Objective: To Compare the clinical efficacy and safety of meropenem with a 3-hour extended infusion or conventional 30-minute infusion regimen in treatment of hospital acquired pneumonia (HAP) in intensive care unit (ICU) patients.
Methods: An open-label randomized controlled clinical trial was conducted. 100 HAP patients, admitted to ICU of Qilu Hospital of Shandong University, who needed meropenem therapy were enrolled from September 1st, 2012 to September 30th, 2013. The patients were randomly divided into two groups. Patients who did not conform to the study protocol were excluded. A total of 78 patients were included for the study of clinical efficacy evaluation, with 38 cases in study group, and 40 in control group. The patients in study group received intravenous 1 g of meropenem (dissolved in 40 mL saline) within 10 minutes, and followed by the remaining 750 mg by continuous intravenous infusion for 3 hours, and the treatment was repeated every 8 hours. The patients in control group received meropenem by injection of 1 g (dissolved in 40 mL saline), i.e. by intravenous infusion within 30 minutes every 8 hours. This regime was carried out for at least 7 days. Clinical efficacy, bacterial clearance rate, improvement of critical illness scoring, and safety were observed and compared after meropenem withdrawal between two groups.
Results: Compared with control group, the clinical cure rate and 28-day survival rate in study group were significantly increased [clinical cure rate: 71.1% (27/38) vs. 42.5% (17/40), χ² = 6.461, P=0.011; survival rate: 81.6% (31/38) vs. 60.0% (24/40), χ² = 4.364, P=0.037]. The improvement of clinical pulmonary infection score (CPIS) and sequential organ failure assessment (SOFA) score in study group were more marked than those in control group (difference of CPIS score: -3.47 ± 2.48 vs. -1.50 ± 2.48, t=-3.513, P=0.001; difference of SOFA score: -2.10 ± 2.38 vs. -1.00 ± 2.21, t=-0.800, P=0.037). There were no significant differences in duration of meropenem treatment, acute physiology and chronic health evaluation II (APACHEII) score, procalcitonin (PCT), duration of mechanical ventilation, ICU stay days, secondary infection, and bacterial clearance rate between two groups. The main adverse reactions observed were transient elevation of liver enzymes and diarrhea in both groups, but no significant difference in their incidence was found between study and control groups [elevated liver enzymes: 28.9% (11/38) vs. 30.0% (12/40), χ² = 0.010, P=0.919; diarrhea: 7.9% (3/38) vs. 10.0% (4/40), χ² = 0.000, P=1.000].
Conclusions: Compared with conventional regime of 30-minute infusion of meropenem in the treatment of HAP in ICU patients, the clinical efficacy can be improved, the severity of the disease can be reduced, the recovery of organ failure and long-term prognosis can be improved with 3 hour extended infusion of meropenem.