title: Negative impact of linezolid on human neutrophil functions in vitro.
abstract: OBJECTIVE
  In a recent phase III clinical trial on linezolid, more patients in the linezolid treatment arm acquired Gram-negative catheter-related bloodstream infections despite the adequate therapy of infections caused by Gram-negative bacteria. We tested our hypothesis that linezolid impairs phagocytosis and the killing of Gram-negative bacteria by polymorphonuclear leukocytes (PMN).
  
  
  METHODS
  The influence of clinically relevant concentrations (5, 20 and 50 mg/l) of linezolid on granulocyte function in vitro was tested. Phagocytosis was determined by flow cytometry, and killing of bacteria was evaluated by plate counting. Chemotaxis was examined by an under-agarose cell migration assay. Gram-positive and Gram-negative bacteria were used.
  
  
  RESULTS
  Linezolid significantly impaired phagocytosis of a specific Escherichia coli strain in a concentration-dependent manner, whereas the effect on Pseudomonas aeruginosa was less prominent. No such effects were observed with a different E. coli strain or Staphylococcus aureus. Neither killing nor the chemotactic behaviour of PMN was significantly affected by linezolid.
  
  
  CONCLUSIONS
  The observed concentration-dependent impairment of the phagocytic function might contribute to the higher frequency of catheter-related Gram-negative bloodstream infections in patients treated with linezolid. Individual patient risk may also depend on the causative Gram-negative strain.
authors: Federal Institute for Drugs and Medical Devices, Biosafety Laboratory, Bonn, Germany.
authors: Thomas
authors: T
authors: Grüger
authors: Thomas
authors: T
authors: Schmidt
authors: Norbert
authors: N
authors: Schnitzler
authors: Sabine
authors: S
authors: Nidermajer
authors: Kerstin
authors: K
authors: Brandenburg
authors: Josef
authors: J
authors: Zündorf
mesh_terms: D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D055499:Catheter-Related Infections / Q000188:drug therapy; D002633:Chemotaxis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005434:Flow Cytometry; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006801:Humans; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D023303:Oxazolidinones / Q000494:pharmacology* / Q000627:therapeutic use; D010587:Phagocytosis / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid