Antibiotics

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 8 | Viewed by 1764

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)

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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 3 | Viewed by 2558

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)

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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 - 02 Nov 2022

Cited by 7 | Viewed by 3160

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)

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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 44 | Viewed by 6591

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)

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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 4 | Viewed by 3079

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 - 06 Oct 2022

Cited by 8 | Viewed by 12969

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

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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 - 01 Oct 2022

Cited by 2 | Viewed by 2307

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)

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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 14 | Viewed by 5688

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)

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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 16 | Viewed by 8612

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)

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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 - 05 Sep 2022

Cited by 3 | Viewed by 2446

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)

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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 - 03 Sep 2022

Cited by 6 | Viewed by 2534

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)

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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 4 | Viewed by 3814

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)

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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 - 04 Aug 2022

Cited by 3 | Viewed by 2617

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)

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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 - 03 Aug 2022

Cited by 5 | Viewed by 4159

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)

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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 - 03 Aug 2022

Cited by 2 | Viewed by 2128

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

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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 - 09 Jul 2022

Cited by 2 | Viewed by 2251

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

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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 - 07 Jul 2022

Cited by 4 | Viewed by 19301

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)

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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 - 06 Jul 2022

Cited by 3 | Viewed by 2165

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)

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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 - 09 Jun 2022

Cited by 2 | Viewed by 2005

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

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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 - 08 Jun 2022

Cited by 2 | Viewed by 2595

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)

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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 - 02 Jun 2022

Cited by 42 | Viewed by 65350

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)

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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 9 | Viewed by 3352

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)

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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 5 | Viewed by 4220

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)

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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 11 | Viewed by 7919

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)

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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 - 03 May 2022

Cited by 8 | Viewed by 3088

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)

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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 43 | Viewed by 4223

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)

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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 20 | Viewed by 4096

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)

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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 15 | Viewed by 6117

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)

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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 12 | Viewed by 4033

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?)

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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 - 08 Mar 2022

Cited by 6 | Viewed by 3718

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)

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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 - 04 Mar 2022

Cited by 30 | Viewed by 8572

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)

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7 pages, 966 KiB

Open AccessEditor’s ChoiceCase Report

Possible COVID-19-Associated Pulmonary Aspergillosis Due to Aspergillus niger in Greece

by Maria Katsiari, Angeliki Mavroidi, Eleftheria Palla, Konstantina Zourla, Theodoros Alonistiotis, Kyriakos Ntorlis, Charikleia Nikolaou, Georgia Vrioni and Athanasios Tsakris

Antibiotics 2022, 11(3), 300; https://doi.org/10.3390/antibiotics11030300 - 23 Feb 2022

Cited by 3 | Viewed by 2062

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes direct damage to the pulmonary epithelium, enabling Aspergillus invasion. Rapid progression and high mortality of invasive aspergillosis have been reported. In the present study, we report a rare case of possible COVID-19-associated pulmonary aspergillosis (CAPA) [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes direct damage to the pulmonary epithelium, enabling Aspergillus invasion. Rapid progression and high mortality of invasive aspergillosis have been reported. In the present study, we report a rare case of possible COVID-19-associated pulmonary aspergillosis (CAPA) caused by A. niger in a Greek patient. Diagnosis was based on ECMM/ISHAM specific criteria and the new algorithm “BM-AspICU” for the invasive pulmonary aspergillosis diagnostic strategy. The fungal isolate was recovered in a non-bronchoalveolar lavage (non-BAL) sample and its identification was performed by standard macroscopic and microscopic morphological studies. MALDI-TOF analysis confirmed the identification of A. niger. In addition, galactomannan antigen and Aspergillus real-time PCR testing were positive in the non-BAL sample, while in serum they proved negative. The A. niger isolate showed an MIC for fluconazole ≥128 μg/mL, for itraconazole and posaconazole 0.25 μg/mL, for voriconazole 0.5 μg/mL, for flucytosine 4 μg/mL, for amphotericin B 1 μg/mL, and for all echinocandins (caspofungin, anidulafungin, micafungin) >8 μg/mL. The patient was initially treated with voriconazole; amphotericin B was subsequently added, when a significant progression of cavitation was demonstrated on chest computed tomography. A. niger was not isolated in subsequent samples and the patient’s unfavorable outcome was attributed to septic shock caused by a pandrug-resistant Acinetobacter baumannii strain. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Fungal Infections)

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14 pages, 2021 KiB

Open AccessEditor’s ChoiceSystematic Review

Safety and Efficacy of Devices Delivering Inhaled Antibiotics among Adults with Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and a Network Meta-Analysis

by Sofia Tejada, Sergio Ramírez-Estrada, Carlos G. Forero, Miguel Gallego, Joan B. Soriano, Pablo A. Cardinal-Fernández, Stephan Ehrmann and Jordi Rello

Antibiotics 2022, 11(2), 275; https://doi.org/10.3390/antibiotics11020275 - 19 Feb 2022

Cited by 4 | Viewed by 3044

Abstract

It remains unknown whether the type of aerosol generating device is affecting efficacy and safety among non-cystic fibrosis bronchiectasis (NCFB) adults. The proposal of this network meta-analysis (NMA) is to evaluate effectiveness and safety of inhaled antibiotics administered via dry powder inhaler (DPI) [...] Read more.

It remains unknown whether the type of aerosol generating device is affecting efficacy and safety among non-cystic fibrosis bronchiectasis (NCFB) adults. The proposal of this network meta-analysis (NMA) is to evaluate effectiveness and safety of inhaled antibiotics administered via dry powder inhaler (DPI) and via nebulizers (SVN) among adult patients with NCFB. Inclusion criteria were randomized-controlled trials, adults (≥18 years) with NCFB, and inhaled antibiotics administered via DPI as intervention. Search strategy was performed in PubMed, Web of Science, and Cochrane Library from 2000 to 2019. Sixteen trials (2870 patients) were included. Three trials (all ciprofloxacin) used DPIs and thirteen used SVN (three ciprofloxacin). Both DPI and SVN devices achieved similar safety outcomes (adverse events, antibiotic discontinuation, severe adverse events, and bronchospasm). Administration of ciprofloxacin via DPI significantly improved time to first exacerbation (87 days, 95% CI 34.3–139.7) and quality of life (MD −7.52; 95% CI −13.06 to −1.98) when compared with via SVN. No other significant differences were documented in clinical efficacy (at least one exacerbation, FEV₁% predicted) and microbiologic response (bacterial eradication, emergence of new potential pathogens, and emergence of antimicrobial resistance) when comparing devices. Our NMA documented that time to first exacerbation and quality of life, were more favorable for DPIs. Decisions on the choice of devices should incorporate these findings plus other criteria, such as simplicity, costs or maintenance requirements. 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)

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16 pages, 1579 KiB

Open AccessEditor’s ChoiceArticle

Stapling of Peptides Potentiates the Antibiotic Treatment of Acinetobacter baumannii In Vivo

by Gina K. Schouten, Felix M. Paulussen, Oscar P. Kuipers, Wilbert Bitter, Tom N. Grossmann and Peter van Ulsen

Antibiotics 2022, 11(2), 273; https://doi.org/10.3390/antibiotics11020273 - 19 Feb 2022

Cited by 6 | Viewed by 3745

Abstract

The rising incidence of multidrug resistance in Gram-negative bacteria underlines the urgency for novel treatment options. One promising new approach is the synergistic combination of antibiotics with antimicrobial peptides. However, the use of such peptides is not straightforward; they are often sensitive to [...] Read more.

The rising incidence of multidrug resistance in Gram-negative bacteria underlines the urgency for novel treatment options. One promising new approach is the synergistic combination of antibiotics with antimicrobial peptides. However, the use of such peptides is not straightforward; they are often sensitive to proteolytic degradation, which greatly limits their clinical potential. One approach to increase stability is to apply a hydrocarbon staple to the antimicrobial peptide, thereby fixing them in an α-helical conformation, which renders them less exposed to proteolytic activity. In this work we applied several different hydrocarbon staples to two previously described peptides shown to act on the outer membrane, L6 and L8, and tested their activity in a zebrafish embryo infection model using a clinical isolate of Acinetobacter baumannii as a pathogen. We show that the introduction of such a hydrocarbon staple to the peptide L8 improves its in vivo potentiating activity on antibiotic treatment, without increasing its in vivo antimicrobial activity, toxicity or hemolytic activity. Full article

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

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52 pages, 4389 KiB

Open AccessEditor’s ChoiceReview

Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them

by Javier Santos-Aberturas and Natalia M. Vior

Antibiotics 2022, 11(2), 195; https://doi.org/10.3390/antibiotics11020195 - 02 Feb 2022

Cited by 6 | Viewed by 5127

Abstract

Bacterial secondary metabolites represent an invaluable source of bioactive molecules for the pharmaceutical and agrochemical industries. Although screening campaigns for the discovery of new compounds have traditionally been strongly biased towards the study of soil-dwelling Actinobacteria, the current antibiotic resistance and discovery crisis [...] Read more.

Bacterial secondary metabolites represent an invaluable source of bioactive molecules for the pharmaceutical and agrochemical industries. Although screening campaigns for the discovery of new compounds have traditionally been strongly biased towards the study of soil-dwelling Actinobacteria, the current antibiotic resistance and discovery crisis has brought a considerable amount of attention to the study of previously neglected bacterial sources of secondary metabolites. The development and application of new screening, sequencing, genetic manipulation, cultivation and bioinformatic techniques have revealed several other groups of bacteria as producers of striking chemical novelty. Biosynthetic machineries evolved from independent taxonomic origins and under completely different ecological requirements and selective pressures are responsible for these structural innovations. In this review, we summarize the most important discoveries related to secondary metabolites from alternative bacterial sources, trying to provide the reader with a broad perspective on how technical novelties have facilitated the access to the bacterial metabolic dark matter. Full article

