Pathogen Distribution and Antimicrobial Susceptibility of Bacterial Bloodstream Infection in AIDS Patients
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摘要:
目的 了解艾滋病住院患者细菌血流感染的患病率、病原菌种类及耐药情况。 方法 回顾性收集上海市公共卫生临床中心2015年至2020年血培养分离出细菌的艾滋病患者资料,分析病原菌种类及相应抗菌药物的耐药情况多重耐药的比例。 结果 艾滋病患者中 2015年至2020年间血流感染细菌检出率为4.48%。革兰阳性菌检出128株(59.3%),83株有耐药报告,对青霉素的耐药率为94%,对红霉素的耐药率为91.4%,未检出利奈唑胺、替加环素、万古霉素、喹奴普汀/达福普汀耐药者,多重耐药率38.6%,39.7%的细菌对5类以上抗菌药耐药。革兰阴性菌检出88株(40.7%),70株有耐药报告,对氨苄西林的耐药率为81.6%,喹诺酮类、碳青霉烯类和头孢菌素对革兰阴性菌都有较高的敏感性,多重耐药率14.4%,12.8%的细菌对5类以上抗菌药耐药。 结论 艾滋病合并细菌性血流感染者,革兰阳性菌多重耐药率更高,治疗时可以选择利奈唑胺、替加环素、万古霉素及喹奴普汀/达福普汀。喹诺酮类、碳青霉烯类和头孢菌素对革兰阴性菌较敏感。 Abstract:Objective To explore the prevalence of bacterial bloodstream infection in AIDS patients, and to learn the pathogen species drug resistance among AIDS patients . Methods We retrospectively collected the data of AIDS patients with bacteria isolated from blood culture in Shanghai Public Health Clinical Center from 2015 to 2020. The species of pathogenic bacteria and the antibiotic resistance were analyzed, and the proportion of multiple resistance was also calculated. Results The positive rate of bacteria in bloodstream between 2015 and 2020 was 4.48% in AIDS patients. 128 strains (59.3%) of gram-positive bacteria were detected, 83 strains were reported to be resistant to penicillin, and the resistance rate to erythromycin was 94% and 91.4% No Linezolide, Tigecycline, Vancomycin, Quinolputin/ Dapoptine resistance were detected. The multiple drug resistance rate was 38.6%, and 39.7% of the bacteria were resistant to more than 5 classes of antibiotics. Gram-negative bacteria were detected in 88 patients (40.7%), and drug resistance was reported in 70 patients , the resistance rate to Ampicillin was 81.6%. Quinolones, Carbopenems and Cephalosperins all had high sensitivity to gram-negative bacteria. The multiple drug resistance rate was 14.4%, and 12.8% of the bacteria were resistant to more than 5 classes of antibiotics. Conclusions For AIDS patients with bacterial blood flow infection, the multiple drug resistance rate of gram-positive bacteria is higher, linezolid, tigecycline, vancomycin and quinuptine/daphoputin can be selected for treatment . Quinolones, Carbopenems, and Cephalosperins all have high sensitivity to gram-negative bacteria. -
Key words:
- HIV /
- AIDS /
- Bloodstream infection /
- Bacterium /
- Drug sensitivity
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血流感染(bloodstream infection,BSI)是由各种病原微生物在循环血流中一过性、间歇性或持续性存在而导致机体发生的全身性、感染性疾病[1]。艾滋病住院患者由于身体虚弱、免疫功能低下发生血流感染的机会增加,而且致病病原菌构成较为复杂。研究显示[2],与非HIV感染者相比,菌血症是艾滋病患者死亡的主要原因之一。国内外研究均显示对于晚期艾滋病患者,血流感染的发病率高于20%[3-4]。无论在发达国家还是发展中国家,抗生素耐药都是艾滋病患者面临的一个新的公共卫生问题[5-6]。分析艾滋病患者血流感染的病原菌耐药情况,有助于及时选择合理有效的抗菌药物,降低病死率,改善预后。本研究回顾性分析了上海市公共卫生临床中心艾滋病住院患者中血培养检出细菌者的临床资料,了解病原菌构成、流行趋势及耐药情况,以期对临床诊治提供参考。
1. 对象与方法
1.1 研究对象
上海市公共卫生临床中心2015年1月至2020年12月艾滋病住院患者。纳入标准:(1)经HIV确证实验室确认为HIV感染;(2)年龄大于18岁;(3) 血培养检出细菌。排除标准:(1)虽经血培养检出细菌,但患者并无感染相关诱因及临床表现,判定为标本污染者;(2)培养出分枝杆菌者。同一患者重复分离出相同菌株时仅纳入第1次分离结果。
1.2 病原学检测
血培养按照《临床微生物学血培养操作规范》操作,药敏试验按照《临床检验管理与技术规程》进行。血培养及鉴定采用法国生物梅里埃公司ATB Expression自动细菌鉴定仪进行鉴定和药敏试验。
1.3 研究内容
了解2015至2020年细菌检出率变化趋势,同时分析研究对象的药敏结果,对检出率较高的前5位革兰阳性菌和革兰阴性菌耐药情况进行整理,分析病原菌对抗菌药的耐药情况。
本研究为回顾性、匿名的资料收集方法,未涉及患者隐私,故伦理审查中同意免除知情同意签字。
1.4 统计学处理
EXCEL收集整理数据,SPSS 20.0统计分析。服从正态分布的计量资料用
$ \bar x \pm s $ 描述,不服从正态分布的用M(P25,P75)描述,计数资料用[n(%)]描述。2. 结果
2.1 研究对象一般情况
血培养检出细菌的205例患者,平均年龄(44.5±15.3)岁,男性占92.8%,中位CD4为37(10,158)个/μL。CD4 < 100个/μL者128例(62.4%),100~200个/μL有35例(17.1%),200个/μL以上有34例(16.6%)。中位白细胞5.23(3.3,8.7)×109/L,中性粒细胞3.68(2.2,6.4)×109/L,血红蛋白102(83,120)g/L,白蛋白30.47(27,35.6)g/L,C反应蛋白45.6(11,116)mg/L,降钙素原0.35 (0.10,1.26) ng/mL。各年患者情况,见表1。
表 1 2015-2020年血培养检出细菌的艾滋病患者基本情况[n(%)]Table 1. Basic information of AIDS patients with bacteria detected in blood cultures from 2015 to 2020 [n(%)]项目 2015年(n = 45) 2016年(n = 30) 2017年(n = 34) 2018年(n = 29) 2019年(n = 30) 2020年(n = 39) 年龄(岁) 44.4 ± 15.84 42.3 ± 15.3 45.3 ± 12.9 39.3 ± 13.2 45.2 ± 14.9 48.9 ± 18.8 性别 男 42(93.3) 26(86.7) 32(94.1) 28(96.6) 27(90) 37(94.9) 女 3(6.7) 4(13.3) 2(5.9) 1(3.4) 3(10) 2(5.1) CD4(个/μL) 35(13,151) 32(9.5,134) 37.5(9,164.7) 20(3.5,146.2) 40(13,165) 84(10.5,274) 白细胞(×109/L) 5.3(3.8,8.6) 5.2(3.8,8.4) 4.9(3.7,8.6) 3.9(2.9,7.9) 6.27(3.2,9.1) 5.4(2.7,10.2) 中性粒细胞(×109/L) 3.5(.1,4.9) 3.4(1.9,6.8) 3.6(2.6,5.9) 3.3(2.2,6.6) 4.8(2.1,8.2) 4.1(2.0,8.5) 血红蛋白(g/L) 101(84,115) 112(98,128) 109(78,121) 91(69,107) 113(91,128) 102(81,119) 白蛋白(g/L) 30(16.2,36.3) 34.6(26.2,38.4) 30.3(25.2,34.6) 28.8(24.7,32.7) 32.9(28.4,35.6) 30.6(27,34.9) C反应蛋白(mg/L) 26(9.7,112.5) 27.9(7.2,126.2) 30(7,98) 78.6(32.2,124.0) 53.6(10.5,131.5) 63(19.8,110.8) 降钙素原( ng/mL) 0.19(0.07,0.8) 0.37(0.06,1.6) 0.17(0.07,1.1) 0.58(0.1,1.9) 0.35(0.14,0.71) 0.4(0.2,1.56) 2.2 各年血培养细菌检测人数及检出率变化趋势
血培养的人数在2015和2016年较少,2017至2020年相对较多且检测人数波动较小。4 824例艾滋病血培养患者中共检出细菌216株,总体检出率为4.48%。检出细菌阳性率2015年较高,之后呈下降的趋势,2020年有所上升,见图1。
2.3 各年检出细菌种类
