目的 探讨哌拉西林他唑巴坦负荷剂量两步输注与传统延长输注治疗重症监护病房革兰阴性菌（GNB）致重症医院获得性肺炎（HAP）的临床疗效。方法 选择2019年5月—2022年11月入住衡水市人民医院重症监护病房（ICU）的多重耐药革兰阴性菌（GNB）致重症医院获得性肺炎患者150例，按照随机数字表分为对照组和治疗组，每组各75例。对照组静脉泵入注射用哌拉西林钠他唑巴坦钠，4.5 g加入生理盐水100 mL，静脉泵持续输注3 h，1次/8 h。治疗组静脉泵入注射用哌拉西林钠他唑巴坦钠，4.5 g加入生理盐水100 mL，前2.25 g采用静脉泵在30 min内输注，后2.25 g采用静脉泵在150 min内持续输注。两组患者均治疗7～14 d。观察两组患者临床疗效，比较治疗前后两组患者细菌清除率，临床感染症状恢复时间，炎性指标降钙素原（PCT）、C反应蛋白（CRP）和白细胞计数（WBC）水平，及住院时间、机械通气时间和治疗总费用。结果 治疗后，治疗组临床总有效率（85.33%）显著高于对照组（70.67%，P＜0.05）。治疗后，治疗组细菌清除率（73.33%）显著高于对照组（56.00%，P＜0.05）。治疗后，治疗组啰音消失时间、咳嗽咳痰消失时间和退热时间均短于对照组（P＜0.05）；治疗后，两组WBC、PCT和CRP均显著下降（P＜0.05），且治疗组比对照组下降更显著（P＜0.05）。治疗后，治疗组在住院时间、机械通气时间和治疗总费用方面均明显小于对照组（P＜0.05）。结论 哌拉西林他唑巴坦负荷剂量两步输注能显著提高入住ICU病房GNB致重症HAP的临床疗效和细菌清除率，能明显缩短症状改善时间，从而缩短患者住院时间和降低治疗费用。

Objective To investigate the efficacy of piperacillin/tazobactam by two-step infusion with loading dose versus traditional extended infusion in the treatment of severe hospital-acquired pneumonia (HAP) caused by gram-negative bacteria (GNB) in ICU. Methods Patients (150 cases) with severe hospital acquired pneumonia caused by multi-drug resistant Gram-negative bacteria (GNB) in Hengshui People’s Hospital from May 2019 to November 2022 were divided into control and treatment group according to random number table, and each group had 75 cases. Patients in the control group were infusion administered with Piperacillin Sodium and Tazobactam Sodium for injection, 4.5 g added into normal saline 100 mL for 3 h, once every 8 h. Patients in the treatment group were infusion administered with Piperacillin Sodium and Tazobactam Sodium for injection, 4.5 g added into normal saline 100 mL, the first 2.25 g was infused within 30 min by intravenous pump, and the last 2.25 g was infused continuously within 150 min. Patients in two groups were treated for 7 — 14 d. After treatment, the clinical evaluation was evaluated, and the bacterial clearance rate, improvement time of clinical infection signs, the levels of inflammatory indexes WBC, PCT and CRP, and hospitalization time, mechanical ventilation time, and total treatment cost in two groups before and after treatment were compared. Results After treatment, the total clinical effective rate of the treatment group (85.33%) was significantly higher than that of the control group (70.67%, P < 0.05). After treatment, the bacterial clearance rate in the treatment group (73.33%) was significantly higher than that in the control group (56.00%, P< 0.05). After treatment, the disappearance time of rale, cough and sputum and body temperature recovery time in the treatment group were shorter than those in the control group (P< 0.05). After treatment, WBC, PCT and CRP in two groups were significantly decreased (P < 0.05), and the decrease in the treatment group was more significant than that in the control group (P < 0.05). After treatment, the treatment group showed significantly lower hospitalization time, mechanical ventilation time, and total treatment cost compared to the control group (P < 0.05). Conclusion Two-step infusion with loading dose of piperacillin and tazobactam can significantly improve the clinical efficacy and bacterial clearance rate of severe hospital-acquired pneumonia caused by gram-negative bacteria in ICU, and can significantly shorten the time of symptom improvement, thus shorten the time of hospitalization and reduce the cost of treatment.

R974

河北省医学科学研究课题计划项目（20220458）