(This article belongs to the Special Issue Challenges and Opportunities in Antibiotic Biosynthesis and Development)

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15 pages, 1624 KiB

Open AccessEditor’s ChoiceReview

Air Ambulance: Antimicrobial Power of Bacterial Volatiles

by Alexander Lammers, Michael Lalk and Paolina Garbeva

Antibiotics 2022, 11(1), 109; https://doi.org/10.3390/antibiotics11010109 - 14 Jan 2022

Cited by 13 | Viewed by 3094

Abstract

We are currently facing an antimicrobial resistance crisis, which means that a lot of bacterial pathogens have developed resistance to common antibiotics. Hence, novel and innovative solutions are urgently needed to combat resistant human pathogens. A new source of antimicrobial compounds could be [...] Read more.

We are currently facing an antimicrobial resistance crisis, which means that a lot of bacterial pathogens have developed resistance to common antibiotics. Hence, novel and innovative solutions are urgently needed to combat resistant human pathogens. A new source of antimicrobial compounds could be bacterial volatiles. Volatiles are ubiquitous produced, chemically divers and playing essential roles in intra- and interspecies interactions like communication and antimicrobial defense. In the last years, an increasing number of studies showed bioactivities of bacterial volatiles, including antibacterial, antifungal and anti-oomycete activities, indicating bacterial volatiles as an exciting source for novel antimicrobial compounds. In this review we introduce the chemical diversity of bacterial volatiles, their antimicrobial activities and methods for testing this activity. Concluding, we discuss the possibility of using antimicrobial volatiles to antagonize the antimicrobial resistance crisis. Full article

(This article belongs to the Special Issue The Ecological Role of Antibiotic Production in Bacteria)

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11 pages, 481 KiB

Open AccessEditor’s ChoiceArticle

Factors Affecting Antibiotic Prescription among Hospital Physicians in a Low-Antimicrobial-Resistance Country: A Qualitative Study

by Ingrid Christensen, Jon Birger Haug, Dag Berild, Jørgen Vildershøj Bjørnholt, Brita Skodvin and Lars-Petter Jelsness-Jørgensen

Antibiotics 2022, 11(1), 98; https://doi.org/10.3390/antibiotics11010098 - 13 Jan 2022

Cited by 8 | Viewed by 3359

Abstract

Antimicrobial resistance (AMR) is a threat to hospital patients. Antimicrobial stewardship programs (ASPs) can counteract AMR. To optimize ASPs, we need to understand what affects physicians’ antibiotic prescription from several contexts. In this study, we aimed to explore the factors affecting hospital physicians’ [...] Read more.

Antimicrobial resistance (AMR) is a threat to hospital patients. Antimicrobial stewardship programs (ASPs) can counteract AMR. To optimize ASPs, we need to understand what affects physicians’ antibiotic prescription from several contexts. In this study, we aimed to explore the factors affecting hospital physicians’ antibiotic choices in a low-resistance country to identify potential targets for future ASPs. We interviewed 14 physicians involved in antibiotic prescription in a Norwegian hospital. The interviews were audiotaped, transcribed verbatim, and analyzed using thematic analysis. The main factors affecting antibiotic prescription were a high work pressure, insufficient staff resources, and uncertainties regarding clinical decisions. Treatment expectations from patients and next of kin, benevolence towards the patients, suboptimal microbiological testing, and limited time for infectious disease specialists to offer advisory services also affected the antibiotic choices. Future ASP efforts should evaluate the system organization and prioritizations to address and manage potential time-pressure issues. To limit the use of broad-spectrum antibiotics, improving microbiology testing and the routines for consultations with infectious disease specialists seems beneficial. We also identified a need among the prescribing physicians for a debate on ethical antibiotic questions. Full article

(This article belongs to the Special Issue Antimicrobial Prescribing and Stewardship, 2nd Volume)

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24 pages, 2260 KiB

Open AccessEditor’s ChoiceReview

Biofilms in Surgical Site Infections: Recent Advances and Novel Prevention and Eradication Strategies

by Andriy Hrynyshyn, Manuel Simões and Anabela Borges

Antibiotics 2022, 11(1), 69; https://doi.org/10.3390/antibiotics11010069 - 07 Jan 2022

Cited by 33 | Viewed by 6081

Abstract

Surgical site infections (SSIs) are common postoperative occurrences due to contamination of the surgical wound or implanted medical devices with community or hospital-acquired microorganisms, as well as other endogenous opportunistic microbes. Despite numerous rules and guidelines applied to prevent these infections, SSI rates [...] Read more.

