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ELife Mar 2023The global spread of antibiotic resistance could be due to a number of factors, and not just the overuse of antibiotics in agriculture and medicine as previously thought.
The global spread of antibiotic resistance could be due to a number of factors, and not just the overuse of antibiotics in agriculture and medicine as previously thought.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Agriculture
PubMed: 36884273
DOI: 10.7554/eLife.86697 -
JAMA Internal Medicine May 2020The requirement of prolonged intravenous antibiotic courses to treat infective endocarditis (IE) is a time-honored dogma of medicine. However, numerous antibiotics are... (Review)
Review
IMPORTANCE
The requirement of prolonged intravenous antibiotic courses to treat infective endocarditis (IE) is a time-honored dogma of medicine. However, numerous antibiotics are now available that achieve adequate levels in the blood after oral administration to kill bacteria. Moreover, prolonged intravenous antibiotic regimens are associated with high rates of adverse events. Accordingly, recent studies of oral step-down antibiotic treatment have stimulated a reevaluation of the need for intravenous-only therapy for IE.
OBSERVATIONS
PubMed was reviewed in October 2019, with an update in February 2020, to determine whether evidence supports the notion that oral step-down antibiotic therapy for IE is associated with inferior outcomes compared with intravenous-only therapy. The search identified 21 observational studies evaluating the effectiveness of oral antibiotics for treating IE, typically after an initial course of intravenous therapy; none found such oral step-down therapy to be inferior to intravenous-only therapy. Multiple studies described an improved clinical cure rate and an improved mortality rate among patients treated with oral step-down vs intravenous-only antibiotic therapy. Three randomized clinical trials also demonstrated that oral step-down antibiotic therapy is at least as effective as intravenous-only therapy in right-sided, left-sided, or prosthetic valve IE. In the largest trial, at 3.5 years of follow-up, patients randomized to receive oral step-down antibiotic therapy had a significantly improved cure rate and mortality rate compared with those who received intravenous-only therapy.
CONCLUSIONS AND RELEVANCE
This review found ample data demonstrating the therapeutic effectiveness of oral step-down vs intravenous-only antibiotic therapy for IE, and no contrary data were identified. The use of highly orally bioavailable antibiotics as step-down therapy for IE, after clearing bacteremia and achieving clinical stability with intravenous regimens, should be incorporated into clinical practice.
Topics: Administration, Intravenous; Administration, Oral; Anti-Bacterial Agents; Drug Administration Schedule; Endocarditis; Humans; Practice Patterns, Physicians'
PubMed: 32227127
DOI: 10.1001/jamainternmed.2020.0555 -
International Journal of Molecular... Aug 2020Although the introduction of antibiotics in medicine has resulted in one of the most successful events and in a major breakthrough to reduce morbidity and mortality... (Review)
Review
Although the introduction of antibiotics in medicine has resulted in one of the most successful events and in a major breakthrough to reduce morbidity and mortality caused by infectious disease, response to these agents is not always predictable, leading to differences in their efficacy, and sometimes to the occurrence of adverse effects. Genetic variability, resulting in differences in the pharmacokinetics and pharmacodynamics of antibiotics, is often involved in the variable response, of particular importance are polymorphisms in genes encoding for drug metabolizing enzymes and membrane transporters. In addition, variations in the human leukocyte antigen (HLA) class I and class II genes have been associated with different immune mediated reactions induced by antibiotics. In recent years, the importance of pharmacogenetics in the personalization of therapies has been recognized in various clinical fields, although not clearly in the context of antibiotic therapy. In this review, we make an overview of antibiotic pharmacogenomics and of its potential role in optimizing drug therapy and reducing adverse reactions.
Topics: Anti-Bacterial Agents; Bacterial Infections; Genome-Wide Association Study; HLA Antigens; Humans; Pharmacogenomic Variants; Precision Medicine
PubMed: 32825180
DOI: 10.3390/ijms21175975 -
Archives of Gynecology and Obstetrics Oct 2019Urinary tract infections (UTIs) are one of the more common infections encountered in everyday clinical practice. They account for 10-20% of all infections treated in...
PURPOSE
Urinary tract infections (UTIs) are one of the more common infections encountered in everyday clinical practice. They account for 10-20% of all infections treated in primary care units and 30-40% of those treated in hospitals. The risk of UTI in the female population is considered to be 14 times higher than in the male population. The prevalence of bacterial etiology results in a large consumption of broad-spectrum antibiotics, which in turn leads to increased rates of resistant uropathogens. Therefore, non-antibiotic prevention and treatment options are now of great importance.
