• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.228-228
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• 1996

1, 흰쥐에서 IPM 단독투여시보다 DHP-I 저해제인 CS와의 병용투여시 AUC가 4배 이상, t$_{1}$2/가 약 3배 증가하였으며 MEPM의 경우는 AUC가 5배 이상, t$_{1}$2/가 약 1.8배 증가하였다. 2. Guinea pig에서 IPM 단독투여시보다 CS와의 병용투여시 AUC가 약 2.5배, t$_{1}$2/가 약 1.4배 증가하였으며 MEPM의 경우는 AUC, t$_{1}$2/ 모두 거의 변함이 없었다. 3. 위의 결과 흰쥐에서 IPM과 MEPM에 대한 CS의 영향이 매우 큰 것으로 나타났으며 따라서 약물동력학적인 파라메타에도 커다란 변화를 주었다. 반대로 Guinea Pig에서는 CS의 병용투여로 IPM의 AUC에만 변동을 주었을 뿐 t$_{l}$ 2/에는 크게 영향을 미치지 않았고 MEPM의 체내동태에는 거의 영향을 미치지 않았다. 4. Guinea pig에서 전체 투여량에 대한 MEPM의 요중회수율은 66.58$\pm$3.44%이었고 IPM의 경우는 7.00$\pm$0.95%이었다. 그러나 DHP-I 저해제인 CS와의 병용투여시 IPM의 요중회수율이 57.77$\pm$11.46%로 증가하여 MEPM과 거의 비슷한 양상을 나타냈다. 이는 guinea pig에서 DHP-I에 의한 IPM의 대사가 CS에 의해 차단됨을 시사하는 것이라고 사료되며 guinea pig에 존재하는 DHP-I은 MEPM보다 IPM에 대해 더 높은 친화도를 갖는 것으로 사료된다. 5. Carbapenem계 항생제의 약물동력학적 스크리닝을 위한 소동물로는 흰쥐보다도 guinea pig가 적합한 것으로 생각되나 동물종차에 의한 약물동력학적 연구 및 DHP-I의 활성에 대한 연구가 더 면밀히 이루어져야 할 것으로 생각되며 BO-2727, panipenem, biapenem 등 다른 carbapenem 항생제에 대한 광범위한 약물동력학적 연구가 진행되어 새로운 carbapenem계 항생제 개발에 따른 인체내 거동을 예측할 수 있는 치적의 실험동물모델이 확립되어야 할 것이다.

• Korean Journal of Clinical Pharmacy
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• v.22 no.3
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• pp.234-238
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• 2012

Background: Valproic acid is widely used in the treatment of generalized tonic-clonic and partial seizures. The carbapenem class is the most potent and widest spectrum of antimicrobial activity. Concomitant administration of carbapenems and valproic acid has been reported to decrease the serum concentration of valproic acid, which is sometimes associated with seizures. The purpose of this study is to evaluate the changes in valproic acid concentration and half life and the frequency of seizure during concomitant administration of valproic acid and carbapenems. Method: This study was performed retrospectively on total 40 cases with identified valproic acid concentration during concomitant administration of valproic acid and carbapenems at Kangbuk Samsung Hospital from February 1st, 2006 to October 31st, 2011. Patients were classified into 3 groups: ertapenem group (n=14), imipenem group (n=12), meropenem group (n=14). Results: The mean serum concentrations in each group during combined treatment were $9.50{\pm}8.84$, $21.88{\pm}8.17$ and $10.62{\pm}8.67$ mg/L, respectively (p < 0.001). The mean half-lives in each group during concurrent use of valproic acid and carbapenems were $3.18{\pm}0.81$, $4.63{\pm}1.97$ and $2.67{\pm}1.69$ hr, respectively (p < 0.001). The valproic acid serum concentration decreased by 75.5%, 54.1% and 84.1% and the half-life of valporoic acid decreased by 65.6%, 35.7% and 73.5%, respectively. Total cases with seizure were 12(30%) with 5(35.7%) in the ertapenem group, 3 (25.0%) in the imipenem group and 4(28.6%) in the meropenem group (p=0.911). There were no specific factors to influence on seizure development during combined treatment. Conclusion: Concurrent use of carbapenems and valproic acid should be avoided. If concomitant administration is essential, very close serum concentration monitoring and clinical observation are necessary.

