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

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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. Result: Among 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 (r(1)=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.