METHODS
A systematic literature search was performed for the last 20 years (1999-2019) and the efficiencies of these eight different non-antibiotic interventions were analysed and discussed.
RESULTS
This article provides an overview on non-antibiotic options for management of UTI, including the application of cranberry products, the phytodrug Canephron N, probiotics, nonsteroidal anti-inflammatory drugs (NSAID), D-mannose, estrogens, vitamins, and immunotherapy.
CONCLUSIONS
The last 20 years of research on non-antibiotic approaches in UTI have not brought conclusive evidence that antibiotic usage can be replaced completely by non-antibiotic options. Hence, antibiotics still remain a gold standard for UTI treatment and prevention. However, changing the therapeutic strategy by including non-antibiotic measures in the management of UTI could be successful in avoiding antimicrobial resistance at least to some extent.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Female; Humans; Male; Urinary Tract Infections
PubMed: 31350663
DOI: 10.1007/s00404-019-05256-z -
Sheng Wu Gong Cheng Xue Bao = Chinese... Aug 2022(Ashby) Downson is a quarantine pest for importing plants to China that causes leaf scald bacterial disease on sugarcane. . produces a potent phytotoxin/antibiotic... (Review)
Review
(Ashby) Downson is a quarantine pest for importing plants to China that causes leaf scald bacterial disease on sugarcane. . produces a potent phytotoxin/antibiotic called albicidin. As a pathogenic factor, albicidin causes typical white leaf stripes by inhibiting plastid DNA gyrase and disturbing chloroplast differentiation. Meanwhile, the antibacterial activity of albicidin gives . a competitive advantage against rival bacteria during their colonization. Furthermore, albicidin has a rapid bactericidal activity against a variety of Gram-positive and Gram-negative pathogenic bacteria of human species at nanomolar concentrations, making it a potential antimicrobial drug for clinical application. This article reviews the advances of albicidin from the aspects of its molecular structure, traditional extraction methods, mechanism of action, biosynthetic genes and processes, chemical synthesis method and improvement, in order to provide insights into the prevention and treatment of the sugarcane leaf scald disease, and the development of new antibiotics.
Topics: Anti-Bacterial Agents; China; Humans; Organic Chemicals; Xanthomonas
PubMed: 36002407
DOI: 10.13345/j.cjb.210832 -
Current Opinion in Microbiology Aug 2023Antimicrobial susceptibility testing is the cornerstone of antibiotic treatments. Yet, active drugs are frequently unsuccessful in vivo and most clinical trials... (Review)
Review
Antimicrobial susceptibility testing is the cornerstone of antibiotic treatments. Yet, active drugs are frequently unsuccessful in vivo and most clinical trials investigating antibiotics fail. So far, bacterial survival strategies, other than drug resistance, have been largely ignored. As such, drug tolerance and persisters, allowing bacterial populations to survive during antibiotic treatments, could fill a gap in antibiotic susceptibility testing. Therefore, it remains critical to establish robust and scalable bacterial viability measures and to define the clinical relevance of bacterial survivors across various bacterial infections. If successful, these tools could improve drug design and development to prevent tolerance formation or target bacterial survivors, to ultimately reduce treatment failures and curb resistance evolution.
Topics: Humans; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Drug Tolerance
PubMed: 37245488
DOI: 10.1016/j.mib.2023.102328 -
Frontiers in Cellular and Infection... 2022Antibiotic persisters are a sub-population of bacteria able to survive in the presence of bactericidal antibiotic despite the lack of heritable drug resistance... (Review)
Review
Antibiotic persisters are a sub-population of bacteria able to survive in the presence of bactericidal antibiotic despite the lack of heritable drug resistance mechanisms. This phenomenon exists across many bacterial species and is observed for many different antibiotics. Though these bacteria are often described as "multidrug persisters" very few experiments have been carried out to determine the homogeneity of a persister population to different drugs. Further, there is much debate in the field as to the origins of a persister cell. Is it formed spontaneously? Does it form in response to stress? These questions are particularly pressing in the field of , where persisters may play a crucial role in the required length of treatment and the development of multidrug resistant organisms. Here we aim to interpret the known mechanisms of antibiotic persistence and how they may relate to improving treatments for , exposing the gaps in knowledge that prevent us from answering the question: Are all antibiotic persisters created equal?
