目的：评价抗生素干预策略执行后院内感染的产超广谱β-内酰胺酶（ESBLs）大肠埃希菌（ECO）与肺炎克雷伯菌(KPN)阳性率的变化，探索合理的干预模式及干预的合适时期及监测指标。方法：从2004年12月到2007年12月，监测中南大学湘雅二医院病房常见抗生素的年消耗量（DDD/1 000 patient-days表示）及其耐药率、院内感染的产超广谱β-内酰胺酶的肺炎克雷伯菌（ESBLs-KPN）和产超广谱β-内酰胺酶的大肠埃希菌（ESBsL-ECO）的阳性率；2005年1月至2007年12月对研究科室实施抗生素的综合干预策略。干预科室设为试验组，医院内条件相当的其他科室设为对照组（ICU除外）。结果：干预前（2004年），试验组ESBLs-KPN(43.90%)和ESBLs-ECO(45.83%)阳性率均高于对照组ESBLs-KPN (28.04%)和ESBLs-ECO(24.90%) (P＜0.05)；干预后试验组ESBLs-KPN阳性率呈显著下降趋势，由26.47%下降至17.65%(P＜0.05)；而对照组ESBLs-KPN和ESBLs-ECO阳性率呈显著上升趋势，前者由34.18%上升至52.94%(P＜0.05)，后者由47.03%上升至63.78%(P＜0.05)，且干预后试验组ESBLs-KPN和ESBLs-ECO阳性率均低于对照组ESBLs-KPN和ESBLs-ECO阳性率(P＜0.05)。试验组减少了头孢他啶(CAZ)、头孢哌酮/舒巴坦(CFS)、亚胺培南(IMP)的消耗量，增加了头孢吡肟(FEP)的消耗量 (P＜0.05)；对照组增加了CAZ，FEP和CFS 的消耗量。结论： 长期抗生素综合干预策略的实施可能有益于降低ESBLs-KPN和ESBLs-ECO的流行。

ObjectiveTo evaluate the change of extended spectrum β-lactamase (ESBLs) Producing Klebsiella Pneumoniae （ESBLs-KPN） and Escherichia coli （ESBLs-ECO） causing nosocomial infection after antimicrobial intervention. MethodsWe regularly monitored the data on the yearly consumption ［defined as daily dose (DDD) per 1 000 patient-days］ of frequently used antibiotics from Dec. 2004 to Dec. 2007. From Jan. 2005 to Dec. 2007, we monitored the resistance of frequently used antibiotics and the timely integrative antimicrobial intervention was based on the outcome of antimicrobial resistance. We also monitored the isolation rate of ESBLs-KPN and ESBLs-ECO causing nosocomial infection. The departments studied were the experimental group and other comparable medical departments were the control group(ICU was excluded).ResultsThe isolation rate of ESBLs-KPN (43.90%) and ESBLs-ECO (45.83%) in the experimental group was higher than that in the control group (28.04% and 24.90%, respectively) before the intervetion (P＜0.05). The isolation rate of ESBLs-KPN decreased (from 26.47% to 17.65%) in the experimental group and that in the control group increased ( ESBLs-KPN: from 34.18% to 52.94%; ESBLs-ECO: from 47.13% to 63.78%) from 2005 to 2007 (P＜0.05). The isolation rate of ESBLs-KPN and ESBLs-ECO in the experimental group was lower than that in the control group after the antimicrobial intervention (P＜0.05). Usage of ceftazidime and cefoperazone/sulbactam and imipenem was reduced and the consumption of cefepime was increased in the experimental group (P＜0.05). Consumption of ceftazidime and cefoperazone/sulbactam and cefepime was increased. ConclusionThe prevalence of ESBLs-KPN and ESBLs-ECO may be decreased after the integrative antimicrobial intervention.

［1］Perez F, Endimiani A, Hujer K M,et al. The continuing challenge of ESBLS［J］. Curr Opin Pharmacol, 2007, 7(5): 459-469.
