Uptake, intracellular activity, and influence of rifampin on normal function of polymorphonuclear leukocytes

Abstract

Quinone and hydroquinone forms of rifampin accumulated in normal polymorphonuclear leukocytes (PMN) (maximal cellular to extracellular concentration ratio [C/Emax] ± standard error of the mean, 9.36 ± 0.54 and 8.82 ± 0.65, respectively, after 5 to 10 min) and chronic granulomatous disease PMN (C/Emax, 13.76 0.77 and 14.29, respectively). Uptake of rifampin was influenced by incubation temperature and extracellular pH but not by phorbol myristate acetate stimulation or metabolic inhibitors. At extracellular concentrations between 0.06 and 5.0 mg/liter, rifampin significantly reduced the number of staphylococci surviving inside chronic granulomatous disease PMN, thus compensating for the bactericidal defect inherent with this disease. Spontaneous migration and chemotaxis of normal PMN were unaffected by rifampin. However, phagocytosis of yeast particles and oxygen consumption of stimulated PMN were moderately depressed, and O2-production and chemiluminescence were significantly depressed in a dose-dependent manner. The bactericidal activity of normal PMN was not impaired. Inhibition of chemiluminescence and O2-release were also observed in a cell-free system. We conclude that rifampin possesses favorable characteristics for the effective elimination of intracellular microorganisms. Further studies are needed to evaluate the in vivo significance of ion scavenging by rifampin, which could be hazardous to immunocompromised patients.

Antimicrobial Activity against Intraosteoblastic Staphylococcus aureus

“…Within this context, the low activity of vancomycin on intracellular staphylococci can consequently lie in its slow uptake and modest cellular accumulation compared to teicoplanin, a more lipophilic glycopeptide, which shows a more extensive and faster accumulation (25,26). Conversely, the good intracellular activity of clindamycin, fluoroquinolones, and rifampin can be explained by their well-known rapid accumulation in eukaryotic cells (27)(28)(29). However, fluoroquinolones are mainly located in the cytosol, whereas clindamycin and rifampin are distributed both in the cytosol and phagosomes, likely allowing these molecules to target all intracellular S. aureus cells (30).…”

Intracellular pharmacodynamics of antibiotics

“…PMNs incubated with chlortetracyclines have been shown to display a perinuclear fluorescent signal [60], but the data have never been further confirmed and no attempt at further studying the localization of tetracyclines by other techniques has been reported. Among ansamycins, rifampin accumulates from 2-to 10-fold according to the studies [61][62][63], whereas rifapentine shows a much higher accumulation (up to 60-to 80-fold [64]). The mechanism of this accumulation as well as the subcellular distribution of ansamycins remain, however, unknown.…”

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

“…The use of appropriate controls using cell-free oxidant-generating systems can help to characterize the target of antibiotic action. Among the drugs which have been recognized to display such effects are rifampin, which quenches superoxide anion (151), and cyclines, which scavenge hypochlorous acid (HOCl) (132), as does clofazimine (394) and various aminothiazolyl cephalosporins (215a). Penicillin G and ampicillin inhibit the chemiluminescence of PMNs and cell-free systems by scavenging HOCl and hydrogen peroxide (40,126), whereas chloramphenicol increases it (40).…”