Antibiotics

12 pages, 1627 KiB

Open AccessArticle

Comparison of Three Endodontic Irrigant Regimens against Dual-Species Interkingdom Biofilms: Considerations for Maintaining the Status Quo

by Om Alkhir Alshanta, Saeed Alqahtani, Suror Shaban, Khawlah Albashaireh, William McLean and Gordon Ramage

Antibiotics 2020, 9(9), 634; https://doi.org/10.3390/antibiotics9090634 - 22 Sep 2020

Cited by 8 | Viewed by 4010

Abstract

Endodontic infections are often interkingdom biofilms, though current clinical management rarely considers this phenomenon. This study aimed to evaluate new and standard endodontic antimicrobial regimens against simple and complex Candida albicans and Enterococcus faecalis mono- and dual-species biofilms. C. albicans and E. faecalis [...] Read more.

Endodontic infections are often interkingdom biofilms, though current clinical management rarely considers this phenomenon. This study aimed to evaluate new and standard endodontic antimicrobial regimens against simple and complex Candida albicans and Enterococcus faecalis mono- and dual-species biofilms. C. albicans and E. faecalis mono- and dual-species biofilms were grown upon Thermanox™ coverslips and treated for 5 min with 3% NaOCl, 3% NaOCl followed by 17% EDTA, or 9% HEDP dissolved in 3% NaOCl. The number of cells remaining immediately after treatment at 0 h and after 72 h of regrowth were assessed using real-time quantitative PCR. All three treatment arms showed a similar positive antimicrobial effect on C. albicans and E. faecalis in both mono- and dual-species biofilms following initial treatment, resulting in ≥98% reduction in colony forming equivalent (CFE). Regardless of species or biofilm type (mono- or dual- species), the antimicrobial effect of NaOCl:HEDP mixture was comparable to that of NaOCl alone, with both showing significant regrowth after 72 h, whereas sequential treatment with NaOCl and EDTA consistently prevented significant regrowth. Our data suggest that sequential irrigation with NaOCl and EDTA remains the antimicrobial strategy of choice as it significantly reduces biofilm persistence and regrowth in our experimental dual-species biofilm conditions. Full article

(This article belongs to the Special Issue Oral Microorganisms and Inactivation of Oral Biofilms)

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22 pages, 3717 KiB

Open AccessArticle

Repurposing Disulfiram (Tetraethylthiuram Disulfide) as a Potential Drug Candidate against Borrelia burgdorferi In Vitro and In Vivo

by Hari-Hara S. K. Potula, Jahanbanoo Shahryari, Mohammed Inayathullah, Andrey Victorovich Malkovskiy, Kwang-Min Kim and Jayakumar Rajadas

Antibiotics 2020, 9(9), 633; https://doi.org/10.3390/antibiotics9090633 - 22 Sep 2020

Cited by 21 | Viewed by 7341

Abstract

Lyme disease caused by the Borrelia burgdorferi (Bb or B. burgdorferi) is the most common vector-borne, multi-systemic disease in the USA. Although most Lyme disease patients can be cured with a course of the first line of antibiotic treatment, some patients [...] Read more.

Lyme disease caused by the Borrelia burgdorferi (Bb or B. burgdorferi) is the most common vector-borne, multi-systemic disease in the USA. Although most Lyme disease patients can be cured with a course of the first line of antibiotic treatment, some patients are intolerant to currently available antibiotics, necessitating the development of more effective therapeutics. We previously found several drugs, including disulfiram, that exhibited effective activity against B. burgdorferi. In the current study, we evaluated the potential of repurposing the FDA-approved drug, disulfiram for its borreliacidal activity. Our results indicate disulfiram has excellent borreliacidal activity against both the log and stationary phase B. burgdorferi sensu stricto B31 MI. Treatment of mice with disulfiram eliminated the B. burgdorferi sensu stricto B31 MI completely from the hearts and urinary bladder by day 28 post infection. Moreover, disulfiram-treated mice showed reduced expressions of inflammatory markers, and thus they were protected from histopathology and cardiac organ damage. Furthermore, disulfiram-treated mice showed significantly lower amounts of total antibody titers (IgM and IgG) at day 21 and total IgG2b at day 28 post infection. FACS analysis of lymph nodes revealed a decrease in the percentage of CD19+ B cells and an increase in total percentage of CD3+ T cells, CD3+ CD4+ T helpers, and naive and effector memory cells in disulfiram-treated mice. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic for treating Lyme disease. Full article

(This article belongs to the Special Issue Drugs Repurposing for the Treatment of Bacterial Infections)

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18 pages, 596 KiB

Open AccessReview

Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance

by Matteo Bassetti, Antonio Vena, Chiara Sepulcri, Daniele Roberto Giacobbe and Maddalena Peghin

Antibiotics 2020, 9(9), 632; https://doi.org/10.3390/antibiotics9090632 - 22 Sep 2020

Cited by 50 | Viewed by 7393

Abstract

The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment [...] Read more.

The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii. Full article

(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)

14 pages, 3979 KiB

Open AccessArticle

Antimicrobial Resistance, an Update from the Ward: Increased Incidence of New Potential Pathogens and Site of Infection-Specific Antibacterial Resistances

by Irene Stefanini, Martina Boni, Paola Silvaplana, Paola Lovera, Stefania Pelassa, Giuseppe De Renzi and Barbara Mognetti

Antibiotics 2020, 9(9), 631; https://doi.org/10.3390/antibiotics9090631 - 22 Sep 2020

Cited by 7 | Viewed by 3416

Abstract

In order to monitor the spread of antimicrobial resistance, the European Union requires hospitals to be equipped with infection control centers. With this aim, we analyzed 1583 bacterial strains isolated from samples of different origin from patients with community-onset and nosocomial infections in [...] Read more.

In order to monitor the spread of antimicrobial resistance, the European Union requires hospitals to be equipped with infection control centers. With this aim, we analyzed 1583 bacterial strains isolated from samples of different origin from patients with community-onset and nosocomial infections in a public tertiary University Hospital on the outskirts of Turin, Italy. Statistical analyses of the isolates (source, type) and their antimicrobial resistance (AMR) were performed. The survey revealed infections associated with bacterial species considered as not-commensal and not-pathogenic, hence potentially emerging as new threats for human health. Conversely to the general observation of nosocomial strains being more resistant to antibiotics compared to community-acquired strains, nosocomial strains isolated in this study were more resistant only to 1/42 tested antibiotics (tetracycline). By adopting an ecological approach, we observed that blood infections are associated with the broadest range of species compared to infections affecting other areas and we obtained clear indications on the antibiotics that should be preferred in the treatment of infections at specific body sites. Future investigations carried out on a larger geographical scale will clarify whether these indications are limited to the geographical region investigated over this study, or whether the same trends are visible at national or international level. Full article

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

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11 pages, 790 KiB

Open AccessArticle

Current Antibiotic Resistance Trends of Uropathogens in Central Europe: Survey from a Tertiary Hospital Urology Department 2011–2019

by Jan Hrbacek, Pavel Cermak and Roman Zachoval

Antibiotics 2020, 9(9), 630; https://doi.org/10.3390/antibiotics9090630 - 22 Sep 2020

Cited by 45 | Viewed by 4908

Abstract

Monitoring of pathogen resistance profiles is necessary to guide empirical antibiotic therapy before culture and sensitivity results become available. The aim of this study was to describe current antibiotic resistance patterns of five most frequent causative uropathogens in a Department of Urology of [...] Read more.

