Bone Marrow Toxicity by Silver Sulfadiazine

The effect of silver sulfadiazine (SSD) on the production of granulocytes and macrophages was studied in a murine model of cutaneous injury. Application of SSD daily to mice receiving a 10 percent full-thickness total body surface area burn injury failed to demonstrate consistent suppression of the bone marrow at one, four or seven days postinjury. Mice undergoing a 10 percent full-thickness skin excision (SE) and daily SSD application (SE plus SSD) had a near 50 percent reduction in total peripheral blood leukocyte counts in comparison with a control group and untreated mice that were skin-excised (SE-U) (p < 0.03) to 0.002) on day one postinjury and maintained this reduction compared with SE-U at days four and seven postinjury. The absolute number of granulocytes in SE plus SSD was only 10 percent of control or SE-U (p < 0.04 to 0.002) at day one postinjury and remained less than SE-U at four and seven days postinjury. Femoral bone marrow assay of granulocyte-macrophage progenitor cells (GM-CFC) revealed a marked reduction in nucleated bone marrow cells for SE plus SSD compared with respect to control at days one and seven and SE-U at days four and seven (p < 0.02 to 0.001). GM-CFC were significantly depressed in SE plus SSD on day one compared with C and SE-U and day four compared with SE-U (p < 0.01 to 0.001), but returned to control values by day seven. When SSD (0.5 to 500.0 micrograms per milliliter) was added to culture plates containing maximally stimulated normal murine or human bone marrow cells, the colony count was depressed in a dose-dependent manner. In vitro SSD is directly cytotoxic to myelopoietic tissue, and in vivo, alters the myeloid cell compartment. These observations in combination may explain the transient leukopenia frequently observed in patients receiving topical chemoprophylaxis with SSD.