Factors influencing the biological inactivation of high protein bound beta-lactam antibiotics in vitro

C Henning, A M Bergholm, S Holm
APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica 1988, 96 (11): 997-1001
Unpredictable inactivation of antimicrobial agents may cause erratic results in pharmacokinetic studies. In this study we followed the inactivation of the high protein bound beta-lactams flucloxacillin, dicloxacillin and ceftriaxone in vitro. The antibiotics were added to pools of human and rabbit sera, ultrafiltrates of these pools, rabbit interstitial fluid, phosphate buffered saline (PBS), rabbit albumin in PBS and sodium dodecyl sulphate (SDS) treated preparations of human sera. Ceftriaxone was relatively stable but different serum pools varied significantly in their flucloxacillin and dicloxacillin inactivating capacity. The dominating inactivation took place within five minutes after the addition of antibiotics to serum. The inactivating factor was heat stable at 56 degrees C, 0.5 h, of relatively high molecular weight, and not related to albumin. The inactivating capacity could be diminished by SDS-treatment of serum suggesting a lipoprotein nature.

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