Correlation Analysis of Drug Resistance Characteristics of Pathogenic Bacteria in Inpatients with Diabetic Foot Infection
-
摘要:
目的 分析糖尿病足感染(DFI)患者多重耐药菌(MDRO)的细菌分布特点、耐药特点和相关危险因素。 方法 收集2019年1月至2023年12月云南省第三人民医院内分泌科收治的300例糖尿病足感染患者的临床资料,根据药物敏感试验结果及基本资料匹配,分为MDRO组(n = 60)、非MDRO组(n = 240),回顾性分析MDRO的病原菌分布、耐药特点及DFI患者发生MDRO感染的相关危险因素。 结果 60例MDRO感染患者共培养出MDRO 62株,单种MDRO感染58株,混合MDRO感染4株,其中2例患者分别培养出2种MDRO。在这些菌株中,革兰阳性菌有45株,所占比例为72.58%,且均为金黄色葡萄球菌;革兰阴性菌为17株,占比 27.42%,主要包括铜绿假单胞菌、阴沟肠杆菌和肺炎克雷伯菌。常见的MDRO中金黄色葡萄球菌对青霉素G、苯唑西林完全耐药(100%),对红霉素、克林霉素耐药性较高( > 80%),对替加环素、万古霉素未产生耐药;肺炎克雷伯菌、阴沟肠杆菌对头孢菌素类抗生素耐药明显,对亚胺培南、阿米卡星耐药率低;铜绿假单胞菌对替卡西林/克拉维酸钾、亚胺培南、替加环素、复方新诺明100%耐药,对头孢吡肟、环丙沙星、庆大霉素、阿米卡星未产生耐药。两组患者的地区分布、糖尿病足病程、下肢动脉病变、静脉血浆葡萄糖、糖化血红蛋白比较差异有统计学意义(P < 0.05)。二分类Logistic回归分析显示,地区、糖尿病足病程是DFI患者MDRO感染的独立危险因素(P < 0.05)。 结论 云南部分地区DFI患者MDRO分布主要为革兰阳性菌,不同病原菌对抗生素的敏感性不同,多种因素导致DFI患者发生MDRO感染,有助于临床工作者及早识别MDRO感染的DFI高危患者并为临床治疗提供经验性参考依据。 Abstract:Objective To analyze the bacterial distribution characteristics, drug resistance characteristics and related risk factors of multidrug-resistant organisms (MDRO) in patients with diabetic foot infection (DFI) in some areas of Yunnan Province to provide empirical reference for clinical treatment. Methods Clinical data of 300 DFI patients admitted to the Department of Endocrinology of the Third People's Hospital of Yunnan Province from January 2019 to December 2023 were collected. Based on the results of drug sensitivity tests and matching of basic data, patients were divided into the MDRO group (n = 60) and the non-MDRO group (n = 240). A retrospective analysis was conducted on the distribution of pathogenic bacteria, drug resistance characteristics of MDRO and risk factors for MDRO infection in DFI patients. Results In 60 patients with MDRO infections, 62 strains of MDRO were cultured, with 58 strains from single MDRO infections and 4 strains from mixed MDRO infections. Of the 60 patients, 2 were cultured for 2 types of MDRO. Among the strains, there were 45 gram-positive bacteria (72.58%) which were all Staphylococcus aureus, there were 17 strains of gram-negative bacteria (27.42%) mainly including Pseudomonas aeruginosa, Enterobacter cloacae and Klebsiella pneumoniae. Among common MDRO, Staphylococcus aureus showed complete resistance to penicillin G and oxacillin(100%), with high resistance to erythromycin and clindamycin ( > 80%), but no resistance to tigacycline vancomycin was observed;The resistance of Klebsiella pneumoniae and Enterobacter cloacae to cephalosporin antibiotics was obvious, and the resistance rate to imipenem and amikacin was low; Pseudomonas aeruginosa was 100% resistant to ticacillin/clavulanate potassium, imipenem, tigacycline and cotrimoxazole, but showed no resistance to cefepime, ciprofloxacin, gentamicin and amikacin. There were statistically significant differences between the two groups in regional distribution, duration of diabetic foot, lower extremity arterial disease, venous plasma glucose levels and glycosylated hemoglobin (P < 0.05). Binary Logistic regression analysis showed that region and duration of diabetic foot disease were independent risk factors for MDRO infection in DFI patients (P < 0.05). Conclusion In some areas of Yunnan Province, the distribution of MDRO in DFI patients is mainly gram-positive bacteria, with varying antibiotic sensitivities among different pathogens. Multiple factors lead to MDRO infections in DFI patients, which assists clinical practitioners in early identification of high-risk DFI patients with MDRO infections and provide empirical reference for clinical treatment. -
Key words:
- Diabetic foot infection /
- Pathogen resistance /
- Risk factor /
- Management measures
-
表 1 DFI患者MDRO培养及分布情况[n(%)]
Table 1. Culturing and distribution of MDRO in DFI patients [n(%)]
多重耐药菌 株数(n = 62) 构成比(%) 革兰阳性菌: 45 72.58 1.金黄色葡萄球菌 45 72.58 革兰阴性菌: 17 27.42 1.铜绿假单胞菌 7 11.30 2.阴沟肠杆菌 3 4.84 3.肺炎克雷伯菌 3 4.84 4.普通变形杆菌 1 1.61 5.奇异变形杆菌 1 1.61 6.摩根摩式菌 1 1.61 7.鲍曼不动杆菌 1 1.61 表 2 常见MDRO对常用抗菌药物的耐药率[n(%)]
Table 2. Resistance rates of common MDRO to commonly used antibacterial drugs [n(%)]
抗生素 金黄色葡萄球菌(n = 45) 肺炎克雷伯菌(n = 3) 阴沟肠杆菌(n = 3) 铜绿假单胞菌(n = 7) 耐药菌株数量 比例(%) 耐药菌株数量 比例(%) 耐药菌株数量 比例(%) 耐药菌株数量 比例(%) 青霉素G 45 100.00 − − − − − − 苯唑西林 45 100.00 − − − − − − 氨苄西林 − − 3 100.00 2 66.66 − − 哌拉西林 − − 1 33.33 1 33.33 3 42.85 头孢呋辛 − − 3 100.00 3 100.00 − − 头孢呋辛酯 − − 2 66.66 2 66.66 − − 头孢西丁 − − 3 100.00 3 100.00 − − 头孢他啶 − − 3 100.00 3 100.00 6 85.71 头孢曲松 − − 3 100.00 3 100.00 − − 头孢吡肟 − − 3 100.00 1 33.33 0 0.00 头孢唑啉 − − 3 100.00 3 100.00 − − 替卡西林/克拉维酸钾 − − − − − − 7 100.00 阿莫西林/克拉维酸 − − 3 100.00 3 100.00 − − 哌拉西林/他唑巴坦 − − 3 100.00 3 100.00 2 28.57 头孢哌酮/舒巴坦 − − 3 100.00 3 100.00 5 71.42 氨苄西林/舒巴坦 − − 3 100.00 3 100.00 − − 厄他培南 − − 3 100.00 2 66.66 − − 亚胺培南 − − 1 33.33 1 33.33 7 100.00 美罗培南 − − 3 100.00 0 0.00 6 85.71 氨曲南 − − 2 66.66 2 66.66 4 57.14 环丙沙星 6 13.33 3 100.00 2 66.66 0 0.00 莫西沙星 7 15.55 − − − − − − 左旋氧氟沙星 11 24.44 2 66.66 2 66.66 4 57.14 替加环素 0 0.00 − − 0 0.00 7 100.00 万古霉素 0 0.00 − − − − − − 复方新诺明 9 20.00 3 100.00 2 66.66 7 100.00 庆大霉素 7 15.55 2 66.66 2 66.66 0 0.00 阿米卡星 − − 2 66.66 0 0.00 0 0.00 四环素 13 28.88 − − − − − − 利福平 2 4.44 − − − − − − 达托霉素 1 2.22 − − − − − − 红霉素 36 80.00 − − − − − − 克林霉素 37 82.22 − − − − − − 表 3 DFI患者MDRO感染的相关因素分析[n(%)/($\bar x \pm s $)/ M(P25,P75)]
Table 3. Analysis of related factors for MDRO infection in DFI patients [n(%)/($\bar x \pm s $)/ M(P25,P75)]
相关因素 多重耐药组 非多重耐药组 t/χ2 P 性别 男 47(78.3) 188(78.3) 0.0001 1.000 女 13(21.7) 52(21.7) 年龄(岁) 60.87 ± 12.58 60.76 ± 12.15 −0.061 0.951 住院天数(d) 14.00(13.00,16.75) 15.00(13.00,18.00) −1.343 0.179 地区 昆明市 53(88.3) 232(96.7) 5.373 0.020* 其他地区 7(11.7) 8(3.3) 吸烟史(年) 有 22(36.7) 95(39.6) 0.443 0.801 无 38(63.3) 144(60.0) 饮酒史(年) 有 11(18.3) 35(14.6) 0.520 0.471 无 49(81.7) 205(85.4) 糖尿病病程(年) 10.00(5.00,17.00) 10.00(7.00,20.00) −1.033 0.301 糖尿病足病程(d) < 30 21(35.0) 131(54.6) 7.365 0.007* ≥30 39(65.0) 109(45.4) Wagner分级(级) 1~2级 8(13.3) 43(17.9) 2.290 0.318 3级 35(58.3) 114(47.5) 4~5级 17(28.3) 83(34.6) 颈部动脉病变 有 9(15.0) 40(16.7) 0.098 0.755 无 51(85.0) 200(83.3) 下肢动脉病变 有 28(46.7) 152(63.3) 5.739 0.017* 无 32(53.3) 87(36.3) BMI(kg/m2) 22.84(20.47,25.17) 22.86(21.36,24.60) −0.087 0.931 白细胞(109/L) 8.3000 (6.55,11.03)8.97(7.08,13.31) −1.631 0.103 血红蛋白(g/L) 116.03 ± 21.42 117.39 ± 23.13 0.413 0.680 中性粒细胞百分比(%) 73.10(64.60,79.67) 73.75(65.92,83.80) −0.805 0.421 降钙素原(ng/mL) 0.16(0.10,0.31) 0.17(0.07,0.49) −0.743 0.457 IL-6(pg/mL) 32.42(26.18,35.87) 37.42(12.12,72.16) −1.671 0.095 CRP(mg/L) 34.95(8.31,79.65) 47.17(10.65,96.27) −0.985 0.324 血沉(mm/h) 78.00(38.00,91.50) 78.00(50.75,85.00) −0.212 0.832 白蛋白(g/L) 34.45 ± 6.17 33.92 ± 6.14 −0.594 0.553 静脉血浆葡萄糖(mmol/L) 7.44(5.35,10.28) 9.43(6.36,14.36) −2.603 0.009* 糖化血红蛋白(%) 8.43(7.08,9.72) 8.95(7.66,11.20) −2.287 0.022* 甘油三酯(mmol/L) 1.15(0.89,1.37) 1.15(0.84,1.68) −0.691 0.490 总胆固醇(mmol/L) 3.26(2.93,3.91) 3.34(2.79,4.35) −0.567 0.571 高密度脂蛋白(mmol/L) 0.93(0.81,1.10) 0.93(0.78,1.20) −0.126 0.899 低密度脂蛋白(mmol/L) 1.84(1.49,2.37) 1.84(1.45,2.49) −0.206 0.837 *P < 0.05。 表 4 分类变量的赋值说明
Table 4. Assignment description of categorical variables
分类变量 赋值说明 地区 0 = 昆明地区,1 = 其他地区(包括大理白族自治州、楚雄彝族自治州、红河哈尼族彝族自治州和临沧市) 糖尿病足病程 0 = < 30 d,1 = ≥30 d 下肢动脉病变 0 = 无,1 = 有 表 5 DFI患者MDRO感染的二分类Logistic回归分析
Table 5. Binary Logistic regression analysis of MDRO infection in DFI patients
主要危险因素 B SE WaLd P OR 95% CI 地区 1.194 0.563 4.491 0.034∗ 3.229 1.094~9.950 糖尿病足病程 0.663 0.315 4.430 0.035∗ 1.941 1.047~3.601 下肢动脉病变 −0.564 0.301 3.517 0.061 0.569 0.315~1.026 静脉血浆葡萄糖 −0.042 0.028 2.218 0.136 0.959 0.907~1.013 糖化血红蛋白 0.002 0.057 0.001 0.971 1.004 0.896~1.120 *P < 0.05。 -
[1] Wang A,Lv G,Cheng X,et al. Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition)[J]. Burns Trauma,2020,8:tkaa017. doi: 10.1093/burnst/tkaa017 [2] 谷涌泉,冉兴无,郭连瑞,等. 中国糖尿病足诊治指南[J]. 中国临床医生杂志,2024,52(11):1287-1296. doi: 10.3969/j.issn.2095-8552.2024.11.007 [3] Zhang P,Lu J,Jing Y,et al. Global epidemiology of diabetic foot ulceration: A systematic review and meta-analysis †[J]. Annals of Medicine,2017,49(2):106-116. doi: 10.1080/07853890.2016.1231932 [4] 中华医学会糖尿病学分会,中华医学会感染病学分会,中华医学会组织修复与再生分会. 中国糖尿病足防治指南(2019版)(Ⅰ)[J]. 中华糖尿病杂志,2019,11(2):92-108. doi: 10.3760/cma.j.issn.1674-5809.2019.02.004 [5] 赵晨旭,周慧敏. 《中国糖尿病足诊治指南》解读[J]. 中国临床医生杂志,2021,49(12):1405-1408. doi: 10.3969/j.issn.2095-8552.2021.12.007 [6] 徐斌,李阳阳. 糖尿病足多重耐药菌感染的分布及耐药性的危险因素分析[J]. 实用医院临床杂志,2021,18(4):188-192. doi: 10.3969/j.issn.1672-6170.2021.04.054 [7] American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2019[J]. Diabetes Care,2019,42(Suppl 1):S13-S28. [8] Lipsky B A,Senneville É,Abbas Z G,et al. Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update)[J]. Diabetes/Metabolism Research and Reviews,2020,36(Suppl 1):e3280. [9] Clinical and Laboratory Standards Institute. M100S. Performance standards for antimicrobial susceptibility testing: twenty-sixth edition[S]. Wayne,PA: CLSI,2016. [10] 黄勋,邓子德,倪语星,等. 多重耐药菌医院感染预防与控制中国专家共识[J]. 