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The Cochrane Database of Systematic... Jun 2018Bronchiectasis is a chronic airway disease characterised by a destructive cycle of recurrent airway infection, inflammation and tissue damage. Antibiotics are a main... (Review)
Review
BACKGROUND
Bronchiectasis is a chronic airway disease characterised by a destructive cycle of recurrent airway infection, inflammation and tissue damage. Antibiotics are a main treatment for bronchiectasis. The aim of continuous therapy with prophylactic antibiotics is to suppress bacterial load, but bacteria may become resistant to the antibiotic, leading to a loss of effectiveness. On the other hand, intermittent prophylactic antibiotics, given over a predefined duration and interval, may reduce antibiotic selection pressure and reduce or prevent the development of resistance. This systematic review aimed to evaluate the current evidence for studies comparing continuous versus intermittent administration of antibiotic treatment in bronchiectasis in terms of clinical efficacy, the emergence of resistance and serious adverse events.
OBJECTIVES
To evaluate the effectiveness of continuous versus intermittent antibiotics in the treatment of adults and children with bronchiectasis, using the primary outcomes of exacerbations, antibiotic resistance and serious adverse events.
SEARCH METHODS
On 1 August 2017 and 4 May 2018 we searched the Cochrane Airways Review Group Specialised Register (CAGR), CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. On 25 September 2017 and 4 May 2018 we also searched www.clinicaltrials.gov, the World Health Organization (WHO) trials portal, conference proceedings and the reference lists of existing systematic reviews.
SELECTION CRITERIA
We planned to include randomised controlled trials (RCTs) of adults or children with bronchiectasis that compared continuous versus intermittent administration of long-term prophylactic antibiotics of at least three months' duration. We considered eligible studies reported as full-text articles, as abstracts only and unpublished data.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results and full-text reports.
MAIN RESULTS
We identified 268 unique records. Of these we retrieved and examined 126 full-text reports, representing 114 studies, but none of these studies met our inclusion criteria.
AUTHORS' CONCLUSIONS
No randomised controlled trials have compared the effectiveness and risks of continuous antibiotic therapy versus intermittent antibiotic therapy for bronchiectasis. High-quality clinical trials are needed to establish which of these interventions is more effective for reducing the frequency and duration of exacerbations, antibiotic resistance and the occurrence of serious adverse events.
Topics: Adult; Anti-Bacterial Agents; Bronchiectasis; Child; Humans
PubMed: 29860722
DOI: 10.1002/14651858.CD012733.pub2 -
Journal of Infection in Developing... Mar 2009Development of resistance to antimicrobial agents and increase of cost as the result of unnecessary and inappropriate use of antibiotics has become a global health...
BACKGROUND
Development of resistance to antimicrobial agents and increase of cost as the result of unnecessary and inappropriate use of antibiotics has become a global health problem. Therefore many strategies, which are aimed at optimizing antibiotic therapy, have been developed until now. In Turkey, an antibiotic restriction policy as a governmental solution was applied to decrease the antibiotic use and especially costs by Ministry of Health in 2003. The aim of this study is to evaluate the rational antibiotic use and the impact of the implementation of new restriction policy, with their reinforcement by infectious disease specialist, on the hospital wide use of antibiotics.
METHODOLOGY
The data of the inpatients received antibiotics (n=495) during January-June 2006 were compared with our previous study performed by the same methodology before the restriction policy in 1998. In both studies, prospective active daily surveillance of patients was performed by three infectious disease specialists. The appropriateness of antibiotic therapy was determined using the criteria described by Kunin and Jones. The data were analyzed by using SPSS for Windows.
RESULTS
While the rate of antibiotic use decreased from 16.6% to 11.3%, rational use increased after the restriction policy (p<0.001). Besides the specific antibiotic use increasing, prophylactic antibiotic use was found decreased (p<0.001). Mostly determined irrationality was the prophylactic uses in both studies. As expected, infectious disease specialist examinations resulted in an increase in the appropriate antibiotic use.
CONCLUSIONS
The restriction policy was effective in decreasing the antibiotic consumption and increasing the rational antibiotic prescription in our hospital.
