细菌性肝脓肿菌群分布与耐药性分析的多中心回顾性研究(附897例报告)

Bacterial flora distribution and antimicrobial resistance of pyogenic liver abscess: a multicenter retrospective study (A report of 897 cases)

  • 摘要: 目的:探讨国内多中心细菌性肝脓肿患者菌群分布及其耐药性情况。
    方法:采用回顾性描述性研究方法。收集2007年10月至2018年4月国内3家医疗中心收治的897例(哈尔滨医科大学附属第一医院656例、华中科技大学同济医学院附属同济医院109例、海军军医大学东方肝胆外科医院132例)细菌性肝脓肿患者的临床资料;男582例,女315例;年龄为(59±11)岁,年龄范围为6~86岁。观察指标:(1)菌群分布情况。(2)细菌耐药性情况。正态分布的计量资料以Mean±SD表示,偏态分布的计量资料以M(范围)表示。计数资料以绝对数或百分比表示。
    结果:(1)菌群分布情况:897例患者中,脓液细菌培养为肺炎克雷伯杆菌为733例,大肠埃希菌75例,金黄色葡萄球菌11例,草绿色链球菌10例,肺炎克雷伯杆菌肺炎亚种9例,β-溶血链球菌7例,鲍曼不动杆菌6例,中间链球菌、屎肠球菌各5例,木糖氧化产碱菌木糖氧化亚种3例,奇异变形杆菌、咽峡链球菌、阴沟肠杆菌阴沟亚种各2例,差异柠檬酸杆菌、普通变形杆菌、侵肺巴斯德菌、弗劳地柠檬酸杆菌、河生肠杆菌、嗜麦芽窄食单胞菌、鲁氏不动杆菌、唾液链球菌、链球菌属细菌、鸟肠球菌、粪肠球菌、产酸克雷伯菌、表皮葡萄球菌各1例,脓液细菌培养为双重细菌12例,多重细菌2例。(2)细菌耐药性情况:①肺炎克雷伯杆菌和大肠埃希菌耐药性情况,脓液细菌培养为肺炎克雷伯杆菌对氨苄西林、哌拉西林、头孢唑啉、头孢呋辛、头孢噻肟、头孢曲松、头孢他啶、头孢替坦、头孢吡肟、头孢西丁、阿莫西林/克拉维酸、氨苄西林/舒巴坦、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、氨曲南、亚胺培南、美洛培南、厄他培南、庆大霉素、妥布霉素、阿米卡星、替加环素、环丙沙星、左氧氟沙星、复方新诺明耐药率分别为99.79%(474/475)、4.09%(7/171)、12.18%(82/673)、7.34%(49/668)、2.34%(4/171)、1.96%(11/562)、5.85%(10/171)、0(0/562)、0.55%(4/733)、1.42%(9/635)、0(0/733)、2.46%(18/733)、0.55%(4/733)、0.27%(2/733)、1.36%(10/733)、0.14%(1/733)、0(0/733)、0.36%(2/562)、0.95%(7/733)、0.41%(3/733)、0(0/733)、0(0/562)、1.64%(12/733)、0.95%(7/733)、4.50%(33/733)。脓液细菌培养为大肠埃希菌,对上述抗菌药物耐药率分别为78.67%(59/75)、40.91%(18/44)、65.33%(49/75)、56.00%(42/75)、38.64%(17/44)、41.94%(13/31)、20.00%(15/75)、3.23%(1/31)、25.33%(19/75)、5.77%(3/52)、18.67%(14/75)、32.00%(24/75)、8.00%(6/75)、16.00%(12/75)、37.33%(28/75)、1.33%(1/75)、0(0/75)、0(0/31)、40.00%(30/75)、14.67%(11/75)、1.33%(1/75)、0(0/31)、54.67%(41/75)、37.33%(28/75)、52.00%(39/75)。②其他革兰氏阴性菌耐药性情况:肺炎克雷伯杆菌肺炎亚种对氨苄西林、头孢唑啉、头孢呋辛、头孢曲松、头孢他啶、头孢替坦、头孢吡肟、阿莫西林/克拉维酸、氨苄西林/舒巴坦、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、氨曲南、亚胺培南、美洛培南、厄他培南、庆大霉素、妥布霉素、阿米卡星、环丙沙星、左氧氟沙星、复方新诺明耐药率分别为8/8、0/5、0/5、0/1、0/9、0/2、0/9、0/8、0/9、0/9、0/6、0/9、0/9、0/7、0/1、0/9、0/8、0/9、0/9、0/9、0/9。鲍曼不动杆菌对头孢曲松、头孢他啶、头孢吡肟、氨苄西林/舒巴坦、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、氨曲南、亚胺培南、美洛培南、庆大霉素、妥布霉素、阿米卡星、替加环素、环丙沙星、左氧氟沙星、复方新诺明耐药率分别为2/6、4/6、3/6、0/6、4/6、1/6、2/6、4/6、2/6、4/6、4/6、3/6、0/6、4/6、2/6、3/6。木糖氧化产碱菌木糖氧化亚种细菌对氨苄西林、头孢唑啉、头孢呋辛、头孢他啶、头孢吡肟、阿莫西林/克拉维酸、哌拉西林/他唑巴坦、氨曲南、亚胺培南、庆大霉素、妥布霉素、阿米卡星、环丙沙星、左氧氟沙星耐药率分别为3/3、3/3、3/3、1/3、1/3、1/3、0/3、3/3、2/3、3/3、3/3、3/3、3/3、1/3。③革兰氏阳性菌耐药性情况:金黄色葡萄球菌对青霉素、氨苄西林、哌拉西林、头孢唑啉、头孢呋辛、头孢噻肟、头孢他啶、头孢吡肟、头孢西丁、阿莫西林/克拉维酸、氨苄西林/舒巴坦、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、氨曲南、亚胺培南、美洛培南、庆大霉素、妥布霉素、阿米卡星、四环素、替加环素、环丙沙星、左氧氟沙星、莫西沙星、复方新诺明、利奈唑胺、红霉素、克林霉素、万古霉素、替考拉宁、利福平耐药率分别为2/6、6/8、4/5、4/5、4/5、4/5、4/5、4/5、4/5、4/5、4/5、4/5、4/5、3/5、2/5、2/5、3/8、3/5、3/5、0/8、0/8、3/8、3/11、0/5、1/8、0/8、0/8、2/6、3/3、1/3、0/3。草绿色链球菌对青霉素、氨苄西林、头孢曲松、头孢哌酮/舒巴坦、庆大霉素、四环素、环丙沙星、左氧氟沙星、莫西沙星、利奈唑胺、红霉素、克林霉素、万古霉素、替考拉宁、利福平耐药率分别为3/10、0/8、0/7、0/7、2/8、6/10、0/8、0/8、0/7、0/5、4/10、6/10、0/5、0/5、0/3。