title: Cellular uptake and cell-associated activity of third generation cephalosporins.
abstract: The ability of the third generation cephalosporins to penetrate human polymorphonuclear leukocytes (PMNs) and their antibacterial activity against cell-associated Staphylococcus aureus (SA) and Haemophilus influenzae, type b (Hib) were studied. Utilizing radioactive uptake experiments, the cellular to extracellular concentration ratios were determined to be less than one for all cephalosporins at 10 and 120 min: cefotaxime (0.08 +/- 0.02, 0.34 +/- 0.08), ceftizoxime (0.21 +/- 0.11, 0.52 +/- 0.18), ceftriaxone (0.12 +/- 0.04, 0.38 +/- 0.23), and N-formimidoyl thienamycin (0.18 +/- 0.09, 0.33 +/- 0.14). Third generation cephalosporins were similar to penicillin in their exclusion from PMNs. The killing of cell-associated SA and Hib were evaluated in a preopsonized cell-associated bacterial assay with radiolabelled SA/Hib (cfu/cpm) comparing activity of PMNs + antibiotics to the PMN cell control (no antibiotics) at 0.5, 2, and 4 h. PMNs alone killed less than or equal to 0.5 log SA/Hib over 4 h. Clindamycin killed significantly more SA (p less than 0.01) than all other antibiotics; nafcillin killed significantly fewer SA (p less than 0.05) than all other antibiotics. Although each third generation cephalosporin showed good activity against cell-associated Hib, chloramphenicol had a significantly greater effect (p less than 0.05). N-formimidoyl thienamycin demonstrated good activity only after the concentration was increased in vitro to 8 micrograms/ml. Although cellular penetration of antibiotics may be important in the eradication of cell-associated pathogens, the overall cellular activity would appear to be multifactorial.
mesh_terms: D000328:Adult; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D002511:Cephalosporins / Q000097:blood* / Q000494:pharmacology; D006193:Haemophilus influenzae / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D002511:Cephalosporins