기본 항생제에 내성을 보인 그람 음성 간균에 대한 2차적 항생제 감수성 검사 결과

김정숙,이채훈,김경동 영남대학교 의과대학 1993 Yeungnam University Journal of Medicine Vol.10 No.1

1992년 12월부터 1993년 4월까지 영남대학교 의과대학 부속병원 임상병리과 세균검사실에 의뢰된 입원환자검체를 대상으로 1차 항생제 감수성 검사에서 모든 항생제에 내성을 보인 그람음성간균에 대해 2차 항생제 감수성 검사를 실시하여 그 결과를 분석하였다. 1차 항생제 감수성 검사에서 모든 항생제에 내성을 보인 균주의 빈도는 A. baumanni, E. cloacae, E. coli, P. aeruginosa, Serratia species순이었다. 소변에서는 기본 항생제에 내성을 보인 균종은 E. coli가, 호흡기와 창상감염에서는 A. baumanni가 가장 많았으며, P. aeruginosa는 모든 검체에서 높은 빈도로 분리되었다. 2차 항생제 감수성 검사에서 전 검체의 53%가 모든 2차 항생제에 대해 내성을 보였다. ceftazidime, aztreonam, ciprofloxacine 등은 상대적으로 항균효과가 높았으나, cefamandole은 모든 균종에서 효과가 없는 것으로 나타났다. Major pathogenic Gram-negative organisms such as P. aeruginosa, Serratia species, E. coli, Enterobacter species which are isolated from the specimens in large medical centers are greatly resistant to the commonly used antibiotics. Gram-negative bacilli, which had been isolated in Yeungnam University Hospital during the period from December 1992 to April 1993 and turned out to be resistant to the primary antibiotics susceptibility test for chloramphenicol, ampicillin, cephalothin, gentamicin, tetracyclin, amikin and tobramycin, were subjected to the secondary antibiotics susceptibility test for aztreonam, ceftazidime, ciprofloxacine, cefotaxime, cefamandole, piperacillin, ticarcillin and sulfamethoxazole trimethopime. Out of 315 tested organisms, 167 organisms (53%) were resistant to all secondary antibiotics in vitro. Antimicrobial activity of ceftazidime (37.1%), aztreonam (11.%), ciprofloxacine (7.9%) against Gram negative bacilli were slightly more active than other antibiotics tested, while cefamandole was not active to all the Gram-negative bacilli tested. According to the specimens, E. coli was the most frequently resistant organisms to the primary antibiotics from urine, A. baumanii, from respiratory system and wounds, and P. aeruginosa from various specimens. In summary, Gram negative bacilli resistant to the primarily applied antibiotics also were resistant to the secondary antibiotics. Rearrangement of the antibiotics disks for the antibiotic susceptibility test should be considered.

그람 음성 간균에서 16S rRNA Methylase 생성 빈도와 생성 세균의 내성 양상

이경원,이혁민,고은미,김창기,염종화,정윤섭 대한임상미생물학회 2010 Annals of clinical microbiology Vol.13 No.1

Background: Recently a novel plasmid-mediated resistant mechanism that conferred high-level resistance to aminoglycoside via methylation of 16S rRNA was reported. The aims of this study were to determine the prevalence of the 16S rRNA methylase genes and to characterize the coresistance to other antibiotics in Gram-negative bacilli. Methods: Consecutive non-duplicate Gram-negative bacilli were isolated from clinical specimens at a Korean secondary- and tertiary-care hospital from July 2006to June 2007. The antimicrobial susceptibility was tested by the CLSI agar dilution method,and PCR was performed to detect the 16S rRNA methylase genes in the arbekacin-resistant isolates. Results: In Gram-negative bacilli, the proportions of 16S rRNA methylase gene-positive isolates were 5%(75/1,471) in the secondary-carehospital and 4%(48/1,251) in the tertiary-care hospital, and the positive rates by species were 1% Escherichiae coli 16% (10/1,062), Klebsiella pneumoniae 16% (75/460), K. oxytoca 2% (1/44), Citrobacter spp. 9% (7/82), Enterobacter spp. 2% (4/181), Serratia marcescens 6% (6/100), Proteus miriabilis 4% (2/57), Achromobacter xylosoxidans 20% (1/5), Pseudomonas aeruginosa <1% (1/505), Acinetobacter spp. 10% (11/112), and Stenotrophomonas maltophilia 2% (1/66),respectively. Among 16S rRNA methylase-positive isolates from secondary- and tertiary-care hospitals,93% (70/75) and 90% (43/48), respectively, were armA positive, and others, except one rmtA positive isolate, were positive for the rmtB gene, according to PCR results. The rates of ESBL-positive and cefoxitin-resistant K. pneumoniae were 59% and 92%,respectively. In addition, 91% of 16S rRNA methylase-producing K. pneumoniae were positive for qnrB. There were no MBL producers among 16S rRNA methylase-producing Pseudomonas and Acinetobacter species. Conclusion: The novel aminoglycoside-resistant mechanisms involving16S rRNA methylase were prevalent and widely distributed among Gram-negative bacilli in Korea, and other resistance mechanisms were commonly associated with 16S rRNA methylasemediated resistance in Korea. (Korean J Clin Microbiol 2010;13:19-26)

