• 약학회지
• /
• 제39권4호
• /
• pp.360-366
• /
• 1995

1-$\beta$-Methyl carbapenem-2-substituted pyrroudine derivatives. CRB 529 and CRB 550, were synthesized as investigational carbapenem derivatives. It has been reported that the in vitro antibacterial activities of the compounds against G(+) and G(-) bacteria were almost the same or more effective than those of imipenem (IPM) and meropenem (MEPM), and also showed better in vivo efficacy than MEPM and inlipeneni/cilastatin (IPM/CS) against representative G(-) organisms, P. aeruginosa and MRSA organisms, S. aureus. The antibacterial activities, pharmacokinetics and protective efficacy of IPM/CS and CRB 529 and CRB 550 wereconducted after subcutaneous or intravenous administration to mice and rats. The pharmacokinetic parameters of CRB 529 and CRB 550 in mice were as follows: the observed maximal serum concentrations (C$_{max}$) following I.V. administration were 87.5 and 101 $\mu\textrm{g}$/ml for CRB 529 and CRB 550, respectively, and 63.6 $\mu\textrm{g}$/ml for IPM/CS. The half-lives (t$_{1/2}$) were 14.0 and 12.0 n-dn for CRB 529 and CRB 550, respectively, and 14.8 min for IPM/CS. In rats, $C_{max}$ after I.V. administration were 74.0 and 91.8 $\mu\textrm{g}$/ml for CRB 529 and CRB 550, respectively, and 41.2 $\mu\textrm{g}$/ml for IPM/CS. The tissue levels of CRB 529 and CRB 550 and IPM/CS after I.V. administration at a dose of 20 mg/kg decreased by the following order: lung, heart, kindney, liver and spleen for CRB 529, lddney, liver. lung, heart and spleen for CRB 550 and kidney, lung, liver, heart, spleen and brain for IPM/CS. In systemic infection, CRB 529 and CRB 550 showed excellent efficacies against P. aeruginosa and S. aureus (MRSA) at a dose of 5 mg/kg. The PD$_{50s}$ were 0.80, 0.36 mg/kg for CRB 529 and CRB 550, respectively, and 3.22 mg/kg for IPM/CS against P. aeruginosa. The corresponding values against S. aureus (MRSA) were 76.0, 55.3 mg/kg for CRB 529 and CRB 550, respectively, and 146 mg/kg for IPM/CS. In local infection, the antibacterial activities of CRB 529 and CRB 550 were more effective than those of IPM/CS against intrarenal infection with E. coli and P. aeruginosa and also showed as effective as IPM/CS against respiratory tract infection with E. coli and P. aeruginosa at a dose of 5 mg/kg.

• Pediatric Infection and Vaccine
• /
• 제27권1호
• /
• pp.45-52
• /
• 2020

목적: Carbapenem-resistant Acinetobacter baumannii (CRAB)에 의한 인공호흡기연관 폐렴(ventilator-associated pneumonia, VAP)의 치료에 있어 고용량 ampicillin-sulbactam과 colistin의 병합요법 치료효과를 살펴보기 위한 예비 연구이다. 방법: 2017년도 6월부터 2018년도 8월까지 17명의 CRAB VAP 환자를 후향적으로 분석하였다. 10명(58.8%)의 환자는 고용량 ampicillin-sulbactam과 colistin 병합요법(병합치료군)으로 치료받았으며, 나머지 7명은 colistin 단독치료를 하였거나 colistin을 포함 또는 미포함하는 다양한 항균제의 병합치료(기타치료군)를 하였다. 본 연구는 두 그룹간의 임상 및 세균학적 결과를 비교하였다. 결과: 병합치료군에서 항균제 사용 후 발열기간은 1.30±1.70일이었고, 기타치료군에서는 1.71±1.49일이었다. 기관내관 흡인물 검체에서 균이 음전 될 때까지의 평균 기간은 병합치료군에서 3.40±1.71일 기타치료군에서 11.80±8.86일이었다(P=0.030). 항균제 치료 30일 이내 사망률은 병합치료균에서 1/10 (10%)이고 기타치료군에서 3/7 (42.9%)이었다. 결론: 소아의 CRAB에 의한 인공호흡기연관 폐렴 환자에서 고용량 ampicillin-sulbactam과 colistin의 병합요법이 임상적 예후를 개선시킬 수 있을 것으로 기대된다.