Surgical site infections (SSIs) are common postoperative occurrences due to contamination of the surgical wound or implanted medical devices with community or hospital-acquired microorganisms, as well as other endogenous opportunistic microbes. Despite numerous rules and guidelines applied to prevent these infections, SSI rates are considerably high, constituting a threat to the healthcare system in terms of morbidity, prolonged hospitalization, and death. Approximately 80% of human SSIs, including chronic wound infections, are related to biofilm-forming bacteria. Biofilm-associated SSIs are extremely difficult to treat with conventional antibiotics due to several tolerance mechanisms provided by the multidrug-resistant bacteria, usually arranged as polymicrobial communities. In this review, novel strategies to control, i.e., prevent and eradicate, biofilms in SSIs are presented and discussed, focusing mainly on two attractive approaches: the use of nanotechnology-based composites and natural plant-based products. An overview of new therapeutic agents and strategic approaches to control epidemic multidrug-resistant pathogenic microorganisms, particularly when biofilms are present, is provided alongside other combinatorial approaches as attempts to obtain synergistic effects with conventional antibiotics and restore their efficacy to treat biofilm-mediated SSIs. Some detection and real-time monitoring systems to improve biofilm control strategies and diagnosis of human infections are also discussed. Full article

(This article belongs to the Special Issue Nature Inspired Antibiotic Adjuvants to Face the Problem of Multidrug Resistance and Biofilm Infections)

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26 pages, 11164 KiB

Open AccessEditor’s ChoiceArticle

Antimicrobial Resistance and Environmental Health: A Water Stewardship Framework for Global and National Action

by Rachel A. Kaiser, Lina Taing and Himesh Bhatia

Antibiotics 2022, 11(1), 63; https://doi.org/10.3390/antibiotics11010063 - 05 Jan 2022

Cited by 11 | Viewed by 4236

Abstract

Antimicrobial resistance (AMR) is a global health crisis that affects all life on Earth. In 2015, the World Health Organization developed guidance to combat AMR in accordance with a One Health framework considering human, animal, and environment sectors of planetary health. This study [...] Read more.

Antimicrobial resistance (AMR) is a global health crisis that affects all life on Earth. In 2015, the World Health Organization developed guidance to combat AMR in accordance with a One Health framework considering human, animal, and environment sectors of planetary health. This study reviewed global guidance and 25 National Action Plans to evaluate thematic priorities in One Health AMR approaches using a novel framework that additionally facilitated the identification of water-related stewardship gaps, as water resources are recognized as the primary environmental AMR reservoir and dissemination pathway. This review found that global and national stewardship primarily focuses on mitigating antibiotic use in the human and animal sectors, overlooking environmental drivers, particularly diverse environmental waters. The findings of this study highlight the need to broaden the scope of water-related AMR concerns beyond water, sanitation, and hygiene (WASH) infrastructure for water supply and wastewater treatment, and account for environmental waters in AMR development and dissemination, particularly in low-income countries where half a billion people rely on environmental waters to meet daily needs. Equitably accounting for water environments, supplies, and waste in AMR prevention, mitigation, surveillance, and innovation can significantly enhance the integration of environmental objectives in One Health AMR stewardship. Full article

(This article belongs to the Special Issue Policy Design, Implementation and Governance of Antimicrobial Resistance)

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32 pages, 15897 KiB

Open AccessEditor’s ChoiceReview

Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition

by Abolfazl Dashtbani-Roozbehani and Melissa H. Brown

Antibiotics 2021, 10(12), 1502; https://doi.org/10.3390/antibiotics10121502 - 07 Dec 2021

Cited by 40 | Viewed by 6539

Abstract

The increasing emergence of antimicrobial resistance in staphylococcal bacteria is a major health threat worldwide due to significant morbidity and mortality resulting from their associated hospital- or community-acquired infections. Dramatic decrease in the discovery of new antibiotics from the pharmaceutical industry coupled with [...] Read more.

The increasing emergence of antimicrobial resistance in staphylococcal bacteria is a major health threat worldwide due to significant morbidity and mortality resulting from their associated hospital- or community-acquired infections. Dramatic decrease in the discovery of new antibiotics from the pharmaceutical industry coupled with increased use of sanitisers and disinfectants due to the ongoing COVID-19 pandemic can further aggravate the problem of antimicrobial resistance. Staphylococci utilise multiple mechanisms to circumvent the effects of antimicrobials. One of these resistance mechanisms is the export of antimicrobial agents through the activity of membrane-embedded multidrug efflux pump proteins. The use of efflux pump inhibitors in combination with currently approved antimicrobials is a promising strategy to potentiate their clinical efficacy against resistant strains of staphylococci, and simultaneously reduce the selection of resistant mutants. This review presents an overview of the current knowledge of staphylococcal efflux pumps, discusses their clinical impact, and summarises compounds found in the last decade from plant and synthetic origin that have the potential to be used as adjuvants to antibiotic therapy against multidrug resistant staphylococci. Critically, future high-resolution structures of staphylococcal efflux pumps could aid in design and development of safer, more target-specific and highly potent efflux pump inhibitors to progress into clinical use. Full article

(This article belongs to the Special Issue Antibacterial, Antibiofilm and Anti-virulence Activity Research of Both Natural and Synthetic Products)

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36 pages, 3978 KiB

Open AccessEditor’s ChoiceReview

Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo and Clinical Application

by Katarzyna M. Danis-Wlodarczyk, Daniel J. Wozniak and Stephen T. Abedon

Antibiotics 2021, 10(12), 1497; https://doi.org/10.3390/antibiotics10121497 - 06 Dec 2021

Cited by 39 | Viewed by 9914

Abstract

Over the past few decades, we have witnessed a surge around the world in the emergence of antibiotic-resistant bacteria. This global health threat arose mainly due to the overuse and misuse of antibiotics as well as a relative lack of new drug classes [...] Read more.

