[Treatment study of hospital acquired pneumonia by optimizing dosing regimen of piperacillin/tazobactam:prolonged vs. regular infusion].

Objective: To observe the serum concentration and evaluate clinical efficacy of piperacillin/tazobactam (TZP) prolonged infusion time in treatment of hospital acquired pneumonia (HAP).

Methods: Fifty HAP patients admitted to intensive care unit (ICU) from March 1 to October 31, 2012 were enrolled. The bacterial drug sensitivity results showed that the minimum inhibitory concentration (MIC) of TZP was 8 mg/L or 16 mg/L. According to completely randomized grouping method, the patients were divided into treatment group (n=25) and control group (n=25). The therapeutic regimen in control group was TZP 4.5 g, in regular infusion every 6 hours and finished in 30 minutes; the treatment group was TZP 4.5 g, in prolonged infusion every 6 hours by using infusion pump for continuous intravenous infusion 3 hours. Acute physiology and chronic health evaluation II(APACHEII) score, clinical pulmonary infection score (CPIS) and procalcitonin (PCT) level were compared between the two groups 3 days after treatment. The treatment success rate, remedial treatment rate, antibiotic costs were recorded in both groups. Blood specimen was collected at 0.5, 1, 2, 3, 4, 6 hours at the beginning of administration, and the blood drug concentration of piperacillin and tazobactam was determined using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS).

Results: The PCT (2.16±0.17 μg/L vs. 4.77±0.25 μg/L), CPIS score(6.21±1.14 μg/L vs. 6.92±1.35 μg/L) and remedial treatment rate (12.0% vs. 52.0%) of the treatment group were significantly lower than those of the control group after administration for 3 days (P<0.05 or P<0.01), and APACHEII score was slightly lower than that in control group (21.38±7.37 vs. 22.15±5.46, P>0.05). After active remedial treatment, there were no significant difference in the treatment success rate (88.0% vs. 80.0%) and relapse rate (4.2% vs. 7.7%) between treatment group and control group (both P>0.05). But the antibiotic costs in treatment group were significantly lower than that of control group (4330.38±1087.24 Yuan vs. 5506.15±1361.73 Yuan, P<0.01). The treatment course of antibacterials in treatment group was significantly shorter than that in control group (6.00±1.05 days vs. 8.20±1.03 days, P<0.01). The infection by Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae was monitored, TZP serum concentration administrated at 0.5-6 hours in the treatment group was higher than MIC, but in the control group, TZP blood concentration was lower than MIC after administration for 2-3 hours. In treatment group, the percentage of duration of blood drug level higher than MIC account for dosing interval (%T>MIC) was 86.82%, while in the control group, the %T>MIC was 42.84%.

Conclusions: TZP prolonged the infusion time dosing regimens using in Gram negative bacteria induced by high MIC value of HAP have more stable plasma concentration, curative clinical effect and reduce the cost of treatment.