• 한국미생물·생명공학회지
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• 제51권4호
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• pp.517-525
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• 2023

다제내성 P. aeruginosa (MRPA)의 출현과 확산은 전 세계적으로 심각한 문제가 되었다. 특히 metallo-β-lactamases (MBLs)의 carbapenem 고도내성 관여 정도는 심각한 수준이며, 특히 P. aeruginosa는 장내세균 속 균종과는 달리 새로운 클론들이 지속적으로 나타나고 기존에 확산되었던 우세 클론을 대체하는 과정이 매우 빠르게 진행되고 있다. 이에 본 연구에서는 2017년 9월부터 2019년 9월까지 부산의 한 종합병원에서 다양한 의료용 시료로부터 분리된 18균주의 P. aeruginosa 균주에 대한 항균제 내성 유전자 분석과 DNA 염기서열 분석을 통한 Integron의 유전자 카세트 분석 및 접합에 의한 Plasmid 전달 분석을 수행하며 이에 대한 역학관계를 조사하고자 하였다. 18균주 모두 XDR 표현형을 보이는 균주였으며, Colistin(100%)을 제외한 대부분의 항생제에 내성을 나타냈으나, aztreonam(22.2%), ceftazidime(16.6%)에 일부 감수성을 보였다. 균주의 66.7%는 다양한 항균제 내성을 나타내는 Class1 integron을 가지고 있었으며, 접합에 의한 Plasmid전달도 성공적으로 이루어졌다(83.3%). 이는 이전의 장내세균에 대한 연구결과보다 25.8% 상향한 결과를 보여 공중보건에 대한 심각한 역학관점의 고찰을 필요로 한다. 특히, IMP-6 ST235 (66.7%)가 주를 이루며, VIM-2 ST357 (16.7), IMP-1 ST446 (16.7)이 확인되었다. 흥미롭게도, 국내에서는 아직까지 보고된 바가 없는 IMP-1 생성 ST446의 확인은 또 다른 MRPA 고위험 클론의 생성과 유행이라는 관점에서 주목할 만하다.

• Natural Product Sciences
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• 제25권2호
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• pp.172-180
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• 2019

Infections with Pseudomonas aeruginosa are difficult to treat not only because it is often associated with multidrug-resistant infections but also it is able to form biofilm. The aim of this study was to evaluate the antibiofilm and anti-Quorum Sensing (QS) activities of Thymbra capitata essential oils (EOs) against Beta Lactamase (BL) producing P. aeruginosa and the reference strain P. aeruginosa 10145. GC/MS analysis showed that thymol (23.25%) is the most dominant compound in T. capitata EOs. The MICs of T. capitata EOs against P. aeruginosa (BL) and P. aeruginosa 10145 were 1.11%. At sub MIC (0.041, 0.014 and 0.0046%), the EOs of T. capitata remarkably inhibited the biofilm formation of both strains tested and complete inhibition of the biofilm formation was reported at 0.041%. The EOs of T. capitata were found to inhibit the swarming motility, aggregation ability and hydrophobic ability of P. aeruginosa (BL) and P. aeruginosa 10145. Interestingly, the EOs of T. capitata reduce the production of three secreted virulence factors that regulated by QS system including pyocyanin, rhamnolipids and LasA protease. The potent antibiofilm and anti-QS activities of T. capitata EOs can propose it as a new antibacterial agent to control pseudomonas infections.

• Pediatric Infection and Vaccine
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• 제30권1호
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• pp.47-54
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• 2023

최근 광범위 항생제 사용의 증가로 인한 다제내성 그람 음성균의 출현이 전 세계적으로 문제가 되고 있다. 특히 다제내성 녹농균(multidrug-resistant Pseudomonas aeruginosa) 감염의 치료는 어려우며 중환자의 사망률을 증가시키는 원인이 된다. 세프톨로잔-타조박탐(ceftolozane-tazobactam, Zerbaxa^TM)은 5세대 세팔로스포린과 베타락탐 분해효소저해제로 다제내성 녹농균에 의한 복잡성 요로감염과 복잡성 복강내 감염의 치료에 효과가 있는 것으로 입증되었다. 본지에서 저자들은 소아청소년 혈액암 환자에서 발생한 다제내성 녹농균에 의한 균혈증을 세프톨로잔-타조박탐을 사용하여 성공적으로 치료한 국내 첫 번째 사례를 보고하고자 한다.

• Archives of Plastic Surgery
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• 제34권6호
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• pp.691-696
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• 2007

Purpose: The emergency of multi-drug resistant stains of bacteria represents a challenge in the field of plastic surgery. Especially, MRSA(methycillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa have strong pathogenicity as well as multi-drug resistance so that they have become a lot more problematic strains. This study has been planned to reduce the bacterial burden by applying $Acticoat^{(R)}$(Smith & Nephew Healthcare, Hull, England)dressing into the chronic wounds infected by multi-drug resistant strains and to facilitate their healing. Methods: Nanocrystalline silver dressings($Acticoat^{(R)}$) were applied to chronic wound infected by MRSA or Pseudomonas aeruginosa. Multi-drug resistant bacteria were smeared over a slide glass using sterilized cotton swabs and gram stains were performed directly before and after applying $Acticoat^{(R)}$ dressings at 1, 24, 48 and 72 hours. The gram-stained slides were observed using an optical microscope magnified 1000 times(${\times}1000$). The bacterial counts of the control group(0 hour) were compared to those of the experimental groups(1, 24, 48, and 72 hour). Paired T-test was used to assess a statistical significance. MRSA was cultured in two BAPs(blood agar plate) and two MacConkey plates with streak plate method. None were interventions on one culture plate, while on the other culture plate, $Acticoat^{(R)}$ was placed in a square shape and cultured for 72 hours at $37^{\circ}C$, then plates were examined. Pseudomonas aeruginosa was cultured in the same manner as MRSA. Results: There are the large amount of declination of bacterial counts with statistical significance after $Acticoat^{(R)}$ dressing. The bacteria grew in culture plate without specific intervention, but no bacteria grew in culture plate with applying of $Acticoat^{(R)}$ dressing. Conclusion: We believe that $Acticoat^{(R)}$ dressing could be used as an effective method of treating chronic wounds which are infected by multi-drug resistant organisms.

• Journal of Microbiology and Biotechnology
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• 제26권2호
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• pp.408-420
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• 2016

This study proposes an alternative approach for the use of chitosan silver-based dressing for the control of foot infection with multidrug-resistant bacteria. Sixty-five bacterial isolates were isolated from 40 diabetic patients. Staphylococcus aureus (37%) and Pseudomonas aeruginosa (18.5%) were the predominant isolates in the ulcer samples. Ten antibiotics were in vitro tested against diabetic foot clinical bacterial isolates. The most resistant S. aureus and P. aeruginosa isolates were then selected for further study. Three chitosan sources were tested individually for chelating silver nanoparticles. Squilla chitosan silver nanoparticles (Sq. Cs-Ag⁰) showed the maximum activity against the resistant bacteria when mixed with amikacin that showed the maximum synergetic index. This, in turn, resulted in the reduction of the amikacin MIC value by 95%. For evaluation of the effectiveness of the prepared dressing using Artemia salina as the toxicity biomarker, the LC₅₀ was found to be 549.5, 18,000, and 10,000 μg/ml for amikacin, Sq. Cs-Ag⁰, and dressing matrix, respectively. Loading the formula onto chitosan hydrogel dressing showed promising antibacterial activities, with responsive healing properties for the wounds in normal rats of those diabetic rats (polymicrobial infection). It is quite interesting to note that no emergence of any side effect on either kidney or liver biomedical functions was noticed.

• Journal of Microbiology and Biotechnology
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• 제17권10호
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• pp.1733-1737
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• 2007

A total of 2,280 nonduplicate clinical isolates of Pseudomonas aeruginosa, obtained nationwide from Korean non-tertiary care hospitals from 2002 to 2005, were identified and their susceptibilities to aminoglycosides, antipseudomonal penicillins, carbapenems, cephalosporins, monobactams, and quinolones were studied, together with their production of ${\beta}$-lactamases. Using disk diffusion and minimum inhibitory concentration tests, it was found that 2.9% of isolates were multidrug-resistant (MDR) P. aeruginosa. An EDTA-disk synergy test, PCR amplification with specifically designed primers, and direct sequencing of the PCR products showed that the $bla_{OXA-10}$, $bla_{VIM-2}$, $bla_{OXA-2}$, $bla_{OXA-17}$, $bla_{PER-1}$, $bla_{SHV-12}$, and $bla_{IMP-1}$ genes were carried by 34.3%, 26.9%, 3.0%,3.0%, 1.5%, 1.5%, and 1.5% of 67 MDR P. aeruginosa isolates, respectively. The prevalence of MDR P. aeruginosa was three-fold higher, compared with that from the United States. More than two types of ${\beta}$-lactamase genes were carried by 10.4% of isolates. The most prevalent ${\beta}$-lactamase genes were $bla_{VIM-2}$ and $bla_{OXA-10}$. This study is the first description of MDR P. aeruginosa trom non-tertiary care hospitals in Korea and the coexistence of the $bla_{VIM-2}$, $bla_{IMP-1}$, or $bla_{PER-1} in these clinical isolates.

• 한국미생물·생명공학회지
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• 제47권4호
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• pp.651-661
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• 2019

Targeting the pathogen viability using drugs is associated with development of drug resistance due to selective pressure. Hence, there is an increased interest in developing agents that target bacterial virulence. In this study, the inhibitory effect of ciclopirox, an antifungal agent with iron chelation potential, on the microbial virulence factors was evaluated in 26 clinical MDR Pseudomonas aeruginosa isolates collected from Alexandria Main University Hospital, a tertiary hospital in Egypt. Treatment with 9 ㎍/ml ciclopirox inhibited the hemolytic activity in 70% isolates, reduced pyocyanin production, decreased protease secretion in 46% isolates, lowered twitching and swarming motility, and decreased biofilm formation by 1.5- to 4.5-fold. The quantitative real-time PCR analysis revealed that treatment with ciclopirox downregulated the expression levels of alkaline protease (aprA) and pyocyanin (phzA1). Ciclopirox is used to treat hematological malignancies and the systemic administration of ciclopirox is reported to have adequate oral absorption with a satisfactory drug safety profile. It is important to calculate the appropriate clinical dose and therapeutic index to reposition ciclopirox from a topical antifungal agent to a promising virulence-modifying agent agent against P. aeruginosa, a problematic Gram-negative pathogen.

• 대한임상검사과학회지
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• 제54권2호
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• pp.119-124
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• 2022

녹농균(Pseudomonas aeruginosa), 대장균(Escherichia coli) 및 포도알균(Staphylococcus aureus)은 기회감염균이다. 또한 이들 세균은 다제내성(Multiple-Drug Resistance, MDR) 세균의 성질을 가지는 것으로 알려져 있다. 녹농균, 대장균, 포도알균에 대한 다양한 효능을 지닌 6가지 발효액의 항균활성을 분석하였다. 발효액을 섭취했을 때 대장균에서 유전적 발현 변화가 일어나는지 알아보기 위해 annealing control primer를 사용하여 유전자발현 분석을 수행하였다. 디스크확산법을 통해 무화과식초와 대봉감식초가 다른 발효액에 비해 억제대의 크기가 가장 크게 나타났고, 토종약초발효소는 항균효과가 없었다. 대장균에 5% 무화과식초를 처리하여 21일간 매일 계대배양하여 Escherichia coli O157:H7 OmpW gene for outer membrane protein W 유전자 발현이 감소하며, Synthetic construct Lao1 gene for L-amino acid oxidase, complete cds 유전자가 발현이 증가함을 확인하였다. 발효액 중에서 특히 무화과식초를 섭취하는 것은 우리 주변에 항상 존재하는 대장균에 대해 방어능력을 더욱 단단하게 가질 수 있음을 의미하며, 나아가 다제내성균에 대한 천연치료제로 유용하게 쓰일 수 있기를 기대한다.