Ticarcillin/clavulanic Acid의 호기성 그람음성 간균에 대한 시험관내 항균력

정윤섭,이경원,권오헌 대한감염학회 1995 감염 Vol.27 No.2

목적: Ticarcillin/clavulanic acid(TICCV)는 β-lactamase에 안정한 광범위 penicillin제제이다. 외국에서는 이 항균제에 내성인 Enterobacteriaceae가 드물다고 하나 우리나라 균주의 내성은 연구 보고된바 없다. 이 연구에서는 우리나라에서 분리되는 그람음성 간균에 대한 항균력을 시험하고자 하였다. 방법: 세브란스병원 환자 검체에서 분리된 호기성 그람음성 간균에 대한 TICCV의 항균력을 carbenicillin, piperacillin 및 ticarcillin과 NCCLS 한천희석법으로 비교하였다. 결과:E.coli, K.oxytoca, P.mirabilis, P.vulgaris, Providencia sp., Y.enterocolitica, A.baumannii, X.maltophilia에 대한 TiCCV의 MIC90은 carbenicillin, piperacillin 및 ticarcillin보다 낮았다. E.cloacae, E.aerogenes, S.marcescens, P.aeruginosa 이외의 모든 균종은 TICCV에 대한 내성율이 다른 항균제에 대한 내성을 보다 낮았다. 결론: TiCCV의 시험관내 항균력 시험결과로 미루어 볼 때, 이 항균제는 carbenicillin, piperacillin 혹은 ticarcillin보다 호기성 그람음성 간균에 의한 감염 치료에 더 유용할 것이라는 결론을 얻었다. Background: Resistance of gram-negative bacilli is mostly due to production of β-lactamases. Resistance of enterobacteriaceae to ticarcillin/clavulanic acid(TICCV), reported to be rare in the United States, is not known in Korea. The aim of this study was to determine the activity of TICCV against aerobic gram-negative bacilli. Methods: Activity of TICCV was compared with those of carbenicillin, piperacillin and ticarcillin by the NCCLS agar dilution method against aerobic gram-negative bacilli isolated from patients at a tertiary care hospital. Results: MIC90 of TICCV were low against E.coli, K.oxytoca, P.mirabilis, P. nulgaris, Providencia sp., Y.enterocolitica, A. baumannii and X. maltophilia. Resistance rates to TICCV were low, except for E.cloacae, E. aerogenes, S. marcescens and P. aeruginosa. Conclusions: The in vitro test result indicated that TICCV should be more effective than the other antimicrobial agents for the treatment of infections due to aerobic gramvegative bacilli.

