• 약학회지
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• 제48권6호
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• pp.364-368
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• 2004

The prevalence of resistance to a range of macrolides was determined for clinical isolates of common respiratory pathogens using NCCLS testing methods and interpretative criter ia.71.4% of Streptococcus pneumoniae, 62.3% of Staphylococcus aureus, 50.8% of coagulase-negative staphylococci and 4.4% of Strpetococcus pyogenes were erythromycin resistant. Also, the rates of resistance to other macrolides and clindamycin in these clinical isolates were as high as to eryth -romycin. Almost all of the macrolide-resistant isolates were positive for erm of the methylase gene, or mef of the efflux gene.

• Archives of Pharmacal Research
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• 제28권11호
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• pp.1228-1232
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• 2005

Four compounds, including two novel macrolides, were isolated from an endophyte Streptomyces sp. Is9131 of Maytenus hookeri. Spectral data indicated that these compounds were dimeric dinactin (1), dimeric nonactin (2), cyclo-homononactic acid (3), and cyclo-nonactic acid (4). Bioassay results showed that dimeric dinactin had strong antineoplastic activity and antibacterial activity.

• 약학회지
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• 제41권4호
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• pp.530-532
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• 1997

The MICs of various macrolide, lincosamide and streptogramin B antibiotics against highly erythromycin-resistant Escherichia coli 209K strain were evaluated. E. coli 209K showed high MICs against 14-membered macrolides and the relatively weaker resistance to 16-membered macrolides, lincosamides and streptogramin B. The macrolide-phosphotransferase K from E. coli 209K showed greater substrate specificity to the 14-membered macrolide antibiotics than to the 16-membered macrolide antibiotics, lincosamide and streptogramin B. Therefore, it was considered that the high resistance was due to the macrolide-phosphotransferase K.

• Tuberculosis and Respiratory Diseases
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• 제81권1호
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• pp.80-87
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• 2018

Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of $T_H2$ process and increased $T_H1$ and/or $T_H17$ process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon ${\gamma}$, and tumor necrosis factor ${\alpha}$ in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.101.3-102
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• 2000

• Clinical and Experimental Pediatrics
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• 제51권10호
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• pp.1031-1037
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• 2008

Macrolide antimicrobial agents including erythromycin, roxithromycin, clarithromycin, and azithromycin are commonly used in the treatment of respiratory tract infections in children. Newer macrolides that have structural modifications of older drug erythromycin show improved change in the spectrum of activity, dosing, and administration. However, recent studies reported that increasing use of macrolide antibiotics is the main force driving the development of macrolide resistance in streptococci. In particular, azithromycin use is more likely to select for macrolide resistance with Streptococcus pneumoniae than is clarithromycin use, a possible reflection of its much longer half life. Recently, erythromycin resistance rates of S. pneumoniae and Streptococcus pyogenes are rapidly increasing in Korea. Two main mechanisms of acquired macrolide resistance have been described, altered binding site on the bacterial ribosome encoded by the ermB gene and active macrolide efflux pump encoded by the mef gene. Relationship between the susceptibility of S. pneumoniae and the response to macrolides has been shown in studies of acute otitis media, but less clear in cases of pneumonia. This article reviews the spectrum of activity, pharmacokinetic properties, mechanisms of action and resistance, and clinical implication of resistance on the treatment of respiratory tract infections in children.

• Clinical and Experimental Pediatrics
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• 제62권6호
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• pp.199-205
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• 2019

Although Mycoplasma pneumoniae pneumonia (MPP) has been generally susceptible to macrolides, the emergence of macrolide-resistant MPP (MRMP) has made its treatment challenging. MRMP rapidly spread after the 2000s, especially in East Asia. MRMP is more common in children and adolescents than in adults, which is likely related to the frequent use of macrolides for treating M. pneumoniae infections in children. MRMP is unlikely to be related to clinical, laboratory, or radiological severity, although it likely prolongs the persistence of symptoms and the length of hospital stay. Thereby, it causes an increased burden of the disease and poor quality of life for the patient as well as a societal socioeconomic burden. To date, the only alternative treatments for MRMP are secondary antimicrobials such as tetracyclines (TCs) or fluoroquinolones (FQs) or systemic corticosteroids; however, the former are contraindicated in children because of concerns about potential adverse events (i.e., tooth discoloration or tendinopathy). A few guidelines recommended TCs or FQs as the second-line drug of choice for treating MRMP. However, there have been no evidence-based guidelines. Furthermore, safety issues have not yet been resolved. Therefore, this article aimed to review the benefits and risks of therapeutic alternatives for treating MRMP in children and review the recommendations of international or regional guidelines and specific considerations for their practical application.

• 한국식품위생안전성학회지
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• 제28권1호
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• pp.19-23
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• 2013

본 논문에서는 축산물 중 닭고기 내 마크로라이드계(MLs) 항생물질(spiramycin, josamycin, tilmicosin, 그리고 tylosin) 4종을 분석하기 위하여, 액-액 추출 과정을 거쳐서 PDA 검출기가 장착된 액체크로마토그래피를 이용하여 MLs를 효율적으로 동시분석하는 방법을 확립하였다. 컬럼은 Unison UK-C18 ($150mm{\times}3mm$ id, $3{\mu}m$), 이동상 용매는 0.1% TFA와 0.1% TFA in ACN로 기울기 용리를 사용하였으며, 유속은 0.7 mL/min, 그리고, 주입량은 $10{\mu}L$로 설정하여 분석하였다. 확립된 분석조건으로, 표준검정 곡선은 $50-1000{\mu}g/kg$의 농도범위에서 상관계수가 0.9975 이상의 양호한 직선성을 나타내었으며, 회수율은 저, 중, 고농도로 첨가하여 분석한 결과, 80.4-99.1%를 나타내었다. 검출한계는 $8.8-19.6{\mu}g/kg$이었고, 정량한계는 $26.6-59.4{\mu}g/kg$이었으며, 일내(intra-day)와 일간(inter-day) 정밀도(CV%)는 0.9-13.2%, 2.4-13.1%이었다. 따라서, 확립된 분석방법은 축산물 중 닭고기 시료 내 MLs를 효과적으로 분석하는데 이용될 수 있을 것으로 사료된다.