β-溶血链球菌对试验抗菌药物耐药率均为0。④复合细菌耐药性情况:双重细菌耐药性情况,肺炎克雷伯杆菌合并革兰氏阴性菌中肺炎克雷伯杆菌对头孢替坦、头孢西丁、氨苄西林/舒巴坦、美洛培南、厄他培南、妥布霉素、替加环素、复方新诺明耐药率均为0;鲍曼不动杆菌对厄他培南、左氧氟沙星、复方新诺明耐药率均为0;大肠埃希菌对头孢他啶、头孢西丁、阿莫西林/克拉维酸、哌拉西林/他唑巴坦、亚胺培南、美洛培南、厄他培南、妥布霉素、阿米卡星、替加环素耐药率均为0;弗劳地柠檬酸杆菌除对左氧氟沙星、复方新诺明耐药率为1/1外对其他试验抗菌药物耐药率均为0。大肠埃希菌合并革兰氏阳性菌中大肠埃希菌对头孢替坦、头孢吡肟、头孢西丁、头孢哌酮/舒巴坦、美洛培南、妥布霉素、阿米卡星耐药率均为0;粪肠球菌对青霉素、氨苄西林、左氧氟沙星、莫西沙星、利奈唑胺、万古霉素和替考拉宁耐药率均为0;铅黄肠球菌对氨苄西林、四环素、左氧氟沙星、莫西沙星、利奈唑胺和红霉素耐药率均为0;人葡萄球菌亚种对左氧氟沙星、莫西沙星、利奈唑胺、万古霉素、替考拉宁和利福平耐药率均为0;屎肠球菌对四环素、利奈唑胺、万古霉素和替考拉宁耐药率均为0。多重细菌肺炎克雷伯杆菌+大肠埃希菌+金黄色葡萄球菌金黄亚种+铜绿假单胞菌+光滑球拟酵母菌中肺炎克雷伯杆菌对头孢曲松、头孢他啶、头孢替坦、头孢吡肟、头孢西丁、氨苄西林/舒巴坦、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、氨曲南、亚胺培南、妥布霉素、阿米卡星、左氧氟沙星耐药率均为0。大肠埃希菌对头孢他啶、头孢替坦、头孢吡肟、氨苄西林/舒巴坦、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、氨曲南、亚胺培南、阿米卡星耐药率均为0。金黄色葡萄球菌金黄亚种对头孢曲松、头孢他啶、头孢替坦、头孢吡肟、氨苄西林/舒巴坦、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、氨曲南、亚胺培南、妥布霉素、阿米卡星、替加环素、莫西沙星、复方新诺明、替考拉宁、万古霉素、利奈唑胺、克林霉素耐药率均为0。铜绿假单胞菌对头孢他啶、头孢吡肟、哌拉西林/他唑巴坦、亚胺培南、庆大霉素、妥布霉素、阿米卡星、环丙沙星、左氧氟沙星耐药率均为0。光滑球拟酵母菌对5-氟胞嘧啶、氟康唑、伊曲康唑、伏立康唑耐药率均为0。肺炎克雷伯杆菌+大肠埃希菌+鲍曼不动杆菌1例中肺炎克雷伯杆菌对头孢替坦、头孢吡肟、哌拉西林/他唑巴坦、亚胺培南、厄他培南、妥布霉素、环丙沙星、左氧氟沙星耐药率为0。大肠埃希菌对阿莫西林/克拉维酸、哌拉西林/他唑巴坦、亚胺培南、美洛培南耐药率均为0。鲍曼不动杆菌对复方新诺明耐药率为0。
    结论:肺炎克雷伯杆菌是细菌性肝脓肿主要致病菌,其次是大肠埃希菌。肺炎克雷伯杆菌和大肠埃希菌对美洛培南、替加环素耐药率均为0,肺炎克雷伯杆菌肺炎亚种等其他革兰氏阴性菌对厄他培南耐药率为0,金黄色葡萄球菌等革兰氏阳性菌对利奈唑胺耐药率为0,患者应根据药物敏感性试验合理应用抗菌药物。

     

    Abstract: Objective:To investigate the bacterial flora distribution and antimicrobial resistance of patients with pyogenic liver abscess (PLA) in multi-centers of China.
    Methods:The retrospective and descriptive study was conducted. The clinical data of 897 patients with PLA at 3 medical centers in China from October 2007 to April 2018 were collected, including 656 cases in the First Hospital of Harbin Medical University, 109 cases in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology and 132 cases in the Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University. There were 582 males and 315 females, aged (59±11)years, with a range of 6-86 years. Observation indicators: (1) bacterial flora distribution; (2) bacterial resistance. Measurement data with normal distribution were represented as Mean±SD and measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages.
    Results:(1) Bacterial flora distribution: among 897 patients, 733 cases of Klebsiella pneumoniae, 75 cases of Escherichia coli, 11 cases of Staphylococcus aureus, 10 cases of Streptococcus viridians, 9 cases of Klebsiella pneumoniae subsp. pneumoniae, 7 cases of β-emolytic streptococcus, 6 cases of Acinetobacter baumannii, 5 cases of Streptococcus intermadius, 5 cases of Enterococcus faecium, 3 cases of Alcaligenes xylosoxidans subsp. xylosoxidans, 2 cases of Proteus mirabilis, 2 cases of