Tigecycline-based combination therapy for ventilator associated pneumonia due to multidrug-resistant Acinetobacter baumannii *

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(1.Department of Intensive care unit;2.Department of Respiratory and critical care unit,The Second people's Hospital of Wu Hu Affiliated to Wannan Medical College,Wuhu,Anhui 241000;3.Biology Department of The Universtiy of Liverpool,UK　L693BX)

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Tigecycline-based combination therapy for ventilator associated pneumonia due to multidrug-resistant Acinetobacter baumannii*

ZHALei1,3,XUQian-cheng1,YANGGang2,CHENShang-hua1,SHENWen-wen1,LIANGXi-quan1

(1.Department of Intensive care unit;2.Department of Respiratory and critical care unit,The Second people's Hospital of Wu Hu Affiliated to Wannan Medical College,Wuhu,Anhui 241000;3.Biology Department of The Universtiy of Liverpool,UKL693BX)

Objective:To evaluate the effectiveness of tigecycline-based combination therapy for ventilator associated pneumonia due to multidrug-resistant Acinetobacter baumannii.Methods:This study was conducted by retrospective analysis,a total 65patients with ventilator associated pneumonia caused by multidrug-resistant Acinetobacter baumannii were enrolled and classified into two groups，the tigecycline group(38 cases)and non-tigecycline group(27cases)depended on whether used tigecycline. Data collected from medical record including clinical outcomes，microbiological outcomes，laboratory data of infection (White blood cell and Procalcitonin) on 7th day, duration of antibiotics use，length of Intensive care unit stay，length of hospital stay，14-day mortality and in-hospital mortality.Result:There were no statistical differences in clinical outcomes，infection index on 7th day,duration of antibiotics use，length of ICU stay,length of hospital stay,14-day mortality and In-hospital mortality.But as for the microbiological outcomes,tigecycline group has a higher microbiological eradication rate(29/76.3% vs. 12/44.4%,P=0.00),whereas non-tigecycline group has a higher replacement or superinfection rate(10/37.0% vs. 4/10.5%,P=0.01).Conclusion:Tigecycline-based combination therapy is comparable in clinical outcomes and with a favorable microbiological outcomes, when contrasted to other-based combination therapy.

Tigecycline;Ventilator associated pneumonia(VAP);Multidrug-resistant Acinetobacter baumannii(MDRAB)

0　INTRODUCTION

Acinetobacter baumannii is one of the most common pathogens in modern healthcare setting[1].Its versatile genetic mechanism,which permit it quickly to gain resistant ability,tolerate harsh environment and be the major organism caused healthcare-associated infections(HAI),including ventilator associated pneumonia(VAP),blood stream infection(BSI),meningitis,urinary tract infection(UTI),complicated intra-abodominal infection(IAI),wound infection and even sepsis in immunocompromised patients,and associated with increased mortality,length of hospital stay and economical burden[2-4].Moreover,infections due to multidrug-resistant Acinetobacter baumannii(MDRAB) are prevalent,especially carbapenem-resistant organisms become more common,take serious challenge to clinical participant[5-6].The mainstream treatment strategy for MDRAB was colistin-based therapy,but due to its nephrotoxicity,central nervous system toxicity,rapidly raised resistance rate and unsatisfied clinical outcomes,which urgent us to find a new treatment strategy[7].Tigecycline as the first commercially glycylcycline,is a broad spectrum antibiotic with potent activity against MDRAB in vitro,and be an considerable alternative[8].Nevertheless,there is limited study focuing on tigecycline treat for ventilator associated pneumonia(VAP) caused by MDRAB.Therefore,we conducted this retrospective analysis,aiming to evaluate the effectiveness of tigecycline against MDRAB in VAP.

1　MATERIALS AND METHODS

1.1Patient recruitment and Data collection

We retrospectively analyzed patients diagnosed with VAP caused by MDRAB in a tertiary hospital,from January 2012 to March 2015.Inclusion criteria:Diagnosed with VAP due to MDRAB;age>18 years;received combination therapy(based on tigecycline or not);Exclusion criteria were:died within 48 hours after starting antibiotics treatment;switch antibiotics within 48 hours;tigecycline as empirical treatment involving pathogens other than MDRAB;concurrent infection other than lung;Acute Kidney Injury;Chronic Kidney Disease above stage 3; severe live failure;disease in advanced stage.This study was approved by Ethics Committee of the hospital.

