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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 -
Clinical Infectious Diseases : An... Feb 2023Doxycycline has been recommended as a treatment option for non-severe community-acquired pneumonia (CAP) in adults. We sought to review the evidence for the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Doxycycline has been recommended as a treatment option for non-severe community-acquired pneumonia (CAP) in adults. We sought to review the evidence for the efficacy of doxycycline in adult patients with mild-to-moderate CAP.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of doxycycline versus comparator to assess the clinical efficacy. The primary outcome was the clinical cure rate. Random effects model meta-analyses were used to generate pooled odds ratio (OR) and evaluate heterogeneity (I2). Risk of bias (RoB) and quality of evidence (QoE) were evaluated using the Cochrane Risk of Bias 2.0 tool and GRADE methods, respectively.
RESULTS
We included 6 RCTs with 834 clinically evaluable patients. The trials were performed between 1984 and 2004. Comparators were 3 macrolides (roxithromycin, spiramycin, and erythromycin) and 3 fluoroquinolones (ofloxacin, fleroxacin, and levofloxacin). Four trials had an overall high RoB. The clinical cure rate was similar between the doxycycline and comparator groups (87.2% [381/437] vs 82.6% [328/397]; OR 1.29 [95% confidence interval {CI}: .73-2.28]; I2 = 30%; low QoE). Subgroup analysis of two studies with a low RoB showed significantly higher clinical cure rates in the doxycyline group (87.1% [196/225] vs 77.8% [165/212]; OR 1.92 [95% CI: 1.15-3.21]; P = .01; I2 = 0%). Adverse event rates were comparable between the doxycycline and comparator groups.
CONCLUSIONS
The efficacy of doxycycline was comparable to macrolides or fluoroquinolones in mild-to-moderate CAP and thus represents a viable treatment option. Considering the lack of recent trials, it warrants large-scale clinical trials.
Topics: Adult; Humans; Doxycycline; Randomized Controlled Trials as Topic; Anti-Bacterial Agents; Macrolides; Fluoroquinolones; Pneumonia
PubMed: 35903011
DOI: 10.1093/cid/ciac615 -
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 -
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 -
Journal of Global Antimicrobial... Dec 2022Macrolide-resistant Bordetella pertussis (MRBP) has been emerging and prevailing in mainland China since 2011. In this study, we aimed to investigate the genotype and...
OBJECTIVES
Macrolide-resistant Bordetella pertussis (MRBP) has been emerging and prevailing in mainland China since 2011. In this study, we aimed to investigate the genotype and macrolide resistance of circulating B. pertussis in East and Southeast Asia using genetic analyses.
METHODS
A total of 302 DNA extracts from clinical specimens and isolates from 2010 to 2020 were analyzed: 145 from Vietnam, 76 from Cambodia, 48 from Taiwan, and 33 from Japan. Genotypes were determined by multilocus variable-number tandem-repeat analysis (MLVA). Macrolide-resistant A2047G mutation in B. pertussis 23S rRNA was investigated using the duplex Cycleave real-time polymerase chain reaction (PCR) assay. Whole-genome sequencing was performed on two MRBP isolates that were identified for the first time in Taiwan.
RESULTS
Overall, 286 DNA extracts (95%) generated a complete MLVA genotype and 283 DNA extracts (94%) yielded a complete result for the A2047G mutation analysis. The A2047G mutation was detected in 18 DNA extracts: fourteen from Vietnam, one from Cambodia, two from Taiwan, and one from Japan. Most of them (78%) showed the genotypes MT104 and MT195, which have previously been reported in Chinese MRBP isolates. Further, the Taiwanese MRBP isolates were classified into the MT104 clade of Chinese MRBP isolates.
CONCLUSION
After MRBP emerged and spread in mainland China, it may have spread to East and Southeast Asia in the 2010s. Continued surveillance targeting the A2047G mutation of MRBP is needed to prevent further spread of this emerging pathogen.
Topics: Humans; Bordetella pertussis; Macrolides; Whooping Cough; Anti-Bacterial Agents; Genotype; Drug Resistance, Bacterial; Mutation; Asia, Southeastern; Asia, Eastern
PubMed: 36270447
DOI: 10.1016/j.jgar.2022.10.007 -
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 -
Tuberkuloz Ve Toraks Dec 2021Macrolides are antibiotics with antiviral, anti-inflammatory and immunomodulatory effects in together with their bacteriostatic effects. In addition to its beneficial... (Review)
Review
Macrolides are antibiotics with antiviral, anti-inflammatory and immunomodulatory effects in together with their bacteriostatic effects. In addition to its beneficial effects on chronic respiratory diseases such as COPD, cystic fibrosis, diffuse panbronchiolitis, and bronchiectasis, its effects on uncontrolled severe asthma and asthma exacerbations have been the subject of research in recent years. In randomized controlled trials, azithromycin, a macrolide, has been shown to reduce asthma exacerbations and significantly improve asthma-related quality of life in both eosinophilic and non-eosinophilic asthma phenotypes. However, there are also differences such as doses, durations and some studies not showing its effectiveness in severe eosinophilic asthma. In the GINA report, azithromycin can be recommended as an add-on therapy in patients with uncontrolled non-T2 severe asthma despite high-dose inhaled corticosteroid/ long-acting beta2-agonist/long-acting antimuscariniric treatments, or in T2 severe asthma patients whose asthma is not under control despite biologic therapy. In this review, the use of macrolides, especially azithromycin, in the treatment of asthma, immunomodulatory activities and safety profiles are discussed on the basis of current studies and guidelines.
Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Humans; Macrolides; Quality of Life
PubMed: 34957746
DOI: 10.5578/tt.20219610 -
Respiratory Investigation Mar 2024The evidence for macrolide therapy in adult asthma is not properly established and remains controversial. We conducted a systematic review and meta-analysis to examine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The evidence for macrolide therapy in adult asthma is not properly established and remains controversial. We conducted a systematic review and meta-analysis to examine the efficacy and safety of macrolide therapy for adult asthma.
METHODS
We searched randomized controlled trials from MEDLINE via the PubMed, CENTRAL, and Ichushi Web databases. The primary outcome was asthma exacerbation. The secondary outcomes were serious adverse events (including mortality), asthma-related quality of life (symptom scales, Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire), rescue medication (puffs/day), respiratory function (morning peak expiratory flow, evening peak flow, and forced expiratory volume in 1 s), bronchial hyperresponsiveness, and minimum oral corticosteroid dose. Of the 805 studies, we selected seven studies for the meta-analysis, which was conducted using a random-effects model.
SYSTEMATIC REVIEW REGISTRATION
University Hospital Medical Information Network Clinical Trials Registry (UMIN000050824).
RESULTS
No significant difference between macrolide and placebo for asthma exacerbations was observed (risk ratio 0.71, 95 % confidence interval [CI] 0.46-1.09; p = 0.12). Macrolide therapy for adult asthma showed a significant improvement in rescue medication with short-acting beta-agonists (mean difference -0.41, 95 % CI -0.78 to -0.04; p = 0.03). Macrolide therapy did not show more serious adverse events (odd ratio 0.61, 95 % CI 0.34-1.10; p = 0.10) than those with placebo. The other secondary outcomes were not significantly different between the macrolide and placebo groups.
CONCLUSIONS
Macrolide therapy for adult asthma may be more effective than placebo and could be a treatment option.
Topics: Adult; Humans; Macrolides; Quality of Life; Disease Progression; Asthma; Anti-Bacterial Agents; Adrenal Cortex Hormones
PubMed: 38211545
DOI: 10.1016/j.resinv.2023.12.015 -
Sexually Transmitted Infections Feb 2021In recent years, resistance in (MG) to first-line (azithromycin) and second-line (moxifloxacin) treatment has been increasingly reported worldwide, however, no data...
OBJECTIVES
In recent years, resistance in (MG) to first-line (azithromycin) and second-line (moxifloxacin) treatment has been increasingly reported worldwide, however, no data regarding the south of Spain are available.
METHODS
To determine resistance rates, MG-positive samples collected from June 2018 to June 2019 were analysed by sequencing the 23S rRNA and parC genes.
RESULTS
A total of 77 patients (24 men having sex with men (MSM), 30 heterosexual men and 23 women) were included. Resistance-associated mutations against macrolide and fluoroquinolones were found in 36.4% (95% CI 25.7% to 48.1%) and 9.1% (95% CI 3.7% to 17.8%) of the patients, respectively. Being MSM and having had another STI in the last year were significantly associated with macrolide-resistant MG infection, while no associations were found with resistance to fluoroquinolones.
CONCLUSIONS
Testing for resistance to first-line and second-line drugs against MG should be recommended for the general population and mandatory for the MSM population. We suggest that empiric azithromycin use for STI management should be avoided.
Topics: Adult; Anti-Bacterial Agents; Azithromycin; DNA Topoisomerase IV; Drug Resistance, Bacterial; Female; Fluoroquinolones; Heterosexuality; Homosexuality, Male; Humans; Macrolides; Male; Moxifloxacin; Mutation; Mycoplasma genitalium; RNA, Ribosomal, 23S; Sequence Analysis, DNA; Spain; Young Adult
PubMed: 32661071
DOI: 10.1136/sextrans-2019-054386 -
The Journal of International Medical... Feb 2022To analyse macrolide resistance and molecular characteristics of clinical isolates from western China, and to explore the relationship between macrolide-resistance and...
OBJECTIVE
To analyse macrolide resistance and molecular characteristics of clinical isolates from western China, and to explore the relationship between macrolide-resistance and genotypes.
METHODS
Susceptibilities of clinical isolates to erythromycin, azithromycin and clarithromycin were determined by epsilometer test (E-test). Isolated strains were sequenced to ascertain the presence of the 23S rRNA gene A2047G mutation. Strains were typed using multilocus antigen sequence typing, multilocus variable-number tandem-repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE).
RESULTS
Of 58 strains isolated in this study, 46 were macrolide-resistant and 12 were macrolide sensitive. All macrolide-resistant strains carried the A2047G mutation and were the //// genotype; the MLVA types were MT195 (19/58), MT55 (13/58) and MT104 (14/58), and the PFGE profiles were classified into BpSR23 (17/58) and BpFINR9 (29/58) types. None of the macrolide-sensitive strains carried the A2047G mutation; genotypes were ( or )////, and all were MT27. PFGE profiles differed from the macrolide-resistant strains.
CONCLUSIONS
clinical isolates from western China were severely resistant to macrolides. Genotypes differed between macrolide-resistant and macrolide-sensitive strains, and there may be a correlation between acquisition of macrolide resistance and changes in specific molecular types.
Topics: Anti-Bacterial Agents; Bordetella pertussis; Drug Resistance, Bacterial; Genotype; Humans; Macrolides; Whooping Cough
PubMed: 35225710
DOI: 10.1177/03000605221078782