• 미생물학회지
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• 제30권5호
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• pp.360-365
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• 1992

Sataphylococcus aureus의 퀴놀론계 약물에 대한 내성 기착을 이해하고자 ofloxacin에 내성을 보이는 임상 채취 8 균주의 Sataphylococcus aureus (ORSA)에 대하여 MIC 검사, gyrA 유전자 부근의 Southern 분석 및 아미노산 26번에서 121번까지를 포함하는 290bp의 gyrA 유전자 일부(gyrA-290)의 염기 서열 분석을 행하였다. ORSA 들은 퀴놀론계 약물에 대하여 높은 수준의내성을 보였으며(8-250 배의 MIC 증가), ${\beta}-lactam$계 약물에 대하여도 상당한 수준의 내성(2-32배의 MIC 증가)을 보였다. 하지만 ORSA 들은 vancomycin에 관한 감수성의 변화를 보이지는 않았다. ORSA에 대하여 Southern 분석을 실시한 결과, HindIII, PstI 및 AluI의 경우에는 gyrA 유전자 부근에서 RFLP가 발견되었다. GyrA 유전자를 더 분석하고자 gryA-290 부분을 중합효소 연쇄반응(PCR)으로 증폭하여 pTZ 벡터에 클론하였다. gryA-290의 염기 서열을 분석한 결과, 8 ORSA 균주 모두에 관하여 점 돌연변이의 결과로 Ser-84이 Leu-84으로 치환됨이 밝혀졌다. 이로서 gyrA 유전자의 84번째 아미노산의 치환이 Staphylococcus aureus의 퀴놀론 내성 발현의 중요한 기작 중 하나일 가능성이 있다고 생각된다.

• 한국미생물·생명공학회지
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• 제34권4호
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• pp.342-351
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• 2006

병원내 항생제 다제 내성을 일으키는 CTX-M형 ESBL을 생성하는 E. coli와 Klebsielia pneumoniae의 생성현황을 조사하고 이들 균주로 인한 감염증치료와 역학적 조사연구에 도움이 되고자 효소의 유전형을 규명하였다. 2005년 7월-12월에 부산에 소재하고 있는 2개의 종합병원에서 분리된 E. coli와 K. pneumoniae 각각 153주, 52주를 수집하였다. 그 중에서 ESBL을 생성 하는 균주를 검출하기 위해 Double disk synergy test를 시행하여서 E. coli 23주와 K. pneumoniae 13주를 분리하였다. 균주의 동정은 Vitek system GNI card(bioMerieux Vitek Inc., Hazelwood, Mo., U.S.A.)로 확인하였고, 항생제감수성시험은 disk diffusion method 와 agar dilution method를 사용하였다. 분리된 균주들의 내성을 일으키는 ESBL유전형을 규명하기 위하여 Isoelectric focusing(IEF), polymerase chain reaction test, DNA sequencing을 시행하였다. A병원의 13주와 B병원의 10주로 총 23주의 E. coli(15.0%)와 A병원의 7주와 B병원의 6주로 K. pneumoniae 13주(25.0%)가 double disk synergy test 양성으로 ESBL 생성균주로 판정하였다. ESBL 생성 36균주를 대상으로 bla$_{TEM}$, bla$_{SHV}$, bla$_{CTX-M}$ 유전자 검출을 위한 PCR을 시행한 결과 bla$_{TEM}$ 유전자는 13주(36.1%), bla$_{SHV}$ 유전자는 13주(36.1%), bla$_{CTX-M}$ 유전자는 32주(88.9%)가 양성반응을 보여서 bla$_{CTX-M}$ 유전자를 가진 균주가 가장 많이 나타났다. 그리고, bla$_{TME}$, bla$_{SHV}$ 두 가지 유전자를 가지고 있는 균주는 1주(2.8%)만 나타났고 bla$_{TEM}$, bla$_{CTX-M}$두 가지 유전자를 가지고 있는 균주는 9주(25.0%), bla$_{SHV}$, bla$_{CTX-M}$ 두 가지 유전자를 가지고 있는 균주가 10주(27.8%)로 나타나 bla$_{CTX-M}$을 포함하는 복합유전자가 많이 증가함을 알 수 있었다. 또한 CTX-M형 ESBL을 생성하는 E. coli와 K. pneumoniae에 대한 cefutaxime의 MIC는 256 $\mu$g/m1 이상으로 ceftazidime의 16-256 $\mu$g/mL 이상보다 높은 분포를 보였다. 즉, CTX-M형 ESBL 유전자를 지닌 균주에 대한 cefotaxim의 MIC는 ceftazidime의 MIC에 비해서 상대적으로 높은 양상을 보였다. 이러한 결과는 국내의 대학병원 뿐 만 아니라 일반종합병원에서도 CTX-M형 ESBL 생성 E. coli와 K. pneumoniae가 존재하며 확산 중임을 시사한다. 앞으로 CTX-M형 ESBL의 만연과 변종 CTX-M형 ESBL의 출연을 감시하기 위한 정기적인 연구와 조사가 필요한 것으로 생각한다.