• 한국미생물생명공학회:학술대회논문집
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• 한국미생물생명공학회 2002년도 학술발표대회
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• pp.18-25
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• 2002

The pikromycin biosynthetic system in Streptomyces venezuleae is unique for its ability to produce two groups of antibiotics that include the 12-membered ring macrolides methymycin and neomethymycin, and the 14-membered ring macrolides narbomycin and pikromycin. The metabolic pathway also contains two post polyketide-modification enzymes, a glycosyltransferase and P450 hydroxylase that have unusually broad substrate specificities. In order to explore further the substrate flexibility of these enzymes a series of hybrid polyketide synthases were constructed and their metabolic products characterized. The plasmid-based replacement of the multifunctional protein subunits of the pikromycin PKS in S. venezuelae by the corresponding subunits from heterologous modular PKSs resulted in recombinant strains that produce both 12- and 14-membered ring macrolactones with predicted structural alterations. In all cases, novel macrolactones were produced and further modified by the DesVII glycosyltransferase and PikC hydroxylase leading to biologically active macrolide structures. These results demonstrate that hybrid PKSs in S. venezuelae can produce a multiplicity of new macrolactones that are modified further by the highly flexible DesVII glycosyltransferase and PikC hydroxylase tailoring enzymes. This work demonstrates the unique capacity of the S. venezuelae pikromycin pathway to expand the toolbox of combinatorial biosynthesis and to accelerate the creation of novel biologically active natural products. The polyketide backbone of rifamycin B is assembled through successive condensation and ${\beta}$-carbonyl processing of the extender units by the modular rifamycin PKS. The eighth module, in the RifD protein, contains nonfunctional DH domain and functional KR domain, which specify the reduction of the ${\beta}$-carbonyl group resulting in the C-21 bydroxyl of rifamycin B. A four amino acid substitution and one amino acid deletion were introduced in the putative NADPH binding motif in the proposed KR domain encoded by rifD. This strategy of mutation was based on the amino acid sequences of the corresponding motif of the KR domain of module 3 in the RifA protein, which is believed dysfunctional, so as to introduce a minimum alteration and retain the reading frame intact, yet ensure loss of function. The resulting strain produces linear polyketides, from tetraketide to octaketide, which are also produced by a rifD disrupted mutant as a consequence of premature termination of polyketide assembly. Much of the structural diversity within the polyketide superfamily of natural products is due to the ability of PKSs to vary the reduction level of every other alternate carbon atom in the backbone. Thus, the ability to introduce heterologous reductive segments such as ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) into modules that naturally lack these activities would increase the power of the combinatorial biosynthetic toolbox. The dehydratase domain of module 7 of the rifamycin PKS, which is predicted to be nonfunctional in view of the sequence of the apparent active site, was replaced with its functional homolog from module 7 of rapamycin-producing polyketide synthase. The resulting mutant strain behaved like a rifC disrupted mutant, i.e., it accumulated the heptaketide intermediate and its precursors. This result points out a major difficulty we have encountered with all the Amycolatopsis mediterranei strain containing hybrid polyketide synthases: all the engineered strains prepared so far accumulate a plethora of products derived from the polyketide chain assembly intermediates as major products instead of just analogs of rifamycin B or its ansamycin precursors.

• 한국미생물·생명공학회지
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• 제36권4호
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• pp.360-365
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• 2008

식품 내의 잔류 항생물질의 검사는 주로 미생물의 생육 억제 여부를 통한 생물학적인 분석을 이용한다. 이러한 방법은 여러 가지 계열의 항생제들에 대한 미생물의 민감성을 토대로 이용되고 있다. 그러나 현재 사용하고 있는 미생물들로는 동물용의약품으로 허가되어 식용동물에 사용되고 있는 점점 다양해지는 항생제 및 합성항균제를 식품에서 모두 검출할 수는 없다는 한계가 있다. 그러므로 본 연구는 검출 가능한 항생제 및 합성항균제 계열의 범위를 확대하고, 각 약품별 감도를 증진시키기 위한 새로운 방법들을 조사하였다. B. megaterium ATCC 9885, B. subtilis ATCC 6633, B. cereus ATCC l1778 and Geobacillus stearothermophilus (B. stearothermophilus) ATCC 10149를 사용한 검사의 민감성은 macrolides, quinolones와 monensin, chloramphenicol에 대한 검출 감도가 낮았다. 반면에 M. luteus(K. rhizophila) ATCC 9341는 macrolides에 대한 높은 검출 감도를 나타냈고, E. coli ATCC l1303는 quinolones와 aminoglycosides에 대한 높은 민감성을 나타냈다. 결론적으로, 두 균주의 추가로 검출가능한 항생제 및 합성항균제의 범위를 확대하였으며, 검출감도를 높일 수 있게 되었다.