CLINICAL PHARMACOKINETICS OF PIPERACILLIN -TAZOBACTAM COMBINATION IN INFECTED MAJOR BURN PATIENTS

The pathophysiology associated with major burns is complex and subject to a state of flux. The emergence of bacterial resistance is a topic of current interest in this area. The combination of beta-lactamase in hibitors with powerful penicillins is a new concept and an attractive potential solution to this worrying problem. Serum and urinary kinetic s, clinical safety and microbiological efficacy of Tazocilline(R) (Led erle Laboratories), a synergistic and fixed association of 4 g of pipe racillin (PPR) and 0,5 g of tazobactam (TZB) were studied in 7 (22 to 50 years old and weight 48 to 105 kg) infected (Pseudomonas aeruginosa and various enterobacteria) major burn patients. Treatment involved o ne dose every 6 h. Mean body surface area affected by 3rd degree burns was 32,3 +/- 2,1 %, The study took place in accordance with current e thical guidelines. Two series of blood samples were drawn after the Is t (D1) and the 9th (D3 at steady state) dose; urine was collected duri ng these same periods. Serum and urinary PPR and TZB levels were measu red by HPLC. A non-compartimental method was used for kinetic and grap hic analysis of concentration-time pairs. Safety and efficacy of treat ment were excellent. There was no systemic accumulation of Tazocilline (R). Residual concentrations measured on D1 and D3 were above the MIC far the organism responsible for infection i.e. CminD1 = 22,1 +/- 3,9, CminD3 = 12,5 +/- 1,7 for PPR and, CminD1 = 2,0 +/- 0,4, CminD3 = 1,4 +/- 0,2 for TZB. There was no statistically significant difference be tween pharmacokinetics parameters determined for D1 and D3, Evidence w as found in burn patients, in comparison with healthy subjects, of a m arked increase in apparent volumes of distribution, in such a way that the apparent elimination half-life of Tazocilline(R) was notably prol onged i.e. 1,6 +/- 0,2 vs 0,6 +/- 0,1 hr for PPR and, 1,7 +/- 0,2 vs 0 ,8 +/- 0,1 hr for TZB. These findings indicate the possibility of non- renal trans-lesional diffusion of PPR-TZB in burn patients, which coul d be a co-factor in terms of the success of treatment. The high degree of polarity of the association would further support this hypothesis, It has been shown here that recommended regimen for administration of PPR-TZB need to be high in major burn patients, The data obtained are important and valuable information, suitable for immediate applicatio n in everyday clinical practice.