Data were collected from medical record included following:age,gender,primary disease attributed to mechanical ventilation,onset of VAP;laboratory data of infection;culture results of airway specimens;combination antibiotics and duration;time of switch antibiotics and reason;mechanical ventilation duration;length of ICU stay;length of hospital stay and Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)scores during ICU stay.Specimens were collected from airway,included sputum,tracheal aspirate and bronchoalveolar lavage(BAL)fluid.

1.2Definitions

MDRAB[9，4]was defined as Acinetobacter baumannii stain was resistant to at least there different classes of antimicrobial agents,including cephalosporins,aminoglycosides,fluoroquinolones and sulbactam.VAP diagnosis was made according to guideline and criteria published by American Thoracic Society and Centers for Disease Control and Prevention[10-11]:when a new,persistent,progressive radiographic lung infiltrate was present≥48 hours following tracheal intubation and when two or more of the following clinical criteria were met:new onset of purulent bronchial secretions;body temperature>38.8 ℃ or <35.5 ℃;and white blood cell count>10×109·L-1or < 4×109·L-1;VAP occur within the first 4 days of tracheal intubation were defined as early-onset VAP,while those occur on or after 5th day were defined as late-onset VAP.The positive culture results of samples suggested MDRAB as suspected pathogen was determined by attending physicians and professors major in pulmonary department and ICU.The duration of antibiotics use was decided by attending physicians who are responsible for patients according to clinical sign,symptom and laboratory results.The decisions to begin and end the tigecycline treatment were also made by the attending physician and the duration of tigecycline treatment was decided according to its clinical responses(de-escalation or conversion).Steroid use was defined as corticosteroid therapy being administered within 14 days of infection.

Clinical outcomes at the end of treatment,which determined by professors according to clinical sign,symptom and laboratory results,defined as success(completed improvement),failure(stationary or even worsen);Microbiological outcomes,defined as eradication(sterile culture results during and after the antibiotic therapy course) and failure,which can be divided into No-eradication(Continuously positive culture results of the same pathogen induced the initial VAP),replacement(positive culture results other than AB and be treated as the pathogen of VAP during the therapy course)and superinfection(Continuously positive culture results of MDRAB and other new pathogens related to antibiotic treatment).

Mortality,including overall mortality and attributable mortality(death related to MDRAB,not related to other conditions).

Groups and Evaluation indexPatients were classified into two groups，the tigecycline group and non-tigecycline group depended on whether used tigecycline.Tigecycline was given in standard regimen of a 100 mg loading dose followed by 50 mg every 12h and combination antibiotics were prescribed according to drug instruction.Evaluated indexes were:clinical outcomes,microbiological outcomes,mortality,duration of antibiotics use,length of ICU stay,length of hospital stay and PCT,WBC on day 7th.

Statistical analysisContinuous data were described by mean and standard deviation,and categorical data were describe as count and percentage.Continuous variables were compared with student’s t-test,and categorical data were compared by Fisher’s exact test and pearson’s chi-square test.All data were analyzed with SPSS version 22.0 statistical software(SPSS,Chicago,IL,USA).A p-value<0.5 was considered statistically significant.

2　RESULTS

2.1Patient characteristics

A total 96 patients matched inclusion criteria and 31 patients were excluded according to exclusion criteria.Eventually,65 patients were recruited which was consisted of tigecycline group(38 patients) and non-tigecycline group(27 patients).There were no significant differences in age,gender and primary disease(P>0.05).Tigecycline group contained more late-onset VAP patients and relatively higher APACHEⅡscore,whereas non-tigecycline group has a higher PCT and WBC,but differences were not any statistically significant(P>0.05).Total 25 patients enrolled in this study(14 patients in tigecycline group,11 patients in non-tigecycline group,P=0.75)were treated with hydrocortisone(200mg per-day) due to unstable hemodynamics(Table 1).Drug susceptibility test revealed tigecycline was the most sensitive agent, account for 94.7%(36/38) and 96.3%(26/27) in the two groups,respectively.Whereas isolated strains sensitive to imipenem only account for 42.1%(16/38) and 44.4%(12/27)(Table 2).The common combination regimens used together with tigecycline were cefperazone/sulbactam,imipenem/cilastatin and piperacillin/tazobactam,while in the non-tigecycline group,piperacillin/tazolactam,cefperazone/sulbactam,respiratory quinolones,carbapenems and amikacin were preferred antibiotics(33.3%,51.8%,37.0%,14.8% and 59.3%,respectively),which were according to antimicrobial susceptibility results or experimental regimen decided by attending physicians and professors who are responsible for patients.And the detailed combination regimens were shown in table 3(Table 3).

Table 1　Clinical and demographic characteristics of patients with ventilator associated pneumonia involving MDRAB

COPD：chronic obstructive pulmonary diseases;CVD:Cerebral-vascular disease;VAP:Ventilator associated pneumonia;

APACHEⅡ:Acute Physiology and Chronic Health Evaluation;WBC:white blood cell;PCT:procalcitonin.

Table 2　The drug susceptibility test results of Acinetobacter baumanni in the two groups

TGC,tigecycline;AMK,amikacin;CEF/SUL,cefperazone/sulbactam;IMP,imipenem;CIP,ciprofloxacin;

SMZ,sulfamethoxazole;PIP/TAZ,piperacillin/tazolactam.

Table 3　The regimens of combination therapy in the two groups

TGC,tigecycline;AMK,amikacin;CEF/SUL,cefperazone/sulbactam;IMP,imipenem;

CIP,ciprofloxacin;PIP/TAZ,piperacillin/tazolactam.

2.2OutcomesClinical outcomes,14-day mortality,in-hospital mortality(including overall mortality and attributable mortality),laboratory result of infection on day 7th,duration of antibiotics use,length of ICU stay and length of hospital stay in the two groups did not show any statistically significant differences(P>0.05).View on microbiological outcomes,compared with non-tigecycline group,microbiological eradication rate is higher in tigecycline group(29/76.9% vs 12/44.4%,P=0.00),whereas in non-tigecycline group there is a large amount of microbiological replacement or superinfection(10/37.0% vs 4/10.5%,P=0.01).The major replacement or superinfection pathogen in tigecycline group was Pseudomonas aeruginosa,and there was no significant between the two groups(4/10.5% vs 1/3.7%,P=0.58).In non-tigecycline group,the main pathogen of replacement or superinfecion was methicillin-resistant Staphylococcus aureus(MRSA),and was statistical difference(8/27.6% vs 0/0.0%,P=0.00).A COPD patient in non-tigecycline group was found concurrent infection with Aspergillus(table 4).

Table 4Outcomes of patients with VAP involving MDRAB treated with tigecycline based combination therapy or other-based combination therapy.

GroupClinicaloutcomesSuccess　　FailureMicrobiologicaloutcomesEradication　Non?Eradicationreplacement/SuperinfecionLengthofICUstayLengthofhospitalstayDurationofantibioticsuseTigecycline23(60．5%)15(39．5%)29(76．3%)5(13．2%)4(10．5%)18．72±9．4728．41±12．5212．35±4．28Non?Tigecycline17(62．9%)10(37．1%)12(44．4%)5(22．2%)10(37．0%)17．07±10．5129．70±13．7413．74±5．17P?value0．840．000．800．010．490．690．24GroupLaboratorydataon7thdayWBC　　　PCT14?daymortalityOverall　AttributedtoMDRABIn?hospitalmortalityOverall　AttributedtoMDRABReplacement/SuperinfecionPseudomonasaeruginosa　　MRSA　　AspergillusTigecycline8．54±1．280．69±0．414(10．5%)2(5．2%)17(44．7%)12(31．5%)4(10．5%)0(0．0%)0(0．0%)Non?Tigecycline9．07±1．750．78±0．324(14．8%)1(3．7%)11(40．7%)8(29．6%)1(3．7%)8(27．6%)1(3．7%)P?value0．160．340．890．760．740．860．580．000．41

MDRAB:multidrug-resistant Acinetobacter baumannii;MRSA:methicillin-resistant Staphylococcus aureus;WBC:white blood cell;PCT:procalcitonin

3　DISSCUSSION

Ventilator associated pneumonia as a common nosocomial infection,involving a broad spectrum pathogens,especially MDR organisms in late-onset VAP,in which multidrug-resistant Acinetobacter baumannii as a big challenge, made clinical treatment more and more difficult[11-12].The mainstream treatment strategy for MDRAB was colistin-based therapy[13].However,due to the prevalence of colistin-resistant strains and carbopenem-resistant strains,there is few alternative agents for clinician to choose[14].Tigecycline as a broad spectrum antibiotic with potent activity in vitro,including colistin-resistant strains,and be a new choice for VAP caused by MDRAB[15].Nevertheless,the efficacy of tigecycline in VAP due to MDRAB is still controversial.Freire AT et al.[16]conducted a study focused on HAP,illustrate there was no statistical significance of mortality between tigecycline group and imipenem group(14.1% vs 12.2%),but subgroup analysis of VAP showed a relatively higher mortality in tigecycline group without any statistically different,in which the reason maybe relate to superinfection.Another study about MDRAB[17],mortality in tigecycline group and imipenem/cilastatin group did not show any statistically significant,but in tigecycline group the unfavarable event was even lower(P<0.05).The results in our study are consistent with previous research,the main clinical outcomes(14 days mortality and in hospital mortality) is relatively equal in two groups,but better microbiological outcomes in tigecycline group.By further analysis,we find the main pathogen of replacement or superinfecion was Pseudomonas aeruginosa.Although there was no statistical difference,we also shoud take the property of tigecycline that was intrinsically resisted to Pseudomonas aeruginosa into consideration[18，8],and the non-statistical difference can be explained by the usage of anti-Pseudomonas combination agents in tigecycline gourp(Cefperazone/Sulbactam 17cases，Imipenem/Cilastatin 9 cases，Piperacillin/Tazobactam12 cases).Analyzed characteristics of replacement or superinfection organisms in non-tigecycline group,we find the major pathogen was MRSA with statistically significant(P=0.00).This interesting phenomenon,also found in other study16,can be a clinical clue to prove that tigecycline also has potent activity to MRSA.The correlation was poor between clinical and microbiological outcomes in our study(Figure 1,P=0.15),also demonstrated in other studies[19-20],can be explained as the false negative culture results affected by antibiotics usage during treatment course.

Chuang YC et al.[21]reported that treated with tigecycline resulted in higher mortality when compared with patients who were received colistin(61% vs. 44%),and in this study,inferior efficacy of tigecycline might be due to A.baumannii isolates with higher tigecycline MIC(56% paitents in tigecycline group with MIC>2 mg·L-1).Depended on this hypothesis,some experts suggested using high dose of tigecycline to improve outcomes of MDR pathogens.Burkhadt O et al.[22]viewed form pharmacokinetic-pharmaco dynamic(PK-PD) aspect,illustrated that tigecycline in infected patients are expected to be a higher lung concentration,but standard doses are probably inadequate to reach maximally efficacy, especially against MDR pathogens on the upper end of the MIC distribution(1 to 2 mg·mL-1). And a study[23]also suggested that although tigecycline is concentrated in tissues,including lung parenchyma,the concentration in epithelial lining fluid is relatively low,especially compared to MICs of tigecycline to Acinetobacter baumannii.A retrospective study[24]evaluated high dose versus standard dose of tigecycline in critically ill patients with severe infection,in VAP subgroup,the only independent predictor of clinical cure was the use of high tigecycline dose (OR 6.25;95% CI 1.59 to 24.57;P=0.009).This conclusion also be confirmed in a Phase2 clinical trial[25].Therefore,the strategy of high dose tigecycline for MDR pathogens maybe a new study direction we need focus on in the future.

This study has several limitations.First of all,the suspected pathogen was determined by attending physicians according to qualitative cultures instead of quantitative cultures,and which made the identification of colonization or infection of A.baumanni much more subjective other than objective,but this was because of the nature of retrospective study and can not be avoided in this study.However,if we used the quantitive cultures as the idetification of infectious pathogen based on the threshold growth of 105CFU·mL-1,the sensitivity and specificity of the diagnosis were 76% and 75%,respectively[26].It also could generate bias in this way.Second,we did not analyse univariate and multivariate risk factors for clinical failure and 14-day mortality,especially those patients who were accepted corticosteriod therapy.A study[27]has illustrated that steriod use was associated with increased clinical failure rates.Third,tigecycline as a salvage treatment for VAP due to MDRAB,during the study,we should evaluate the adverse reactions of this new regimen,but also because the study was retrospective,we can not extract adequate and accurate data from the medical records for the analysis of adverse reactions.However,we also did not find any life threaten adverse event happened according to the medical records.

In conclusion,tigecycline-based combination therapy for VAP due to MDRAB is comparable to other-based combination therapy in clinical outcomes and with a favorable microbiological outcomes.Due to potent activity of combination agents against MDRAB,we can not define the exact role of tigecycline in combination therapy strategy,and with the natural limitation of retrospective study method and small sample of this study,the randomized,multi-center,large sample,pharmacokinetic-pharmacodynamic based studies are warranted.

Conflictofinterest:None.

[1]Richet H,Pe. F.Nosocomial infections caused by Acinetobacter baumannii:a major threat worldwide[J].Infect Control Hosp Epidemiol,2006,27(7):645-646.

[2]Lin M F,Lan C Y.Antimicrobial resistance in Acinetobacter baumannii:From bench to bedside[J].World Journal of Clinical Cases,2014,2(12):1297-1305.

[3]Maragakis L L,Perl T M.Acinetobacter baumannii: Epidemiology,Antimicrobial Resistance,and Treatment Options[J].Clinical Infectious Diseases,2008,46(8):1254-1263.

[4]Peleg A Y,Seifert H,Dl. P.Acinetobacter baumannii: emergence of a successful pathogen[J].Clinical Microbiology Reviews,2008,21(3):538-582.

[5]Gootz T D,Marra A.Acinetobacter baumannii:an emerging multidrug-resistant threat[J].Expert Review of Anticancer Therapy,2008,6(3):309-325.

[6]Viehman J A,Nguyen M H,Doi Y.Treatment Options for Carbapenem-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections[J].Drugs,2014,74(12):1315-1333.

[7]Neonakis I K.Confronting multidrug-resistant Acinetobacter baumannii:a review[J].International Journal of Antimicrobial Agents,2011,37(2):102-109.

[8]Zhanel G G,Karlowsky J A,Rubinstein E,et al.Tigecycline:a novel glycylcycline antibiotic[J].Expert Review of Anti-infective Therapy,2014,4(1):9-25.

[9]Gordon N C,Dw. W.Multidrug-resistant Acinetobacter baumannii: mechanisms of virulence and resistance[J].Int J Antimicrob Agents,2010,35(3):219-226.

[10]Centers for disease control,National Healthcare safety Network.Device-associated Module:Ventilator-associated event protocol.January 2013[DB/OL].available on the National Healthcare Safety Network website(www.cdc.gov/nhsn).

[11]American Thoracic Society.Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia[J].American Journal of Respiratory & Critical Care Medicine,2005,171(4):388-416.

[12]Garnacho-Montero J.Acinetobacter baumannii ventilator-associated pneumonia:epidemiological and clinical findings[J].Intensive Care Medicine,2005,31(5):649-655.

[13]Garnacho-Montero J,Corcia-Palomo Y,Amaya-Villar R,et al.How to treat VAP due to MDR pathogens in ICU patients[J].Bmc Infectious Diseases,2014,14(1):1-7.

[14]Perez F.Global challenge of multidrug-resistant Acinetobacter baumannii[J].Antimicrobial Agents & Chemotherapy,2007,51(10):3471-3484.

[15]Arroyo L A,Mateos I,González V,et al.In vitro activities of tigecycline, minocycline, and colistin-tigecycline combination against multi- and pandrug-resistant clinical isolates of Acinetobacter baumannii group[J].Antimicrobial Agents & Chemotherapy,2009,53(3):1295-1296.

[16]Freire A T,Melnyk V,Kim M J,et al.Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia[J].Diagnostic Microbiology & Infectious Disease,2010,68(2):140-151.

[17]Lee Y T,Tsao S M,Pr. H.Clinical outcomes of tigecycline alone or in combination with other antimicrobial agents for the treatment of patients with healthcare-associated multidrug-resistant Acinetobacter baumannii infections[J].European Journal of Clinical Microbiology,2013,32(9):1211-1220.

[18]Frampton J E,Mp. C.Tigecycline[J].Drugs,2005,65(18):2623-2635.

[19]Gordon N C,Dw. W.A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacter baumannii with tigecycline[J].Journal of Antimicrobial Chemotherapy,2009,63(4):775-780.

[20]Shin J A,Chang Y S,Kim H J,et al.Clinical outcomes of tigecycline in the treatment of multidrug-resistant Acinetobacter baumannii infection[J].Yonsei Medical Journal,2012,53(5):974-984.

[21]Chuang Y C.Effectiveness of tigecycline-based versus colistin-based therapy for treatment of pneumonia caused by multidrug-resistant Acinetobacter baumannii in a critical setting:a matched cohort analysis[J].Bmc Infectious Diseases,2014,14(8):31-32.

[22]Burkhardt O,Rauch K,Kaever V,et al.Tigecycline possibly underdosed for the treatment of pneumonia: a pharmacokinetic viewpoint[J].International Journal of Antimicrobial Agents,2009,34(1):101-102.

[23]Jr C J.Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline[J].International Journal of Antimicrobial Agents,2005,25(6):523-529.

[24]De P G,Montini L,Pennisi M,et al.High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria[J].Critical Care,2014,18(3):206-214.

[25]Ramirez J,Dartois N,Gandjini H,et al.Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia[J].Antimicrob Agents Chemother,2013,57(4):1756-1762.

[26]Cook D,Mandell L.Endotracheal aspiration in the diagnosis of ventilator-associated pneumonia[J].Chest,2000,117(4 Suppl 2):195S-197S.

[27]Kim W Y,Moon J Y,Huh J W,et al.Comparable Efficacy of Tigecycline versus Colistin Therapy for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Pneumonia in Critically Ill Patients[J].PLoS ONE,2016,11(3):e0150642.

基于替加環(huán)素的聯(lián)合用藥方案對多重耐藥鮑曼不動桿菌所致呼吸機相關(guān)性肺炎的療效分析

查磊1,3，徐前程1，楊剛2，陳尚華1，沈雯雯1，梁希泉1

(皖南醫(yī)學(xué)院附屬蕪湖市第二人民醫(yī)院 1.重癥醫(yī)學(xué)科；2.呼吸內(nèi)科，安徽蕪湖241000；3.利物浦大學(xué)生物學(xué)院,英國L693BX)

目的：研究基于替加環(huán)素的聯(lián)合用藥方案對多重耐藥鮑曼不動桿菌所致呼吸機相關(guān)性肺炎的治療效果。方法：采用回顧性分析，對納入研究的65例多重耐藥鮑曼不動桿菌(MDRAB)所致呼吸機相關(guān)性肺炎(VAP)患者，根據(jù)是否使用替加環(huán)素分為替加環(huán)素組(38例)和非替加環(huán)素組(27例)。分析兩組臨床效果、微生物效果、治療第7天感染指標[血漿降鈣素原(PCT)濃度、白細胞(WBC)計數(shù)]、抗生素使用時間、ICU住院時間、醫(yī)院住院時間以及14天病死率及院內(nèi)病死率。結(jié)果：兩組患者臨床治療效果、14天病死率、院內(nèi)病死率(包括總病死率及歸因于MRAB病死率)，第7天感染指標、抗生素使用時間、ICU住院時間、醫(yī)院住院時間等方面差異均無統(tǒng)計學(xué)意義(均P>0.05)。但在微生物治療效果方面替加環(huán)素組清除率較非替加環(huán)素高(29/76.3%比12/44.4%，P=0.00)，非替加環(huán)素組病原菌替換或多重感染率高(10/37.0%比4/10.5%，P=0.01)。結(jié)論：基于替加環(huán)素的聯(lián)合用藥方案對于MDRAB所致VAP療效與其他聯(lián)合用藥方案無明顯差異，但可顯著提高細菌清除率。

替加環(huán)素；呼吸機相關(guān)性肺炎；多重耐藥鮑曼不動桿菌

2016-04-14)(責(zé)任編輯：敖慧斌)

Chen Shanghua,female, Associated professor.E-mail:chenshanghua7021@163.com

R563.1Document code：AArticle ID：1001-5779(2016)04-0567-07

10.3969/j.issn.1001-5779.2016.04.020

*Acknowledgements:This study was supported by the scholar research fund from The Second people's Hospital of WuHu Affiliated to Wannan Medical College (2015-06-10-36) to focus on Acinetobacter baumannii infection researches