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Frontiers in Cellular and Infection... 2023Traditional drug susceptibility testing cannot be performed in clinical laboratories due to the slow-growing characteristics of when cultured . Sanger sequencing is the...
BACKGROUND
Traditional drug susceptibility testing cannot be performed in clinical laboratories due to the slow-growing characteristics of when cultured . Sanger sequencing is the standard method for detecting drug resistance-associated mutations. It has been used in some laboratories to guide the choice of macrolide antibiotics for infected patients. Furthermore, resistance to fluoroquinolone has become another emerging clinical challenge.
OBJECTIVE
Sequencing analysis can detect unknown mutations, but it is time-consuming, requires professional analytical skills and the appropriate testing equipment. The main objective of this study was to establish a nested real-time PCR method for the simultaneous detection of and genotypes in relation to the macrolide and fluoroquinolone resistance.
RESULTS
105 MG-positive samples and 27 samples containing other pathogens were used for validation. The limit of the nested real-time PCR detection was 500 copies/reaction and there was no cross-reaction with , , , , , , and , but the assay cross-reacted with . Compared with sequencing results, the sensitivity of was 100% (95% CI; 93.3 -100), the specificity was 94.3% (95% CI; 79.4 - 99.0), the overall consistency was 98% (95% CI; 92.5 - 99.7) and value was 0.96 ( < 0.001); the sensitivity of was 100% (95% CI; 93.4 - 100), the specificity was 89.7% (95% CI; 71.5 - 97.3) and the overall consistency was 96.9% (95% CI; 90.7 - 99.2) with a value of 0.92 ( < 0.001).
CONCLUSIONS
The results of this sensitive and rapid alternative for identifying resistant genotypes of are intuitive and easy to interpret, especially for mixed MG populations. Although the relevant primers need further adjustment, this reliable method would provide an effective diagnostic tool for the selection of antibiotics in clinical practice.
Topics: Humans; Fluoroquinolones; Mycoplasma genitalium; RNA, Ribosomal, 23S; Real-Time Polymerase Chain Reaction; Macrolides; Microbial Sensitivity Tests; Drug Resistance, Bacterial; Mycoplasma Infections; Mycobacterium tuberculosis; Anti-Bacterial Agents; Mutation
PubMed: 37928183
DOI: 10.3389/fcimb.2023.1271392 -
Journal of the Formosan Medical... Jun 2020Mycobacterium avium complex (MAC) is the major pathologic nontuberculous mycobacteria causing lung disease (LD) in humans worldwide. Although the burden of MAC-LD has... (Review)
Review
Mycobacterium avium complex (MAC) is the major pathologic nontuberculous mycobacteria causing lung disease (LD) in humans worldwide. Although the burden of MAC-LD has increased over the past two decades, treatment remains difficult because of intolerance of long-term antibiotics, lack of adherence to guidelines, and disease recurrence. The current guidelines recommend antibiotic initiation for patients with MAC-LD and severe disease and in those with disease progression. Thus, physicians should consider antibiotic treatment for patients with MAC-LD and cavitary pulmonary lesions or symptomatic non-cavitary nodular bronchiectasis pattern at initial visits and also for those with clinical deterioration during follow-up. The standard three-drug regimen should be macrolide, rifamycin, and ethambutol. Physicians should monitor side effects in patients and maintain the regimen for 12 months, beginning from when sputum conversion has been obtained. With adherence to guideline-based therapy, treatment is successful in two thirds of treatment-naïve patients without macrolide resistance. Without adherence, macrolide resistance can occur, which leads to poor outcomes in patients with MAC-LD. Although the discovery of new treatment options is warranted, adherence to guidelines remains most crucial in treating patients with MAC-LD. It is worth mentioning that the majority of current recommendations are based on observational studies or small-scale clinical trials.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Lung Diseases; Macrolides; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies
PubMed: 32446754
DOI: 10.1016/j.jfma.2020.05.006 -
Otolaryngology--head and Neck Surgery :... Dec 2023To evaluate the efficacy and safety of macrolide antibiotics therapy in patients with chronic rhinosinusitis (CRS) receiving endoscopic sinus surgery. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate the efficacy and safety of macrolide antibiotics therapy in patients with chronic rhinosinusitis (CRS) receiving endoscopic sinus surgery.
DATA SOURCES
PubMed, Web of Science, Embase, and Cochrane Library.
REVIEW METHODS
The electronic databases were comprehensively searched on June 2, 2022, for randomized controlled trials on macrolide antibiotics in the treatment of patients undergoing CRS endoscopic surgery. The primary outcome measures were the sinonasal outcome test (SNOT) score and the visual analog scale (VAS) score. The secondary outcome measures were the nasal endoscopy score (NES), the sinus computed tomography score, and adverse events.