E test를 이용한 그람음성 간균의 항균제 MIC측정

김재룡,김영재 啓明大學校 醫科大學 1997 계명의대학술지 Vol.16 No.2

For the adequate treatment to infectious disease, it is necessary to identify the etiologic organisms and evaluate the susceptibility to antimicrobial agents. As the patterns of resistance to various antimicrobial agents is persistently changing, the significance of the antimicrobial susceptibility test is enhanced more and more. We investigated that the usefulness of the E test(AB Biodisk, Solna, Sweden) for antimicrobial susceptibility test to gram negative bacilli. From December, 1996 to March, 1997,118 strains of gram negative bacilli isolated from Dongsan Medical Center, Keimyung University were investigated. The minimal inhibitory concentration(MIC) was estimated by E test. Antimicrobial agents used in E test were imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin, gentamicin, ceftriaxone, amikacin, amoxicillin/clavulanic acid, aztreonam, cefotaxime, cefuroxime, and piperacillin. The criteria for antimicrobial susceptibillity was the guidelines of the National Committee for Clinical Laboratory Standards(1993). Among the 118 strains of gram negative bacilli analyzed by E test, A. baumanii, E. coli, P. aeruginosa and K. pneumoniae were each 20. 19. 26. and 9 strains. In the cases of A. baumanii, all strains were sensitive to imipenem and MIC range was 0.5-2㎍/mL, MIC50 WAS 0.5㎍/mL, and MI90 was 2 ㎍/mL. The half of the strains were sensitive to aztreonam, and the majority were resistant to most antimicrobial agents, except amikacin, aztreonam and imipenem. Among 19 strains of E. coli, all strains were sensitive to imipenem and MIc range was 0.13-2 ㎍/mL, MIC50 was 0.5㎍/mL, and MIC90 was 2 ㎍/mL. The majority were resistant to amoxicillin/clavulanic acid and piperacillin(9 and 12 strains). In the 26 strains of P. aeruginosa, 22 strains were sensitive to imipenem and each 2 strains were imtermediate and resistant to resistant to imipenem. MIC range to imipenem was 0.38-64 ㎍/mL, MIC50 was 2 ㎍/mL, and MIC90 was 8 ㎍/mL. Most of strains were sensitive to ceftazidime, piperacillin/tazobactam, ciprofloxacin, amikacin, aztreonam, and piperacillin, but most of strains were resistant to gentamicin, ceftriaxone, amoxicillin/clavulanic acid, cefotaxime, cefuroxime. The E test had been found to be valuable and to be a rapid, convenient and reliable method for estimating MIC and detecting high-resistance to various antimicrobial agents.

Molecular Characterization and Prevalence of 16S Ribosomal RNA Methylase Producing Bacteria in Amikacin Resistant Gram-negative Bacilli Isolated from Clinical Specimens

Kyung-A Shin,Seock Yeon Hwang,Seung Bok Hong 대한의생명과학회 2012 Biomedical Science Letters Vol.18 No.3

Recently, the prevalence of 16S rRNA methylase conferring high-level resistance to aminoglycosides has been increasing in Gram-negative bacilli globally. We determined the prevalence and genotype of these methylase-producing bacteria, and characterized the co-resistance to β-lactam antibiotics and quinolone in Gram-negative clinical isolates collected in 2010 at a hospital in Korea. Among 65 amikacin-resistant isolates screened from 864 Gram-negative bacilli (GNB), 16S rRNA methylase genes were detected from 49 isolates, including Acinetobacter baumannii (43), Klebsiella pneumoniae (2), Proteus mirabilis (2) and Serratia marcescens (1), Empedobacter brevis (1). All of the 16S rRNA methylase genotype was armA and no variant sequences of amplified PCR products for armA were noted. The 16S rRNA methylase producing bacteria showed much higher resistance to aminoglycoside for Enterobacteriaceae and glucose non-fermenting (NF)-GNB and to imipenem for glucose NF-GNB, than the non-producing isolates. All of the 16S rRNA methylase producing Enterobacteriaceae had the extended-spectrum-β-lactamase. In addition, two K. pneumoniae concurrently produced both plasmid-mediated AmpC β-lactamase and qnrB gene. All of the amikacinresistant A. baumannii (43) co-harbored armA 16S rRNA methylase and blaOXA-23 carbapenemase. In conclusion, 16S rRNA methylase producing bacteria were very prevalent among GNB in South Korea, and were commonly associated with co-resistance, including carbapenem and quinolone.

임상 검체분리 Pseudomonas spp. 및 Acinetobacter spp.에서 검출된 blaVIM-2 카세트 보유 인테그론 구조의 다양성

염종화,신희봉,윤동은,정윤섭 대한임상미생물학회 2012 Annals of clinical microbiology Vol.15 No.4

Background: Metallo-β-lactamase-mediated carbapenem resistance has been increasingly reported in Pseudomonas, Acinetobacter and other Gram-negative bacilli (GNB) in many countries. A few studies showed highly variable structure of MBL-gene cassette-carrying integrons. The aim of this study was to determine the structure of blaVIM-2-carrying integrons in Pseudomonas and Acinetobacter. Methods: blaVIM-2-carrying GNB were isolated at a Korean hospitals during the years 1995-1999 and 2005. The size of blaVIM-2-carrying integrons was estimated by the PCR products. Representative integrons were sequenced by the dideoxy-chain termination method. The MICs of antimicrobial agents were tested by the CLSI agar dilution methods. Results: During the years 1995-1999 and 2005, the approximate size of the blaVIM-2-carrying class 1 integrons was 3-7 kb in 35 Pseudomonas isolates and 3-5 kb in 24 Acinetobacter isolates. The integrons carried one-five resistance gene cassettes in addition to the blaVIM-2 cassette. Other resistance gene cassettes found were blaOXA-1, aacA1, aac(6’)-I, and aac(6’)-II. Interestingly, sequences homologous to part of a putative class II intron were inserted into the recombination site of the last cassette in four of nine integrons. The class 1 integron from P. aeruginosa isolates had fused orf/IntI1 in a downstream leftward inverted repeat (IRi). Conclusion: According to period, the size and structure of blaVIM-2-carrying integrons are quite variable,but an identical one is also present in a different genus,indicating high mobility of the blaVIM-2 cassette and horizontal transfer of the whole integron. We suggest that the class 1 integron containing the blaVIM-2gene is spreading horizontally among Gram- negative bacilli and is undergoing continuous development in Korea.

