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Frontiers in Cellular and Infection... 2023is an important pathogen causing upper and lower respiratory tract infections in children and other age groups. Macrolides are the recommended treatments of choice for...
is an important pathogen causing upper and lower respiratory tract infections in children and other age groups. Macrolides are the recommended treatments of choice for infections. However, macrolide resistance in is increasing worldwide, which complicates the treatment strategies. The mechanisms of macrolide resistance have been extensively studied focusing on the mutations in and ribosomal proteins. Since the secondary treatment choice for pediatric patients is very limited, we decided to look for potential new treatment strategies in macrolide drugs and investigate possible new mechanisms of resistance. We performed an selection of mutants resistant to five macrolides (erythromycin, roxithromycin, azithromycin, josamycin, and midecamycin) by inducing the parent strain M129 with increasing concentrations of the drugs. The evolving cultures in every passage were tested for their antimicrobial susceptibilities to eight drugs and mutations known to be associated with macrolide resistance by PCR and sequencing. The final selected mutants were also analyzed by whole-genome sequencing. Results showed that roxithromycin is the drug that most easily induces resistance (at 0.25 mg/L, with two passages, 23 days), while with midecamycin it is most difficult (at 5.12 mg/L, with seven passages, 87 days). Point mutations C2617A/T, A2063G, or A2064C in domain V of were detected in mutants resistant to the 14- and 15-membered macrolides, while A2067G/C was selected for the 16-membered macrolides. Single amino acid changes (G72R, G72V) in ribosomal protein L4 emerged during the induction by midecamycin. Genome sequencing identified sequence variations in , , , , and in one of the () genes in the mutants. Mutants induced by the 14- or 15-membered macrolides were resistant to all macrolides, while those induced by the 16-membered macrolides (midecamycin and josamycin) remained susceptible to the 14- and 15-membered macrolides. In summary, these data demonstrated that midecamycin is less potent in inducing resistance than other macrolides, and the induced resistance is restrained to the 16-membered macrolides, suggesting a potential benefit of using midecamycin as a first treatment choice if the strain is susceptible.
Topics: Humans; Child; Anti-Bacterial Agents; Mycoplasma pneumoniae; Macrolides; Roxithromycin; Josamycin; RNA, Ribosomal, 23S; Microbial Sensitivity Tests; Drug Resistance, Bacterial; Pneumonia, Mycoplasma
PubMed: 37284499
DOI: 10.3389/fcimb.2023.1186017 -
The Cochrane Database of Systematic... Jan 2021Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by persistent respiratory symptoms and airflow limitation. Acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by persistent respiratory symptoms and airflow limitation. Acute exacerbations punctuate the natural history of COPD and are associated with increased morbidity and mortality and disease progression. Chronic airflow limitation is caused by a combination of small airways (bronchitis) and parenchymal destruction (emphysema), which can impact day-to-day activities and overall quality of life. In carefully selected patients with COPD, long-term, prophylactic use of antibiotics may reduce bacterial load, inflammation of the airways, and the frequency of exacerbations.
OBJECTIVES
To assess effects of different prophylactic antibiotics on exacerbations, quality of life, and serious adverse events in people with COPD in three separate network meta-analyses (NMAs), and to provide rankings of identified antibiotics.
SEARCH METHODS
To identify eligible randomised controlled trials (RCTs), we searched the Cochrane Airways Group Specialised Register of trials and clinical trials registries. We conducted the most recent search on 22 January 2020.
SELECTION CRITERIA
We included RCTs with a parallel design of at least 12 weeks' duration evaluating long-term administration of antibiotics prophylactically compared with other antibiotics, or placebo, for patients with COPD.
