本文選題：舒巴坦　切入點：替加環(huán)素　出處：《泰山醫(yī)學(xué)院》2013年碩士論文

【摘要】：目的 隨著醫(yī)療技術(shù)的發(fā)展，大量廣譜藥物、糖皮質(zhì)激素、免疫抑制劑的使用，鮑曼不動桿菌已成為院內(nèi)獲得性感染的重要病原菌，尤其是多重耐藥、廣泛耐藥和全耐藥鮑曼不動桿菌，由于其快速獲得和傳播耐藥性的能力，近年已呈世界性流行，成為臨床治療的棘手問題。2011年中國CHINET細菌耐藥性監(jiān)測網(wǎng)數(shù)據(jù)也表明鮑曼不動桿菌感染形勢非常嚴峻，不動桿菌在呼吸道的檢出率僅次于大腸埃希菌與肺炎克雷伯菌，鮑曼不動桿菌是引起肺部感染出現(xiàn)率增高較快的細菌，已成為肺部院內(nèi)感染的主要病原體，它同樣也可引發(fā)泌尿系感染、繼發(fā)性腦膜炎、敗血癥等。鮑曼不動桿菌對重癥監(jiān)護病房（ICU）患者威脅很大，易在ICU引起爆發(fā)流行。最近有關(guān)英國和美國在伊拉克和阿富汗的軍事和非軍事人員感染耐藥鮑曼不動桿菌的報道進一步說明鮑曼不動桿菌感染的嚴重性。由于臨床感染多為耐藥菌株，臨床治療非常困難，甚至是無藥可用。目前，對于泛耐藥菌株，臨床常選擇替加環(huán)素聯(lián)合舒巴坦治療，取得了一定的療效，但對于兩者是否具有協(xié)同性尚不清楚，本研究通過觀察兩者單藥及聯(lián)合的MIC，以其能為臨床用藥提供科學(xué)依據(jù)。材料和方法 菌株：實驗用鮑曼不動桿菌均取自2011年4月至2012年9月濟南軍區(qū)總醫(yī)院從臨床標(biāo)本中分離并鑒定的廣泛耐藥耐鮑曼不動桿菌32株（痰標(biāo)本24株，分泌物4株，引流液2株，腦脊液2株）。 標(biāo)準(zhǔn)質(zhì)控菌株：大腸埃希菌ATCC25922，大腸埃希菌ATCC35218(為監(jiān)控β內(nèi)酰胺/β-內(nèi)酰胺酶抑制劑紙片用)由濟南軍區(qū)總醫(yī)院細菌室提供。 抗菌藥物：(1)氨芐西林/舒巴坦、環(huán)丙沙星、左氧氟沙星、美洛培南、亞胺培南、慶大霉素、妥布霉素、丁胺卡那、哌拉西林、哌拉西林/他唑巴坦、頭孢吡肟、頭孢曲松、頭孢噻肟、多西環(huán)素、米諾環(huán)素、復(fù)方新諾明、頭孢哌酮/舒巴坦的藥敏紙片均購自O(shè)xoid賽默飛世爾生物化學(xué)制品北京有限公司。（2）進口注射用替加環(huán)素，50mg/支輝瑞制藥有限公司提供。（3）注射用舒巴坦，0.5g/支齊魯制藥有限公司提供。 方法：選取濟南軍區(qū)總醫(yī)院臨床感染標(biāo)本，常規(guī)培養(yǎng)，分離細菌，經(jīng)VITEK全自動分析儀來鑒定鮑曼不動桿菌，采用紙片擴散法用多種抗生素進行藥敏實驗，選取廣泛耐藥鮑曼不動桿菌32株。首先無菌操作將100ul微量肉湯分別加入滅菌的96孔聚苯乙烯板中，然后將替加環(huán)素與舒巴坦兩種藥物分別在96孔板中連續(xù)倍比稀釋，最后將濃度為3×105CFU/ml的菌懸液100ul加入孔中，孔中菌最終濃度為1.5×105CFU/ml，過夜培養(yǎng)后分別測定替加環(huán)素與舒巴坦最小抑菌濃度，再根據(jù)兩種藥物所測得最小抑菌濃度，采用棋盤格微量肉湯稀釋法測定（橫向為舒巴坦的降梯度方向，則縱向為替加環(huán)素的降梯度方向）兩藥各自的最小抑菌濃度，再根據(jù)替加環(huán)素與舒巴坦聯(lián)合用藥前后的最小抑菌濃度（MIC）計算部分抑菌濃度（FIC）。最后選取兩藥表現(xiàn)出協(xié)同作用的菌株應(yīng)用時間殺菌曲線法進一步評價兩藥的相互作用關(guān)系的信息。 結(jié)果 通過WHONET5.4軟件中選取經(jīng)VITEK-2分析儀鑒定32株鮑曼不動桿菌，，再次通過紙片擴散法進行藥敏試驗，所選取32株不動桿菌均為廣泛耐藥的鮑曼不動桿菌。17種抗菌藥物對32株泛耐藥鮑曼不動桿菌的檢測結(jié)果顯示:氨芐西林/舒巴坦、環(huán)丙沙星、左氧氟沙星、美洛培南、亞胺培南、慶大霉素、妥布霉素、丁胺卡那、哌拉西林、哌拉西林/他唑巴坦、頭孢吡肟、頭孢曲松、頭孢噻肟、多西環(huán)素、米諾環(huán)素、復(fù)方新諾明、頭孢哌酮/舒巴坦耐藥率均為100%。 舒巴坦對32株XDRAB的MIC范圍為32~128ug/ml，MIC90為128ug/ml，替加環(huán)素對32株XDRAB的MIC范圍為0.5~1ug/ml，MIC90為1ug/ml。舒巴坦和替加環(huán)素聯(lián)用，協(xié)同作用28.2%（9/32）、相加作用62.5%（20/32）、無相關(guān)作用9.3%（3/32），無拮抗作用。對于棋盤格微量肉湯法所測9株表現(xiàn)為協(xié)同的XDR鮑曼不動桿菌，選取舒巴坦、替加環(huán)素兩藥濃度均為0.5×MIC應(yīng)用時間殺菌曲線法，所選9株XDR鮑曼不動桿菌均表現(xiàn)為協(xié)同作用，未見兩藥聯(lián)合出現(xiàn)拮抗作用。 結(jié)論 舒巴坦與替加環(huán)素聯(lián)合對XDR鮑曼不動桿菌多表現(xiàn)出協(xié)同或相加作用，臨床上治療由XDRAB引起的重癥感染，可根據(jù)藥敏試驗采用舒巴坦與替加環(huán)素聯(lián)合應(yīng)用。
[Abstract]:objective
With the development of medical technology, broad-spectrum drugs, corticosteroids, immunosuppressive drugs, Bauman Acinetobacter has become an important pathogen of nosocomial infection, especially multidrug-resistant, extensively drug-resistant and drug resistance of Acinetobacter Bauman, due to its ability to quickly obtain and spread of drug resistance, in recent years has been in the world pop,.2011 become the thorny issue of clinical treatment of China CHINET bacterial resistance monitoring network data also show that Bauman Acinetobacter infection situation is very serious, Acinetobacter in respiratory rate after Escherichia coli and Klebsiella pneumoniae, Bauman Acinetobacter is caused by lung infection occurrence rate of bacteria has increased faster, become the main pathogens of nosocomial infection in the lungs, it also can cause urinary tract infection, secondary meningitis, septicemia. Bauman Acinetobacter in ICU (ICU) patients The threat of a large, easy to cause the outbreak of ICU. Recently the United Kingdom and the United States in Iraq and Afghanistan military and non military personnel infected with drug-resistant Acinetobacter Bauman reported that Bauman did not move further serious infection. The infection for clinical drug resistant strains, the clinical treatment is very difficult, or even no drugs available. At present, the pan resistant strains, the clinical choice of tigecycline combined with sulbactam treatment has certain curative effect, but both are cooperative is not clear, this study observed both alone and in combination with MIC, which can provide scientific basis for clinical medication. Materials and methods
Strain: the Acinetobacter baumannii from Bauman's laboratory was isolated from the clinical specimens and identified 32 strains of extensively drug-resistant Acinetobacter baumannii from April 2011 to September 2012. There were 24 sputum specimens, 4 secretions, 2 draining fluid and 2 cerebrospinal fluid in the General Hospital of Jinan Military Area, from April 2011 to September 2012.
Standard quality control strain: Escherichia coli ATCC25922, Escherichia coli ATCC35218 (for monitoring beta lactam / beta lactamase inhibitor disk), provided by General Hospital of Jinan Military Area bacteriology room.
Antibiotics: (1) ampicillin / sulbactam, levofloxacin, ciprofloxacin, meropenem, imipenem, gentamicin, tobramycin, amikacin, piperacillin, piperacillin / tazobactam, cefepime, cefotaxime, ceftriaxone, doxycycline, minocycline, compound sulfamethoxazole Ming, Cefoperazone / sulbactam, the drug sensitive slips were purchased from Oxoid thermofisher biochemical products Co. Ltd. of Beijing. (2) imported Tigecycline for Injection, 50mg/ branch of Pfizer Inc to provide. (3) with sulbactam injection, 0.5g/ Qi Lu Pharmaceutical Company Limited.
Methods: specimens of clinical infection, General Hospital of Jinan Military Area, conventional culture, bacterial isolates by VITEK automatic analyzer to identify Bauman Acinetobacter, the drug sensitive experiment was performed with multiple antibiotics disk diffusion method, wide selection of resistant Bauman Acinetobacter 32 strains. First, 96 hole polystyrene board 100ul broth were added to sterilized bacteria then, tigecycline and sulbactam were two drugs in 96 well plate continuous dilution, the concentration of 3 * 105CFU/ml bacterial suspension 100ul into the hole, the hole in the final concentration of bacteria is 1.5 * 105CFU/ml, after overnight incubation of tigecycline and sulbactam minimum inhibition the concentration were determined according to two kinds of drugs measured by minimal inhibitory concentration was determined by the checkerboard microdilution method (transverse gradient direction, sulbactam is longitudinal for tigecycline gradient direction) two drugs The minimum inhibitory concentration respectively, then according to add ring with minimal inhibitory concentration before and after sulbactam combination (MIC) to calculate the fractional inhibitory concentration (FIC). Finally two drugs showed bactericidal curve with strain time method of synergy further evaluation of two drug interactions between information.
Result
Through the WHONET5.4 software in the VITEK-2 analyzer and identification of 32 strains of Bauman Acinetobacter, again drug sensitive test was performed by disk diffusion method, selected 32 strains of Acinetobacter were extensively drug resistant Acinetobacter Bauman.17 antimicrobial agents against 32 strains of Pan resistant Acinetobacter Bauman test results showed: ampicillin / sulbactam sulbactam, levofloxacin, ciprofloxacin, meropenem, imipenem, gentamicin, tobramycin, amikacin, piperacillin, piperacillin / tazobactam, cefepime, cefotaxime, ceftriaxone, doxycycline, minocycline, cotrimoxazole, Cefoperazone / sulbactam are 100%.
Shubatan of 32 strains of XDRAB MIC range of 32~128ug/ml, MIC90 128ug/ml, MIC range of tigecycline against 32 strains of XDRAB 0.5~1ug/ml, MIC90 1ug/ml. Shubatan and tigecycline combined, synergistic effects of 28.2% (9/32), additive effect (20/32), 62.5% no 9.3% (3 /32). No antagonism. The checkerboard microdilution broth method in 9 strains showed a synergistic XDR Bauman Acinetobacter, selected Shubatan, tigecycline two concentration was 0.5 * MIC application time killing curve method, selected 9 strains of Bauman Acinetobacter XDR showed synergistic effect, no two the drug combination of antagonism.
conclusion
Shubatan combined with tegacycline showed more synergistic or synergistic effects on Acinetobacter XDR XDRAB. In clinic, the severe infection caused by XDRAB can be treated in clinic, and the combination of Shubatan and tegacycline should be applied according to the susceptibility test.

【學(xué)位授予單位】：泰山醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R563.1

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