• 대한의생명과학회지
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• 제19권3호
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• pp.245-253
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• 2013

To provide reference data or guideline for empirical treatment of bloodstream infection, we studied a change pattern in causative microorganisms and antimicrobial susceptibility in a general hospital at Gyeonggi province during five years. We retrospectively reviewed the frequency of causative microorganisms and antimicrobial susceptibility results of 5,782 microorganisms isolated from blood culture in a general hospital during the period from January 2008 to December 2012. The most common pathogens were Escherichia coli (14.7%), Staphylococcus aureus (7.5%), Streptococcus viridans group (4.9%), and Klebsiella pneumoniae (4.1%). The multiple microorganisms were isolated in 4.3% of bloodstream infection patients. The average contamination rate of blood culture during five years was 3.0%. Methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and penicillin-resistant Streptococcus pneumoniae were isolated at 62%, 27% and 11%, respectively. Cefotaxime-resistant E. coli and K. pneumoniae was 20% and 18%, respectively. Imipenem-resistant Pseudomonas aeruginosa (IRPA) and Acinetobacter baumannii (IRAB) was 25% and 66%, respectively. E. coli and S. aureus were most common pathogens isolated from blood culture for five years. The increase of multidrug-resistant microorganisms, such as MRSA, VRE, ESBL, IRPA and IRAB, requires more strict control of antibiotics and causes the need of the more updated guideline for the treatment of blood stream infection.

• Annals of Clinical Microbiology
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• 제21권4호
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• pp.80-85
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• 2018

배경: 본 연구는 국내 병원에서 분리된 methicillin 내성 Staphylococcus aureus (MRSA), vancomycin 내성 Enterococcus faecium (VREFM) 및 다제 내성 multidrug-resistant Pseudomonas aeruginosa (MRPA) 등에 대한 구리, 유기(구리 78%, 주석 22%), stainless steel의 살균력을 비교 실험하여, 국내 병원 환경에 의한 항생제 내성 균주 교차 감염을 예방하는 데 구리와 유기의 활용성을 분석하고자 하였다. 방법: MRSA, VREFM, MRPA 균주는 2017년 의정부성모병원에서 분리 동정된 wild type 3균주씩을 혼합하여 사용하였으며 모두 항생제 다제 내성 균주로 나타났다. MRSA, VREFM, MRPA 균주 각각을 Tryptic soy broth (Oxoid, England)에 접종하여 $35^{\circ}C$에서 24시간 배양한 후, 각각 초기 접종균액의 균수를 $10^5\;log\;CFU/mL$로 조정하였다. 구리, 유기, stainless steel 용기에 준비된 MRSA, VREFM, MRPA 접종균액 100 mL씩을 각각 접종한 후, 습도가 유지되도록 덮개를 덮은 후 $35^{\circ}C$ incubator에서 초기부터 9일까지 생존균수를 측정하였다. 결과: 본 연구결과 국내에서 분리된 항생제 다제 내성 MRSA, VREFM, MRPA 균주에 대한 구리 및 유기의 살균효과를 확인하였다. Stainless steel의 살균력은 구리 및 유기에 비해 매우 미약하였고, MRSA 및 VREFM에 비해 MRPA의 살균효과가 크게 나타났다. 결론: 교차감염을 예방하기 위하여 병원 내 문손잡이, 수도꼭지, 침대레일 등에 구리나 유기를 적용하여, 장기간 실험을 진행하고 있는 국외 사례와 같이, 국내 병원에서도 구리와 유기를 이용한 병원 내 교차 감염 예방 연구가 필요하다고 생각한다.