Monitoring of pathogen resistance profiles is necessary to guide empirical antibiotic therapy before culture and sensitivity results become available. The aim of this study was to describe current antibiotic resistance patterns of five most frequent causative uropathogens in a Department of Urology of a tertiary referral centre in Central Europe over a period of nine years. The Hospital Department of Clinical Microbiology database was used to extract data on all positive urine samples from inpatients in the Department of Urology between 2011 and 2019. Numbers of susceptible and resistant isolates per year were calculated for five most frequent uropathogens: Escherichia coli, Enterococcus spp., Klebsiella spp., Pseudomonas aeruginosa, and Proteus spp. Antimicrobial agents selected for the survey included: ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam; cefuroxime, cefotaxime, ceftazidime and cefepime; ciprofloxacin and ofloxacin; gentamicin and amikacin; ertapenem, meropenem and imipenem; trimethoprim-sulfamethoxazole (co-trimoxazole), nitrofurantoin, colistin, and vancomycin. High resistance rates of Gram-negative uropathogens were demonstrated to most common antimicrobials, with statistically significant increasing or decreasing trends in some cases. No carbapenem-resistant Enterobacteriaceae were isolated. Vancomycin-resistant Enterococcus spp. strains were rare in our population. Full article

(This article belongs to the Special Issue Antibiotics Use and Antimicrobial Resistance in Hospital)

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16 pages, 3951 KiB

Open AccessArticle

Exploration of Chemical Diversity and Antitrypanosomal Activity of Some Red Sea-Derived Actinomycetes Using the OSMAC Approach Supported by LC-MS-Based Metabolomics and Molecular Modelling

by Noha M. Gamaleldin, Walid Bakeer, Ahmed M. Sayed, Yara I. Shamikh, Ahmed O. El-Gendy, Hossam M. Hassan, Hannes Horn, Usama Ramadan Abdelmohsen and Wael N. Hozzein

Antibiotics 2020, 9(9), 629; https://doi.org/10.3390/antibiotics9090629 - 22 Sep 2020

Cited by 20 | Viewed by 4821

Abstract

In the present study, we investigated the actinomycetes associated with the Red Sea-derived soft coral Sarcophyton glaucum in terms of biological and chemical diversity. Three strains were cultivated and identified to be members of genera Micromonospora, Streptomyces, and Nocardiopsis; out [...] Read more.

In the present study, we investigated the actinomycetes associated with the Red Sea-derived soft coral Sarcophyton glaucum in terms of biological and chemical diversity. Three strains were cultivated and identified to be members of genera Micromonospora, Streptomyces, and Nocardiopsis; out of them, Micromonospora sp. UR17 was putatively characterized as a new species. In order to explore the chemical diversity of these actinobacteria as far as possible, they were subjected to a series of fermentation experiments under altering conditions, that is, solid and liquid fermentation along with co-fermentation with a mycolic acid-containing strain, namely Nocardia sp. UR23. Each treatment was found to affect these actinomycetes differently in terms of biological activity (i.e., antitrypanosomal activity) and chemical profiles evidenced by LC-HRES-MS-based metabolomics and multivariate analysis. Thereafter, orthogonal projections to latent structures discriminant analysis (OPLS-DA) suggested a number of metabolites to be associated with the antitrypanosomal activity of the active extracts. The subsequent in silico screenings (neural networking-based and docking-based) further supported the OPLS-DA results and prioritized desferrioxamine B (3), bafilomycin D (10), and bafilomycin A1 (11) as possible antitrypanosomal agents. Our approach in this study can be applied as a primary step in the exploration of bioactive natural products, particularly those from actinomycetes. Full article

(This article belongs to the Special Issue Novel Antibiotics from Actinomycetes)

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16 pages, 1644 KiB

Open AccessArticle

Antibacterial Activity of Essential Oils and Trametes versicolor Extract against Clavibacter michiganensis subsp. michiganensis and Ralstonia solanacearum for Seed Treatment and Development of a Rapid In Vivo Assay

by Laura Orzali, Maria Teresa Valente, Valeria Scala, Stefania Loreti and Nicoletta Pucci

Antibiotics 2020, 9(9), 628; https://doi.org/10.3390/antibiotics9090628 - 21 Sep 2020

Cited by 23 | Viewed by 4899

Abstract

Clavibacter michiganensis subsp. michiganensis (Smith) Davis et al. (Cmm) and Ralstonia solanacearum Yabuuchi et al. (Smith) (Rs) are important seed-borne bacterial pathogens of tomato (Solanum lycopersicum) listed as A2 pests in the EPPO (European and Mediterranean Plant Protection Organization) region. At [...] Read more.

Clavibacter michiganensis subsp. michiganensis (Smith) Davis et al. (Cmm) and Ralstonia solanacearum Yabuuchi et al. (Smith) (Rs) are important seed-borne bacterial pathogens of tomato (Solanum lycopersicum) listed as A2 pests in the EPPO (European and Mediterranean Plant Protection Organization) region. At present, there are few strategies to control these pathogens, and seed control with eco-compatible approaches is widely encouraged. In this work, the essential oils (EOs) of oregano (Origanum vulgare), garlic (Allium sativum), basil (Ocimum basilicum), cinnamon (Cinnamomum zeylanicum), clove buds (Syzygium aromaticum), thyme (Thymus vulgaris), and Trametes versicolor extract (Tve) were tested in vitro for their antimicrobial activity against Cmm and Rs (broth microdilution method). The tested EOs and the Tve extract caused a significant inhibition of bacterial growth, with very promising MBC (minimum bactericidal concentration) and MIC90 (minimum inhibitory concentration causing a 90% growth inhibition) values. Moreover, an in vivo germination test showed no major reduction in seed germination when the substances were applied as seed treatment. A rapid molecular screening method has been developed, through real-time PCR, for the specific quantification of Cmm in the presence of a vegetable matrix to test in vivo the antimicrobial efficacy of oregano and cinnamon oil on seed treatment without resorting to whole plant essays, which are time- and space-consuming. Full article

(This article belongs to the Special Issue Plant's Defense against Pathogens)

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19 pages, 1975 KiB

Open AccessArticle

Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates

by Yu Zai, Yuan Ying, Zhuming Ye, Mei Zhou, Chengbang Ma, Zhanzhong Shi, Xiaoling Chen, Xinping Xi, Tianbao Chen and Lei Wang

Antibiotics 2020, 9(9), 627; https://doi.org/10.3390/antibiotics9090627 - 21 Sep 2020

Cited by 18 | Viewed by 3745

Abstract

DMPC-10A (ALWKKLLKK-Cha-NH₂) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid [...] Read more.

DMPC-10A (ALWKKLLKK-Cha-NH₂) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala¹ and Trp³ remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae using the Galleria mellonella larva model and displayed synergistic activities with gentamicin against carbapenem-resistant K. pneumoniae strains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens. Full article

(This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides)

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15 pages, 2389 KiB

Open AccessArticle

Clinical Significance of Carbapenem-Tolerant Pseudomonas aeruginosa Isolated in the Respiratory Tract

by Momoyo Azuma, Keiji Murakami, Rina Murata, Keiko Kataoka, Hideki Fujii, Yoichiro Miyake and Yasuhiko Nishioka

Antibiotics 2020, 9(9), 626; https://doi.org/10.3390/antibiotics9090626 - 21 Sep 2020

Cited by 5 | Viewed by 2739

Abstract

We often come across difficult to treat infections—even after administering appropriate antibiotics according to the minimal inhibitory concentration of the causative bacteria. Antibiotic tolerance has recently started to garner attention as a crucial mechanism of refractory infections. However, few studies have reported the [...] Read more.