［2］夏国俊,张春华，李楠,等.抗菌药物临床应用指导原则［M］.北京：中国中医药出版社，2004：160-218.
XIA Guojun,ZHANG Chunhua, LI Nan,et al.The guideline of clinical application about antibiotics［M］.Beijing:China Press Traditional Chinese Medcine, 2004：160-218.
［3］WHO Collaborating Centre for Drug Statistics Methodology.Guidelines for ATC classification and DDD assignment［M］. 6th ed. Oslo, Norway: World Health Organization, 2003.
［4］Slama T G, Amin A, Brunton S A, et al. Council for appropriate and rational antibiotic therapy (CARAT). A clinician’s guide to the appropriate and accurate use of antibiotics: the Council for Appropriate and Rational Antibiotic Therapy (CARAT) criteria ［J］. Am J Med, 2005,118 (7A):1S-6S.
［5］McGowan JE Jr. Resistance in nonfermenting gram-negative bacteria:multidrug resistance to the maximum［J］.Am J Infect Control,2006,34(5suppl 1):S29-S37.
［6］裴保香，郭绍来，王睿，等.大肠埃希菌耐药性与头孢菌素类用量变化的相关性分析［J］.中华医院感染学杂志，2004，14（4）:373-376.
PEI Baoxiang,GUO Shaolai,WANG Rui, et al. Correlation between the yearly quantity variations of clinical prescription of cephalosporins and the resistance of escherichia coli［J］. Chinese Journal of Nosocomiology, 2004，14（4）:373-736.
［7］Bradford P A. Extended-spectrum beta-lactamases in the 21st century: Characterization, epidemiology, and detection of this important resistance threat［J］. Clin Microbiol Rev, 2001,14(4):933-951.
［8］朱惠莉, 王亚岚, 周伊南,等. 产超广谱β-内酰胺酶肺炎克雷伯氏菌和大肠埃希氏菌呼吸道感染的临床分析［J］.中国抗生素杂志，2001,26 (3): 190.
ZHU Huili, WANG Yalan, ZHOU Yinan, et al. Clinical analysis of Klebsiella pneumoniae and Escherichia coli producing extended-spectrum beta-lactamases in patients with respiratory tract infection［J］. China J Antibiot, 2001,26 (3): 190.
［9］王爱茶,叶爱菊,卢芝君.大肠埃希菌和肺炎克雷伯菌诱导产ESBLs的危险因素和耐药分析［J］. 中国微生态学杂志,2008,20(2):184-185.
WANG Aicha,YE Aiju,LU Zhijun.The risk factors and antimicrobial resistance of ESBLs-producing Klebsiella pneumoniae and Escherichia coli［J］. Chinese Journal of Microecology, 2008,20(2):184-185.
［10］刘兴态,汪华,曾蓉. 产ESBLs 肺炎克雷伯菌和大肠埃希菌的检测及耐药性分析［J］. 检验医学与临床,2007,4 (3):182-183.
LIU Xinghua,WANG Hua,ZENG Rong. Analysis on the detection and antimicrobial resistance of ESBLs-producing Klebsiella pneumoniae and Escherichia coli［J］.Laboratory Medicine and Clinic, 2007,4 (3):182-183.
［11］Endimiani A, Paterson D L. Optimizing therapy for infections cau sed by enterobacteriaceae producing extended-spectrum Beta-lactamases［J］. Semin Respir Crit Care Med, 2007, 28(6):646-655.
［12］Paterson D L.Resistance in gram-negative bacteria: enterobacteriaceae［J］. Am J Med,2006,119(6 Suppl 1):S20-S28.
［13］Martínez J A, Aguilar J, Almela M,  et al. Prior use of carbapenems may be a significant risk factor for extended-spectrum {beta}-lactamase producing Escherichia coli or Klebsiella spp. in patients with bacteraemia ［J］.J Antimicrob Chemother, 2006, 58(5):1082-1085.