• 한국임상약학회지
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• 제20권3호
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• pp.255-261
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• 2010

Cefprozil is a broad-spectrum oral beta-lactam cephalosporin consisting of cis- and trans-isomeric mixture whose ratio is approximately 90:10. Cefprozil is used to treat certain infections caused by bacteria such as bronchitis and ear, skin, and throat infections. The purpose of the present study was to evaluate the bioequivalence of two cefprozil tablets, $Cefzil^{(R)}$ tablet 250 mg (BMS Pharmaceutical Korea., Ltd.) and Procezil tablet 250 mg (Hanmi Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of cefprozil from the two cefprozil formulations were tested using KP VIII Apparatus I method with water dissolution media. Thirty five healthy male subjects, $24.00{\pm}1.53$ years in age and $69.77{\pm}9.99$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After four tablets containing 1000 mg as cefprozil were orally administered, blood samples were taken at predetermined time intervals and the concentrations of cefprozil in serum were determined using HPLC/UV detector. The dissolution profiles of two formulations were similar in water tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ on the basis of total-cefprozil were calculated, and computer program (K-BE Test 2002) was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Cefzil^{(R)}$ tablets, were -0.81%, -3.00% and -6.83% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.9515~log 1.0454 and log 0.9613~log 1.0465 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Procezil tablet was bioequivalent to $Cefzil^{(R)}$ tablet.

• 한국임상약학회지
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• 제15권2호
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• pp.75-81
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• 2005

Community acquired pneumonia (CAP) remains a prevalent and potentially life threatening illness. American Thoracic Society and Infectious Disease Society America recommend combination therapies with ${\beta}-lactam$ plus a macrolide or a fluoroquinolone monotherapy for the empirical treatment of CAP. The aim of this study was to compare moxifloxacin monotherapy with cephalosporin plus azithromycin combination therapies. From January 2004 to March 2005, 18 patients in the moxifloxacin group(MG) and 21 patients in the cefuroxime or ceftriaxone plus azithromycin group(CAG) with CAP were retrospectively reviewed with regard to clinical, laboratory and microbiological data. Each patient was stratified into mild (risk class I-II), moderate (risk class III) and severe (risk class VI, V) group according to and PSI (Pneumonia Severity Index) score. Each group was compared for microbiological eradication, clinical assessment, the length of hospital stay. As results, Total 39 patients with CAP were reviewed. The appropriateness of admission was 83.3% in MC vs. 76.2% in CAC. The mean length of the hospital day was for 8.31 days vs. 7.39 days, days switching parenteral to oral antibiotics in 5.19 days vs. 5.28 days, clinical improvement in 2.43 days vs. 2.61 days in MG vs. CAC. Radiological improvement required 3.75 days vs 3.63 days in MG vs. CAG and bacteriological eradication rate at discharge was the same in the both groups. Mortality rate was 11.1% (2 of 18) vs 14.3% (3 of 21) in MG vs. CAG (p=0.77). Drug cost of the mean 5 hospital days requiring parenteral antibiotics was the most inexpensive in moxifloxacin group for the 147,045 won, and ceftriaxone 1g-azithromycin group for the 170,285 won, cefuroxime bid-azithromycin group for the 207,800 won, ceftriaxone 2g-azithromycin group far the 220,570 won, cefuroxime tid-azithromycin group for the 251,700 won. There was no significant statistical difference in clinical, bacterial, radiological cure and hospital days, and switch to oral days. In conclusion, that i.v. moxifloxacin monotherapy was as effective as azithromycin plus cefuroxime or ceftriaxone combination therapies fur the treatment of CAP. In drug cost analysis, moxifloxacin is less expensive than CAG.

