Lexithromycin

Roxithromycin is a broad-spectrum antibiotic widely used in human and livestock. It is continually released and accumulated in our natural environment. It exhibited an extreme resistance to microbial biodegradation and has a serious impact on ecosystem and human health. It is in urgent need of establishing a rapid and efficient method for the detection of environmental roxithromycin. This study was based on capture-SELEX to select aptamers against roxithromycin from an initial library containing randomized ssDNA sequences. Candidate aptamers were obtained by 16 rounds of capture-SELEX process. Competent clones were prepared for sequencing. Clone Ap01 was chosen for further characterization. SYBR Green I fluorescence assays showed high affinity with roxithromycin. The dissociation constant of Ap01 was 0.46 ± 0.08 μM. Ap01 bound specifically to roxithromycin with capable of distinguish from non-roxithromycin macrolides. There was no cross reaction with the detected non-macrolide compounds. Accordingly, a colorimetric aptasensor has been developed. It has been demonstrated that the detection limit achieved 0.077 μM. To proof the concept, detections of roxithromycin contained in tap water and lake water were evaluated. It laid a foundation for further study on the detection of roxithromycin in actual aquatic environments.

BACKGROUND Recently, some case reports have been published on the macrolide antimicrobials azithromycin and clarithromycin as the cause of thrombocytopenia. The publicly accessible databases of the European Medicine Agency and the WHO drug monitoring program contain dozens of reports of roxithromycin-associated thrombocytopenia. CASE REPORT We described the case of a 78-year-old woman presenting to our unit with petechial lesions of the palate, 2 hematomas of the tongue, and purpuric macules in the abdomen and in the left lower limb 4 days after a course of roxithromycin. She presented to the Emergency Department with 3 out-of-range blood test results: neutrophils (11 960/mL; range: 1500-7000/mL), platelet count (3000/mL; range: 150 000-400 000/mL), and lactate dehydrogenase (379 IU/L; range: 135-225 IU/L). Thrombocytopenia occurred in the absence of aggregates and observed nucleolated lymphocytes. Lymphoproliferative pathologies and thrombotic microangiopathy were excluded by the hematologist. To rule out neoplastic lesions, an abdominal ultrasound examination was made. Antibody screening was performed for antinuclear antibodies, extractable nuclear antigen, antineutrophil cytoplasmic antibodies (all negative), and for Parvovirus B-19 (IgM negative, IgG positive), as well as HHV-6 and HHV-8 (both negative), to exclude an autoimmune or viral etiology. She recovered after intravenous methylprednisolone 60 mg/day and intravenous-immunoglobulin therapy 400 mg/kg/day. After 9 days, the patient was discharged with resolution of skin and buccal lesions. Her platelet count was 515 000/mL. CONCLUSIONS To the best of our knowledge, this is the first case of roxithromycin-associated acute autoimmune thrombocytopenia reported in the medical literature. We suggest that clinicians should consider this drug to be among the possible causes of drug-induced thrombocytopenia.

