Antibiotics

14 pages, 1870 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Physicochemical and Biological Characterization of Encapsulated Olive Leaf Extracts for Food Preservation

by Wafa Medfai, Imen Oueslati, Emilie Dumas, Zina Harzalli, Christophe Viton, Ridha Mhamdi and Adem Gharsallaoui

Antibiotics 2023, 12(6), 987; https://doi.org/10.3390/antibiotics12060987 - 31 May 2023

Cited by 4 | Viewed by 1851

Abstract

Phenolic compounds in olive leaves have an excellent antioxidant activity and good antimicrobial properties. These bioactive molecules have beneficial properties for health, arousing great scientific and commercial interest. This study reports lyophilized olive leaf extracts (OLE) encapsulated by spray-drying using maltodextrins, maltodextrins–pectin and [...] Read more.

Phenolic compounds in olive leaves have an excellent antioxidant activity and good antimicrobial properties. These bioactive molecules have beneficial properties for health, arousing great scientific and commercial interest. This study reports lyophilized olive leaf extracts (OLE) encapsulated by spray-drying using maltodextrins, maltodextrins–pectin and maltodextrins–gum Arabic as encapsulating agents. Lyophilized OLE were collected from two varieties cultivated in a harsh pedo-climatic conditions of the arid region of Tunisia. The effects of the genetic factor and the different encapsulating agents on the physicochemical properties of microcapsules and their behavior during storage, as well as their antimicrobial activities, were studied. Microcapsules successfully passed heat treatment and storage conditions and their antimicrobial activities were preserved. The encapsulating agent combination improved the encapsulation efficiency and the product yield in Zarrazi variety compared to Dhokar one. In addition, Dhokar variety microparticles showed the best heat stability at 4 and 25 °C after 90 days of storage and the higher inhibition percent against bacteria. The results of the present study evidenced that the best conditions for OLE encapsulation were obtained when the maltodextrins–pectin and maltodextrins–gum Arabic were combined to form a hybrid coating material. Full article

(This article belongs to the Special Issue Antimicrobials Agents: Latest Advances and Prospects)

► Show Figures

Figure 1

11 pages, 832 KiB

Open AccessEditor’s ChoiceArticle

Comparison of Cefepime with Piperacillin/Tazobactam Treatment in Patients with Hospital-Acquired Pneumonia

by Bo-Guen Kim, Danbee Kang, Kyung Hoon Min, Juhee Cho and Kyeongman Jeon

Antibiotics 2023, 12(6), 984; https://doi.org/10.3390/antibiotics12060984 - 30 May 2023

Cited by 3 | Viewed by 8000

Abstract

Although cefepime and piperacillin/tazobactam are commonly prescribed for the treatment of hospital-acquired pneumonia (HAP), which one is the superior therapy remains unclear. Using Korean National Health Insurance Service data from January 2018 to December 2018, we compared the clinical outcomes of patients with [...] Read more.

Although cefepime and piperacillin/tazobactam are commonly prescribed for the treatment of hospital-acquired pneumonia (HAP), which one is the superior therapy remains unclear. Using Korean National Health Insurance Service data from January 2018 to December 2018, we compared the clinical outcomes of patients with HAP who were treated with cefepime and those treated with piperacillin/tazobactam. Data from 9955 adult patients with HAP, of whom 1502 (15%) received cefepime and 8453 (85%) received piperacillin/tazobactam, were retrieved for primary analysis. Tube feeding, suctioning, positioning care, and intensive care unit admission were more common among patients who received piperacillin/tazobactam. Treatment outcomes, including rates of in-hospital mortality, pneumonia-related readmission, and all-cause mortality within 6 months after discharge, were comparable between the two groups. In a subgroup analysis of data from patients who required tube feeding, the risk for in-hospital mortality was significantly higher among those who received cefepime (fully adjusted odds ratio, 1.43; 95% confidence interval, 1.04–1.97; p = 0.042). Treatment outcomes did not differ between patients who received cefepime and those who received piperacillin/tazobactam treatment, but among patients who were at risk for aspiration, such as those receiving tube feeding, those who received piperacillin/tazobactam had lower rates of in-hospital mortality. Full article

(This article belongs to the Special Issue Antibiotics Use and Therapy in Gram-Negative Bacterial Infection)

► Show Figures

Figure 1

17 pages, 1794 KiB

Open AccessEditor’s ChoiceReview

Insect Antimicrobial Peptides: Advancements, Enhancements and New Challenges

by Matteo Dho, Valentina Candian and Rosemarie Tedeschi

Antibiotics 2023, 12(6), 952; https://doi.org/10.3390/antibiotics12060952 - 24 May 2023

Cited by 14 | Viewed by 3987

Abstract

Several insects are known as vectors of a wide range of animal and human pathogens causing various diseases. However, they are also a source of different substances, such as the Antimicrobial Peptides (AMPs), which can be employed in the development of natural bioactive [...] Read more.

Several insects are known as vectors of a wide range of animal and human pathogens causing various diseases. However, they are also a source of different substances, such as the Antimicrobial Peptides (AMPs), which can be employed in the development of natural bioactive compounds for medical, veterinary and agricultural applications. It is well known that AMP activity, in contrast to most classical antibiotics, does not lead to the development of natural bacterial resistance, or at least the frequency of resistance is considered to be low. Therefore, there is a strong interest in assessing the efficacy of the various peptides known to date, identifying new compounds and evaluating possible solutions in order to increase their production. Moreover, implementing AMP modulation in insect rearing could preserve insect health in large-scale production. This review describes the current knowledge on insect AMPs, presenting the validated ones for the different insect orders. A brief description of their mechanism of action is reported with focus on proposed applications. The possible effects of insect diet on AMP translation and synthesis have been discussed. Full article

(This article belongs to the Special Issue Potential of Antimicrobial Peptides for an Exciting Future)

► Show Figures

Figure 1

13 pages, 1875 KiB

Open AccessEditor’s ChoiceArticle

Assessing the Antimicrobial Properties of Honey Protein Components through In Silico Comparative Peptide Composition and Distribution Analysis

by Andrzej Łyskowski, Michał Miłek and Małgorzata Dżugan

Antibiotics 2023, 12(5), 830; https://doi.org/10.3390/antibiotics12050830 - 28 Apr 2023

Viewed by 1856

Abstract

The availability of reference proteomes for two honeybee species (Apis mellifera and Apis cerana cerana) opens the possibility of in silico studies of diverse properties of the selected protein fractions. The antimicrobial activity of honey is well established and related to [...] Read more.

The availability of reference proteomes for two honeybee species (Apis mellifera and Apis cerana cerana) opens the possibility of in silico studies of diverse properties of the selected protein fractions. The antimicrobial activity of honey is well established and related to its composition, including protein components. We have performed a comparative study on a selected fraction of the honey-related proteins, as well as other bee-secreted proteins, utilizing a publicly available database of established and verified peptides with antimicrobial properties. Using a high-performance sequence aligner (diamond), protein components with antimicrobial peptide sequences were identified and analyzed. The identified peptides were mapped on the available bee proteome sequences, as well as on model structures provided by the AlphaFold project. The results indicate a highly conserved localization of the identified sequences within a limited number of the protein components. Putative antimicrobial fragments also show high sequence-based similarity to the multiple peptides contained in the reference databases. For the 2 databases used, the lowest calculated percentage of similarity ranged from 30.1% to 32.9%, with a respective average of 88.5% and 79.3% for the Apis mellifera proteome. It was revealed that the antimicrobial peptides (AMPs) site is a single, well-defined domain with potentially conserved structural features. In the case of the examples studied in detail, the structural domain takes the form of the two β-sheets, stabilized by α-helices in one case, and a six-β-sheet-only domain localized in the C-terminal part of the sequence, respectively. Moreover, no significant differences were found in the composition of the antibacterial fraction of peptides that were identified in the proteomes of both species. Full article

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

► Show Figures

Graphical abstract

15 pages, 3597 KiB

Open AccessEditor’s ChoiceArticle

D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides

by Maria Veronica Humpola, Roque Spinelli, Melina Erben, Virginia Perdomo, Georgina Guadalupe Tonarelli, Fernando Albericio and Alvaro Sebastian Siano

Antibiotics 2023, 12(5), 821; https://doi.org/10.3390/antibiotics12050821 - 27 Apr 2023

Cited by 4 | Viewed by 1889

Abstract

Here we designed and synthesized analogs of two antimicrobial peptides, namely C10:0-A2, a lipopeptide, and TA4, a cationic α-helical amphipathic peptide, and used non-proteinogenic amino acids to improve their therapeutic properties. The physicochemical properties of these analogs were analyzed, including their retention time, [...] Read more.

Here we designed and synthesized analogs of two antimicrobial peptides, namely C10:0-A2, a lipopeptide, and TA4, a cationic α-helical amphipathic peptide, and used non-proteinogenic amino acids to improve their therapeutic properties. The physicochemical properties of these analogs were analyzed, including their retention time, hydrophobicity, and critical micelle concentration, as well as their antimicrobial activity against gram-positive and gram-negative bacteria and yeast. Our results showed that substitution with D- and N-methyl amino acids could be a useful strategy to modulate the therapeutic properties of antimicrobial peptides and lipopeptides, including enhancing stability against enzymatic degradation. The study provides insights into the design and optimization of antimicrobial peptides to achieve improved stability and therapeutic efficacy. TA4(dK), C10:0-A2(6-NMeLys), and C10:0-A2(9-NMeLys) were identified as the most promising molecules for further studies. Full article

(This article belongs to the Special Issue Antimicrobial Peptides from Natural Sources to Synthetic Optimization)

► Show Figures

Figure 1

14 pages, 692 KiB

Open AccessEditor’s ChoiceArticle

Biocide Susceptibility and Antimicrobial Resistance of Escherichia coli Isolated from Swine Feces, Pork Meat and Humans in Germany

by David Attuy Vey da Silva, Ralf Dieckmann, Oliwia Makarewicz, Anita Hartung, Astrid Bethe, Mirjam Grobbel, Vitaly Belik, Mathias W. Pletz, Sascha Al Dahouk and Szilvia Neuhaus

Antibiotics 2023, 12(5), 823; https://doi.org/10.3390/antibiotics12050823 - 27 Apr 2023

Cited by 4 | Viewed by 2584

Abstract

Phenotypic susceptibility testing of Escherichia (E.) coli is an essential tool to gain a better understanding of the potential impact of biocide selection pressure on antimicrobial resistance. We, therefore, determined the biocide and antimicrobial susceptibility of 216 extended-spectrum β-lactamase-producing (ESBL) and [...] Read more.

Phenotypic susceptibility testing of Escherichia (E.) coli is an essential tool to gain a better understanding of the potential impact of biocide selection pressure on antimicrobial resistance. We, therefore, determined the biocide and antimicrobial susceptibility of 216 extended-spectrum β-lactamase-producing (ESBL) and 177 non-ESBL E. coli isolated from swine feces, pork meat, voluntary donors and inpatients and evaluated associations between their susceptibilities. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of benzalkonium chloride, chlorhexidine digluconate (CHG), chlorocresol (PCMC), glutaraldehyde (GDA), isopropanol (IPA), octenidine dihydrochloride and sodium hypochlorite (NaOCl) showed unimodal distributions, indicating the absence of bacterial adaptation to biocides due to the acquisition of resistance mechanisms. Although MIC₉₅ and MBC₉₅ did not vary more than one doubling dilution step between isolates of porcine and human origin, significant differences in MIC and/or MBC distributions were identified for GDA, CHG, IPA, PCMC and NaOCl. Comparing non-ESBL and ESBL E. coli, significantly different MIC and/or MBC distributions were found for PCMC, CHG and GDA. Antimicrobial susceptibility testing revealed the highest frequency of resistant E. coli in the subpopulation isolated from inpatients. We observed significant but weakly positive correlations between biocide MICs and/or MBCs and antimicrobial MICs. In summary, our data indicate a rather moderate effect of biocide use on the susceptibility of E. coli to biocides and antimicrobials. Full article

(This article belongs to the Section Antibiotics in Animal Health)

► Show Figures

Figure 1

14 pages, 2183 KiB

Open AccessEditor’s ChoiceArticle

Sorangicin A Is Active against Chlamydia in Cell Culture, Explanted Fallopian Tubes, and Topical In Vivo Treatment

by Simon Graspeuntner, Katharina Koethke, Celeste Scholz, Lea Semmler, Mariia Lupatsii, Laura Kirchhoff, Jennifer Herrmann, Katharina Rox, Kathrin Wittstein, Nadja Käding, Lars C. Hanker, Marc Stadler, Mark Brönstrup, Rolf Müller, Kensuke Shima and Jan Rupp

Antibiotics 2023, 12(5), 795; https://doi.org/10.3390/antibiotics12050795 - 22 Apr 2023

Cited by 2 | Viewed by 2356

Abstract

Current treatment of Chlamydia trachomatis using doxycycline and azithromycin introduces detrimental side effects on the host’s microbiota. As a potential alternative treatment, the myxobacterial natural product sorangicin A (SorA) blocks the bacterial RNA polymerase. In this study we analyzed the effectiveness of SorA [...] Read more.

