This study introduced Macrolid antibiotic class including effects, classification, pharmacokinetics, indication of treatment, and future prospects
Macrolides ; Pharmacokinetics

Diffuse panbronchiolitis is a new respiratory tract disease and was initially found in Japan. Strong association between race-dependent antigens and diffuse panbronchiolitis suggests a genetic predisposition to the disease. 14-member ring and 15-member ring macrolides have been proved to have significant therapeutical effect on diffuse panbronchiolitis. The discovery of diffuse panbronchiolitis and the advent of macrolide therapy for this disease suggests that clinicians should pay more attention to racial difference of some diseases and never overlook any accidental phenomenon in clinical practice.
Bronchiolitis ; drug therapy ; Humans ; Macrolides ; therapeutic use

Macrolide antibiotics are a class of broad-spectrum antibiotics with the macrolide as core nucleus. Recently, antibiotic pollution has become an important environmental problem due to the irregular production and abuse of macrolide antibiotics. Microbial degradation is one of the most effective methods to deal with antibiotic pollution. This review summarizes the current status of environmental pollution caused by macrolide antibiotics, the degradation strains, the degradation enzymes, the degradation pathways and the microbial processes for degrading macrolide antibiotics. Moreover, the critical challenges on the biodegradation of macrolide antibiotics were also discussed.
Anti-Bacterial Agents ; Biodegradation, Environmental ; Macrolides

The fcl gene encodes GDP-fucose synthase, which catalyzes two-step differential isomerase and reductase reactions in the synthesis of GDP-L-fucose from GDP-D-mannose. It also participates in the biosynthesis of amino sugar and ribose sugar, and is one of the key enzymes to regulate the metabolism of sugar and nucleotides in organisms. The presence of fcl gene in Saccharopolyspora pogona was found through sequencing result of genome. The mutant S. pogona-fcl and S. pogona-Δfcl were constructed by gene engineering technology. The results showed that the gene had an effects on growth and development, protein expression and transcriptional level, insecticidal activity, and biosynthesis of butenyl-spinosyn of Saccharopolyspora pogona. The results of HPLC analysis showed that the yield of butenyl-spinosyn in S. pogona-Δfcl was 130% compared with that in S. pogona, which reduced by 25% in S. pogona-fcl. The results of determination of insecticidal activity showed that S. pogona-Δfcl had a stronger insecticidal activity against Helicoverpa armigera than that of S. pogona, while the S. pogona-fcl had a lower insecticidal activity against Helicoverpa armigera compared with S. pogona. Scanning electron microscopy (SEM) was used to observe the morphology of the mycelia. It was found that the surface of the S. pogona-Δfcl was wrinkled, and the mycelium showed a short rod shape. There was no significant difference in mycelial morphology between S. pogona-fcl and S. pogona. Aboved all showed that deletion of fcl gene in S. pogona hindered the growth and development of mycelia, but was beneficial to increase the biosynthesis of butenyl-spinosyn and improve insecticidal activity. Whereas the fcl gene over-expression was not conducive to the biosynthesis of butenyl-spinosyn and reduced their insecticidal activity. SDS-PAGE results showed that the difference of protein expression among the three strains was most obvious at 96 hours, which was identified by real-time fluorescence quantitative polymerase chain reaction, the results showed that there were significant differences of related genes in transcriptional levels among the three strains. Based on the results of the study, a network metabolic control map was constructed to analyze the effect of fcl gene on growth and the regulation pathway of butenyl-spinosyn biosynthesis, which provided an experimental basis for revealing the regulation mechanism of butenyl-spinosyn biosynthesis and related follow-up studies.
Bacterial Proteins ; Genetic Engineering ; Insecticides ; Macrolides ; Saccharopolyspora

Chronic Disease ; Humans ; Macrolides ; therapeutic use ; Sinusitis ; drug therapy

