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Herbert A. Kirst - One of the best experts on this subject based on the ideXlab platform.
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Introduction to the Macrolide antibiotics
Macrolide Antibiotics, 2002Co-Authors: Herbert A. KirstAbstract:Macrolide antibiotics are an old and well-established class of antimicrobial agents that have long played a significant role in the chemotherapy of infectious diseases[1-3]. Among the most important characteristics of the Macrolide class are a moderately broad spectrum of antimicrobial activity, an orally effective route of administration, and a relatively high margin of safety (high therapeutic index). Although Macrolides have been the primary antibiotic of choice for a few indications, they have also played a very critical role as an alternative drug of choice, particularly as an alternative to the penicillins. Over the past two decades, the Macrolide class has undergone a remarkable resurgence that has been characterized by 1) the discovery and commercial development of several important new semi-synthetic derivatives exhibiting a variety of improved features and 2) clinical efficacy in the treatment of several infectious diseases not originally associated with Macrolide therapy. The subsequent chapters of this book will 1) document the clinical progress that has been made thus far in utilizing the more recent semi-synthetic Macrolides, 2) update our knowledge and understanding about the biosynthetic origins of the Macrolides and the mechanisms involved in their antibacterial activity and in microbial resistance to them, and 3) look toward the future emergence of additional new Macrolides potentially arising from the discovery and development pipelines of several pharmaceutical research organizations.
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Recent developments with Macrolide antibiotics
Expert Opinion on Therapeutic Patents, 1998Co-Authors: Herbert A. KirstAbstract:Macrolide antibiotics have recently experienced a significant renaissance with the introduction of several new semi-synthetic derivatives, and subsequent research has identified many additional opportunities for useful new agents. Modifications at position C-3 of erythromycin have been especially promising, yielding ‘ketolides’ such as HMR 3647, as well as other investigational compounds from Taisho and Abbott. Within 16-membered Macrolides, new series of derivatives of the leucomycins and repromicin have been disclosed by Meiji Seika and Pfizer, respectively. Advances in the molecular biology and genetics of Macrolide-producing organisms have now made feasible the directed biosynthesis of new hybrid structures by methodologies that it is becoming possible to employ on a combinatorial scale. Finally, non-anti-infective activities associated with the Macrolides are being pursued, especially with the gastrointestinal prokinetic Macrolides (motilides).
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Macrolide antibiotics in food-animal health
Expert Opinion on Investigational Drugs, 1997Co-Authors: Herbert A. KirstAbstract:Several 14- and 16-membered-ring Macrolide antibiotics have acquired important roles in the modern production of food animals. Macrolide antibiotics exhibit many similar antimicrobial properties whether used in veterinary or human medicine. In addition to their direct inhibitory action on micro-organisms, Macrolides exert a variety of subinhibitory concentration (sub-MIC) effects that are being increasingly recognised as important factors in the explanation of therapeutic results. Macrolides achieve wide tissue distribution and high intracellular concentrations that contribute prominently to their efficacy. Another important factor governing efficacy is the complex interaction between Macrolides, micro-organisms, and phagocytes that may enable the host defence system to enhance the antibiotic’s inhibitory action. A potential role for Macrolides in modulating inflammatory processes has also been recognised. In both sub-MIC effects and interactions with the host immune system, different Macrolides exert dif...
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Macrolide antibiotics in food-animal health.
Expert opinion on investigational drugs, 1997Co-Authors: Herbert A. KirstAbstract:Several 14- and 16-membered-ring Macrolide antibiotics have acquired important roles in the modern production of food animals. Macrolide antibiotics exhibit many similar antimicrobial properties whether used in veterinary or human medicine. In addition to their direct inhibitory action on micro-organisms, Macrolides exert a variety of subinhibitory concentration (sub-MIC) effects that are being increasingly recognised as important factors in the explanation of therapeutic results. Macrolides achieve wide tissue distribution and high intracellular concentrations that contribute prominently to their efficacy. Another important factor governing efficacy is the complex interaction between Macrolides, micro-organisms, and phagocytes that may enable the host defence system to enhance the antibiotic's inhibitory action. A potential role for Macrolides in modulating inflammatory processes has also been recognised. In both sub-MIC effects and interactions with the host immune system, different Macrolides exert different responses that may reinforce or oppose each other. This complexity of responses requires additional studies in appropriate disease states and animal species in order to elucidate a more comprehensive understanding and explanation of in vivo outcomes.