Over the past few decades, we have witnessed a surge around the world in the emergence of antibiotic-resistant bacteria. This global health threat arose mainly due to the overuse and misuse of antibiotics as well as a relative lack of new drug classes in development pipelines. Innovative antibacterial therapeutics and strategies are, therefore, in grave need. For the last twenty years, antimicrobial enzymes encoded by bacteriophages, viruses that can lyse and kill bacteria, have gained tremendous interest. There are two classes of these phage-derived enzymes, referred to also as enzybiotics: peptidoglycan hydrolases (lysins), which degrade the bacterial peptidoglycan layer, and polysaccharide depolymerases, which target extracellular or surface polysaccharides, i.e., bacterial capsules, slime layers, biofilm matrix, or lipopolysaccharides. Their features include distinctive modes of action, high efficiency, pathogen specificity, diversity in structure and activity, low possibility of bacterial resistance development, and no observed cross-resistance with currently used antibiotics. Additionally, and unlike antibiotics, enzybiotics can target metabolically inactive persister cells. These phage-derived enzymes have been tested in various animal models to combat both Gram-positive and Gram-negative bacteria, and in recent years peptidoglycan hydrolases have entered clinical trials. Here, we review the testing and clinical use of these enzymes. Full article

(This article belongs to the Special Issue Bacteriolysins and Other Phage-Based Strategies to Combat Bacterial Infections)

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12 pages, 2200 KiB

Open AccessEditor’s ChoiceArticle

Characterization and Molecular Determinants for β-Lactam Specificity of the Multidrug Efflux Pump AcrD from Salmonella typhimurium

by Jenifer Cuesta Bernal, Jasmin El-Delik, Stephan Göttig and Klaas M. Pos

Antibiotics 2021, 10(12), 1494; https://doi.org/10.3390/antibiotics10121494 - 06 Dec 2021

Cited by 4 | Viewed by 2569

Abstract

Gram-negative Tripartite Resistance Nodulation and cell Division (RND) superfamily efflux pumps confer various functions, including multidrug and bile salt resistance, quorum-sensing, virulence and can influence the rate of mutations on the chromosome. Multidrug RND efflux systems are often characterized by a wide substrate [...] Read more.

Gram-negative Tripartite Resistance Nodulation and cell Division (RND) superfamily efflux pumps confer various functions, including multidrug and bile salt resistance, quorum-sensing, virulence and can influence the rate of mutations on the chromosome. Multidrug RND efflux systems are often characterized by a wide substrate specificity. Similarly to many other RND efflux pump systems, AcrAD-TolC confers resistance toward SDS, novobiocin and deoxycholate. In contrast to the other pumps, however, it in addition confers resistance against aminoglycosides and dianionic β-lactams, such as sulbenicillin, aztreonam and carbenicillin. Here, we could show that AcrD from Salmonella typhimurium confers resistance toward several hitherto unreported AcrD substrates such as temocillin, dicloxacillin, cefazolin and fusidic acid. In order to address the molecular determinants of the S. typhimurium AcrD substrate specificity, we conducted substitution analyses in the putative access and deep binding pockets and in the TM1/TM2 groove region. The variants were tested in E. coli ΔacrBΔacrD against β-lactams oxacillin, carbenicillin, aztreonam and temocillin. Deep binding pocket variants N136A, D276A and Y327A; access pocket variant R625A; and variants with substitutions in the groove region between TM1 and TM2 conferred a sensitive phenotype and might, therefore, be involved in anionic β-lactam export. In contrast, lower susceptibilities were observed for E. coli cells harbouring deep binding pocket variants T139A, D176A, S180A, F609A, T611A and F627A and the TM1/TM2 groove variant I337A. This study provides the first insights of side chains involved in drug binding and transport for AcrD from S. typhimurium. Full article

(This article belongs to the Special Issue The Structural and Functional Study of Efflux Pumps Belonging to the RND Transporters Family from Gram-Negative Bacteria)

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19 pages, 552 KiB

Open AccessEditor’s ChoiceReview

Predicting Antimicrobial Activity at the Target Site: Pharmacokinetic/Pharmacodynamic Indices versus Time–Kill Approaches

by Wisse van Os and Markus Zeitlinger

Antibiotics 2021, 10(12), 1485; https://doi.org/10.3390/antibiotics10121485 - 04 Dec 2021

Cited by 7 | Viewed by 3612

Abstract

Antibiotic dosing strategies are generally based on systemic drug concentrations. However, drug concentrations at the infection site drive antimicrobial effect, and efficacy predictions and dosing strategies should be based on these concentrations. We set out to review different translational pharmacokinetic-pharmacodynamic (PK/PD) approaches from [...] Read more.

