthcare level in South Africa. An observational, analytic, cross-sectional study was undertaken to assess key factors associated with empiric antibiotic prescribing among private sector general practitioners (GPs) in the eThekwini district in South Africa, particularly for patients with acute respiratory infections (ARIs). A semi-structured web-based questionnaire was used between November 2020–March 2021. One hundred and sixteen (55.5%) responding GPs prescribed antibiotics empirically for patients with ARIs more than 70% of the time, primarily for symptom relief and the prevention of complications. GPs between the ages of 35–44 years (OR: 3.38; 95%CI: 1.15–9.88), >55 years (OR: 4.75; 95% CI 1.08–21) and in practice < 15 years (OR: 2.20; 95%CI: 1.08–4.51) were significantly more likely to prescribe antibiotics empirically. Three factors—workload/time pressures; diagnostic uncertainty, and the use of a formulary, were significantly associated with empiric prescribing. GPs with more experience and working alone were slightly less likely to prescribe antibiotics empirically. These findings indicate that a combination of environmental factors are important underlying contributors to the development of AMR. As a result, guide appropriate interventions using a health system approach, which includes pertinent prescribing indicators and targets. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Infection Control)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Antibiotics, Volume 11, Issue 10 (October 2022) – 179 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI