• Title/Summary/Keyword: Extended-spectrum ${\beta}$-lactamases

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Formulation of Ceftriaxone Conjugated Gold Nanoparticles and Their Medical Applications against Extended-Spectrum β-Lactamase Producing Bacteria and Breast Cancer

  • El-Rab, Sanaa M.F. Gad;Halawani, Eman M.;Hassan, Aziza M.
    • Journal of Microbiology and Biotechnology
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    • v.28 no.9
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    • pp.1563-1572
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    • 2018
  • Gold nanoparticles (AuNP) and their conjugates have been gaining a great deal of recognition in the medical field. Meanwhile, extended-spectrum ${\beta}$-lactamases (ESBL)-producing bacteria are also demonstrating a challenging problem for health care. The aim of this study was the biosynthesis of AuNP using Rosa damascenes petal extract and conjugation of ceftriaxone antibiotic (Cef-AuNP) in inhibiting ESBL-producing bacteria and study of in vitro anticancer activity. Characterization of the synthesized AuNP and Cef-AuNP was studied. ESBL-producing strains, Acinetobacter baumannii ACI1 and Pseudomonas aeruginosa PSE4 were used for testing the efficacy of Cef-AuNP. The cells of MCF-7 breast cancer were treated with previous AuNP and Cef-AuNP at different time intervals. Cytotoxicity effects of apoptosis and its molecular mechanism were evaluated. Ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy established the formation of AuNP and Cef-AuNP. Transmission electron microscope demonstrated that the formed nanoparticles were of different shapes with sizes of 15~35 nm and conjugation was established by a slight increase in size. Minimum inhibitory concentration (MIC) values of Cef-AuNP against tested strains were obtained as 3.6 and $4{\mu}g/ml$, respectively. Cef-AuNP demonstrated a decrease in the MIC of ceftriaxone down to more than 27 folds on the studied strains. The biosynthesized AuNP displayed apoptotic and time-dependent cytotoxic effects in the cells of MCF-7 at a concentration of $0.1{\mu}g/ml$ medium. The Cef-AuNP have low significant effects on MCF-7 cells. These results enhance the conjugating utility in old unresponsive ceftriaxone with AuNP to restore its efficiency against otherwise resistant bacterial pathogens. Additionally, AuNP may be used as an alternative chemotherapeutic treatment of MCF-7 cancer cells.

Genotypic Detection of Extended-Spectrum β-Lactamase-Producing of Klebsiella pneumoniae (Extended-Spectrum β-Lactamase 생성 Klebsiella pneumoniae 균주의 유전형 검출)

  • Yook, Keun-Dol;Yang, Byoung-Seon;Park, Jin-Sook
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.14 no.3
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    • pp.1191-1196
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    • 2013
  • Among Gram-negative pathogens in Korea, the incidence of resistance to third generation cephalosporins is becoming an ever-increasing problem. The production of extended-spectrum ${\beta}$-lactamase (ESBL) is the main mechanism of bacterial resistance to a third-generation cephalosporins and monobactams. Accurate identification of the ESBL genes are necessary for surveillance and epidemiological studies of the mode of transmission in the hospital. This study was conducted to detect the genes encoding ESBL of 46 K. penumoniae isolated from Daejeon, Chungnam and Chungbuk regional university hospitals from February to August in 2012. The phenotypes of the isolated specimens were examined according to the combination disc test (CDT) by the Clinical and Laboratory Standards Institute (CLSI). Forty two ESBL producing K. penumoniae isolates could be detected using ceftazidime (CAZ) discs with and without clavulanate (CLA). By CDT, 42 K. pneumoniae strains were confirmed to be ESBL strains. Genotyping was performed by multiplex PCR with type-specific primers. By PCR analysis, TEM gene in 46 strains, SHV gene in 37 strains and CTX-M genes in 14 strains were identified. Ten isolates did carry genes encoding ESBLs of all types TEM, SHV and CTX-M. The multiplex polymerase chain reaction (PCR) analysis was better to detect and differentiate ESBL producing K. penumoniae strains in clinical isolates.

