• Title/Summary/Keyword: lactamase

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Susceptibility of β-Lactam Antibiotics and Genetic Mutation of Drug-Resistant Mycobacterium tuberculosis Isolates in Korea

  • Park, Sanghee;Jung, Jihee;Kim, Jiyeon;Han, Sang Bong;Ryoo, Sungweon
    • Tuberculosis and Respiratory Diseases
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    • v.85 no.3
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    • pp.256-263
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    • 2022
  • Background: Mycobacterium tuberculosis (Mtb) is resistant to the β-lactam antibiotics due to a non-classical transpeptidase in the cell wall with β-lactamase activity. A recent study showed that meropenem combined with clavulanate, a β-lactamase inhibitor, was effective in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). However, in Korea, clavulanate can only be used as drugs containing amoxicillin. In this study, we investigated the susceptibility and genetic mutations of drug-resistant Mtb isolates to amoxicillin-clavulanate and meropenem-clavulanate to improve the diagnosis and treatment of drug-resistant TB patients. Methods: The minimum inhibitory concentration (MIC) of amoxicillin-clavulanate and meropenem-clavulanate was examined by resazurin microtiter assay. We used 82 MDR and 40 XDR strains isolated in Korea and two reference laboratory strains. Mutations of drug targets blaC, blaI, ldtA, ldtB, dacB2, and crfA were analyzed by polymerase chain reaction and DNA sequencing. Results: The MIC90 values of amoxicillin/clavulanate and meropenem/clavulanate in drug-resistant Mtb isolates were 64/2.5 and 16/2.5 mg/L, respectively. Gene mutations related to amoxicillin/clavulanate and meropenem/clavulanate resistance could not be identified, but T448G mutation was found in the blaC gene related to β-lactam antibiotics' high susceptibility. Conclusion: Our results provide clinical consideration of β-lactams in treating drug-resistant TB and potential molecular markers of amoxicillin-clavulanate and meropenem-clavulanate susceptibility.

Analyses of Clinical Characteristics and Hematologic Studies of Confirmed Infants by Extended Spectrum $\beta$-lactamase Producing Escherichia coli or Klebsiella pneumonia in Neonatal Intensive Care Unit (단일병원 신생아 중환자실에서 Extended Spectrum $\beta$-lactamase 를 생성하는 Escherichia coli 혹은 Klebsiella pneumoniae가 확인된 신생아들의 임상적 특징 및 혈액학적 검사의 분석)

  • Lee, Sun-Geun;Choi, Min-Hwan;Shim, Gyu-Hong;Chey, Myoung-Jae
    • Neonatal Medicine
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    • v.18 no.2
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    • pp.265-271
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    • 2011
  • Purpose: Extended spectrum $\beta$-lactamase (ESBL) producing organism is an important cause of infections in the neonatal intensive care unit (NICU) since 1990s. The aim of this study is to investigate the differences of clinical characteristics and hematologic studies between neonates with ESBL-positive organism and those with ESBL-negative organism. Methods: The subjects included 48 neonates admitted to NICU at Inje University Sanggye Paik Hospital from January 2005 to September 2010, from whom a total of 58 Escherichia coli or Klebsiella pneumonia were detected. The data were categorized in 2 groups, neonates with ESBL-positive and ESBL-negative. We compared clinical characteristics and hematologic studies between two groups. Results: Of 48 neonates and 53 isolates, ESBL-positive were 18 neonates and 20 isolates. Both ESBL-positive and ESBL-negative isolates were largely found in urine, each with 10 and 23. Of 20 ESBL-positive isolates, 13 (65%) and 7 (35%) were ESBL producing Escherichia coli and Klebsiella pneumonia, respectively. ESBL-positive neonates were associated with low 1 and 5 minutes Apgar scores (P=0.002 and P=0.001, respectively), more uses of oxygen (56% vs. 27%; P=0.005), longer duration of oxygen uses (15.8${\pm}$38.43 days vs. 4.3${\pm}$12.5 days; P=0.008) and more frequent anemia (33% vs. 7%; P=0.040). Conclusion: ESBL-positive neonates may have more anemia and lower Apgar score at birth. We can consider the use of cabapenem earlier if infant with previous antibiotics is confirmed to be infected with ESBL-positive organisms.