Current treatment of Chlamydia trachomatis using doxycycline and azithromycin introduces detrimental side effects on the host’s microbiota. As a potential alternative treatment, the myxobacterial natural product sorangicin A (SorA) blocks the bacterial RNA polymerase. In this study we analyzed the effectiveness of SorA against C. trachomatis in cell culture, and explanted fallopian tubes and systemic and local treatment in mice, providing also pharmacokinetic data on SorA. Potential side effects of SorA on the vaginal and gut microbiome were assessed in mice and against human-derived Lactobacillus species. SorA showed minimal inhibitory concentrations of 80 ng/mL (normoxia) to 120 ng/mL (hypoxia) against C. trachomatis in vitro and was eradicating C. trachomatis at a concentration of 1 µg/mL from fallopian tubes. In vivo, SorA reduced chlamydial shedding by more than 100-fold within the first days of infection by topical application corresponding with vaginal detection of SorA only upon topical treatment, but not after systemic application. SorA changed gut microbial composition during intraperitoneal application only and did neither alter the vaginal microbiota in mice nor affect growth of human-derived lactobacilli. Additional dose escalations and/or pharmaceutical modifications will be needed to optimize application of SorA and to reach sufficient anti-chlamydial activity in vivo. Full article

► Show Figures

Figure 1

21 pages, 1439 KiB

Open AccessEditor’s ChoiceReview

Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia: Host, Pathogen, and Treatment

by Joshua B. Parsons, Annette C. Westgeest, Brian P. Conlon and Vance G. Fowler, Jr.

Antibiotics 2023, 12(3), 455; https://doi.org/10.3390/antibiotics12030455 - 24 Feb 2023

Cited by 15 | Viewed by 6548

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a devastating pathogen responsible for a variety of life-threatening infections. A distinctive characteristic of this pathogen is its ability to persist in the bloodstream for several days despite seemingly appropriate antibiotics. Persistent MRSA bacteremia is common and is [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) is a devastating pathogen responsible for a variety of life-threatening infections. A distinctive characteristic of this pathogen is its ability to persist in the bloodstream for several days despite seemingly appropriate antibiotics. Persistent MRSA bacteremia is common and is associated with poor clinical outcomes. The etiology of persistent MRSA bacteremia is a result of the complex interplay between the host, the pathogen, and the antibiotic used to treat the infection. In this review, we explore the factors related to each component of the host–pathogen interaction and discuss the clinical relevance of each element. Next, we discuss the treatment options and diagnostic approaches for the management of persistent MRSA bacteremia. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Richard Proctor—Outstanding Contributions in the Fields of Persistent Staphylococcus aureus Infections)

► Show Figures

Figure 1

18 pages, 1712 KiB

Open AccessEditor’s ChoiceArticle

Investigation of α,ω-Disubstituted Polyamine-Cholic Acid Conjugates Identifies Hyodeoxycholic and Chenodeoxycholic Scaffolds as Non-Toxic, Potent Antimicrobials

by Kenneth Sue, Melissa M. Cadelis, Thomas Troia, Florent Rouvier, Marie-Lise Bourguet-Kondracki, Jean Michel Brunel and Brent R. Copp

Antibiotics 2023, 12(2), 404; https://doi.org/10.3390/antibiotics12020404 - 17 Feb 2023

Cited by 2 | Viewed by 1754

Abstract

With the increased incidence of antibiotic resistance, the discovery and development of new antibacterials is of increasing importance and urgency. The report of the natural product antibiotic squalamine in 1993 has stimulated a lot of interest in the study of structurally simplified cholic [...] Read more.

With the increased incidence of antibiotic resistance, the discovery and development of new antibacterials is of increasing importance and urgency. The report of the natural product antibiotic squalamine in 1993 has stimulated a lot of interest in the study of structurally simplified cholic acid-polyamine derivatives. We report the synthesis of a focused set of deoxycholic acid-polyamine conjugates and the identification of hyodeoxycholic acid derivatives as being potently active towards S. aureus MRSA and some fungal strains, but with no attendant cytotoxicity or hemolytic properties. Analogue 7e exhibited bactericidal activity towards a range of Gram-positive bacteria, while preliminary investigation of its mechanism of action ruled out the bacterial membrane as being a primary cellular target as determined using an ATP-release bioluminescence assay. Full article

(This article belongs to the Special Issue Discovery and Development of the Novel Antimicrobial Agent)

► Show Figures

Graphical abstract

27 pages, 6477 KiB

Open AccessEditor’s ChoiceArticle

Antimicrobial Activity of an Fmoc-Plantaricin 149 Derivative Peptide against Multidrug-Resistant Bacteria

by Gabriela Marinho Righetto, José Luiz de Souza Lopes, Paulo José Martins Bispo, Camille André, Julia Medeiros Souza, Adriano Defini Andricopulo, Leila Maria Beltramini and Ilana Lopes Baratella da Cunha Camargo

Antibiotics 2023, 12(2), 391; https://doi.org/10.3390/antibiotics12020391 - 15 Feb 2023

Cited by 6 | Viewed by 6993

Abstract

Antimicrobial resistance poses a major threat to public health. Given the paucity of novel antimicrobials to treat resistant infections, the emergence of multidrug-resistant bacteria renewed interest in antimicrobial peptides as potential therapeutics. This study designed a new analog of the antimicrobial peptide Plantaricin [...] Read more.

Antimicrobial resistance poses a major threat to public health. Given the paucity of novel antimicrobials to treat resistant infections, the emergence of multidrug-resistant bacteria renewed interest in antimicrobial peptides as potential therapeutics. This study designed a new analog of the antimicrobial peptide Plantaricin 149 (Pln149-PEP20) based on previous Fmoc-peptides. The minimal inhibitory concentrations of Pln149-PEP20 were determined for 60 bacteria of different species and resistance profiles, ranging from 1 mg/L to 128 mg/L for Gram-positive bacteria and 16 to 512 mg/L for Gram-negative. Furthermore, Pln149-PEP20 demonstrated excellent bactericidal activity within one hour. To determine the propensity to develop resistance to Pln149-PEP20, a directed-evolution in vitro experiment was performed. Whole-genome sequencing of selected mutants with increased MICs and wild-type isolates revealed that most mutations were concentrated in genes associated with membrane metabolism, indicating the most likely target of Pln149-PEP20. Synchrotron radiation circular dichroism showed how this molecule disturbs the membranes, suggesting a carpet mode of interaction. Membrane depolarization and transmission electron microscopy assays supported these two hypotheses, although a secondary intracellular mechanism of action is possible. The molecule studied in this research has the potential to be used as a novel antimicrobial therapy, although further modifications and optimization remain possible. Full article

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

► Show Figures

Figure 1

17 pages, 895 KiB

Open AccessEditor’s ChoiceReview

Antimicrobial Peptides against Bacterial Pathogens: Innovative Delivery Nanosystems for Pharmaceutical Applications

by Esther Imperlini, Federica Massaro and Francesco Buonocore

Antibiotics 2023, 12(1), 184; https://doi.org/10.3390/antibiotics12010184 - 16 Jan 2023

Cited by 13 | Viewed by 4767

Abstract

The introduction of antibiotics has revolutionized the treatment and prevention of microbial infections. However, the global spread of pathogens resistant to available antibiotics is a major concern. Recently, the WHO has updated the priority list of multidrug-resistant (MDR) species for which the discovery [...] Read more.

The introduction of antibiotics has revolutionized the treatment and prevention of microbial infections. However, the global spread of pathogens resistant to available antibiotics is a major concern. Recently, the WHO has updated the priority list of multidrug-resistant (MDR) species for which the discovery of new therapeutics is urgently needed. In this scenario, antimicrobial peptides (AMPs) are a new potential alternative to conventional antibiotics, as they show a low risk of developing antimicrobial resistance, thus preventing MDR bacterial infections. However, there are limitations and challenges related to the clinical impact of AMPs, as well as great scientific efforts to find solutions aimed at improving their biological activity, in vivo stability, and bioavailability by reducing the eventual toxicity. To overcome some of these issues, different types of nanoparticles (NPs) have been developed for AMP delivery over the last decades. In this review, we provide an update on recent nanosystems applied to AMPs, with special attention on their potential pharmaceutical applications for the treatment of bacterial infections. Among lipid nanomaterials, solid lipid NPs and lipid nanocapsules have been employed to enhance AMP solubility and protect peptides from proteolytic degradation. In addition, polymeric NPs, particularly nanogels, are able to help in reducing AMP toxicity and also increasing AMP loading. To boost AMP activity instead, mesoporous silica or gold NPs can be selected due to their easy surface functionalization. They have been also used as nanocarriers for different AMP combinations, thus synergistically potentiating their action against pathogens. Full article

(This article belongs to the Special Issue Reviews on Antimicrobial Peptides)

► Show Figures

Figure 1

33 pages, 17163 KiB

Open AccessEditor’s ChoiceReview

Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria

by Nina Compagne, Anais Vieira Da Cruz, Reinke T. Müller, Ruben C. Hartkoorn, Marion Flipo and Klaas M. Pos

Antibiotics 2023, 12(1), 180; https://doi.org/10.3390/antibiotics12010180 - 15 Jan 2023

Cited by 44 | Viewed by 7332

Abstract

Antimicrobial resistance (AMR) has become a major problem in public health leading to an estimated 4.95 million deaths in 2019. The selective pressure caused by the massive and repeated use of antibiotics has led to bacterial strains that are partially or even entirely [...] Read more.

Antimicrobial resistance (AMR) has become a major problem in public health leading to an estimated 4.95 million deaths in 2019. The selective pressure caused by the massive and repeated use of antibiotics has led to bacterial strains that are partially or even entirely resistant to known antibiotics. AMR is caused by several mechanisms, among which the (over)expression of multidrug efflux pumps plays a central role. Multidrug efflux pumps are transmembrane transporters, naturally expressed by Gram-negative bacteria, able to extrude and confer resistance to several classes of antibiotics. Targeting them would be an effective way to revive various options for treatment. Many efflux pump inhibitors (EPIs) have been described in the literature; however, none of them have entered clinical trials to date. This review presents eight families of EPIs active against Escherichia coli or Pseudomonas aeruginosa. Structure–activity relationships, chemical synthesis, in vitro and in vivo activities, and pharmacological properties are reported. Their binding sites and their mechanisms of action are also analyzed comparatively. Full article

(This article belongs to the Special Issue Efflux Pumps in Bacteria: What They Do and How We Can Stop Them)

► Show Figures

Figure 1

11 pages, 1912 KiB

Open AccessEditor’s ChoiceArticle

Effective Biofilm Eradication on Orthopedic Implants with Methylene Blue Based Antimicrobial Photodynamic Therapy In Vitro

by Julia Prinz, Marianne Wink, Sonja Neuhaus, Markus C. Grob, Heinrich Walt, Philipp P. Bosshard and Yvonne Achermann

Antibiotics 2023, 12(1), 118; https://doi.org/10.3390/antibiotics12010118 - 8 Jan 2023

Cited by 4 | Viewed by 5791

Abstract

Periprosthetic joint infections (PJI) are difficult to treat due to biofilm formation on implant surfaces, often requiring removal or exchange of prostheses along with long-lasting antibiotic treatment. This in vitro study investigated the effect of methylene blue photodynamic therapy (MB-PDT) on PJI-causing biofilms [...] Read more.

Periprosthetic joint infections (PJI) are difficult to treat due to biofilm formation on implant surfaces, often requiring removal or exchange of prostheses along with long-lasting antibiotic treatment. This in vitro study investigated the effect of methylene blue photodynamic therapy (MB-PDT) on PJI-causing biofilms on different implant materials. MB-PDT (664 nm LED, 15 J/cm²) was tested on different Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Cutibacterium acnes strains in both planktonic form and grown in early and mature biofilms on prosthetic materials (polyethylene, titanium alloys, cobalt–chrome-based alloys, and bone cement). The minimum bactericidal concentration with 100% killing (MBC_100%) was determined. Chemical and topographical alterations were investigated on the prosthesis surfaces after MB-PDT. Results showed a MBC_100% of 0.5–5 μg/mL for planktonic bacteria and 50–100 μg/mL for bacteria in biofilms—independent of the tested strain, the orthopedic material, or the maturity of the biofilm. Material testing showed no relevant surface modification. MB-PDT effectively eradicated common PJI pathogens on arthroplasty materials without damage to the materials, suggesting that MB-PDT could be used as a novel treatment method, replacing current, more invasive approaches and potentially shortening the antibiotic treatment in PJI. This would improve quality of life and reduce morbidity, mortality, and high health-care costs. Full article

(This article belongs to the Special Issue New and Innovative Applications of Antimicrobial Photodynamic Therapy, 2nd Edition)

► Show Figures

Figure 1

14 pages, 3551 KiB

Open AccessEditor’s ChoiceArticle

Efficient AntiMycolata Agents by Increasing the Lipophilicity of Known Antibiotics through Multicomponent Reactions

by Angela Trejo, Carme Masdeu, Irene Serrano-Pérez, Marina Pedrola, Narcís Juanola, Ouldouz Ghashghaei, Guadalupe Jiménez-Galisteo, Rodolfo Lavilla, Francisco Palacios, Concepción Alonso and Miguel Viñas

Antibiotics 2023, 12(1), 83; https://doi.org/10.3390/antibiotics12010083 - 3 Jan 2023

Cited by 2 | Viewed by 3504

Abstract

New antibiotic agents were prepared using Povarov and Ugi multicomponent reactions upon the known drugs sulfadoxine and dapsone. The prepared derivatives, with increased lipophilicity, showed improved efficiency against Mycolata bacteria. Microbiological guidance for medicinal chemistry is a powerful tool to design new and [...] Read more.

New antibiotic agents were prepared using Povarov and Ugi multicomponent reactions upon the known drugs sulfadoxine and dapsone. The prepared derivatives, with increased lipophilicity, showed improved efficiency against Mycolata bacteria. Microbiological guidance for medicinal chemistry is a powerful tool to design new and effective antimicrobials. In this case, the readily synthesized compounds open new possibilities in the search for antimicrobials active on mycolic acid-containing bacteria. Full article

(This article belongs to the Special Issue New Methodologies of Antibiotic Therapy: Drug Design and Diagnostic Tools)

► Show Figures

Figure 1

37 pages, 1659 KiB

Open AccessEditor’s ChoiceReview

The Blood–Brain Barrier and Pharmacokinetic/Pharmacodynamic Optimization of Antibiotics for the Treatment of Central Nervous System Infections in Adults

by Nicholas Haddad, Maddie Carr, Steve Balian, James Lannin, Yuri Kim, Courtney Toth and Jennifer Jarvis

Antibiotics 2022, 11(12), 1843; https://doi.org/10.3390/antibiotics11121843 - 19 Dec 2022

Cited by 18 | Viewed by 25887

Abstract

Bacterial central nervous system (CNS) infections are serious and carry significant morbidity and mortality. They encompass many syndromes, the most common being meningitis, which may occur spontaneously or as a consequence of neurosurgical procedures. Many classes of antimicrobials are in clinical use for [...] Read more.

Bacterial central nervous system (CNS) infections are serious and carry significant morbidity and mortality. They encompass many syndromes, the most common being meningitis, which may occur spontaneously or as a consequence of neurosurgical procedures. Many classes of antimicrobials are in clinical use for therapy of CNS infections, some with established roles and indications, others with experimental reporting based on case studies or small series. This review delves into the specifics of the commonly utilized antibacterial agents, updating their therapeutic use in CNS infections from the pharmacokinetic and pharmacodynamic perspectives, with a focus on the optimization of dosing and route of administration that have been described to achieve good clinical outcomes. We also provide a concise synopsis regarding the most focused, clinically relevant information as pertains to each class and subclass of antimicrobial therapeutics. CNS infection morbidity and mortality remain high, and aggressive management is critical in ensuring favorable patient outcomes while averting toxicity and upholding patient safety. Full article

(This article belongs to the Special Issue Optimizing Antibiotics’ Pharmacokinetic/Pharmacodynamic (PK/PD) and Tissue Concentrations)

► Show Figures

Figure 1

21 pages, 1668 KiB

Open AccessEditor’s ChoiceReview

β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity

by João Gonçalves Pereira, Joana Fernandes, Ana Rita Duarte and Susana Mendes Fernandes

Antibiotics 2022, 11(12), 1839; https://doi.org/10.3390/antibiotics11121839 - 18 Dec 2022

Cited by 11 | Viewed by 5460

Abstract

Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in [...] Read more.

Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time β-lactam antibiotic dose adjustments according to the patient’s condition are critical. The continuous infusion of β-lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to β-lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that β-lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time β-lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome. Full article

(This article belongs to the Special Issue Antibiotics Treatment Optimization in Vulnerable Populations)

► Show Figures

Figure 1

15 pages, 544 KiB

Open AccessEditor’s ChoiceReview

How to Identify Invasive Candidemia in ICU—A Narrative Review

by Joana Alves, Carles Alonso-Tarrés and Jordi Rello

Antibiotics 2022, 11(12), 1804; https://doi.org/10.3390/antibiotics11121804 - 12 Dec 2022

Cited by 15 | Viewed by 4535

Abstract

The incidence of invasive fungal infection in ICUs has increased over time, and Candida spp. is the most common cause. Critical care patients are a particular set of patients with a higher risk of invasive fungal infections; this population is characterized by extensive [...] Read more.

The incidence of invasive fungal infection in ICUs has increased over time, and Candida spp. is the most common cause. Critical care patients are a particular set of patients with a higher risk of invasive fungal infections; this population is characterized by extensive use of medical devices such as central venous lines, arterial lines, bladder catheters, hemodialysis and mechanical intubation. Blood cultures are the gold standard diagnosis; still, they are not an early diagnostic technique. Mannan, anti-mannan antibody, 1,3-β-D-glucan, Candida albicans germ tube antibody, Vitek 2, PNA-FISH, MALDI-TOF, PCR and T2Candida panel are diagnostic promising microbiological assays. Scoring systems are tools to distinguish patients with low and high risk of infection. They can be combined with diagnostic tests to select patients for pre-emptive treatment or antifungal discontinuation. Candidemia is the focus of this narrative review, an approach to contributing factors and diagnosis, with an emphasis on critical care patients. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Rello—Outstanding Contributions in the Fields of Management of Severe Infections and Sepsis)

► Show Figures

Figure 1

15 pages, 753 KiB

Open AccessEditor’s ChoiceReview

When and How to Use MIC in Clinical Practice?

by Sophie Magréault, Françoise Jauréguy, Etienne Carbonnelle and Jean-Ralph Zahar

Antibiotics 2022, 11(12), 1748; https://doi.org/10.3390/antibiotics11121748 - 3 Dec 2022

Cited by 14 | Viewed by 14667

Abstract

Bacterial resistance to antibiotics continues to be a global public health problem. The choice of the most effective antibiotic and the use of an adapted dose in the initial phase of the infection are essential to limit the emergence of resistance. This will [...] Read more.

Bacterial resistance to antibiotics continues to be a global public health problem. The choice of the most effective antibiotic and the use of an adapted dose in the initial phase of the infection are essential to limit the emergence of resistance. This will depend on (i) the isolated bacteria and its resistance profile, (ii) the pharmacodynamic (PD) profile of the antibiotic used and its level of toxicity, (iii) the site of infection, and (iv) the pharmacokinetic (PK) profile of the patient. In order to take account of both parameters to optimize the administered treatment, a minimal inhibitory concentration (MIC) determination associated with therapeutic drug monitoring (TDM) and their combined interpretation are required. The objective of this narrative review is thus to suggest microbiological, pharmacological, and/or clinical situations for which this approach could be useful. Regarding the microbiological aspect, such as the detection of antibiotic resistance and its level, the preservation of broad-spectrum β-lactams is particularly discussed. PK-PD profiles are relevant for difficult-to-reach infections and specific populations such as intensive care patients, cystic fibrosis patients, obese, or elderly patients. Finally, MIC and TDM are tools available to clinicians, who should not hesitate to use them to manage their patients. 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

Figure 1

26 pages, 10397 KiB

Open AccessEditor’s ChoiceReview

Antimicrobial and Cell-Penetrating Peptides: Understanding Penetration for the Design of Novel Conjugate Antibiotics

by Andreas Hadjicharalambous, Nikolaos Bournakas, Hector Newman, Michael J. Skynner and Paul Beswick

Antibiotics 2022, 11(11), 1636; https://doi.org/10.3390/antibiotics11111636 - 16 Nov 2022

Cited by 20 | Viewed by 7405

Abstract

Antimicrobial peptides (AMPs) are short oligopeptides that can penetrate the bacterial inner and outer membranes. Together with cell-penetrating peptides (CPPs), they are called membrane active peptides; peptides which can translocate across biological membranes. Over the last fifty years, attempts have been made to [...] Read more.

Antimicrobial peptides (AMPs) are short oligopeptides that can penetrate the bacterial inner and outer membranes. Together with cell-penetrating peptides (CPPs), they are called membrane active peptides; peptides which can translocate across biological membranes. Over the last fifty years, attempts have been made to understand the molecular features that drive the interactions of membranes with membrane active peptides. This review examines the features of a membrane these peptides exploit for translocation, as well as the physicochemical characteristics of membrane active peptides which are important for translocation. Moreover, it presents examples of how these features have been used in recent years to create conjugates consisting of a membrane active peptide, called a “vector”, attached to either a current or novel antibiotic, called a “cargo” or “payload”. In addition, the review discusses what properties may contribute to an ideal peptide vector able to deliver cargoes across the bacterial outer membrane as the rising issue of antimicrobial resistance demands new strategies to be employed to combat this global public health threat. Full article

(This article belongs to the Special Issue Reviews on Antimicrobial Peptides)

► Show Figures

Figure 1

16 pages, 6910 KiB

Open AccessEditor’s ChoiceArticle

Design of Antimicrobial Peptides with Cell-Selective Activity and Membrane-Acting Mechanism against Drug-Resistant Bacteria

by Seong-Cheol Park, Hyosuk Son, Young-Min Kim, Jong-Kook Lee, Soyoung Park, Hye Song Lim, Jung Ro Lee and Mi-Kyeong Jang

Antibiotics 2022, 11(11), 1619; https://doi.org/10.3390/antibiotics11111619 - 13 Nov 2022

Cited by 12 | Viewed by 2496

Abstract

Antimicrobial peptides (AMPs) can combat drug-resistant bacteria with their unique membrane-disruptive mechanisms. This study aimed to investigate the antibacterial effects of several membrane-acting peptides with amphipathic structures and positional alterations of two tryptophan residues. The synthetic peptides exhibited potent antibacterial activities in a [...] Read more.