Increasing Carbapenem-Resistant Gram-Negative Bacilli and Decreasing Metallo-β-Lactamase Producers over Eight Years from Korea

이양순,용동은,김창기,정혜선,정석훈,이경원,정윤섭 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.2

The trends and types of carbapenemase-producing Gram-negative bacilli were analyzedfrom clinical specimens collected between 2005 and 2012 at a Korean teaching hospital. The proportions of carbapenem-resistant Acinetobacter spp. increasedmarkedly to 66%. Metallo-β-lactamase producers significantly decreased and the majority shifted from the blaVIM-2 type to the blaIMP-1 type.

Gentamicin 내성 호기성 그람 음성 간균에 대한 Astromicin의 시험관내 항균력

김양리,유진홍,신완식,강진한,강문원 대한화학요법학회 1994 대한화학요법학회지 Vol.12 No.2

Aminoglycosides have been widely used in many aerobic gram-negative infections, but their use is limited by development of resistance and toxicities. Astromicin is known to be a new aminoglycoside that is less influenced by aminoglycoside-modifying enzymes and has relatively low toxicity. We evaluated in vitro activities of astromicin against 413 strains of gentamicin-resistant aerobic gram-negative bacilli(63 stains of A. baumannii, 60 strains of E.coli, 56 strains of E.cloacae, 82 strains of K.pneumoniae, 60 strains of P.aeruginosa, 60 strains of S.marcescens, 16 strains of C.freundii and 16 strains of P.mirabilis) with standard agar dilution method, and compared with other 3 aminoglycosides; tobramycin, amikacin, and arbekacin. Astromicin is two to eightfolds as effective as amikacin against C.freundii, E.cloacae, E.coli, K.pneumoniae, and P.mirabilis. In vitro activity of astromicin against A.baumannii is better than that of amikacin, but worse than that of arbekacin. It has better activity against S.marcescens compared with amikacin and arbekacin. Amikacin shows best activity against Paeruginosa. Tobramycin has poor acitivity against all organisms in this study except E.coli.

Metallo-β-lactamase 생성 그람음성 간균

용동은 대한임상미생물학회 2009 Annals of clinical microbiology Vol.12 No.3

Among gram-negative bacteria, rate of antibiotic resistance has been increasing. As a result, carbapenem is now considered as a last resort of therapeutic regimens for gram-negative bacterial infections. The choice of antibiotics has been impeded by the spread of organisms producing metallo-β-lactamases (MBL), which can confer resistance to nearly all β-lactams. MBLs have extremely diverse structures and are carried by various organisms including human pathogens. This review will focus on the classification and current status of MBL reported in Korea.

레클레르시아 아데카르복시라타에 의한 각막궤양 1예

이기일,정성근,황형빈 대한안과학회 2014 대한안과학회지 Vol.55 No.6

Purpose: To report a case of corneal ulcer caused by Leclercia adecarboxylata in an immunocompetent patient. Case summary: A previously healthy 43-year-old female presented with right ocular pain and was referred to our clinic under the impression of corneal abrasion and secondary infection. The patient was treated at a local clinic for 3 days using artificial tears, therapeutic contact lens, topical antibiotics, and anti-inflammatory eye drops but showed no improvement. Gram staining, bacterial and fungal cultures and antibiotic sensitivity test were performed from a corneal scrape. The cultures revealed growth of Leclercia adecarboxylata. The patient was treated with moxifloxacin and ofloxacin eye drops. After 2 weeks of treatment, the infection resolved without remaining scars. Conclusions: Reportedly, Leclercia adecarboxylata affects humans only as an opportunistic pathogen or part of polymicrobial infections. However, in the present case, Leclercia adecarboxylata was isolated as a single pathogen in an immunocompetent patient which is the first clinical report of this microorganism found in an ocular sample. Therefore, if antibiotic-susceptible gram-negative bacilli are found in opthalmologic samples, the above bacteria should be considerd in the diagnosis. J Korean Ophthalmol Soc 2014;55(6):918-922