병원획득 Klebsiella pneumoniae 균혈증 분석을 통해 본 Ciprofloxacin 내성과 Extended- Spectrum β-Lactamase생성 간의 연관성
The Close Relationship between Ciprofloxacin Resistance and Extended-Spectrum β-Lactamase Production : Analysis of 154 Consecutive Nosocomially-Acquired Klebsiella pneumoniae Bacteremia
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목 적 : K. pneumoniae는 ciprofloxacin내성 증가가 전세계적으로 문제가 되고있는 extended-spectrum beta- lactamase (ESBL)를 생성하는 대표적인 세균으로 최근 외국에서 ciprofloxacin 내성과 ESBL 생성사이에 관련이 있다는 2-3편의 보고들이 있었다. 본 연구에서는 병원획득 K. pneumoniae 패혈증이 있었던 환자들을 대상으로 ciprofloxacin 내성과 관련된 인자를 알아보고자 하였다. 재료 및 방법 : 2001년1월부터 2002년12월 사이에 2200병상의 3차 의료기관인 한 대학병원에서 입원 후 72시간 이후에 나간 혈액배양에서 K. pneumoniae가 배양된 입원환자를 대상으로 의무기록과 전산기록을 분석하여 환자의 성별, 나이, 병동, 기저질환, 이전의 항생제 사용력, 패혈증 발생당시까지의 재원기간, 이전 입원력, 원인균의ESBL 생성유무 등을 파악하였고 이들 변수가 ciprofloxacin 내성과 관련이 있는지를 분석하였다. 재발성 패혈증의 경우는 첫 번째 경우만을 분석에 포함하였다. 결 과 : 연구대상 환자는 총154명이었고 K. pneumoniae의 ciprofloxacin에 대한 내성률은 28.6% (44/154)였다. Ciprofloxacin 내성균주 중 ESBL 생성균주의 비율은 95.5% (42/44)였고 ciprofloxacin 감수성균주에서 ESBL 생성균주의 비율은 24.5% (27/110)였다(P<0.001). ESBL생성외에 단변량 분석에서 유의한 관련을 보인 변수로는 남자, 나이가 많은 경우, 패혈증 당시 중환자실 재원, 기저질환이 고형암, 혈액암, 담도계 질환인 경우, 패혈증 발생이전 1달 이내의 항생제 사용력, 3세대 cephalosporin, metronidazole, fluroquinolone, carbapenem 투여력이 있었다. 다변량 로지스틱 분석을 시행 하였을 때는 나이가 많은 경우(Adjusted odds ratio[AOR]; 1.04, 95% confidence interval[CI]; 1.01-1.06)와 ESBL 생성(AOR; 81.35, 95% CI; 17.76-372.53)이 유의하게 ciprofloxacin 내성과 관련이 있었다. 결 론:패혈증을 일으킨 병원획득 K. pneumoniae에서의 ciprofloxacin 내성은 ESBL 생성과 유의한 관련을 보였고 향후 이에 관련된 원인이나 기전을 분석하기위한 분자역학적․분자생물학적 연구가 필요하겠다
Abstract
Background:Strains of ciprofloxacin-resistant Klebsiella pneumoniae have emerged worldwide. We investigated the epidemiology of ciprofloxacin resistance and its relationship to ESBL production in nosocomial K. pneumoniae bacteremia. Materials and Methods:Using the computerized database of clinical microbiology, we identified all patients whose blood culture had yielded K. pneumoniae between January 2001 and December 2002 at a 2200-bed university-affiliated tertiary-care hospital. During the study period, total of 392 episodes of K. pneumoniae bacteremia were documented of which 163 episodes were acquired nosocomially. 9 cases of recurrent episodes were excluded. Results:The resistance rates to ciprofloxacin was 28.6% (44/154). ESBL-production was significantly more common in ciprofloxacin-resistant isolates than in ciprofloxacin-susceptible isolates (95.9% [42/44] vs. 24.5% [27/110], P<0.001). In univariate analysis, following factors were significantly associated with resistance to ciprofloxacin: older age, male sex, ICU admission at the time of bacteremia, prior use of antibiotics within 1 month before bacteremia, solid tumor, hematological malignancy, or biliary disease as underlying disease, and ESBL-production. The prior use of 3rd- generation cephalosprins, metronidazole, fluroquinolone, or carbapenem were also risk factors. Independent risk factors for ciprofloxacin resistance were older age (adjusted odds ratio [AOR]; 1.04, 95% confidence interval [CI]; 1.01-1.06) and ESBL production (AOR; 81.35, 95% CI; 17.76-372.53). Conclusion:The close relationship between ciprofloxacin resistance and ESBL production was documented in nosocomial K. pneumoniae bacteremia. Further epidemiological and molecular studies to determine factors and mechanisms involved in the relationship are needed.
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