• Microbiology and Biotechnology Letters
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• v.31 no.2
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• pp.201-204
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• 2003

Glycopeptide antibiotics, teicoplanin was purified from a mutant strain of Actinoplanes teichomyceticus ATCC31121, A. teichomyceticus MSL2211. We developed a simple procedure to separate and purify the teicoplanin from the fermentation broth. Teicoplanin was purified by two-step purification system, hydrophobic adsorption and sugar affinity chromatography in combination with HPLC analysis based on the properties of hydrophobic acyl chain and sugar moiety in teicoplanin. Teicoplanin was separated from the culture broth by Diaion HP-20 and further purified by concanavalin A affinity column chromatography. As an adsorbent resin, Diaion HP-20 in broth eliminated toxic effects on growth, reduced feedback repression of teicoplanin production, and assisted In rapid recovery of teicoplanin. The teicoplanin displayed the final yield of 80% and 95% of purity.

• Korean Journal of Microbiology
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• v.37 no.4
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• pp.299-304
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• 2001

Teicoplanin is a kind of glycopeptide antibiotics produced by Actinoplanes teichomyceticus, and used in the clinical antibiotic such as vancomycin against methicillin-resistant Stabphylococcus aureus (MRSA). Actino planes teichomyceticus ATCC 31121 was mutated with UV to obtain a superior mutant strain with increased level of teicoplanin production. In this investigation, lethal curve was obtained and the optimal condition to induce mutagenesis was determined to isolate the desirable mutant strain. It was also confirmed that teicoplanin activities by agar diffusion method was compared with the parent strain. One mutant strain, T991014-1 with the highest productivity, was finally selected, and was characterized through the various tests such as amylase activity, protease activity, halotolerance, antibiotic resistance, autotoxicity, and productivity. Ad fermentation characteristics of the mutant strain were also studied.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.325-328
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• 2001

Teicoplanin is a glycopeptide antibiotic produced by Actinoplanes teichomyceticus novo sp. A TCC 31121. It is active against Gram-positive bacteria and it is under evaluation for use in man. Teicoplanin mixture in fermentation broth contains major amounts of teicoplanin $A_1$ and $A_2$ and a minor amount tcicoplanin of $A_3$. Commercial teicoplanin product is composed of five major components of very similar polarity, designated T-$A_2$-l, 2, 3, 4 and 5, and the more polor component, designated T -$A_3$. The culture conditions were studied in order that hydrophilic teicoplanin $A_2$ components are more produced but hydrophobic teicoplanin $A_1$ with lower bioactivity are less produced in submerged culture. Effects of culture pH and nutrients on the biosynthes ratio of teicoplanin $A_1$ and $A_2$ were confirmed in flask culture using MOPS buffer system through TLC, bioautography and bioassay. It was elucidated that optimal pH is 7.4 for teicoplanin $A_2$ biosynthesis but is 5.2 for teicoplanin $A_1$ biosynthesis, and that trace elements stimulate $A_2$ production but malt extract stimulate $A_1$production.

• Korean Journal of Clinical Pharmacy
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• v.11 no.1
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• pp.19-29
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• 2001

Teicoplanin, a glycopeptide antibiotic, has potential for use as an alternative to vancomycin in the treatment of gram-positive bacterial infections. However, unlike vancomycin, there is a lack of study on teicoplanin's efficacy and safety and the guideline for its use is not available, yet. The objective of this study was to investigate and evaluate the pattern of teicoplanin usage in a university hospital. A retrospective study was performed on 72 adult patients, who took teicoplanin for 3 continuous days at D. University hospital from 1 January 1999 to 30 June 2000. The microorganisms treated with teicoplanin were methicillin-resistant Staphylocorcus aureus $(69\%)$, coagulase-negative Staphylococci $(12\%)$, Enterococcus $(4\%)$, vancomycin-resistant Enterococci $(2\%)$, Streptococci $(2\%)$, and Bacillus $(1\%)$. The types of infection treated with teicoplanin were surgical wound infection $(58\%)$, lower respiratory infection $(11\%)$, bactremia $(7\%)$, urinary tract infection $(5\%)$, pleural fluid infection $(4\%)$, and peritoneal fluid infection $(2\%)$. The mean duration of teicoplanin usage was 16.5 days and teicoplanin was used with 1.4 other antibiotics, which were aminoglycosides (isepamicin, amikacin, netilmicin, astromicin) or quinolones (ciprofloxacin, tosufloxacin) or the third generation cephalosporin (ceftazidime). Only 24 cases $(28.6\%)$ met with the criteria for the justification of use, and the rest of 60 cases $(71.4\%)$ did not meet the criteria. In 84 cases $(100\%)$, blood culture tests were performed prior to the initial dose of teicoplanin. In 83 cases $(99\%)$, serum creatinine were conducted before the initial doses. In 45 cases $(53.6\%)$, serum creatinine was monitored at least twice weekly. In 55 cases $(65.5\%)$, WBC was tested at least twice weekly. In 84 cases $(100\%)$, body temperature was monitored at least once per nursing shift. In 15 cases out of 56 cases, maximum temperature decreased at least 1 degree within 3 days of teicoplanin use. In 15 case out of 35 cases, WBC values were within the normal range after treatment. In 23 cases $(27.4\%)$, dosage regimen was appropriate. Drug-related adverse effects were reported in 13 cases. Nephrotoxicity (progressively increasing SCr. or sustained SCr increase of $\geq$0.5 mg/dl from baseline) was noted in five cases. Neutropenia (absolute neutrophil count <1,500 $cells/mm^3$) was noted in one case and eosinophilia (total eosinophil count >350 $cells/mm^3$) was noted in seven cases. A more strict control on use of teicoplanin is required, considering that teicoplanin is categorized as one of restricted antibiotics.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.57-57
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• 1992

Teicoplanin은 actinoplanes teicomyceticus의 발효산물로서 vancomycin과 같은 glycopeptide 계열의 항균제이며, 그 작용기전은 세포벽 합성과정중 peptidoglycan의 중합을 억제하는 것으로 vancomycin과 유사하나 vancomycin과 달리 근육에 주사할 수 있으며 "red man's syndrome"이 생기지 않고 vancomycin보다 반감기가 길다. 그람양성균 감염증에 대한 teicoplanin의 효능 및 안전성을 조사하기 위하여, 그람양성균에 의한 감염증 또는 그람양성균과 그람음성균에 의한 혼합감염증이 확인되거나 의심되었던 환자 46명을 대상으로 teicoplanin과 vancomycin을 투여하였다. 투약 환자중 임상적인 반응을 평가할 수 있는 환자의 수는 vancomycin의 경우 투약환자 22명중 21명, teicoplanin의 경우 24명중 19명이였다. Vancomycin군중 임상적 반응의 평가에서 제외된 1명은 수술 후 흉막강에 MRSA 에 의한 농양으로 투약 29일째에 뇌출혈로 사망하였던 예로, 추적-배양검사에서는 MRSA가 제거 되었다. Teicoplanin군에서는 항균제 투여 중 간경변증에 의한 식도출혈 1예, 수술후 위장관 출혈 1예, 뇌 색전중 1예가 사망하였고, 1예는 Teicoplanin에 의한 심한 피부발진으로, 다른 1예는 봉와직염의 임상진단이 조직검사결과 악성종양의 근육침범으로 밝혀져 투약을 중단하였다.

• 한국생물공학회:학술대회논문집
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• 2000.04a
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• pp.299-302
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• 2000

Actinoplanes teichomyceticus ATCC 31121 was mutated with UV to obtain a superior mutant strain with increasing level of teicoplanin production. In this investigation lethal curve was obtained and the optimal condition to induce mutagenesis was determined and to isolate the desirable mutant strain. It was also confirmed that teicoplanin activities by agar diffusion method to be compared to the mother strain. One mutant strain, T991014-1 that had the highest teicoplanin productivity was finally selected for further investigation including fermentation pattern. The mutant was characterized by the various tests such as amylase activity, protease activity, antibiotic resistance, autotoxicity, and productivity.

• Journal of Microbiology and Biotechnology
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• v.15 no.4
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• pp.787-791
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• 2005

Mutation and its pilot-scale fermentation were conducted for the production of teicoplanin from Actinoplanes teichomyceticus. The fermentation medium was optimized by replacement and Plackett-Burman experimental design. A maximum production of 1,500 mg/l teicoplanin was obtained by pilot-scale fermentation in an optimized medium containing (g/l): 30 g maltodextrin, 5 g glucose, 5 g yeast extract, 5 g soybean meal, 0.5 g $MgSO_4{\cdot}7H_2O$, 0.1 g NaCl, 0.1 g $CaCl_2{\cdot}2H_2O$, and 50 g Diaion HP-20. The production of teicoplanin was improved 3-fold from the parental strain by mutation, media optimization, and fermentation, and laboratory-scale fermentation was successfully demonstrated in a pilot-scale fermenter for the industrial production of teicoplanin.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.331-331
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• 1994

최근 개발된 Teicoplanin은 glycopeptide계의 항생제로서 vancomycin과 그 작용 기전이 비슷하지만, 근육 주사가 가능하고, 반감기가 길어서 하루 한번 주사하여도 되며, 빨리 주입하더라도 red man syndrome이생기지 않는 장점이 있다. 이 연구의 목적은 그람 양성균에 의한 감염증을 치료하는데 teicoplanin이 효과적이고 안전한지를 vancomycin과 비교하는 것이다. 대상 환자 및 방법: 서울대학교병원에 입원하여 그람 양성균 감염증이 확인되거나 강력히 의심되는 환자를 대상으로 하였다. 감염증의 종류는 패혈증, 골수염, 하기도 감염증, 감염성 관절염, 피부 및 연조직 감염증, 요로 감염증으로 하였다. 대상 환자를 무작위로 teicoplanin또는 vancomycin군에 무작위 배정하였다. Teinoplanin은 처음에 loading을 위하여 400mg씩 12시간마다 3회 주사하고 이후에는 증증 감염이면 하루에 400mg, 중등중이면 200mg씩을 주사하였다. Vancomycin은 500mg을 6시간마다 또는 1. 0g을 12시간마다 정맥주사하였다. 치료 기간은 요로 감염증 5-10일, 하기도 감염증 5-10일, 패혈증 14-21일, 골수염 21-42일, 세균성 관절염 21-42일, 피부 및 연조직 감염증 5-10일로 하였다.

• Journal of Microbiology and Biotechnology
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• v.14 no.3
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• pp.612-619
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• 2004

A competitive direct enzyme-linked immunosorbent assay (cdELISA) was developed for selective and rapid detection of a glycopeptide antibiotic, teicoplanin (TP). TP was conjugated to bovine serum albumin (BSA) for use as an immunogen. Repeated subcutaneous injections of 0.5 mg of the conjugate was effective in generating specific polyclonal antibody (PAb) toward TP in rabbits, as determined by cdELISA. TP-horseradish peroxidase conjugate (TP-HRP) was used as an enzyme marker. The cdELISA was developed based on a competition reaction between TP-BSA PAb and TP-HRP conjugate. The TP-BSA PAb was highly sensitive (detection limit, 0.3 ng/ml and specific toward teicoplanin, showing no cross-reactivity to other glycopeptide antibiotics including vancomycin. There were good correlations ($r^2$=0.84 and 0.76, respectively) between cdELISA and microbiological assay, and high-performance liquid chromatography. The cdELISA system developed in this work is expected to be useful not only for selective and rapid monitoring of TP but also for study of TP pharmacokinetics.

• Quality Improvement in Health Care
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• v.3 no.2
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• pp.26-35
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• 1997

Background : Glycopeptide antibiotics are the only drugs for treatment of infections due to beta-lactam-resistant Gram-positive bacteria. As the incidence of infection and colonization with vancomycin-resistant enterococci(VRE) rapidly increases, the hospital infection control practices advisory committee(HICPAC) recommends prudent vancomycin use to detect, prevent and control infection and colonization with VRE. Methods : The inpatients admitted from September to December, 1996 in Pusan National University Hospital, with Gram-positive bacterial infections were evaluated retrospectively to see whether the administrations of glycopeptide antibiotics were appropriate or not, upon comparison with the recommendations for preventing the spread of vancomycin resistance by HICPAC. Results : Teicoplanin has been chosen more frequently than vancomycin of the glycopeptide antibiotics. The indications of administration of glycopeptides in patients with pneumonia, wound infections, sepsis, and in febrile or neutropenic patients with malignancies were appropriate, but the use of glycopeptides for elimination of merely colonized bacteria in the oral cavity could not be excluded. Inappropriate use of glycopeptides was 10.6%, and inappropriately long-term use without positive culture for beta-lactam-resistant Gram-positive organisms was about 40% of total days of drug use. Conclusion : It seems essential for the quality assurance committee to make a plan in teaching the HICPAC recommendations to the medical practitioners who prescribed the glycopeptides inappropriately or used for irrelevantly long to his patient, monitor and survey their use of glycopeptides prospectively and periodically, and if there are repeated inappropriate prescriptions, a certain penalty would be given to the practitioners.