Distribution and Antimicrobial Susceptibility of Bacteria in the Oral Cavity of Smokers or Non-Smokers (흡연자와 비흡연자간의 구강 내 세균 분포 및 항균제 감수성)

  • Jeong, Hyun-Ja;Kim, Su-Jung
    • Korean Journal of Microbiology
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    • v.46 no.4
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    • pp.334-340
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    • 2010
  • It is well known that smoking as well as drinking is a factor of stomatopathy, however there are few investigations about comparison of oral flora between smokers and non-smokers. In this study, we isolated the oral flora of 30 smokers and 30 non-smokers and cultured them on blood agar plates. The isolated pathogenic microorganisms were tested for antibiotic susceptibility and resistance using the Kirby-Bauer antibiotic testing method. Each colony was stained using the Gram staining method and was identified by an automatic identifier, known as the VITEK system. We isolated 41 colonies from smokers' oral cavity, and they were sorted as 63% of Gram-positive cocci, 29% of Gram-negative cocci, 3% of Gram-positive bacilli, and 5% of Gram-negative bacilli by gram staining, whereas 38 colonies were isolated from non-smoters' oral cavity, and their proportions were 55% of Gram-positive cocci, 26% of Gram-negative cocci, 3% of Gram-positive bacilli, and 16% of Gram-negative bacilli. The VITEK system revealed specific distribution of bacteria species that Streptococcus mutans (6/41), Gemella morillorum (6/41), Streptococcus oralis (2/41), Streptococcus pneumoniae (1/41), Staphylococcus aureus (3/41), Streptococcus anginosus (1/41), Streptococcus intermedius (1/41), Streptococcus uberis (1/41), and Streptococcus sanguinis (1/41) in smokers oral cavity whereas Streptococcus sanguinis (8/38), Staphylococcus aureus (1/38), Staphylococcus auricularis (1/38), Streptococcus uberis (1/38), Streptococcus intermedius (1/38), Streptococcus mutans (1/38), and Streptococcus oralis (1/38) in those of non-smokers'. Three cases of Staphylococcus aureus from smokers produced Beta-lactamase and were identified methicillin-resistance Staphylococcus aureus (MRSA). However one case of Staphylococcus aureus from non-smoker did not produce Beta-lactamase and was sensitive to methicillin. In conclusion, the distribution of oral flora was different between smokers' and non-smokers' oral cavity, especially Gemella morillorum and MRSA were predominantly found in smoker's oral cavity. These results are useful in the treatment and prevention of patients with stomatopathy caused by smoking.

Molecular-epidemiologic study on outbreak of colonization by extended spectrum β-lactamase producing Klebsiella pneumoniae in neonatal intensive care unit (신생아 중환자실에서 extended spectrum β-lactamase를 생성하는 Klebsiella pneumoniae 집단 보균 발생의 분자 역학적 조사 및 추적관찰)

  • Jun, Nu-Lee;Kim, Mi-Na;Jeong, Jae-Sim;Kim, Yang-Soo;Kim, Ellen Ai-Rhan;Kim, Ki-Soo;Pi, Soo-Young
    • Clinical and Experimental Pediatrics
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    • v.49 no.2
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    • pp.150-156
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    • 2006
  • Purpose : The aims of this study included assessment of molecular-epidemiologic features during an outbreak of colonization of extended spectrum ${\beta}$-lactamase producing Klebsiella pneumoniae(ESBL-KPN) and re-evaluation of their colonized status one year later. Methods : Rectal swab cultures for ESBL-KPN from all hospitalized infants and newly admitted infants were obtained during the outbreak of colonization from July to December, 2000. The pattern of XbaI-digested chromosomal DNA of isolates were analyzed by pulsed-field gel electrophoresis. Weekly rectal swab cultures were obtained during the outbreak until patients were either discharged or decolonized. Patients discharged after being colonized had follow up stool cultures a year later. Results : A total of 80 patients(28.5 percent) were colonized. Of those, 53 whose pulsed-field gel electrophoresis(PFGE) was possible only once, were ESBL-KPN grouped into six cluster clones and 10 single clones : 28 patients(52.8 percent) were colonized with type A, the most common clone, followed by type B in 11 patients(20.8 percent). Of those 12 patients in whom serial PFGE was done more than twice, type A was predominant. Narrowed-down in strains occurred from types A, B, C, D and three single clones at initiation of the study into types A and type B after three months of strict infection control. Among 75 patients(93.7 percent) who were sent home after being colonized, 30 patients were re-called for stool cultures a year later : All of them were decolonized. Conclusion : This study demonstrates the importance of infection control as the diversity of ESBL-KPN strains could be narrowed into fewer strains. Colonization of ESBL-KPN could be reversed upon return to the community.

Isolation of Multidrug-Resistant Salmonella typhimurium DT104 from Swine in Korea

  • Lee, Ki-Eun;Lee, Yeon-Hee
    • Journal of Microbiology
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    • v.45 no.6
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    • pp.590-592
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    • 2007
  • We report the isolation of Salmonella enterica serotype Typhimurium phage type DT104 (CCARM 8104) from swine in Korea. The CCARM 8104 isolate was resistant to nalidixic acid and showed reduced susceptibility to quinolones. The CCARM 8104 isolate had a missense mutation, Asp87Asn, in the quinolone resistance-determining region in gyrA and produced PSE-1. The CCARM 8104 isolate carried two different class 1 integrons, and the PSE-1 ${\beta}$-lactamase gene was inserted into a 1,200 bp class 1 integron. The presence of DT104 with pse-1 in an integron located in a plasmid and reduced susceptibility to quinolone in swine pose a significant threat of possible horizontal spread between swine and humans.

