INFLUENCE OF FORTY-TWO ANTIMICROBIALAGENTS ON THE CHEMILUMINESCENCE RESPONSE OF HUMAN PHAGOCYTIC CELLS

Abstract

Chemiluminescence (CL) is a sensitive indicator of phagocytosis and intracellular killing. The effect of forty-two antimicrobial agents on the luminol-enhanced CL of polymorphonuclear leukocytes (PMN) or whole blood was studied. After 10 min preincubation of cells with each drug at various concentrations, the CL response of phagocytic cells stimulated with non-opsonized zymosan or phorbol myristate acetate (PMA) was measured for 20 min. At therapeutic concentrations, sulfamethoxazole (SMX) and trimethoprim (TMP) showed significant CL suppression. Minocycline (MINO) and doxycycline (DOXY) also reduced CL at rather high concentrations (more than 12.5μg/ml). However, twenty-seven β-lactam antibiotics, four aminoglycosides, erythromycin, clindamycin, fosfomycin, vancomycin and three antifungal agents did not inhibit CL at therapeutic concentrations. None of the antimicrobial agents enhanced the CL response from phagocytic cells in our study.
These results suggest that MINO, DOXY, SMX and TMP clinically cause a reduction in the antimicrobicidal activity of phagocytic cells. Especially in the treatment of immunocompromised patients with already-impaired antimicrobicidal activity, those drugs that inhibit the CL response in vitro may further reduce or suppress the function of phagocytic cells. However, the clinical significance of these observations remains to be determined.