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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 -
Clinical Infectious Diseases : An... Jun 2021The Infectious Diseases Society of America recommends either a fluoroquinolone or a macrolide as a first-line antibiotic treatment for Legionella pneumonia, but it is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The Infectious Diseases Society of America recommends either a fluoroquinolone or a macrolide as a first-line antibiotic treatment for Legionella pneumonia, but it is unclear which antibiotic leads to optimal clinical outcomes. We compared the effectiveness of fluoroquinolone versus macrolide monotherapy in Legionella pneumonia using a systematic review and meta-analysis.
METHODS
We conducted a systematic search of literature in PubMed, Cochrane, Scopus, and Web of Science from inception to 1 June 2019. Randomized controlled trials and observational studies comparing macrolide with fluoroquinolone monotherapy using clinical outcomes in patients with Legionella pneumonia were included. Twenty-one publications out of an initial 2073 unique records met the selection criteria. Following PRISMA guidelines, 2 reviewers participated in data extraction. The primary outcome was mortality. Secondary outcomes included clinical cure, time to apyrexia, length of hospital stay (LOS), and the occurrence of complications. The review and meta-analysis was registered with PROSPERO (CRD42019132901).
RESULTS
Twenty-one publications with 3525 patients met inclusion criteria. The mean age of the population was 60.9 years and 67.2% were men. The mortality rate for patients treated with fluoroquinolones was 6.9% (104/1512) compared with 7.4% (133/1790) among those treated with macrolides. The pooled odds ratio assessing risk of mortality for patients treated with fluoroquinolones versus macrolides was 0.94 (95% confidence interval, .71-1.25, I2 = 0%, P = .661). Clinical cure, time to apyrexia, LOS, and the occurrence of complications did not differ for patients treated with fluoroquinolones versus macrolides.
CONCLUSIONS
We found no difference in the effectiveness of fluoroquinolones versus macrolides in reducing mortality among patients with Legionella pneumonia.
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Fluoroquinolones; Humans; Legionella; Macrolides; Male; Middle Aged; Pneumonia
PubMed: 32296816
DOI: 10.1093/cid/ciaa441 -
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 -
Critical Care (London, England) May 2023Patients with community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU) have high mortality rates during the acute infection and up to ten years... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Patients with community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU) have high mortality rates during the acute infection and up to ten years thereafter. Recommendations from international CAP guidelines include macrolide-based treatment. However, there is no data on the long-term outcomes of this recommendation. Therefore, we aimed to determine the impact of macrolide-based therapy on long-term mortality in this population.
METHODS
Registered patients in the MIMIC-IV database 16 years or older and admitted to the ICU due to CAP were included. Multivariate analysis, targeted maximum likelihood estimation (TMLE) to simulate a randomised controlled trial, and survival analyses were conducted to test the effect of macrolide-based treatment on mortality six-month (6 m) and twelve-month (12 m) after hospital admission. A sensitivity analysis was performed excluding patients with Pseudomonas aeruginosa or MRSA pneumonia to control for Healthcare-Associated Pneumonia (HCAP).
RESULTS
3775 patients were included, and 1154 were treated with a macrolide-based treatment. The non-macrolide-based group had worse long-term clinical outcomes, represented by 6 m [31.5 (363/1154) vs 39.5 (1035/2621), p < 0.001] and 12 m mortality [39.0 (450/1154) vs 45.7 (1198/2621), p < 0.001]. The main risk factors associated with long-term mortality were Charlson comorbidity index, SAPS II, septic shock, and respiratory failure. Macrolide-based treatment reduced the risk of dying at 6 m [HR (95% CI) 0.69 (0.60, 0.78), p < 0.001] and 12 m [0.72 (0.64, 0.81), p < 0.001]. After TMLE, the protective effect continued with an additive effect estimate of - 0.069.
CONCLUSION
Macrolide-based treatment reduced the hazard risk of long-term mortality by almost one-third. This effect remains after simulating an RCT with TMLE and the sensitivity analysis for the HCAP classification.
Topics: Humans; Macrolides; Community-Acquired Infections; Pneumonia; Anti-Bacterial Agents; Intensive Care Units; Survival Analysis; Hospital Mortality; Hospitalization; Male; Female; Middle Aged; Aged; Aged, 80 and over; Treatment Outcome
PubMed: 37259125
DOI: 10.1186/s13054-023-04466-x -
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 -
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 -
Emerging Infectious Diseases May 2023Clindamycin and β-lactam antibiotics have been mainstays for treating invasive group A Streptococcus (iGAS) infection, yet such regimens might be limited for strains...
Clindamycin and β-lactam antibiotics have been mainstays for treating invasive group A Streptococcus (iGAS) infection, yet such regimens might be limited for strains displaying MLS phenotypes. We investigated 76 iGAS isolates from 66 patients in West Virginia, USA, during 2020-2021. We performed emm typing using Centers for Disease Control and Prevention guidelines and assessed resistance both genotypically and phenotypically. Median patient age was 42 (range 23-86) years. We found 76% of isolates were simultaneously resistant to erythromycin and clindamycin, including all emm92 and emm11 isolates. Macrolide resistance was conferred by the plasmid-borne ermT gene in all emm92 isolates and by chromosomally encoded ermA, ermB, and a single mefA in other emm types. Macrolide-resistant iGAS isolates were typically resistant to tetracycline and aminoglycosides. Vulnerability to infection was associated with socioeconomic status. Our results show a predominance of macrolide-resistant isolates and a shift in emm type distribution compared with historical reports.
Topics: Humans; Erythromycin; Anti-Bacterial Agents; Clindamycin; Macrolides; West Virginia; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Streptococcal Infections; Streptococcus pyogenes; Phenotype
PubMed: 37080963
DOI: 10.3201/eid2905.221421 -
Molecules (Basel, Switzerland) Aug 2021The solvatomorphism of the anthelmintic drug moxidectin is investigated, and a new solvatomorph with nitromethane is reported. Moreover, the hitherto unknown crystal...
The solvatomorphism of the anthelmintic drug moxidectin is investigated, and a new solvatomorph with nitromethane is reported. Moreover, the hitherto unknown crystal structures of the solvatomorphs with ethanol and 2-propanol are reported and discussed. The thermal characterization of these solvatomorphs through variable-temperature powder X-ray diffraction analysis (VT-PXRD) is also described, providing new insights into the crystallochemistry of this active pharmaceutical ingredient.
Topics: Crystallography, X-Ray; Hydrogen Bonding; Macrolides; Molecular Conformation; Powder Diffraction; Solvents; Temperature
PubMed: 34443452
DOI: 10.3390/molecules26164869 -
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