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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 -
ELife Jun 2022Phenotypic variations between individual microbial cells play a key role in the resistance of microbial pathogens to pharmacotherapies. Nevertheless, little is known...
Phenotypic variations between individual microbial cells play a key role in the resistance of microbial pathogens to pharmacotherapies. Nevertheless, little is known about cell individuality in antibiotic accumulation. Here, we hypothesise that phenotypic diversification can be driven by fundamental cell-to-cell differences in drug transport rates. To test this hypothesis, we employed microfluidics-based single-cell microscopy, libraries of fluorescent antibiotic probes and mathematical modelling. This approach allowed us to rapidly identify phenotypic variants that avoid antibiotic accumulation within populations of , , and . Crucially, we found that fast growing phenotypic variants avoid macrolide accumulation and survive treatment without genetic mutations. These findings are in contrast with the current consensus that cellular dormancy and slow metabolism underlie bacterial survival to antibiotics. Our results also show that fast growing variants display significantly higher expression of ribosomal promoters before drug treatment compared to slow growing variants. Drug-free active ribosomes facilitate essential cellular processes in these fast-growing variants, including efflux that can reduce macrolide accumulation. We used this new knowledge to eradicate variants that displayed low antibiotic accumulation through the chemical manipulation of their outer membrane inspiring new avenues to overcome current antibiotic treatment failures.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Proteins; Macrolides; Microbial Sensitivity Tests; Pseudomonas aeruginosa
PubMed: 35670099
DOI: 10.7554/eLife.74062 -
International Journal of Molecular... Oct 2020Macrolide antibiotics are macrocyclic compounds that are clinically used and prescribed for the treatment of upper and lower respiratory tract infections. They inhibit... (Review)
Review
Macrolide antibiotics are macrocyclic compounds that are clinically used and prescribed for the treatment of upper and lower respiratory tract infections. They inhibit the synthesis of bacterial proteins by reversible binding to the 23S rRNA at or near the peptidyl transferase center. However, their excellent antibacterial profile was largely compromised by the emergence of bacterial resistance. Today, fighting resistance to antibiotics is one of the greatest challenges in medicinal chemistry. Considering various physicochemical properties of macrolides, understanding their structure and interactions with macromolecular targets is crucial for the design of new antibiotics efficient against resistant pathogens. The solid-state structures of some macrolide-ribosome complexes have recently been solved, throwing new light on the macrolide binding mechanisms. On the other hand, a combination of NMR spectroscopy and molecular modeling calculations can be applied to study free and bound conformations in solution. In this article, a description of advanced physicochemical methods for elucidating the structure and interactions of macrolide antibiotics in solid state and solution will be provided, and their principal advantages and drawbacks will be discussed.
Topics: Anti-Bacterial Agents; Computer Simulation; Cryoelectron Microscopy; Crystallography, X-Ray; Macrolides; Magnetic Resonance Spectroscopy; Molecular Dynamics Simulation; Ribosomes
PubMed: 33096889
DOI: 10.3390/ijms21207799 -
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 Clinical Microbiology Apr 2023Because nontuberculous mycobacterial pulmonary disease is a considerable health burden, a simple and clinically applicable analytical protocol enabling the...
Because nontuberculous mycobacterial pulmonary disease is a considerable health burden, a simple and clinically applicable analytical protocol enabling the identification of subspecies and drug-resistant disease is required to determine the treatment strategy. We aimed to develop a simplified workflow consisting only of direct sequencing of mycobacterial growth indicator tube cultures (MGIT-seq). In total, 138 patients were prospectively enrolled between April 2021 and May 2022, and culture-positive MGIT broths were subjected to sequencing using MinION, a portable next-generation sequencer. Sequence analysis was conducted to identify species using core genome multilocus sequence typing and to predict macrolide and amikacin (AMK) resistance based on previously reported mutations in , and (41). The results were compared to clinical tests for species identification and drug susceptibility. A total of 116 patients with positive MGIT cultures were included in the analysis. MGIT-seq yielded 99.1% accuracy in species-level identification and identified 98 isolates (84.5%) at the subspecies level. Macrolide and AMK resistance were detected in 19.4% and 1.9% of Mycobacterium avium complex (MAC) and Mycobacterium abscessus isolates. The predicted macrolide and AMK resistance was consistent with the results of conventional drug susceptibility tests, with specificities of 97.6% and 100.0%, respectively. Direct MGIT-seq has achieved comprehensive identification and drug resistance detection of nontuberculous mycobacteria, which could be applicable to determine the treatment strategy by a single test in clinical practice.
Topics: Humans; Nontuberculous Mycobacteria; Prospective Studies; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Amikacin; Macrolides; Microbial Sensitivity Tests
PubMed: 36946719
DOI: 10.1128/jcm.01626-22 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Aug 2023Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The... (Review)
Review
Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The research on tacrolimus production was mainly focused on biosynthesis methods, within which there are still some bottlenecks. This review summarizes the progress made in tacrolimus biosynthesis modification of metabolic pathways and control of fermentation process, with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.
Topics: Tacrolimus; Immunosuppressive Agents; Fermentation; Macrolides; Anti-Bacterial Agents
PubMed: 37622350
DOI: 10.13345/j.cjb.220994 -
Frontiers in Cellular and Infection... 2023With the widespread use of macrolide antibiotics in China, common pathogens causing children's infections, such as , (including , ), , , and , have shown varying... (Review)
Review
With the widespread use of macrolide antibiotics in China, common pathogens causing children's infections, such as , (including , ), , , and , have shown varying degrees of drug resistance. In order to provide such problem and related evidence for rational use of antibiotics in clinic, we reviewed the drug resistance of common bacteria to macrolides in children recent 20 years.
Topics: Drug Resistance, Bacterial; Macrolides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Humans; Child; China
PubMed: 37637457
DOI: 10.3389/fcimb.2023.1181633 -
Marine Drugs Apr 2019Currently, the increasing resistance of microorganisms to antibiotics is a serious problem. Marine organisms are the source of thousands of substances, which also have... (Review)
Review
Currently, the increasing resistance of microorganisms to antibiotics is a serious problem. Marine organisms are the source of thousands of substances, which also have antibacterial and antifungal effects. Among them, marine macrolides are significant. In this review, the antibacterial and/or antifungal activities of 34 groups of marine macrolides are presented. Exemplary groups are chalcomycins, curvulides, halichondramides, lobophorins, macrolactins, modiolides, scytophycins, spongistatins, or zearalanones. In the paper, 74 antibiotics or their analog sets, among which 29 with antifungal activity, 25 that are antibacterial, and 20 that are both antifungal and antibacterial are summarized. Also, 36 macrolides or their sets are produced by bacteria, 18 by fungi, ten by sponges, seven by algae, two by porifera, and one by nudibranch. Moreover, the chemical structures of representatives from each of the 34 groups of these antibiotics are presented. To summarize, marine organisms are rich in natural macrolides. Some of these may be used in the future in the treatment of bacterial and fungal infections. Marine macrolides can also be potential drugs applicable against pathogens resistant to currently known antibiotics.
Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Aquatic Organisms; Bacteria; Fungi; Humans; Macrolides
PubMed: 31018512
DOI: 10.3390/md17040241