Macrolide use in the treatment of critically ill patients with pneumonia: Incidence, correlates, timing and outcomes.
BACKGROUND
Macrolide antibiotics are commonly used to treat pneumonia despite increasing antimicrobial resistance. Evidence suggests that macrolides may also decrease mortality in severe sepsis via immunomodulatory properties.


OBJECTIVE
To evaluate the incidence, correlates, timing and mortality associated with macrolide-based treatment.


METHODS
A population-based cohort of critically ill adults with pneumonia at five intensive care units in Edmonton, Alberta, was prospectively followed over two years. Data collected included disease severity (Acute Physiology and Chronic Health Evaluation [APACHE] II score), pneumonia severity (Pneumonia Severity Index score), comorbidities, antibiotic treatments at presentation and time to effective antibiotic. The independent association between macrolide-based treatment and 30-day all-cause mortality was examined using multivariable Cox regression. A secondary exploratory analysis examined time to effective antimicrobial therapy.


RESULTS
The cohort included 328 patients with a mean Pneumonia Severity Index score of 116 and a mean APACHE II score of 17; 84% required invasive mechanical ventilation. Ninety-one (28%) patients received macrolide-based treatments, with no significant correlates of treatment except nursing home residence (15% versus 30% for nonresidents [P=0.02]). Overall mortality was 54 of 328 (16%) at 30 days: 14 of 91 (15%) among patients treated with macrolides versus 40 of 237 (17%) for nonmacrolides (adjusted HR 0.93 [95% CI 0.50 to 1.74]; P=0.8). Patients who received effective antibiotics within 4 h of presentation were less likely to die than those whose treatment was delayed (14% versus 17%; adjusted HR 0.50 [95% CI 0.27 to 0.94]; P=0.03).


CONCLUSIONS
Macrolide-based treatment was not associated with lower 30-day mortality among critically ill patients with pneumonia, although receipt of effective antibiotic within 4 h was strongly predictive of survival. Based on these results, timely effective treatment may be more important than choice of antibiotics.
Divisions of Critical Care Medicine and Infectious Diseases, University of Alberta, Edmonton, Alberta;
Wendy I
WI
Sligl
Division of Infectious Diseases, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta;
Holly
H
Hoang
Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta;
Dean T
DT
Eurich
Department of Medicine, Faculty of Medicine, Harvard University, Boston, Massachusetts, USA;
Atul
A
Malhotra
Department of Medicine, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia;
Thomas J
TJ
Marrie
Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta.
Sumit R
SR
Majumdar
Critical care; Intensive care; Lung; Macrolides; Mortality; Pneumonia