ENTRY OF SANFETRINEM INTO HUMAN POLYMORPHONUCLEAR GRANULOCYTES AND ITS CELL-ASSOCIATED ACTIVITY AGAINST INTRACELLULAR, PENICILLIN-RESISTANTSTREPTOCOCCUS-PNEUMONIAE

The entry of antibiotics into phagocytes is necessary for activity aga inst intracellular pathogens. The ability of sanfetrinem, the first me mber of a new class of antibiotics, to penetrate human polymorphonucle ar granulocytes and its consequences upon subsequent phagocytosis and killing of ingested penicillin-resistant Streptococcus pneumoniae have been evaluated. Sanfetrinem penetrated into human polymorphonuclear l eukocytes (PMNs) at all concentrations tested, with cellular concentra tion/extracellular concentration ratios of 6.6 to 5.03 and 4.21 when s anfetrinem was used at 0.25 to 0.5 and 1 mu g/ml, respectively, within 30 min of incubation. The uptake was complete within 5 min and was no t energy dependent, since it was not affected by cell viability, envir onmental temperature, or the addition of a metabolic inhibitor. At a c oncentration of one-half the MIG, sanfetrinem significantly enhanced h uman PMN phagocytosis and increased intracellular bactericidal activit y against penicillin-resistant S. pneumoniae. Following preexposure of PMNs to a concentration of one-half the MIC of sanfetrinem, there was a significant increase in both phagocytosis and killing compared with that for the controls, indicating the ability of sanfetrinem to inter act with biological membranes and remain active within PMNs, Preexposu re of streptococci to sanfetrinem made penicillin-resistant S, pneumon iae more susceptible to the bactericidal mechanisms of human PMNs than untreated organisms.