Background:Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation and distortion of the smaller airways. Bacterial colonisation of the damaged airways leads to chronic cough and sputum production, often with breathlessness and further structural damage to the airways. Long-term macrolide antibiotic therapy may suppress bacterial infection and reduce inflammation, leading to fewer exacerbations, fewer symptoms, improved lung function, and improved quality of life. Further evidence is required on the efficacy of macrolides in terms of specific bacterial eradication and the extent of antibiotic resistance.Objectives:To determine the impact of macrolide antibiotics in the treatment of adults and children with bronchiectasis.Search methods:We identified trials from the Cochrane Airways Trials Register, which contains studies identified through multiple electronic searches and handsearches of other sources. We also searched trial registries and reference lists of primary studies. We conducted all searches on 18 January 2018.Selection criteria:We included randomised controlled trials (RCTs) of at least four weeks' duration that compared macrolide antibiotics with placebo or no intervention for the long-term management of stable bronchiectasis in adults or children with a diagnosis of bronchiectasis by bronchography, plain film chest radiograph, or high-resolution computed tomography. We excluded studies in which participants had received continuous or high-dose antibiotics immediately before enrolment or before a diagnosis of cystic fibrosis, sarcoidosis, or allergic bronchopulmonary aspergillosis. Our primary outcomes were exacerbation, hospitalisation, and serious adverse events.Data collection and analysis:Two review authors independently screened the titles and abstracts of 103 records. We independently screened the full text of 40 study reports and included 15 trials from 30 reports. Two review authors independently extracted outcome data and assessed risk of bias for each study. We analysed dichotomous data as odds ratios (ORs) and continuous data as mean differences (MDs) or standardised mean differences (SMDs). We used standard methodological procedures as expected by Cochrane.Main results:We included 14 parallel-group RCTs and one cross-over RCT with interventions lasting from 8 weeks to 24 months. Of 11 adult studies with 690 participants, six used azithromycin, four roxithromycin, and one erythromycin. Four studies with 190 children used either azithromycin, clarithromycin, erythromycin, or roxithromycin.We included nine adult studies in our comparison between macrolides and placebo and two in our comparison with no intervention. We included one study with children in our comparison between macrolides and placebo and one in our comparison with no intervention.In adults, macrolides reduced exacerbation frequency to a greater extent than placebo (OR 0.34, 95% confidence interval (CI) 0.22 to 0.54; 341 participants; three studies; I2= 65%; moderate-quality evidence). This translates to a number needed to treat for an additional beneficial outcome of 4 (95% CI 3 to 8). Data show no differences in exacerbation frequency between use of macrolides (OR 0.31, 95% CI 0.08 to 1.15; 43 participants; one study; moderate-quality evidence) and no intervention. Macrolides were also associated with a significantly better quality of life compared with placebo (MD -8.90, 95% CI -13.13 to -4.67; 68 participants; one study; moderate-quality evidence). We found no evidence of a reduction in hospitalisations (OR 0.56, 95% CI 0.19 to 1.62; 151 participants; two studies; I2= 0%; low-quality evidence), in the number of participants with serious adverse events, including pneumonia, respiratory and non-respiratory infections, haemoptysis, and gastroenteritis (OR 0.49, 95% CI 0.20 to 1.23; 326 participants; three studies; I2= 0%; low-quality evidence), or in the number experiencing adverse events (OR 0.83, 95% CI 0.51 to 1.35; 435 participants; five studies; I2= 28%) in adults with macrolides compared with placebo.In children, there were no differences in exacerbation frequency (OR 0.40, 95% CI 0.11 to 1.41; 89 children; one study; low-quality evidence); hospitalisations (OR 0.28, 95% CI 0.07 to 1.11; 89 children; one study; low-quality evidence), serious adverse events, defined within the study as exacerbations of bronchiectasis or investigations related to bronchiectasis (OR 0.43, 95% CI 0.17 to 1.05; 89 children; one study; low-quality evidence), or adverse events (OR 0.78, 95% CI 0.33 to 1.83; 89 children; one study), in those receiving macrolides compared to placebo. The same study reported an increase in macrolide-resistant bacteria (OR 7.13, 95% CI 2.13 to 23.79; 89 children; one study), an increase in resistance to Streptococcus pneumoniae (OR 13.20, 95% CI 1.61 to 108.19; 89 children; one study), and an increase in resistance to Staphylococcus aureus (OR 4.16, 95% CI 1.06 to 16.32; 89 children; one study) with macrolides compared with placebo. Quality of life was not reported in the studies with children.Authors' conclusions:Long-term macrolide therapy may reduce the frequency of exacerbations and improve quality of life, although supporting evidence is derived mainly from studies of azithromycin, rather than other macrolides, and predominantly among adults rather than children. However, macrolides should be used with caution, as limited data indicate an associated increase in microbial resistance. Macrolides are associated with increased risk of cardiovascular death and other serious adverse events in other populations, and available data cannot exclude a similar risk among patients with bronchiectasis.