We often come across difficult to treat infections—even after administering appropriate antibiotics according to the minimal inhibitory concentration of the causative bacteria. Antibiotic tolerance has recently started to garner attention as a crucial mechanism of refractory infections. However, few studies have reported the correlation between clinical outcomes and antibiotic tolerance. This study aims to clarify the effect of antibiotic tolerance on clinical outcomes of respiratory tract infection caused by Pseudomonas aeuginosa (P. aeruginosa). We examined a total of 63 strains isolated from sputum samples of different patients and conducted a retrospective survey with the medical records of 37 patients with imipenem-sensitive P. aeruginosa infections. Among them, we selected 15 patients with respiratory infections, and they were divided into high-tolerance minimal bactericidal concentration for adherent bacteria (MBC^AD)/minimal inhibitory concentration for adherent bacteria (MIC^AD) ≥ 32 (n = 9) group and low-tolerance MBC^AD/MIC^AD ≤ 16 (n = 6) group for further investigations. The findings indicated that the high-tolerance group consisted of many cases requiring hospitalization. Chest computed tomography findings showed that the disease was more extensive in the high-tolerance group compared to the low-tolerance group. Regarding the bacterial phenotypic characterization, the high-tolerance group significantly upregulated the production of the virulence factors compared to the low-tolerance group. Our study provided evidence that carbapenem tolerance level is a potent prognostic marker of P. aeruginosa infections, and carbapenem tolerance could be a potential target for new antimicrobial agents to inhibit the progression of persistent P. aeruginosa infections. Full article

(This article belongs to the Special Issue Interference of Bacterial Signaling as a New Strategy for Treatment of AMR Pathogens)

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14 pages, 2759 KiB

Open AccessArticle

Figainin 1, a Novel Amphibian Skin Peptide with Antimicrobial and Antiproliferative Properties

by Carlos José Correia Santana, Ana Carolina Martins Magalhães, Agenor C. M. dos Santos Júnior, Carlos André Ornelas Ricart, Beatriz D. Lima, Alice da Cunha Morales Álvares, Sonia Maria de Freitas, Osmindo Rodrigues Pires, Jr., Wagner Fontes and Mariana S. Castro

Antibiotics 2020, 9(9), 625; https://doi.org/10.3390/antibiotics9090625 - 21 Sep 2020

Cited by 18 | Viewed by 3861

Abstract

Amphibian skin secretions are abundant in bioactive compounds, especially antimicrobial peptides. These molecules are generally cationic and rich in hydrophobic amino acids, have an amphipathic structure and adopt an α-helical conformation when in contact with microorganisms membranes. In this work, we purified and [...] Read more.

Amphibian skin secretions are abundant in bioactive compounds, especially antimicrobial peptides. These molecules are generally cationic and rich in hydrophobic amino acids, have an amphipathic structure and adopt an α-helical conformation when in contact with microorganisms membranes. In this work, we purified and characterized Figainin 1, a novel antimicrobial and antiproliferative peptide from the cutaneous secretion of the frog Boana raniceps. Figainin 1 is a cationic peptide with eighteen amino acid residues—rich in leucine and isoleucine, with an amidated C-terminus—and adopts an α-helical conformation in the presence of trifluoroethanol (TFE). It displayed activity against Gram-negative and especially Gram-positive bacteria, with MIC values ranging from 2 to 16 µM, and showed an IC₅₀ value of 15.9 µM against epimastigote forms of T. cruzi; however, Figanin 1 did not show activity against Candida species. This peptide also showed cytolytic effects against human erythrocytes with an HC₅₀ of 10 µM, in addition to antiproliferative activity against cancer cells and murine fibroblasts, with IC₅₀ values ranging from 10.5 to 13.7 µM. Despite its adverse effects on noncancerous cells, Figainin 1 exhibits interesting properties for the development of new anticancer agents and anti-infective drugs against pathogenic microorganisms. Full article

(This article belongs to the Special Issue Development of Antimicrobial Peptides from Amphibian)

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17 pages, 668 KiB

Open AccessArticle

Prevalence and Antibiotic Resistance of ESKAPE Pathogens Isolated in the Emergency Department of a Tertiary Care Teaching Hospital in Hungary: A 5-Year Retrospective Survey

by Ria Benkő, Márió Gajdács, Mária Matuz, Gabriella Bodó, Andrea Lázár, Edit Hajdú, Erika Papfalvi, Peter Hannauer, Péter Erdélyi and Zoltán Pető

Antibiotics 2020, 9(9), 624; https://doi.org/10.3390/antibiotics9090624 - 19 Sep 2020

Cited by 43 | Viewed by 7103

Abstract

Antibiotic treatments initiated on Emergency Departments (ED) are empirical. Therefore, knowledge of local susceptibility patterns is important. Despite this, data on expected pathogens and their resistance profile are scarce from EDs internationally. The study aim was to assess the epidemiology and resistance patterns [...] Read more.

Antibiotic treatments initiated on Emergency Departments (ED) are empirical. Therefore, knowledge of local susceptibility patterns is important. Despite this, data on expected pathogens and their resistance profile are scarce from EDs internationally. The study aim was to assess the epidemiology and resistance patterns of bacterial isolates from a tertiary-care ED over 5 years, focusing on ESKAPE bacteria (including the Enterobacterales group). After removal of duplicates, n = 6887 individual bacterial isolates were recovered, out of which n = 4974 (72.22%) were ESKAPE isolates. E. coli was the most frequent isolate (2193, 44.1%), followed by the Klebsiella genus (664; 13.4%). The third most frequent isolate was S. aureus (561, 11.3%). In total, multi-drug resistance (MDR) was present in 23.8% and was most prevalent in A. baumanii (65.5%), P. mirabilis (42.7%), and K. pneumoniae (32.6%). MRSA was isolated in 19.6%, while ESBL-producing Enterobacterales in 17.7%, and these were associated with remarkably higher resistance to other antibacterials as well. Difficult-to-treat resistance (DTR) was detected in 0.5%. The frequent isolation of some ESKAPE bacteria and the detected considerable acquired resistance among ED patients raise concern. The revealed data identified problematic pathogens and will guide us to set up the optimal empiric antibiotic protocol for clinicians. Full article

(This article belongs to the Special Issue Antibiotics Use and Antimicrobial Resistance in Hospital)

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19 pages, 1771 KiB

Open AccessReview

Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria

by Rachael E. Impey, Daniel A. Hawkins, J. Mark Sutton and Tatiana P. Soares da Costa

Antibiotics 2020, 9(9), 623; https://doi.org/10.3390/antibiotics9090623 - 19 Sep 2020

Cited by 57 | Viewed by 10701

Abstract

The global increase in multi-drug-resistant bacteria is severely impacting our ability to effectively treat common infections. For Gram-negative bacteria, their intrinsic and acquired resistance mechanisms are heightened by their unique cell wall structure. The cell wall, while being a target of some antibiotics, [...] Read more.

The global increase in multi-drug-resistant bacteria is severely impacting our ability to effectively treat common infections. For Gram-negative bacteria, their intrinsic and acquired resistance mechanisms are heightened by their unique cell wall structure. The cell wall, while being a target of some antibiotics, represents a barrier due to the inability of most antibacterial compounds to traverse and reach their intended target. This means that its composition and resulting mechanisms of resistance must be considered when developing new therapies. Here, we discuss potential antibiotic targets within the most well-characterised resistance mechanisms associated with the cell wall in Gram-negative bacteria, including the outer membrane structure, porins and efflux pumps. We also provide a timely update on the current progress of inhibitor development in these areas. Such compounds could represent new avenues for drug discovery as well as adjuvant therapy to help us overcome antibiotic resistance. Full article

(This article belongs to the Special Issue Novel Targets and Mechanisms in Antimicrobial Drug Discovery)

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6 pages, 185 KiB

Open AccessCommentary

The Primary Care Perspective on the Norwegian National Strategy against Antimicrobial Resistance

by Guri Rørtveit and Gunnar Skov Simonsen

Antibiotics 2020, 9(9), 622; https://doi.org/10.3390/antibiotics9090622 - 19 Sep 2020

Cited by 3 | Viewed by 3184

Abstract

A national strategy to combat antimicrobial resistance (AMR) has been subject to cyclic processes in Norway since 1998. In 2020, a renewed process cycle was launched. Here, we describe the process and the approach of the process. In addition, we describe two concepts [...] Read more.