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Semi-synthetic derivatives of 16-membered Macrolide antibiotics
Progress in Medicinal Chemistry, 1994Co-Authors: Herbert A. KirstAbstract:Publisher Summary This chapter focuses on semi-synthetic derivative of 16-membered Macrolide antibiotics. Macrolides are a large and diverse class of natural products isolated from the culture broths of certain soil micro-organisms. Several members of this class have been commercially developed as antibiotics to treat susceptible pathogens in clinical and/or veterinary medicine. These fermentation-derived compounds have also been extensively utilized as starting materials for the synthesis of many derivatives by both chemical and biochemical methods. Several useful semi-synthetic derivatives which have arisen from these efforts have contributed substantially to the current renaissance that the Macrolide antibiotics are enjoying. The fermentation-derived Macrolides are classified according to the ring size and substitution pattern of their aglycones—that is, their core lactone ring systems lacking the amino and/or neutral sugars usually present in the complete molecular structure. The two predominant families possess either a 14- or a 16-membered aglycone. The 16-membered Macrolide antibiotics are generally divided into two principal families, the leucomycin-related family and the tylosin-related family, on the basis of the substitution pattern of their aglycones.
Richard K. Albert - One of the best experts on this subject based on the ideXlab platform.
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Macrolide antibiotics and the risk of cardiac arrhythmias
American Journal of Respiratory and Critical Care Medicine, 2014Co-Authors: Richard K. Albert, Joseph L SchullerAbstract:Randomized, controlled trials have demonstrated that chronic therapy with Macrolide antibiotics reduces the morbidity of patients with cystic fibrosis, non–cystic fibrosis bronchiectasis, chronic obstructive pulmonary disease, and nontuberculous mycobacterial infections. Lower levels of evidence indicate that chronic Macrolides are also effective in treating patients with panbronchiolitis, bronchiolitis obliterans, and rejection after lung transplant. Macrolides are known to cause torsade des pointes and other ventricular arrhythmias, and a recent observational study prompted the FDA to strengthen the Warnings and Precautions section of azithromycin drug labels. This summary describes the electrophysiological effects of Macrolides, reviews literature indicating that the large majority of subjects experiencing cardiac arrhythmias from Macrolides have coexisting risk factors and that the incidence of arrhythmias in absence of coexisting risk factors is very low, examines recently published studies describin...
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chronic Macrolide therapy in inflammatory airways diseases
Chest, 2010Co-Authors: Adam L Friedlander, Richard K. AlbertAbstract:Long-term therapy with the Macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time, Macrolides have been found to have a large number of antiinflammatory properties in addition to being antimicrobials. These observations provided the rationale for many studies performed over the last decade to assess the usefulness of Macrolides in other inflammatory airways diseases, such as cystic fibrosis, asthma, COPD, and bronchiolitis obliterans syndrome. This review summarizes the immunomodulatory properties of Macrolides and the results of these recent studies demonstrating their potential for being disease-modifying agents.
Debra A. Mangino - One of the best experts on this subject based on the ideXlab platform.
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A Treatment Alternative for Bronchiolitis Obliterans Organizing Pneumonia
2017Co-Authors: Diane E. Stover, Debra A. ManginoAbstract:Some Macrolides have been found to exert anti-inflammatory effects. Lung diseases such as asthma, panbronchiolitis, cystic fibrosis, and bronchiectasis are thought to respond to the immunomodulatory properties of Macrolides. We report three cases of idiopathic bronchiolitis obliterans organizing pneumonia, now called cryptogenic organizing pneumonia, and three cases of radiation-related bronchiolitis obliterans organizing pneumonia that responded to Macrolide therapy. An explanation of why Macrolides may have anti-inflammatory effects in patients with these syndromes is discussed. These cases help to reinforce accumulating data that Macrolides are beneficial as anti-inflammatory agents and organizing pneumonia may be another pulmonary disease that can benefit from such therapy. (CHEST 2005; 128:3611–3617)
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Macrolides a treatment alternative for bronchiolitis obliterans organizing pneumonia
Chest, 2005Co-Authors: Diane E. Stover, Debra A. ManginoAbstract:Some Macrolides have been found to exert anti-inflammatory effects. Lung diseases such as asthma, panbronchiolitis, cystic fibrosis, and bronchiectasis are thought to respond to the immunomodulatory properties of Macrolides. We report three cases of idiopathic bronchiolitis obliterans organizing pneumonia, now called cryptogenic organizing pneumonia, and three cases of radiation-related bronchiolitis obliterans organizing pneumonia that responded to Macrolide therapy. An explanation of why Macrolides may have anti-inflammatory effects in patients with these syndromes is discussed. These cases help to reinforce accumulating data that Macrolides are beneficial as anti-inflammatory agents and organizing pneumonia may be another pulmonary disease that can benefit from such therapy.
Fernando Baquero - One of the best experts on this subject based on the ideXlab platform.
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streptococcus pyogenes resistance to erythromycin in relation to Macrolide consumption in spain 1986 1997
Journal of Antimicrobial Chemotherapy, 2000Co-Authors: Juan J Granizo, Lorenzo Aguilar, J Casal, Rafael Dalre, Fernando BaqueroAbstract:The relationship between Streptococcus pyogenes resistance to erythromycin and Macrolide consumption in Spain was studied. Erythromycin resistance was highly correlated with the consumption of total Macrolides (r � 0.88, P < 0.01). When Macrolides were grouped into posological subgroups according to their pharmacokinetic and pharmacodynamic properties and analysed separately, erythromycin resistance appeared to be related mainly to those Macrolides taken twice daily (bd) (r � 0.86, P < 0.01) and those taken once daily (od) (r � 0.87, P < 0.01), but not to those taken four (qds) or three times a day (tds) (r � ‐0.04, P � 0.90). A progressive increase in the erythromycin resistance curve was seen after the consecutive introduction of both bd and od Macrolides, which contributed to the increase in the total Macrolide consumption, replacing tds Macrolide prescription. Although this ecological analysis cannot establish an unequivocal causal relationship between antibiotic consumption and S. pyogenes resistance, the data are consistent with the hypothesis that widespread use of Macrolides, mainly of bd and od Macrolides, resulted in an increased prevalence of S. pyogenes resistant to erythromycin in Spain.
David J Serisier - One of the best experts on this subject based on the ideXlab platform.
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risks of population antimicrobial resistance associated with chronic Macrolide use for inflammatory airway diseases
The Lancet Respiratory Medicine, 2013Co-Authors: David J SerisierAbstract:Summary Macrolide antibiotics have established efficacy in the management of cystic fibrosis and diffuse panbronchiolitis—uncommon lung diseases with substantial morbidity and the potential for rapid progression to death. Emerging evidence suggests benefits of maintenance Macrolide treatment in more indolent respiratory diseases including chronic obstructive pulmonary disease and non-cystic fibrosis bronchiectasis. In view of the greater patient population affected by these disorders (and potential for Macrolide use to spread to disorders such as chronic cough), widespread use of Macrolides, particularly azithromycin, has the potential to substantially influence antimicrobial resistance rates of a range of respiratory microbes. In this Personal View, I explore theories around population (rather than patient) Macrolide resistance, appraise evidence linking Macrolide use with development of resistance, and highlight the risks posed by injudicious broadening of their use, particularly of azithromycin. These risks are weighed against the potential benefits of Macrolides in less aggressive inflammatory airway disorders. A far-sighted approach to maintenance Macrolide use in non-cystic fibrosis inflammatory airway diseases is needed, which minimises risks of adversely affecting community Macrolide resistance: combining preferential use of erythromycin and restriction of Macrolide use to those patients at greatest risk represents an appropriately cautious management approach.