• 생명과학회지
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• 제8권1호
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• pp.40-50
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• 1998

Staphylococuus aureus and Escherichia coli is increasingly responsible for outbreaks of nosocomial infection around the world. Because serious infections due to these organisms currently necessiate use of non-$\beta$-lactam antimicrobial therapy and because strains is ofen resistant to many antimicrobial agents, infections with this organism are difficult to treat. Isolated strains from post operaton wounds of PNU hospital patient were tested for the antimicrobial susceptibility, resistant pattern and combined action to the 6 antibiotics. The minimal inhibitory concentraction of each antibiotic anc antibiotics combining in various ratios were measured by checkerboard dilution method. the synergism was determined through calculating the fractional inhibitory concentraction index (FICI). In case of S. aureus, 15 strains was shown to be highly sensitive to streptomycin and 13 strains to cephalothin. In case of E. coli, it is excellent senstitive 16 strains, sensitive 4 strains on cefoperazone, as like S. aureus, and thus the sensitive is most to be 66%. As the result of gaining MIC from S. aureus upon agar dilution method, MIC$_{50}$ was 8$\mu$g/ml, MIC$_{90}$ was 16$\mu$g/ml and thus the streptomycine is shown to be lowest. In case of E, coli, S. MIC$_{50}$ was 4$\mu$g/ml, MIC$_{90}$ was 16$\mu$g/ml, in streptomycin and thus is shown to be lower than S. aureus. As the result of comparing the resistance aspect of combining the antibiotics on S. aureus and E. coli, the resistant strain can be known to be reduced to the large range more than each 40% than combining with only aminoglycoside-series or cephalosporine-series. As the result of combining aminoglycoside-series, streptomycin and cephalothin or cefuroxime sensitive to S. aureus and E. coli in the above mentioned results, the increase or imporovement of effect is over 73% and 80%, respectively, thus the case od combining 2 antibiotics is shown to be better in the effect. Isolated strains from operating wounds were for the antimicrobial susceptibility. In case of S. aureus 15 strains was shown to be sensitive very much on streptomycin. In case of E. coli it is excellent sensitive 16 strains. As the results of combining aminoglycosides-series, streptomycin and cephalosporine series, cephalothin and cefuroxime, the increase or improvement of effect is over 73%, thus case of combining 2 antibiotics is shown to be better in the effect.

• 생명과학회지
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• 제27권4호
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• pp.476-481
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• 2017

항산화, 항알러지, 항염증, 항암, 항고혈압, 항균 활성을 나타내는 폴리페놀 화합물은 고등식물에 의해 생산되는 2차 대사산물이다. 일반적으로 폴리페놀 화합물은 플라보노이드와 비 플라보노이드 화합물로 나뉘며 병원균에 대한 항균활성은 비 플라보노이드 화합물에 비해 플라보노이드 화합물이 우수하다. 항균활성을 나타내는 플라보노이드 화합물은 칼콘, 플라반-3-올(카테킨), 플라바논, 플라본, 플라보놀, 프로안토시아니딘 등이며 플라보놀 화합물은 그람 음성 세균(Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella melaninogenica, Prevotella oralis)과 그람 양성 세균(Actinomyces naeslundii, Lactobacillus acidophilus, Staphylococcus aureus)에 대해 항균활성을 나타낸다. 비 플라보노이드 화합물 중에서 항균활성을 나타내는 화합물은 커피산, 갈릭산, 페룰산 등이며 그람 양성 세균(Listeria monocytogenes, S. aureus)과 그람 음성 세균(Escherichia coli, Pseudomonas aeruginosa)에 대해 젠타마이신, 스트렙토마이신보다 우수한 항균활성을 나타낸다. 플라본 화합물인 캠퍼롤과 퀘세틴은 단독 사용보다는 리팜피신, 시플록사신과 병용하였을 떄 S. aureus와 메티실린 내성 S. aureus (MRSA)에 대해 시너지 효과를 나타내었고, 에피갈로카테킨 갈레이트(EGCG)는 베타락탐계 항생제와 병용했을 때 MRSA 에 대한 대해 시너지 효과를 나타내었다. 특히 한국 녹차에서 분리된 에피카테킨, 에피갈로카테킨, 에피갈로카테킨 갈레이트, 갈로카테킨 갈레이트 등의 차 폴리페놀류는 임상에서 분리한 MRSA에 대해 항균활성을 나타내었고 옥사실린과 병용했을 때 시너지 효과를 나타내었다.