• 대한임상검사과학회지
• /
• 제51권3호
• /
• pp.301-308
• /
• 2019

다제내성 P. aeruginosa의 출현과 확산은 전 세계적으로 중요한 문제가 되고 있다. P. aeruginosa에 의한 발병은 일부 몇몇 세포 관련 및 세포외 병독성 인자의 생성에 기인한다. 본 연구에서는 대전지역의 3차 병원에서 분리된 carbapenem 내성 P. aeruginosa를 대상으로 병독성 인자의 분포와 항균제 내성 양상을 조사하였다. 항균제 감수성 시험은 디스크 확산법으로 확인하였고, 병독성 유전자의 분석을 위해 PCR과 염기서열분석을 수행하였다. 또한, 다제내성 P. aeruginosa의 sequence type (ST)은 multilocus sequence typing (MLST)을 통해 확인하였다. 32균주의 carbapenem 내성 P. aeruginosa 중, 14균주(43.8%)가 다제내성이었으며, 주요 ST는 ST235 (10균주, 71.4.%)임을 확인하였다. 병독성 유전자는 32균주 모두에서 확인되었고, 이 중 가장 높은 빈도로 확인된 병독성 유전자는 toxA, plcN, phzM (100.%)이었다. 또한, 32균주는 모두 8개 이상의 병독성 유전자를 가지고 있었으며, 9균주(28.1%)가 15개의 병독성 유전자를 가지고 있었다. exoU 유전자는 다제내성 P. aeruginosa 균주의 71.4%에서 확인되었다. 이러한 결과는 exoU 유전자가 다제내성 P. aeruginosa 균주의 지속성에 대한 예측 표지자가 될 수 있을 것으로 사료된다.

• 한국미생물·생명공학회지
• /
• 제51권4호
• /
• pp.500-506
• /
• 2023

Carbapenem 내성 Klebsiella pneumoniae (Carbapenem-resistant K. pneumonia, CRKP)는 전 세계적인 공중 보건 문제로 대두되고 있다. 최근 Klebsiella pneumoniae carbapenemase-2 (KPC-2) 생성 sequence type (ST)307은 CRKP의 주요 클론으로 확인되었으며, 국내에서 ST307의 확산이 보고되었다. 본 연구에서는 2020년 3월부터 2021년 12월까지 대전지역의 3차 병원에서 분리된 CRKP 50균주를 대상으로, 분자 특성과 항균제 내성 양상을 조사하였다. 역학적 관계는 multilocus sequence typing (MLST)를 통해 분석하였고, 항균제 감수성 검사는 디스크 확산법을 통해 확인하였다. PCR과 DNA 염기서열분석은 carbapenemase 유전자 확인을 위해 수행하였다. CRKP감염은 남성과 60세 이상의 환자에서 훨씬 더 빈번하게 확인되었다. CRKP 50균주 중 46균주(92.0%)는 다제내성(MDR)을 보였고, 44균주(88.0%)는 carbapenemase-producing K. pneumoniae (CPKP)로 확인되었다. 주요 carbapenemase 유형은 KPC-2 (36균주, 72.0%)였으며, New Delhi metallo-enzyme-1 (NDM-1)과 NDM-5는 각각 7균주(14.0%)와 1균주(2.0%)에서 확인되었다. 특히, KPC-2 생성 K. pneumoniae의 88.9% (32/36)가 ST307에 속한 반면, NDM-1,-5 생성 K. pneumoniae의 87.5% (7/8)가 non-ST307에 속한 것을 확인하였다. 이러한 결과는 ST307의 확산 뿐만 아니라 non-ST307의 발달을 예방하기 위한 적절한 감염관리와 효과적인 감시체계가 필요하다고 사료된다.

• 약학회지
• /
• 제40권2호
• /
• pp.212-217
• /
• 1996

Streptomyces cattleya is a producer of carbapenem antibiotics, thienamycin and N-acetylthienamycin, which have potent and broad-spectrum antibacterial activities. We stud ied on strain improvement for antibiotic productivity of S. cattleya by transformation technique which employed S.cattleya protoplasts and chromosomal DNAs of glutamic acid producers: Corynebacterium glutamicum and Arthrobacter simplex. 150 Transformant strains were cultured and bioassayed using Bacillus subtilis and Staphylococcus aureus as test organisms. 8.7% of transformants tested showed 1.4~2.6 fold higher productivities than wild type which produced $1.61{\pm}0.67{\mu}g/ml$. The best transformant produced $8.36{\pm}2.84{\mu}g/ml$ carbapenems.

• Bulletin of the Korean Chemical Society
• /
• 제7권2호
• /
• pp.148-150
• /
• 1986

A potential carbapenem template, 4-(2-methoxyethyl)-2-azetidinone (3), was prepared in seven steps from 5,6-dihydro-2H-pyran-2-one (5).

• Clinical and Experimental Pediatrics
• /
• 제64권6호
• /
• pp.284-285
• /
• 2021

• 대한의생명과학회지
• /
• 제22권2호
• /
• pp.29-36
• /
• 2016

Among the several agents causing carbapenem resistance of Acinetobacter baumannii, the most common cause is OXA-23 ${\beta}$-lactamase, which is known to hydrolyze carbapenem. To effectively control dissemination of carbapenem-resistant Acinetobacter baumannii (CRAB), development of both rapid and easy-to-use detection methods are required. The aim of this study is to develop a novel immunochromatographic assay (ICA) for rapid detection of OXA-23 ${\beta}$-lactamase. Of the seven monoclonal antibodies (mAbs) screened by ELISA, four mAbs (4G6, 4H6, 6G4, 9A4) exhibited high reactivity. Of these four specific antibodies, the combination of 6G4/4G6 showed the greatest reactivity and this combination of mAbs (6G4/4G6 mAbs) was used to develop the OXA-23 ${\beta}$-lactamase ICA. Of 102 A. baumannii isolates tested, the OXA-23 ${\beta}$-lactamase ICA results were consistent with PCR analysis except one false positive and one false negative isolate. The overall sensitivity and specificity were 98.36% and 97.56%, respectively. In conclusion, to the best of our knowledge, we have developed the first specific antibody set to detect OXA-23 ${\beta}$-lactamase using an ICA kit. This novel ICA can be used as a reliable and easy-to-use immunological assay for detection of OXA-23 ${\beta}$-lactamase producing CRAB in clinical laboratories.

• 대한임상검사과학회지
• /
• 제42권2호
• /
• pp.71-80
• /
• 2010

Pseudomonas aeruginosa are important nosocomial pathogens. Their resistance to carbapenem is increasing and causing concerns in Korea. An increasing prevalence of carbapenem resistance mediated by acquired carbapenemase is being reported. Over a 10 month-period from July 2007 to April 2008, 32 strains of imipenem-nonsusceptible P. auruginosa were isolated from Kangwon National University Hospital. To determine the prevalence and genotypes of the carbapenemase-producing clinical isolates, the antibiotic susceptibility was determined by Microscan Walkaway 96 SI System and the carbapenem activity was detected by the modified Hodge test and the imipenem-EDTA-SMA double-disk synergy test. The metallo-${\beta}$-lactamase gene and OXA-type ${\beta}$-lactamase gene reported in Korea were detected by PCR. As for the result of PCR, 30 isolates of P. aeruginosa were found to have $bla_{IMP-1}$-like and 1 isolate was found to have $bla_{IMP-1}$-like and $bla_{IMP-2}$. No clinical isolates were found to have $bla_{SIM-1}$, $bla_{OXA-23}$-like and $bla_{OXA-24}$-like. Random amplified polymorphic DNA (RAPD)-PCR and dendrogram for genetical similarity to band patterns of each clinical isolates were examined. P. aeruginosa were grouped into 7 clusters of up to 50% of similarity index. In the P. aeruginosa group, PS3 was resistant to the most antibiotics, PS1 was susceptible to the most antibiotics. PS7 was resistant to aztreonam unlike other groups. This is the first report of prevalence of carbapenemase in Chuncheon.

• 한국미생물·생명공학회지
• /
• 제34권4호
• /
• pp.352-356
• /
• 2006

CW-270031, an injectable carbapenem, is a novel synthesized pyrrolidinyl-thio carbapenems. It was evaluated for its in vitro antibacterial activities in comparison with those of imipenem and meropenem against standard strains and clinical isolated strains, CW-270031 was more active than imipenem against gram-negative (E. coli and Klebsiella oxytoca) clinical isolates, but it was slightly active than meropenem. Against Klebsiella aeruginosa CW-118 MIC were 0.048 $\mu$g/ml for CW-270031, 0.19 $\mu$g/ml for imipenem. Against clinical E. coli MIC range were 0.012$\sim$0.195 $\mu$g/ml for CW-270031, 0.097$\sim$0.39 $\mu$g/ml for imipenem. Against clinical Klebsiella oxytoca MIC$_{50}$ were 0.09 $\mu$g/ml for CW-270031, 0.39 $\mu$g/ml for imipenem. Against gram-positive standard strains and clinical CW-270031 was slightly more activity than meropenem, but CW-270033 was less active than imipenem against these tested isolates. The subcutaneous injection of CW-270031 in mice revealed that the half-life of CW-270031 in serum was about 13 min, long than that of meropenem (10.6 min). CW-270031. was stable to hydrolysis by dog renal dehydropeptidase I (DHP-l) enzyme, to an more stabilities shown by meropenem.