Antimicrobial peptides (AMPs) can combat drug-resistant bacteria with their unique membrane-disruptive mechanisms. This study aimed to investigate the antibacterial effects of several membrane-acting peptides with amphipathic structures and positional alterations of two tryptophan residues. The synthetic peptides exhibited potent antibacterial activities in a length-dependent manner against various pathogenic drug-resistant and susceptible bacteria. In particular, the location of tryptophan near the N-terminus of AMPs simultaneously increases their antibacterial activity and toxicity. Furthermore, the growth inhibition mechanisms of these newly designed peptides involve cell penetration and destabilization of the cell membrane. These findings provide new insights into the design of peptides as antimicrobial agents and suggest that these peptides can be used as substitutes for conventional antibiotics. Full article

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

► Show Figures

Figure 1

12 pages, 3693 KiB

Open AccessEditor’s ChoiceArticle

Deep Transfer Learning Enables Robust Prediction of Antimicrobial Resistance for Novel Antibiotics

by Yunxiao Ren, Trinad Chakraborty, Swapnil Doijad, Linda Falgenhauer, Jane Falgenhauer, Alexander Goesmann, Oliver Schwengers and Dominik Heider

Antibiotics 2022, 11(11), 1611; https://doi.org/10.3390/antibiotics11111611 - 12 Nov 2022

Cited by 10 | Viewed by 3570

Abstract

Antimicrobial resistance (AMR) has become one of the serious global health problems, threatening the effective treatment of a growing number of infections. Machine learning and deep learning show great potential in rapid and accurate AMR predictions. However, a large number of samples for [...] Read more.

Antimicrobial resistance (AMR) has become one of the serious global health problems, threatening the effective treatment of a growing number of infections. Machine learning and deep learning show great potential in rapid and accurate AMR predictions. However, a large number of samples for the training of these models is essential. In particular, for novel antibiotics, limited training samples and data imbalance hinder the models’ generalization performance and overall accuracy. We propose a deep transfer learning model that can improve model performance for AMR prediction on small, imbalanced datasets. As our approach relies on transfer learning and secondary mutations, it is also applicable to novel antibiotics and emerging resistances in the future and enables quick diagnostics and personalized treatments. Full article

(This article belongs to the Special Issue Machine Learning for Antimicrobial Resistance Prediction)

► Show Figures

Figure 1

23 pages, 661 KiB

Open AccessEditor’s ChoiceReview

Recent Advances in the Application of Bacteriophages against Common Foodborne Pathogens

by Kinga Hyla, Izabela Dusza and Aneta Skaradzińska

Antibiotics 2022, 11(11), 1536; https://doi.org/10.3390/antibiotics11111536 - 2 Nov 2022

Cited by 13 | Viewed by 4321

Abstract

Bacteriophage potential in combating bacterial pathogens has been recognized nearly since the moment of discovery of these viruses at the beginning of the 20th century. Interest in phage application, which initially focused on medical treatments, rapidly spread throughout different biotechnological and industrial fields. [...] Read more.

Bacteriophage potential in combating bacterial pathogens has been recognized nearly since the moment of discovery of these viruses at the beginning of the 20th century. Interest in phage application, which initially focused on medical treatments, rapidly spread throughout different biotechnological and industrial fields. This includes the food safety sector in which the presence of pathogens poses an explicit threat to consumers. This is also the field in which commercialization of phage-based products shows the greatest progress. Application of bacteriophages has gained special attention particularly in recent years, presumably due to the potential of conventional antibacterial strategies being exhausted. In this review, we present recent findings regarding phage application in fighting major foodborne pathogens, including Salmonella spp., Escherichia coli, Yersinia spp., Campylobacter jejuni and Listeria monocytogenes. We also discuss advantages of bacteriophage use and challenges facing phage-based antibacterial strategies, particularly in the context of their widespread application in food safety. Full article

(This article belongs to the Special Issue Bacteriophage Therapy: Recent Developments and Applications of a Renaissance Weapon)

► Show Figures

Figure 1

17 pages, 2612 KiB

Open AccessEditor’s ChoiceReview

Antimicrobial Peptides—Mechanisms of Action, Antimicrobial Effects and Clinical Applications

by Jasminka Talapko, Tomislav Meštrović, Martina Juzbašić, Matej Tomas, Suzana Erić, Lorena Horvat Aleksijević, Sanja Bekić, Dragan Schwarz, Suzana Matić, Marijana Neuberg and Ivana Škrlec

Antibiotics 2022, 11(10), 1417; https://doi.org/10.3390/antibiotics11101417 - 16 Oct 2022

Cited by 93 | Viewed by 11340

Abstract

The growing emergence of antimicrobial resistance represents a global problem that not only influences healthcare systems but also has grave implications for political and economic processes. As the discovery of novel antimicrobial agents is lagging, one of the solutions is innovative therapeutic options [...] Read more.

The growing emergence of antimicrobial resistance represents a global problem that not only influences healthcare systems but also has grave implications for political and economic processes. As the discovery of novel antimicrobial agents is lagging, one of the solutions is innovative therapeutic options that would expand our armamentarium against this hazard. Compounds of interest in many such studies are antimicrobial peptides (AMPs), which actually represent the host’s first line of defense against pathogens and are involved in innate immunity. They have a broad range of antimicrobial activity against Gram-negative and Gram-positive bacteria, fungi, and viruses, with specific mechanisms of action utilized by different AMPs. Coupled with a lower propensity for resistance development, it is becoming clear that AMPs can be seen as emerging and very promising candidates for more pervasive usage in the treatment of infectious diseases. However, their use in quotidian clinical practice is not without challenges. In this review, we aimed to summarize state-of-the-art evidence on the structure and mechanisms of action of AMPs, as well as to provide detailed information on their antimicrobial activity. We also aimed to present contemporary evidence of clinical trials and application of AMPs and highlight their use beyond infectious diseases and potential challenges that may arise with their increasing availability. Full article

(This article belongs to the Special Issue Reviews on Antimicrobial Peptides)

► Show Figures

Figure 1

17 pages, 321 KiB

Open AccessEditor’s ChoiceReview

A Proposal for a Classification Guiding the Selection of Appropriate Antibiotic Therapy for Intra-Abdominal Infections

by Massimo Sartelli, Francesco Cristini, Federico Coccolini, Francesco Maria Labricciosa, Walter Siquini and Fausto Catena

Antibiotics 2022, 11(10), 1394; https://doi.org/10.3390/antibiotics11101394 - 12 Oct 2022

Cited by 5 | Viewed by 3996

Abstract

Adequately controlling the source of infection and prescribing appropriately antibiotic therapy are the cornerstones of the management of patients with intra-abdominal infections (IAIs). Correctly classifying patients with IAIs is crucial to assessing the severity of their clinical condition and deciding the strategy of [...] Read more.

Adequately controlling the source of infection and prescribing appropriately antibiotic therapy are the cornerstones of the management of patients with intra-abdominal infections (IAIs). Correctly classifying patients with IAIs is crucial to assessing the severity of their clinical condition and deciding the strategy of the treatment, including a correct empiric antibiotic therapy. Best practices in prescribing antibiotics may impact patient outcomes and the cost of treatment, as well as the risk of “opportunistic” infections such as Clostridioides difficile infection and the development and spread of antimicrobial resistance. This review aims to identify a correct classification of IAIs, guiding clinicians in the selection of the best antibiotic therapy in patients with IAIs. Full article

26 pages, 726 KiB

Open AccessEditor’s ChoiceReview

The Risk and Clinical Implications of Antibiotic-Associated Acute Kidney Injury: A Review of the Clinical Data for Agents with Signals from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) Database

by Kalin M. Clifford, Ashley R. Selby, Kelly R. Reveles, Chengwen Teng, Ronald G. Hall 2nd, Jamie McCarrell and Carlos A. Alvarez

Antibiotics 2022, 11(10), 1367; https://doi.org/10.3390/antibiotics11101367 - 6 Oct 2022

Cited by 15 | Viewed by 16805

Abstract

Antibiotic-associated acute kidney injury (AA-AKI) is quite common, especially among hospitalized patients; however, little is known about risk factors or mechanisms of why AA-AKI occurs. In this review, the authors have reviewed all available literature prior to 1 June 2022, with a large [...] Read more.

Antibiotic-associated acute kidney injury (AA-AKI) is quite common, especially among hospitalized patients; however, little is known about risk factors or mechanisms of why AA-AKI occurs. In this review, the authors have reviewed all available literature prior to 1 June 2022, with a large number of AKI reports. Information regarding risk factors of AA-AKI, mechanisms behind AA-AKI, and treatment/management principles to decrease AA-AKI risk were collected and reviewed. Patients treated in the inpatient setting are at increased risk of AA-AKI due to common risk factors: hypovolemia, concomitant use of other nephrotoxic medications, and exacerbation of comorbid conditions. Clinicians should attempt to correct risk factors for AA-AKI, choose antibiotic therapies with decreased association of AA-AKI to protect their high-risk patients, and narrow, when clinically possible, the use of antibiotics which have decreased incidence of AKI. To treat AKI, it is still recommended to discontinue all offending nephrotoxic agents and to renally adjust all medications according to package insert recommendations to decrease patient harm. Full article

► Show Figures

Figure 1

10 pages, 616 KiB

Open AccessEditor’s ChoiceArticle

Current Practices and Opportunities for Outpatient Parenteral Antimicrobial Therapy in Hospitals: A National Cross-Sectional Survey

by Hester H. Stoorvogel, Marlies E. J. L. Hulscher, Heiman F. L. Wertheim, Ed P. F. Yzerman, Maarten Scholing, Jeroen A. Schouten and Jaap ten Oever

Antibiotics 2022, 11(10), 1343; https://doi.org/10.3390/antibiotics11101343 - 1 Oct 2022

Cited by 3 | Viewed by 2907

Abstract

This nationwide study assessed how outpatient parenteral antimicrobial therapy (OPAT) is organised by Dutch acute care hospitals, the barriers experienced, and how an OPAT program affects the way hospitals organised OPAT care. We systematically developed and administered a survey to all 71 Dutch [...] Read more.

This nationwide study assessed how outpatient parenteral antimicrobial therapy (OPAT) is organised by Dutch acute care hospitals, the barriers experienced, and how an OPAT program affects the way hospitals organised OPAT care. We systematically developed and administered a survey to all 71 Dutch acute care hospitals between November 2021 and February 2022. Analyses were primarily descriptive and included a comparison between hospitals with and without an OPAT program. Sixty of the 71 hospitals (84.5%) responded. Fifty-five (91.7%) performed OPAT, with a median number of 20.8 (interquartile range [IQR] 10.3–29.7) patients per 100 hospital beds per year. Of these 55 hospitals, 31 (56.4%) had selection criteria for OPAT and 34 (61.8%) had a protocol for laboratory follow-up. Sixteen hospitals (29.1%) offered self-administered OPAT (S-OPAT), with a median percentage of 5.0% of patients (IQR: 2.3%–10.0%) actually performing self-administration. Twenty-five hospitals (45.5%) had an OPAT-related outcome registration. The presence of an OPAT program (22 hospitals, 40.0%) was significantly associated with aspects of well-organised OPAT care. The most commonly experienced barriers to OPAT implementation were a lack of financial, administrative, and IT support and insufficient time of healthcare staff. Concluding, hospital-initiated OPAT is widely available in the Netherlands, but various aspects of well-organised OPAT care can be improved. Implementation of a team-based OPAT program can contribute to such improvements. The observed variation provides leads for further scientific research, guidelines, and practical implementation programs. Full article

(This article belongs to the Special Issue Antibiotics in Public Health: Reasonable Application and Stewardship)

► Show Figures

Figure 1

28 pages, 634 KiB

Open AccessEditor’s ChoiceReview

Epidemiology, Mechanisms of Resistance and Treatment Algorithm for Infections Due to Carbapenem-Resistant Gram-Negative Bacteria: An Expert Panel Opinion

by Nicola Coppola, Alberto Enrico Maraolo, Lorenzo Onorato, Riccardo Scotto, Federica Calò, Luigi Atripaldi, Anna Borrelli, Antonio Corcione, Maria Giovanna De Cristofaro, Emanuele Durante-Mangoni, Amelia Filippelli, Gianluigi Franci, Maria Galdo, Gaspare Guglielmi, Pasquale Pagliano, Alessandro Perrella, Ornella Piazza, Marco Picardi, Rodolfo Punzi, Ugo Trama and Ivan Gentile Show full author list Hide full author list

Antibiotics 2022, 11(9), 1263; https://doi.org/10.3390/antibiotics11091263 - 17 Sep 2022

Cited by 22 | Viewed by 7141

Abstract

Antimicrobial resistance represents a serious threat for global health, causing an unacceptable burden in terms of morbidity, mortality and healthcare costs. In particular, in 2017, carbapenem-resistant organisms were listed by the WHO among the group of pathogens for which novel treatment strategies are [...] Read more.

