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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 -
European Journal of Pediatrics Jul 2024Mycoplasma pneumoniae (MP) is an important cause of community-acquired pneumonia in children and young adolescents. Despite macrolide antibiotics effectiveness as a... (Review)
Review
UNLABELLED
Mycoplasma pneumoniae (MP) is an important cause of community-acquired pneumonia in children and young adolescents. Despite macrolide antibiotics effectiveness as a first-line therapy, persistence of fever and/or clinical deterioration sometimes may complicate treatment and may even lead to severe systemic disease. To date, there is no consensus on alternative treatment options, optimal dosage, and duration for treating severe, progressive, and systemic MP pneumonia after macrolide treatment failure. Macrolide-resistant MP pneumonia and refractory MP pneumonia are the two major complex conditions that are clinically encountered. Currently, the vast majority of MP isolates are resistant to macrolides in East Asia, especially China, whereas in Europe and North America, whereas in Europe and North America prevalence is substantially lower than in Asia, varying across countries. The severity of pneumonia and extrapulmonary presentations may reflect the intensity of the host's immune reaction or the dissemination of bacterial infection. Children infected with macrolide-resistant MP strains who receive macrolide treatment experience persistent fever with extended antibiotic therapy and minimal decrease in MP-DNA load. Alternative second-line agents such as tetracyclines (doxycycline or minocycline) and fluoroquinolones (ciprofloxacin or levofloxacin) may lead to clinical improvement after macrolide treatment failure in children. Refractory MP pneumonia reflects a deterioration of clinical and radiological findings due to excessive immune response against the infection. Immunomodulators such as corticosteroids and intravenous immunoglobulin (IVIG) have shown promising results in treatment of refractory MP pneumonia, particularly when combined with appropriate antimicrobials. Corticosteroid-resistant hyperinflammatory MP pneumonia represents a persistent or recrudescent fever despite corticosteroid therapy with intravenous methylprednisolone at standard dosage.
CONCLUSION
This report summarizes the clinical significance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drugs, with a stepwise approach to the management of MP pneumonia recommended from the viewpoint of clinical practice.
WHAT IS KNOWN
• Although MP pneumonia is usually a benign self-limited infection with response macrolides as first line therapy, severe life-threatening cases may develop if additional treatment strategies are not effectively implemented. • Macrolide-resistant and refractory MP pneumonia are two conditions that may complicate the clinical course of MP pneumonia, increasing the risk for exacerbation and even death.
WHAT IS NEW
• This report summarizes the clinical relevance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drug therapies. • A practical stepwise approach to the management of MP pneumonia is developed based on a comprehensive analysis of existing evidence and expert opinion.
Topics: Humans; Pneumonia, Mycoplasma; Anti-Bacterial Agents; Child; Macrolides; Mycoplasma pneumoniae; Drug Resistance, Bacterial; Community-Acquired Infections; Adolescent
PubMed: 38634891
DOI: 10.1007/s00431-024-05519-1 -
JAMA Jul 2023
Topics: Humans; Infant, Newborn; Azithromycin; Neonatal Sepsis; Female; Pregnancy; Anti-Bacterial Agents; Peripartum Period
PubMed: 37432437
DOI: 10.1001/jama.2023.8328 -
Trends in Microbiology Dec 2023Antibiotics often contain ester bonds. The macrocyclic lactones of macrolides are pre-eminent examples in which ester bonds are essential to the form and function of...
Antibiotics often contain ester bonds. The macrocyclic lactones of macrolides are pre-eminent examples in which ester bonds are essential to the form and function of antibiotics. Bacterial macrolide esterases that hydrolyze these macrocyclic lactones to confer antimicrobial resistance (AMR) are the topic of this forum. We provide insight into their role in agricultural systems and discuss their emergence and their potential extensibility to bioremediation efforts.
Topics: Macrolides; Esterases; Anti-Bacterial Agents; Lactones; Esters; Drug Resistance, Bacterial
PubMed: 37689489
DOI: 10.1016/j.tim.2023.08.008 -
Journal of Global Antimicrobial... Sep 2023Mycobacterium avium (M. avium) complex bacteria cause opportunistic infections in humans. Treatment yields cure rates of 60% and consists of a macrolide, a rifamycin,...
OBJECTIVES
Mycobacterium avium (M. avium) complex bacteria cause opportunistic infections in humans. Treatment yields cure rates of 60% and consists of a macrolide, a rifamycin, and ethambutol, and in severe cases, amikacin. Mechanisms of antibiotic tolerance remain mostly unknown. Therefore, we studied the contribution of efflux and amikacin modification to antibiotic susceptibility.
METHODS
We characterised M. avium ABC transporters and studied their expression together with other transporters following exposure to clarithromycin, amikacin, ethambutol, and rifampicin. We determined the effect of combining the efflux pump inhibitors berberine, verapamil and CCCP (carbonyl cyanide m-chlorophenyl hydrazone), to study the role of efflux on susceptibility. Finally, we studied the modification of amikacin by M. avium using metabolomic analysis.
