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Wiley Interdisciplinary Reviews.... 2014Despite the wide success of antibiotics, the treatment of bacterial infections still faces significant challenges, particularly the emergence of antibiotic resistance.... (Review)
Review
Despite the wide success of antibiotics, the treatment of bacterial infections still faces significant challenges, particularly the emergence of antibiotic resistance. As a result, nanoparticle drug delivery platforms including liposomes, polymeric nanoparticles, dendrimers, and various inorganic nanoparticles have been increasingly exploited to enhance the therapeutic effectiveness of existing antibiotics. This review focuses on areas where nanoparticle approaches hold significant potential to advance the treatment of bacterial infections. These areas include targeted antibiotic delivery, environmentally responsive antibiotic delivery, combinatorial antibiotic delivery, nanoparticle-enabled antibacterial vaccination, and nanoparticle-based bacterial detection. In each area we highlight the innovative antimicrobial nanoparticle platforms and review their progress made against bacterial infections.
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Delivery Systems; Humans; Nanomedicine; Nanoparticles
PubMed: 25044325
DOI: 10.1002/wnan.1282 -
Annals of the New York Academy of... Jul 2021Antibiotic resistance is a worldwide and growing clinical problem. With limited drug development in the antibacterial space, combination therapy has emerged as a... (Review)
Review
Antibiotic resistance is a worldwide and growing clinical problem. With limited drug development in the antibacterial space, combination therapy has emerged as a promising strategy to combat multidrug-resistant bacteria. Antibacterial combinations can improve antibiotic efficacy and suppress antibacterial resistance through independent, synergistic, or even antagonistic activities. Combination therapies are famously used to treat viral and mycobacterial infections and cancer. However, antibacterial combinations are only now emerging as a common treatment strategy for other bacterial infections owing to challenges in their discovery, development, regulatory approval, and commercial/clinical deployment. Here, we focus on discovery-where the sheer scale of combinatorial chemical spaces represents a significant challenge-and discuss how combination therapy can impact the treatment of bacterial infections. Despite these challenges, recent advancements, including new in silico methods, theoretical frameworks, and microfluidic platforms, are poised to identify the new and efficacious antibacterial combinations needed to revitalize the antibacterial drug pipeline.
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Combinations; Drug Resistance, Bacterial; Microbial Sensitivity Tests
PubMed: 34212403
DOI: 10.1111/nyas.14649 -
Microbiology (Reading, England) Dec 2022Bacteria withstand antibiotic onslaughts by employing a variety of strategies, one of which is persistence. Persistence occurs in a bacterial population where a... (Review)
Review
Bacteria withstand antibiotic onslaughts by employing a variety of strategies, one of which is persistence. Persistence occurs in a bacterial population where a subpopulation of cells (persisters) survives antibiotic treatment and can regrow in a drug-free environment. Persisters may cause the recalcitrance of infectious diseases and can be a stepping stone to antibiotic resistance, so understanding persistence mechanisms is critical for therapeutic applications. However, current understanding of persistence is pervaded by paradoxes that stymie research progress, and many aspects of this cellular state remain elusive. In this review, we summarize the putative persister mechanisms, including toxin-antitoxin modules, quorum sensing, indole signalling and epigenetics, as well as the reasons behind the inconsistent body of evidence. We highlight present limitations in the field and underscore a clinical context that is frequently neglected, in the hope of supporting future researchers in examining clinically important persister mechanisms.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Multiple, Bacterial; Quorum Sensing; Antitoxins; Drug Resistance, Bacterial
PubMed: 36748698
DOI: 10.1099/mic.0.001266 -
International Journal of Antimicrobial... Sep 2022Pharmacokinetic/pharmacodynamic (PKPD) models have emerged as valuable tools for the characterization and translation of antibiotic effects, and consequently for drug... (Review)
Review
Pharmacokinetic/pharmacodynamic (PKPD) models have emerged as valuable tools for the characterization and translation of antibiotic effects, and consequently for drug development and therapy. In contrast to traditional PKPD concepts for antibiotics such as minimum inhibitory concentration and PKPD indices, PKPD models enable description of the continuous, often species- or population-dependent time course of antimicrobial effects, commonly considering mechanistic pathogen- and drug-related knowledge. This review presents a comprehensive overview of previously published PKPD models describing repeated measurements of antibiotic effects. A literature review was conducted to identify PKPD models based on: (i) antibiotic compounds; (ii) Gram-positive or Gram-negative pathogens; and (iii) in-vitro or in-vivo longitudinal colony-forming unit data. In total, 132 publications were identified that were released between 1963 and 2021, including models based on exposure to single antibiotics (n=92) and drug combinations (n=40), as well as different experimental settings (e.g. static/traditional dynamic/hollow-fibre/animal time-kill models, n=90/27/32/11). An interactive, fully searchable table summarizes the details of each model, namely variants and mechanistic elements of PKPD submodels capturing observed bacterial growth, regrowth, drug effects and interactions. Furthermore, the review highlights the main purposes of PKPD model development, including the translation of preclinical PKPD to clinical settings, and the assessment of varied dosing regimens and patient characteristics for their impact on clinical antibiotic effects. In summary, this comprehensive overview of PKPD models will assist in identifying PKPD modelling strategies to describe growth, killing, regrowth and interaction patterns for pathogen-antibiotic combinations over time, and ultimately facilitate model-informed antibiotic translation, dosing and drug development.