A national strategy to combat antimicrobial resistance (AMR) has been subject to cyclic processes in Norway since 1998. In 2020, a renewed process cycle was launched. Here, we describe the process and the approach of the process. In addition, we describe two concepts from philosophy of science that may help to frame the process: AMR is an example of a super wicked problem, and post-normal science provides tools to analyze the problem from a new angle. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Primary Care)

14 pages, 2646 KiB

Open AccessCommunication

Characterization of the Bacteriophage-Derived Endolysins PlySs2 and PlySs9 with In Vitro Lytic Activity against Bovine Mastitis Streptococcus uberis

by Niels Vander Elst, Sara B. Linden, Rob Lavigne, Evelyne Meyer, Yves Briers and Daniel C. Nelson

Antibiotics 2020, 9(9), 621; https://doi.org/10.3390/antibiotics9090621 - 19 Sep 2020

Cited by 24 | Viewed by 5544

Abstract

Bovine mastitis, an infection of the cow’s mammary gland, is frequently caused by Streptococcus uberis and causes major economic losses in the dairy industry. The intramammary administration of antibiotics currently remains the predominant preventive and therapeutic measure. These antimicrobial compounds, of which some [...] Read more.

Bovine mastitis, an infection of the cow’s mammary gland, is frequently caused by Streptococcus uberis and causes major economic losses in the dairy industry. The intramammary administration of antibiotics currently remains the predominant preventive and therapeutic measure. These antimicrobial compounds, of which some are considered critical in human health care, are frequently applied as dry therapy resulting in their consistent overuse. Therefore, the use of antibiotics in the dairy sector is being questioned. We here identified two endolysins, i.e., PlySs2 and PlySs9, respectively derived from Streptococcus suis serotype-2 and -9 prophages, with lytic activity against S. uberis in an in vitro setting. Both endolysins gave clear lysis zones in spot-on-plate assays and caused a reduction of the optical density in a turbidity reduction assay. In depth characterization identified PlySs9 as the more potent endolysin over PlySs2 with a lower MIC value and about one additional log of killing. PlySs2 and PlySs9 were challenged to a panel of subclinical and clinical S. uberis milk isolates and were both able to lyse all strains tested. Molecular dissection of these endolysins in catalytic and cell wall binding subdomains resulted in major loss of killing and binding activity, respectively. Taken together, we here propose PlySs2 and PlySs9 as candidate compounds to the current antimicrobial arsenal known against bovine mastitis-causing S. uberis as future add-on or replacement strategy to the currently used intramammary antibiotics. Full article

(This article belongs to the Special Issue Bacteriophages: An Inspiration for the Development of New Antimicrobial and Antibiofilm Agents)

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15 pages, 653 KiB

Open AccessReview

Synergies with and Resistance to Membrane-Active Peptides

by Adam Kmeck, Robert J. Tancer, Cristina R. Ventura and Gregory R. Wiedman

Antibiotics 2020, 9(9), 620; https://doi.org/10.3390/antibiotics9090620 - 19 Sep 2020

Cited by 13 | Viewed by 4831

Abstract

Membrane-active peptides (MAPs) have long been thought of as the key to defeating antimicrobial-resistant microorganisms. Such peptides, however, may not be sufficient alone. In this review, we seek to highlight some of the common pathways for resistance, as well as some avenues for [...] Read more.

Membrane-active peptides (MAPs) have long been thought of as the key to defeating antimicrobial-resistant microorganisms. Such peptides, however, may not be sufficient alone. In this review, we seek to highlight some of the common pathways for resistance, as well as some avenues for potential synergy. This discussion takes place considering resistance, and/or synergy in the extracellular space, at the membrane, and during interaction, and/or removal. Overall, this review shows that researchers require improved definitions of resistance and a more thorough understanding of MAP-resistance mechanisms. The solution to combating resistance may ultimately come from an understanding of how to harness the power of synergistic drug combinations. Full article

(This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides)

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18 pages, 977 KiB

Open AccessArticle

Amidochelocardin Overcomes Resistance Mechanisms Exerted on Tetracyclines and Natural Chelocardin

by Fabienne Hennessen, Marcus Miethke, Nestor Zaburannyi, Maria Loose, Tadeja Lukežič, Steffen Bernecker, Stephan Hüttel, Rolf Jansen, Judith Schmiedel, Moritz Fritzenwanker, Can Imirzalioglu, Jörg Vogel, Alexander J. Westermann, Thomas Hesterkamp, Marc Stadler, Florian Wagenlehner, Hrvoje Petković, Jennifer Herrmann and Rolf Müller

Antibiotics 2020, 9(9), 619; https://doi.org/10.3390/antibiotics9090619 - 18 Sep 2020

Cited by 12 | Viewed by 4918

Abstract

The reassessment of known but neglected natural compounds is a vital strategy for providing novel lead structures urgently needed to overcome antimicrobial resistance. Scaffolds with resistance-breaking properties represent the most promising candidates for a successful translation into future therapeutics. Our study focuses on [...] Read more.

The reassessment of known but neglected natural compounds is a vital strategy for providing novel lead structures urgently needed to overcome antimicrobial resistance. Scaffolds with resistance-breaking properties represent the most promising candidates for a successful translation into future therapeutics. Our study focuses on chelocardin, a member of the atypical tetracyclines, and its bioengineered derivative amidochelocardin, both showing broad-spectrum antibacterial activity within the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) panel. Further lead development of chelocardins requires extensive biological and chemical profiling to achieve favorable pharmaceutical properties and efficacy. This study shows that both molecules possess resistance-breaking properties enabling the escape from most common tetracycline resistance mechanisms. Further, we show that these compounds are potent candidates for treatment of urinary tract infections due to their in vitro activity against a large panel of multidrug-resistant uropathogenic clinical isolates. In addition, the mechanism of resistance to natural chelocardin was identified as relying on efflux processes, both in the chelocardin producer Amycolatopsis sulphurea and in the pathogen Klebsiella pneumoniae. Resistance development in Klebsiella led primarily to mutations in ramR, causing increased expression of the acrAB-tolC efflux pump. Most importantly, amidochelocardin overcomes this resistance mechanism, revealing not only the improved activity profile but also superior resistance-breaking properties of this novel antibacterial compound. Full article

(This article belongs to the Special Issue Novel Targets and Mechanisms in Antimicrobial Drug Discovery)

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12 pages, 1220 KiB

Open AccessArticle

Antifungal Packaging Film to Maintain Quality and Control Postharvest Diseases in Strawberries

by Valentina Trinetta, Austin McDaniel, Konstantinos G. Batziakas, Umut Yucel, Londa Nwadike and Eleni Pliakoni

Antibiotics 2020, 9(9), 618; https://doi.org/10.3390/antibiotics9090618 - 18 Sep 2020

Cited by 27 | Viewed by 4265

Abstract

Strawberries are a highly perishable crop with postharvest losses than reach up to 40%. Cost-effective and sustainable technologies in the form of active packing films can provide a solution. Antimicrobial packaging films were produced from pullulan polymer and Solid Lipid Nanoparticles (SLN) containing [...] Read more.

