단일병원 신생아 중환자실에서 Extend Spectrum β - Lactamase 생성 균주 출현의 역학 및 임상적 특징 = Clinical Characteristics and Epidemiologic Study of Infection Due to Extended Spectrum β - Lactamase Producing Organism in a Neonatal Intensive Care Unit

다국어 초록 (Multilingual Abstract)

Purpose:The extended-spectrum β-lactamase(ESBL) producing organism have emerged to be an important pathogen in neonatal intensive care unit(NICU). This study was conducted to investigate incidence, characteristics and risk factors associated with ESBL organism among newborns in NICU.
Methods:The subjects included 98 newborns admitted to NICU at Asan Medical Center between September 1998 to July 2002, from whom a total of 177 ESBL organisms were detected. Annual number of isolates, distribution of cultured sites, types of illness and patient profile were retrospectively reviewed and risk factors associated with the infection were identified between control group of 115 non-infected newborns.
Results:Of 177 ESBL isolates, 150(84.7%) and 27(15.3%) were ESBL producing K. pneumoniae and E. coli, respectively. The annual number of isolates were 2(1.1%), 23(13.0%), 126(71.2%), 17(9.6%) and 9(5.1%) for years 1998 to 2002. The annual incidence of sepsis due to ESBL organism was 2.9 %, 8.2%, 17.8%, 3.1% and 2.8% for years 1998 to 2002:Year 2000 being an outbreak. The ESBL organisms were largely found in bronchial aspirates and urine. The infected patients were younger gestational age. The mean cultivation period was at 29.1±2.8 days. The risk factors for infection included, in the order of frequency, total parenteral nutrition, central venous catheterization, ventilator care, respiratory distress syndrome and dexamethasone therapy.
Conclusion:Awareness of increasing infection due to ESBL producing organism in NICU is important not only for infection control but also placing a great limit in use of antibiotics, especially in premature infants.

국문 초록 (Abstract)

목 적 : 국내에서 ESBL 생성 균주는 1990년대 후반에 급증하여 본원에서도 1999년 자료에 의하면 전체 병원 감염의 E. coli와 K. pneumoniae의 20-30%가 ESBL 생성 균주였다. 신생아 중환자에서 이러한 균주의 감염은 치료 및 예후에 중요한 인자로 작용될 것으로 생각되어 이 균주들의 출현율과 이 균주와 관련된 위험인자를 알아보고자 본 연구를 시행하였다.방 법 : 1998년 9월부터 2002년 7월까지 3년 11개월간 신생아 중환자실에 입원했던 환아 중 임상검체에서 ESBL 생성 균주가 분리된 환아 98명, 177균주를 대상으로 하였다. 각 연도별, 배양부위별 발생률을 비교하고, 병록지를 토대로 임상적 특징을 조사하여 위험인자를 알아보았다. 대조군은 같은 시기에 입원한 환아로 균주가 배양되지 않은 115명으로 하였다.결 과 : 총 177균주 중 ESBL 생성 K. pneumoniae가 150균주(84.7%)였고, E. coli가 27균주(15.3%)였다. 연도별 발생률은 1998년 2균주(1.1%), 1999년 23균주(13.0%), 2000년 126균주(71.2%), 2001년 17균주(9.6%), 2002년 9균주(5.1%)로 2000년도에 가장 많았다. ESBL 생성 균주에 의한 패혈증은 7.7%(15/ 196례)였고, 연도별로 1998년과 1999년에 각각 2.9%(1/34례), 8.2%(4/49례)였다가 2000년도에 집단 발생하면서 17.8%(8/45례)로 증가했고, 2001년, 2002년에 각각 3.1%(1/32례), 2.8%(1/36례)로 감소하는 양상을 보였다. 배양부위는 집단보균 발생으로 인한 균주를 제외하고 기관내 흡인물과 소변이 각각 19균주(10.7%)로 가장 많았고, 혈액, 상처주위 농양, 복수액, 중심 정맥 도관 말단부 순이었다. 대상 환아군은 대조군과 비교하였을 때 재태기간의 차이가 있었으나, 출생체중, 성별비, 사망, 생존비의 차이는 없었다. 재원기간은 환아군에서 유의하게 길었고, ESBL생성균주가 배양되는 시기는 입원 후 29.1±2.8일이었다. 관련된 위험인자로는 총 정맥 영양 시행, 중심 정맥 도관 삽입, 비위 도관 삽입, 인공 호흡기 치료, 서팩턴트 치료, 스테로이드 치료의 빈도순으로 많았다.