分别对216株细菌中革兰阳性菌和阴性菌按年份分部情况,见表2。检出革兰阳性菌128株(59.3%)其中表皮葡萄球菌21株(9.7%),凝固酶阴性葡萄球菌18株(8.3%),人葡萄球菌17株(7.9%)(其中4株为人葡萄球菌人亚种),溶血葡萄球菌15株(6.9%),金黄色葡萄球菌14株(6.5%),头状葡萄球菌9株(4.2%)。革兰阴性菌88株(40.7%)中,沙门菌属24株(11.1%),大肠埃希菌19株(8.8%),肺炎克雷伯杆菌12株(5.6%),铜绿假单胞菌10株(4.6%),鲍曼不动杆菌4株(1.8%)。11例患者同时检出两种细菌,分别为溶血葡萄球菌+沙门菌属,肺炎克雷伯杆菌+大肠埃希菌,凝固酶阴性葡萄球菌+革兰阳性菌,铜绿假单胞菌+停乳链球菌似马亚种,大肠埃希菌+革兰阴性杆菌,鲍曼不动杆菌+金黄色葡萄球菌,缓症链球菌+纹带棒杆菌,溶血葡萄球菌+铅黄肠球菌,表皮葡萄球菌+头状葡萄球菌,短稳杆菌+人葡萄球菌,医院不动杆菌+副血链球菌。
表 2 2015-2020年艾滋病住院患者中血培养细菌构成情况[n(%)]Table 2. Composition of blood culture bacteria in AIDS inpatients from 2015 to 2020 [n(%)]病原菌 2015年
(n = 720)2016年
(n = 696)2017年
(n = 894)2018年
(n = 849)2019年
(n = 846)2020年
(n = 819)革兰阳性菌(n = 128) 表皮葡萄球菌 (n = 21) 4(0.56) 2(0.29) 3(0.34) 3(0.35) 4(0.47) 5(0.61) 凝固酶阴性葡萄球菌 (n = 18) 8(1.11) 5(0.72) 2(0.22) 2(0.23) 1(0.12) 0(0) 溶血葡萄球菌 (n = 15) 5(0.69) 1(0.14) 1(0.11) 3(0.35) 2(0.24) 3(0.37) 人葡萄球菌 (n = 17) 3(0.42) 3(0.43) 1(0.11) 2(0.23) 1(0.12) 7(0.85) 金黄色葡萄球菌 (n = 14) 4(0.56) 0(0) 3(0.34) 3(0.35) 1(0.12) 3(0.37) 头状葡萄球菌 (n = 9) 0(0) 2(0.29) 3(0.34) 0(0) 2(0.24) 2(0.24) 链球菌属(n = 9) 2(0.28) 2(0.29) 2(0.22) 0(0) 2(0.24) 1(0.12) 其他少见G+菌(n = 25) 8(1.11) 4(0.57) 5(0.56) 1(0.12) 3(0.35) 4(0.49) 革兰阴性菌(n = 88) 沙门菌属 (n = 24) 3(0.42) 3(0.43) 5(0.56) 6(0.71) 4(0.47) 3(0.37) 大肠埃希菌 (n = 19) 3(0.42) 4(0.57) 2(0.22) 3(0.35) 3(0.35) 4(0.49) 肺炎克雷伯杆菌 (n = 12) 3(0.42) 0(0) 3(0.34) 0(0) 5(0.59) 1(0.12) 铜绿假单胞菌 (n = 10) 1(0.14) 0(0) 1(0.11) 2(0.23) 4(0.47) 2(0.24) 鲍曼不动杆菌 (n = 4) 1(0.14) 0(0) 1(0.11) 0(0) 0(0) 2(0.24) 其他少见G-菌(n = 19) 2(0.28) 4(0.57) 5(0.56) 4(0.47) 1(0.12) 3(0.37) 2.4 细菌耐药情况
检出的216株细菌中有153株有耐药检测报告。
2.4.1 革兰阳性细菌耐药情况
革兰阳性菌未检出利奈唑胺、替加环素、万古霉素、喹奴普汀/达福普汀耐药者。表皮葡萄球菌耐药率最高的是青霉素G和红霉素,均为100%,其次为苯唑西林(85.7%)、SMZ(83.8%)、克林霉素(80%)。金黄色葡萄球菌耐药率最高的是青霉素G(91.7%),其次为红霉素(76.9%),克林霉素(64.3%)。溶血葡萄球菌耐药率最高的是红霉素(100%),其次是环丙沙星、左氧氟沙星、青霉素G和苯唑西林均为92.3%。人葡萄球菌耐药率最高的是青霉素G(100%),其次是红霉素(92.9%)、克林霉素(78.6%)、苯唑西林(78.6%)。头状葡萄球菌耐药率最高的是青霉素G(100%),其次是红霉素(75%)。见表3。革兰阳性菌对青霉素的总体耐药率为94%,对红霉素的总体耐药率为91.4%。
表 3 2015-2020年艾滋病住院患者血培养革兰阳性细菌耐药情况 [n(%)]Table 3. Drug resistance of Gram-positive bacteria in blood culture of AIDS inpatients from 2015 to 2020 [n(%)]革兰阳性细菌 克林霉素 环丙沙星 莫西沙星 左氧氟沙星 红霉素 青霉素G 庆大霉素 四环素 苯唑西林 利福平 SMZ 表皮葡萄球菌 n = 15 n = 14 n = 12 n = 14 n = 15 n = 13 n-14 n = 14 n = 14 n = 13 n = 12 S 3(20) 4(28.6) 4(33.3) 4(28.6) 0(0) 0(0) 6(42.8) 9(64.3) 2(14.3) 7(53.8) 2(16.7) I 0(0) 9(64.3) 1(8.3) 1(7.1) 0(0) 0(0) 3(21.4) 0(0) 0(0) 0(0) 0(0) R 12(80) 1(7.1) 7(58.3) 9(64.3) 15(100) 13(100) 5(35.7) 5(35.7) 12(85.7) 6(46.1) 10(83.3) 金黄色葡萄球菌 n = 14 n = 14 n = 9 n = 12 n = 13 n = 12 n = 14 n = 13 n = 13 n = 13 n = 13 S 5(35.7) 10(71.4) 8(88.9) 11(91.7) 3(23.1) 1(8.3) 12(85.7) 9(69.2) 9(69.2) 12(92.3) 8(61.5) I 0(0) 1(7.1) 0(0) 0(0) 0(0) 0(0) 1(7.1) 0(0) 0(0) 0(0) 0(0) R 9(64.3) 3(21.4) 1(11.1) 1(8.3) 10(76.9) 11(91.7) 1(7.1) 4(30.7) 4(30.8) 1(7.7) 5(38.5) 溶血葡萄球菌 n = 13 n = 13 n = 12 n = 13 n = 13 n = 13 n = 12 n = 12 n = 13 n = 12 n = 12 S 3(23.1) 1(7.7) 1(7.7) 1(7.7) 0(0) 1(7.7) 3(25) 10(83.3) 1(7.7) 7(58.3) 5(41.7) I 0(0) 0(0) 4(30.8) 0(0) 0(0) 0(0) 1(8.3) 0(0) 0(0) 0(0) 0(0) R 10(76.9) 12(92.3) 7(53.8) 12(92.3) 13(100) 12(92.3) 8(66.7) 2(16.6) 12(92.3) 5(41.7) 7(58.3) 人葡萄球菌 n = 14 n = 14 n = 14 n = 14 n = 14 n = 12 n = 13 n = 14 n = 14 n = 14 n = 14 S 2(14.3) 3(21.4) 3(21.4) 3(21.4) 1(7.1) 0(0) 12(92.3) 5(35.7) 3(21.4) 10(71.4) 4(28.6) I 1(7.1) 2(14.3) 3(21.4) 1(7.1) 0(0) 0(9) 1(7.7) 0(0) 0(0) 0(0) 0(0) R 11(78.6) 9(64.3) 8(57.1) 10(71.4) 13(92.9) 12(100) 0(0) 9(64.3) 11(78.6) 4(28.6) 10(71.4) 头状葡萄球菌 n = 8 n = 8 n = 7 n = 7 nN=8 n = 7 n = 8 n = 8 n = 8 n = 8 n = 8 S 6(75) 5(62.5) 4(57.1) 4(57.1) 2(25) 0(0) 7(87.5) 6(75) 5(62.5) 6(75) 6(75) I 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) R 2(25) 3(37.5) 3(42.8) 3(42.8) 6(75) 7(100) 1(12.5) 2(25) 3(37.5) 2(25) 2(25) 注:S:敏感,I:中介,R:耐药。 2.4.2 革兰阴性细菌耐药情况
大肠埃希菌耐药率最高的是氨苄西林(88.9%),其次是头孢曲松(72.2%)。沙门菌属耐药率最高的是氨苄西林(80%)。肺炎克雷伯杆菌耐药率最高的是氨苄西林(100%),其次是头孢曲松(54.5%)。铜绿假单胞菌耐药率最高的是氨苄西林和头孢曲松,均为100%。鲍曼不动杆菌耐药率最高的是氨苄西林、氨曲南和阿米卡星,均为100%,其次是庆大霉素、头孢曲松、头孢比肟和亚胺培南,均为66.7%,见表4。革兰阴性菌对氨苄西林的总体耐药率为81.6%。
表 4 2015~2020年艾滋病住院患者血培养革兰阴性细菌耐药情况[n(%)]Table 4. Drug resistance of Gram-negative bacteria in blood culture of AIDS inpatients from 2015 to 2020 [n(%)]革兰阴性细菌 环丙沙星 左氧氟沙星 庆大霉素 氨苄西林 头孢曲松 头孢他啶 头孢比肟 氨曲南 阿米卡星 亚胺培南 美罗培南 大肠埃希菌 n = 17 n = 18 n = 18 n = 18 n = 18 n = 18 n = 15 n = 18 n = 17 n = 17 n = 5 S 6(35.3) 6(33.3) 13(72.2) 2(11.1) 5(27.8) 15(83.3) 13(86.7) 13(72.2) 17(100) 17(100) 5(100) I 0(0) 2(11.1) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) R 11(64.7) 10(55.6) 5(27.8) 16(88.9) 13(72.2) 3(16.7) 2(13.3) 5(27.8) 0(0) 0(0) 0(0) 沙门菌属 n = 12 n = 4 - n = 15 n = 11 n = 11 n = 1 n = 1 - n = 1 - S 6(50) 1(25) - 3(20) 10(90.9) 10(90.9) 1(100) 1(100) - 1(100) - I 6(50) 3(75) - 0(0) 0(0) 0(0) 0(0) 0(0) - 0(0) - R 0(0) 0(0) - 12(80) 1(9.1) 1(9.1) 0(0) 0(0) - 0(0) - 肺炎克雷伯杆菌 n = 11 n = 11 n = 11 n = 7 n = 11 n = 11 n = 11 n = 11 n = 11 n = 11 n = 5 S 5(45.4) 6(54.5) 6(54.5) 0(0) 5(45.5) 6(54.5) 6(54.5) 6(54.5) 8(72.7) 8(72.7) 3(60) I 1(9.2) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) R 5(45.4) 5(45.5) 5(45.5) 7(100) 6(54.5) 5(45.5) 5(45.5) 5(45.5) 3(27.3) 3(27.3) 2(40) 铜绿假单胞菌 n = 6 n = 6 n = 7 n = 2 n = 2 n = 6 n = 6 n = 4 n = 6 n = 6 n = 2 S 6(100) 5(83.3) 6(85.7) 0(0) 0(0) 5(83.3) 6(100) 3(75) 6(100) 5(83.3) 2(100) I 0(0) 1(16.7) 0(0) 0(0) 0(0) 1(16.7) 0(0) 0(0) 0(0) 0(0) 0(0) R 0(0) 0(0) 1(14.3) 2(100) 2(100) 0(0) 0(0) 1(25) 0(0) 1(16.7) 0(0) 鲍曼不动杆菌 n = 2 n = 3 n = 3 n = 2 n = 3 n = 2 n = 3 n = 1 n = 1 n = 3 n = 2 S 1(50) 1(33.3) 1(33.3) 0(0) 0(0) 1(50) 1(33.3) 0(0) 0(0) 1(33.3) 1(50) I 0(0) 1(33.3) 0(0) (0) 1(33.3) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) R 1(50) 1(33.3) 2(66.7) 2(100) 2(66.7) 1(50) 2(66.7) 1(100) 1(100) 2(66.7) 1(50) 注:S:敏感,I:中介,R:耐药。 2.4.3 细菌多重耐药情况
有耐药结果的153株细菌中,革兰阳性菌多重耐药率38.6%(59/153),39.7%(33/83)的细菌对5类以上抗菌药耐药;革兰阴性菌多重耐药率14.4%(22/153),12.8%(9/70)的细菌对5类以上抗菌药耐药。总体对5类以上抗菌药耐药的比例为26.1%。多重耐药发生率最高的是表皮葡萄球菌(100%),其次是人葡萄球菌(92.8%)、溶血葡萄球菌(92.3%)、鲍曼不动杆菌(66.7%)、金黄色葡萄球菌(57.1%)、大肠埃希菌(55.6%)及肺炎克雷伯杆菌(45.4%),见表5。
表 5 2015-2020年艾滋病住院患者血培养细菌多重耐药情况[n(%)]Table 5. Multiple drug resistance of blood culture bacteria of AIDS inpatients from 2015 to 2020 [n(%)]细菌 R0 R1 R2 R3 R4 R5 ≥R6 革兰阳性菌(n = 83) 表皮葡萄球菌(n = 15) 0(0) 0(0) 0(0) 4(26.7) 1(6.6) 3(20) 7(46.7) 人葡萄球菌(n = 14) 0(0) 0(0) 1(7.1) 0(0) 4(28.6) 2(14.3) 7(50) 金黄色葡萄球(n = 14) 0(0) 2(14.3) 4(28.6) 1(7.1) 4(28.6) 2(14.3) 1(7.1) 溶血葡萄球菌(n = 13) 0(0) 0(0) 1(7.7) 0(0) 4(30.8) 1(7.7) 7(53.8) 头状葡萄球菌(n = 8) 0(0) 1(12.5) 4(50) 0(0) 1(12.5) 0(0) 2(25) 链球菌属(n = 6) 0(0) 1(16.7) 1(16.7) 3(50) 1(16.7) 0(0) 0(0) 其他少见G+(n = 13) 1(7.6) 1(7.6) 3(23.1) 1(7.6) 2(15.5) 0(0) 1(7.6) 革兰阴性菌(n = 70) 沙门菌属(n = 21) 7(33.3) 13(61.9) 1(4.8) 0(0) 0(0) 0(0) 0(0) 大肠埃希菌(n = 18) 1(5.6) 5(27.8) 2(11.1) 7(38.9) 3(16.6) 0(0) 0(0) 肺炎克雷伯杆菌(n = 11) 4(36.4) 1(9.1) 1(9.1) 0(0) 1(9.1) 1(9.1) 3(27.2) 铜绿假单胞菌(n = 7) 4(57.1) 0(0) 2(28.6) 0(0) 0(0) 1(14.3) 0(0) 鲍曼不动杆菌(n = 3) 1(33.3) 0(0) 0(0) 0(0) 0(0) 1(33.3) 1(33.3) 其他少见G-菌(n = 10) 3(30) 2(20) 1(10) 2(20) 0(0) 2(20) 0(0) 注:R0:对检测的抗菌药种类都敏感,R1:对1类抗菌药耐药,R2:对2类抗菌药耐药,R3:对3类抗菌药耐药,R4:对4类抗菌药耐药,R5:对5类抗菌药耐药,R6:对6类及以上抗菌药耐药。 3. 讨论
细菌血流感染是艾滋病患者较常见的严重感染之一,此类患者CD4及血清白蛋白水平较低,C反应蛋白和降钙素原升高,Kiertiburanakul[7]的研究显示艾滋病合并血流感染患者CD4中位数为32个/μL,与本研究结果相似。有研究[8]也证实了白蛋白降低及C反应蛋白升高是艾滋病合并血流感染患者预后不良的独立危险因素。
艾滋病血流感染中最常见的是葡萄球菌[9]。本研究中细菌以革兰阳性菌为主占59.3%,多数为葡萄球菌。而革兰阴性菌以沙门菌和大肠埃希菌多见,与高慧等[10]的研究结果相似。也有研究显示沙门菌属是艾滋病合并败血症的最常见病原菌,且发生多重耐药的比例较高[11]。本研究发现革兰阳性菌对青霉素和红霉素耐药率最高,总体耐药率为94%和91.4%,这可能与长期广泛使用有关。坦桑尼亚的研究[12]也发现肺炎球菌对青霉素的耐药率为82.1%。本研究中金黄色葡萄球菌对喹诺酮类较敏感。培养出的革兰阳性菌对利奈唑胺、替加环素、万古霉素、喹奴普汀/达福普汀均敏感,与杨宗兴等[1]的研究结果一致。革兰阴性菌对氨苄西林的总体耐药率为81.6%。埃塞俄比亚的研究[13,14]也发现氨苄西林的耐药率高达88%~100%。本研究中大肠埃希菌对阿米卡星和碳青霉烯类均较敏感,沙门菌属对喹诺酮类、碳青霉烯类和头孢菌素都有较好的敏感性,埃塞俄比亚一项对腹泻患者的研究[15]也表明头孢曲松和环丙沙星具有较好的敏感性。本研究显示肺炎克雷伯杆菌对阿米卡星和亚胺培南较敏感,铜绿假单胞菌对环丙沙星、阿米卡星、头孢比肟、美罗培南有较好的敏感性。国内其他研究[16-17]也显示革兰阴性杆菌总体对碳青霉烯类、头孢吡肟、氨曲南、头孢他啶、左氧氟沙星及 β 内酰胺酶抑制剂复合制剂保持较高敏感性。
本研究发现26.1%的细菌对5类以上抗菌药耐药,低于Jemal等[18]的研究40.7%的患者对5类以上抗菌药耐药,而与在埃塞俄比亚冈达尔的研究[19]结果29%相似。细菌发生多重耐药的比例较高,尤其是革兰阳性菌,这可能与长期广泛使用抗生素有关。表皮葡萄球菌多重耐药发生率为100%,人葡萄球菌多重耐药发生率92.8%。革兰阴性菌中的大肠埃希菌多重耐药发生率为55.6%,而沙门菌属没有发现有多重耐药的菌株。
本研究发现革兰阳性菌多重耐药率高于革兰阴性菌,庆幸的是革兰阳性菌中没有发现利奈唑胺、替加环素、万古霉素、喹奴普汀/达福普汀耐药的菌株。喹诺酮类、碳青霉烯类和头孢菌素对革兰阴性菌都有较高的敏感性。
研究局限性:所纳入血培养阳性患者中,相当一部分患者存在基础疾病,如肿瘤化疗;处于临床较为严重的消耗状态,如长期卧床;出于治疗目的而留置深静脉、导尿管或呼吸机辅助通气,因此增加了院内感染可能。多数非本地患者由于病情严重而转来本院,合并症较多,故本次回顾性研究未能分析研究对象的预后。
综上所述,艾滋病合并细菌性血流感染往往处于疾病的危险阶段。明确各地艾滋病患者的血流感染致病菌分布及耐药结果,对于及时经验性治疗具有参考价值,有助于提升疗效,降低病死率。
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表 1 2015-2020年血培养检出细菌的艾滋病患者基本情况[n(%)]
Table 1. Basic information of AIDS patients with bacteria detected in blood cultures from 2015 to 2020 [n(%)]
项目 2015年(n = 45) 2016年(n = 30) 2017年(n = 34) 2018年(n = 29) 2019年(n = 30) 2020年(n = 39) 年龄(岁) 44.4 ± 15.84 42.3 ± 15.3 45.3 ± 12.9 39.3 ± 13.2 45.2 ± 14.9 48.9 ± 18.8 性别 男 42(93.3) 26(86.7) 32(94.1) 28(96.6) 27(90) 37(94.9) 女 3(6.7) 4(13.3) 2(5.9) 1(3.4) 3(10) 2(5.1) CD4(个/μL) 35(13,151) 32(9.5,134) 37.5(9,164.7) 20(3.5,146.2) 40(13,165) 84(10.5,274) 白细胞(×109/L) 5.3(3.8,8.6) 5.2(3.8,8.4) 4.9(3.7,8.6) 3.9(2.9,7.9) 6.27(3.2,9.1) 5.4(2.7,10.2) 中性粒细胞(×109/L) 3.5(.1,4.9) 3.4(1.9,6.8) 3.6(2.6,5.9) 3.3(2.2,6.6) 4.8(2.1,8.2) 4.1(2.0,8.5) 血红蛋白(g/L) 101(84,115) 112(98,128) 109(78,121) 91(69,107) 113(91,128) 102(81,119) 白蛋白(g/L) 30(16.2,36.3) 34.6(26.2,38.4) 30.3(25.2,34.6) 28.8(24.7,32.7) 32.9(28.4,35.6) 30.6(27,34.9) C反应蛋白(mg/L) 26(9.7,112.5) 27.9(7.2,126.2) 30(7,98) 78.6(32.2,124.0) 53.6(10.5,131.5) 63(19.8,110.8) 降钙素原( ng/mL) 0.19(0.07,0.8) 0.37(0.06,1.6) 0.17(0.07,1.1) 0.58(0.1,1.9) 0.35(0.14,0.71) 0.4(0.2,1.56) 表 2 2015-2020年艾滋病住院患者中血培养细菌构成情况[n(%)]
Table 2. Composition of blood culture bacteria in AIDS inpatients from 2015 to 2020 [n(%)]
病原菌 2015年
(n = 720)2016年
(n = 696)2017年
(n = 894)2018年
(n = 849)2019年
(n = 846)2020年
(n = 819)革兰阳性菌(n = 128) 表皮葡萄球菌 (n = 21) 4(0.56) 2(0.29) 3(0.34) 3(0.35) 4(0.47) 5(0.61) 凝固酶阴性葡萄球菌 (n = 18) 8(1.11) 5(0.72) 2(0.22) 2(0.23) 1(0.12) 0(0) 溶血葡萄球菌 (n = 15) 5(0.69) 1(0.14) 1(0.11) 3(0.35) 2(0.24) 3(0.37) 人葡萄球菌 (n = 17) 3(0.42) 3(0.43) 1(0.11) 2(0.23) 1(0.12) 7(0.85) 金黄色葡萄球菌 (n = 14) 4(0.56) 0(0) 3(0.34) 3(0.35) 1(0.12) 3(0.37) 头状葡萄球菌 (n = 9) 0(0) 2(0.29) 3(0.34) 0(0) 2(0.24) 2(0.24) 链球菌属(n = 9) 2(0.28) 2(0.29) 2(0.22) 0(0) 2(0.24) 1(0.12) 其他少见G+菌(n = 25) 8(1.11) 4(0.57) 5(0.56) 1(0.12) 3(0.35) 4(0.49) 革兰阴性菌(n = 88) 沙门菌属 (n = 24) 3(0.42) 3(0.43) 5(0.56) 6(0.71) 4(0.47) 3(0.37) 大肠埃希菌 (n = 19) 3(0.42) 4(0.57) 2(0.22) 3(0.35) 3(0.35) 4(0.49) 肺炎克雷伯杆菌 (n = 12) 3(0.42) 0(0) 3(0.34) 0(0) 5(0.59) 1(0.12) 铜绿假单胞菌 (n = 10) 1(0.14) 0(0) 1(0.11) 2(0.23) 4(0.47) 2(0.24) 鲍曼不动杆菌 (n = 4) 1(0.14) 0(0) 1(0.11) 0(0) 0(0) 2(0.24) 其他少见G-菌(n = 19) 2(0.28) 4(0.57) 5(0.56) 4(0.47) 1(0.12) 3(0.37) 表 3 2015-2020年艾滋病住院患者血培养革兰阳性细菌耐药情况 [n(%)]
Table 3. Drug resistance of Gram-positive bacteria in blood culture of AIDS inpatients from 2015 to 2020 [n(%)]
革兰阳性细菌 克林霉素 环丙沙星 莫西沙星 左氧氟沙星 红霉素 青霉素G 庆大霉素 四环素 苯唑西林 利福平 SMZ 表皮葡萄球菌 n = 15 n = 14 n = 12 n = 14 n = 15 n = 13 n-14 n = 14 n = 14 n = 13 n = 12 S 3(20) 4(28.6) 4(33.3) 4(28.6) 0(0) 0(0) 6(42.8) 9(64.3) 2(14.3) 7(53.8) 2(16.7) I 0(0) 9(64.3) 1(8.3) 1(7.1) 0(0) 0(0) 3(21.4) 0(0) 0(0) 0(0) 0(0) R 12(80) 1(7.1) 7(58.3) 9(64.3) 15(100) 13(100) 5(35.7) 5(35.7) 12(85.7) 6(46.1) 10(83.3) 金黄色葡萄球菌 n = 14 n = 14 n = 9 n = 12 n = 13 n = 12 n = 14 n = 13 n = 13 n = 13 n = 13 S 5(35.7) 10(71.4) 8(88.9) 11(91.7) 3(23.1) 1(8.3) 12(85.7) 9(69.2) 9(69.2) 12(92.3) 8(61.5) I 0(0) 1(7.1) 0(0) 0(0) 0(0) 0(0) 1(7.1) 0(0) 0(0) 0(0) 0(0) R 9(64.3) 3(21.4) 1(11.1) 1(8.3) 10(76.9) 11(91.7) 1(7.1) 4(30.7) 4(30.8) 1(7.7) 5(38.5) 溶血葡萄球菌 n = 13 n = 13 n = 12 n = 13 n = 13 n = 13 n = 12 n = 12 n = 13 n = 12 n = 12 S 3(23.1) 1(7.7) 1(7.7) 1(7.7) 0(0) 1(7.7) 3(25) 10(83.3) 1(7.7) 7(58.3) 5(41.7) I 0(0) 0(0) 4(30.8) 0(0) 0(0) 0(0) 1(8.3) 0(0) 0(0) 0(0) 0(0) R 10(76.9) 12(92.3) 7(53.8) 12(92.3) 13(100) 12(92.3) 8(66.7) 2(16.6) 12(92.3) 5(41.7) 7(58.3) 人葡萄球菌 n = 14 n = 14 n = 14 n = 14 n = 14 n = 12 n = 13 n = 14 n = 14 n = 14 n = 14 S 2(14.3) 3(21.4) 3(21.4) 3(21.4) 1(7.1) 0(0) 12(92.3) 5(35.7) 3(21.4) 10(71.4) 4(28.6) I 1(7.1) 2(14.3) 3(21.4) 1(7.1) 0(0) 0(9) 1(7.7) 0(0) 0(0) 0(0) 0(0) R 11(78.6) 9(64.3) 8(57.1) 10(71.4) 13(92.9) 12(100) 0(0) 9(64.3) 11(78.6) 4(28.6) 10(71.4) 头状葡萄球菌 n = 8 n = 8 n = 7 n = 7 nN=8 n = 7 n = 8 n = 8 n = 8 n = 8 n = 8 S 6(75) 5(62.5) 4(57.1) 4(57.1) 2(25) 0(0) 7(87.5) 6(75) 5(62.5) 6(75) 6(75) I 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) R 2(25) 3(37.5) 3(42.8) 3(42.8) 6(75) 7(100) 1(12.5) 2(25) 3(37.5) 2(25) 2(25) 注:S:敏感,I:中介,R:耐药。 表 4 2015~2020年艾滋病住院患者血培养革兰阴性细菌耐药情况[n(%)]
Table 4. Drug resistance of Gram-negative bacteria in blood culture of AIDS inpatients from 2015 to 2020 [n(%)]
革兰阴性细菌 环丙沙星 左氧氟沙星 庆大霉素 氨苄西林 头孢曲松 头孢他啶 头孢比肟 氨曲南 阿米卡星 亚胺培南 美罗培南 大肠埃希菌 n = 17 n = 18 n = 18 n = 18 n = 18 n = 18 n = 15 n = 18 n = 17 n = 17 n = 5 S 6(35.3) 6(33.3) 13(72.2) 2(11.1) 5(27.8) 15(83.3) 13(86.7) 13(72.2) 17(100) 17(100) 5(100) I 0(0) 2(11.1) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) R 11(64.7) 10(55.6) 5(27.8) 16(88.9) 13(72.2) 3(16.7) 2(13.3) 5(27.8) 0(0) 0(0) 0(0) 沙门菌属 n = 12 n = 4 - n = 15 n = 11 n = 11 n = 1 n = 1 - n = 1 - S 6(50) 1(25) - 3(20) 10(90.9) 10(90.9) 1(100) 1(100) - 1(100) - I 6(50) 3(75) - 0(0) 0(0) 0(0) 0(0) 0(0) - 0(0) - R 0(0) 0(0) - 12(80) 1(9.1) 1(9.1) 0(0) 0(0) - 0(0) - 肺炎克雷伯杆菌 n = 11 n = 11 n = 11 n = 7 n = 11 n = 11 n = 11 n = 11 n = 11 n = 11 n = 5 S 5(45.4) 6(54.5) 6(54.5) 0(0) 5(45.5) 6(54.5) 6(54.5) 6(54.5) 8(72.7) 8(72.7) 3(60) I 1(9.2) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) R 5(45.4) 5(45.5) 5(45.5) 7(100) 6(54.5) 5(45.5) 5(45.5) 5(45.5) 3(27.3) 3(27.3) 2(40) 铜绿假单胞菌 n = 6 n = 6 n = 7 n = 2 n = 2 n = 6 n = 6 n = 4 n = 6 n = 6 n = 2 S 6(100) 5(83.3) 6(85.7) 0(0) 0(0) 5(83.3) 6(100) 3(75) 6(100) 5(83.3) 2(100) I 0(0) 1(16.7) 0(0) 0(0) 0(0) 1(16.7) 0(0) 0(0) 0(0) 0(0) 0(0) R 0(0) 0(0) 1(14.3) 2(100) 2(100) 0(0) 0(0) 1(25) 0(0) 1(16.7) 0(0) 鲍曼不动杆菌 n = 2 n = 3 n = 3 n = 2 n = 3 n = 2 n = 3 n = 1 n = 1 n = 3 n = 2 S 1(50) 1(33.3) 1(33.3) 0(0) 0(0) 1(50) 1(33.3) 0(0) 0(0) 1(33.3) 1(50) I 0(0) 1(33.3) 0(0) (0) 1(33.3) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) R 1(50) 1(33.3) 2(66.7) 2(100) 2(66.7) 1(50) 2(66.7) 1(100) 1(100) 2(66.7) 1(50) 注:S:敏感,I:中介,R:耐药。 表 5 2015-2020年艾滋病住院患者血培养细菌多重耐药情况[n(%)]
Table 5. Multiple drug resistance of blood culture bacteria of AIDS inpatients from 2015 to 2020 [n(%)]
细菌 R0 R1 R2 R3 R4 R5 ≥R6 革兰阳性菌(n = 83) 表皮葡萄球菌(n = 15) 0(0) 0(0) 0(0) 4(26.7) 1(6.6) 3(20) 7(46.7) 人葡萄球菌(n = 14) 0(0) 0(0) 1(7.1) 0(0) 4(28.6) 2(14.3) 7(50) 金黄色葡萄球(n = 14) 0(0) 2(14.3) 4(28.6) 1(7.1) 4(28.6) 2(14.3) 1(7.1) 溶血葡萄球菌(n = 13) 0(0) 0(0) 1(7.7) 0(0) 4(30.8) 1(7.7) 7(53.8) 头状葡萄球菌(n = 8) 0(0) 1(12.5) 4(50) 0(0) 1(12.5) 0(0) 2(25) 链球菌属(n = 6) 0(0) 1(16.7) 1(16.7) 3(50) 1(16.7) 0(0) 0(0) 其他少见G+(n = 13) 1(7.6) 1(7.6) 3(23.1) 1(7.6) 2(15.5) 0(0) 1(7.6) 革兰阴性菌(n = 70) 沙门菌属(n = 21) 7(33.3) 13(61.9) 1(4.8) 0(0) 0(0) 0(0) 0(0) 大肠埃希菌(n = 18) 1(5.6) 5(27.8) 2(11.1) 7(38.9) 3(16.6) 0(0) 0(0) 肺炎克雷伯杆菌(n = 11) 4(36.4) 1(9.1) 1(9.1) 0(0) 1(9.1) 1(9.1) 3(27.2) 铜绿假单胞菌(n = 7) 4(57.1) 0(0) 2(28.6) 0(0) 0(0) 1(14.3) 0(0) 鲍曼不动杆菌(n = 3) 1(33.3) 0(0) 0(0) 0(0) 0(0) 1(33.3) 1(33.3) 其他少见G-菌(n = 10) 3(30) 2(20) 1(10) 2(20) 0(0) 2(20) 0(0) 注:R0:对检测的抗菌药种类都敏感,R1:对1类抗菌药耐药,R2:对2类抗菌药耐药,R3:对3类抗菌药耐药,R4:对4类抗菌药耐药,R5:对5类抗菌药耐药,R6:对6类及以上抗菌药耐药。 -
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