Topics: Anti-Bacterial Agents; Communicable Diseases; Drug Prescriptions; Drug Resistance, Microbial; Female; Health Policy; Humans; Male; Middle Aged; Turkey
PubMed: 19755736
DOI: 10.3855/jidc.54 -
Journal of Biomedical Science Mar 2022Bacteriophages (phages) may be used as an alternative to antibiotic therapy for combating infections caused by multidrug-resistant bacteria. In the last decades, there... (Review)
Review
Bacteriophages (phages) may be used as an alternative to antibiotic therapy for combating infections caused by multidrug-resistant bacteria. In the last decades, there have been studies concerning the use of phages and antibiotics separately or in combination both in animal models as well as in humans. The phenomenon of phage-antibiotic synergy, in which antibiotics may induce the production of phages by bacterial hosts has been observed. The potential mechanisms of phage and antibiotic synergy was presented in this paper. Studies of a biofilm model showed that a combination of phages with antibiotics may increase removal of bacteria and sequential treatment, consisting of phage administration followed by an antibiotic, was most effective in eliminating biofilms. In vivo studies predominantly show the phenomenon of phage and antibiotic synergy. A few studies also describe antagonism or indifference between phages and antibiotics. Recent papers regarding the application of phages and antibiotics in patients with severe bacterial infections show the effectiveness of simultaneous treatment with both antimicrobials on the clinical outcome.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Bacteriophages; Biofilms; Drug Resistance, Multiple, Bacterial; Humans
PubMed: 35354477
DOI: 10.1186/s12929-022-00806-1 -
Biochemical Pharmacology Jun 2017Most pharmaceutical companies have stopped or have severely limited investments to discover and develop new antibiotics to treat the increasing prevalence of infections... (Review)
Review
Most pharmaceutical companies have stopped or have severely limited investments to discover and develop new antibiotics to treat the increasing prevalence of infections caused by multi-drug resistant bacteria, because the return on investment has been mostly negative for antibiotics that received marketing approved in the last few decades. In contrast, a few small companies have taken on this challenge and are developing new antibiotics. This review describes those antibiotics in late-stage clinical development. Most of them belong to existing antibiotic classes and a few with a narrow spectrum of activity are novel compounds directed against novel targets. The reasons for some of the past failures to find new molecules and a path forward to help attract investments to fund discovery of new antibiotics are described.
Topics: Animals; Anti-Bacterial Agents; Drug Discovery; Drug Industry; Humans
PubMed: 27687641
DOI: 10.1016/j.bcp.2016.09.025 -
Chemical Communications (Cambridge,... May 2023Antibiotic resistance is an enormous problem that is accountable for over a million deaths annually, with numbers expected to significantly increase over the coming... (Review)
Review
Antibiotic resistance is an enormous problem that is accountable for over a million deaths annually, with numbers expected to significantly increase over the coming decades. Although some of the underlying causes leading up to antibiotic resistance are well understood, many of the molecular processes involved remain elusive. To better appreciate at a molecular level how resistance emerges, customized chemical biology tools can offer a solution. This Feature Article attempts to provide an overview of the wide variety of tools that have been developed over the last decade, by highlighting some of the more illustrative examples. These include the use of fluorescent, photoaffinity and activatable antibiotics and bacterial components to start to unravel the molecular mechanisms involved in resistance. The antibiotic crisis is an eminent global threat and requires the continuous development of creative chemical tools to dissect and ultimately counteract resistance.
Topics: Drug Resistance, Microbial; Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial
PubMed: 37039397
DOI: 10.1039/d3cc00759f -
Current Opinion in Pediatrics Apr 2016Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and... (Review)
Review
PURPOSE OF REVIEW
Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and variation in antibiotic utilization, discusses the emergence of resistant organisms, and presents data from human neonates and animal models demonstrating the impact of antibiotics on the microbiome, and how microbiome alterations impact health. The importance of antibiotic stewardship is also discussed.
RECENT FINDINGS
Infections increase neonatal morbidity and mortality. Furthermore, the clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic-induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs.
SUMMARY
The review encourages practitioners to assess local antibiotic use with regard to local microbiology, and to adopt steps to reduce infections and use antibiotics wisely.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Drug Utilization; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Microbiota; Practice Patterns, Physicians'
PubMed: 26886785
DOI: 10.1097/MOP.0000000000000338 -
ACS Infectious Diseases Mar 2022The paradigm of antivirulence therapy dictates that bacterial pathogens are specifically disarmed but not killed by neutralizing their virulence factors. Clearance of... (Review)
Review
The paradigm of antivirulence therapy dictates that bacterial pathogens are specifically disarmed but not killed by neutralizing their virulence factors. Clearance of the invading pathogen by the immune system is promoted. As compared to antibiotics, the pathogen-selective antivirulence drugs hold promise to minimize collateral damage to the beneficial microbiome. Also, selective pressure for resistance is expected to be lower because bacterial viability is not directly affected. Antivirulence drugs are being developed for stand-alone prophylactic and therapeutic treatments but also for combinatorial use with antibiotics. This Review focuses on drug modalities that target bacterial exotoxins after the secretion or release-upon-lysis. Exotoxins have a significant and sometimes the primary role as the disease-causing virulence factor, and thereby they are attractive targets for drug development. We describe the key pre-clinical and clinical trial data that have led to the approval of currently used exotoxin-targeted drugs, namely the monoclonal antibodies bezlotoxumab (toxin B/TcdB, ), raxibacumab (anthrax toxin, ), and obiltoxaximab (anthrax toxin, ), but also to challenges with some of the promising leads. We also highlight the recent developments in pre-clinical research sector to develop exotoxin-targeted drug modalities, i.e., monoclonal antibodies, antibody fragments, antibody mimetics, receptor analogs, neutralizing scaffolds, dominant-negative mutants, and small molecules. We describe how these exotoxin-targeted drug modalities work with high-resolution structural knowledge and highlight their advantages and disadvantages as antibiotic alternatives.