DATA COLLECTION AND ANALYSIS
This Cochrane Review collected and updated pair-wise data from two previous Cochrane Reviews. Searches were updated and additional studies included. We conducted three separate network meta-analyses (NMAs) within a Bayesian framework to assess three outcomes: exacerbations, quality of life, and serious adverse events. For quality of life, we collected data from St George's Respiratory Questionnaire (SGRQ). Using previously validated methods, we selected the simplest model that could adequately fit the data for every analysis. We used threshold analysis to indicate which results were robust to potential biases, taking into account each study's contributions to the overall results and network structure. Probability ranking was performed for each antibiotic class for exacerbations, quality of life, and serious adverse events.
MAIN RESULTS
Characteristics of studies and participants Eight trials were conducted at multiple sites that included hospital clinics or academic health centres. Seven were single-centre trials conducted in hospital clinics. Two trials did not report settings. Trials durations ranged from 12 to 52 weeks. Most participants had moderate to severe disease. Mean age ranged from 64 years to 73 years, and more males were recruited (51% to 100%). Forced expiratory volume in one second (FEV₁) ranged from 0.935 to 1.36 L. Most participants had previous exacerbations. Data from 12 studies were included in the NMAs (3405 participants; 16 treatment arms including placebo). Prophylactic antibiotics evaluated were macrolides (azithromycin and erythromycin), tetracyclines (doxycyclines), quinolones (moxifloxacin) and macrolides plus tetracyclines (roxithromycin plus doxycycline). Risk of bias and threshold analysis Most studies were at low risk across domains, except detection bias, for which only seven studies were judged at low risk. In the threshold analysis for exacerbations, all comparisons in which one antibiotic was compared with another were robust to sampling variation, especially macrolide comparisons. Comparisons of classes with placebo were sensitive to potential bias, especially macrolide versus placebo, therefore, any bias in the comparison was likely to favour the active class, so any adjustment would bring the estimated relative effect closer to the null value, thus quinolone may become the best class to prevent exacerbations. Exacerbations Nine studies were included (2732 participants) in this NMA (exacerbations analysed as time to first exacerbation or people with one or more exacerbations). Macrolides and quinolones reduced exacerbations. Macrolides had a greater effect in reducing exacerbations compared with placebo (macrolides: hazard ratio (HR) 0.67, 95% credible interval (CrI) 0.60 to 0.75; quinolones: HR 0.89, 95% CrI 0.75 to 1.04), resulting in 127 fewer people per 1000 experiencing exacerbations on macrolides. The difference in exacerbations between tetracyclines and placebo was uncertain (HR 1.29, 95% CrI 0.66 to 2.41). Macrolides ranked first (95% CrI first to second), with quinolones ranked second (95% CrI second to third). Tetracyclines ranked fourth, which was lower than placebo (ranked third). Contributing studies were considered as low risk of bias in a threshold analysis. Quality of life (SGRQ) Seven studies were included (2237 participants) in this NMA. SGRQ scores improved with macrolide treatment compared with placebo (fixed effect-fixed class effect: mean difference (MD) -2.30, 95% CrI -3.61 to -0.99), but the mean difference did not reach the minimally clinical important difference (MCID) of 4 points. Tetracyclines and quinolones did not improve quality of life any more than placebo, and we did not detect a difference between antibiotic classes. Serious adverse events Nine studies were included (3180 participants) in the NMA. Macrolides reduced the odds of a serious adverse event compared with placebo (fixed effect-fixed class effect: odds ratio (OR) 0.76, 95% CrI 0.62 to 0.93). There was probably little to no difference in the effect of quinolone compared with placebo or tetracycline plus macrolide compared with placebo. There was probably little to no difference in serious adverse events between quinolones or tetracycline plus macrolide. With macrolide treatment 49 fewer people per 1000 experienced a serious adverse event compared with those given placebo. Macrolides ranked first, followed by quinolones. Tetracycline did not rank better than placebo. Drug resistance Ten studies reported drug resistance. Results were not combined due to variation in outcome measures. All studies concluded that prophylactic antibiotic administration was associated with the development of antimicrobial resistance.
