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Chemistry (Weinheim An Der Bergstrasse,... Mar 2020The nargenicin family of antibiotic macrolides comprise a group of bacterial natural products with a rare ether bridged cis-decalin moiety and a narrow spectrum of... (Review)
Review
The nargenicin family of antibiotic macrolides comprise a group of bacterial natural products with a rare ether bridged cis-decalin moiety and a narrow spectrum of activity. Most family members were identified almost four decades ago and were placed on the shelf due to the numbers of broad-spectrum compounds available at the time. However, in light of rising rates of antimicrobial resistance, there has been a renewed interest in the use of narrow-spectrum antimicrobials. Here, we review the history of this family of compounds, including synthetic approaches, and highlight the recently uncovered genetic basis for nargenicin production. Given the renewed pharmaceutical interest in these compounds, we also investigate structure-activity relationships among these molecules, with a view to the future development of members of this unusual antibiotic family.
Topics: Anti-Bacterial Agents; Bridged-Ring Compounds; Humans; Lactones; Macrolides; Naphthalenes; Structure-Activity Relationship
PubMed: 31667915
DOI: 10.1002/chem.201904053 -
Microbiology Spectrum Dec 2023This study first reported the effector kinetics of the new non-fluorinated quinolone, nemonoxacin, against macrolide-resistant (MRMP) and macrolide susceptible (MSMP)...
This study first reported the effector kinetics of the new non-fluorinated quinolone, nemonoxacin, against macrolide-resistant (MRMP) and macrolide susceptible (MSMP) strains along with other antimicrobial agents. The time-kill assays and pharmacodynamic analysis showed that nemonoxacin has significant mycoplasmacidal activity against MRMP and MSMP. This study paves the road to establish appropriate dosing protocols of a new antimicrobial drug for children infected with .
Topics: Child; Humans; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Anti-Bacterial Agents; Quinolones; Macrolides; Drug Resistance, Bacterial; Microbial Sensitivity Tests
PubMed: 37975686
DOI: 10.1128/spectrum.02431-23 -
Respiratory Care May 2018Antibiotics have previously demonstrated anti-inflammatory properties, and they have been linked to therapeutic benefit in several pulmonary conditions that feature... (Review)
Review
Antibiotics have previously demonstrated anti-inflammatory properties, and they have been linked to therapeutic benefit in several pulmonary conditions that feature inflammation. Previous research suggests that these anti-inflammatory properties may be beneficial in the treatment of COPD. This review assesses the potential benefit of prophylactic, long-term, and low-dose antibiotic therapy in COPD, and whether any effects seen are anti-inflammatory in nature. Randomized, controlled trials comparing antibiotic therapy with placebo in subjects with stable COPD were evaluated. Twelve trials involving 3,784 participants and a range of antibiotics were included: azithromycin (6 studies, 1,972 participants), clarithromycin (1 study, 67 participants), erythromycin (3 studies, 254 participants), roxithromycin (1 study, 191 participants), and moxifloxacin (2 studies, 1,198 participants). In vitro, in vivo, and ex vivo experimental study designs exploring the mechanisms via which antibiotics may act in subjects with stable COPD were evaluated. Azithromycin and erythromycin showed the greatest effect in subjects with COPD, with evidence suggesting improvement in exacerbation-related outcomes and health status, as measured by the St George Respiratory Questionnaire. An increase in antibiotic resistance was reported in 2 studies. The macrolide class of antibiotics exhibited convincing anti-inflammatory properties with relevance to COPD, implicating several pathways as potential mechanisms of action. In conclusion, the therapeutic benefit of macrolide antibiotics in subjects with stable COPD is consistent with anti-inflammatory properties, and macrolides should be considered as a potential therapy in COPD. Safety concerns regarding antibiotic resistance need to be addressed before widespread use in clinical practice.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Humans; Immunologic Factors; Inflammation; Macrolides; Pulmonary Disease, Chronic Obstructive; Treatment Outcome
PubMed: 29463692
DOI: 10.4187/respcare.05943 -
BMC Microbiology Aug 2023The microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as...
BACKGROUND
The microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as antibiotics. Several studies have demonstrated that commonly used antibiotics can have sustained impacts on the diversity and the composition of the gut microbiome. The impact of the two most overused antibiotics, azithromycin, and amoxicillin, in the human microbiome has not been thoroughly described. In this study, we recruited a group of individuals and unrelated controls to decipher the effects of the commonly used antibiotics amoxicillin and azithromycin on their gut microbiomes.
RESULTS
We characterized the gut microbiomes by metagenomic sequencing followed by characterization of the resulting microbial communities. We found that there were clear and sustained effects of the antibiotics on the gut microbial community with significant alterations in the representations of Bifidobacterium species in response to azithromycin (macrolide antibiotic). These results were supported by significant increases identified in putative antibiotic resistance genes associated with macrolide resistance. Importantly, we did not identify these trends in the unrelated control individuals. There were no significant changes observed in other members of the microbial community.
