• 대한수의학회지
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• 제43권1호
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• pp.113-120
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• 2003

The antimicrobial effect of ${\beta}$-lactam antibiotics, which had ${\beta}$-lactamase inhibitor activity, on Staphylococcus aureus isolated from mastitis was investigated in this study. Out of 166 isolates, 99 isolates (59.6%) produced ${\beta}$-lactamase, and 98 isolates of 99 were ${\beta}$-lactamase positive in above $12.5{\mu}g/m{\ell}$ MIC of penicillin. In the providence distribution, ${\beta}$-lactamase production rate of 4 providence, Gangwon, Gyeonggi, Chungcheong, and Jeolla was 100%, 65.7%, 58.8%, and 50.0%, respectively. Antibiotic activities of ${\beta}$-lactam antibiotics against lactamase positive isolates also were investigated. Antimicrobial effects of ampicillin/sulbactam or amoxicillin/clavulanic acid treated group were better than ampicillin or amoxicillin treated group. In antimicrobial effects on intracellular S aureus, there was no difference 1 hour and 4 hour treatment in control, ampicillin, and amoxicillin group, but in 18 hours treatment, ampicillin/sulbactam or amoxicillin/clavulanic acid had a better effect than ampicillin or amoxicillin (p<0.05).

• 생명과학회지
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• 제8권6호
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• pp.723-728
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• 1998

$\beta$-lactam계 항생물질에 강한 내성을 가지는 세균 Bacillus subtilis J105는 항생물질 존재 하에서 $\beta$-lactamase를 유도생산하여 내성이 더 강해진다. 배지에 항생물질이 존재하지 않을 때는 내성을 유도하는 $\beta$-lactamase의 생산은 15시간 만에 plateau에 달했다. 그러나 배지 중에 ampicillin(500$\mu\textrm{g}$/$m\ell$)이 존재할 때는 배양 25시간 만에 효소 생산이 plateau에 달하나 항생물질 비존재시와 비교하면 효소 활성은 약 20배인 2,900 units/$m\ell$나 많이 생산하는 것을 알 수 있었다. 또한, ampicillin 처리한 것과 무처리 균주를 여러 $\beta$-lactam계 항생물질에 적용하여 MIC를 비교해 본 결과 ampicillin 처리 균주의 MIC가 2~27배 가량 높은 것을 알 수 있었다. 이것은 본 균주가 ampicillin 처리함으로서 $\beta$-lactamase 생산을 유도하여 내성을 증가시킨 것으로 사료된다. 본 내성균주는 penicillin뿐만 아니라 cephalosporin계 항생물질에 대해서도 $\beta$-lactamase 생산을 유도하는 것을 알았다. 그 중에서도 300$\mu\textrm{g}$/$m\ell$의 cloxacillin이 효소생산유도에 가장 최적 농도였다. 항생물질 첨가 시기를 균의 생육시 기별로 조사한 결과 대수증식기가 가장 효과적인 결론을 얻었다. 이상의 결과로 본 내성균주는 다양한 $\beta$-lactam계 항생물질에 의하여 내성이 강하게 유도되는 특이적인 균주임을 시사한다.

• Childhood Kidney Diseases
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• 제21권2호
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• pp.128-135
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• 2017

Purpose: Extended-spectrum ${\beta}$-lactamase-producing bacteria-induced urinary tract infections are increasing and require more potent antibiotics such as carbapenems. We evaluated the clinical significance of extended-spectrum ${\beta}$-lactamase -urinary tract infection in children younger than 5 years to select proper antibiotics and determine prognostic factors. Differences were compared between age groups. Methods: We retrospectively studied 288 patients with their first febrile urinary tract infection when they were younger than 5 years. Patients were divided into extended-spectrum ${\beta}$-lactamase-positive and extended-spectrum ${\beta}$-lactamasenegative urinary tract infection groups. Clinical characteristics and outcomes were compared between the groups; an infant group was separately analyzed (onset age younger than 3 months). Results: Extended-spectrum ${\beta}$-lactamase urinary tract infection occurred in 11 % patients who had more frequent previous hospitalization (P=0.02) and higher recurrence rate (P=0.045). During the antimicrobial susceptibility test, the extended-spectrum ${\beta}$-lactamase-positive urinary tract infection group showed resistance to third-generation cephalosporins; however, 98% patients responded clinically. In the infant group, extended-spectrum ${\beta}$-lactamase-positive urinary tract infection occurred in 13% patients and was associated with a longer pre-onset hospitalization history (P=0.002), higher C-reactive protein level (P=0.04), and higher recurrence rate (P=0.02) than that in the older group. Conclusion: Extended-spectrum ${\beta}$-lactamase urinary tract infection requires more attention because of its higher recurrence rate. The antimicrobial susceptibility test demonstrated resistance to third-generation cephalosporins, but they can be used as first-line empirical antibiotics because of their high clinical response rate. Aminoglycosides can be second-line antibiotics before starting carbapenems when third-generation cephalosporins do not show bactericidal effects for extended-spectrum ${\beta}$-lactamase urinary tract infection.

• 약학회지
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• 제39권3호
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• pp.276-282
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• 1995

Compared to the first and second-generation cephalosporins, the third-generation cephalosporins are remarkably stable against hydrolysis by the $\beta$-lactamases produced by aerobic gram-negative bacilli, such as Enterobacteriaceae. Among these bacteria, the most prevalent plasmid-encoded $\beta$-lactamase is TEM-1 $\beta$-lactamase belonging to class A or group 2b. This enzyme is produced constitutively and is principally active against peniciflins and old cephalosporins rather than third-generafion cephalosporins, carbapenems and mmobactams. However, new TEM type $\beta$-lactamases including TEM-9 and TEM-12 evolved through point mutations in a gene encoding $\beta$-lactamase have been discovered from patients during chemotherapy. These $\beta$-lactamases are known to be capable of hydrolyzing most of the third-generatim cephalosporins. To study the prevalence of $\beta$-lactamases from clinical isolates collected in Korea. the minimal inhibitory concentratims(MICs) of several third-generation cephalosporins against 628 clinical isolates were determined by agar dilution methods, and $\beta$-lactamas-producing bacteria were isolated by use of cefinase disc. By polymerase chain reaction (PCR) method, clinical isolates harboring a gene for TEM type $\beta$-lactamase were identified among the $\beta$-lactamase producing strains. Twentiy three percent of the clinical isolates was resistant to the thirdgeneration cephalosporins, and more than 90% of resistant cells produced various $\beta$-lactamases. TFM type $\beta$-lactamases were dominant in gram-negative bacilli, such as Escherichia coli, Klebsiella pneumoniae, Enterobacter species. These results suggest the necessity of the development of new cephalosporins which are stable against $\beta$-lactamases like TEM.

• 대한수의학회지
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• 제25권1호
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• pp.61-67
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• 1985

One hundred and twenty seven strains of Gram-negative rods (72 E. coli, 45 Klebsieila pneumoniae, 8 Enterobacter spp. and 2 Pseudomonas aeruginosa) isolated from bovine mastitis were examined for resistance to ampicilin, carbenicillin and cefazolin, ${\beta}$-lactamase activity and transferable ${\beta}$-lactamase plasmids. Stains resistant to ampicillin were 13.9% in E. coli, 93.3% in Klebsiella pneumoniae, 87.5% in Enterobacter. spp. and all in Pseudomonas aeruginosa, Resistance of E. coli, Klebsiella pneumoniae and Enterobacter spp. to ampicillin was due to the ${\beta}$-lactamases, but all Pseudomonas aeruginosa exhibited a high level of the non-enzymic resistance. Transferable plasmid-mediated ${\beta}$-lactamase synthesis was demonstrated in 61.9% of Klebsiella pneumoniae, 50% of E. coli and 42.9% of Enterobacter spp. The same ${\beta}$-lactamase plasmids specified different resistance levels to various ${\beta}$-lactam antibiotics in different recipients.

• 약학회지
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• 제41권4호
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• pp.462-472
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• 1997

In this approach, the antimicrobial activities of the compounds were compared with the ${\beta}$-lactam antibiotics against ${\beta}$-lactamase producing strains in vitro. Heteroc yclyl exomethylenepenam derivatives were several numbers of 6-exomethylenepenam sodiums (CH1240, CH1245, CH1250, CH2140, CH2145, CH2150). The inhibitory concentraion assay of six compounds were compared with clavulanic acid, sulbactam, tazobactam. Clavulanic acid, sulbactam and tazobactam are used as inhibitors of a variety of plasmid-mediated beta-lactamases. In vitro ${\beta}$-lactamase inhibitory assay, CH1240 and CH2140 were more active than clavulanic acid, sulbactam and tazobactam against ${\beta}$-lactamases overally. And in vitro comparative antimicrobial susceptibility test of six inhibitors were performed with mixed forms of ampicillin, cefotaxime, amoxicillin, ticarcillin, piperacillin, cefoperazone against ${\beta}$-lactamase producing 31 species strains. Consequently CH2140 and CH1240 among the six compounds enhanced the activity of the ${\beta}$-lactams for 31 ${\beta}$-lactamase producing strains.

• 약학회지
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• 제41권5호
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• pp.658-665
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• 1997

Identification of a soil microorganism strain X-8, producer of ${\beta}$-lactamase inhibitor, based on its morphological, physiological, biochemical and chemotaxonomical characteristics was performed. The strain X-8 was identified as Pseudomonas sp. The beta-lactamase inhibitor produced by this strain was highly achieved in fermentation medium contained glucose 0.5%, urea 0.25%, $K_2HPO_4{\cdot}3H_2O\;0.5%,\;MgSO_4{\cdot}7H_2O\;0.5%,\;FeSO_4{\cdot}7H_2O\;0.01%,\;CuSO_4,\;ZnSO_4,\;MnSO_4\;0.02%$. The beta-lactamase inhibitor was not extracted by organic solvent such as n-butanol and ethyl acetate but remained in aqueous layer. The n-butanol extract showed antimicrobial activity against M. smegmatis. The ${\beta}$-lactamase inhibitor was stable at pH 7.0~8.0 and 4$^{\circ}C$ for 24h. The ${\beta}$-lactamase inhibitor was bound on ion exchanger Diaion WA-30 and HP-20 and eluted with 2N-$NH_4OH$ and acetone, respectively.

• Journal of Microbiology and Biotechnology
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• 제3권3호
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• pp.174-180
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• 1993

A strain SMF14 producing an extracellular $\beta$-lactamase was isolated from soil and identified to be a strain of Streptomyces aureofaciens. $\beta$-Lactamase was purified from the cell free culture broth through batchwise hydroxyapatite adsorption, anion exchange chromatography on DEAE Sephadex A-50, gel filtration on Sephadex G-75, and adsorption chromatography on hydroxyapatite. The molecular mass was estimated to be about 43 kDa by SDS-PAGE. The $\beta$-lactamase had substrate specificity to penicillins and it was inhibited by clavulanic acid, being classified to the group 2a of penicillinase.. The optimal reaction pH and temperature were pH 6.0~7.5 and $50^{\circ}C$. The $K_m, and V_{max}$ values of $\beta$-lactamase for penicillin G were calculated to be 1.72 mM and 5.4$\times$$10^5 \mu M \cdot min^{-1}$, respectively.

• 미생물학회지
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• 제43권2호
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• pp.116-123
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• 2007

본 연구는 부산지역 하천에서 plasmid 매개성 광범위 ${\beta}-lactam$ 분해효소(extended spectrum ${\beta}-lactamase;\;ESBL$)를 생성하는 세균을 분리하여 생성된 광범위 ${\beta}-lactam$ 분해효소를 유형별로 분류하기 위함이다. Escherichia coli 6균주와 Klebsiella pneumoniae 15균주가 피전달균주인 Escherichia coli J53 $Azid^{R}$에 plasmid 매개성 광범위 ${\beta}-lactam$ 분해효소 생성 인자를 전달하였다. PCR 후 얻은 유전인자를 plasmid로 매개된 광범위 ${\beta}-lactam$ 분해효소 유전자의 염기서열 분석결과, E. coli와 K. pneumoniae 유전자를 BCM Search Launcher 및 GenBank nucleotide database를 통하여 검색한 결과 ESBL 유형은 TEM-52형과 SHV-12형이었다. TEM-52는 E. coli와 K. pneumoniae 양쪽에서 분리되었다. 그러나 SHV-12는 K. pneumoniae에서만 분리되었다. 이상의 결과로부터 plasmid 매개성 광범위 ${\beta}-lactam$ 분해효소를 생성하는 세균이 한국에서는 이미 임상범위를 넘어 자연계까지 확산되었음을 알 수 있었다.

• Archives of Pharmacal Research
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• 제24권6호
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• pp.590-596
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• 2001

A new extended-spectrum ${\beta}-lactamase$ with an isoelectric point (pl) of 6.2 was detected in Klebsiella pneumoniae Fl 61 that was isolated from a patient with infection. This strain was highly resistant to the third or fourth generation cephalosporins such as cceftazidime ceftriaxone, cefoperzaone, and cefpirome. Analysis of this strain by the double disk diffusion test showed synergies between amoxicillin-clavulanate (AMX-CA) and cefotaxime, and AMX-CA and aztreonam, which suggested that this strain produced a extended-spectrum ${\beta}-lactamase$ (ESBL). Cenetic analysis revealed that the resistance was due to the presence of a 9.4-kb plasmic, designated as pkpl 61, encoding for new ${\beta}-lactamase$ gene (bla). Sequence analysis showed that a new bla gene of pkpl 61 differed from $bla_{TEM-1}$ by three mutations leading to the following amino acid substitutions: $Val_{84}{\rightarrow}lie,{\;}Ala_{184}{\rightarrow}Val,{\;}and{\;}Gly_{238}{\rightarrow}Ser$. These mutations have not been reported previously in the TIM type ${\beta}-lactamases$ produced by clinical strains. The novel ${\beta}-lactamase$ was overexpressed in E. coli and purified by ion exchange chromatography on Q-Sepharose and CM-Sepharose, and then further purified by gel filtration on Sehadex G-200. The catalytic activity of th8 purified ${\beta}-lactamase$ was confirmed by the nitrocefin disk.