AUTHORS' CONCLUSIONS
This NMA evaluated the safety and efficacy of different antibiotics used prophylactically for COPD patients. Compared to placebo, prolonged administration of macrolides (ranked first) appeared beneficial in prolonging the time to next exacerbation, improving quality of life, and reducing serious adverse events. No clear benefits were associated with use of quinolones or tetracyclines. In addition, antibiotic resistance was a concern and could not be thoroughly assessed in this review. Given the trade-off between effectiveness, safety, and risk of antibiotic resistance, prophylactic administration of antibiotics may be best reserved for selected patients, such as those experiencing frequent exacerbations. However, none of the eligible studies excluded patients with previously isolated non-tuberculous mycobacteria, which would contraindicate prophylactic administration of antibiotics, due to the risk of developing resistant non-tuberculous mycobacteria.
Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Load; Bayes Theorem; Bias; Disease Progression; Female; Forced Expiratory Volume; Humans; Macrolides; Male; Middle Aged; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quality of Life; Quinolones; Randomized Controlled Trials as Topic; Tetracyclines; Treatment Outcome
PubMed: 33448349
DOI: 10.1002/14651858.CD013198.pub2 -
Natural Product Reports Aug 2022Covering: 2000 to 2022Natural products are a vital source of compounds for use in agriculture, medicine, cosmetics, and other fields. Macrolides are a wide group of... (Review)
Review
Covering: 2000 to 2022Natural products are a vital source of compounds for use in agriculture, medicine, cosmetics, and other fields. Macrolides are a wide group of natural products found in plants and microorganisms. They are a group of polyketides constituted of different-sized rings and characterized by the presence of a lactone group. These compounds show different biological activities, such as antiviral, antiparasitic, antifungal, antibacterial, immunosuppressive, herbicidal, and cytotoxic activities. This review is focused on macrolides isolated from fungal sources, examining their biological activities, stereochemistry, and structure-activity relationships. The review reports the chemical and biological characterization of fungal macrolides isolated in the last four decades, with assistance from SciFinder searches. A critical evaluation of the most recent reviews covering this area is also provided. The content provided in this review is of interest to chemists focusing on natural substances, plant pathologists and physiologists, botanists, mycologists, biologists, and pharmacologists. Furthermore, it is of interest to farmers and agri-food specialists and those working in the medicinal and cosmetic industries due to the potential practical application of macrolides. Politicians could also be interested in this class of natural compound, as the practical application of these macrolides in the above-cited fields could reduce environmental pollution and increase consumer satisfaction with respect to food, providing reduced or zero risk to human and animal health along with increased nutraceutical value.
Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Biological Products; Humans; Macrolides; Plants; Polyketides
PubMed: 35723218
DOI: 10.1039/d2np00025c -
Toxins May 2021Macrolides are a diverse class of hydrophobic compounds characterized by a macrocyclic lactone ring and distinguished by variable side chains/groups. Some of the most... (Review)
Review
Macrolides are a diverse class of hydrophobic compounds characterized by a macrocyclic lactone ring and distinguished by variable side chains/groups. Some of the most well characterized macrolides are toxins produced by marine bacteria, sea sponges, and other species. Many marine macrolide toxins act as biomimetic molecules to natural actin-binding proteins, affecting actin polymerization, while other toxins act on different cytoskeletal components. The disruption of natural cytoskeletal processes affects cell motility and cytokinesis, and can result in cellular death. While many macrolides are toxic in nature, others have been shown to display therapeutic properties. Indeed, some of the most well known antibiotic compounds, including erythromycin, are macrolides. In addition to antibiotic properties, macrolides have been shown to display antiviral, antiparasitic, antifungal, and immunosuppressive actions. Here, we review each functional class of macrolides for their common structures, mechanisms of action, pharmacology, and human cellular targets.
Topics: Animals; Anti-Bacterial Agents; Cytoskeleton; Humans; Hydrophobic and Hydrophilic Interactions; Macrolides; Marine Toxins
PubMed: 34065929
DOI: 10.3390/toxins13050347 -
Emerging Microbes & Infections Dec 2022The objective of this paper is to explore the characteristics of (MP) epidemics in Beijing, China. Patients with acute respiratory tract infection (ARTI) were enrolled...
