Inpatient Mortality Among Patients Prescribed Piperacillin/Tazobactam Comparing Intermittent and Extended Infusion Dosing Strategies Open Access

Wilks, Kassidy (Spring 2018)

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Background: The emergence of antibiotic resistant infections is a major public health concern, and hospitals are assessing optimal dosing strategies of certain antibiotics to improve their effectiveness. Piperacillin/tazobactam is a commonly used broad-spectrum intravenous antibiotic in hospitalized patients, and has been associated with improved outcomes when using extended infusion (EI) compared to intermittent infusion (II) dosing in smaller studies in specific populations.

Objective: Determine whether inpatient mortality differs between EI and II piperacillin/tazobactam among the general hospital population.

Methods: Adults admitted to 2 hospitals from March 28, 2009 until March 27, 2015 who were administered piperacillin/tazobactam were included if they had a length of stay >1 day. The relationship between inpatient mortality and dosing regimen was assessed. Univariate, bivariate logistic regression, interaction assessment, and multivariate logistic regression were conducted.

Results: The study included 21,964 patients. Significant variables in the bivariate analysis were EI dosing compared to II, age ≥65 versus <65, Hospital B versus A , ICU versus ward, CCI ≥3 versus CCI <3, male sex versus female, African American versus Caucasian race, and sepsis versus no sepsis. Significant interactions included unit type and sepsis, sepsis and CCI, and CCI and unit type. In multivariate analysis, the odds of inpatient mortality among patients prescribed EI dosing compared to II was 0.70 (95% CI: 0.63, 0.78). Significant predictors included age ≥65 compared to <65, Hospital B versus A, ICU versus ward, and sepsis status, and interactions between unit type and sepsis, unit type and CCI, and sepsis and CCI. Sensitivity analyses did not change the observed OR when restricting the population to patients who had ≥3 days of therapy (OR 0.75, 95% CI: 0.65, 0.86) or patients without sepsis (OR 0.75, 95% CI: 0.65, 0.86). No significant difference was seen in patients who had a positive susceptible blood culture (OR 1.04, 95% CI: 0.56, 1.94).


Discussion: Inpatient mortality outcomes are similar when utilizing both EI and II, and EI may be associated with a lower mortality rate. Using EI as a dosing strategy may help decrease the incidence of antibiotic-resistant infections due to the misuse of antibiotics.  


Table of Contents

Literature Review... 1

Overview of Antibiotic Resistance. 1

Drivers of Antibiotic Resistance. 1

Combating Antibiotic Resistance. 3

Antibiotic Utilization. 4

Manuscript.. 6

Abstract. 6

Introduction. 7

Methods. 8

Study design and population. 8

Data. 8

Data Analysis. 9

Results. 12

Univariate and Bivariate Analyses 12

Interaction and Confounding Assessment 13

Interrupted Time Series Analysis. 16

Discussion. 18

References. 23

Tables. 26

Figures. 43

Public Health Importance and Future Directions. 46

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