Strawberries are a highly perishable crop with postharvest losses than reach up to 40%. Cost-effective and sustainable technologies in the form of active packing films can provide a solution. Antimicrobial packaging films were produced from pullulan polymer and Solid Lipid Nanoparticles (SLN) containing 1% w/w cinnamaldehyde. Strawberries were stored at 3 °C for 10 days and 12 °C for 6 days. Microbial and physical quality parameters were evaluated during storage. A reduction of approximately 2 Log CFU/g in yeast and mold population was observed for treated strawberries stored at 3 °C as compared to the control (p < 0.05). Yeast and molds counts were significantly lower on day 2 and 4 at 12 °C for treated samples. Strawberries packaged with the active films demonstrated lower respiration rates and the retention of bright red color at both storage temperatures. Active pullulan films were effective in maintaining the desired strawberry quality and reducing fungal decay during refrigerated storage. Full article

(This article belongs to the Special Issue Development of Novel Anti-microbials to Reduce Bacterial Contamination of Food)

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12 pages, 473 KiB

Open AccessArticle

Changes in Clinical Characteristics of Community-Acquired Acute Pyelonephritis and Antimicrobial Resistance of Uropathogenic Escherichia coli in South Korea in the Past Decade

by Ki Tae Kwon, Bongyoung Kim, Seong-yeol Ryu, Seong-Heon Wie, Jieun Kim, Hyun-uk Jo, Se Yoon Park, Kyung-Wook Hong, Hye In Kim, Hyun ah Kim, Mi-Hee Kim, Mi Hyun Bae, Yong-Hak Sohn, Jieun Kim, Yangsoon Lee and Hyunjoo Pai

Antibiotics 2020, 9(9), 617; https://doi.org/10.3390/antibiotics9090617 - 18 Sep 2020

Cited by 10 | Viewed by 3162

Abstract

This study examined changes in the clinical characteristics of community-acquired acute pyelonephritis (CA-APN) in South Korea between the period 2010–2011 and 2017–2018. We recruited all CA-APN patients aged ≥19 years who visited eight hospitals in South Korea from September 2017 to August 2018, [...] Read more.

This study examined changes in the clinical characteristics of community-acquired acute pyelonephritis (CA-APN) in South Korea between the period 2010–2011 and 2017–2018. We recruited all CA-APN patients aged ≥19 years who visited eight hospitals in South Korea from September 2017 to August 2018, prospectively. Data collected were compared with those from the previous study in 2010–2012, with the same design and participation from 11 hospitals. A total of 617 patients were enrolled and compared to 818 patients’ data collected in 2010–2011. Escherichia coli was the most common causative pathogen of CA-APN in both periods (87.3% vs. 86.5%, p = 0.680). E. coli isolates showed significantly higher antimicrobial resistance against fluoroquinolone (32.0% vs. 21.6%, p < 0.001), cefotaxime (33.6% vs. 8.3%, p < 0.001), and trimethoprim/sulfamethoxazole (37.5% vs. 29.2%, p = 0.013) in 2017–2018 than in 2010–2011. Total duration of antibiotic treatment increased from 16.55 ± 9.68 days in 2010–2011 to 19.12 ± 9.90 days in 2017–2018 (p < 0.001); the duration of carbapenem usage increased from 0.59 ± 2.87 days in 2010–2011 to 1.79 ± 4.89 days in 2010–2011 (p < 0.001). The median hospitalization was higher for patients in 2017–2018 than in 2010–2011 (9 vs. 7 days, p < 0.001). In conclusion, antimicrobial resistance of E. coli to almost all antibiotic classes, especially third generation cephalosporin, increased significantly in CA-APN in South Korea. Consequently, total duration of antibiotic treatment, including carbapenem usage, increased. Full article

(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)

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14 pages, 773 KiB

Open AccessArticle

Surveillance of Antibiotic Resistance of Maltose-Negative Staphylococcus aureus in South African Dairy Herds

by Joanne Karzis, Inge-Marié Petzer, Edward F. Donkin, Vinny Naidoo and Eric M.C. Etter

Antibiotics 2020, 9(9), 616; https://doi.org/10.3390/antibiotics9090616 - 18 Sep 2020

Cited by 3 | Viewed by 3182

Abstract

Antibiotic resistance has been reported since the 1940s in both human and veterinary medicine. Many years of monitoring milk samples in South Africa led to identification of a novel maltose-negative Staphylococcus aureus (S. aureus) strain, which appears to be an emerging pathogen. [...] Read more.

Antibiotic resistance has been reported since the 1940s in both human and veterinary medicine. Many years of monitoring milk samples in South Africa led to identification of a novel maltose-negative Staphylococcus aureus (S. aureus) strain, which appears to be an emerging pathogen. In this study, the susceptibility of this strain to antibiotics was evaluated over time, during diverse seasons in various provinces and according to somatic cell count (SCC) categories. A data set of 271 maltose-negative S. aureus isolates, from milk samples of 117 dairy herds, was examined using the disk diffusion method, between 2010 and 2017. This study also compared the susceptibility testing of 57 maltose-negative and 57 maltose-positive S. aureus isolated from 38 farms, from three provinces using minimum inhibitory concentration (MIC). The MIC results for the maltose-negative S. aureus isolates showed highest resistance to ampicillin (100%) and penicillin (47.4) and lowest resistance (1.8%) to azithromycin, ciprofloxacin and erythromycin. The maltose-negative S. aureus isolates showed overall significantly increased antibiotic resistance compared to the maltose-positive strains, as well as multidrug resistance. Producers and veterinarians should consider probability of cure of such organisms (seemingly non-chronic) when adapting management and treatment, preventing unnecessary culling. Full article

(This article belongs to the Special Issue Staphylococcus spp. in Animals: Resistance to Antimicrobials, Virulence and Genetic Lineages)

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14 pages, 2302 KiB

Open AccessArticle

Evaluation of Intravenous Fosfomycin Disodium Dosing Regimens in Critically Ill Patients for Treatment of Carbapenem-Resistant Enterobacterales Infections Using Monte Carlo Simulation

by Pannee Leelawattanachai, Thitima Wattanavijitkul, Taniya Paiboonvong, Rongpong Plongla, Tanittha Chatsuwan, Sang Usayaporn, Wichit Nosoongnoen and Preecha Montakantikul

Antibiotics 2020, 9(9), 615; https://doi.org/10.3390/antibiotics9090615 - 18 Sep 2020

Cited by 16 | Viewed by 5621

Abstract

There are limited intravenous fosfomycin disodium (IVFOS) dosing regimens to treat carbapenem-resistant Enterobacterales (CRE) infections. This study aimed to use Monte Carlo simulation (MCS) for evaluation of IVFOS dosing regimens in critically ill patients with CRE infections. The dosing regimens in critically ill [...] Read more.

There are limited intravenous fosfomycin disodium (IVFOS) dosing regimens to treat carbapenem-resistant Enterobacterales (CRE) infections. This study aimed to use Monte Carlo simulation (MCS) for evaluation of IVFOS dosing regimens in critically ill patients with CRE infections. The dosing regimens in critically ill patients with various creatinine clearance were evaluated with MCS using minimum inhibitory concentration (MIC) distributions of fosfomycin against CRE clinical isolates in Thailand and the 24 h area under the plasma drug concentration–time curve over the minimum inhibitory concentration (AUC_0-24/MIC) of ≥21.5 to be a target for IVFOS. The achieved goal of the probability of target attainment (PTA) and a cumulative fraction of response (CFR) were ≥90%. A total of 129 non-duplicated CRE clinical isolates had MIC distributions from 0.38 to >1024 mg/L. IVFOS 8 g every 8 h, 1 h, or 4 h infusion, could achieve approximately 90% PTA of AUC_0-24/MIC target to treat CRE infections with MICs ≤ 128 mg/L. According to PTA target, an IVFOS daily dose to treat carbapenem-resistant Escherichia coli based on Clinical Laboratory Standards Institute (CLSI) breakpoints for urinary tract infections and one to treatment for CRE infections based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were 16 g/day and 8 g/day, respectively. All dosing regimens of IVFOS against CRE achieved CFR ≤ 70%. This study proposes the IVFOS dosing regimens based on CLSI and EUCAST breakpoints for the treatment of CRE infections. However, further clinical studies are needed to confirm the results of these findings. Full article