Topics: Animals; Anti-Bacterial Agents; Drug Combinations; Microbial Sensitivity Tests; Models, Biological
PubMed: 35691605
DOI: 10.1016/j.ijantimicag.2022.106616 -
The ISME Journal Apr 2021Accumulating evidence suggests that the response of bacteria to antibiotics is significantly affected by the presence of other interacting microbes. These interactions... (Review)
Review
Accumulating evidence suggests that the response of bacteria to antibiotics is significantly affected by the presence of other interacting microbes. These interactions are not typically accounted for when determining pathogen sensitivity to antibiotics. In this perspective, we argue that resistance and evolutionary responses to antibiotic treatments should not be considered only a trait of an individual bacteria species but also an emergent property of the microbial community in which pathogens are embedded. We outline how interspecies interactions can affect the responses of individual species and communities to antibiotic treatment, and how these responses could affect the strength of selection, potentially changing the trajectory of resistance evolution. Finally, we identify key areas of future research which will allow for a more complete understanding of antibiotic resistance in bacterial communities. We emphasise that acknowledging the ecological context, i.e. the interactions that occur between pathogens and within communities, could help the development of more efficient and effective antibiotic treatments.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Ecology; Microbiota
PubMed: 33219299
DOI: 10.1038/s41396-020-00832-7 -
Annals of Clinical Microbiology and... Feb 2018Infection in surgical incision often results in poor wound healing, and one of the main factors for wound infection is the use of antimicrobial agents. Rational use of... (Review)
Review
Infection in surgical incision often results in poor wound healing, and one of the main factors for wound infection is the use of antimicrobial agents. Rational use of antibiotics is one of the key factors to prevent incision infection in general surgery. The number of current clinical studies on antibiotic use before and during surgery is greater than that of systematic studies on antibiotic use after surgery. For the rational use of antibiotics and improvement of wound healing rate, researchers around the world have gradually focused on the use of antibiotics after surgery. Despite the familiarity on the concept of "rational use of antibiotics", few clear and systematic studies were conducted to elucidate the effect of different antibiotics on wound healing. Therefore, this review focuses on the use of different types of antimicrobial agents in surgical wounds.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Humans; Surgical Wound; Surgical Wound Infection; Wound Healing
PubMed: 29397046
DOI: 10.1186/s12941-018-0254-0 -
Molecules (Basel, Switzerland) May 2023Antibiotics are administered to livestock at subtherapeutic levels to promote growth, and their degradation in manure is slow. High antibiotic concentrations can inhibit... (Review)
Review
Antibiotics are administered to livestock at subtherapeutic levels to promote growth, and their degradation in manure is slow. High antibiotic concentrations can inhibit bacterial activity. Livestock excretes antibiotics via feces and urine, leading to their accumulation in manure. This can result in the propagation of antibiotic-resistant bacteria and antibiotic resistance genes (ARGs). Anaerobic digestion (AD) manure treatment technologies are gaining popularity due to their ability to mitigate organic matter pollution and pathogens, and produce methane-rich biogas as renewable energy. AD is influenced by multiple factors, including temperature, pH, total solids (TS), substrate type, organic loading rate (OLR), hydraulic retention time (HRT), intermediate substrates, and pre-treatments. Temperature plays a critical role, and thermophilic AD has been found to be more effective in reducing ARGs in manure compared to mesophilic AD, as evidenced by numerous studies. This review paper investigates the fundamental principles of process parameters affecting the degradation of ARGs in anaerobic digestion. The management of waste to mitigate antibiotic resistance in microorganisms presents a significant challenge, highlighting the need for effective waste management technologies. As the prevalence of antibiotic resistance continues to rise, urgent implementation of effective treatment strategies is necessary.