The objective of this paper is to explore the characteristics of (MP) epidemics in Beijing, China. Patients with acute respiratory tract infection (ARTI) were enrolled from 35 sentinel hospitals in Beijing, 2015-2020. Their medical records were reviewed and respiratory specimens were collected for assay for nucleic acids of 24 respiratory pathogens, including MP. The genotypes of MP were analysed using a real-time PCR method. The domain V of 23s rRNA gene was sequenced to identify macrolide-resistant mutations. A total of 41,677 specimens of ARTI patients were included, with an MP positive rate of 6.16%. MP prevalence mainly occurred between August and January, and peaked in October. The increase in the MP detection rate was coincident with the elevation of the reported number of patients with pneumonia in the 35 sentinel hospitals. One or more respiratory pathogens were co-detected in 27.1% of the MP-positive patients. Type 1 MP remained predominant, and the macrolide-resistant rate of MP had exceeded over 90%. A2063G mutation accounted for 99.0% of macrolide-resistant MP infections. MP epidemic in Beijing mainly occurred between August and January with a remarkable high macrolide-resistant rate. MP is one of the important contributors to the pneumonia epidemic in autumn and winter in Beijing.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Epidemics; Epidemiologic Studies; Humans; Macrolides; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Respiratory Tract Infections
PubMed: 35582916
DOI: 10.1080/22221751.2022.2078228 -
Current Opinion in Gastroenterology Jan 2023Campylobacter is a major foodborne pathogen that infects the human intestinal tract. This review discusses the current status of antibiotic resistance, transmission of... (Review)
Review
PURPOSE OF REVIEW
Campylobacter is a major foodborne pathogen that infects the human intestinal tract. This review discusses the current status of antibiotic resistance, transmission of antibiotic resistance genes, and strategies to combat the global Campylobacter epidemic.
RECENT FINDINGS
Over the past 18 months, articles on Campylobacter antibiotic resistance have been published in ∼39 countries. Antibiotic-resistant Campylobacter have been detected in humans, livestock, poultry, wild animals, the environment, and food. Campylobacter spp. are resistant to a wide spectrum of antimicrobial agents, including the antibiotics quinolones, macrolides, tetracyclines, aminoglycosides, and chloramphenicols. Multidrug resistance is a globally emerging problem. Continuous antibiotic pressure promotes the spread of drug-resistant Campylobacter spp. Additionally, Campylobacter is well adapted to acquiring foreign drug resistance genes, including ermB, optrA, fexA, and cfrC, which are usually acquired from gram-positive bacteria.
SUMMARY
The widespread use of antibiotics has caused a global epidemic of drug-resistant Campylobacter infections. Many countries are actively reducing the use of antibiotics and adopting alternatives in the livestock and poultry industries to control the spread of drug-resistant Campylobacter spp.
Topics: Animals; Humans; Campylobacter; Drug Resistance, Microbial; Campylobacter Infections; Anti-Bacterial Agents; Macrolides
PubMed: 36504031
DOI: 10.1097/MOG.0000000000000901 -
The Lancet. Microbe Jun 2024
Topics: Humans; China; Pneumonia, Mycoplasma; Macrolides; Mycoplasma pneumoniae; Anti-Bacterial Agents; Drug Resistance, Bacterial
PubMed: 38244553
DOI: 10.1016/S2666-5247(23)00405-6 -
Seminars in Respiratory and Critical... Aug 2021A significant proportion of bronchiectasis patients are chronically infected by potentially pathogenic microorganisms which may lead to frequent exacerbations and worse... (Review)
Review
A significant proportion of bronchiectasis patients are chronically infected by potentially pathogenic microorganisms which may lead to frequent exacerbations and worse clinical outcomes. Current bronchiectasis guidelines recommend long-term inhaled antibiotics and/or oral macrolides as a part of patient management. In recent years, an increasing amount of evidence assessing the impact of these treatments on patient outcomes has been collected. Inhaled antibiotics have demonstrated significant improvements in sputum bacterial load, but their impact on patient quality of life, lung function, and exacerbation rate has not been consistent across trials. In this regard, recent post hoc analyses of inhaled antibiotics trials in bronchiectasis patients have shown that sputum bacterial load may be a key biomarker to predict treatment response in these patients. Oral macrolides, on the other hand, have proven to reduce exacerbation frequency and improve quality of life, but potential drug-related adverse effects and the increase in bacterial resistance are relevant. This review aims to summarize current important evidence for long-term antibiotic treatment in bronchiectasis patients.
