Different Dosages Of Tigecycline In The Treatment Of Ventilator-associated Pneumonia Due To Multidrug-resistant Pathogens

Background:The extensive uses of tigecycline(TGC)to treat ventilator-associated pneumonia(VAP)has aroused worldwide concerns.The efficacy about tigecycline have been reported recently.However,few studies about its adverse events(AEs).Our study aims to analyze the efficacy and safety of the regimen with different dosages in the treatment of VAP due to multidrug-resistant(MDR)pathogens.Methods:The clinical data of 134 patients who were diagnosed with VAP from January 2013 to December 2015 in the NeuroScience Care Unit(NCU)of our hospital were analyzed retrospectively.99 patients were male and 35 female,aged 15 to 94 years,with an average of(60.80±18.10)years.Duration of TGC treatment was 4 to 53 days,the average(11.39±6.27).54 patients received the standard dose group(SD,50 mg every 12 hours after a 100 mg loading dose intravenous infusion),69 in the high dose(HD,100 mg every 12 hours intravenous infusion of full course)and 11 between the two dosages(BD,100mg for 3?5 days at first,followed by 50 mg every 12 hours intravenous infusion).Acinetobacter baumannii was isolated in 104 and Klebsiella pneumoniae in 48.The incidence of clinical effectiveness and the occurrence time of AEs,and the factors of 28-day mortality were explored.Results:The results showed that the clinical effective rate in the HD group(48/69,69.6%)was higher than that in the SD group(19/54,35.2%)and the BD group(5/11,45.5%)(?2=14.73,p=0.001);HD group manifested higher bacterial clearance rate of Acinetobacter baumannii(27/69,51.9%)and Klebsiella pneumoniae(14/69,66.7%),p<0.05.The time required for CRP decreased by 50%(3.93±1.93 days)and duration of TGC regimen(9.63±3.92 days)in the HD group was shorter than that in the control groups,and the differences were numerically significant(p<0.01).The logistics regression analysis showed that APACHE ? score was independent predictor of clinical failure(OR=0.78,95%CI:0.70?0.88),while the HD regimen(OR=5.07,95%CI:2.04?12.57)and initial appropriate antibiotic treatment(OR=6.49,95%CI:2.28?18.5)were significantly associated with clinical effectiveness.There was no statistic difference in the incidence of AEs and the 2 8-day mortality among the three groups(p>0.05).Liver dysfunction occurred the latest(10.83±7.08),and total bilirubin(TBIL)increased significantly after SD of TGC treatment(p=0.004).Patients with septic shock,MODS and higher APACHE ? score were of high risk in mortality.Conclusions:The high-dose regimen was associated with better outcomes for the treatment of VAP patients,especially for the MDR Gram-negative bacilli infection.TGC was relatively safe and tolerable in ICU patients.The risk of side effects was related to the TGC duration,while not increased as the dosage rose.Inappropriate antimicrobial treatment might lead to clinical treatment failure.The severity and complications of patients were the important factors leading to the 28-day death of VAP patients,while not caused by adverse reactions of tigicycline.