Antimicrobial resistance represents a serious threat for global health, causing an unacceptable burden in terms of morbidity, mortality and healthcare costs. In particular, in 2017, carbapenem-resistant organisms were listed by the WHO among the group of pathogens for which novel treatment strategies are urgently needed. Fortunately, several drugs and combinations have been introduced in recent years to treat multi-drug-resistant (MDR) bacteria. However, a correct use of these molecules is needed to preserve their efficacy. In the present paper, we will provide an overview on the epidemiology and mechanisms of resistance of the most common MDR Gram-negative bacteria, proposing a treatment algorithm for the management of infections due to carbapenem-resistant bacteria based on the most recent clinical evidence. Full article

(This article belongs to the Special Issue Carbapenem-Resistant Organisms (CRO) as Leading Cause of Hospital Associated Infections)

► Show Figures

Figure 1

11 pages, 1289 KiB

Open AccessEditor’s ChoiceReview

SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Clostridioides difficile Infection (rCDI)

by Sahil Khanna, Matthew Sims, Thomas J. Louie, Monika Fischer, Kerry LaPlante, Jessica Allegretti, Brooke R. Hasson, Allyson T. Fonte, Christopher McChalicher, David S. Ege, Jessica A. Bryant, Timothy J. Straub, Christopher B. Ford, Matthew R. Henn, Elaine E. L. Wang, Lisa von Moltke and Mark H. Wilcox

Antibiotics 2022, 11(9), 1234; https://doi.org/10.3390/antibiotics11091234 - 10 Sep 2022

Cited by 30 | Viewed by 10034

Abstract

Clostridioides difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20–25% of patients with a primary infection experience a recurrence, and the risk of recurrence [...] Read more.

Clostridioides difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20–25% of patients with a primary infection experience a recurrence, and the risk of recurrence increases with subsequent episodes to greater than 40%. The leading risk factor for CDI is broad-spectrum antibiotics, which leads to a loss of microbial diversity and impaired colonization resistance. Current FDA-approved CDI treatment strategies target toxin or toxin-producing bacteria, but do not address microbiome disruption, which is key to the pathogenesis of recurrent CDI. Fecal microbiota transplantation (FMT) reduces the risk of recurrent CDI through the restoration of microbial diversity. However, FDA safety alerts describing hospitalizations and deaths related to pathogen transmission have raised safety concerns with the use of unregulated and unstandardized donor-derived products. SER-109 is an investigational oral microbiome therapeutic composed of purified spore-forming Firmicutes. SER-109 was superior to a placebo in reducing CDI recurrence at Week 8 (12% vs. 40%, respectively; p < 0.001) in adults with a history of recurrent CDI with a favorable observed safety profile. Here, we discuss the role of the microbiome in CDI pathogenesis and the clinical development of SER-109, including its rigorous manufacturing process, which mitigates the risk of pathogen transmission. Additionally, we discuss compositional and functional changes in the gastrointestinal microbiome in patients with recurrent CDI following treatment with SER-109 that are critical to a sustained clinical response. Full article

(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)

► Show Figures

Figure 1

14 pages, 1544 KiB

Open AccessEditor’s ChoiceArticle

In Vitro and In Vivo Antimicrobial Activity of the Novel Peptide OMN6 against Multidrug-Resistant Acinetobacter baumannii

by Janna Michaeli, Shira Mandel, Shelly Maximov, Jonathan Zazoun, Paola Savoia, Nimmi Kothari, Thomas Valmont, Livia Ferrari, Leonard R. Duncan, Stephen Hawser, Moshe Cohen-Kutner and Niv Bachnoff

Antibiotics 2022, 11(9), 1201; https://doi.org/10.3390/antibiotics11091201 - 5 Sep 2022

Cited by 6 | Viewed by 3234

Abstract

The rapid worldwide spread of antimicrobial resistance highlights the significant need for the development of innovative treatments to fight multidrug-resistant bacteria. This study describes the potent antimicrobial activity of the novel peptide OMN6 against a wide array of drug-resistant Acinetobacter baumannii clinical isolates. [...] Read more.

The rapid worldwide spread of antimicrobial resistance highlights the significant need for the development of innovative treatments to fight multidrug-resistant bacteria. This study describes the potent antimicrobial activity of the novel peptide OMN6 against a wide array of drug-resistant Acinetobacter baumannii clinical isolates. OMN6 prevented the growth of all tested isolates, regardless of any pre-existing resistance mechanisms. Moreover, in vitro serial-passaging studies demonstrated that no resistance developed against OMN6. Importantly, OMN6 was highly efficacious in treating animal models of lung and blood infections caused by multidrug-resistant A. baumannii. Taken together, these results point to OMN6 as a novel antimicrobial agent with the potential to treat life-threatening infections caused by multidrug-resistant A. baumannii avoiding resistance. Full article

(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria)

► Show Figures

Figure 1

33 pages, 4361 KiB

Open AccessEditor’s ChoiceSystematic Review

Point-of-Care and Rapid Tests for the Etiological Diagnosis of Respiratory Tract Infections in Children: A Systematic Review and Meta-Analysis

by Giulia Brigadoi, Andrea Gastaldi, Marco Moi, Elisa Barbieri, Sara Rossin, Annalisa Biffi, Anna Cantarutti, Carlo Giaquinto, Liviana Da Dalt and Daniele Donà

Antibiotics 2022, 11(9), 1192; https://doi.org/10.3390/antibiotics11091192 - 3 Sep 2022

Cited by 14 | Viewed by 3360

Abstract

Fever is one of the most common causes of medical evaluation of children, and early discrimination between viral and bacterial infection is essential to reduce inappropriate prescriptions. This study aims to systematically review the effects of point-of-care tests (POCTs) and rapid tests for [...] Read more.

Fever is one of the most common causes of medical evaluation of children, and early discrimination between viral and bacterial infection is essential to reduce inappropriate prescriptions. This study aims to systematically review the effects of point-of-care tests (POCTs) and rapid tests for respiratory tract infections on changing antibiotic prescription rate, length of stay, duration of therapy, and healthcare costs. Embase, MEDLINE, and Cochrane Library databases were systematically searched. All randomized control trials and non-randomized observational studies meeting inclusion criteria were evaluated using the NIH assessment tool. A meta-analysis was performed to assess the effects of rapid influenza diagnostic tests and film-array respiratory panel implementation on selected outcomes. From a total of 6440 studies, 57 were eligible for the review. The analysis was stratified by setting and POCT/rapid test type. The most frequent POCTs or rapid tests implemented were the Rapid Influenza Diagnostic Test and film-array and for those types of test a separate meta-analysis assessed a significant reduction in antibiotic prescription and an improvement in oseltamivir prescription. Implementing POCTs and rapid tests to discriminate between viral and bacterial infections for respiratory pathogens is valuable for improving appropriate antimicrobial prescriptions. However, more studies are needed to assess these findings in pediatric settings. Full article

(This article belongs to the Special Issue Antibiotics in Public Health: Reasonable Application and Stewardship)

► Show Figures

Figure 1

24 pages, 1452 KiB

Open AccessEditor’s ChoiceReview

Successful Integration of Clinical Pharmacists in an OPAT Program: A Real-Life Multidisciplinary Circuit

by Sara Ortonobes, Abel Mujal-Martínez, María de Castro Julve, Alba González-Sánchez, Rafael Jiménez-Pérez, Manuel Hernández-Ávila, Natalia De Alfonso, Ingrid Maye-Pérez, Teresa Valle-Delmás, Alba Rodríguez-Sánchez, Jessica Pino-García and Mònica Gómez-Valent

Antibiotics 2022, 11(8), 1124; https://doi.org/10.3390/antibiotics11081124 - 19 Aug 2022

Cited by 8 | Viewed by 4886

Abstract

Outpatient parenteral antimicrobial therapy (OPAT) programs encompass a range of healthcare processes aiming to treat infections at home, with the preferential use of the intravenous route. Although several barriers arise during the implementation of OPAT circuits, recent cumulative data have supported the effectiveness [...] Read more.

Outpatient parenteral antimicrobial therapy (OPAT) programs encompass a range of healthcare processes aiming to treat infections at home, with the preferential use of the intravenous route. Although several barriers arise during the implementation of OPAT circuits, recent cumulative data have supported the effectiveness of these programs, demonstrating their application in a safe and cost-effective manner. Given that OPAT is evolving towards treating patients with higher complexity, a multidisciplinary team including physicians, pharmacists, and nursing staff should lead the program. The professionals involved require previous experience in infectious diseases treatment as well as in outpatient healthcare and self-administration. As we describe here, clinical pharmacists exert a key role in OPAT multidisciplinary teams. Their intervention is essential to optimize antimicrobial prescriptions through their participation in stewardship programs as well as to closely follow patients from a pharmacotherapeutic perspective. Moreover, pharmacists provide specialized counseling on antimicrobial treatment technical compounding. In fact, OPAT elaboration in sterile environments and pharmacy department clean rooms increases OPAT stability and safety, enhancing the quality of the program. In summary, building multidisciplinary teams with the involvement of clinical pharmacists improves the management of home-treated infections, promoting a safe self-administration and increasing OPAT patients’ quality of life. Full article

(This article belongs to the Special Issue Antibiotic Use and Stewardship in Hospital)

► Show Figures

Figure 1

15 pages, 6720 KiB

Open AccessEditor’s ChoiceReview

The Structures and Binding Modes of Small-Molecule Inhibitors of Pseudomonas aeruginosa Elastase LasB

by Virgyl Camberlein, Gwenaëlle Jézéquel, Jörg Haupenthal and Anna K. H. Hirsch

Antibiotics 2022, 11(8), 1060; https://doi.org/10.3390/antibiotics11081060 - 4 Aug 2022

Cited by 9 | Viewed by 3529

Abstract

Elastase B (LasB) is a zinc metalloprotease and a crucial virulence factor of Pseudomonas aeruginosa. As the need for new strategies to fight antimicrobial resistance (AMR) constantly rises, this protein has become a key target in the development of novel antivirulence agents. [...] Read more.

Elastase B (LasB) is a zinc metalloprotease and a crucial virulence factor of Pseudomonas aeruginosa. As the need for new strategies to fight antimicrobial resistance (AMR) constantly rises, this protein has become a key target in the development of novel antivirulence agents. The extensive knowledge of the structure of its active site, containing two subpockets and a zinc atom, led to various structure-based medicinal chemistry programs and the optimization of several chemical classes of inhibitors. This review provides a brief reminder of the structure of the active site and a summary of the disclosed P. aeruginosa LasB inhibitors. We specifically focused on the analysis of their binding modes with a detailed representation of them, hence giving an overview of the strategies aiming at targeting LasB by small molecules. Full article

(This article belongs to the Special Issue Nontraditional Antibiotics—Challenges and Triumphs, 2nd Volume)

► Show Figures

Figure 1

14 pages, 2214 KiB

Open AccessEditor’s ChoiceArticle

Expansion of the pRAS3 Plasmid Family in Aeromonas salmonicida subsp. salmonicida and Growing Evidence of Interspecies Connections for These Plasmids

by Kim C. Fournier, Valérie E. Paquet, Sabrina A. Attéré, Judith Farley, Hélène Marquis, Hubert Gantelet, Christian Ravaille, Antony T. Vincent and Steve J. Charette

Antibiotics 2022, 11(8), 1047; https://doi.org/10.3390/antibiotics11081047 - 3 Aug 2022

Cited by 4 | Viewed by 2581

Abstract

Aeromonas salmonicida subsp. salmonicida is a pathogenic bacterium responsible for furunculosis in salmonids. Following an outbreak of furunculosis, the infection can be treated with antibiotics, but it is common to observe ineffective treatment due to antibiotic resistance. This bacterium has a wide variety [...] Read more.

