title: Differential effects of clindamycin on neutrophils of healthy donors and septic patients.
abstract: Antibiotics are frequently administered to ICU patients in case of bacterial infections. Little is known, however, about the interference of antibiotics with neutrophil host defence mechanisms in patients with sepsis and multiple organ dysfunction syndrome (MODS). With our study, evidence for differential clindamycin effects on neutrophils in healthy donors and septic patients without or with MODS was sought. Functional parameters (oxidative response and phagocytosis) and fMLP receptor expression were analysed. The study was approved by the local ethical board. Venous blood was drawn from healthy donors and septic patients. Neutrophils in PBS were incubated with 0, 5, 25 or 125 microg/ml clindamycin and analysed flow cytometrically. Neutrophils of patients with sepsis and MODS showed a significantly higher basal activation compared to healthy donors. Clindamycin application led to a dose-dependent significant suppression of the fMLP-induced oxidative response in patients with sepsis and MODS, but not in healthy donors or septic patients in the absence of MODS. In patients with sepsis and MODS, phagocytosis of Escherichia coli and Staphylococcus aureus was significantly suppressed by clindamycin 125 microg/ml. In both other treatment groups, clindamycin did not affect phagocytosis. fMLP receptor expression was not altered by clindamycin. High-dose clindamycin selectively suppresses functional responses of neutrophils in septic patients with MODS. Simultaneously applied drugs, such as general anaesthetics, may potentiate this modulation of antibacterial defence and inflammation.
authors.affiliation: Department of Anaesthesiology, University of Regensburg, Franz-Josef-Allee 11, 93042 Regensburg, Germany. sigrid.wittmann@klinik.uni-regensburg.de
authors.forename: Sigrid
authors.initials: S
authors.lastname: Wittmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Arlt
authors.forename: Gregor
authors.initials: G
authors.lastname: Rothe
authors.forename: Dieter
authors.initials: D
authors.lastname: Fröhlich
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002981:Clindamycin / Q000494:pharmacology*; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D009102:Multiple Organ Failure / Q000097:blood / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D044042:Receptors, Formyl Peptide / Q000096:biosynthesis / Q000276:immunology; D018805:Sepsis / Q000097:blood / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D044042:Receptors, Formyl Peptide; D002981:Clindamycin