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Revista Espanola de Quimioterapia :... May 2019The discovery of fosfomycin more than 40 years ago was an important milestone in antibiotic therapy. The antibiotic's usefulness, alone or in combination, for treating... (Review)
Review
The discovery of fosfomycin more than 40 years ago was an important milestone in antibiotic therapy. The antibiotic's usefulness, alone or in combination, for treating infections caused by multidrug-resistant microorganisms is clearer than ever. Both the European Medicines Agency and the US Food and Drug Administration have open processes for reviewing the accumulated information on the use of fosfomycin and the information from new clinical trials on this compound. The agencies' objectives are to establish common usage criteria for Europe and authorize the sale of fosfomycin in the US, respectively. Fosfomycin's single mechanism of action results in no cross-resistance with other antibiotics. However, various fosfomycin-resistance mechanisms have been described, the most important of which, from the epidemiological standpoint, is enzymatic inactivation, which is essentially associated with a gene carrying a fosA3-harboring plasmid. Fosfomycin has been found more frequently in Asia in extended-spectrum beta-lactamase-producing and carbapenemase-producing Enterobacterales. Although fosfomycin presents lower intrinsic activity against Pseudomonas aeruginosa compared with that presented against Escherichia coli, fosfomycin's activity has been demonstrated in biofilms, especially in combination with aminoglycosides. The current positioning of fosfomycin in the therapeutic arsenal for the treatment of infections caused by multidrug-resistant microorganisms requires new efforts to deepen our understanding of this compound, including those related to the laboratory methods employed in the antimicrobial susceptibility testing study.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Fosfomycin; Humans; Microbial Sensitivity Tests
PubMed: 31131587
DOI: No ID Found -
International Journal of Environmental... Sep 2022The problem of environmental pollution caused by the abuse of antibiotics has received increasing attention. However, only in recent years have antibiotic pollution and... (Review)
Review
The problem of environmental pollution caused by the abuse of antibiotics has received increasing attention. However, only in recent years have antibiotic pollution and its risk assessment to the environment been deeply studied. Although there has been a large number of reports about the input, occurrence, destination, and influence of antibiotics in the past 10 years, systemic knowledge of antibiotics in the groundwater environment is still lacking. This review systematically expounds the sources, migration and transformation, pollution status, and potential risks to the ecological environment of antibiotics in groundwater systems, by integrating 10 years of existing research results. The results showed that 47 kinds of antibiotics in four categories, mainly sulfonamides and fluoroquinolones, have been detected; antibiotics in groundwater species will induce the production of resistance genes and cause ecological harm. In view of the entire process of antibiotics entering groundwater, the current antibiotic control methods at various levels are listed, including the control of the discharge of antibiotics at source, the removal of antibiotics in water treatment plants, and the treatment of existing antibiotic contamination in groundwater. Additionally, the future research direction of antibiotics in groundwater is pointed out, and suggestions and prospects for antibiotic control are put forward.
Topics: Anti-Bacterial Agents; China; Environmental Monitoring; Environmental Pollution; Fluoroquinolones; Groundwater; Sulfonamides; Water Pollutants, Chemical
PubMed: 36141524
DOI: 10.3390/ijerph191811256 -
Microbiology (Reading, England) Sep 2023Antibiotic chemotherapy is widely regarded as one of the most significant medical advancements in history. However, the continued misuse of antibiotics has contributed... (Review)
Review
Antibiotic chemotherapy is widely regarded as one of the most significant medical advancements in history. However, the continued misuse of antibiotics has contributed to the rapid rise of antimicrobial resistance (AMR) globally. , a major human pathogen, has become synonymous with multidrug resistance and is a leading antimicrobial-resistant pathogen causing significant morbidity and mortality worldwide. This review focuses on (1) the targets of current anti-staphylococcal antibiotics and the specific mechanisms that confirm resistance; (2) an in-depth analysis of recently licensed antibiotics approved for the treatment of infections; and (3) an examination of the pre-clinical pipeline of anti-staphylococcal compounds. In addition, we examine the molecular mechanism of action of novel antimicrobials and derivatives of existing classes of antibiotics, collate data on the emergence of resistance to new compounds and provide an overview of key data from clinical trials evaluating anti-staphylococcal compounds. We present several successful cases in the development of alternative forms of existing antibiotics that have activity against multidrug-resistant . Pre-clinical antimicrobials show promise, but more focus and funding are required to develop novel classes of compounds that can curtail the spread of and sustainably control antimicrobial-resistant infections.
