Activity of antibiotics against Staphylococcus aureus within polymorphonuclear neutrophils

Abstract

The intracellular location of certain strains of Staphylococcus aureus serves as a reservoir of bacteria which is thought to be important in therapy of recurrent infections in humans and in chronic staphylococcal mastitis in dairy cows. This overview summarizes data pertaining to the intracellular survival of Staphylococcus aureus within polymorphonuclear neutrophils (PMNs) both in vitro and in vivo in the face of antibiotic treatment. While compounds such as rifampin, clindamycin, erythromycin, and ciprofloxacin have been shown to be rapidly taken up by PMNs, the ability of antibiotics to concentrate within PMNs did not strictly correlate with their ability to kill intracellular Staphylococcus aureus. Rifampin and ciprofloxacin have been shown to be the most effective intraphagocytic killing agents, while clindamycin and erythromycin were inactive in these in vitro assays. In vivo, in therapy of Staphylococcus aureus arthritis and peritonitis in humans and in certain mouse models rifampin has generally been shown to be more effective than comparator antibiotics. In a staphylococcal subcutaneous abscess model, however, clindamycin was very effective in curing the Staphylococcus aureus abscesses in this system where PMNs were the primary inflammatory cells involved. The intracellular bacterial counts decreased as rapidly as the extracellular bacteria. Rifampin was also effective in the abscess model but ciprofloxacin was ineffective at the highest doses tested. The relevance of in vitro and in vivo models and the importance of PMNs as a reservoir of infection in staphylococcal diseases in humans and the dairy cow are discussed.