Synthesis of 6-Exomethylene Sulbactam Derivatives (6-엑소메칠렌 Sulbactam 유도체의 합성)

  • 임채욱;정홍식;임철부
    • YAKHAK HOEJI
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    • v.46 no.6
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    • pp.381-386
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    • 2002
  • The synthesis of new 6-exomethylene sulbactam derivatives with 5-methyl-1,3,4-thiadiazole was described. The 6,6-dibromopenam 5 was reacted with $CH_3$MgBr and carbaldehyde 4 to afford the 6-bromo-6-(1-hydroxy-1-methyl)penicillanate 6, which was treated with acetic anhydride to give acetoxy compound 7. The deacetobromination of acetoxy compound 7 with zinc and acetic acid gave 6-exomethylen penams, Z-isomer 8 and E-isomer 9, which was oxidized to sulfones 10 by m-CPBA. The p-methoxybenzyl compounds 6-10 were deprotected by AlCl$_3$ and neutralized with NaOH solution to give the sodium salts 11-15.

Removal of Contaminating TEM-la $\beta-Lactamase$ Gene from Commercial Taq DNA Polymerase

  • Song Jae Seok;Lee Jung Hun;Lee Jung-Hyun;Jeong Byeong Chul;Lee Won-Keun;Lee Sang Hee
    • Journal of Microbiology
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    • v.44 no.1
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    • pp.126-128
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    • 2006
  • This study confirms that Taq DNA polymerase could be contaminated with the $blaTEM-1_a$ gene. It also proposes two different methods that could be used to overcome DNA contamination: (i) DNase I treatment prior to PCR amplification; and (ii) the use of a highly purified Taq DNA polymerase which was devoid of detectable contamination.

신규베타락탐계 항생제 합성과 항균성

  • 고옥현;김경수;하재천;고봉석
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.171-171
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    • 1994
  • Cephem ring의 C-7위치에 aminothiazoly lmethoxyimino기를 가진 화합물들이 항균활성을 증가시키고, G(-)균의 외막투과성을 촉진시킬뿐 아니라 광범위항균 spectrum을 갖게 하고 $\beta$-lactamase에 안정하며 PBP(penicillin binding protein)에 대한 결합친화성을 증가시킨다는 보고에 따라 본 저자는 C-7위치에 cefotaxime구조와 같이 aminothiazolylmethoxyimino acetamido moiety를 고정시키고 항균활성을 증가시키기 위하여 약리활성이 기대되는 5-(substituted)-2H-tetrazole유도체들을 합성하여 C-3 위치에 도입시킨 새로운 화합물 7$\beta$-〔(z)-2-(2-aminothiazol-4-yl)-2_(methoxyimino)acetamido〕-3-〔5-(substituted)tetrazol-2-yl〕 methyl-3-cephem-4-carboxylic acid 유도체를 합성하여 B. subtilis ATCC 6633, M. luteus ATCC 1004, E. coli KCTC 1039, E. coli ESS, K. pncumonia KCTC 1560, P. aeruginosa IF0 13130, S. typhimurium KCTC 1925, S. typhimurium SL 1102, 및 C. albicans ATCC 10231 등의 균과 fungus에 대하여 기존의 cefotaxime과 cefazoline을 대조물질로 사용하여 항균력을 비교하였다. 이들 화합물들은 대체적으로 M. luteus ATCC 6633, E. coli ESS, S. typhimurium SL 1102 균에 대해서는 cefotaxime보다 항균력이 우수하였으나 P. aeruginosa IF0 13130에 대해서는 항균력이 저하되었고 cefazolin보다는 대체적으로 항균력이 우수하였다.

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Synthesis and $\beta$-lactamase inhibitory activity of 6-exomethylene penamsulfone derivatives - II (Synthesis of 6-exomethylene penamsulfone derivatives)

  • Yim, Chul-Bu;Youm, Jeong-Rok;Im, Chae-Uk;Park, Hee-Suk;Oh, Jeong-Suk;Park, Kye-Hwan
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.160-160
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    • 1996
  • $\beta$-Lactam계 항생제 내성균의 문제를 해결할 수 있는 $\beta$-lactamase억제제의 개발을 위해서, cephalosporinase에 특히 높은 억제활성을 갖는 새로운 6-exomethylene penamsulfones 화합물을 합성하였다. Dibromopenamsulfone과 thioalkyl triazole-4-carboxaldehyde을 반응시키고, acetic anhydride와 Zn으로 처리하여 E-form과 Z-form의 6-exomethylene penam sulfones을 합성하였다. 이것을 AlCl$_3$으로 deprotection시킨 후, NaOH로 처리하여 6-exomethylene penamsulfone의 Na-salt form으로 목적물질을 합성하였다.

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