Topics: Humans; Anti-Bacterial Agents; Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Anti-Infective Agents; Staphylococcus; Microbial Sensitivity Tests
PubMed: 37656158
DOI: 10.1099/mic.0.001387 -
The Lancet. Infectious Diseases Mar 2022Standard doses of antibiotics do not efficiently treat chronic infections of the soft tissue and bone. In this Personal View, we advocate for improving treatment of... (Review)
Review
Standard doses of antibiotics do not efficiently treat chronic infections of the soft tissue and bone. In this Personal View, we advocate for improving treatment of these infections by taking the infectious microenvironment into account. The infectious microenvironment can cause sensitive bacteria to lose their susceptibility to antibiotics that are effective in standard laboratory susceptibility testing. We propose that bacteria behave substantially different in standard laboratory conditions than they do in actual infections. The infectious microenvironment could impose changes in growth and metabolic activity that result in increased protection against antibiotics. Therefore, we advocate that improved antibiotic treatment of chronic infection is achievable when antibiotics are recommended on the basis of susceptibility testing in relevant in vitro conditions that resemble actual infectious microenvironments. We recommend establishing knowledge of the relevant conditions of the chemical and physical composition of the infectious microenvironment. Recent advances in RNA sequencing, metabolomics, and microscopy have made it possible for the characterisation of the microenvironment of infections and to validate the clinical relevance of in vitro conditions to actual infections.
Topics: Anti-Bacterial Agents; Bacteria; Humans
PubMed: 34506737
DOI: 10.1016/S1473-3099(21)00122-5 -
Annual Review of Microbiology Sep 2018The ribosome is a major antibiotic target. Many types of inhibitors can stop cells from growing by binding at functional centers of the ribosome and interfering with its... (Review)
Review
The ribosome is a major antibiotic target. Many types of inhibitors can stop cells from growing by binding at functional centers of the ribosome and interfering with its ability to synthesize proteins. These antibiotics were usually viewed as general protein synthesis inhibitors, which indiscriminately stop translation at every codon of every mRNA, preventing the ribosome from making any protein. However, at each step of the translation cycle, the ribosome interacts with multiple ligands (mRNAs, tRNA substrates, translation factors, etc.), and as a result, the properties of the translation complex vary from codon to codon and from gene to gene. Therefore, rather than being indiscriminate inhibitors, many ribosomal antibiotics impact protein synthesis in a context-specific manner. This review presents a snapshot of the growing body of evidence that some, and possibly most, ribosome-targeting antibiotics manifest site specificity of action, which is modulated by the nature of the nascent protein, the mRNA, or the tRNAs.
Topics: Anti-Bacterial Agents; Protein Binding; Protein Biosynthesis; Protein Synthesis Inhibitors; RNA, Ribosomal; Ribosomal Proteins; Ribosomes
PubMed: 29906204
DOI: 10.1146/annurev-micro-090817-062329 -
Lab on a Chip Feb 2022The emergence and spread of multidrug resistant bacterial strains and concomitant dwindling of effective antibiotics pose worldwide healthcare challenges. To address...
The emergence and spread of multidrug resistant bacterial strains and concomitant dwindling of effective antibiotics pose worldwide healthcare challenges. To address these challenges, advanced engineering tools are developed to personalize antibiotic treatments by speeding up the diagnostics that is critical to prevent antibiotic misuse and overuse and make full use of existing antibiotics. Meanwhile, it is necessary to investigate novel antibiotic strategies. Recently, repurposing mono antibiotics into combinatorial antibiotic therapies has shown great potential for treatment of bacterial infections. However, widespread adoption of drug combinations has been hindered by the complexity of screening techniques and the cost of reagent consumptions in practice. In this study, we developed a combinatorial nanodroplet platform for automated and high-throughput screening of antibiotic combinations while consuming orders of magnitude lower reagents than the standard microtiter-based screening method. In particular, the proposed platform is capable of creating nanoliter droplets with multiple reagents in an automatic manner, tuning concentrations of each component, performing biochemical assays with high flexibility (, temperature and duration), and achieving detection with high sensitivity. A biochemical assay, based on the reduction of resazurin by the metabolism of bacteria, has been characterized and employed to evaluate the combinatorial effects of the antibiotics of interest. In a pilot study, we successfully screened pairwise combinations between 4 antibiotics for a model strain.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Escherichia coli; Microbial Sensitivity Tests; Pilot Projects
PubMed: 35015012
DOI: 10.1039/d1lc00865j -
Biosensors Jun 2018Antibiotic resistance and, accordingly, their pollution because of uncontrolled usage has emerged as a serious problem in recent years. Hence, there is an increased... (Review)
Review
Antibiotic resistance and, accordingly, their pollution because of uncontrolled usage has emerged as a serious problem in recent years. Hence, there is an increased demand to develop robust, easy, and sensitive methods for rapid evaluation of antibiotics and their residues. Among different analytical methods, the aptamer-based biosensors (aptasensors) have attracted considerable attention because of good selectivity, specificity, and sensitivity. This review gives an overview about recently-developed aptasensors for antibiotic detection. The use of various aptamer assays to determine different groups of antibiotics, like β-lactams, aminoglycosides, anthracyclines, chloramphenicol, (fluoro)quinolones, lincosamide, tetracyclines, and sulfonamides are presented in this paper.
Topics: Anti-Bacterial Agents; Aptamers, Peptide; Biosensing Techniques; Humans
PubMed: 29891818
DOI: 10.3390/bios8020054 -
Critical Care (London, England) May 2016Infections occur frequently in critically ill patients and their management can be challenging for various reasons, including delayed diagnosis, difficulties identifying... (Review)
Review
Infections occur frequently in critically ill patients and their management can be challenging for various reasons, including delayed diagnosis, difficulties identifying causative microorganisms, and the high prevalence of antibiotic-resistant strains. In this review, we briefly discuss the importance of early infection diagnosis, before considering in more detail some of the key issues related to antibiotic management in these patients, including controversies surrounding use of combination or monotherapy, duration of therapy, and de-escalation. Antibiotic pharmacodynamics and pharmacokinetics, notably volumes of distribution and clearance, can be altered by critical illness and can influence dosing regimens. Dosing decisions in different subgroups of patients, e.g., the obese, are also covered. We also briefly consider ventilator-associated pneumonia and the role of inhaled antibiotics. Finally, we mention antibiotics that are currently being developed and show promise for the future.
Topics: Anti-Bacterial Agents; Critical Illness; Humans
PubMed: 27184564
DOI: 10.1186/s13054-016-1285-6 -
Naunyn-Schmiedeberg's Archives of... Nov 2021The term "antibiotics" is a broadly used misnomer to designate antibacterial drugs. In a recent article, we have proposed to replace, e.g., the term "antibiotics" by... (Review)
Review
The term "antibiotics" is a broadly used misnomer to designate antibacterial drugs. In a recent article, we have proposed to replace, e.g., the term "antibiotics" by "antibacterial drugs", "antibiosis" by "antibacterial therapy", "antibiogram" by "antibacteriogram", and "antibiotic stewardship" by "antibacterial stewardship" (Seifert and Schirmer Trends Microbiol, 2021). In the present article, we show that many traditional terms related to antibiotics are used much more widely in the biomedical literature than the respective scientifically precise terms. This practice should be stopped. Moreover, we provide arguments to end the use of other broadly used terms in the biomedical literature such as "narrow-spectrum antibiotics" and "reserve antibiotics", "chemotherapeutics", and "tuberculostatics". Finally, we provide several examples showing that antibacterial drugs are used for non-antibacterial indications and that some non-antibacterial drugs are used for antibacterial indications now. Thus, the increasing importance of drug repurposing renders it important to drop short designations of drug classes such as "antibiotics". Rather, the term "drug" should be explicitly used, facilitating the inclusion of newly emerging indications such as antipsychotic and anti-inflammatory. This article is part of an effort to implement a new rational nomenclature of drug classes across the entire field of pharmacology.
Topics: Anti-Bacterial Agents; Antibiosis; Antimicrobial Stewardship; Drug Repositioning; Humans; Microbial Sensitivity Tests; Terminology as Topic
PubMed: 34536087
DOI: 10.1007/s00210-021-02144-9 -
Advanced Drug Delivery Reviews Nov 2014Many currently used antibiotics suffer from issues such as systemic toxicity, short half-life, and increased susceptibility to bacterial resistance. Although most... (Review)
Review
Many currently used antibiotics suffer from issues such as systemic toxicity, short half-life, and increased susceptibility to bacterial resistance. Although most antibiotic classes are administered systemically through oral or intravenous routes, a more efficient delivery system is needed. This review discusses the chemical conjugation of antibiotics to polymers, achieved by forming covalent bonds between antibiotics and a pre-existing polymer or by developing novel antibiotic-containing polymers. Through conjugating antibiotics to polymers, unique polymer properties can be taken advantage of. These polymeric antibiotics display controlled, sustained drug release and vary in antibiotic class type, synthetic method, polymer composition, bond lability, and antibacterial activity. The polymer synthesis, characterization, drug release, and antibacterial activities, if applicable, will be presented to offer a detailed overview of each system.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Delayed-Action Preparations; Drug Delivery Systems; Drug Design; Drug Liberation; Drug Resistance, Bacterial; Half-Life; Humans; Polymers
PubMed: 24751888
DOI: 10.1016/j.addr.2014.04.006