RESULTS
A total of 8 studies were included, involving 606 patients who used macrolide for a long time. Meta-analysis showed that no significant difference was observed in SNOT (standardized mean difference [SMD] = -0.13; 95% confidence interval [CI]: -0.38 to 0.13, I = 0%) and VAS (SMD = -0.10; 95% CI, -0.88 to 0.68, I = 81%) between the macrolide and placebo groups. However, macrolide outperformed the placebo in improving NES (SMD = -0.32; 95% CI, -0.62 to -0.03, I = 21%). The use of macrolide did not increase the incidence of adverse events.
CONCLUSION
Long-term use of macrolide after CRS surgery may not significantly improve the quality of life and disease severity of the patients but may play a role in improving postoperative NES in patients with CRS. There is still no sufficient evidence to determine whether the disease phenotype of CRS or the patient's race will affect the efficacy of long-term use of macrolide after CRS.
Topics: Humans; Macrolides; Quality of Life; Rhinitis; Nasal Polyps; Sinusitis; Anti-Bacterial Agents; Chronic Disease; Endoscopy
PubMed: 37548067
DOI: 10.1002/ohn.461 -
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 -
The Lancet. Microbe Dec 2023The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy,...
BACKGROUND
The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria.
METHODS
Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
FINDINGS
Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
INTERPRETATION
Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.
FUNDING
European Research Council.
Topics: Animals; Infant, Newborn; Humans; Treponema pallidum; Anti-Bacterial Agents; Azithromycin; Syphilis; Macrolides; Linezolid; Ceftriaxone; Globus Pallidus; Drug Resistance, Bacterial; Amoxicillin; Treponema
PubMed: 37827185
DOI: 10.1016/S2666-5247(23)00219-7 -
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 -
Pediatric Research Apr 2022Macrolide antibiotics are one of the most commonly used broad-spectrum antibiotics. They have an inhibitory effect on a variety of respiratory pathogens; besides, they... (Review)
Review
Macrolide antibiotics are one of the most commonly used broad-spectrum antibiotics. They have an inhibitory effect on a variety of respiratory pathogens; besides, they have non-anti-infective effects, including anti-inflammatory, regulating airway secretion, immune regulation, and other effects. A growing number of studies have shown that the non-anti-infective effects of macrolides have important and potential value in the treatment of pediatric chronic airway diseases; the therapy was described as "long-term, low-dose usage"; unfortunately, there is no guideline or consensus that applies to children. To better carry out the mechanism and clinical research of non-anti-infective effect and promote its rational use in children, the authors summarize the evidence of the usage of long-term, low-dose macrolide antibiotic therapy (LLMAT) in the treatment of chronic airway diseases in children and the progress in recent years. IMPACT: This review summarizes the evidence (mostly in recent 5 years) of the usage of long-term, low-dose macrolide antibiotic therapy in the treatment of chronic airway diseases. The recent studies and guidelines support and enrich the point that long-term, low-dose macrolide antibiotic therapy has potential benefit for children with severe asthma, CF, non-CF bronchiectasis, and BO, which provides clinical references and is of clinical interest. Long-term, low-dose macrolide antibiotic therapy has good safety, and no serious events have been reported; however, potential cardiac side effects and macrolide resistance should be clinically noted.
Topics: Anti-Bacterial Agents; Asthma; Bronchiectasis; Child; Drug Resistance, Bacterial; Humans; Macrolides; Pulmonary Disease, Chronic Obstructive
PubMed: 34120139
DOI: 10.1038/s41390-021-01613-4 -
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 -
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 -
Nature Communications Jul 2023Antibiotic resistance ABC-Fs (ARE ABC-Fs) are translation factors that provide resistance against clinically important ribosome-targeting antibiotics which are...
Antibiotic resistance ABC-Fs (ARE ABC-Fs) are translation factors that provide resistance against clinically important ribosome-targeting antibiotics which are proliferating among pathogens. Here, we combine genetic and structural approaches to determine the regulation of streptococcal ARE ABC-F gene msrD in response to macrolide exposure. We show that binding of cladinose-containing macrolides to the ribosome prompts insertion of the leader peptide MsrDL into a crevice of the ribosomal exit tunnel, which is conserved throughout bacteria and eukaryotes. This leads to a local rearrangement of the 23 S rRNA that prevents peptide bond formation and accommodation of release factors. The stalled ribosome obstructs the formation of a Rho-independent terminator structure that prevents msrD transcriptional attenuation. Erythromycin induction of msrD expression via MsrDL, is suppressed by ectopic expression of mrsD, but not by mutants which do not provide antibiotic resistance, showing correlation between MsrD function in antibiotic resistance and its action on this stalled complex.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Macrolides; Abducens Nerve Diseases; Accommodation, Ocular
PubMed: 37393329
DOI: 10.1038/s41467-023-39553-8