CONCLUSIONS
As we continue to focus on the role that the gut microbiome plays and how disturbances induced by antibiotics might affect our overall health, elucidating members of the community most affected by their use is of critical importance to understanding the impacts of common antibiotics on those who take them. Clinical Trial Registration Number NCT05169255. This trial was retrospectively registered on 23-12-2021.
Topics: Humans; Anti-Bacterial Agents; Amoxicillin; Azithromycin; Metagenomics; Macrolides; Drug Resistance, Bacterial
PubMed: 37528343
DOI: 10.1186/s12866-023-02949-z -
Journal of Medical Microbiology Jun 2022Nontuberculous mycobacteria (NTM) infections are increasing worldwide and are relatively resistant to many of the first- and second-line drugs to treat tuberculosis....
Nontuberculous mycobacteria (NTM) infections are increasing worldwide and are relatively resistant to many of the first- and second-line drugs to treat tuberculosis. Macrolide antibiotics, such as clarithromycin and azithromycin, are the key drugs for treating NTM infections. Fidaxomicin is a macrolide antibiotic that is widely used in treating infections, and has high activity against especially multidrug-resistant tuberculosis (MDR-TB) and has no cross-resistance with rifampicin. Fidaxomicin may have activity against NTM strains. To find that whether the macrolide antibiotic fidaxomicin has activity against NTM strains. Fidaxomicin used in this study was firstly tested on reference strains and has shown to be effective and workable. And then 28 rapidly growing mycobacteria (RGM), 12 slowly growing mycobacteria (SGM) reference strains and 103 NTM clinical isolates were tested by the microplate-based AlamarBlue assay (MABA) method to determine the MICs. Fidaxomicin, rifampicin and clarithromycin were tested against omplex subspecies 14 . and 5 . strains for inducible resistance determination. In total, 21 out of 28 RGM and 9 of 12 SGM reference strains have the MICs of fidaxomicin at or below 1 µg ml. Fidaxomicin also showed low MIC values for some clinical isolates including complex, complex, , and . Fidaxomicin also has no inducible macrolide resistance in complex in comparison with clarithromycin. Fidaxomicin has high activity against most of the NTM reference strains and some prevalent NTM clinical isolates. This promising finding warrants further investigation on the actions of fidaxomicn and as a potential antibiotic for NTM treatment.
Topics: Anti-Bacterial Agents; Clarithromycin; Clostridioides difficile; Drug Resistance, Bacterial; Fidaxomicin; Humans; Macrolides; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Rifampin
PubMed: 35708979
DOI: 10.1099/jmm.0.001549 -
The Journal of Antimicrobial... May 2017Solithromycin, a ketolide/macrolide antibiotic, has recently been reported to be free of the expected QT-prolonging effect of macrolides. It appears that its keto...
Solithromycin, a ketolide/macrolide antibiotic, has recently been reported to be free of the expected QT-prolonging effect of macrolides. It appears that its keto substitution provides a structural basis for this observation, as the other two tested ketolides also have minimal QT effect.Among non-cardiovascular therapies, antimicrobials probably carry the greatest potential to cause cardiac arrhythmias. This is a result of their propensity to bind to the delayed rectifier potassium channel, IKr, inducing QT prolongation and risk of torsades de pointes ventricular tachycardia, their frequent interference with the metabolism of other QT prolongers and their susceptibility to metabolic inhibition by numerous commonly used drugs.Unfortunately, there is evidence that medical practitioners do not take account of the QT/arrhythmia risk of antimicrobials in their prescribing practices. Education on this topic is sorely needed. When a macrolide is indicated, a ketolide should be considered in patients with a QT risk.
Topics: Anti-Bacterial Agents; Education, Medical; Humans; Ketolides; Long QT Syndrome; Macrolides; Potassium Channels, Inwardly Rectifying; Practice Patterns, Physicians'; Torsades de Pointes; Triazoles
PubMed: 28160473
DOI: 10.1093/jac/dkw591 -
Journal of Microbiology, Immunology,... Jun 2023Macrolide-resistant Mycoplasma pneumoniae (MRMP) infection is increasing worldwide. However, its clinical significance is still uncertain.
The clinical significance of and the factors associated with macrolide resistance and poor macrolide response in pediatric Mycoplasma pneumoniae infection: A retrospective study.
BACKGROUND
Macrolide-resistant Mycoplasma pneumoniae (MRMP) infection is increasing worldwide. However, its clinical significance is still uncertain.
METHODS
The data of the Laboratory Medicine Department of Chang Gung Memorial Hospital in northern Taiwan was searched for children with molecular confirmed macrolide-susceptible Mycoplasma pneumoniae (MSMP) and MRMP infections between January 2011 and December 2018. The clinical features, laboratory data, and chest image presentations were compared between patients with MRMP and MSMP infections and between patients with good and poor macrolide response, respectively.