Topics: Anti-Bacterial Agents; Bacillus anthracis; Bacterial Toxins; Clostridioides difficile; Exotoxins
PubMed: 35099182
DOI: 10.1021/acsinfecdis.1c00296 -
International Journal of Molecular... Sep 2022As a result of antibiotic overuse, bacterial antibiotic resistance has become a severe threat to worldwide public health. The development of more effective antimicrobial... (Review)
Review
As a result of antibiotic overuse, bacterial antibiotic resistance has become a severe threat to worldwide public health. The development of more effective antimicrobial therapies and alternative antibiotic strategies is urgently required. The role played by bacterial membrane vesicles (BMVs) in antibiotic resistance has become a current focus of research. BMVs are nanoparticles derived from the membrane components of Gram-negative and Gram-positive bacteria and contain diverse components originating from the cell envelope and cytoplasm. Antibiotic stress stimulates the secretion of BMVs. BMVs promote and mediate antibiotic resistance by multiple mechanisms. BMVs have been investigated as conceptually new antibiotics and drug-delivery vehicles. In this article, we outline the research related to BMVs and antibiotic resistance as a reference for the intentional use of BMVs to combat antibiotic resistance.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Cell Membrane; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial
PubMed: 36232856
DOI: 10.3390/ijms231911553 -
ACS Infectious Diseases Nov 2023The need for new antibiotics is urgent. Antimicrobial resistance is rising, although currently, many more people die from drug-sensitive bacterial infections. The... (Review)
Review
The need for new antibiotics is urgent. Antimicrobial resistance is rising, although currently, many more people die from drug-sensitive bacterial infections. The continued evolution of drug resistance is inevitable, fueled by pathogen population size and exposure to antibiotics. Additionally, opportunistic pathogens will always pose a threat to vulnerable patients whose immune systems cannot efficiently fight them even if they are sensitive to available antibiotics, according to clinical microbiology tests. These problems are intertwined and will worsen as human populations age, increase in density, and experience disruptions such as war, extreme weather events, or declines in standard of living. The development of appropriate drugs to treat all the world's bacterial infections should be a priority, and future success will likely require combinations of multiple approaches. However, the highest burden of bacterial infection is in Low- and Middle-Income Countries, where limited medical infrastructure is a major challenge. For effectively managing infections in these contexts, small-molecule-based treatments offer significant advantages. Unfortunately, support for ongoing small-molecule antibiotic discovery has recently suffered from significant challenges related both to the scientific difficulties in treating bacterial infections and to market barriers. Nevertheless, small-molecule antibiotics remain essential and irreplaceable tools for fighting infections, and efforts to develop novel and improved versions deserve ongoing investment. Here, we first describe the global historical context of antibiotic treatment and then highlight some of the challenges surrounding small-molecule development and potential solutions. Many of these challenges are likely to be common to all modalities of antibacterial treatment and should be addressed directly.
Topics: Humans; Anti-Bacterial Agents; Bacterial Infections
PubMed: 37819866
DOI: 10.1021/acsinfecdis.3c00189 -
International Journal of Molecular... Oct 2023Bacterial antibiotic resistance, especially the emergence of multidrug-resistant (MDR) strains, urgently requires the development of effective treatment strategies. It... (Review)
Review
Bacterial antibiotic resistance, especially the emergence of multidrug-resistant (MDR) strains, urgently requires the development of effective treatment strategies. It is always of interest to delve into the mechanisms of resistance to current antibiotics and target them to promote the efficacy of existing antibiotics. In recent years, non-antibiotic compounds have played an important auxiliary role in improving the efficacy of antibiotics and promoting the treatment of drug-resistant bacteria. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against MDR bacteria. In this review, we first briefly summarize the main resistance mechanisms of current antibiotics. In addition, we propose several strategies to enhance antibiotic action based on resistance mechanisms. Then, the research progress of non-antibiotic compounds that can promote antibiotic-resistant bacteria through different mechanisms in recent years is also summarized. Finally, the development prospects and challenges of these non-antibiotic compounds in combination with antibiotics are discussed.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Bacteria; Drug Resistance, Bacterial; Microbial Sensitivity Tests
PubMed: 37895172
DOI: 10.3390/ijms242015493