Pharmacokinetics Of Aerosolized Amikacin And Its Effect In The Treatment Of Ventilator-associated Pneumonia Due To Gram-negative Bacilli

Objective:To study the pharmacokinetic features of nebulized amikacin in sputum and serum of patients with ventilator-associatied pneumonia due to gram-negative bacilli, and to evaluate the efficacy and safety of inhaled amikacin as adjunct therapy in the treatment of ventilator-associated pneumonia caused by Gram-negative bacilli;Methods:1. Pharmacokinetics:20patients who met the diagnostic criteria of ventilator-associated pneumonia were assigned to two groups equally:besides intravenous antibiotic therapy, one group inhaled AMK200mg qd, and another group inhaled AMK400mg qd. Sputum samples and blood samples were taken from two groups respectively at the time0,1h,2h,4h,6h,8h,12h,24h after the atomization,and stored in-70℃condition.Amikacin concentrations in serum and sputum were detected by LC/MC/MC system at the end of trial.2. Clinical effect assessmentThe experiment was designed to be a randomized controlled double-blind pilot trial;51patients with VAP due to Gram-negative bacilli collected in the Department of Emergency&Critical Care Medicine of a tertiary hospital during the period Jan.2010-Dec.2011were randomised to control group(24cases) or experimental group(27cases). The control group was given the routine intravenous antibiotics in the basis of evidence-based guideline according to attending physicion’s clinical experience combined with5ml normal saline nebulized, while the experimental group was given400mg amikacin in5ml normal saline nebulized. The routine blood test, renal function test, arterial blood gas analysis, CXR, and bacteriological examination were undergone at the randomization,3rd day and7th day of experiment, weaning, survival, temperature were recorded daily. All patients were followed up to4weeks after the7days’study to make sure whether to survive or wean from mechanical ventilation. Results:Pharmacokinetic features:Not only amikacin concentration in serum but also in sputum decreased gradually,which peaked immediately after the end of the atomization. The peak of sputum amikacin concentration and serum amikacin concentration was1428μg/ml (1181.0-1676.0) and1.11μg/ml (0.74-1.48) respectively in group400mg, while the peak of sputum amikacin concentration and serum amikacin concentration was383.1μg/ml (100.1-666.1) and0.27μg/ml (0.14-0.40) respectively in group200mg.Clinical effect:1. There was no significant statistical difference in fatality rate and weaning rate between expremental group and control group at the7th day and28th day of study.2. During the study, patients’CPIS score, WBC, temperature declined gradually and oxygen index improved gradually in both groups. Moreover, CPIS score, WBC, temperature and oxgeny index in expremental group declined and improved more significantly than control group, and there was significant statistical difference between two groups at the7th day of study(p<0.05).3. Patients’CRP and PCT declined gradually during the study in both groups, but there was no significant difference between two groups(p>0.05).4. At the7th day of study, more patients in control group need additional antibiotics to control infenction than expremental group (41.7%vs14.8%), and the statistical difference between two groups was significant(p=0.032).5. At the3rd day and7th day of study, bacterial resistance rate in both groups increased,but there was no significant difference between two groups.6. At the3rd day and7th day of study, the serum creatinine did not elevated obviously in both groups, and there was no significant difference between two groups.Conclusion:1. The drug concentration in airway secretion by inhaled amikacin is much higher than MIC values of Gram-negative bacilli, and serum amikacin concentrations are far lower than the concentration of its renal toxicity, so aerosolized amikacin might be a safe and effective treatment of VAP due to Gram-negative bacilli. 2. Nebulized amikacin as adjuvant therapy in the treatment of ventilator-associated pneumonia don’t have an obvious impact on patients’fatality rate and weaning rate, but could improve patients’lung infection syndrome and oxgeny index, decrease patients’ WBC and systemic usage of antibiotics, and don’t impare patients’renal fuction and increase bacterial resistance, which is a safe and effective therapy.