BACKGROUND: Although the incidence of resistance to macrolides in group A streptococci (GAS) was low in the past, high incidences have now been reported from several countries. We tried to find out trends of the incidence of erythromycin-resistant GAS in Korea before and after adopting the separation of the dispensary from medical practice in the middle of the year 2000. METHODS: Five hundred thirty two isolates from children with suspected pharyngotonsillitis from 1998 through 2002 were serotyped by T-agglutination. Minimal inhibitory concentrations of 330 out of 532 isolates were determined by agar dilution methods. RESULTS: The prevalent T-serotypes were T12 (36.1%), T4 (12.8%), T1 (10.9%), T2/28 (8.8%), and nontypable (7.1%). Resistance rates to erythromycin (EM) by year were 46.2% in 1998, 18.4% in 1999, 15.4% in 2000, 27.6% in 2001, 36.5% in 2002. T12 in 1999 and 2000 were 36.4% and 25.9%, respectively, which seem to be lower than any other year. This relative low percentage of T12 is associated with increasing percentage of T1 in the same year. The frequency of T12, T1,and T4 were high in each group of isolates of Seoul and Masan. From this viewpoint, there was a similarity between the distribution of T-serotypes of both groups of Seoul and Masan. CONCLUSION: The frequency of serotype T12 and T4 of GAS were relatively high in Korea from 1998 through 2002. The low rate of EM resistance in 1999 and 2000 seemed to be caused by a sudden increase of T1. The increasing rate of EM resistance from 2000 to 2002 seemed to be caused by the increase in consumption of new macrolides and the increase of T12.
Agar ; Child ; Erythromycin ; Humans ; Incidence* ; Korea* ; Macrolides ; Seoul

14- to 16-membered macrolide antibiotics (MA) are clinically important anti-infective drugs. With the rapid emergence of bacterial resistance, there is an urgent need to develop novel MA to counter drug-resistant bacteria. The targeted optimization of MA can be guided by analyzing the interaction between the MA and its ribosomal targets, and the desired MA derivatives can be obtained efficiently when combining with the rapidly developed metabolic engineering approaches. In the past 30 years, metabolic engineering approaches have shown great advantages in engineering the biosynthesis of MA to create new derivatives and to improve their production. These metabolic engineering approaches include modification of the structural domains of the polyketide synthase (PKS) and post-PKS modification enzymes as well as combinatorial biosynthesis. In addition, the R&D (including the evaluation of its antimicrobial activities and the optimization through metabolic engineering) of carrimycin, a new 16-membered macrolide drug, are described in details in this review.
Anti-Bacterial Agents ; Bacteria/genetics* ; Macrolides ; Metabolic Engineering ; Polyketide Synthases

BACKGROUND: Although the incidence of resistance to macrolides in group A streptococci (GAS) was low in the past, high incidences have now been reported from several countries. We tried to find out trends of the incidence of erythromycin-resistant GAS in Korea before and after adopting the separation of the dispensary from medical practice in the middle of the year 2000. METHODS: Five hundred thirty two isolates from children with suspected pharyngotonsillitis from 1998 through 2002 were serotyped by T-agglutination. Minimal inhibitory concentrations of 330 out of 532 isolates were determined by agar dilution methods. RESULTS: The prevalent T-serotypes were T12 (36.1%), T4 (12.8%), T1 (10.9%), T2/28 (8.8%), and nontypable (7.1%). Resistance rates to erythromycin (EM) by year were 46.2% in 1998, 18.4% in 1999, 15.4% in 2000, 27.6% in 2001, 36.5% in 2002. T12 in 1999 and 2000 were 36.4% and 25.9%, respectively, which seem to be lower than any other year. This relative low percentage of T12 is associated with increasing percentage of T1 in the same year. The frequency of T12, T1,and T4 were high in each group of isolates of Seoul and Masan. From this viewpoint, there was a similarity between the distribution of T-serotypes of both groups of Seoul and Masan. CONCLUSION: The frequency of serotype T12 and T4 of GAS were relatively high in Korea from 1998 through 2002. The low rate of EM resistance in 1999 and 2000 seemed to be caused by a sudden increase of T1. The increasing rate of EM resistance from 2000 to 2002 seemed to be caused by the increase in consumption of new macrolides and the increase of T12.
Agar ; Child ; Erythromycin ; Humans ; Incidence* ; Korea* ; Macrolides ; Seoul

Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The research on tacrolimus production was mainly focused on biosynthesis methods, within which there are still some bottlenecks. This review summarizes the progress made in tacrolimus biosynthesis via modification of metabolic pathways and control of fermentation process, with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.
Tacrolimus ; Immunosuppressive Agents ; Fermentation ; Macrolides ; Anti-Bacterial Agents

OBJECTIVE: To compare the efficacy of Clarithromycin versus Methylprednisolone in the treatment of non-eosinophilic nasal polyposis.

DESIGN: Randomized Controlled Trial

SETTING: Tertiary Government Training Hospital

PARTICIPANTS: Forty  two (42) patients with Chronic Rhinosinusitis with determination of eosinophil count.  Both groups were further randomized into a treatment arm given Clarithromycin (CLA) 500mg/ day and another arm given Methylprednisolone (METH) 32 mg/ day tampering to 8 mg/ day for 15 days. All participants underwent pre- and post-treatment evaluation via anterior rhinoscopy, Sino-Nasal Outcome Test (SNOT-22) and Endoscopic Appearance (EA) Scoring. Date were encoded and subjected to statistical analysis using Mann-Whitney U test.

RESULTS: For the 9 participants in the non-eosinophilic group, 4 were given CLA and 5 were given METH. The CLA arm showed significant improvement in SNOT-22 scores by the 15th day (p= .007). The METH arm did not demonstrate significant improvement by the 7th (p= .44) or 15th day (p= .22). Comparison in the improvement in SNOT-22 scores between the two arms showed that on both 7th and 15th days, CLA outperformed METH (p= 0.26 and p= .004, respectively). For the EA scoring, both the CLA and METH groups significantly improved by the 7th (p= .27 and p= 0.017, respectively) and 15th day (p= .013 and p= .027, respectively). Comparison in the improvement of EA scores between the two arms showed significant difference on the 15th day (p= .01) with the CLA performing better than METH. Overall, the results suggest that the CLA arm performed significantly better than METH arm in the treatment of non-eosinophilic patients.

Of the 33 eosinophilic patients, 17 were given CLA and 16 were given METH. The CLA arm showed significant improvement in SNOT-22 scores by the 15th day (p< .001) while the METH arm both on 7th (p= .033) and 15th day (p< .001). Comparison of the improvement in SNOT-22 results between the two arms showed no significant difference (7th day p= .494; 15th day p= .587). For the EA scoring, both treatment groups showed significant improvement by the 7th and 15th day (p< .001). Comparison on the improvement in EA scores between the two arms showed significant difference (p< .001) on both 7th and 15th day, suggesting that METH was more effective than CLA. Overall, the results showed that both CLA and METH were effective in the treatment of eosinophilic nasal polyps. However, METH was significantly better than CLA in terms of superior EA scores.

CONCLUSION: In terms of improving symptoms and well-being, as well as decreasing nasal polyp size and reducing discharge and edema as reflected in superios SNOT 22 and EA scores, Clarithromycin was significantly more effective than Methylprednisolone in the treatment of non-eosinophilic nasal polyps. While both Clarithromycin and Methylprednisolone were shown to be effective in the treatment of eosinophilic nasal polyps, Methylprednisolone was significantly better in that Clarithromycin in terms of EA scores. A biopsy for tissue eosinophilic cell count prior to treatment is recommended to establish the predominant inflammatory cell in nasal polyps in order to provide appropriate targeted treatment, i.e. Clarithromycin for non-eosinophilic nasal polyps and Methylprednisolone for eosinophilic polyps.