Faropenem enhances superoxide anion production by human neutrophils in vitro

J Antimicrob Chemother. 1999 Sep;44(3):337-41. doi: 10.1093/jac/44.3.337.

Abstract

Neutrophils are important cellular components in the defence against infections and many studies in vitro have shown that some antibiotics affect neutrophil function. We examined the effect of faropenem, a new oral penem antibiotic on neutrophil killing function by determining the generation of superoxide anion in vitro. The production of superoxide anion was measured by chemiluminescence amplified by a Cypridina luciferin analogue in the presence of N-formyl-Met-Leu-Phe (fMLP). Faropenem significantly enhanced chemiluminescence in a dose-dependent manner. The effect of faropenem was maximal at 5 min of incubation time and continued for at least 30 min. The effect of faropenem was also observed when neutrophils were stimulated by a calcium ionophore (ionomycin), while the effect of faropenem did not change in the presence of 12-O-tetra-decanoylphorbolmyristate acetate. Cytosol Ca2+ concentration ([Ca2+]i) monitored with Fura-2 increased in response to fMLP, however, faropenem did not influence the response of [Ca2+]i to fMLP. Our results suggest that faropenem enhanced the generation of superoxide anion by neutrophils, probably at the site where cytosol Ca2+ regulates NADPH oxidase. Faropenem might be potentially advantageous in the treatment of infections because a synergic interaction of antibodies and cytocidal neutrophils is necessary for the early eradication of the pathogenic bacteria.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Calcium / metabolism
  • Dose-Response Relationship, Drug
  • Firefly Luciferin / chemistry
  • Humans
  • Ionomycin / chemistry
  • Lactams*
  • Luminescent Measurements
  • N-Formylmethionine Leucyl-Phenylalanine / chemistry
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Superoxides / metabolism*
  • Time Factors
  • beta-Lactams

Substances

  • Anti-Bacterial Agents
  • Lactams
  • beta-Lactams
  • Superoxides
  • Ionomycin
  • N-Formylmethionine Leucyl-Phenylalanine
  • Firefly Luciferin
  • fropenem
  • Calcium