抗菌药物专项管理对使用指标及革兰阴性多重耐药菌检出率的影响

Impact of antimicrobial stewardship program on antimicrobial usage and detection rate of multidrug-resistant gram-negative bacteria

目的分析实施抗菌药物专项管理前后使用指标及革兰阴性多重耐药菌(MDR-GNB)检出率的变化,评估实施专项管理的效果。方法温州医科大学附属第二医院、育英儿童医院于2011年12月开始开展抗菌药物专项管理活动,2014—2017年进一步加大管理力度。回顾性分析管理前(2010—2011年)、管理后(2012—2013年为第一阶段、2014—2015年为第二阶段、2016—2017年为第三阶段),各阶段全院抗菌药物门诊、急诊、住院患者使用率及抗菌药物使用强度(AUD)、第三代头孢菌素AUD和碳青霉烯类抗菌药物AUD;统计同期产超广谱β内酰胺酶(ESBLs)大肠埃希菌和肺炎克雷伯菌,耐碳青霉烯类抗菌药物大肠埃希菌和肺炎克雷伯菌,耐碳青霉烯类抗菌药物鲍曼不动杆菌和铜绿假单胞菌的检出率,并与各抗菌药物使用指标作相关性分析。结果管理前和管理后三个阶段门诊抗菌药物使用率分别为55.2%(560 578/1 015 540)、38.1%(493 554/1 296 336)、26.8%(378 602/1 411 595)、23.1%(347 817/1 502 817);急诊抗菌药物使用率为75.6%(429 582/568 230)、61.4%(382 558/623 138)、43.6%(265 102/608 071)、35.1%(218 484/622 397),住院抗菌药物使用率为76.0%(30 568/40 221)、53.7%(30 437/56 636)、49.9%(37 395/74 895)、50.3%(35 493/70 544),整治后均明显下降(χ^2=297 811.798、3 155 704.783、5 592.037,P均<0.01);住院患者AUD分别为38.43、31.80、21.65、19.41,第三代头孢菌素AUD分别为13.83、11.21、6.20、6.84,管理后均明显下降(r=-0.878,-0.781,P均<0.05),碳青霉烯类抗菌药物AUD分别为1.94、1.77、1.87、1.93,无显著变化(r=0.123,P>0.05)。共收集细菌11 289株,其中大埃希菌5 589株,肺炎克雷伯菌2 823株,鲍曼不动杆菌1 637株,铜绿假单胞菌1 240株,管理前、管理后三个阶段产ESBLs大肠埃希菌检出率分别为75.4%(1 034/1 371)、66.6%(893/1 341)、57.8%(834/1 443)、46.7%(670/1 434);产ESBLs肺炎克雷伯菌检出率为78.7%(547/695)、67.5%(455/674)、49.3%(421/854)、32.5%(195/600),均显著下降(χ^2=266.204;328.805,P均<0.01);耐碳青霉烯类抗菌药物鲍曼不动杆菌检出率分别为28.2%(115/408)、26.7%(126/472)、24.3%(125/515)、12.0%(29/242),也显著下降(χ^2=18.112,P<0.01);耐碳青霉烯类抗菌药物铜绿假单胞菌检出率分别为11.3%(40/355)、18.5%(58/313)、13.4%(46/343)、7.0%(16/229),以管理后第三阶段下降最明显;耐碳青霉烯类抗菌药物大肠埃希菌和肺炎克雷伯菌的检出率维持在低水平(<5%)。产ESBLs大肠埃希菌和肺炎克雷伯菌的检出率与各使用指标均呈显著正相关(r1=0.930、0.974、0.746、0.958、0.842;r2=0.910、0.960、0.765、0.963、0.898,P均<0.05)。结论实施专项管理能有效降低抗菌药物使用率,减少MDR-GNB的产生,对于促进抗菌药物合理使用,减少细菌耐药有积极意义。

Objective Analyze the changes of indicator of antimicrobial usage and detection rate of multidrug-resistant gram-negative bacteria (MDR-GNB), in order to evaluate the impact of antimicrobial stewardship program (ASP). Methods The antimicrobial stewardship program was implemented since December 2011 at the Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical University. Intensified effort was made from 2014 to 2017. We divided the program into four stages, one before ASP (2010-2011) and three after ASP (2012-2013 as the first, 2014-2015 as the second and 2016-2017 as the third post-ASP stages). The usage rates in outpatient,emergency department and inpatient, along with the antibiotic use density (AUD, defined as daily doses/per 100 patient-days), the AUD of the third-generation cephalosporins and carbapenems in inpatient were reviewed retrospectively. The detection rates of extended-spectrum β-lactamases (ESBLs)-producing Escherichia coli, ESBLs-producing Klebsiella pneumonia, carbapenem-resistant E. coli, carbapenem-resistant Klebsiella pneumonia, carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Pseudomonas aeruginosa were also analyzed at the same time. The correlation analysis between the detection rate of MDR-GNB and the indicator of antimicrobial usage was made. ResultAmong four stages, the usage rates were 55.2%(560 578/1 015 540), 38.1%(493 554/1 296 336), 26.8%(378 602/1 411 595) and 23.1%(347 817/1 502 817) in outpatient, 75.6%(429 582/568 230), 61.4%(382 558/623 138), 43.6%(265 102/608 071) and 35.1%(218 484/622 397) in emergency department, and 76.0%(30 568/40 221), 53.7%(30 437/56 636), 49.9%(37 395/74 895) and 50.3%(35 493/70 544) in inpatient, respectively. All indicators decreased significantly (χ^2=297 811.798, 3 155 704.783, 5 592.037, P<0.01). The AUD in inpatient was 38.4,31.8,21.7 and 19.41,and the AUD of the third-generation cephalosporins were 13.83, 11.21, 6.20 and 6.84, respectively, which decreased significantly after ASP (r=-0.878,-0.781, P<0.05). The AUD of carbapenems were 1.94,1.77,1.87 and 1.93, respectively (r=0.123, P>0.05). A total of 11 289 strains of bacteria were collected, including 5 589 strains of E. coli, 2 823 strains of K.pneumoniae, 1 637 strains of A. baumandii, and 1 240 strains of P. aeruginosa.The detection rates of ESBLs-producing E.coli and ESBLs -producing K. pneumoniae in four stages were 75.4%(1 034/1 371), 66.6%(893/1 341), 57.8%(834/1 443), 46.7%(670/1 434) and 78.7%(547/695), 67.5%(455/674), 49.3%(421/854), 32.5%(195/600), respectively,both decreased significantly (χ^2=266.204;328.805, P<0.01). The detection rates of Carbapenem-resistant A. baumannii were 28.2%(115/408), 26.7%(126/472), 24.3%(125/515) and 12.0%(29/242) respectively,and showed significant decreasing trend after ASP (χ^2=18.112, P<0.01). The detection rates of carbapenem-resistant P. aeruginosa were 11.3%(40/355), 18.5%(58/313), 13.4%(46/343) and 7.0%(16/229), respectively,with the most obvious decrease in the third stage after ASP. The detection rates of carbapenem-resistant E. coli and carbapenem-resistant K. pneumonia were continuously lower (<5%). There were positive correlations between the detection rates of ESBLs-producing E. coli and K. pneumoniae and all usage indicators (r1=0.930, 0.974, 0.746, 0.958, 0.842;r^2=0.910, 0.960, 0.765, 0.963, 0.898, P<0.05). Conclusion The antimicrobial stewardship program can effectively reduce both the usage of antimicrobial and the production of MDR-GNB, which has great value to promote rational clinical use of antimicrobials and reduce bacterial resistance.