Impact of macrolide therapy on mortality for patients with severe sepsis due to pneumonia

Abstract

Recent studies suggest that macrolides may have beneficial effects for patients at risk for certain infections. The current authors examined the effect of macrolide therapy on 30-and 90-day mortality for patients with severe sepsis caused by pneumonia.A retrospective cohort study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had chest radiography consistent with, and had a discharge diagnosis of pneumonia and clinical criteria of severe sepsis. Subjects were considered to be on macrolides if they received at least one dose within 48 h of admission.Severe sepsis was present in 237 (30.1%) subjects, out of whom 104 (43.9%) received macrolides. Mortality was 20.3% at 30 days and 24.5% at 90 days. In the multivariable analysis, the use of macrolide was associated with decreased mortality at 30 days (hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.2-0.7) and at 90 days (HR 0.3, 95% CI 0.2-0.6) in patients with severe sepsis and in patients with macrolide-resistant pathogens (HR 0.1, 95% CI 0.02-0.5).Macrolide use was associated with decreased mortality in patients with severe sepsis due to pneumonia and macrolide-resistant pathogens. Confirmatory studies are needed to determine whether macrolide therapy may be protective for patients with sepsis.

Impact of macrolide therapy on mortality of HIV-infected patients with community-acquired pneumonia in a tertiary teaching hospital

“…12,14,15 This finding was not supported by the results of the present study, which included only HIV-infected patients.…”

“…This study demonstrated a lower 30 and 60-day mortality with the use of macrolides, even among patients who had severe sepsis caused by a microorganism resistant to this antibiotic class (hazard ratio: 0.10; 95% CI: 0.02-0.49; p = 0.005). 15 The immunomodulatory effects of macrolides are yet to be clarified, as there are studies that suggest interference with neutrophil action 16,17 and another study that demonstrates a decrease in pneumolysin production by Streptococcus pneumoniae. 18 A study in particular demonstrates that azithromycin can have a biphasic effect, initially increasing the bactericidal effects of neutrophils and subsequently, when the microorganism has been eliminated, inducing the apoptosis of the latter and interrupting inflammation, leading to a decrease in tissue damage and time of disease.…”

“…Among these, the most important is the immunomodulation of the inflammatory response and the interference with the pathogenicity of the etiological agent, as there are studies that have demonstrated the benefit of the therapy with macrolides even in patients with microorganisms resistant to this antibiotic class. 15,16 A North-American retrospective and multicentric study, carried out in 2009, included patients with CAP and severe sepsis and excluded HIV-infected patients. This study demonstrated a lower 30 and 60-day mortality with the use of macrolides, even among patients who had severe sepsis caused by a microorganism resistant to this antibiotic class (hazard ratio: 0.10; 95% CI: 0.02-0.49; p = 0.005).…”

“…14 Other studies have demonstrated benefits with regimens that contain macrolides, when compared to regimens without this class of antibiotic agent. 12,15 Additionally, the benefit of combined therapy over monotherapy have been demonstrated. 13 Considering that, to date, there is no consensus regarding the best empiric therapy for HIV-infected patients admitted to the hospital due to CAP, this study was carried out with the objective of assessing the impact of combining a macrolide to the beta-lactam therapy in this population.…”

Treatment with anti‐inflammatory drugs in community‐acquired pneumonia

“…However, two large prospective cohort studies showed no difference between these two regimens [66,67]. In a retrospective study in patients with severe sepsis owing to pneumonia caused by any microorganism, macrolide use was associated with decreased mortality, even in patients with macrolideresistant pathogens [68]. In a prospective observational study, Martin-Loeches et al [69] found a lower mortality rate in intubated patients with severe CAP who were treated with combination therapy including macrolides compared with patients treated without macrolide antibiotics.…”