RESULTS
Clustering shows conservation between M. avium and M. tuberculosis and transporters from most bacterial subfamilies (2-6, 7a/b, 10-12) were found. The largest number of transporter encoding genes was up-regulated after clarithromycin exposure, and the least following amikacin exposure. Only berberine increased the susceptibility to clarithromycin. Finally, because of the limited effect of amikacin on transporter expression, we studied amikacin modification and showed that M. avium, in contrast to M. abscessus, is not able to modify amikacin.
CONCLUSION
We show that M. avium carries ABC transporters from all major families important for antibiotic efflux, including homologues shown to have affinity for drugs included in treatment. Efflux inhibition in M. avium can increase susceptibility, but this effect is efflux pump inhibitor- and antibiotic-specific. Finally, the lack of amikacin modifying activity in M. avium is important for its activity.
Topics: Humans; Amikacin; Mycobacterium avium; Clarithromycin; Ethambutol; Berberine; Anti-Bacterial Agents; Mycobacterium avium Complex; Membrane Transport Proteins; Mycobacterium tuberculosis; ATP-Binding Cassette Transporters
PubMed: 37453496
DOI: 10.1016/j.jgar.2023.07.007 -
Nature Communications Jul 2023The ever-growing rise of antibiotic resistance among bacterial pathogens is one of the top healthcare threats today. Although combination antibiotic therapies represent...
The ever-growing rise of antibiotic resistance among bacterial pathogens is one of the top healthcare threats today. Although combination antibiotic therapies represent a potential approach to more efficiently combat infections caused by susceptible and drug-resistant bacteria, only a few known drug pairs exhibit synergy/cooperativity in killing bacteria. Here, we discover that well-known ribosomal antibiotics, hygromycin A (HygA) and macrolides, which target peptidyl transferase center and peptide exit tunnel, respectively, can act cooperatively against susceptible and drug-resistant bacteria. Remarkably, HygA slows down macrolide dissociation from the ribosome by 60-fold and enhances the otherwise weak antimicrobial activity of the newest-generation macrolide drugs known as ketolides against macrolide-resistant bacteria. By determining a set of high-resolution X-ray crystal structures of drug-sensitive wild-type and macrolide-resistant Erm-methylated 70S ribosomes in complex with three HygA-macrolide pairs, we provide a structural rationale for the binding cooperativity of these drugs and also uncover the molecular mechanism of overcoming Erm-type resistance by macrolides acting together with hygromycin A. Altogether our structural, biochemical, and microbiological findings lay the foundation for the subsequent development of synergistic antibiotic tandems with improved bactericidal properties against drug-resistant pathogens, including those expressing erm genes.
Topics: Macrolides; Anti-Bacterial Agents; Cinnamates; Hygromycin B; Ketolides; Protein Synthesis Inhibitors; Bacteria; Drug Resistance, Bacterial
PubMed: 37452045
DOI: 10.1038/s41467-023-39653-5 -
Chembiochem : a European Journal of... Mar 2024Lincosamides are naturally occurring antibiotics isolated from Streptomyces sp. Currently, lincomycin A and its semisynthetic analogue clindamycin are used as clinical... (Review)
Review
Lincosamides are naturally occurring antibiotics isolated from Streptomyces sp. Currently, lincomycin A and its semisynthetic analogue clindamycin are used as clinical drugs. Due to their unique structures and remarkable biological activities, derivatizations of lincosamides via semi-synthesis and biosynthetic studies have been reported. This review summarizes the structures and biological activities of lincosamides, and the recent studies of lincosamide biosynthetic enzymes.
Topics: Anti-Bacterial Agents; Lincosamides; Lincomycin; Macrolides
PubMed: 38165257
DOI: 10.1002/cbic.202300840 -
Clinical Infectious Diseases : An... Nov 2023Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change.
BACKGROUND
Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change.
METHODS
We initiated surveillance in sexual health clinics in 6 cities, selecting a quota sample of urogenital specimens tested for gonorrhea and/or chlamydia. We abstracted patient data from medical records and detected MG and macrolide-resistance mutations (MRMs) by nucleic acid amplification testing. We used Poisson regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs, adjusting for sampling criteria (site, birth sex, symptom status).
RESULTS
From October-December 2020 we tested 1743 urogenital specimens: 57.0% from males, 46.1% from non-Hispanic Black persons, and 43.8% from symptomatic patients. MG prevalence was 16.6% (95% CI: 14.9-18.5%; site-specific range: 9.9-23.5%) and higher in St Louis (aPR: 1.9; 1.27-2.85), Greensboro (aPR: 1.8; 1.18-2.79), and Denver (aPR: 1.7; 1.12-2.44) than Seattle. Prevalence was highest in persons <18 years (30.4%) and declined 3% per each additional year of age (aPR: .97; .955-.982). MG was detected in 26.8%, 21.1%, 11.8%, and 15.4% of urethritis, vaginitis, cervicitis, and pelvic inflammatory disease (PID), respectively. It was present in 9% of asymptomatic males and 15.4% of asymptomatic females, and associated with male urethritis (aPR: 1.7; 1.22-2.50) and chlamydia (aPR: 1.7; 1.13-2.53). MRM prevalence was 59.1% (95% CI: 53.1-64.8%; site-specific range: 51.3-70.6%). MRMs were associated with vaginitis (aPR: 1.8; 1.14-2.85), cervicitis (aPR: 3.5; 1.69-7.30), and PID cervicitis (aPR: 1.8; 1.09-3.08).
CONCLUSIONS
MG infection is common in persons at high risk of sexually transmitted infections; testing symptomatic patients would facilitate appropriate therapy. Macrolide resistance is high and azithromycin should not be used without resistance testing.
Topics: Female; Humans; Male; Anti-Bacterial Agents; Urethritis; Mycoplasma genitalium; Uterine Cervicitis; Sexual Health; Macrolides; Drug Resistance, Bacterial; Pelvic Inflammatory Disease; Vaginitis; Mycoplasma Infections; Prevalence
PubMed: 37402645
DOI: 10.1093/cid/ciad405 -
Research in Social & Administrative... Aug 2023Antimicrobial resistance (AMR) is a global healthcare challenge that governments and health systems are tackling primarily through antimicrobial stewardship (AMS). This...
Antimicrobial resistance (AMR) is a global healthcare challenge that governments and health systems are tackling primarily through antimicrobial stewardship (AMS). This should, improve antibiotic use, avoid inappropriate prescribing, reduce prescription numbers, aligning with national/international AMS targets. In primary care in the United Kingdom (UK) antibiotics are mainly prescribed for patients with urinary and respiratory symptoms (22.7% and 46% of all antibiotic prescriptions respectively). This study aimed to capture the time-series trends (2014-2022) for commonly prescribed antibiotics for respiratory and urinary tract infections in primary care in England. Trends for Amoxicillin, Amoxicillin sodium, Trimethoprim, Clarithromycin, Erythromycin, Erythromycin ethylsuccinate, Erythromycin stearate, Doxycycline hyclate, Doxycycline monohydrate and Phenoxymethylpenicillin (Penicillin V) were determined. In doing so providing evidence regarding meeting UK antibiotic prescribing rate objectives (a 15% reduction in human antibiotic use 2019-2024). Time series trend analysis of 62,949,272 antibiotic prescriptions from 6,370 General Practices in England extracted from the National Health Service (NHS) Business Services Authority web portal were explored. With additional investigation of prescribing rate trends by quintiles of the Index of Multiple Deprivation (IMD). Overall, there is a downwards trend in antibiotic prescribing for those explored. There is an association between IMD, geographical location, and higher antibiotic prescribing levels (prescribing hot spots). England has a well-documented North-South divide of health inequalities, this is reflected in antibiotic prescribing. The corona virus pandemic (COVID-19) impacted on AMS, with a rise in doxycycline and trimethoprim prescriptions notable in higher IMD areas. Since then, prescribing appears to have returned to pre-pandemic levels in all IMDs and continued to decline. AMS efforts are being adhered to in primary care in England. This study provides further evidence of the link between locality and poorer health outcomes (reflected in higher antibiotic prescribing). Further work is required to address antibiotic use in hot spot areas.
Topics: Humans; Anti-Bacterial Agents; State Medicine; COVID-19; Amoxicillin; Doxycycline; Inappropriate Prescribing; Penicillin V; Trimethoprim; Erythromycin; Primary Health Care; Practice Patterns, Physicians'
PubMed: 37183105
DOI: 10.1016/j.sapharm.2023.05.001 -
Respiratory Medicine Oct 2023Macrolide-resistant Mycobacterium avium complex (MAC) disease is very difficult to cure. Macrolide-resistance emerges in patients and is largely preventable by...
BACKGROUND
Macrolide-resistant Mycobacterium avium complex (MAC) disease is very difficult to cure. Macrolide-resistance emerges in patients and is largely preventable by appropriate screening and treatment practices.
METHODS
Patients with macrolide-resistant MAC isolates between March 2019 and March 2022 were retrieved from the mycobacteriology reference laboratory database at Radboudumc, Nijmegen, the Netherlands. Clinical consultation reports were extracted from the database to assess the cause of macrolide resistance.
RESULTS
Sixteen patients with macrolide-resistant MAC disease were included, from a total of 815 patients with MAC isolates (2%); Macrolide monotherapy in bronchiectasis or CF was the most frequent cause of development of macrolide-resistance MAC disease (n = 8; 50%). Short (n = 3; mean duration 9 months, range 6-12) or guideline non-compliant (n = 2) treatment regimens and patient non-adherence (n = 2) were other key causes of macrolide-resistance.
CONCLUSIONS
Macrolide monotherapy after inappropriate screening is the most frequent cause of macrolide-resistant Mycobacterium avium complex disease in the Netherlands. Educational efforts are needed to prevent this.
Topics: Humans; Mycobacterium avium Complex; Anti-Bacterial Agents; Macrolides; Mycobacterium avium-intracellulare Infection; Drug Resistance, Bacterial; Lung Diseases
PubMed: 37481170
DOI: 10.1016/j.rmed.2023.107366