Streptococcus isthmus, 2 cases of Enterobacter cloacae subsp. cloacae, 1 case of Citrobacter koseri, 1 case of Proteus vulgaris, 1 case of Pasteurella pneumotropica, 1 case of Curobacter freudii, 1 case of Enterobacter amnigenus, 1 case of Stenotrophomonas maltophilia, 1 case of Acinetobacter lwoffii, 1 case of Streptococcus salivarius, 1 case of Streptococcus bacterium, 1 case of Enterococcus avium, 1 case of Enterococcus faecalis, 1 case of Klebsiella oxytoca, and 1 case of Staphylococcus epidermidis were cultured in the pus respectively. There were 12 cases of double bacterial infection, and 2 cases of multiple bacterial infections. (2) Bacterial resistance. ① Resistance of Klebsiella pneumoniae and Escherichia coli: the drug resistance rates of Klebsiella pneumoniae to ampicillin, piperacillin, cefazolin, cefuroxime, cefotaxime, ceftriaxone, ceftazidime, cefotetan, cefepime, cefoxitin, amoxicillin/carat Retinoic acid, ampicillin/sulbactam, piperacillin/tazobactam, cefoperazone/sulbactam, aztreonam, imipenem, meropenem, ertapenem, gentamicin, tobramycin, amikacin, tigaricycline, ciprofloxacin, levofloxacin, and trimethoprim sulfamethoxazole were 99.79%(474/475), 4.09%(7/171), 12.18%(82/673), 7.34%(49/668), 2.34%(4/171), 1.96%(11/562), 5.85%%(10/171), 0(0/562), 0.55%(4/733), 1.42%(9/635), 0(0/733), 2.46%(18/733), 0.55%(4/733), 0.27%(2/733), 1.36%(10/733), 0.14%(1/733), 0(0/733), 0.36%(2/562), 0.95%(7/733), 0.41%(3/733), 0(0/733), 0(0/562), 1.64%(12/733), 0.95%(7/733), and 4.50%(33/733), respectively. The drug resistance rates of Escherichia coli to above antibiotics were 78.67%(59/75), 40.91%(18/44), 65.33%(49/75), 56.00%(42/75), 38.64%(17/44), 41.94%(13/31), 20.00%(15/75), 3.23%(1/31), 25.33%(19/75), 5.77%(3/52), 18.67%(14/75), 32.00%(24/75), 8.00%(6/75), 16.00%(12/75), 37.33%(28/75), 1.33%(1/75), 0(0/75), 0(0/31), 40.00%(30/75), 14.67%(11/75), 1.33%(1/75), 0(0/31), 54.67%(41/75), 37.33%(28/75), and 52.00%(39/75), respectively. ② Drug resistance of other Gram-negative bacteria: the drug resistance rates of Klebsiella pneumoniae subsp. pneumoniae to ampicillin, cefazolin, cefuroxime, ceftriaxone, ceftazidime, cefotetan, cefepime, amoxicillin/carat Retinoic acid, ampicillin/sulbactam, piperacillin/tazobactam, cefoperazone/sulbactam, aztreonam, imipenem, meropenem, ertapenem, gentamicin, tobramycin, amikacin, ciprofloxacin, levofloxacin, and trimethoprim sulfamethoxazole were 8/8, 0/5, 0/5, 0/1, 0/9, 0/2, 0/9, 0/8, 0/9, 0/9, 0/6, 0/9, 0/9, 0/7, 0/1, 0/9, 0/8, 0/9, 0/9, 0/9, and 0/9. The drug resistance rates of Acinetobacter baumannii to ceftriaxone, ceftazidime, cefepime, ampicillin/sulbactam, piperacillin/tazobactam, cefoperazone/sulbactam, aztreonam, imipenem, meropenem, gentamicin, tobramycin, amikacin, tigaricycline, ciprofloxacin, levofloxacin, and trimethoprim sulfamethoxazole were 2/6, 4/6, 3/6, 0/6, 4/6, 1/6, 2/6, 4/6, 2/6, 4/6, 4/6, 3/6, 0/6, 4/6, 2/6, and 3/6, respectively. The drug resistance rates of Alcaligenes xylosoxidans subsp. xylosoxidans to ampicillin, cefazolin, cefuroxime, ceftazidime, cefepime, amoxicillin/carat Retinoic acid, piperacillin/tazobactam, aztreonam, imipenem, gentamicin, tobramycin, amikacin, ciprofloxacin, and levofloxacin were 3/3, 3/3, 3/3, 1/3, 1/3, 1/3, 0/3, 3/3, 2/3, 3/3, 3/3, 3/3, 3/3, and 1/3. ③ Drug resistance of other Gram-positive bacteria: the drug resistance rates of Staphylococcus aureus to penicillin, ampicillin, piperacillin, cefazolin, cefuroxime, cefotaxime, ceftazidime, cefepime, cefoxitin, amoxicillin/carat Retinoic acid, ampicillin/sulbactam, piperacillin/tazobactam, cefoperazone/sulbactam, aztreonam, imipenem, meropenem, gentamicin, tobramycin, amikacin, tetracycline, tigaricycline, ciprofloxacin, levofloxacin, moxifloxacin, trimethoprim sulfamethoxazole, linezolid, erythromycin, clindamycin, vancomycin, teicoplanin, and rifampin were 2/6, 6/8, 4/5, 4/5, 4/5, 4/5, 4/5, 4/5, 4/5, 4/5, 4/5, 4/5, 4/5, 3/5, 2/5, 2/5, 3/8, 3/5, 3/5, 0/8, 0/8, 3/8, 3/11, 0/5, 1/8, 0/8, 0/8, 2/6, 3/3, 1/3, and 0/3. The drug resistance rates of Streptococcus viridians to penicillin, ampicillin, ceftriaxone, cefoperazone/sulbactam, gentamicin, tetracycline, ciprofloxacin, levofloxacin, moxifloxacin, linezolid, erythromycin, clindamycin, vancomycin, teicoplanin, and rifampin were 3/10, 0/8, 0/7, 0/7, 2/8, 6/10, 0/8, 0/8, 0/7, 0/5, 4/10, 6/10, 0/5, 0/5, and 0/3. The drug resistance rates of β-emolytic streptococcus to antibacterial agents were 0. ④ Drug resistance of complex bacteria. For the 12 patients with double bacterial infection, in the Klebsiella pneumoniae combined with Gram-negative bacteria, the drug resistance rates of Klebsiella pneumoniae to cefotetan, cefoxitin, ampicillin/sulbactam, meropenem, ertapenem, tobramycin, tigecycline, and trimethoprim sulfamethoxazole were 0. The drug resistance rates of Acinetobacter baumannii to ertapenem, levofloxacin, and trimethoprim sulfamethoxazole were 0. The drug resistance rates of Escherichia coli to ceftazidime, cefoxitin, amoxicillin/clavulanic acid, piperacillin/tazobactam, imipenem, meropenem, ertapenem, tobramycin, amikacin, and tigecycline were 0. Citrobacter florida was sensitive to other antibiotics than levofloxacin and trimethoprim cotrimoxazole. In the Escherichia coli combined with Gram-positive bacteria, the drug resistance rates of Escherichia coli to cefotetan, cefepime, cefoxitin, cefoperazone/sulbactam, meropenem, tobramycin, and amikacin were 0. The drug resistance rates of Enterococcus faecalis to penicillin, ampicillin, levofloxacin, moxifloxacin, linezolid, vancomycin, and teicoplanin were 0. The drug resistance rates of Enterococcus casselifavus to ampicillin, tetracycline, levofloxacin, moxifloxacin, linezolid, and erythromycin were 0. The drug resistance rates of Staphylococcus hominis subspecies to levofloxacin, moxifloxacin, linezolid, vancomycin, teicoplanin, and rifampicin were 0. The drug resistance rates of Enterococcus faecium to tetracycline,linezolid, vancomycin, and teicoplanin were 0. In the multiple bacterial infections of Klebsiella pneumoniae + Escherichia coli + Staphylococcus aureus subspecies + Pseudomonas aeruginosa + Torulopsis glabrata, the drug resistance rates of Klebsiella pneumoniae to ceftriaxone, ceftazidime, cefotetan, cefepime, cefoxitin, ampicillin/sulbactam, piperacillin/tazobactam, cefoperazone/sulbactam, aztreonam, imipenem, tobramycin, amikacin, and levofloxacin were 0. The drug resistance rates of Escherichia coli to ceftazidime, cefotetan, cefepime, ampicillin/sulbactam, piperacillin/tazobactam, cefoperazone/sulbactam, aztreonam, imipenem, and amikacin were 0. The drug resistance rates of Staphylococcus aureus subspecies to ceftriaxone, ceftazidime, cefotetan, cefepime, ampicillin/sulbactam, piperacillin/tazobactam, cefoperazone/sulbactam, aztreonam, imipenem, tobramycin, amikacin, tigecycline, moxifloxacin, cotrimoxazole, teicoplanin, vancomycin, linezolid, and clindamycin were 0. The drug resistance rates of Pseudomonas aeruginosa to ceftazidime, cefepime, piperacillin/tazobactam, imipenem, gentamicin, tobramycin, amikacin, ciprofloxacin, and levofloxacin were 0. The drug resistance rates of Torulopsis glabrata to 5-fluorocytosine, fluconazole, itraconazole, and voriconazole were 0. In the multiple bacterial infections of Klebsiella pneumoniae + Escherichia coli + Acinetobacter baumannii, the drug resistance rates of Klebsiella pneumoniae to cefotetan, cefepime, piperacillin/tazobactam, imipenem, ertapenem, tobramycin, ciprofloxacin, and levofloxacin were 0. The drug resistance rates of Escherichia coli to amoxicillin/clavulanic acid, piperacillin/tazobactam, imipenem, meropenem were 0. The drug resistance ratets of Acinetobacter baumannii to trimethoprim sulfamethoxazole was 0.
    Conclusions: Klebsiella pneumoniae is the main pathogen of PLA, followed by Escherichia coli. Klebsiella pneumoniae and Escherichia coli are sensitive to meropenem and tigecycline. Klebsiella pneumoniae subsp. pneumoniae and other Gram-negative bacteria are sensitive to ertapenem. Staphylococcus aureus are sensitive to Linezolid. Antibiotics are selected after drug sensitivity test for patients.

     

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