• 한국임상약학회지
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• 제8권2호
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• pp.83-88
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• 1998

Improved knowledge of the time course of antimicrobial activity should provide useful information for designing optimal dosage regimen. In contrast to $\beta$-lactam, aminoglycosides tend to induce a prolonged postantibiotic effect against aerobic or facultative gram negative rods and clinical outcome was significantly correlated with achieving peak serum concentrations. The objective of this study was to compare the efficacy, safety of e same total daily dose of amikacin and gentamicin given either twice or thrice daily in the treatment of patients. Consecutive patients over 20 years old with a suspected or confirmed infection for which an aminoglycosides was indicated were eligible. Exclusion criteria were known allergy to aminoglycosides, renal impairment, granulocytopenia and pregnancy. Patients were treated with intravenous amikacin 15 mg/kg/day or gentamicin 4.5 mg/kg/day either in two devided or in three devided. Seventy-four patients with infection were enrolled in this study of amikacin twice daily (A2, n=29), gentamicin twice daily (G2, n=8) vs amikacin thrice daily (A3, n=30), gentamicin thrice daily (G3, n=7). Baseline characteristics were comparable in G2 and G3. The clinical cure rate (including partial improve) were $89.0\%\;and\;86.0\%$ in A2 group and A3 group respectively. The bacteriologic cure rate were $99.0\%\;and\;85.7\%$ in A2 group and in A3 group respectively. The clinical and bacteriologic effects were difficult to compare G2 with G3, because of the small numbers of patients. The serum creatinin rose in $3.44\%$ (1 in 29) of patients in the A2 group compared to $13.3\%$ (4 in 30) in e A3 group. Although audiometry was not performed, there was no clinical evidence of ototoxicity in any of the patients. In our opinion, twice-daily regimen of aminoglycosides is more effective and less nephrotoxic than thrice-daily regimen.

• 대한본초학회지
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• 제28권1호
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• pp.59-64
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• 2013

Objectives : Methicillin-Resistant Staphylococcus aureus (MRSA) is a cephalosporin and beta-lactam antibiotic-resistant strains. In most cases, that is spread from infected patients and infection rates are growing increasingly. Thus, accordingly, increased resistance to antibiotics is causing serious problems in the world. Therefore, there is a need to develop alternative antimicrobial drugs for the treatment of infections diseases. Methods : The antibacterial activities of Sinhyowoldosan were evaluated against 3 strains of Methicillin-resistant staphylococcus aureus(MRSA) and 1 standard Methicillin-susceptible S. aureus (MSSA) strain by using the disc diffusion method, minimal inhibitory concentrations (MICs) assay, colorimetric assay using MTT test, checkerboard dilution test and time-kill assay was performed under dark. Results : The MIC (minimum inhibitory concentration) of Sinhyowoldosan water extract against S. aureus strains ranged from 500 to 2,000 ${\mu}g/mL$, so we have confirmed it on a strong antibacterial effect. Also, the combinations of Sinhyowoldosan water extract and conventional antibiotics exhibited improved inhibition of MRSA with synergy effect. We suggest that Sinhyowoldosan water extract against MRSA have antibacterial activity, it has potential as alternatives to antibiotic agent. the combination test was used, Triton X-100 (TX) and DCCD for measurement of membrane permeability and inhibitor of ATPase. As a result, antimicrobial activity of SH is affected by the cell membrane were assessed. Conclusion : We suggest that the Sinhyowoldosan water extract lead the treatment of bacterial infection to solve the resistance and remaining side-effect problems that are the major weak points of traditional antibiotics.

