Comparing Inpatient Mortality After a Switch from Traditional to Alternative Dosing of Meropenem Open Access

Abstract

Meropenem is broad spectrum antibiotic used to treat a variety of serious and potentially life-threating infections. Based on pharmacologic modeling, smaller, more frequent dosing of this drug may provide a marginal benefit to patients by optimizing pharmacokinetics. Previous small-scale studies had not identified significant inferiority with the implementation of the alternative dosing method of meropenem. Therefore, this retrospective cohort study aimed to investigate whether the implementation of the alternative dosing method is deemed inferior to the traditional method in terms of inpatient mortality in a large scale academic facility which implemented alternative dosing. The inpatient mortality rate of patients who received meropenem with traditional dosing regimen during 2009 (n=572) in the hospital were compared to that of patients who received meropenem with alternative dosing regimen from February 2010 to January 2011 (n=684). Among the patients who received traditional dosing and alternative dosing, similar proportion of patients died in the hospital (17.5% vs. 15.8%, p=0.42). In multivariable analysis, controlling for age, intensive care unit drug administration, and Charlson comorbidity index, the odds ratio of having alternative dosing method vs. traditional dosing method among patients who died in the hospital is 0.78 (p=0.13), and is not statistically significant. Also, the results of the Kaplan-Meier survival analysis shows no significant difference in survival between patients who received traditional dosing and those who received alternative dosing (log-rank test p=0.80). The inpatient mortality change of patients before and after the implementation was assessed with interrupted time series analysis, and it shows similar, both decreasing, slopes of change in inpatient mortality before and after the implementation. This study also assessed the change in defined daily doses (DDD) to confirm the true implementation of the alternative method. The slopes individually show increase in DDD, with a dramatic downshift after time of implementation. The DDD data has an overall decreasing trend for the entire study course. While less amount of meropenem is administered the same results can be reached. Hospitals, especially those with low resources, can implement the alternative dosing method to treat infections with less amount of meropenem.

Table of Contents

Introduction...1

Methods...3

Null Hypothesis...3

Alternative Hypothesis...4

Study Population...4

Baseline Characteristics...5

Statistical Analysis...5

Outcomes...7

Results...8

Study Population...8

Total Inpatient Mortality Counts...8

Univariate Analysis...8

Multivariate Analysis...9

Survival Analysis...10

Interrupted Time Series Analysis...11

Defined Daily Dose...11

Inpatient Mortality...11

Discussion...13

Strengths and Limitations...14

Future Directions...15

Public Health Implications...15

References...17

Tables and Figures...20

Table 1. Demographic Information of the Study Population by Dosing Method...20

Table 2. Table of Odds Ratios Calculated with Multivariable Logistic Regression...21

Table 3. Demographic Information of the Study Population by Inpatient Mortality...22

Figure 1. Kaplan-Meier Survival Analysis of Traditional vs. Alternative Dosing of Meropenem (P-value of Log Rank Test Displayed)...23

Figure 2. Time Interrupted Series Analysis of the Change of Slope of Defined Daily Dose Before and After the Implementation of Alternative Dosing of Meropenem...24

Figure 3. Time Interrupted Series Analysis of the Change of Slope of Inpatient Mortality Rate per 100 Patients Who Received Meropenem Before and After the Implementation of Alternative Dosing of Meropenem...25

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Medicine and Surgery Health Sciences, Epidemiology
Keyword	Meropenem Dosing Regimen Meropenem Antibiotics Antimicrobial Stewardship Program
Committee Chair / Thesis Advisor	Jacob, Jesse Thomas, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs Hospital or other health care provider

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