Interaction of DA-1131,A New Carbapenem Antibiotic, with bacterial $\beta$-lactamases

  • Park, Seong-Hak;Kim, Gye-Won;Kim, Ji-Young;Lim, Geun-Jho;Chung, Dong-Yun;Kim, Won-Bae;Junnick Yang
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.237-237
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    • 1996
  • DA-1131, imipenem(IPM) 및 meropenem(MEPM)은 각종 $\beta$-lactamase를 산생하는 세균에 대하여 우수한 항균력을 나타내었으나 cefpirome(CPR), ceftazidime(CAZ) 및 azthreonam(AZT)의 경우에는 extended broad spectrum cephalosporinase 산생 균주를 포함하여 일부 균주의 내성획득이 확인되었다. DA-ll3l의 $\beta$-lactamase Inducible activity는 DA-1131, IPM 및 MEPM이 거의 동일하였으며, imipenemase 산생균주로 동점된 Serratia marcescens 11001이 산생하는 $\beta$-lactamase이외의 효소에는 대부분 가수분해되지 않는 결과를 나타내었다. S. marcescens 11001이 산생하는 $\beta$-lactamase에 대한 효소역학상수는 DA-1131, IPM 및 MEPM에서 모두 유사하였고, $\beta$-lactamase에 대한 affinity도 큰 차이를 나타내지 않았다.

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Detection of CTX-M and TEM type extended-spectrum β-lactamases in Escherichia coli isolated from livestocks in Korea (국내 가축 유래 대장균에서 CTX-M 및 TEM형 extended-spectrum β-lactamases의 검출)

  • Cho, Jae-Keun;Sung, Myung-Suk;Kim, Jin-Hyun;Kim, Ki-Seuk
    • Korean Journal of Veterinary Service
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    • v.34 no.1
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    • pp.37-43
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    • 2011
  • This study was conducted to investigate the prevalence and genotypes of extended-spectrum ${\beta}$-lactamase (ESBL) in 377 Escherichia coli isolated from healthy and sick animals. Two isolates (0.5%), each of which were isolated from diseased swine and chicken, respectively, were confirmed as ESBL producing isolates by double disk synergy test, and showed a multidrug resistant phenotype. Minimum inhibitory concentration of cefotaxime for the two ESBL producing isolates were 3~4 times higher than those of ceftazidime, respectively. By PCR and sequencing, one isolate from swine have both $bla_{CTX-15}$ and $bla_{TEM-1}$, and one isolate from chicken have $bla_{CTX-15}$ and $bla_{TEM-116}$. Also, these genes were transferred to E. coli J53 by conjugation. These two isolates showed unrelated pulsed-field gel electrophoresis. To our knowledge, this is the first time that $bla_{TEM-116}$ gene was identified in E. coli isolated from animals in Korea. These results suggest more prudent use of third- generation cephalosporins, and surveillance and monitoring for ESBL producing E. coli in both animals and their environments should be necessary.

Virulence, Resistance Genes, and Transformation Amongst Environmental Isolates of Escherichia coli and Acinetobacter spp.

  • Doughari, Hamuel James;Ndakidemi, Patrick Alois;Human, Izanne Susan;Benade, Spinney
    • Journal of Microbiology and Biotechnology
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    • v.22 no.1
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    • pp.25-33
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    • 2012
  • The association of verotoxic E. coli and Acinetobacter spp. with various antibiotic-resistant, diarrhogenic, and nosocomial infections has been a cause for concern worldwide. E. coli and A. haemolyticus isolated on a number of selective media were screened for virulence factors, antibiotic resistance, and transformation of resistance genes. Out of 69 E. coli isolates obtained, 25 (35.23%), 14 (20.30%), and 28 (40.58%) were positive for Vtx1&2, Vtx1, and Vtx2, respectively, 49 (71.015%) for extendedspectrum beta-lactamases (ESBLs), 34 (49.28%) for serum resistance, 57 (82.61%) for cell surface hydrophobicity, 48 (69.57%) for gelatinase production, and 37 (53.62%) for hemolysin production. For the 14 A. haemolyticus isolates, only 2 (14.29%) in each case from all the samples investigated were positive for Vtx1, Vtx2 and Vtx1&2 respectively, 8 (57.14%) for ESBLs, 7 (50.00%) for serum resistance, 11 (78.57%) for cell surface hydrophobicity, 4 (28.57%) for gelatinase production, and 8 (57.14%) for hemolysin production. Although transformation occurred among the E. coli and Acinetobacter isolates (transformation frequency: $13.3{\times}10^{-7}-53.4^{-7}$), there was poor curing of the plasmid genes, a confirmation of the presence of stable antibiotic-resistant genes (DNA concentration between 42.7 and 123.8 ${\mu}g$) and intragenetic transfer of multidrug-resistant genes among the isolates. The isolates were potentially virulent and contained potentially transferable antibiotic resistance genes. Detection of virulence factors, antibiotic resistance genes, and transformation among these isolates is a very significant outcome that will influence approaches to proactive preventive and control measures and future investigations. However, continued surveillance for drug resistance among these bacteria and further investigation of the mechanism of action of their virulence factors are a necessity.