참고문헌 (Reference)

1 "β-lactamases in laboratory and clinical resistance" 8 : 557-584, 1995

2 "β-lactamases in laboratory and clinical resistance" 8 : 557-584, 1995

3 "The crisis in antibiotic resistance" 257 : 1064-1073, 1992

4 "The characteristics of extended spectrum β-lactamases in Korean isolates of Enterobacteriaceae" 39 : 514-519, 1998

5 "TEM- and SHV- derived extended spectrum β-lactamase : Relationship between selection, structure and function" 35 : 7-22, 1995

6 "Prevalence of important pathogens and antimicrobial activity of parenteral drugs at numerous medical centers in the United States, I. Study on the threat of emerging resistance : real or perceived? Fluroquinolone resistance surveillance group" 19 : 203-215, 1994

7 "Piperacillin/tazobactam in the treatment of Klebsiella pneumoniae infection in neonates" 15 : 47-51, 1998

8 "Outbreak of nosocomial infections due to Klebsiella pneumoniae producing SHV-4 beta- lactamase" 9 : 797-803, 1990

9 "Outbreak of nosocomial infection caused by Klebsiella pneumoniae producing extended spectrum β-lactamase in a neonatal intensive care unit" 2 : 13-28, 1997

10 "Outbreak of infection in two UK hospitals caused by a strain of Klebsiella pneumoniae resistant to cefotaxime, and ceftazidime" 20 : 97-103, 1992

11 "Outbreak of extended spectrum β-lactamase producing Klebsiella pneumoniae in a neonatal unit" 80 : F64-F68, 1999

12 "Novel plasmid-mediated β-lactamase(TEM-10)conferring selective resistance to ceftazidime and aztreonam in clinical isolates of Klebsiella pneumoniae" 33 : 1451-1456, 1989

13 "Nosocomial outbreak of Klebsiella infection resistant to late- generation cephalosporins" 119 : 353-358, 1993

14 "Molecular epidemiology of an outbreak of multiresistant Klebsiella pneumoniae in a Tunisian neonatal ward" 52 : 427-433, 2003

15 "Molecular epidemiology of an SHV-5 extended spectrum β-lactamase in Enterobacteriaceae isolated from infants in a neonatal intensive care unit" 21 : 915-923, 1995

16 "Molecular epidemiologic analysis of a cluster of Klebsiella pneumoniae infection in neonatal intensive care unit" 43 : 477-483, 2000

17 "Invasive disease due to extended spectrum β-lactamase producing klebsiella pneumoniae in a neonatal unit:the possible role of cockroaches" 44 : 13-17, 2000

18 "Inactivation of antibiotics and the dissemination of resistance genes" 264 : 375-382, 1994

19 "Hospital-acquired infections in the neonatal intensive care unit-Klebsiella pneumoniae" 26 : 340-345, 2002

20 "Gene sequence and biochemical characterization of FOX-1 from Klebsiella pneumoniae, a new i-type plasmid mediated β-lactamase with two molecular variants" 2150-2157, 1994

21 "Extended spectrum β-lactamase producing Klebsiella pneumoniae in a neonatal intensive care unit:risk factors for infection and colonization" 53 : 198-206, 2003

22 "Extended broad-spectrum β-lactamase conferring transferable resistance to newer β-lactam agents in Enterobacteriaceae:hospital prevalence and susceptibility pattern" 10 : 867-878, 1988

23 "Evaluation of MicroScan Neg Combo Panel Type 21 to detect ESBL" 2 : 158-166, 1999

24 "Clinical and molecular-biologic study of extended spectrum β-lactamase producing Klebsiella pneumoniae in a neonatal intensive care unit" 8 : 25-32, 2001

25 "Activity of sulbactam in combination with ceftriaxone in vitro and in experimental endocarditis caused by Escherichia coli producing SHV-2- like β-lactamase" 34 : 581-586, 1990

26 "A simultaneous outbreak on a neonatal unit of two strains of multiple antibiotic resistant Klebsiella pneumoniae controllable only by ward closure" 49 : 183-192, 2001