Aeromonas salmonicida subsp. salmonicida is a pathogenic bacterium responsible for furunculosis in salmonids. Following an outbreak of furunculosis, the infection can be treated with antibiotics, but it is common to observe ineffective treatment due to antibiotic resistance. This bacterium has a wide variety of plasmids responsible for this resistance. Among them, pRAS3 carries a tetracycline resistance gene. Several variants of this plasmid have been discovered over the years (pRAS3-3432 and pRAS3.1 to 3.4). During the present study, two new variants of the plasmid pRAS3 were identified (pRAS3.5 and pRAS3-3759) in strains of A. salmonicida subsp. salmonicida. Plasmid pRAS3-3759, which has been found in many strains from the same region over the past three years, has an additional genetic element identical to one found in pRAS3-3432. This genetic element was also found in Chlamydia suis, a swine pathogen. In this study, we analyzed the bacteria’s resistance to tetracycline, the number of copies of the plasmids, and the growth of the strains that carry five of the pRAS3 variants (pRAS3.3 to 3.5, pRAS3-3432, and pRAS3-3759). The results show no particular trend despite the differences between the plasmids, except for the resistance to tetracycline when analyzed in an isogenic background. Blast analysis also revealed the presence of pRAS3 plasmids in other bacterial species, which suggests that this plasmid family has widely spread. This study once again highlights the ability of A. salmonicida subsp. salmonicida to adapt to furunculosis antibiotic treatments, and the still-growing family of pRAS3 plasmids. Full article

► Show Figures

Figure 1

14 pages, 1129 KiB

Open AccessEditor’s ChoiceReview

Antibiotic Allergy De-Labeling: A Pathway against Antibiotic Resistance

by Inmaculada Doña, Marina Labella, Gádor Bogas, Rocío Sáenz de Santa María, María Salas, Adriana Ariza and María José Torres

Antibiotics 2022, 11(8), 1055; https://doi.org/10.3390/antibiotics11081055 - 3 Aug 2022

Cited by 10 | Viewed by 5127

Abstract

Antibiotics are one of the most frequently prescribed drugs. Unfortunately, they also are the most common cause for self-reported drug allergy, limiting the use of effective therapies. However, evidence shows that more than 90% of patients labeled as allergic to antibiotics are not [...] Read more.

Antibiotics are one of the most frequently prescribed drugs. Unfortunately, they also are the most common cause for self-reported drug allergy, limiting the use of effective therapies. However, evidence shows that more than 90% of patients labeled as allergic to antibiotics are not allergic. Importantly, the label of antibiotic allergy, whether real or not, constitutes a major public health problem as it directly impacts antimicrobial stewardship: it has been associated with broad-spectrum antibiotic use, often resulting in the emergence of bacterial resistance. Therefore, an accurate diagnosis is crucial for de-labeling patients who claim to be allergic but are not really allergic. This review presents allergy methods for achieving successful antibiotic allergy de-labeling. Patient clinical history is often inaccurately reported, thus not being able to de-label most patients. In vitro testing offers a complementary approach but it shows limitations. Immunoassay for quantifying specific IgE is the most used one, although it gives low sensitivity and is limited to few betalactams. Basophil activation test is not validated and not available in all centers. Therefore, true de-labeling still relies on in vivo tests including drug provocation and/or skin tests, which are not risk-exempt and require specialized healthcare professionals for results interpretation and patient management. Moreover, differences on the pattern of antibiotic consumption cause differences in the diagnostic approach among different countries. A multidisciplinary approach is recommended to reduce the risks associated with the reported penicillin allergy label. Full article

(This article belongs to the Special Issue Combating Antibiotic Resistance with Precision Medicine: The Value of Diagnostic)

► Show Figures

Figure 1

20 pages, 1210 KiB

Open AccessEditor’s ChoiceArticle

Association between Antibiotic Consumption and Resistance in Mink Production

by Nanett Kvist Nikolaisen, Mette Fertner, Desiree Corvera Kløve Lassen, Chaza Nazih Chehabi, Amir Atabak Ronaghinia, Mariann Chriél, Vibeke Frøkjær Jensen, Lars Bogø Jensen, Karl Pedersen and Tina Struve

Antibiotics 2022, 11(7), 927; https://doi.org/10.3390/antibiotics11070927 - 9 Jul 2022

Cited by 4 | Viewed by 2927

Abstract

Antibiotic consumption is considered to be a main driver of antibiotic resistant bacteria. Mink breeding follows a distinctive seasonal reproduction cycle, and all of the mink produced in the northern hemisphere are bred, born, and pelted around the same time of year. Some [...] Read more.

Antibiotic consumption is considered to be a main driver of antibiotic resistant bacteria. Mink breeding follows a distinctive seasonal reproduction cycle, and all of the mink produced in the northern hemisphere are bred, born, and pelted around the same time of year. Some of the diseases are age-related, which is reflected in the seasonal variation of antibiotic consumption. The seasonality makes mink a good model for the investigation of the association between antibiotic consumption and resistance. The objectives of this study were (1) to monitor the farm level of antibiotic resistance during one production cycle and (2) to assess the potential associations between antibiotic consumption and resistance. Twenty-four farms were included in this study (Denmark n = 20, Iceland n = 2, and The Netherlands n = 2), following a cohort of animals born in 2018. Staphylococcus delphini and Escherichia coli were isolated from samples of the carcasses and faeces and were collected randomly. The isolates were susceptibility tested and subsequently divided into the sensitive wildtype (WT) and the resistant non-wildtype (NWT) populations. The antibiotic consumption relative to the sampling periods was assessed as having a short-term or a long-term impact, i.e., in two explanatory factors. For both S. delphini and E. coli, a large between-farm variation of NWT profiles was detected. In the final multivariable, generalized linear mixed models, significant associations between NWT isolates and the consumption of specific antibiotics were found: the short-term use of tetracyclines in the growth period was associated with the occurrence of tetracycline NWT E. coli in the growth period (OR: 11.94 [1.78; 89.28]), and the long-term use of macrolide and tetracyclines was associated with the occurrence of erythromycin NWT S. delphini in the weaning period (OR: 18.2 [2.26; 321.36]) and tetracycline NWT S. delphini in the growth period (OR: 8.2 [1.27; 63.31]), respectively. Farms with zero consumption in the study years prior to sampling also had a substantial proportion of NWT isolates, indicating that NWT isolates are persistent and/or widely spread in the environment. Generally, a high occurrence of tetracycline NWTs was observed. NWT isolates with resistance against the most commonly used antibiotics were found on all the farms, stressing the need for routine surveillance and the prudent use of antibiotics. The results offer a preview of the complex relationship between consumption and resistance, demonstrating some significant associations between use and resistance. Moreover, antibiotic-resistant bacteria are present even on farms with no antibiotic consumption over extended periods, and theoretical explanations supported by the data are offered. Full article

► Show Figures

Figure 1

37 pages, 623 KiB

Open AccessEditor’s ChoiceArticle

Efficacy of Short-Term High Dose Pulsed Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-Infections: A Report of Three Cases and Literature Review

by Richard I. Horowitz and Phyllis R. Freeman

Antibiotics 2022, 11(7), 912; https://doi.org/10.3390/antibiotics11070912 - 7 Jul 2022

Cited by 5 | Viewed by 24915

Abstract

Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A seven- to eight-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission [...] Read more.

Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A seven- to eight-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission in approximately 50% of patients for one year or longer, with published culture studies indicating higher doses of dapsone demonstrate efficacy against resistant biofilm forms of Borrelia burgdorferi. The purpose of this study was, therefore, to evaluate higher doses of dapsone in the treatment of resistant CLD/PTLDS and associated co-infections. A total of 25 patients with a history of Lyme and associated co-infections, most of whom had ongoing symptoms despite several courses of DDDCT, took one or more courses of high dose pulsed dapsone combination therapy (200 mg dapsone × 3–4 days and/or 200 mg BID × 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in eight major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just the treatment length, positively affected outcomes. High dose pulsed dapsone combination therapy may represent a novel therapeutic approach for the treatment of resistant CLD/PTLDS, and should be confirmed in randomized, controlled clinical trials. Full article

(This article belongs to the Special Issue Antimicrobial Combination Therapy to Treat Difficult-to-Treat Infections: From Bench to the Bedside)

► Show Figures

Figure 1

14 pages, 1187 KiB

Open AccessEditor’s ChoiceArticle

Antibacterial Activity against Clinical Isolates and In Vivo Efficacy of Coralmycins

by Ha-Young Choi, Bo-Min Kim, Young-Rok Kim, Taehui Yang, Sunjoo Ahn, Dongeun Yong, Jin-Hwan Kwak and Won-Gon Kim

Antibiotics 2022, 11(7), 902; https://doi.org/10.3390/antibiotics11070902 - 6 Jul 2022

Cited by 3 | Viewed by 2703

Abstract

Coralmycins, such as coralmycin A and DH-coralmycin A, have novel molecular skeletons and have been reported to exhibit potent antibacterial activity against standard Gram-positive bacterial strains. Here, the in vitro antibacterial activity against an extensive clinical isolate collection, time-kill kinetics, pharmacokinetics (PK), and [...] Read more.

Coralmycins, such as coralmycin A and DH-coralmycin A, have novel molecular skeletons and have been reported to exhibit potent antibacterial activity against standard Gram-positive bacterial strains. Here, the in vitro antibacterial activity against an extensive clinical isolate collection, time-kill kinetics, pharmacokinetics (PK), and in vivo efficacy of coralmycins were studied. Coralmycin A showed potent antibacterial activity with an MIC₉₀ of 1 mg/L against 73 clinical methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci isolates, which was 2–8 times higher than the corresponding activities of DH-coralmycin A, vancomycin, daptomycin, and linezolid, and against 73 vancomycin-resistant Enterococcus and Streptococcus pneumoniae isolates, which was 4–16 times higher than the corresponding activities of DH-coralmycin A, daptomycin, and linezolid. Pharmacokinetic analysis after i.v. injection showed that coralmycins have a moderate volume of distribution and moderate-to-high clearance in mice. The coralmycin A and DH-coralmycin A bioavailability values were 61.3% and 11.7%, respectively, after s.c. administration. In a mouse respiratory tract infection model, coralmycin A showed bacteriostatic and bactericidal in vivo efficacies at an s.c. administration of 4 and 100 mg/kg bid, respectively; these efficacies were similar to those of vancomycin at 4 and 20 mg/kg bid, respectively. The present findings indicate that coralmycin A has great potential as a new class of antibiotic for treating infections caused by multidrug-resistant Gram-positive bacteria. Full article

(This article belongs to the Special Issue Discovery and Development of Novel Antibacterial Agents)

► Show Figures

Figure 1

14 pages, 1590 KiB

Open AccessEditor’s ChoiceArticle

Enhanced Antibacterial Activity of Dermaseptin through Its Immobilization on Alginate Nanoparticles—Effects of Menthol and Lactic Acid on Its Potentialization

by Noura Hazime, Yanath Belguesmia, Alexandre Barras, Mohamed Amiche, Rabah Boukherroub and Djamel Drider

Antibiotics 2022, 11(6), 787; https://doi.org/10.3390/antibiotics11060787 - 9 Jun 2022

Cited by 4 | Viewed by 2606

Abstract

Dermaseptin B2 (DRS-B2) is an antimicrobial peptide secreted by Phyllomedusa bicolor, which is an Amazonian tree frog. Here, we show that the adsorption of DRS-B2 on alginate nanoparticles (Alg NPs) results in a formulation (Alg NPs + DRS-B2) with a remarkable antibacterial [...] Read more.

