Clinical pharmacological study of tazobactam/piperacillin in patients with community-acquired pneumonia

A clinical pharmacological study of tazobactam/piperacillin(TAZ/PIPC), a β-lactamase inhibitor combined with penicillin antibiotic, was conducted on patients with community-acquired pneumonia, together with population pharmacokinetics(PPK) and pharmacokinetics-pharmacodynamics(PK-PD) analysis. Results confirmed TAZ/PIPC dosage propriety for this group of patients. 1. PPK analysis: Patients with pneumonia were compared to healthy adult volunteers for PIPC and TAZ PK parameters. Systemic clearance was lower and the half-life (t₁/₂) was longer in those with pneumonia than in healthy volunteers. The steady-state volume of distribution (V) of TAZ in patients with pneumonia was 1.23 times and of PIPC 1.30 times as large as those in healthy adult volunteers. C_max in blood was lower in patients with pneumonia. 2. Clinical effect Response three days after treatment was 11.6% (5/43 patients) and time to completion/discontinuation of treatment was 86.0% (37/43 patients). Improvement seven days after completion of treatment was 81.4% (35/43 patients). 3. PK-PD analysis: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis were detected in 24 patients, and all cases were judged to have "disappeared." Calculated time above MIC (%) was 100% in all cases but one (94.6%). When TAZ/PIPC was administered three times a day (4.5 g x 3) or four times a day (4.5 g x 4) to patients with pneumonia whose Ccr was 120 mL/min, MIC allowing time above MIC (%) exceeding 30% were 32 μg/mL and 64 μg/mL. 4. Safety: Drug-related adverse events numbering 54 were recognized in 24 patients, i.e., an incidence of 40.0%. Of laboratory test abnormalities, 32 adverse events recognized in 16 patients were regarded as drugrelated i.e., an incidence of 26.7%. Given these results, the appropriate TAZ/PIPC dosage adopted for treatment of community-acquired pneumonia is three times daily at 4.5 g.