Antibiotic dosing strategies are generally based on systemic drug concentrations. However, drug concentrations at the infection site drive antimicrobial effect, and efficacy predictions and dosing strategies should be based on these concentrations. We set out to review different translational pharmacokinetic-pharmacodynamic (PK/PD) approaches from a target site perspective. The most common approach involves calculating the probability of attaining animal-derived PK/PD index targets, which link PK parameters to antimicrobial susceptibility measures. This approach is time efficient but ignores some aspects of the shape of the PK profile and inter-species differences in drug clearance and distribution, and provides no information on the PD time-course. Time–kill curves, in contrast, depict bacterial response over time. In vitro dynamic time–kill setups allow for the evaluation of bacterial response to clinical PK profiles, but are not representative of the infection site environment. The translational value of in vivo time–kill experiments, conversely, is limited from a PK perspective. Computational PK/PD models, especially when developed using both in vitro and in vivo data and coupled to target site PK models, can bridge translational gaps in both PK and PD. Ultimately, clinical PK and experimental and computational tools should be combined to tailor antibiotic treatment strategies to the site of infection. Full article

(This article belongs to the Special Issue 10th Anniversary of Antibiotics—Recent Advances in Pharmacodynamics of Antibiotics)

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15 pages, 3305 KiB

Open AccessEditor’s ChoiceArticle

Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials

by Susanne Paukner, David Mariano, Anita F. Das, Gregory J. Moran, Christian Sandrock, Ken B. Waites and Thomas M. File, Jr.

Antibiotics 2021, 10(12), 1489; https://doi.org/10.3390/antibiotics10121489 - 04 Dec 2021

Cited by 4 | Viewed by 3171

Abstract

Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with [...] Read more.

Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5–7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5–10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality (M. pneumoniae 71.2% [52/73]; L. pneumophila 96.9% [63/65]; C. pneumoniae 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0–2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4–96.6%; moxifloxacin 90.3–96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1–89.7%; moxifloxacin 74.2–97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens. Full article

(This article belongs to the Special Issue One Health in Mycoplasmas: Antimicrobial Susceptibility and Resistance in Mycoplasmas Infecting Humans, Animals, Plants and Insects)

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18 pages, 1788 KiB

Open AccessEditor’s ChoiceArticle

Effect of Ursolic and Oleanolic Acids on Lipid Membranes: Studies on MRSA and Models of Membranes

by Sandrine Verstraeten, Lucy Catteau, Laila Boukricha, Joelle Quetin-Leclercq and Marie-Paule Mingeot-Leclercq

Antibiotics 2021, 10(11), 1381; https://doi.org/10.3390/antibiotics10111381 - 11 Nov 2021

Cited by 9 | Viewed by 2421

Abstract

Staphylococcus aureus is an opportunistic pathogen and the major causative agent of life-threatening hospital- and community-acquired infections. A combination of antibiotics could be an opportunity to address the widespread emergence of antibiotic-resistant strains, including Methicillin-Resistant S. aureus (MRSA). We here investigated the potential [...] Read more.

Staphylococcus aureus is an opportunistic pathogen and the major causative agent of life-threatening hospital- and community-acquired infections. A combination of antibiotics could be an opportunity to address the widespread emergence of antibiotic-resistant strains, including Methicillin-Resistant S. aureus (MRSA). We here investigated the potential synergy between ampicillin and plant-derived antibiotics (pentacyclic triterpenes, ursolic acid (UA) and oleanolic acid (OA)) towards MRSA (ATCC33591 and COL) and the mechanisms involved. We calculated the Fractional Inhibitory Concentration Index (FICI) and demonstrated synergy. We monitored fluorescence of Bodipy-TR-Cadaverin, propidium iodide and membrane potential-sensitive probe for determining the ability of UA and OA to bind to lipoteichoic acids (LTA), and to induce membrane permeabilization and depolarization, respectively. Both pentacyclic triterpenes were able to bind to LTA and to induce membrane permeabilization and depolarization in a dose-dependent fashion. These effects were not accompanied by significant changes in cellular concentration of pentacyclic triterpenes and/or ampicillin, suggesting an effect mediated through lipid membranes. We therefore focused on membranous effects induced by UA and OA, and we investigated on models of membranes, the role of specific lipids including phosphatidylglycerol and cardiolipin. The effect induced on membrane fluidity, permeability and ability to fuse were studied by determining changes in fluorescence anisotropy of DPH/generalized polarization of Laurdan, calcein release from liposomes, fluorescence dequenching of octadecyl-rhodamine B and liposome-size, respectively. Both UA and OA showed a dose-dependent effect with membrane rigidification, increase of membrane permeabilization and fusion. Except for the effect on membrane fluidity, the effect of UA was consistently higher compared with that obtained with OA, suggesting the role of methyl group position. All together the data demonstrated the potential role of compounds acting on lipid membranes for enhancing the activity of other antibiotics, like ampicillin and inducing synergy. Such combinations offer an opportunity to explore a larger antibiotic chemical space. Full article