Characterization of CTX-M-Type Extended-Spectrum Beta-Lactamase-Producing Diarrheagenic Escherichia coli Isolates in the Republic of Korea During 2008-2011

  • Kim, Jin Seok;Kim, Junyoung;Kim, Soo-Jin;Jeon, Se-Eun;Oh, Kyung Hwan;Cho, Seung-Hak;Kang, Yeon-Ho;Han, Soon Young;Chung, Gyung Tae
    • Journal of Microbiology and Biotechnology
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    • v.24 no.3
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    • pp.421-426
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    • 2014
  • To characterize the extended-spectrum beta-lactamases (ESBLs) in diarrheagenic Escherichia coli from Korea in 2008-2011, we screened seven enterotoxigenic E. coli (ETEC) and one enteroaggregative E. coli (EAEC) that produce ESBLs from a nationwide survey. All eight isolates produced CTX-M-type ESBLs, including CTX-M-12 (n = 4), CTX-M-14 (n = 2), and CTX-M-15 (n = 2). PCR-based replicon typing indicated that the $bla_{CTX-M-12}$ genes of four ETEC isolates were carried on a conjugative IncF plasmid, whereas the $bla_{CTX-M-14}$ of one EAEC was located on an IncK plasmid. This is the first report of the occurrence of $bla_{CTX-M}$ genes in clinical isolates of EAEC in Korea. The ESBL-producing isolates were shown to be different based on pulsed-field gel electrophoresis and multilocus sequence typing, whereas the four isolates with CTX-M-12 were clonally related. These observations raise an alarm for the spread of plasmid-mediated resistance to ESBL among diarrheagenic E. coli.

Clinical Outcomes of Non-carbapenem Treatment for Urinary Tract Infections Caused by Extended-spectrum β-lactamase-producing Escherichia coli

  • Kim, Eunae;Ahn, Yo Han;Lee, Jung Won;Park, Eujin
    • Childhood Kidney Diseases
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    • v.25 no.1
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    • pp.22-28
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    • 2021
  • Purpose: The purpose of this study was to investigate the clinical outcomes of non-carbapenem treatment for urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) in young children. Methods: We retrospectively reviewed the medical records of children under 2 years of age who were diagnosed and treated for UTIs caused by ESBL-producing E. coli from September 2014 to March 2020. Results: Forty-three children under 2 years of age were treated with non-carbapenem antimicrobials for UTIs caused by ESBL-producing E. coli without bloodstream infections. The overall clinical and microbiological success rates for empirical antimicrobial treatment were 90.7% and 97.7%. Three of the patients (7.0%) experienced a relapse of UTI within a month. An in vitro susceptibility test showed that two patients were sensitive and one was resistant to the antimicrobial treatments. Furthermore, there were no significant differences in the time to defervescence, clinical success, microbiological success, and relapse rate between the susceptible (n=13) and non-susceptible groups (n=30). Conclusion: In this study, the overall relapse rate of patients treated with non-carbapenem antimicrobials was 7.0%. The patients showed high success rates in the clinical and microbiological responses to the non-carbapenems regardless of the results of the in vitro antimicrobial susceptibility test. These results provide evidence that non-carbapenems may be viable alternative treatments for UTIs caused by ESBL-producing E. coli.

Molecular detection of blaVIM, blaBIC, blaKPC, and blaSIM genes from isolated bacteria in retail meats (육류용 고기로부터 분자진단을 이용한 항생제내성 유전자 양상)

  • Hwang, You Jin
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.22 no.6
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    • pp.413-419
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    • 2021
  • The purpose of this study was to investigate the ability to treat and prevent infection by multiple Gram-negative bacterial pathogens as a last choice option in the treatment of serious infections in clinical settings. The global spread of extended-spectrum 𝛽-lactamases (ESBLs) and/or carbapenemases in microorganisms are of enormous concern to health services because they are often associated with multi-drug resistance which significantly restricts the antibiotic treatment options. In this study, the antimicrobial resistance profiles of bacteria isolated from South Korean market-derived meat samples were determined by the disc diffusion method. PCR was used to detect the presence of antibiotic resistance genes and ESBL producing genes. In total, we tested 181 isolated colonies from 36 market-derived meat samples. Single PCR and DNA sequencing results revealed that genes blaVIM, blaBIC, blaKPC, and blaSIM were present in the bacteria isolated from retail meat. The bacteria in the meat were separately sequenced and based on alignment, four different bacteria were identified. These findings suggest that bacteria found in retail meats are a reservoir for the spreading of ESBL blaVIM, blaBIC, blaKPC, and blaSIM resistance genes and bacteria strains.