RESULTS
Records from 158 patients were recovered. Of the enrolled patients 34 (22%) suffered MRMP infection, 27 (17%) had pleural effusions, and 47 (32%) had poor macrolide response. The macrolide resistance rate was 12% in 2011, 20% between 2015 and 2016, and 50% between 2017 and 2018, respectively. Other than a poor macrolide response, the MRMP and MSMP infections are clinically indistinguishable. The presence of pleural effusion and MRMP infections were found to be independently associated with a poor macrolide response, with odds ratios (95% confidence interval) of 14.3 (4.9-42.0) and 14.6 (5.4-40), respectively. The macrolide resistance rate of the patients with a poor macrolide response was 49% and 18% among all the patients enrolled and the patients with a pleural effusion, respectively.
CONCLUSION
The macrolide resistance rate had possibly increased in recent years in Taiwan and should be continuously monitored. In addition, the macrolide response could be misleading in predicting a macrolide resistance especially for the patients with a pleural effusion.
Topics: Child; Humans; Anti-Bacterial Agents; Pneumonia, Mycoplasma; Macrolides; Retrospective Studies; Clinical Relevance; Drug Resistance, Bacterial; Mycoplasma pneumoniae; Pleural Effusion
PubMed: 36737359
DOI: 10.1016/j.jmii.2023.01.010 -
Journal of Medicinal Chemistry Jun 2020This is a review of the macrolide and ketolide field focusing on differentiating the pharmacodynamics and especially the toxicology of the macrolides and ketolides. We...
This is a review of the macrolide and ketolide field focusing on differentiating the pharmacodynamics and especially the toxicology of the macrolides and ketolides. We emphasize the diversity in pharmacodynamics and toxicity of the macrolides and ketolides, resulting from even small structural changes, which makes it important to consider the various different compounds separately, not necessarily as a class. The ketolide, telithromycin, was developed because of rising bacterial macrolide resistance but was withdrawn postapproval after visual disturbances, syncope, myasthenia gravis, and hepatotoxicity were noted. These diverse adverse effects could be attributed to inhibition of nicotinic acetylcholine receptors. Solithromycin, a later generation ketolide, was effective in treating bacterial pneumonia, but it was not approved by the U.S. Food and Drug Administration owing, in part, to its structural similarity to telithromycin. This Miniperspective describes that structurally similar macrolides/ketolides have clearly mechanistically distinct effects. Understanding these effects could help in developing and securing regulatory approval of a new macrolide/ketolide that is active against macrolide-resistant pathogenic bacteria.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Drug-Related Side Effects and Adverse Reactions; Humans; Ketolides; Macrolides
PubMed: 31644280
DOI: 10.1021/acs.jmedchem.9b01159 -
Auris, Nasus, Larynx Apr 2016In 1984, the effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in Japan. The 5-year... (Review)
Review
In 1984, the effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in Japan. The 5-year survival rate for DPB improved from 62.9 to 91.4% after implementation of macrolide therapy. The usefulness of this treatment has since been demonstrated in patients with other chronic airway diseases, such as chronic bronchitis, cystic fibrosis, bronchiectasis, bronchial asthma, and chronic rhinosinusitis (CRS). The new 14-membered macrolides clarithromycin and roxithromycin and the 15-membered macrolide azithromycin are also effective for treating these inflammatory diseases. The mechanism of action of the 14- and 15-membered macrolides may involve anti-inflammatory rather than anti-bacterial activities. Macrolide therapy is now widely used for the treatment of CRS in Japan; it is particularly effective for treating neutrophil-associated CRS and is useful for suppressing mucus hypersecretion. However, macrolide therapy is not effective for eosinophil-predominant CRS, which is characterized by serum and tissue eosinophilia, high serum IgE levels, multiple polyposis, and bronchial asthma. Recent reports have described the clinical efficacy of macrolides in treating other inflammatory diseases and new biological activities (e.g., anti-viral). New macrolide derivatives exhibiting anti-inflammatory but not anti-bacterial activity thus have therapeutic potential as immunomodulatory drugs. The history, current state, and future perspectives of macrolide therapy for treating CRS in Japan will be discussed in this review.
Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Chronic Disease; Clarithromycin; Erythromycin; Haemophilus Infections; History, 20th Century; History, 21st Century; Humans; Japan; Macrolides; Nasal Polyps; Rhinitis; Sinusitis
PubMed: 26441370
DOI: 10.1016/j.anl.2015.08.014 -
Revue Medicale Suisse Nov 2022Macrolides are commonly used antibiotics due to their broad spectrum of activity and good bioavailability. More recently, they have been shown to be effective in certain... (Review)
Review
Macrolides are commonly used antibiotics due to their broad spectrum of activity and good bioavailability. More recently, they have been shown to be effective in certain chronic lung diseases by reducing exacerbation frequency. This narrative review examines the scientific evidence and international recommendation for immunomodulatory macrolides therapy in the most frequent chronic respiratory disorders.
Topics: Humans; Macrolides; Lung Diseases; Anti-Bacterial Agents
PubMed: 36416507
DOI: 10.53738/REVMED.2022.18.805.2206