Topics: Anti-Bacterial Agents; Bronchiectasis; Humans; Macrolides; Quality of Life; Sputum
PubMed: 34261184
DOI: 10.1055/s-0041-1730945 -
Indian Journal of Medical Microbiology 2023As a major causative pathogen of community-acquired pneumonia, Mycoplasma pneumoniae (M. pneumoniae) can cause both upper and lower respiratory tract inflammation as...
BACKGROUND/PURPOSE
As a major causative pathogen of community-acquired pneumonia, Mycoplasma pneumoniae (M. pneumoniae) can cause both upper and lower respiratory tract inflammation as well as extrapulmonary syndromes, especially in infants and the elderly. The emergence of macrolide-resistance has significant effects on the treatment of relevant diseases in children. This study aimed to analyze the genotypes and the macrolide resistance-associated mutations in M. pneumoniae sampled from the pediatric patients in Henan, China.
METHODS
A segment of gene on the 23S rRNA was amplified and sequenced to detect the mutations related to macrolide resistance. Molecular typing was performed by the method named multiple locus variable-number tandem repeat analysis (MLVA) for macrolide-susceptible and macrolide-resistant specimens.
RESULTS
Among the M. pneumoniae-positive samples, 95.7% (111/116) had macrolide-resistant mutation, and all of them consisted of the A2063G mutation. There were only two MLVA types identified in this study, type 4-5-7-2 (51/92, 55.4%) and type 3-5-6-2 (41/92, 44.6%).
CONCLUSION
There was no correlation between MLVA types and macrolide resistance (P > 0.05).
Topics: Infant; Humans; Child; Aged; Mycoplasma pneumoniae; Anti-Bacterial Agents; Pneumonia, Mycoplasma; Macrolides; Drug Resistance, Bacterial; Molecular Typing; China
PubMed: 37945129
DOI: 10.1016/j.ijmmb.2023.100435 -
International Journal of Antimicrobial... Feb 2022Rare actinomycetes are a source of numerous diverse, biologically active secondary metabolites, including macrolides, which have been shown to display several antibiotic... (Review)
Review
Rare actinomycetes are a source of numerous diverse, biologically active secondary metabolites, including macrolides, which have been shown to display several antibiotic activities. The bioactivities and representative structures of 26 groups of macrolides from rare actinomycetes are presented in this review. The most interesting groups, with a wide range of biological activities, are ammocidins, bafilomycins, neomaclafungins, rosaramicins, spinosyns, and tiacumicins. Most macrolides are from the genus, Micromonospora, with smaller contributions from genera such as Saccharothrix, Amycolatopsis, Nocardiopsis and Catenulispora. These macrolides display unique cytotoxic, antibacterial, antifungal, antimicrobial, insecticidal, anti-trypanosomal, antimalarial, antiprotozoal, antimycobacterial and anti-herpetic activity. Considering their bioactivities and diverse structures, macrolides from rare actinomycetes warrant further investigation for future applications in medicine. This work highlights the bioactivities and structures of important classes of macrolides from rare actinomycetes that are already marketed or could be used in medicine in the future.
Topics: Actinobacteria; Actinomyces; Anti-Bacterial Agents; Antifungal Agents; Macrolides
PubMed: 35041941
DOI: 10.1016/j.ijantimicag.2022.106523