Characterization of cefotaxime-resistant Escherichia coli isolated from wastewater treatment plant in Daegu (대구지역 폐수처리장에서 분리한 cefotaxime-resistant Escherichia coli의 특성)

  • Kim, Hwan-Deuk;Park, Dae-Hyun;Lee, Mi-Ree;Kim, Eun-Jeong;Cho, Jae-Keun
    • Korean Journal of Veterinary Service
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    • v.37 no.4
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    • pp.225-231
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    • 2014
  • In this study, 185 cefotaxime-resistant Escherichia coli were isolated from different stages of a wastewater treatment plant (WWTP) in Daegu in Korea. Among them, 99.5% (184 isolates) originated from raw sewage and 0.5% (1 isolates) from the final effluent. Cefotaxime-resistant E. coli were high resistant to ampicillin, piperacillin, cefazolin, cephalothin, cefachlor and cefamandole (99.5~100%). About 93% of the cefotaxime-resistant E. coli were extended-spectrum ${\beta}$-lactamases (ESBL)-producing E. coli. The $bla_{TEM+CTX}$ gene was the most predominant of the ESBL genes (72.5%), followed by $bla_{CTX-M}$ (16.2%), $bla_{TEM}$ (8.7%), $bla_{TEM+CTX+SHV}$ (1.1%), $bla_{TEM+SHV}$, $bla_{TEM+OXA}$, and $bla_{TEM+CTX+SHV}$ (respectvely 0.5%). Class 1 and 2 integron were found in 49.7% and class 3 integron was not found. All of integron positive isolates were multiresistant (i.e. resistant to four or more antibiotics). Our findings showed WWTP is contaminated with antibiotic resistant bacteria with resistance genes.

Prevalence of antimicrobial resistance and integrons in extended-spectrum β-lactamases producing Escherichia coli isolated from Nakdong and Gumho river (낙동강과 금호강에서 분리된 광범위 베타 락탐 분해효소 생성 Escherichia coli 내 항균제 내성 및 integrons의 분포)

  • Cho, Jae-Keun;Kim, Hwan-Deuk;Kwon, Soon-Hyo;Kim, Jin-Hyun;Jang, Sung-Il;Park, Choi-Kyu;Kim, Ki-Seuk
    • Korean Journal of Veterinary Service
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    • v.37 no.1
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    • pp.19-27
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    • 2014
  • This study was conducted to investigate the antimicrobial resistance, presence of ${\beta}$-lactamase genes and integrons in 83 ESBL-producing Escherichia coli isolated from Nakdong river and Geumho river in Daegu. Among the ${\beta}$-lactam antimicrobials, all isolates were resistant to ampicillin, cephalothin, cefamandole and cefotaxime, followed by piperacillin (98.8%), ampicillin/sulbactam (86.7%), aztreonam (60.2%) and cefepime (59.0%), whereas resistance to piperacillin/tazobacram, ticarcillin/clavulanic acid and cefoxitin was less than 30%. Many of the ESBL-producing Escherichia coli were also resistant to non-${\beta}$-lactams antimicrobials such as nalidixic acid (83.1%), sulfonamides (72.3%), ciprofloxacin (62.7%) and gentamicin (38.6%). All isolates showed resistance to seven or more antimicrobial agents. The most frequently detected gene was $bla_{TEM+CTX-M}$ (49.4%), followed by $bla_{CTX-M}$ (27.7%), $bla_{TEM}$ (6.0%) and $bla_{OXA}$ (1.2%). But $bla_{SHV}$ was not found. Class 1 integrons were found in 61.4% (51 isolates) of isolates, however, class 2 and 3 integrons were not detected. The results showed water from Nakdong river and Geumho river is contaminated with ESBL-producing E. coli isolates. These results suggest the need for further investigation of antibiotic resistant bacteria to prevent public health impacts in the water environment.