Dermaseptin B2 (DRS-B2) is an antimicrobial peptide secreted by Phyllomedusa bicolor, which is an Amazonian tree frog. Here, we show that the adsorption of DRS-B2 on alginate nanoparticles (Alg NPs) results in a formulation (Alg NPs + DRS-B2) with a remarkable antibacterial activity against Escherichia coli ATCC 8739 and E. coli 184 strains, which are sensitive and resistant, respectively, to colistin. The antibacterial activity, obtained with this new formulation, is higher than that obtained with DRS-B2 alone. Of note, the addition of lactic acid or menthol to this new formulation augments its antibacterial activity against the aforementioned Gram-negative bacilli. The safety of DRS-B2, and also that of the new formulation supplemented or not with a small molecule such as lactic acid or menthol has been proven on the human erythrocytes and the eukaryotic cell line types HT29 (human) and IPEC-1 (animal). Similarly, their stability was determined under the conditions mimicking the gastrointestinal tract with different conditions: pH, temperature, and the presence of digestive enzymes. Based on all the obtained data, we assume that these new formulations are promising and could be suggested, after in vivo approval and completing regulation aspects, as alternatives to antibiotics to fight infections caused by Gram-negative bacilli such as E. coli. Full article

► Show Figures

Figure 1

11 pages, 1182 KiB

Open AccessEditor’s ChoiceArticle

The Urinary Resistome of Clinically Healthy Companion Dogs: Potential One Health Implications

by Tonatiuh Melgarejo, Nathan Sharp, Janina A. Krumbeck, Guangxi Wu, Young J. Kim and Annika Linde

Antibiotics 2022, 11(6), 780; https://doi.org/10.3390/antibiotics11060780 - 8 Jun 2022

Cited by 2 | Viewed by 3126

Abstract

An interdisciplinary approach to antimicrobial resistance (AMR) is essential to effectively address what is projected to soon become a public health disaster. Veterinary medicine accounts for a majority of antimicrobial use, and mainly in support of industrial food animal production (IFAP), which has [...] Read more.

An interdisciplinary approach to antimicrobial resistance (AMR) is essential to effectively address what is projected to soon become a public health disaster. Veterinary medicine accounts for a majority of antimicrobial use, and mainly in support of industrial food animal production (IFAP), which has significant exposure implications for human and nonhuman animals. Companion dogs live in close proximity to humans and share environmental exposures, including food sources. This study aimed to elucidate the AMR-gene presence in microorganisms recovered from urine from clinically healthy dogs to highlight public health considerations in the context of a species-spanning framework. Urine was collected through cystocentesis from 50 companion dogs in Southern California, and microbial DNA was analyzed using next-generation sequencing. Thirteen AMR genes in urine from 48% of the dogs {n=24} were detected. The most common AMR genes were aph(3′)Ia, and ermB, which confer resistance to aminoglycosides and MLS (macrolides, lincosamides, streptogramins) antibiotics, respectively. Antibiotic-resistance profiles based on the AMR genes detected, and the intrinsic resistance profiles of bacterial species, were inferred in 24% of the samples {n=12} for 57 species, with most belonging to Streptococcus, Staphylococcus, and Corynebacterium genera. The presence of AMR genes that confer resistance to medically important antibiotics suggests that dogs may serve as reservoirs of clinically relevant resistomes, which is likely rooted in excessive IFAP antimicrobial use. Full article

(This article belongs to the Special Issue Antibiotic Use in Veterinary)

► Show Figures

Figure 1

29 pages, 1622 KiB

Open AccessEditor’s ChoiceReview

Insights in the Development and Uses of Alternatives to Antibiotic Growth Promoters in Poultry and Swine Production

by Md Ramim Tanver Rahman, Ismail Fliss and Eric Biron

Antibiotics 2022, 11(6), 766; https://doi.org/10.3390/antibiotics11060766 - 2 Jun 2022

Cited by 75 | Viewed by 68458

Abstract

The overuse and misuse of antibiotics has contributed to the rise and spread of multidrug-resistant bacteria. To address this global public health threat, many countries have restricted the use of antibiotics as growth promoters and promoted the development of alternatives to antibiotics in [...] Read more.

The overuse and misuse of antibiotics has contributed to the rise and spread of multidrug-resistant bacteria. To address this global public health threat, many countries have restricted the use of antibiotics as growth promoters and promoted the development of alternatives to antibiotics in human and veterinary medicine and animal farming. In food-animal production, acidifiers, bacteriophages, enzymes, phytochemicals, probiotics, prebiotics, and antimicrobial peptides have shown hallmarks as alternatives to antibiotics. This review reports the current state of these alternatives as growth-promoting factors for poultry and swine production and describes their mode of action. Recent findings on their usefulness and the factors that presently hinder their broader use in animal food production are identified by SWOT (strength, weakness, opportunity, and threat) analysis. The potential for resistance development as well as co- and cross-resistance with currently used antibiotics is also discussed. Using predetermined keywords, we searched specialized databases including Scopus, Web of Science, and Google Scholar. Antibiotic resistance cannot be stopped, but its spreading can certainly be hindered or delayed with the development of more alternatives with innovative modes of action and a wise and careful use of antimicrobials in a One Health approach. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antibiotic Alternatives in Livestock)

► Show Figures

Graphical abstract

15 pages, 1598 KiB

Open AccessEditor’s ChoiceArticle

Synergism between the Synthetic Antibacterial and Antibiofilm Peptide (SAAP)-148 and Halicin

by Miriam E. van Gent, Tanny J. K. van der Reijden, Patrick R. Lennard, Adriëtte W. de Visser, Bep Schonkeren-Ravensbergen, Natasja Dolezal, Robert A. Cordfunke, Jan Wouter Drijfhout and Peter H. Nibbering

Antibiotics 2022, 11(5), 673; https://doi.org/10.3390/antibiotics11050673 - 17 May 2022

Cited by 12 | Viewed by 4087

Abstract

Recently, using a deep learning approach, the novel antibiotic halicin was discovered. We compared the antibacterial activities of two novel bactericidal antimicrobial agents, i.e., the synthetic antibacterial and antibiofilm peptide (SAAP)-148 with this antibiotic halicin. Results revealed that SAAP-148 was more effective than [...] Read more.

Recently, using a deep learning approach, the novel antibiotic halicin was discovered. We compared the antibacterial activities of two novel bactericidal antimicrobial agents, i.e., the synthetic antibacterial and antibiofilm peptide (SAAP)-148 with this antibiotic halicin. Results revealed that SAAP-148 was more effective than halicin in killing planktonic bacteria of antimicrobial-resistant (AMR) Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus, especially in biologically relevant media, such as plasma and urine, and in 3D human infection models. Surprisingly, SAAP-148 and halicin were equally effective against these bacteria residing in immature and mature biofilms. As their modes of action differ, potential favorable interactions between SAAP-148 and halicin were investigated. For some specific strains of AMR E. coli and S. aureus synergism between these agents was observed, whereas for other strains, additive interactions were noted. These favorable interactions were confirmed for AMR E. coli in a 3D human bladder infection model and AMR S. aureus in a 3D human epidermal infection model. Together, combinations of these two novel antimicrobial agents hold promise as an innovative treatment for infections not effectively treatable with current antibiotics. Full article

(This article belongs to the Topic Novel Antimicrobial Agents: Discovery, Design and New Therapeutic Strategies)

► Show Figures

Figure 1

9 pages, 796 KiB

Open AccessEditor’s ChoiceReview

Use of Novel Antibiograms to Determine the Need for Earlier Susceptibility Testing and Administration for New β-Lactam/β-Lactamase Inhibitors in the United States

by Kenneth P. Klinker, Levita K. Hidayat, Eric Wenzler, Joan-Miquel Balada-Llasat, Mary Motyl, C. Andrew DeRyke and Karri A. Bauer

Antibiotics 2022, 11(5), 660; https://doi.org/10.3390/antibiotics11050660 - 14 May 2022

Cited by 6 | Viewed by 4881

Abstract

Antimicrobial resistance is a global public health threat, and gram-negative bacteria, such as Enterobacterales and Pseudomonas aeruginosa, are particularly problematic with difficult-to-treat resistance phenotypes. To reduce morbidity and mortality, a reduction in the time to effective antimicrobial therapy (TTET) is needed, especially among [...] Read more.

Antimicrobial resistance is a global public health threat, and gram-negative bacteria, such as Enterobacterales and Pseudomonas aeruginosa, are particularly problematic with difficult-to-treat resistance phenotypes. To reduce morbidity and mortality, a reduction in the time to effective antimicrobial therapy (TTET) is needed, especially among critically ill patients. The antibiogram is an effective clinical tool that can provide accurate antimicrobial susceptibility information and facilitate early antimicrobial optimization, decrease TTET, and improve outcomes such as mortality, hospital length of stay, and costs. Guidance is lacking on how to validate the susceptibility to new antibacterial agents. Commonly used traditional and combination antibiograms may not adequately assist clinicians in making treatment decisions. Challenges with the current susceptibility testing of new β-lactam/β-lactamase inhibitor combinations persist, impacting the appropriate antibacterial choice and patient outcomes. Novel antibiograms such as syndromic antibiograms that incorporate resistant gram-negative phenotypes and/or minimum inhibitory concentration distributions may assist in determining the need for earlier susceptibility testing or help define an earlier optimal use of the new β-lactam/β-lactamase inhibitors. The purpose of this review is to emphasize novel antibiogram approaches that are capable of improving the time to susceptibility testing and administration for new β-lactam/β-lactamase inhibitors so that they are earlier in a patient’s treatment course. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship)

► Show Figures

Figure 1

31 pages, 2279 KiB

Open AccessEditor’s ChoiceReview

The Use of Bacteriophages in Biotechnology and Recent Insights into Proteomics

by Ana G. Abril, Mónica Carrera, Vicente Notario, Ángeles Sánchez-Pérez and Tomás G. Villa

Antibiotics 2022, 11(5), 653; https://doi.org/10.3390/antibiotics11050653 - 13 May 2022

Cited by 13 | Viewed by 10102

Abstract

Phages have certain features, such as their ability to form protein–protein interactions, that make them good candidates for use in a variety of beneficial applications, such as in human or animal health, industry, food science, food safety, and agriculture. It is essential to [...] Read more.

Phages have certain features, such as their ability to form protein–protein interactions, that make them good candidates for use in a variety of beneficial applications, such as in human or animal health, industry, food science, food safety, and agriculture. It is essential to identify and characterize the proteins produced by particular phages in order to use these viruses in a variety of functional processes, such as bacterial detection, as vehicles for drug delivery, in vaccine development, and to combat multidrug resistant bacterial infections. Furthermore, phages can also play a major role in the design of a variety of cheap and stable sensors as well as in diagnostic assays that can either specifically identify specific compounds or detect bacteria. This article reviews recently developed phage-based techniques, such as the use of recombinant tempered phages, phage display and phage amplification-based detection. It also encompasses the application of phages as capture elements, biosensors and bioreceptors, with a special emphasis on novel bacteriophage-based mass spectrometry (MS) applications. Full article

(This article belongs to the Special Issue Frontiers in Phage Therapy)

► Show Figures

Figure 1

20 pages, 1132 KiB

Open AccessEditor’s ChoiceArticle

Antimicrobial Susceptibility of Enterococcus Isolates from Cattle and Pigs in Portugal: Linezolid Resistance Genes optrA and poxtA

by Joana Gião, Célia Leão, Teresa Albuquerque, Lurdes Clemente and Ana Amaro

Antibiotics 2022, 11(5), 615; https://doi.org/10.3390/antibiotics11050615 - 3 May 2022

Cited by 12 | Viewed by 3820

Abstract

Enterococci are part of the commensal gut microbiota of mammals, with Enterococcus faecalis and Enterococcus faecium being the most clinically relevant species. This study assesses the prevalence and diversity of enterococcal species in cattle (n = 201) and pig (n = [...] Read more.

