Delayed response or recurrence of clinical
infections may, in part, be due to the inability of certain
antibiotics to penetrate human polymorphonuclear leukocytes (PMN) and exert intracellular antibacterial activity. We determined the penetration of PMN by certain hydrophilic and certain lipophilic
antibiotics, and assessed their activity against intracellular Haemophilus influenzae, type b or Staphylococcus aureus. We found that
penicillin G was excluded from human PMN while
chloramphenicol was concentrated within these cells;
chloramphenicol killed significantly more intracellular H. influenzae than did
penicillin or
ampicillin.
Clindamycin and
trimethoprim penetrated into normal and
chronic granulomatous disease (CGD) PMN equally and were at least transiently concentrated in the cells.
Clindamycin and the combinations
trimethoprim/
sulphamethoxazole and
trimethoprim/
rifampicin were most effective in killing intracellular Staph. aureus in vitro; these
antibiotics reduced the bacterial density in CGD PMN to values comparable to those in normal PMN. The mechanism by which
clindamycin and
rifampicin killed intracellular Staph. aureus appeared to be due to direct antimicrobial activity.
Antibiotics that penetrate into phagocytes may be more effective in
infections due to pathogens capable of intracellular survival.