• 한국환경농학회지
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• 제41권4호
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• pp.335-343
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• 2022

BACKGROUND: Antibiotics used in animal husbandry for disease prevention and treatment have resulted in the rapid progression of antibiotic resistant bacteria which can be introduced into the environment through livestock feces/manure, disseminating antibiotic resistant genes (ARGs). In this study, fecal samples were collected from the livestock farms located in Jeju Island to investigate the relationship between microbial communities and ARGs. METHODS AND RESULTS: Illumina MiSeq sequencing was applied to characterize microbial communities within each fecal sample. Using quantitative PCR (qPCR), ten ARGs encoding tetracycline resistance (tetB, tetM), sulfonamide resistance (sul1, sul2), fluoroquinolone resistance (qnrD, qnrS), fluoroquinolone and aminoglycoside resistance (aac(6')-Ib), beta-lactam resistance (bla_TEM, bla_CTX-M), macrolide resistance (ermC), a class 1 integronsintegrase gene (intI1), and a class 2 integrons-integrase gene (intI2) were quantified. The results showed that Firmicutes and Bacteroidetes were dominant in human, cow, horse, and pig groups, while Firmicutes and Actinobacteria were dominant in chicken group. Among ARGs, tetM was detected with the highest number of copies, followed by sul1 and sul2. Most of the genera belonging to Firmicutes showed positive correlations with ARGs and integron genes. There were 97, 34, 31, 25, and 22 genera in chicken, cow, pig, human, and horse respectively which showed positive correlations with ARGs and integron genes. In network analysis, we identified diversity of microbial communities which correlated with ARGs and integron genes. CONCLUSION(S): In this study, antibiotic resistance patterns in human and livestock fecal samples were identified. The abundance of ARGs and integron genes detected in the samples were associated with the amount of antibiotics commonly used for human and livestocks. We found diverse microbial communities associated with antibiotics resistance genes in different hosts, suggesting that antibiotics resistance can disseminate across environments through various routes. Identifying the routes of ARG dissemination in the environment would be the first step to overcome the challenge of antibiotic resistance in the future.

• 한국식품위생안전성학회지
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• 제39권3호
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• pp.231-238
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• 2024

국내에서 V. parahaemolyticus로 인한 식중독 사고가 지속적으로 보고되고 있으며, 최근 국내 수산물 판매량 및 수산물 양식에 사용되는 항생제 판매량은 증가하는 추세이다. 따라서 본 연구는 국내에 유통되는 수산물에서 분리한 V. parahaemolyticus의 분포, 항생제 감수성, 유전적 특성 및 유전학적 통계를 조사하였다. 79건의 유통 수산물로부터 47건(59.5%)에서 V. parahaemolyticus가 분리되었다. 항생제 내성 양상의 경우, 총 47균주의 분리 균주에서는 ampicillin에 2균주(4.3%)가 내성을 보였으며, 이외 균주는 모든 항생제에 대해 감수성을 보였다. 항생제 내성 유전자의 경우, 모든 균주(100%)로부터 bla_CAR family gene, tet(35), catC가 확인되었으며, 1균주(2.1%)에서는 fos가 확인되었다. 병원성 유전자 여부의 경우, 모든 분리 균주에서 tdh, trh 유전자는 확인되지 않았으나, T3SS1은 모든 균주(100%), T3SS2는 1균주(2.1%)에서 확인되었다. MLST의 경우, 17균주로부터 15가지의 ST가 확인되었으며, ST 658가 3균주, 이외 14가지 ST는 1균주씩 확인되었다. 확인된 ST는 대부분 중국, 태국 등의 환경 분리주로 확인되었으며, ST 396, ST 3042는 중국 임상 분리주로부터 확인되었다. 이로써, 최근 국내에 수산물과 관련한 식중독, 유통량, 항생제 판매량 등의 추세에 따른 위험성에 V. parahaemolyticus에 대한 지속적인 연구가 필요할 것으로 사료되며, 본 연구는 그에 대한 도움이 될 것이라 사료된다.