(This article belongs to the Special Issue Design and Preparation of Antimicrobial Agents)

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11 pages, 648 KiB

Open AccessEditor’s ChoiceArticle

Correlation between Previous Antibiotic Exposure and COVID-19 Severity. A Population-Based Cohort Study

by Carl Llor, Dan Ouchi, Maria Giner-Soriano, Ana García-Sangenís, Lars Bjerrum and Rosa Morros

Antibiotics 2021, 10(11), 1364; https://doi.org/10.3390/antibiotics10111364 - 08 Nov 2021

Cited by 16 | Viewed by 5794

Abstract

We examined the correlation between previous antibiotic exposure and COVID-19 severity using a population-based observational matched cohort study with patient level data obtained for more than 5.8 million people registered in SIDIAP in Catalonia, Spain. We included all patients newly diagnosed with COVID-19 [...] Read more.

We examined the correlation between previous antibiotic exposure and COVID-19 severity using a population-based observational matched cohort study with patient level data obtained for more than 5.8 million people registered in SIDIAP in Catalonia, Spain. We included all patients newly diagnosed with COVID-19 from March to June 2020 and identified all their antibiotic prescriptions in the previous two years. We used a composite severity endpoint, including pneumonia, hospital admission and death due to COVID-19. We examined the influence of high antibiotic exposure (>4 regimens), exposure to highest priority critically important antimicrobials (HPCIA) and recent exposure. Potential confounders were adjusted by logistic regression. A total of 280,679 patients were diagnosed with COVID-19, 146,656 of whom were exposed to at least one antibiotic course (52.3%) during the preceding two years. A total of 25,222 presented severe COVID-19 infection (9%), and the risk of severity was highest among those exposed to antibiotics (OR 1.12; 95% CI: 1.04–1.21). Among all individuals exposed to antibiotics, high, recent and exposure to HPCIAs were correlated with increased COVID severity (OR 1.19; 95% CI: 1.14–1.26; 1.41; 95% CI: 1.36–1.46; and 1.35; 95% CI: 1.30–1.40, respectively). Our findings confirm a significant correlation between previous antibiotic exposure and increased severity of COVID-19 disease. Full article

(This article belongs to the Special Issue Antibiotics Use in Primary Care during COVID-19)

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19 pages, 3645 KiB

Open AccessEditor’s ChoiceArticle

Natural Bred ε²-Phages Have an Improved Host Range and Virulence against Uropathogenic Escherichia coli over Their Ancestor Phages

by Maria Loose, David Sáez Moreno, Michele Mutti, Eva Hitzenhammer, Zehra Visram, David Dippel, Susanne Schertler, Lenka Podpera Tišáková, Johannes Wittmann, Lorenzo Corsini and Florian Wagenlehner

Antibiotics 2021, 10(11), 1337; https://doi.org/10.3390/antibiotics10111337 - 01 Nov 2021

Cited by 5 | Viewed by 2838

Abstract

Alternative treatments for Escherichia coli infections are urgently needed, and phage therapy is a promising option where antibiotics fail, especially for urinary tract infections (UTI). We used wastewater-isolated phages to test their lytic activity against a panel of 47 E. coli strains reflecting [...] Read more.

Alternative treatments for Escherichia coli infections are urgently needed, and phage therapy is a promising option where antibiotics fail, especially for urinary tract infections (UTI). We used wastewater-isolated phages to test their lytic activity against a panel of 47 E. coli strains reflecting the diversity of strains found in UTI, including sequence type 131, 73 and 69. The plaquing host range (PHR) was between 13 and 63%. In contrast, the kinetic host range (KHR), describing the percentage of strains for which growth in suspension was suppressed for 24 h, was between 0% and 19%, substantially lower than the PHR. To improve the phage host range and their efficacy, we bred the phages by mixing and propagating cocktails on a subset of E. coli strains. The bred phages, which we termed evolution-squared ε²-phages, of a mixture of Myoviridae have KHRs up to 23% broader compared to their ancestors. Furthermore, using constant phage concentrations, Myoviridae ε²-phages suppressed the growth of higher bacterial inocula than their ancestors did. Thus, the ε²-phages were more virulent compared to their ancestors. Analysis of the genetic sequences of the ε²-phages with the broadest host range reveals that they are mosaic intercrossings of 2–3 ancestor phages. The recombination sites are distributed over the whole length of the genome. All ε²-phages are devoid of genes conferring lysogeny, antibiotic resistance, or virulence. Overall, this study shows that ε²-phages are remarkably more suitable than the wild-type phages for phage therapy. Full article

(This article belongs to the Special Issue Benefits of Bacteriophages to Combat Antibiotic-Resistant Bacteria)