Topics: Animals; Manure; Livestock; Anaerobiosis; Anti-Bacterial Agents; Bacteria; Genes, Bacterial
PubMed: 37241831
DOI: 10.3390/molecules28104090 -
Microbiology (Reading, England) Feb 2022The polymyxin and lipopeptide classes of antibiotics are membrane-targeting drugs of last resort used to treat infections caused by multi-drug-resistant pathogens.... (Review)
Review
The polymyxin and lipopeptide classes of antibiotics are membrane-targeting drugs of last resort used to treat infections caused by multi-drug-resistant pathogens. Despite similar structures, these two antibiotic classes have distinct modes of action and clinical uses. The polymyxins target lipopolysaccharide in the membranes of most Gram-negative species and are often used to treat infections caused by carbapenem-resistant species such as , and . By contrast, the lipopeptide daptomycin requires membrane phosphatidylglycerol for activity and is only used to treat infections caused by drug-resistant Gram-positive bacteria such as methicillin-resistant and vancomycin-resistant enterococci. However, despite having distinct targets, both antibiotic classes cause membrane disruption, are potently bactericidal and share similarities in resistance mechanisms. Furthermore, there are concerns about the efficacy of these antibiotics, and there is increasing interest in using both polymyxins and daptomycin in combination therapies to improve patient outcomes. In this review article, we will explore what is known about these distinct but structurally similar classes of antibiotics, discuss recent advances in the field and highlight remaining gaps in our knowledge.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Lipopeptides; Methicillin-Resistant Staphylococcus aureus; Polymyxins
PubMed: 35118938
DOI: 10.1099/mic.0.001136 -
Clinical Microbiology Reviews Apr 2018The global incidence of drug-resistant Gram-negative bacillary infections has been increasing, and there is a dire need to develop novel strategies to overcome this... (Review)
Review
The global incidence of drug-resistant Gram-negative bacillary infections has been increasing, and there is a dire need to develop novel strategies to overcome this problem. Intrinsic resistance in Gram-negative bacteria, such as their protective outer membrane and constitutively overexpressed efflux pumps, is a major survival weapon that renders them refractory to current antibiotics. Several potential avenues to overcome this problem have been at the heart of antibiotic drug discovery in the past few decades. We review some of these strategies, with emphasis on antibiotic hybrids either as stand-alone antibacterial agents or as adjuvants that potentiate a primary antibiotic in Gram-negative bacteria. Antibiotic hybrid is defined in this review as a synthetic construct of two or more pharmacophores belonging to an established agent known to elicit a desired antimicrobial effect. The concepts, advances, and challenges of antibiotic hybrids are elaborated in this article. Moreover, we discuss several antibiotic hybrids that were or are in clinical evaluation. Mechanistic insights into how tobramycin-based antibiotic hybrids are able to potentiate legacy antibiotics in multidrug-resistant Gram-negative bacilli are also highlighted. Antibiotic hybrids indeed have a promising future as a therapeutic strategy to overcome drug resistance in Gram-negative pathogens and/or expand the usefulness of our current antibiotic arsenal.
Topics: Anti-Bacterial Agents; Drug Development; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections
PubMed: 29540434
DOI: 10.1128/CMR.00077-17 -
Cell Host & Microbe May 2022Intestinal host-microbiota interactions during the first year of life are critical for infant development. Early-life antibiotic exposures disrupt stereotypical gut... (Review)
Review
Intestinal host-microbiota interactions during the first year of life are critical for infant development. Early-life antibiotic exposures disrupt stereotypical gut microbiota maturation and adversely affect childhood health. Furthermore, antibiotics increase the abundance of resistant bacteria and enrich the resistome-the compendium of antibiotic resistance genes-within the gut microbiota. Here, we discuss acute and persistent impacts of antibiotic exposure during infancy on pediatric health, the gut microbiome, and, particularly, the resistome. Reviewing our current understanding of antibiotic resistance acquisition and dissemination within and between microbiomes, we highlight open questions, which are imperative to resolve in the face of rising bacterial resistance.
Topics: Anti-Bacterial Agents; Bacteria; Child; Drug Resistance, Microbial; Gastrointestinal Microbiome; Humans; Infant; Microbiota
PubMed: 35550670
DOI: 10.1016/j.chom.2022.03.013