| BackgroundAcinetobacter baumannii(AB)has great potential for substantial antimicrobial resistance.Multiple drug antibiotic resistant strains challenges the treatment of infection,resulting in longer hospital stay and higher mortality.The resistance rate of AB to cefoperazone-sulbactam increased from 30.7% to 41%,to minocycline from 31.2% to 44.9%,to imipenem from 57.1% to 67.4%,and to meropenem from 58.3% to71%,(comparing the data of CHINET 2010 and CHINET 2016).The resistance rate to other drugs such as amikacin,ampicillin sulbactam,gentamicin,cefepime,ceftazidime,piperacillin-tazobactam,ciprofloxacin were over 50%.Based on these observations,clinical use of cefoperazone-sulbactam or minocycline alone as an empirical treatment for AB infection may lead to increased treatment failure.According to CHINET2016,the resistance rate of AB to tigecycline was merely 6.6%,so clinicians are more inclined to include tigecycline in the treatment regimen.Tigecycline is the first glycine microbiotic with a very broad antibiotic spectrum,and has in vitro activity against Acinetobacter spp.However,it is still controversial whether to use tigecycline for the treatment of AB.In two observation studies(309 studies and JAMAL studies),the clinical response rates were 82.4%(14/17)and 91.67%(11/12)with a tigecycline 50 mg q12h regimen for the treatment of AB.On the other hand,in a phase III,randomized double-blind trail(RCT)of patients with hospital-acquired pneumonia(HAP)in 2010,the overall clinical response rates of tigecycline(50mg q12h)group was only 62.7%.Tigecycline was not recommended for the treatment of HAP caused by AB in 2016 IDSA and ATS HAP guidelines.A subsequent retrospective study of 63 patients suggested that a higher dose(100mg q12h)was associated with better outcomes.The inconsistency of these studies may be caused by the following reasons:(1)the mechanisms of drug resistance to tigecycline and other commonly used drugs are inconsistent.(2)The sample sizes of the studies were relatively small.The RCT included 67 patients,while the two observational studies included 17 and 12 patients respectively.(3)inconsistency in dosage: three of the four studies used the standard dose of 50 mg q12 h.The study with higher dose(100 mg q12h)shows better clinical outcomes.The efficacy of different dose to clinical outcomes was rare explored.Based on previous studies,we assumed that a more rational treatment for Acinetobacter infections must be based on Meta-analysis and the drug-resistant epidemics in different regions or hospitals.The drug resistance data of AB in Xinqiao Hospital of Army Medical University were more likely to be obtained,and the data integrity of patients with AB infection in Xinqiao Hospital was better.Therefore,we study and evaluate the clinical benefit,safety and tolerability of tigecycline for the treatment of AB infection with different dosage regimens in Xinqiao Hospital.We expected to provide evidance for the theraputic options of AB in the area of similar resistance background,and establish methods to explore treatment regimen in areas with different backgrounds.Methods1.Supplement AB drug resistance data of the three affiliated hospitals(Southwest Hospital,Xinqiao Hospital,and Daping Hospital)of Army Medical University(formerly the Third Military Medical University)to the Chongqing drug resistance monitoring network,to obtain more accurate resistance data in Chongqing province.2.Retrieve RCTs and high-quality cohort studies for the treatment of AB infection with tigecycline-based regimens in the Cochrane Library,EMbase,Pub Med,Web of Science,China Academic Journal(CNKI),Chinese Biomedical Literature Database(CBM),Chinese science and technology periodical full-text database(VIP),and Wanfang database.The literature quality was evaluated according to Cochrane Handbook 5.10.The Meta-analyis was conducted with RevMan 5.14 statistical software.30-day mortality,clinical efficiency and microbial clearance were used as the outcome index.The Meta-analysis will provide better evidence for the treatment of Acinetobacte.3.423 patients of AB infection in Xinqiao Hospital of Army Medical University from January 2015 to October 2016 were included,with 158 patients treated with tigecycline and 265 patients non-tigecycline regimens.30-day mortality,response rate,microbial clearance,length of hopitoal stay,ICU stay and length of antibiotics use were used as indicators for the analysis of clinical efficacy and safety.The relationship of different doses of tigecycline with effectiveness and safety were also explored.Results1.The resistance rate of AB to conventional therapeutic drugs such as cefoperazone-sulbactam,amikacin,meropenem and so on in the region was over 40%,and the resistance rate to tigecycline and minocycline were 2.1% and 26.6% respectively.The resistance rates to cefoperazone-sulbactam,amikacin was significantly higher than the national average level(P<0.05),and the rest of the commonly used drugs such as tigecycline,minocycline,imipenem,meropenem,cefepime,piperacillin-tazobactam,ampicillin sulbactam,ciprofloxacin and piperacillin-tazobactam were significantly lower than the national average level(P <0.05).The drug resistance rate of AB in the three army teaching hospital was found to be quite different,especially for cefoperazone-sulbatan,levofloxacin and imipenem(P<0.05).2.The Meta-analysis indicated that the response rate of tigecycline group is significantly higher than non-tigecycline group(P<0.05).Nevertheless,there is no notable difference between the two groups when microbial clearance and 30-day mortality were compared.3.No significated difference was identified in terms of 30-day mortality,microbial clearance,clinical response,and ICU stay in the two groups.The duration of hospitalization and antibiotics use were longer(P<0.005)in tigecycline group.Compared with the standard dose(50mg q12h),higher dose(100mg q12h)can significantly improve clinical response,microbial clearance,and decresase hospitalization time(P<0.05).Adverse reactions were camparable in groups with different dose(P>0.05).ConclusionsBased on Meta-analysis indicated that the response rate of tigecycline group is significantly higher than non-tigecycline group.Nevertheless,there is no notable difference between the two groups when microbial clearance and 30-day mortality were compared.Based on the drug-resistant background in our study,the Tigecycline-based regimen in the treatment of AB infection is comparable to that of non-tigecycline regiment in terms of 30-day mortality,clinical efficacy.The use of higher dose(100mg q12h)of tigecycline can improve the efficiency of the treatment without increasing the adverse effects. |
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