Enterococci are part of the commensal gut microbiota of mammals, with Enterococcus faecalis and Enterococcus faecium being the most clinically relevant species. This study assesses the prevalence and diversity of enterococcal species in cattle (n = 201) and pig (n = 249) cecal samples collected in 2017. Antimicrobial susceptibility profiles of E. faecium (n = 48) and E. faecalis (n = 84) were assessed by agar and microdilution methods. Resistance genes were screened through PCR and nine strains were analyzed by Whole Genome Sequencing. A wide range of enterococci species was found colonizing the intestines of pigs and cattle. Overall, the prevalence of resistance to critically important antibiotics was low (except for erythromycin), and no glycopeptide-resistant isolates were identified. Two daptomycin-resistant E. faecalis ST58 and ST93 were found. Linezolid-resistant strains of E. faecalis (n = 3) and E. faecium (n = 1) were detected. Moreover, oxazolidinone resistance determinants optrA (n = 8) and poxtA (n = 2) were found in E. faecalis (ST16, ST58, ST207, ST474, ST1178) and E. faecium (ST22, ST2138). Multiple variants of optrA were found in different genetic contexts, either in the chromosome or plasmids. We highlight the importance of animals as reservoirs of resistance genes to critically important antibiotics. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antibiotic Alternatives in Livestock)

► Show Figures

Figure 1

12 pages, 1632 KiB

Open AccessEditor’s ChoiceArticle

Impact of COVID-19 on Antimicrobial Consumption and Spread of Multidrug-Resistance in Bacterial Infections

by Kibum Jeon, Seri Jeong, Nuri Lee, Min-Jeong Park, Wonkeun Song, Han-Sung Kim, Hyun Soo Kim and Jae-Seok Kim

Antibiotics 2022, 11(4), 535; https://doi.org/10.3390/antibiotics11040535 - 18 Apr 2022

Cited by 53 | Viewed by 5177

Abstract

The spread of COVID-19 pandemic may have affected antibiotic consumption patterns and the prevalence of colonized or infected by multidrug-resistant (MDR) bacteria. We investigated the differences in the consumption of antibiotics easily prone to resistance and the prevalence of MDR bacteria during the [...] Read more.

The spread of COVID-19 pandemic may have affected antibiotic consumption patterns and the prevalence of colonized or infected by multidrug-resistant (MDR) bacteria. We investigated the differences in the consumption of antibiotics easily prone to resistance and the prevalence of MDR bacteria during the COVID-19 pandemic (March 2020 to September 2021) compared to in the pre-pandemic period (March 2018 to September 2019). Data on usage of antibiotics and infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA) were obtained from hospitalized patients in four university hospitals. The consumption of penicillin with β-lactamase inhibitors (3.4% in ward, 5.8% in intensive care unit (ICU)), and carbapenems (25.9% in ward, 12.1% in ICU) increased during the pandemic period. The prevalence of MRSA (4.7%), VRE (49.0%), CRE (22.4%), and CRPA (20.1%) isolated in clinical samples from the ward and VRE (26.7%) and CRE (36.4%) isolated in clinical samples from the ICU were significantly increased, respectively. Meanwhile, only the prevalence of CRE (38.7%) isolated in surveillance samples from the ward increased. The COVID-19 pandemic is associated with increased consumption of antibiotics and has influenced the prevalence of infections caused by MDR isolates. Full article

(This article belongs to the Special Issue Social Dimensions of Antibiotic Resistance in Asia - a One Health Perspective)

► Show Figures

Figure 1

18 pages, 1224 KiB

Open AccessEditor’s ChoiceReview

Companion Animals—An Overlooked and Misdiagnosed Reservoir of Carbapenem Resistance

by Joana Moreira da Silva, Juliana Menezes, Cátia Marques and Constança Ferreira Pomba

Antibiotics 2022, 11(4), 533; https://doi.org/10.3390/antibiotics11040533 - 17 Apr 2022

Cited by 26 | Viewed by 5245

Abstract

The dissemination of antimicrobial-resistance is a major global threat affecting both human and animal health. Carbapenems are human use β-lactams of last resort; thus. the dissemination of carbapenemase-producing (CP) bacteria creates severe limitations for the treatment of multidrug-resistant bacteria in hospitalized patients. Even [...] Read more.

The dissemination of antimicrobial-resistance is a major global threat affecting both human and animal health. Carbapenems are human use β-lactams of last resort; thus. the dissemination of carbapenemase-producing (CP) bacteria creates severe limitations for the treatment of multidrug-resistant bacteria in hospitalized patients. Even though carbapenems are not routinely used in veterinary medicine, reports of infection or colonization by carbapenemase-producing Enterobacterales in companion animals are being reported. NDM-5 and OXA-48-like carbapenemases are among the most frequently reported in companion animals. Like in humans, Escherichia coli and Klebsiella pneumoniae are the most represented CP Enterobacterales found in companion animals, alongside with Acinetobacter baumannii. Considering that the detection of carbapenemase-producing Enterobacterales presents several difficulties, misdiagnosis of CP bacteria in companion animals may lead to important animal and public-health consequences. It is of the upmost importance to ensure an adequate monitoring and detection of CP bacteria in veterinary microbiology in order to safeguard animal health and minimise its dissemination to humans and the environment. This review encompasses an overview of the carbapenemase detection methods currently available, aiming to guide veterinary microbiologists on the best practices to improve its detection for clinical or research purposes. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Antimicrobial Use in Companion Animals)

► Show Figures

Figure 1

25 pages, 3276 KiB

Open AccessEditor’s ChoiceReview

Diagnosis of Bloodstream Infections: An Evolution of Technologies towards Accurate and Rapid Identification and Antibiotic Susceptibility Testing

by Kristel C. Tjandra, Nikhil Ram-Mohan, Ryuichiro Abe, Marjan M. Hashemi, Jyong-Huei Lee, Siew Mei Chin, Manuel A. Roshardt, Joseph C. Liao, Pak Kin Wong and Samuel Yang

Antibiotics 2022, 11(4), 511; https://doi.org/10.3390/antibiotics11040511 - 12 Apr 2022

Cited by 27 | Viewed by 8278

Abstract

Bloodstream infections (BSI) are a leading cause of death worldwide. The lack of timely and reliable diagnostic practices is an ongoing issue for managing BSI. The current gold standard blood culture practice for pathogen identification and antibiotic susceptibility testing is time-consuming. Delayed diagnosis [...] Read more.

Bloodstream infections (BSI) are a leading cause of death worldwide. The lack of timely and reliable diagnostic practices is an ongoing issue for managing BSI. The current gold standard blood culture practice for pathogen identification and antibiotic susceptibility testing is time-consuming. Delayed diagnosis warrants the use of empirical antibiotics, which could lead to poor patient outcomes, and risks the development of antibiotic resistance. Hence, novel techniques that could offer accurate and timely diagnosis and susceptibility testing are urgently needed. This review focuses on BSI and highlights both the progress and shortcomings of its current diagnosis. We surveyed clinical workflows that employ recently approved technologies and showed that, while offering improved sensitivity and selectivity, these techniques are still unable to deliver a timely result. We then discuss a number of emerging technologies that have the potential to shorten the overall turnaround time of BSI diagnosis through direct testing from whole blood—while maintaining, if not improving—the current assay’s sensitivity and pathogen coverage. We concluded by providing our assessment of potential future directions for accelerating BSI pathogen identification and the antibiotic susceptibility test. While engineering solutions have enabled faster assay turnaround, further progress is still needed to supplant blood culture practice and guide appropriate antibiotic administration for BSI patients. Full article

(This article belongs to the Special Issue Rapid Diagnostics of the Antimicrobial Resistance)

► Show Figures

Figure 1

8 pages, 833 KiB

Open AccessEditor’s ChoiceOpinion

Persistent Bacterial Infections, Antibiotic Treatment Failure, and Microbial Adaptive Evolution

by Ruggero La Rosa, Helle Krogh Johansen and Søren Molin

Antibiotics 2022, 11(3), 419; https://doi.org/10.3390/antibiotics11030419 - 21 Mar 2022

Cited by 20 | Viewed by 5631

Abstract

Antibiotic resistance is expected by the WHO to be the biggest threat to human health before 2050. In this overview, we argue that this prediction may in fact be too optimistic because it is often overlooked that many bacterial infections frequently ‘go under [...] Read more.

Antibiotic resistance is expected by the WHO to be the biggest threat to human health before 2050. In this overview, we argue that this prediction may in fact be too optimistic because it is often overlooked that many bacterial infections frequently ‘go under the radar’ because they are difficult to diagnose and characterize. Due to our lifestyle, persistent infections caused by opportunistic bacteria—well-known or emerging—show increasing success of infecting patients with reduced defense capacity, and often antibiotics fail to be sufficiently effective, even if the bacteria are susceptible, leaving small bacterial populations unaffected by treatment in the patient. The mechanisms behind infection persistence are multiple, and therefore very difficult to diagnose in the laboratory and to treat. In contrast to antibiotic resistance associated with acute infections caused by traditional bacterial pathogens, genetic markers associated with many persistent infections are imprecise and mostly without diagnostic value. In the absence of effective eradication strategies, there is a significant risk that persistent infections may eventually become highly resistant to antibiotic treatment due to the accumulation of genomic mutations, which will transform colonization into persistence. Full article

(This article belongs to the Special Issue How Far Are We from Predicting the Evolution of Antibiotic Resistance?)

► Show Figures

Figure 1

14 pages, 671 KiB

Open AccessEditor’s ChoiceReview

Understanding microRNAs in the Context of Infection to Find New Treatments against Human Bacterial Pathogens

by Álvaro Mourenza, Blanca Lorente-Torres, Elena Durante, Jesús Llano-Verdeja, Jesús F. Aparicio, Arsenio Fernández-López, José A. Gil, Luis M. Mateos and Michal Letek

Antibiotics 2022, 11(3), 356; https://doi.org/10.3390/antibiotics11030356 - 8 Mar 2022

Cited by 11 | Viewed by 4695

Abstract

The development of RNA-based anti-infectives has gained interest with the successful application of mRNA-based vaccines. Small RNAs are molecules of RNA of <200 nucleotides in length that may control the expression of specific genes. Small RNAs include small interference RNAs (siRNAs), Piwi-interacting RNAs [...] Read more.

The development of RNA-based anti-infectives has gained interest with the successful application of mRNA-based vaccines. Small RNAs are molecules of RNA of <200 nucleotides in length that may control the expression of specific genes. Small RNAs include small interference RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), or microRNAs (miRNAs). Notably, the role of miRNAs on the post-transcriptional regulation of gene expression has been studied in detail in the context of cancer and many other genetic diseases. However, it is also becoming apparent that some human miRNAs possess important antimicrobial roles by silencing host genes essential for the progress of bacterial or viral infections. Therefore, their potential use as novel antimicrobial therapies has gained interest during the last decade. The challenges of the transport and delivery of miRNAs to target cells are important, but recent research with exosomes is overcoming the limitations in RNA-cellular uptake, avoiding their degradation. Therefore, in this review, we have summarised the latest developments in the exosomal delivery of miRNA-based therapies, which may soon be another complementary treatment to pathogen-targeted antibiotics that could help solve the problem caused by multidrug-resistant bacteria. Full article

(This article belongs to the Special Issue Alternative Approaches to Treating Antimicrobial Resistant Infections)

► Show Figures

Figure 1

12 pages, 515 KiB

Open AccessEditor’s ChoiceReview

Review and Comparison of Antimicrobial Resistance Gene Databases

by Márton Papp and Norbert Solymosi

Antibiotics 2022, 11(3), 339; https://doi.org/10.3390/antibiotics11030339 - 4 Mar 2022

Cited by 38 | Viewed by 11105

Abstract

As the prevalence of antimicrobial resistance genes is increasing in microbes, we are facing the return of the pre-antibiotic era. Consecutively, the number of studies concerning antibiotic resistance and its spread in the environment is rapidly growing. Next generation sequencing technologies are widespread [...] Read more.

As the prevalence of antimicrobial resistance genes is increasing in microbes, we are facing the return of the pre-antibiotic era. Consecutively, the number of studies concerning antibiotic resistance and its spread in the environment is rapidly growing. Next generation sequencing technologies are widespread used in many areas of biological research and antibiotic resistance is no exception. For the rapid annotation of whole genome sequencing and metagenomic results considering antibiotic resistance, several tools and data resources were developed. These databases, however, can differ fundamentally in the number and type of genes and resistance determinants they comprise. Furthermore, the annotation structure and metadata stored in these resources can also contribute to their differences. Several previous reviews were published on the tools and databases of resistance gene annotation; however, to our knowledge, no previous review focused solely and in depth on the differences in the databases. In this review, we compare the most well-known and widely used antibiotic resistance gene databases based on their structure and content. We believe that this knowledge is fundamental for selecting the most appropriate database for a research question and for the development of new tools and resources of resistance gene annotation. Full article

(This article belongs to the Special Issue Genetic Background of Antimicrobial Resistance)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI