In vitro toxic effects of certain antibiotics on the fibroblasts of two children with I-cell disease.

Six antibiotics, pefloxacin (Peflacine), fosfomycin (Fosfocine), teicoplanin (Targocid), vancomycin (Vancocine), ceftazidime (Fortum), piperacillin (Piperilline), that may be used as a systematic coverage during bone marrow transplantation have been tested on dermal fibroblasts of one control subject and two I-cell disease patients, along with five subcultures, corresponding to 5 weeks of culture. The possible toxicity of these molecules was assessed. The evaluation of lysosomal enzyme sphingomyelinase activity, detection of free intracellular cholesterol and the light- and electron-microscopic examination of treated cells were used as measures of metabolic interference and cytotoxicity. Our study shows that despite a lack of any metabolic sign of interference (no modification in enzyme activity, no increase in free intracellular cholesterol), all the antibiotics tested induced a cytotoxic effect which was notably amplified in the I-cell populations. This may be due to the lysosomal lipid storage of these cells which modifies the relationship between the antibiotic and the cell by inducing a different kind of lipid-antibiotic interference.