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12 pages, 568 KiB

Open AccessArticle

Antimicrobial Resistance Genes in Porcine Pasteurella multocida Are Not Associated with Its Antimicrobial Susceptibility Pattern

by Máximo Petrocchi-Rilo, César-B. Gutiérrez-Martín, Esther Pérez-Fernández, Anna Vilaró, Lorenzo Fraile and Sonia Martínez-Martínez

Antibiotics 2020, 9(9), 614; https://doi.org/10.3390/antibiotics9090614 - 17 Sep 2020

Cited by 14 | Viewed by 3416

Abstract

Forty-eight Pasteurella multocida isolates were recovered from porcine pneumonic lungs collected from farms in “Castilla y León” (north-western Spain) in 2017–2019. These isolates were characterized for their minimal inhibition concentrations to twelve antimicrobial agents and for the appearance of eight resistance genes: tetA [...] Read more.

Forty-eight Pasteurella multocida isolates were recovered from porcine pneumonic lungs collected from farms in “Castilla y León” (north-western Spain) in 2017–2019. These isolates were characterized for their minimal inhibition concentrations to twelve antimicrobial agents and for the appearance of eight resistance genes: tetA, tetB, bla_ROB1, bla_TEM, ermA, ermC, mphE and msrE. Relevant resistance percentages were shown against tetracyclines (52.1% for doxycycline, 68.7% for oxytetracycline), sulphamethoxazole/trimethoprim (43.7%) and tiamulin (25.0%), thus suggesting that P. multocida isolates were mostly susceptible to amoxicillin, ceftiofur, enrofloxacin, florfenicol, marbofloxacin and macrolides. Overall, 29.2% of isolates were resistant to more than two antimicrobials. The tetracycline resistance genes (tetA and tetB) were detected in 22.9% of the isolates, but none were positive to both simultaneously; bla_ROB1 and bla_TEM genes were found in one third of isolates but both genes were detected simultaneously in only one isolate. The ermC gene was observed in 41.7% of isolates, a percentage that decreased to 22.9% for msrE; finally, ermA was harbored by 16.7% and mphE was not found in any of them. Six clusters were established based on hierarchical clustering analysis on antimicrobial susceptibility for the twelve antimicrobials. Generally, it was unable to foresee the antimicrobial susceptibility pattern for each family and the association of each particular isolate inside the clusters established from the presence or absence of the resistance genes analyzed. Full article

(This article belongs to the Special Issue Optimization of Veterinary Antimicrobial Treatment in Companion and Food Animals)

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14 pages, 1323 KiB

Open AccessArticle

Molecular Characterization and Comparative Genomics of IncQ-3 Plasmids Conferring Resistance to Various Antibiotics Isolated from a Wastewater Treatment Plant in Warsaw (Poland)

by Marta Piotrowska, Lukasz Dziewit, Rafał Ostrowski, Cora Chmielowska and Magdalena Popowska

Antibiotics 2020, 9(9), 613; https://doi.org/10.3390/antibiotics9090613 - 17 Sep 2020

Cited by 11 | Viewed by 4062

Abstract

As small, mobilizable replicons with a broad host range, IncQ plasmids are widely distributed among clinical and environmental bacteria. They carry antibiotic resistance genes, and it has been shown that they confer resistance to β-lactams, fluoroquinolones, aminoglycosides, trimethoprim, sulphonamides, and tetracycline. The previously [...] Read more.

As small, mobilizable replicons with a broad host range, IncQ plasmids are widely distributed among clinical and environmental bacteria. They carry antibiotic resistance genes, and it has been shown that they confer resistance to β-lactams, fluoroquinolones, aminoglycosides, trimethoprim, sulphonamides, and tetracycline. The previously proposed classification system divides the plasmid group into four subgroups, i.e., IncQ-1, IncQ-2, IncQ-3, and IncQ-4. The last two subgroups have been poorly described so far. The aim of this study was to analyze five newly identified IncQ-3 plasmids isolated from a wastewater treatment plant in Poland and to compare them with all known plasmids belonging to the IncQ-3 subgroup whose sequences were retrieved from the NCBI database. The complete nucleotide sequences of the novel plasmids were annotated and bioinformatic analyses were performed, including identification of core genes and auxiliary genetic load. Furthermore, functional experiments testing plasmid mobility were carried out. Phylogenetic analysis based on three core genes (repA, mobA/repB, and mobC) revealed the presence of three main clusters of IncQ-3 replicons. Apart from having a highly conserved core, the analyzed IncQ-3 plasmids were vectors of antibiotic resistance genes, including (I) the qnrS2 gene that encodes fluoroquinolone resistance and (II) β-lactam, trimethoprim, and aminoglycoside resistance genes within integron cassettes. Full article

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

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17 pages, 1146 KiB

Open AccessArticle

Synthesis, ADMET Properties, and In Vitro Antimicrobial and Antibiofilm Activity of 5-Nitro-2-thiophenecarbaldehyde N-((E)-(5-Nitrothienyl)methylidene)hydrazone (KTU-286) against Staphylococcus aureus with Defined Resistance Mechanisms

by Povilas Kavaliauskas, Birute Grybaite, Vytautas Mickevicius, Ruta Petraitiene, Ramune Grigaleviciute, Rita Planciuniene, Philip Gialanella, Alius Pockevicius and Vidmantas Petraitis

Antibiotics 2020, 9(9), 612; https://doi.org/10.3390/antibiotics9090612 - 17 Sep 2020

Cited by 25 | Viewed by 3507

Abstract

The emergence of drug-resistant Staphylococcus aureus is responsible for high morbidity and mortality worldwide. New therapeutic options are needed to fight the increasing antimicrobial resistance among S. aureus in the clinical setting. We, therefore, characterized the in silico absorption, distribution, metabolism, elimination, and [...] Read more.

The emergence of drug-resistant Staphylococcus aureus is responsible for high morbidity and mortality worldwide. New therapeutic options are needed to fight the increasing antimicrobial resistance among S. aureus in the clinical setting. We, therefore, characterized the in silico absorption, distribution, metabolism, elimination, and toxicity (ADMET) and in vitro antimicrobial activity of 5-nitro-2-thiophenecarbaldehyde N-((E)-(5-nitrothienyl)methylidene)hydrazone (KTU-286) against drug-resistant S. aureus strains with genetically defined resistance mechanisms. The antimicrobial activity of KTU-286 was determined by CLSI recommendations. The ADMET properties were estimated by using in silico modeling. The activity on biofilm integrity was examined by crystal violet assay. KTU-286 demonstrated low estimated toxicity and low skin permeability. The highest antimicrobial activity was observed among pan-susceptible (Pan-S) S. aureus (minimal inhibitory concentration (MIC) 0.5–2.0 µg/mL, IC₅₀ = 0.460 µg/mL), followed by vancomycin resistant S. aureus (VRSA) (MIC 4.0 µg/mL, IC₅₀ = 1.697 µg/mL) and methicillin-resistant S. aureus (MRSA) (MIC 1.0–16.0 µg/mL, IC₅₀ = 2.282 µg/mL). KTU-286 resulted in significant (p < 0.05) loss of S. aureus biofilm integrity in vitro. Further studies are needed for a better understanding of safety, synergistic relationship, and therapeutic potency of KTU-286. Full article

(This article belongs to the Special Issue Novel Targets and Mechanisms in Antimicrobial Drug Discovery)

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15 pages, 2904 KiB

Open AccessArticle

Antimicrobial, Antioxidant, and Antiproliferative Effects of Coronilla minima: An Unexplored Botanical Species

by Claudio Ferrante, Paola Angelini, Roberto Venanzoni, Giancarlo Angeles Flores, Bruno Tirillini, Lucia Recinella, Annalisa Chiavaroli, Luigi Brunetti, Sheila Leone, Simonetta Cristina Di Simone, Maria Chiara Ciferri, Gokhan Zengin, Gunes Ak, Luigi Menghini and Giustino Orlando

Antibiotics 2020, 9(9), 611; https://doi.org/10.3390/antibiotics9090611 - 17 Sep 2020

Cited by 16 | Viewed by 4016

Abstract

Coronilla species, belonging to the Coronilla genus (Fabaceae), have long been used in traditional medicine for treating cold, diabetes, pain, and as cardiotonics. The goal of the present study was to explore the phytochemical composition and pharmaco-toxicological properties of C. minima. In this [...] Read more.

Coronilla species, belonging to the Coronilla genus (Fabaceae), have long been used in traditional medicine for treating cold, diabetes, pain, and as cardiotonics. The goal of the present study was to explore the phytochemical composition and pharmaco-toxicological properties of C. minima. In this regard, phenolic content, scavenging/reducing properties and antimicrobial activity toward pathogen bacterial (Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus aureus) and fungal strains (Candida albicans, C. tropicalis, Aspergillus tubigensis and A. minutus) were investigated. Extract effects on human colon cancer HCT116 cell viability were also assayed. Finally, a bioinformatics approach was conducted with the aim to identify putative microbial and human protein targets underlying antibacterial, antimycotic, and antiproliferative effects. Phytochemical investigation suggested that water extract is richer in terms of total flavonoid and phenol content, whereas the hydroalcoholic extract was revealed to be more potent as antioxidant agent. According to bioinformatics analysis, the antibacterial activity of the hydroalcoholic extract could be related to its content in resveratrol. The presence of resveratrol could also explain the hydroalcoholic extract efficacy in reducing HCT116 cell viability. In conclusion, the present study represents the first phytochemical and bio-pharmacological investigation about C. minima. Like other plants belonging to the Fabaceae family, C. minima revealed a good source of resveratrol, which could explain, albeit partially, the efficacy of the hydroalcoholic extract as antimicrobial, antioxidant, and antiproliferative agent. Full article

(This article belongs to the Special Issue Natural Antimicrobial Products from Plants and Fungi: Current Knowledge and Future Prospects)

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29 pages, 46298 KiB

Open AccessReview

Point-of-Care C-Reactive Protein Testing to Reduce Antibiotic Prescribing for Respiratory Tract Infections in Primary Care: Systematic Review and Meta-Analysis of Randomised Controlled Trials

by Nahara Anani Martínez-González, Ellen Keizer, Andreas Plate, Samuel Coenen, Fabio Valeri, Jan Yvan Jos Verbakel, Thomas Rosemann, Stefan Neuner-Jehle and Oliver Senn

Antibiotics 2020, 9(9), 610; https://doi.org/10.3390/antibiotics9090610 - 16 Sep 2020

Cited by 50 | Viewed by 7042

Abstract

C-reactive protein (CRP) point-of-care testing (POCT) is increasingly being promoted to reduce diagnostic uncertainty and enhance antibiotic stewardship. In primary care, respiratory tract infections (RTIs) are the most common reason for inappropriate antibiotic prescribing, which is a major driver for antibiotic resistance. We [...] Read more.

C-reactive protein (CRP) point-of-care testing (POCT) is increasingly being promoted to reduce diagnostic uncertainty and enhance antibiotic stewardship. In primary care, respiratory tract infections (RTIs) are the most common reason for inappropriate antibiotic prescribing, which is a major driver for antibiotic resistance. We systematically reviewed the available evidence on the impact of CRP-POCT on antibiotic prescribing for RTIs in primary care. Thirteen moderate to high-quality studies comprising 9844 participants met our inclusion criteria. Meta-analyses showed that CRP-POCT significantly reduced immediate antibiotic prescribing at the index consultation compared with usual care (RR 0.79, 95%CI 0.70 to 0.90, p = 0.0003, I² = 76%) but not during 28-day (n = 7) follow-up. The immediate effect was sustained at 12 months (n = 1). In children, CRP-POCT reduced antibiotic prescribing when CRP (cut-off) guidance was provided (n = 2). Meta-analyses showed significantly higher rates of re-consultation within 30 days (n = 8, 1 significant). Clinical recovery, resolution of symptoms, and hospital admissions were not significantly different between CRP-POCT and usual care. CRP-POCT can reduce immediate antibiotic prescribing for RTIs in primary care (number needed to (NNT) for benefit = 8) at the expense of increased re-consultations (NNT for harm = 27). The increase in re-consultations and longer-term effects of CRP-POCT need further evaluation. Overall, the benefits of CRP-POCT outweigh the potential harms (NNTnet = 11). Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Primary Care)

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21 pages, 1115 KiB

Open AccessReview

Strategies to Reduce Biofilm Formation in PEEK Materials Applied to Implant Dentistry—A Comprehensive Review

by Renata Scheeren Brum, Luiza Gomes Labes, Cláudia Ângela Maziero Volpato, César Augusto Magalhães Benfatti and Andrea de Lima Pimenta

Antibiotics 2020, 9(9), 609; https://doi.org/10.3390/antibiotics9090609 - 16 Sep 2020

Cited by 27 | Viewed by 5860

Abstract

Polyether-ether-ketone (PEEK) has emerged in Implant Dentistry with a series of short-time applications and as a promising material to substitute definitive dental implants. Several strategies have been investigated to diminish biofilm formation on the PEEK surface aiming to decrease the possibility of related [...] Read more.

Polyether-ether-ketone (PEEK) has emerged in Implant Dentistry with a series of short-time applications and as a promising material to substitute definitive dental implants. Several strategies have been investigated to diminish biofilm formation on the PEEK surface aiming to decrease the possibility of related infections. Therefore, a comprehensive review was carried out in order to compare PEEK with materials widely used nowadays in Implant Dentistry, such as titanium and zirconia, placing emphasis on studies investigating its ability to grant or prevent biofilm formation. Most studies failed to reveal significant antimicrobial activity in pure PEEK, while several studies described new strategies to reduce biofilm formation and bacterial colonization on this material. Those include the PEEK sulfonation process, incorporation of therapeutic and bioactive agents in PEEK matrix or on PEEK surface, PEEK coatings and incorporation of reinforcement agents, in order to produce nanocomposites or blends. The two most analyzed surface properties were contact angle and roughness, while the most studied bacteria were Escherichia coli and Staphylococcus aureus. Despite PEEK’s susceptibility to biofilm formation, a great number of strategies discussed in this study were able to improve its antibiofilm and antimicrobial properties. Full article

(This article belongs to the Special Issue New Insights on Biofilm Antimicrobial Strategies)

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19 pages, 920 KiB

Open AccessArticle

Delayed Antibiotic Prescription by General Practitioners in the UK: A Stated-Choice Study

by Liz Morrell, James Buchanan, Laurence S. J. Roope, Koen B. Pouwels, Christopher C. Butler, Benedict Hayhoe, Michael V. Moore, Sarah Tonkin-Crine, Monsey McLeod, Julie V. Robotham, A. Sarah Walker, Sarah Wordsworth and on behalf of the STEPUP team

Antibiotics 2020, 9(9), 608; https://doi.org/10.3390/antibiotics9090608 - 16 Sep 2020

Cited by 5 | Viewed by 4553

Abstract

Delayed antibiotic prescription in primary care has been shown to reduce antibiotic consumption, without increasing risk of complications, yet is not widely used in the UK. We sought to quantify the relative importance of factors affecting the decision to give a delayed prescription, [...] Read more.

