임상검체에서 분리된 그람 음성 세균들에 대한 Isepamicin의 시험관 내 항균력 = In Vitro Activities of Isepamicin and Other Aminoglycosides against Gram-Negative Organisms

다국어 초록 (Multilingual Abstract)

Background : The increasing incidence of multidrug-resistant gram-negative bacteria causing nosocomial infections is an important clinical problem. Isepamicin is a recently developed aminoglycoside which has been known to have potent activity against gram-negative organisms. We evaluated the in vitro activities of isepamicin and other aminoglycosides against a large number of gram-negative organisms.
Materials and Methods : We tested the in vitro antimicrobial activities of isepamicin, amikacin, gentamicin, and tobramycin against 566 gram-negative organisms collected between January 2006 and June 2006 in Asan Medical Center. Minimal inhibitory concentrations (MICs) were determined and interpreted according to the recommendations of Clinical and Laboratory Standard Institute (CLSI). The breakpoint MIC used for interpretation of isepamicin was MIC≤16 g/mL as susceptible, 32 g/mL as intermediate, and ≥64 g/mL as resistant.
Results : The MIC50/MIC90 of isepamicin for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacter cloacae were 1/2, 0.5/>128, 4/16, 16/>128, and 1/2 g/mL, respectively. The susceptibilities for E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, and E. cloacae were 100%, 86.4%, 89.7%, 50.0%, and 96.6%, respectively. For E. coli, K. pneumoniae, P. aeruginosa, and E. cloacae, isepamicin had better in vitro activities than gentamicin and tobromycin, and had similar activities with amikacin. For A. baumanii, all four tested aminoglycosides had similar in vitro activities.
Conclusion : Isepamicin had excellent in vitro activities against gram-negative organisms, except A. baumanii. The overall in vitro activities were similar with amikacin.

국문 초록 (Abstract)

목 적 : 그람 음성 세균은 다양한 지역사회 및 병원 획득 감염의 원인균이다. 최근에는 병원 감염을 일으키는 그람 음성 세균에서 항균제 내성균의 출현과 확산이 큰 문제가 되고 있다. Isepamicin은 최근에 소개된 gentamicin B의 유도체로 외국에서의 연구에 의하면 그람 음성 세균들에 대한 항균력이 우수함이 보고 된 바 있다. 본 연구에서는 우리나라의 임상 균주들을 대상으로 그람 음성세균에서 isepamicin의 시험관내 항균력을 기존의 아미노배당체 제재들과 비교하여 평가하고자 하였다.
재료 및 방법 : 2006년 1월에서 6월 사이에 서울아산병원 환자에서 분리된 Escherichia coli 113 균주, Klebsiella pneumoniae 110 균주, Pseudomonas aeruginosa 117 균주, Acinetobacter baumannii 108 균주, 그리고 Enterobacter cloacae 118 균주를 대상으로 isepamicin, amikacin, gentamicin, tobramycin에 대한 최소억제농도(minimal inhibitory concentration, MIC)를 한천 희석법(Mueller-Hinton Agar)을 이용하여 측정하였다. 감수성 여부는 CLSI 기준에 따랐으며, isepamicin은 MIC≤16 g/mL를 감수성, MIC=32 g/mL를 중등도 내성, MIC≥64 g/mL를 내성으로 판정하였다.
결 과 : Isepamicin의 E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, E. cloacae에 대한 MIC50/ MIC90은 각각 1/2, 0.5/>128, 4/16, 16/>128, 1/2 g/mL였고, 항균제 감수성률은 차례대로 100%, 86.4%, 89.7%, 50.0%, 96.6%였다. 기존 아미노배당체 제재들과 비교하면 E. coli, K. pneumoniae, P. aeruginosa, E. cloacae에서는 amikacin과 비슷한 감수성률을 보였고, gentamicin과 tobramycin보다 높은 감수성률을 보였다. A. baumannii의 경우 isepamicin의 감수성률이 50.0%로 비교적 낮았지만 amikacin, gentamicin, tobramycin도 각각 50.0%, 46.3%, 47.2%의 감수성률을 나타내어 4가지 항균제가 모두 비슷한 항균력을 보였다.
결 론 : Isepamicin은 그람 음성 세균들에 있어 기존의 아미노배당체 제재들과 비교했을 때 amikacin과는 동등한 시험관내 항균력을 보이고 gentamicin, tobramycin보다 뛰어난 시험관내 항균력을 보여 사용이 유망한 아미노배당체 중 하나라 생각된다.

참고문헌 (Reference)

1 "in vitro comparative evaluation of aminoglycosides at a cancer centre" 39 : 135-138, 2002

2 "in vitro activities of 16 antimicrobial agents against clinical isolates of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in two regional hospitals in Taiwan" 39 : 59-66, 2006

3 "The resistance of recent clinical isolates against isepamycin,other aminoglycosides and injectable beta-lactams" 53 : 46-59, 2000

4 "The changing nature of aminoglycoside resistance mechanisms and the role of isepamicin-a new broad-spectrum aminoglycoside" 7 : 31-44, 1995

5 "Single daily dosing of aminoglycosides in immunocompromised adults:a systematic review" 24 : 810-815, 1997

6 "Resistance to aminoglycoside antibiotics in gram- negative bacilli and staphylococci isolated from blood Report from a European collaborative study European Study Group on Antibiotic Resistance" 131-44, 1990

7 "Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity" 43 : 1549-, 1999

8 "Principles and practice of infectious diseases" Churchill Livingstone 2005

9 "Prevalence of extended-spectrum beta-lactamase-producing Enterobacter cloacae in the Asia-Pacific region results from the SENTRY Antimicrobial Surveillance Program 1998 to 2001" 47 : 3989-3993, 2003

10 "Performance standards for antimicrobial susceptibility testing; sixteenth infromational supplement" Clinical and Laboratory Standards Institute, Wayne, PA. 2006

11 "Once-daily dosing of aminoglycoside antibiotics" 14 : 475-487, 2000

12 "Once-daily aminoglycoside dosing in immunocompetent adults:a meta-analysis" 124 : 717-725, 1996

13 "Multicentre surveillance of Pseudomonas aeruginosa susceptibility patterns in nosocomial infections" 51 : 347-352, 2003

14 "Molecular epidemiology of aminoglycoside resistance in Acinetobacter spp" 47 : 455-456, 1998

15 "Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically" Clinical and Laboratory Standards Institute, Wayne, PA. 2006

16 "In vitro activities of tigecycline and other antimicrobial agents against clinically isolated organisms in Taiwan" 11 : 330-341, 2005

17 "Comparison of in vitro activity of Sch 21420 with those of amikacin" 338-45, 1980

18 "Clinical pharmacokinetics and pharmacodynamics of isepamicin" 38 : 205-223, 2000

19 "An overview of the safety of isepamicin in adults" 7 : 87-93, 1995

20 "Aminoglycoside resistance in Gram- negative blood isolates from various hospitals in Belgium and the Grand Duchy of Luxembourg.Aminoglycoside Resistance Study Group" 44 : 483-488, 1999

21 "Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features" 9 (9): 148-165, 1996

22 "A pragmatic approach to identify extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in Taiwan:in vitro activity of newer and established antimicrobial agents" 48 : 277-282, 2004