Date on Master's Thesis/Doctoral Dissertation

12-2018

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Epidemiology and Population Health

Degree Program

Public Health Sciences with a specialization in Epidemiology, PhD

Committee Chair

Baumgartner, Richard

Committee Co-Chair (if applicable)

Wiemken, Timothy

Committee Member

Wiemken, Timothy

Committee Member

Taylor, Kira

Committee Member

Mattingly, William

Committee Member

Boone, Stephanie

Author's Keywords

macrolide and beta-lactam; community acquired pneumonia; confounding

Abstract

Pneumonia and influenza are one of the leading causes of infectious disease-related deaths worldwide. Current guidelines for the treatment of hospitalized patients with community acquired pneumonia (CAP) include empiric antimicrobial therapy with a macrolide and a beta-lactam. There is little consensus among studies as to which antimicrobial regimen is best. The confusing results seen may very well be due to lack of assessment of confounding by indication (CBI). This analysis was a secondary analysis from Hospitalized Adults with Pneumococcal Pneumonia: Incidence Study (HAPPI). The study participants were those in HAPPI who had received either macrolide and beta-lactam combination therapy or fluoroquinolone mono-therapy within the first 24 hours (n= 3141). The outcomes studied were early clinical stability (ECS) and 30 day mortality. No statistically significant association was found between macrolide and beta-lactam use and ECS using any of the methods used for addressing confounding by indication, logistic regression, propensity score matching, or instrumental variable analysis (Odds Ratio (OR): 0.908, 95% Confidence Interval (CI): 0.780, 1.059; OR: 0.916, 95% CI:0.775, 1.083; OR: 1.551, 95% CI: 0.777, 3.091, respectively). The two methods addressing measured confounding (logistic regression and propensity score matching) had similar OR’s while the method addressing unmeasured confounding (instrumental variable analysis) had a contradictory OR, even though the results were all non significant. No statistically significant association was found between macrolide and beta-lactam use and 30 day mortality using logistic regression, propensity score matching, or instrumental variable analysis (OR: 0.926, 95% CI: 0.692, 1.241; OR: 0.885, 95% CI: 0.748, 1.048; OR: 0.958, 95% CI: 0.603, 1.523, respectively). All three methods looking at combination therapy and 30 day mortality were in agreement. When addressing confounding and CBI more than one method for analysis should be used.

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