中国感染控制杂志,2015,14(1):1-9. doi: 10.3969/j.issn.1671-9638.2015.01.001 [11] Saeedi P,Petersohn I,Salpea P,et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas,9th edition[J]. Diabetes Research and Clinical Practice,2019,157:107843. doi: 10.1016/j.diabres.2019.107843 [12] Zubair M,Ahmad J. Potential risk factors and outcomes of infection with multidrug resistance among diabetic patients having ulcers: 7 years study[J]. Diabetes & Metabolic Syndrome,2019,13(1):414-418. [13] Xia W,He W,Luo T,et al. Risk factors for multidrug-resistant bacterial infections in patients with diabetic foot ulcers: A systematic review and meta-analysis.[J]. Annals of palliative medicine,2021,10(12):12618-12630. doi: 10.21037/apm-21-3406 [14] Matheson E M,Bragg S W,Blackwelder R S. Diabetes-Related foot infections: diagnosis and treatment[J]. American Family Physician,2021,104(4):386-394. [15] Adeyemo A T,Kolawole B,Rotimi V O,et al. Multicentre study of the burden of multidrug-resistant bacteria in the aetiology of infected diabetic foot ulcers[J]. African Journal of Laboratory Medicine,2021,10(1):1261. [16] Guo H,Song Q,Mei S,et al. Distribution of multidrug-resistant bacterial infections in diabetic foot ulcers and risk factors for drug resistance: A retrospective analysis[J]. PeerJ,2023,11:e16162. doi: 10.7717/peerj.16162 [17] Li T,Li Z,Huang L,et al. Cigarette smoking and peripheral vascular disease are associated with increasing risk of ESKAPE pathogen infection in diabetic foot ulcers[J]. Diabetes,Metabolic Syndrome and Obesity: Targets and Therapy,2022,15:3271-3283. [18] Atlaw A,Kebede H B,Abdela A A,et al. Bacterial isolates from diabetic foot ulcers and their antimicrobial resistance profile from selected hospitals in Addis Ababa,Ethiopia[J]. Frontiers in Endocrinology,2022,13:987487. doi: 10.3389/fendo.2022.987487 [19] 邓飞,沈亚非,常红娟. 糖尿病足患者多药耐药菌感染病原学及其影响因素[J]. 中华医院感染学杂志,2023,33(15):2300-2304. [20] Yaghoubi S,Zekiy A O,Krutova M,et al. Tigecycline antibacterial activity,clinical effectiveness,and mechanisms and epidemiology of resistance: narrative review[J]. Eur J Clin Microbiol Infect Dis,2022,41(7):1003-1022. doi: 10.1007/s10096-020-04121-1 [21] 王维霞,王明贵. 基于非劣效性临床试验获批准后替加环素相关的死亡增多[J]. 中国感染与化疗杂志,2012,12(06):476. [22] Uçkay I,Berli M,Sendi P,et al. Principles and practice of antibiotic stewardship in the management of diabetic foot infections[J]. Curr Opin Infect Dis,2019,32(2):95-101. doi: 10.1097/QCO.0000000000000530 [23] 谷宏伟,李希娜,魏华,等. 糖尿病足溃疡患者细菌感染特点及耐药影响因素分析[J]. 临床药物治疗杂志,2022,20(11):76-79. doi: 10.3969/j.issn.1672-3384.2022.11.016 [24] Yan X,Song J fang,Zhang L,et al. Analysis of risk factors for multidrug-resistant organisms in diabetic foot infection[J]. BMC Endocrine Disorders,2022,22(1):46. doi: 10.1186/s12902-022-00957-0 [25] 陈丽华,杨婧,伍勇. 糖尿病足患者足分泌物分离菌分布及多重耐药影响因素分析[J]. 中国抗生素杂志,2018,43(10):1286-1290. doi: 10.3969/j.issn.1001-8689.2018.10.021 [26] Liu X,Ren Q,Zhai Y,et al. Risk factors for multidrug-resistant organisms infection in diabetic foot ulcer[J]. Infection and Drug Resistance,2022,15:1627-1635. doi: 10.2147/IDR.S359157