J Korean Med Sci.  2024 Jun;39(21):e172. 10.3346/jkms.2024.39.e172.

The Impact of an Antimicrobial Stewardship Program on Days of Therapy in the Pediatric Center: An Interrupted Time-Series Analysis of a 19-Year Study

• Kim KR
• Park HJ
• Baek SY
• Choi SH
• Lee BK
• Kim S
• Kim JM
• Kang JM
• Kim SJ
• Choi SR
• Kim D
• Choi Js
• Yoon Y
• Park H
• Kim DR
• Shin A
• Kim S
• Kim YJ

• KMID: 2556289
• DOI: http://doi.org/10.3346/jkms.2024.39.e172

Abstract

Background
We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients.
Methods
A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001–2008) and the post-intervention (2009–2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patientdays, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ² .
Results
The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = −16.5; 95% confidence interval [CI], −30.6 to −2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881).
Conclusion
The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

Keyword

Antimicrobial Stewardship Program; Pediatric Patients; Pediatric Infectious Disease Attending Physician; Antimicrobial Use; Antimicrobial-Resistant Pathogens

Figure

• 

  Fig. 1 Change of proportion of major antibiotic-resistant bacteria isolated from bloodstream infections. The black dashed line indicates the proportion of MRSA in S. aureus isolated from bloodstream infections. The black solid line indicates the proportion of ESBL-producing GNB in E. coli and K. pneumoniae isolated from bloodstream infections.ASP = antimicrobial stewardship program, MRSA = methicillin-resistant Staphylococcus aureus, ESBL = extended-spectrum beta-lactamase, GNB = gram-negative bacteria.aStatistically significant.

• 

  Fig. 2 Interrupted time-series analyses for antimicrobial use from January 2001 to December 2019. (A) Total antimicrobial use. The slope of the total antimicrobial use decreased from 584.5 DOT per 1,000 patient-days in 2009 to 513.0 DOT per 1,000 patient-days in 2019 after ASP implementation in March 2008. The delta slopes for the total antimicrobial use were negative. (B) Cefepime use. The slope of cefepime use decreased after the ASP implementation, and the delta slopes was negative. The grey dotted line indicates antimicrobial use as DOT per 1,000-patient-days. The grey solid line indicates the observed slope during the pre-intervention period and the grey dashed line indicates the expected slope without the implementation. The black solid line indicates the observed slope with implementation during the post-intervention period. The black triangle indicates the delta slopes (sustained effect): The observed slope with ASP implementation minus the expected slope without the implementation. The ‘I’ indicates the change in level (immediate effect), the mean antimicrobial use in the post-intervention minus the mean antimicrobial use in the pre-intervention period.ASP = antimicrobial stewardship programs, DOT = days of therapy.Statistically significant is defined P < 0.05.aStatistically significant.

• 

  Fig. 3 Transient increase of total antimicrobial use as measured by DOT during the post-ASP intervention period. The grey dotted line indicates total antimicrobial use. The grey solid line indicates the slope before Period C of transiently increased DOT. The grey dashed line indicates the expected slope without Period C of transiently increased DOT. The black solid line indicates the slope during the Period C of the transiently increased DOT period. The black dashed line indicates the observed slope after the reinforcement of ASP procedures by the pediatric ID physician. The triangles indicate the delta slopes. Period A: H1N1 influenza pandemic with no ID fellow(s) from April 2009 to April 2010. Period B: No ID fellow(s). Only an ID attending physician managed the ASP from March 2012 to December 2013. Period C: MERS-CoV2 outbreak in Korea and sabbatical leave of pediatric ID attending physician after the outbreak closure from June 2015 to December 2016. Statistically significant is defined P < 0.05. The grey dashed line indicates the period of the transient increase in DOT.DOT = days of therapy, I = the interval from January to June, II = the interval from July to December, pediatric ID = pediatric infectious disease, MERS-CoV2 = Middle East Respiratory Syndrome coronavirus.aStatistically significant.

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