Topics: Anti-Bacterial Agents; Mycobacterium tuberculosis
PubMed: 36061872
DOI: 10.3389/fcimb.2022.933458 -
Expert Opinion on Emerging Drugs Dec 2019: Community-acquired pneumonia is the most common infection leading to hospitalization and death in all age groups, especially in elderly populations. Increasing... (Review)
Review
: Community-acquired pneumonia is the most common infection leading to hospitalization and death in all age groups, especially in elderly populations. Increasing antibiotic resistance among the common bacterial pathogens associated with community-acquired pneumonia, especially Streptococcus pneumoniae and staphylococci, has made its empirical treatment increasingly problematic, highlighting the need for effective antibiotic therapy.: We searched PubMed and ClinicalTrials.gov for English-language reports of phase III clinical trials conducted between 2000 and 2019 concerning the antibiotic treatment of community-acquired pneumonia. We provide a summary of the latest approved drugs for this indication and highlight emerging drugs with a potential indication.: Ceftaroline (a new cephalosporine) and omadacycline (a cycline alternative), either parenterally or orally, are the only two new antibiotics to have been approved by the FDA for the treatment of community-acquired pneumonia in the last five years. Among the antimicrobials in development, Lefamulin (the first pleuromutilin), is currently in phase III development. Among the known antibiotic classes, solithromycin (a macrolide), nemonoxacin (a quinolone), and delafloxacin and zabofloxacin (both fluoroquinolones), have been studied in phase II and III in clinical trials. The availability of these new antibiotics may offer opportunities to improve the empirical treatment for community-acquired pneumonia.
Topics: Animals; Anti-Bacterial Agents; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Community-Acquired Infections; Humans; Pneumonia, Bacterial
PubMed: 31657962
DOI: 10.1080/14728214.2019.1685494 -
EcoSal Plus Mar 2021As the spread of antibiotic resistance threatens our ability to treat infections, avoiding the return of a preantibiotic era requires the discovery of new drugs. While... (Review)
Review
As the spread of antibiotic resistance threatens our ability to treat infections, avoiding the return of a preantibiotic era requires the discovery of new drugs. While therapeutic use of antibiotics followed by the inevitable selection of resistance is a modern phenomenon, these molecules and the genetic determinants of resistance were in use by environmental microbes long before humans discovered them. In this review, we discuss evidence that antibiotics and resistance were present in the environment before anthropogenic use, describing techniques including direct sampling of ancient DNA and phylogenetic analyses that are used to reconstruct the past. We also pay special attention to the ecological and evolutionary forces that have shaped the natural history of antibiotic biosynthesis, including a discussion of competitive versus signaling roles for antibiotics, proto-resistance, and substrate promiscuity of biosynthetic and resistance enzymes. Finally, by applying an evolutionary lens, we describe concepts governing the origins and evolution of biosynthetic gene clusters and cluster-associated resistance determinants. These insights into microbes' use of antibiotics in nature, a game they have been playing for millennia, can provide inspiration for discovery technologies and management strategies to combat the growing resistance crisis.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Humans; Multigene Family; Phylogeny
PubMed: 33734062
DOI: 10.1128/ecosalplus.ESP-0027-2020 -
Biological Chemistry Mar 2022The occurrence of drug-resistant bacteria is drastically rising and new and effective antibiotic classes are urgently needed. However, most of the compounds in... (Review)
Review
The occurrence of drug-resistant bacteria is drastically rising and new and effective antibiotic classes are urgently needed. However, most of the compounds in development are minor modifications of previously used drugs to which bacteria can easily develop resistance. The investigation of inorganic and organometallic compounds as antibiotics is an alternative approach that holds great promises due to the ability of such molecules to trigger metal-specific mechanisms of action, which results in lethal consequences for pathogens. In this review, a selection of concepts to rationally design inorganic and organometallic antibiotics is discussed, highlighting their advantages by comparing them to classical drug discovery programmes. The review concludes with a short perspective for the future of antibiotic drug development and the role metal-based compounds will play in the field.
Topics: Anti-Bacterial Agents; Bacteria; Drug Discovery
PubMed: 34253000
DOI: 10.1515/hsz-2021-0253