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14 pages, 329 KiB

Open AccessEditor’s ChoiceSystematic Review

Antimicrobial Treatment Strategies for Stenotrophomonas maltophilia: A Focus on Novel Therapies

by Jean Gibb and Darren W. Wong

Antibiotics 2021, 10(10), 1226; https://doi.org/10.3390/antibiotics10101226 - 09 Oct 2021

Cited by 29 | Viewed by 8440

Abstract

Stenotrophomonas maltophilia is an urgent global threat due to its increasing incidence and intrinsic antibiotic resistance. Antibiotic development has focused on carbapenem-resistant Enterobacteriaceae, Pseudomonas, and Acinetobacter, with approved antibiotics in recent years having limited activity for Stenotrophomonas. Accordingly, novel treatment strategies for Stenotrophomonas [...] Read more.

Stenotrophomonas maltophilia is an urgent global threat due to its increasing incidence and intrinsic antibiotic resistance. Antibiotic development has focused on carbapenem-resistant Enterobacteriaceae, Pseudomonas, and Acinetobacter, with approved antibiotics in recent years having limited activity for Stenotrophomonas. Accordingly, novel treatment strategies for Stenotrophomonas are desperately needed. We conducted a systemic literature review and offer recommendations based on current evidence for a treatment strategy of Stenotrophomonas infection. Full article

(This article belongs to the Special Issue Epidemiology, Prognosis and Antimicrobial Treatment of Extensively Antibiotic-Resistant Bacterial Infections)

23 pages, 1563 KiB

Open AccessEditor’s ChoiceReview

Enterococcus spp. as a Producer and Target of Bacteriocins: A Double-Edged Sword in the Antimicrobial Resistance Crisis Context

by Ana C. Almeida-Santos, Carla Novais, Luísa Peixe and Ana R. Freitas

Antibiotics 2021, 10(10), 1215; https://doi.org/10.3390/antibiotics10101215 - 07 Oct 2021

Cited by 26 | Viewed by 5318

Abstract

Enterococcus spp. are one of the most frequent producers of bacteriocins (enterocins), which provides them with an advantage to compete in their natural environment, which is the gut of humans and many animals. The enterocins’ activity against microorganisms from different phylogenetic groups has [...] Read more.

Enterococcus spp. are one of the most frequent producers of bacteriocins (enterocins), which provides them with an advantage to compete in their natural environment, which is the gut of humans and many animals. The enterocins’ activity against microorganisms from different phylogenetic groups has raised interest in Enterococcus spp. in different contexts throughout the last decades, especially in the food industry. Nevertheless, some species can also cause opportunistic life-threatening infections and are frequently multidrug-resistant (MDR). Vancomycin-resistant Enterococcus (VRE), in particular, are an ongoing global challenge given the lack of therapeutic options. In this scenario, bacteriocins can offer a potential solution to this persistent threat, either alone or in combination with other antimicrobials. There are a handful of studies that demonstrate the advantages and applications of bacteriocins, especially against VRE. The purpose of this review is to present a current standpoint about the dual role of Enterococcus spp., from important producers to targets needed to be controlled, and the crucial role that enterocins may have in the expansion of enterococcal populations. Classification and distribution of enterocins, the current knowledge about the bacteriocinome of clinical enterococci, and the challenges of bacteriocin use in the fight against VRE infections are particularly detailed. Full article

(This article belongs to the Special Issue Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides)

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20 pages, 696 KiB

Open AccessEditor’s ChoiceReview

Antibiotic Resistance: From Pig to Meat

by Xavier C. Monger, Alex-An Gilbert, Linda Saucier and Antony T. Vincent

Antibiotics 2021, 10(10), 1209; https://doi.org/10.3390/antibiotics10101209 - 05 Oct 2021

Cited by 45 | Viewed by 6640

Abstract

Pork meat is in high demand worldwide and this is expected to increase. Pork is often raised in intensive conditions, which is conducive to the spread of infectious diseases. Vaccines, antibiotics, and other biosafety measures help mitigate the impact of infectious diseases. However, [...] Read more.

Pork meat is in high demand worldwide and this is expected to increase. Pork is often raised in intensive conditions, which is conducive to the spread of infectious diseases. Vaccines, antibiotics, and other biosafety measures help mitigate the impact of infectious diseases. However, bacterial strains resistant to antibiotics are more and more frequently found in pig farms, animals, and the environment. It is now recognized that a holistic perspective is needed to sustainably fight antibiotic resistance, and that an integrated One Health approach is essential. With this in mind, this review tackles antibiotic resistance throughout the pork raising process, including their microbiome; many factors of their environment (agricultural workers, farms, rivers, etc.); and an overview of the impact of antibiotic resistance on pork meat, which is the end product available to consumers. Antibiotic resistance, while a natural process, is a public health concern. If we react, and act, collectively, it is expected to be, at least partially, reversible with judicious antibiotic usage and the development of innovative strategies and tools to foster animal health. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Terrestrial and Aquatic Farmed Animals: An Urgent One Health Issue for Sustainability)

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