Risk Factors And Treatment Of Hospital Infection Caused By Extensively Drug Resistant A. Baumannii

BackgroundAcinetobacter belongs to Pseudomonas Head Of Mora bacteria Branch. There are six kinds of Acinetobacter,namely A.calcoaceticus, A. haemolytius, A. baumanii, A. lwoffi, A.johnsonii and A. junii.The most common one is A. baumanii,which is so highly prevalent in hospital and could survive for a long time in a dry environment that it could cause infection in critically ill patients easily.The reports of CHINET,involving 16 teaching hospitals in main areas of China(including 14 general hospitals and 2 children’s hospitals),showed that non fermentative gram negative bacilli accounts for 26.7% of strains isolated,among which the most common in order were acinetobacter, pseudomonas aeruginosa and stenotrophomonas maltophilia.Among 10120 acinetobacter, A. baumanii accounted for 89.2%. A. baumanii infection is closely related to exposure to antibacterial drugs, invasive operation, longer hospital stay, accepting mechanical ventilation and severe underlying disease.A.baumanii has strong ability of acquiring drug resistance and cloning.The isolation rate of MDRAB,XDRAB and PDRAB increased year by year.And A.baumanii has become one of the most important pathogens of nosocomial infections in China. The reports of CHINET showed that the prevalence of XDRAB in 2013 is 14.6%,which was still severe even though it was lower than 2012(17.6%).Drug resistance of XDRAB varies in different areas and hospitals.An article had recently published by Bai Lihong,concluding that the drug resistance rate to 13 commonly used antibiotics of A. baumanii strains increaseed year by year.The drug resistence rate of A. baumanii to cefperazone-sulbactam, imipenem and meropenem were respectively 4.01%,8.02% and 1.15% in 2007.And they respectively climbed to 76.85%,75.69%,19.54% in 2011.The detection rate of MDRAB and XDRAB increased year after year. The detection rate of MDRAB was 3.72% in 2007,and by 2011 had climbed to 72.94%. And the detection rate of XDRAB was 0.29% in 2007,and by 2011 had climbed to 71.2%. Through analyzing resistance of A. baumanii isolated clinically from Shanghai ruijin hospital from 2008 to 2012,Xu Guiting found that A. baumanii there had strong resistance.In five years, A. baumanii kept high resistance to many antibiotics except cefperazone-sulbactam.All of the drug resistance rate were greater than 55% of A. baumanii to antibiotics like cephalosporins,penicillins and quinolones.Another research about changes of drug resistance of Acinetobacter baumannii from 2006 to 2010 done by the Second Xiangya Hospital of Central South University, stated that the isolation proportion and resistance of Acinetobacter baumannii strains were raising each year,especially to carbapenem (meropenem and imipenem). A. baumanii kept high resistance to many antibiotics except cefperazone-sulbactam and minocycline.How to treat the XDRAB infection is still a global problem.And there are some researches done by scholars at home and abroad.A study indicated that sulbactam or sulbactam-based β-Lactam combined with doxycycline, tigecycline combined with meropenem or sulbactam or tigecycline monotherapy and meropenem combined with doxycycline or sulbactam or sulbactam-based β-Lactam appeared good antibacterial activity in vitro.For the treatment of XDRAB,certain study showed that combination treatment was better than medication alone. A retrospective review was conducted by Moon in 108 patients with Acinetobacter baumannii infection,among which there were 83 patients with XDRAB infection. The review presented that tigecycline was a good choice for treatment of hospital infection caused by XDRAB.Zhao Junxi divided 73 patients of pneumonia caused by XDRAB into two groups.And the research group received combination treatment(imipenem combined with cefperazone-sulbactam),while the control group were treated with cefperazone-sulbactam monotherepy.The result showed that the cure rate of research group was higher than the control group,and mortality lower.As a broad-spectrum antibiotic, carbapenem was effective against XDRAB,but abuse of carbapenem could raise incidence of XDRAB infections. Polymyxin antibiotics remained highly sensitive to almost all of the G-strains.In recent years, many reports showed that polymyxin B was effective against infection caused by MDR-AB or PDR-AB.As 2012 Chinese A. baumanii Infection Diagnosis and Prevention Expert Consensus proposed, the commonly used combination regimens were sulbactam or sulbactam-based β-Lactam, or polymyxin E, or tigecycline based two drugs combinations. When necessary,three drugs combination regimens could be used.The domestic study of treatment of XDRAB have the following characteristics: 1 They are designed mainly to study the treatment of lower respiratory tract infection,but scarce of other sites (such as blood, puncture fluid, secretion and so on).2 Most studies only compare the efficacy of two or three therapeutic regimens. Thus, therapeutic regimens studied are relatively single and can not provide better treatment options for doctors.3 Studies focus on statistical department rather than various departments of the whole hospital.And the quantity of cases studied is less so that they have poor representation.Considering the above characteristics,in this retrospective study,658 cases of nosocomial infections caused by A. baumanii(contains 235 cases of XDRAB infections and 423 cases of non-XDRAB infections) are statistical analysed from different departments of Nanfang Hospital from January 2012 to December 2014,including all the sites of infection (Sputum, throatswabs, hydrothorax, ascites, secretions, blood, cerebrospinal fluid, urine,instruments, puncture fluid)(note:658 patients are divided into three conditions.In the first case, XDRAB were detected once or several times.In the second case,Ab were detected several times,including XDRAB and non-XDRAB.In the third case,non-XDRAB were detected once or several times.XDRAB group included the first and the second cases,and the first detected XDRAB were used to analyse bacterial susceptibility and risk factors.Non-XDRAB group included the third cases,and the first detected non-XDRAB were used to analyse bacterial susceptibility and risk factors).Through analysing drug resistance rate and clinical distribution of 658 Ab strains,this study intends to find out risk factors of XDRAB infection and compare clinical efficacy of various therapeutic regimens in order to provide some references for clinical rational use of antibiotics.The therapeutic regimens were divided into five groups for comparison.Group 1 included tigecycline based group and non-tigecycline group.And group 2 included sulbactam-based β-Lactam based group and non-sulbactam group. Group 3 included tigecycline combined with sulbactam-based P-Lactam group and tigecycline combined with carbapenem group. Group 4 included sulbactam-based β-Lactam combined with tigecycline group,sulbactam-based β-Lactam combined with carbapenem group and sulbactam-based P-Lactam combined with doxycycline group. Group 5 included group of using carbapenem before infection and without the use of carbapenem before infection in tigecycline combined with carbapenem group.MethodsIn this retrospective study,658 cases of nosocomial infections caused by A. baumanii were statistical analysed from different departments of Nanfang Hospital from January 2012 to December 2014.Hospital infection diagnoses were carried out by "Hospital Infection Diagnosis standard"published by public health department. Case control method was used to compare XDRAB infection cases(235 cases) and non-XDRAB infection cases(423 cases) for statistical analysis of XDRAB infection related risk factors.235 cases of nosocomial infections caused by XDRAB were enrolled in this retrospective study to compare clinical efficacy rate and bacterial clearance rate and case fatality rate of various therapeutic regimens above.The research data were analyzed by SPSS 13.0 software, using P<0.05 as the difference was statistically significant.Results1. In three years,658 strains of A. baumanii were enrolled in this study, including 235 XDRAB strains which accounted for 35.71%.The resistance rate of A. baumanii to tigecycline was 0 in 2013. Combination susceptibility test in vitro showed that when tigecycline combined with meropenem, sulbactam or cefoperazone-sulbactam,their combined action was additive effects. When tigecycline combined with meropenem or sulbactam,both of their corresponding concentration-cumulative antibacterial percentage curves presented a left shift.2. The result analyzed by single logistic regression showed that hospital stay greater than or equal to 30 days,diabetes, hypoproteinemia, cerebral vascular accident or cerebral trauma, indwelling catheterization, deep vein catheterization, incision of trachea, tracheal intubation,Surgical operation, the use of carbapenem before infection or the species of antibiotic used greater than or equal to 3 were risk factors related to nosocomial infections caused by XDRAB.3.Compared to tigecycline combined with carbapenem group(18.75%), sulbactam-based β-Lactam combined with carbapenem group(16.67%) and sulbactam-based β-Lactam combined with doxycycline group(51.16%), tigecycline combined with sulbactam-based β-Lactam group had statistically higher rate of bacterial eradication rate(72.09%).In tigecycline combined with carbapenem group, group without the use of carbapenem before infection had statistically higher rate of bacterial eradication rate(75%) than the group using carbapenem before infection(8.33%)(P<0.05).Conclusion1. Combination susceptibility test in vitro showed that tigecyline kept high sensitivity against Ab.And when tigecycline combined with meropenem, sulbactam or cefoperazone-sulbactam,their combined action was additive effects.According to the mean rank,tigecyline combined with meropenem had the best activity against XDRAB among the combinations,followed by tigecyline combined with sulbactam,then was cefoperazone-sulbactam combined with tigecycline.2.Hospital stay greater than or equal to 30d,diabetes, hypoproteinemia, cerebral vascular accident or cerebral trauma, indwelling catheterization, deep vein catheterization, incision of trachea, tracheal intubation, Surgical operation, the use of carbapenem before infection or the species of antibiotic used greater than or equal to 3 were risk factors related to nosocomial infections caused by XDRAB.3 Compared to tigecycline combined with carbapenem group, sulbactam-based β-Lactam combined with carbapenem group and sulbactam-based β-Lactam combined with doxycycline group, tigecycline combined with sulbactam-based (3-Lactam group had statistically higher bacterial eradication rate.In tigecycline combined with carbapenem group, group without the use of carbapenem before infection had statistically higher rate of bacterial eradication rate than the group using carbapenem before infection.