• Korean Journal of Clinical Pharmacy
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• v.30 no.2
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• pp.120-126
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• 2020

Objective: The rising number of carbapenemase-resistant Enterobacteriaceae (CRE) cases has become a concern worldwidely. This study investigated patient characteristics with CRE and analyzed the risk factors associated with its acquisition. Methods: A retrospective review of the electronic medical records of the Kangbuk Samsung Medical Center from May 2016 to April 2019 was performed. The inclusion criterion was hospitalized patients aged ≥18 years with confirmed CRE acquisition. Patients were divided by CRE acquired and non-required patients. CRE acquired patients were those with CRE confirmed by their active surveillance cultures, while non-acquired patients were those with carbapenemase-sensitive Enterobacteriaceae (CSE). If CRE was isolated more than once during hospitalization, only the first isolation was used for data analysis. Patient characteristics, antibiotic used, and the duration of use were compared between two groups using univariate analysis, and the risk factors associated with CRE were analyzed using multiple logistic regression analysis. Results: Among the 73 CRE acquired patients, 44 (60.3%) were positive for carbapenemase-producing Enterobacteriaceae (CPE). Infection from Klebsiella pneumonia (42 cases, 57.5%), Escherichia coli (17 cases, 23.3%), and Enterobacter cloacae (5 cases, 6.8%). The risk of CRE acquisition was significantly increased by 4.99 times [confidence interval (CI), 1.40-17.78; p=0.013] with mechanical ventilation, 3.86 times (CI, 1.59-9.36; p=0.003) with penicillin administration, and 21.19 times (CI, 6.53-68.70; p<0.001) with carbapenem administration. Conclusions: Proper antibiotic use including the selection, frequency, and duration, and patients on mechanical ventilators need close monitoring.

• YAKHAK HOEJI
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• v.41 no.2
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• pp.233-240
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• 1997

The in vitro antibacterial activity of DWP20418 (1R, 5S, 6S)-6-[1-(R)-Hydroxyethyl)-l-methyl-2-[(2S,4S)-2-(piperazinylcarbonyl)-1-(R)-hydroxyethyl)pyrrolidine-4-thio]carb apen-2-em-3-carboxylic acid), a new carbapenem antibiotic, was compared with those of imipenem (IPM) and meropenem (MEPM). DWP20418 was comparable or slightly more superior to MEPM against gram-positive bacteria, and it showed more potent activity to IPM against gram-negative bacteria. DWP20418 was particularly active against MRSA, and its $MIC_{90}$ of methicillin-susceptible S. aureus, low methicillin-resistant S. aureus and high methicillin-resistant S. aureus were 0.391, 25 and 50 ${\mu}g/ml$, respectively. With a view of $MIC_{90}$, DWP20418 was comparable than the other carbapenems against P. aeruginosa and E. coli isolates. The activity of DWP20418 was not affected in the presence of $Mg^{2+},\;Ca^{2+}$ or horse serum. But inoculum size and alterations in pH of medium affected its antibacterial activity. DWP20418 showed rapidly bactericidal activity within 1h, and regrowth was not observed even incubation of 24hrs at the concentrations near the MIC.

• Microbiology and Biotechnology Letters
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• v.49 no.2
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• pp.239-248
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• 2021

The emergence of multidrug-resistant Acinetobacter baumannii has partly increased treatment failure and patient mortality. Class D β-lactamases is an important mechanism of resistance to beta-lactam antibiotics in this species. This study aimed to investigate the relationship between the presence oxacillinase gene and genetic fingerprints of A. baumannii isolates from the intensive care unit of an Egyptian tertiary care hospital. One hundred and twenty A. baumannii clinical isolates were collected. Multiplex PCR was performed to detect genes encoding oxacillinases (OXA-23, OXA-24, OXA-51, OXA-58 and OXA-143). Molecular typing of all collected isolates was performed using random amplified polymorphic DNA (RAPD)-PCR assay. Out of 120 examined isolates, 92, 88 and 84% were resistant to ertapenem, imipenem and meropenem, respectively. The species-specific, commonly present OXA-51 gene was found in all isolates while OXA-23 showed a high prevalence of 88% of isolates. OXA-24 and OXA-143 genes were detected in 3% and 1% of isolates, respectively. No OXA-58 gene was detected. Five clusters consisting of 19 genotypes were detected using RAPD-PCR. Genotype A was the most prevalent, it was observed in 62% of the isolates followed by genotype B (12%). These results revealed that genotypes A and B are common in the hospital. Results also demonstrate that RAPD-PCR is a rapid and reliable method for studying the clonal similarity among A. baumannii isolated from different clinical specimens.

