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Updated: Nov 19, 2025

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
The Kinetics of an Antibiotic Stewardship Intervention: A Quasi-Experimental Study
Tali Shafat1,2,3, Orly Shimoni2,4, Anna Nikonov4
1Infectious Disease Institute, Soroka University Medical Center, Beer Sheba, Israel.
Introduction:
Little is known about the kinetics and different phases of a successful antibiotic stewardship program (ASP) intervention.
Methods:
We analyzed the trends of quarterly antibiotic use measured in defined daily dose (DDD)/100 days hospitalization using the Joinpoint Regression Program and interrupted time series analysis to objectively identify shifts in the trends of antibiotic use. We correlated these changes in trends with the introduction of a hospital-wide ASP intervention.
Results:
The ASP intervention reduced the overall antibiotic use by 33%, from a prior steady state of 76.5 DDD/100 days hospitalization to a post-intervention steady state of 51.2 DDD/100 days hospitalization (p < 0.001). We identified four distinct phases in the trends: prior steady state (A), early intervention (B), accelerated phase (C), and post steady state (D). From A to B a change of slope (-1.46) [SE 0.37, 95% CI -2.23, -0.69 (p = 0.002)]; B to C, a further decrease of slope (-4.70) [SE 0.64, 95% CI -6.03, -3.37 (p = 0.001)]; between periods C and D, straightening out of the slope (+ 6.84) [SE 0.55, 95% CI 5.70, 7.98 (p < 0.001)] to a new post-intervention steady state. It took 1.5 years after completion of the intervention to reach the new steady state.
Conclusions:
We demonstrate that ASP interventions require time to achieve the maximal effect. Successful interventions require physicians to adapt new prescribing behaviors and gain confidence in the change; this adaptation can be a prolonged process and might even take years after the introduction of the ASP. These factors should be considered when planning and implementing ASP interventions.
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