Predictors for individual patient antibiotic treatment effect in hospitalized community-acquired pneumonia patients

Abstract

Objective: Our objective was to identify clinical predictors of antibiotic treatment effects in hospitalized patients with community-acquired pneumonia (CAP) who were not in the intensive care unit (ICU).

Methods: Post-hoc analysis of three prospective cohorts (from the Netherlands and Spain) of adult patients with CAP admitted to a non-ICU ward having received either β-lactam monotherapy, β-lactam + macrolide, or a fluoroquinolone-based therapy as empirical antibiotic treatment. We evaluated candidate clinical predictors of treatment effects in multiple mixed-effects models by including interactions of the predictors with empirical antibiotic choice and using 30-day mortality, ICU admission and length of hospital stay as outcomes.

Results: Among 8562 patients, empirical treatment was β-lactam in 4399 (51.4%), fluoroquinolone in 3373 (39.4%), and β-lactam + macrolide in 790 (9.2%). Older age (interaction OR 1.67, 95% CI 1.23-2.29, p 0.034) and current smoking (interaction OR 2.36, 95% CI 1.34-4.17, p 0.046) were associated with lower effectiveness of fluoroquinolone on 30-day mortality. Older age was also associated with lower effectiveness of β-lactam + macrolide on length of hospital stay (interaction effect ratio 1.14, 95% CI 1.06-1.22, p 0.008).

Conclusions: Older age and smoking could influence the response to specific antibiotic regimens. The effect modification of age and smoking should be considered hypothesis generating to be evaluated in future trials.

Keywords: Antibiotic treatment; Clinical predictors; Community-acquired pneumonia; Outcomes; Treatment effect.