Effect of antimicrobial agents on chemiluminescence of human polymorphonuclear leukocytes in response to phagocytosis

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Abstract
Because antimicrobial agents are frequently administered to patients who are severely predisposed to infection due to granulocytopenia or due to abnormalities in the function of polymorphonuclear leukocytes (PMN), we investigated the possibility that these drugs might impair the microbicidal respiratory burst of PMN. At concentrations within or beyond the range of peak levels achieved in human serum during therapy, 22 antimicrobial agents were screened for their effects on an assay of chemiluminescence in response to phagocytosis of Candida albicans. Rifampicin and the combination of trimethoprim (TMP) and sulphamethoxazole (SMZ) resulted in a pronounced inhibition of the chemiluminescence response of PMN. Inhibition due to absorption of light emitted could not be excluded in the case of rifampicin but was excluded in the case of TMP plus SMZ. The effect of this combination was found to be reversible, dose-dependent, and to occur at concentrations readily achieved in serum during therapy. TMP and SMZ, individually as well as in combination, were found to inhibit the chemiluminescence response of PMN. These findings indicate that TMP and SMZ alter microbicidal function of PMN and suggest the possibility that administration of these drugs to some patients could exacerbate an underlying predisposition to infection.