• Annals of Clinical Microbiology
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• v.22 no.1
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• pp.9-13
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• 2019

Background: The isolation of carbapenemase-producing Enterobacteriaceae (CPE) has become increasingly common. Continuous surveillance for these organisms is essential because their infections are closely related to outbreaks of illness and are associated with high mortality rates. The aim of this study was to develop and evaluate multiplex PCR as a means of detecting several important CPE genes simultaneously. Methods: We aimed to develop a multiplex PCR that could detect seven CPE genes simultaneously. The multiplex PCR was composed of seven primer sets for the detection of KPC, IMP, VIM, NDM-1, GES, OXA-23, and OXA-48. We designed different PCR product sizes of at least 100 bp. We evaluated the performance of this new test using 69 CPE-positive clinical isolates. Also, we confirmed the specificity to rule out false-positive reactions by using 71 carbapenem-susceptible clinical strains. Results: A total of 69 CPE clinical isolates showed positive results and were correctly identified as KPC (N=14), IMP (N=13), OXA-23 (N=12), OXA-48 (N=11), VIM (N=9), GES (N=5), and NDM (N=5) by the multiplex PCR. All 71 carbapenem-susceptible clinical isolates, including Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, showed negative results. Conclusion: This multiplex PCR can detect seven CPE genes at a time and will be useful in clinical laboratories.

• Bulletin of the Korean Chemical Society
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• v.27 no.5
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• pp.705-712
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• 2006

The synthesis of a new series of 1 $\beta$-methylcarbapenems having 5-(1,2-disubstituted ethyl)pyrrolidine moiety are described. Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the pyrrolidine ring was investigated. Among them, compound (IIIc) having 1-methoxyimino-2-hydroxyethyl moiety showed the most potent antibacterial activity.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.233-233
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• 1996

배지의 영향에 대하여 검토하기 위하여 SDA, MHA, NA 및 BHIA를 사용하였으며, 시험균주 중 Pseudomonas aeruginosa에 대하여만 NA에서의 MIC 값이 낮게 나타났을 뿐 나머지 균주에 대하여는 배지에 따른 항균력 변화가 관찰되지 않았으며, 배지의 pH를 5.4-8.4까지 변화시켰을 때 pH 변화에 따른 DA-1131의 유의적인 항균력 변화와 접종균량에 따른 항균력 변화가 관찰되지 않았다. Methicillin-resistant Staphylococcus aureus(MRSA)에 대하여는 DA-1131과 vancomycin 간의 상승 및 상가작용이 관찰되었고, P. aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae 및 Serratia marcescens 등의 균종에 대하여는 ciprofloxacin의 상가작용이 확인되었다. Sisomicin은 P. aeruginosa에 대한 상승 및 상가작용이 인정되었으나 ceftazidime은 DA-1131에 의한 길항작용이 관찰되었다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.236-236
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• 1996

DA-1131은 IPM이 D2 channel 특이적인 세포외막투과성을 나타내는 것과는 달리 D2 channel 이외에 azthreonam 투과경로도 이용하는 것으로 확인되었다. IPM 감수성 및 내성인 P aeruginosa 균주들에 대하여 $\beta$-lactamase의 inducible activity, hydrolytic susceptibility, affinity를 측정한 결과, Inducible activity는 DA-1131, PPM 및 MEPM이 거의 동일하였으며, 3가지 약물 모두 가수분해에 대한 안정성을 나타내었다. 그러나 $\beta$-lactamase에 대한 affinity는 IPM이 가장 컸고, MEPM, DA-1131의 순으로 감소하였다. DA-1131은 P8P2와 PBP3를 동시에 저해하며, IPM은 PBP2의 저해 후 순차적으로 PBP3를 저해하였고 이러한 시험결과는 PBPs blinding pattern과 밀접한 관계가 있는 것으로 알려진 균형태변화로도 확인되었다.

• Bulletin of the Korean Chemical Society
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• v.27 no.8
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• pp.1164-1170
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• 2006

The synthesis of a new series of 1$\beta$-methylcarbapenems having 5-($\alpha,\beta$-disubstituted ethyl)pyrrolidine moiety is described. Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the pyrrolidine ring was investigated. A particular compound (VIh) having $\alpha$-hydroxy-$\beta$-piperazinylethyl substituted moiety showed the most potent activity.