Effect of erythromycin on mortality and the host response in critically ill patients with sepsis: a target trial emulation
Issued Date
2022-12-01
Resource Type
ISSN
13648535
eISSN
1466609X
Scopus ID
2-s2.0-85131106238
Pubmed ID
35610649
Journal Title
Critical Care
Volume
26
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Critical Care Vol.26 No.1 (2022)
Suggested Citation
Reijnders T.D.Y., Peters-Sengers H., van Vught L.A., Uhel F., Bonten M.J.M., Cremer O.L., Schultz M.J., Stuiver M.M., van der Poll T., de Beer F.M., Bos L.D.J., Glas G.J., van Hooijdonk R.T.M., Horn J., Schouten L.R.A., Straat M., Wieske L., Witteveen E., Reijnders T.D.Y., Schuurman A.R., van Engelen T.S.R., Pereverzeva L., Hoogendijk A.J., Huson M.A., Wiewel M.A., Klouwenberg P.M.C.K., Ong D.S.Y., Frencken J.F., Koster-Brouwer M.E., van de Groep K., Verboom D.M. Effect of erythromycin on mortality and the host response in critically ill patients with sepsis: a target trial emulation. Critical Care Vol.26 No.1 (2022). doi:10.1186/s13054-022-04016-x Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85306
Title
Effect of erythromycin on mortality and the host response in critically ill patients with sepsis: a target trial emulation
Author(s)
Reijnders T.D.Y.
Peters-Sengers H.
van Vught L.A.
Uhel F.
Bonten M.J.M.
Cremer O.L.
Schultz M.J.
Stuiver M.M.
van der Poll T.
de Beer F.M.
Bos L.D.J.
Glas G.J.
van Hooijdonk R.T.M.
Horn J.
Schouten L.R.A.
Straat M.
Wieske L.
Witteveen E.
Reijnders T.D.Y.
Schuurman A.R.
van Engelen T.S.R.
Pereverzeva L.
Hoogendijk A.J.
Huson M.A.
Wiewel M.A.
Klouwenberg P.M.C.K.
Ong D.S.Y.
Frencken J.F.
Koster-Brouwer M.E.
van de Groep K.
Verboom D.M.
Peters-Sengers H.
van Vught L.A.
Uhel F.
Bonten M.J.M.
Cremer O.L.
Schultz M.J.
Stuiver M.M.
van der Poll T.
de Beer F.M.
Bos L.D.J.
Glas G.J.
van Hooijdonk R.T.M.
Horn J.
Schouten L.R.A.
Straat M.
Wieske L.
Witteveen E.
Reijnders T.D.Y.
Schuurman A.R.
van Engelen T.S.R.
Pereverzeva L.
Hoogendijk A.J.
Huson M.A.
Wiewel M.A.
Klouwenberg P.M.C.K.
Ong D.S.Y.
Frencken J.F.
Koster-Brouwer M.E.
van de Groep K.
Verboom D.M.
Other Contributor(s)
Abstract
Background: Immunomodulatory therapies that improve the outcome of sepsis are not available. We sought to determine whether treatment of critically ill patients with sepsis with low-dose erythromycin—a macrolide antibiotic with broad immunomodulatory effects—decreased mortality and ameliorated underlying disease pathophysiology. Methods: We conducted a target trial emulation, comparing patients with sepsis admitted to two intensive care units (ICU) in the Netherlands for at least 72 h, who were either exposed or not exposed during this period to treatment with low-dose erythromycin (up to 600 mg per day, administered as a prokinetic agent) but no other macrolides. We used two common propensity score methods (matching and inverse probability of treatment weighting) to deal with confounding by indication and subsequently used Cox regression models to estimate the treatment effect on the primary outcome of mortality rate up to day 90. Secondary clinical outcomes included change in SOFA, duration of mechanical ventilation and the incidence of ICU-acquired infections. We used linear mixed models to assess differences in 15 host response biomarkers reflective of key pathophysiological processes from admission to day 4. Results: In total, 235 patients started low-dose erythromycin treatment, 470 patients served as controls. Treatment started at a median of 38 [IQR 25–52] hours after ICU admission for a median of 5 [IQR 3–8] total doses in the first course. Matching and weighting resulted in populations well balanced for proposed confounders. We found no differences between patients treated with low-dose erythromycin and control subjects in mortality rate up to day 90: matching HR 0.89 (95% CI 0.64–1.24), weighting HR 0.95 (95% CI 0.66–1.36). There were no differences in secondary clinical outcomes. The change in host response biomarker levels from admission to day 4 was similar between erythromycin-treated and control subjects. Conclusion: In this target trial emulation in critically ill patients with sepsis, we could not demonstrate an effect of treatment with low-dose erythromycin on mortality, secondary clinical outcomes or host response biomarkers.