Delayed antibiotic prescription in primary care has been shown to reduce antibiotic consumption, without increasing risk of complications, yet is not widely used in the UK. We sought to quantify the relative importance of factors affecting the decision to give a delayed prescription, using a stated-choice survey among UK general practitioners. Respondents were asked whether they would provide a delayed or immediate prescription in fifteen hypothetical consultations, described by eight attributes. They were also asked if they would prefer not to prescribe antibiotics. The most important determinants of choice between immediate and delayed prescription were symptoms, duration of illness, and the presence of multiple comorbidities. Respondents were more likely to choose a delayed prescription if the patient preferred not to have antibiotics, but consultation length had little effect. When given the option, respondents chose not to prescribe antibiotics in 51% of cases, with delayed prescription chosen in 21%. Clinical features remained important. Patient preference did not affect the decision to give no antibiotics. We suggest that broader dissemination of the clinical evidence supporting use of delayed prescription for specific presentations may help increase appropriate use. Establishing patient preferences regarding antibiotics may help to overcome concerns about patient acceptance. Increasing consultation length appears unlikely to affect the use of delayed prescription. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Primary Care)

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19 pages, 857 KiB

Open AccessReview

Measuring Antibiotic Stewardship Programmes and Initiatives: An Umbrella Review in Primary Care Medicine and a Systematic Review of Dentistry

by Leanne Teoh, Alastair J Sloan, Michael J McCullough and Wendy Thompson

Antibiotics 2020, 9(9), 607; https://doi.org/10.3390/antibiotics9090607 - 16 Sep 2020

Cited by 14 | Viewed by 4598

Abstract

Antibiotic stewardship aims to tackle the global problem of drug-resistant infections by promoting the responsible use of antibiotics. Most antibiotics are prescribed in primary care and widespread overprescribing has been reported, including 80% in dentistry. This review aimed to identify outcomes measured in [...] Read more.

Antibiotic stewardship aims to tackle the global problem of drug-resistant infections by promoting the responsible use of antibiotics. Most antibiotics are prescribed in primary care and widespread overprescribing has been reported, including 80% in dentistry. This review aimed to identify outcomes measured in studies evaluating antibiotic stewardship across primary healthcare. An umbrella review was undertaken across medicine and a systematic review in dentistry. Systematic searches of Ovid Medline, Ovid Embase and Web of Science were undertaken. Two authors independently selected and quality assessed the included studies (using Critical Appraisal Skills Programme for the umbrella review and Quality Assessment Tool for Studies with Diverse Designs for the systematic review). Metrics used to evaluate antibiotic stewardship programmes and interventions were extracted and categorized. Comparisons between medical and dental settings were made. Searches identified 2355 medical and 2704 dental studies. After screening and quality assessment, ten and five studies, respectively, were included. Three outcomes were identified across both medical and dental studies: All focused on antibiotic usage. Four more outcomes were found only in medical studies: these measured patient outcomes, such as adverse effects. To evaluate antibiotic stewardship programmes and interventions across primary healthcare settings, measures of antibiotic use and patient outcomes are recommended. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Primary Care)

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34 pages, 4637 KiB

Open AccessArticle

UHPLC-ESI-QTOF-MS/MS-Based Molecular Networking Guided Isolation and Dereplication of Antibacterial and Antifungal Constituents of Ventilago denticulata

by Muhaiminatul Azizah, Patcharee Pripdeevech, Tawatchai Thongkongkaew, Chulabhorn Mahidol, Somsak Ruchirawat and Prasat Kittakoop

Antibiotics 2020, 9(9), 606; https://doi.org/10.3390/antibiotics9090606 - 15 Sep 2020

Cited by 32 | Viewed by 6930

Abstract

Ventilago denticulata is an herbal medicine for the treatment of wound infection; therefore this plant may rich in antibacterial agents. UHPLC-ESI-QTOF-MS/MS-Based molecular networking guided isolation and dereplication led to the identification of antibacterial and antifungal agents in V. denticulata. Nine antimicrobial agents [...] Read more.

Ventilago denticulata is an herbal medicine for the treatment of wound infection; therefore this plant may rich in antibacterial agents. UHPLC-ESI-QTOF-MS/MS-Based molecular networking guided isolation and dereplication led to the identification of antibacterial and antifungal agents in V. denticulata. Nine antimicrobial agents in V. denticulata were isolated and characterized; they are divided into four groups including (I) flavonoid glycosides, rhamnazin 3-rhamninoside (7), catharticin or rhamnocitrin 3-rhamninoside (8), xanthorhamnin B or rhamnetin 3-rhamninoside (9), kaempferol 3-rhamninoside (10) and flavovilloside or quercetin 3-rhamninoside (11), (II) benzisochromanquinone, ventilatones B (12) and A (15), (III) a naphthopyrone ventilatone C (16) and (IV) a triterpene lupeol (13). Among the isolated compounds, ventilatone C (16) was a new compound. Moreover, kaempferol, chrysoeriol, isopimpinellin, rhamnetin, luteolin, emodin, rhamnocitrin, ventilagodenin A, rhamnazin and mukurozidiol, were tentatively identified as antimicrobial compounds in extracts of V. denticulata by a dereplication method. MS fragmentation of rhamnose-containing compounds gave an oxonium ion, C₆H₉O₃⁺ at m/z 129, while that of galactose-containing glycosides provided the fragment ion at m/z 163 of C₆H₁₁O₅⁺. These fragment ions may be used to confirm the presence of rhamnose or galactose in mass spectrometry-based analysis of natural glycosides or oligosaccharide attached to biomolecules, that is, glycoproteins. Full article

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14 pages, 1883 KiB

Open AccessArticle

Evaluation of Multiple Impacts of Furfural Acetone on Nematodes In Vitro and Control Efficiency against Root-Knot Nematodes in Pots and Fields

by Wanli Cheng, Xue Yang, Li Zeng, Dian Huang, Minmin Cai, Longyu Zheng, Ziniu Yu and Jibin Zhang

Antibiotics 2020, 9(9), 605; https://doi.org/10.3390/antibiotics9090605 - 15 Sep 2020

Cited by 7 | Viewed by 3109

Abstract

Root-knot nematodes (RKNs) seriously endanger agricultural development and cause great economic losses worldwide. Natural product furfural acetone (FAc) is a promising nematicide with strong attractant and nematicidal activities, but baseline information about the impact of FAc on the reproduction, egg hatching, feeding, and [...] Read more.

Root-knot nematodes (RKNs) seriously endanger agricultural development and cause great economic losses worldwide. Natural product furfural acetone (FAc) is a promising nematicide with strong attractant and nematicidal activities, but baseline information about the impact of FAc on the reproduction, egg hatching, feeding, and growth of nematodes and its pest control efficiency in field are lacking. Here, the inhibition effects of FAc on nematodes in vitro and its RKN control efficiency in pot and field were investigated. FAc inhibited the egg hatching of Meloidogyne incognita by 91.7% at 200 mg/L after 2 days and suppressed the reproduction, feeding, and growth of Caenorhabditis elegans in vitro. In pot experiments, FAc in various dosages reduced the disease index of plant root significantly. In field experiments, FAc exhibited control effect on RKNs equivalent to commercial nematicides avermectin and metam sodium, with a reduction in disease index by 36.9% at a dose of 50 mg/plant. FAc also reduced the population density of RKNs in soil, with a reduction rate of 75.3% at the dose of 750 mg/m². No adverse effect was detected on plant growth after FAc application. These results provide compelling evidence for development of FAc as an appropriate alternative for current nematicides. Full article

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