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北京大学学报（医学版） ›› 2022, Vol. 54 ›› Issue (1): 68-76. doi: 10.19723/j.issn.1671-167X.2022.01.011

• 论著 • 上一篇    下一篇

口腔鳞状细胞癌患者修复重建术后感染的病原学特征及感染风险预测模型的构建

苏俊琪1,宋扬1,谢尚2,△()   

  1. 1.北京大学口腔医学院·口腔医院 检验科,北京 100081
    2.北京大学口腔医学院·口腔医院 口腔颌面外科,国家口腔医学中心,国家口腔疾病临床医学研究中心,口腔数字化医疗技术和材料国家工程实验室,口腔数字医学北京市重点实验室,国家卫生健康委员会口腔医学计算机应用工程技术研究中心,国家药品监督管理局口腔生物材料重点实验室,北京 100081
  • 收稿日期:2021-10-10 出版日期:2022-02-18 发布日期:2022-02-21
  • 通讯作者: 谢尚 E-mail:xs2013@hsc.pku.edu.cn
  • 基金资助:
    国家自然科学基金(82002878);北京大学口腔医院青年基金(YS020219)

Analysis of etiological characteristics and establishment of prediction model of postoperative infections in patients undergoing oral squamous cell carcinoma surgery with free flap reconstruction

SU Jun-qi1,SONG Yang1,XIE Shang2,△()   

  1. 1. Department of Clinical Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, China
    2. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & NHC Research Center of Engineering and Technology for Computerized Dentistry & NMPA Key Laboratory for Dental Materials, Beijing 100081, China
  • Received:2021-10-10 Online:2022-02-18 Published:2022-02-21
  • Contact: Shang XIE E-mail:xs2013@hsc.pku.edu.cn
  • Supported by:
    Nation Natural Science Foundation of China(82002878);Peking University Hospital of Stomatology Young Foundation(YS020219)

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摘要：

目的: 旨在发现行根治性肿瘤切除、颈淋巴结清扫并游离皮瓣修复重建术的原发性口腔鳞状细胞癌患者术后感染的病原学特征,并构建感染风险预测模型。方法: 选取2018年1月至2020年12月在北京大学口腔医院行根治性肿瘤切除并游离皮瓣修复重建术的口腔鳞状细胞癌患者1 596例为研究对象,按照患者术后感染发生情况分为感染组(n=154)和未感染组(n=1 442), 分析感染组患者的病原菌特征。以患者是否发生术后感染作为结果变量,采用单因素和多因素Logistic回归分析来确定术后感染的相关因素,并用于构建感染风险预测模型,采用受试者工作特征(receiver operating characteristic,ROC)曲线评估模型的预测效能。结果: 1 596例口腔鳞状细胞癌患者行修复重建术后发生感染154例,感染率为9.65%,感染部位以手术切口和呼吸道为主;共培养分离病原菌268株,其中革兰阴性菌240株,占89.55%,以铜绿假单胞菌(Pseudomonas aeruginosa)和肺炎克雷伯菌(Klebsiella pneumoniae)为主;革兰阳性菌23株,占8.58%,以粪肠球菌(Enterococcus faecalis)和金黄色葡萄球菌(Staphylococcus aureus)为主;真菌5株,占1.87%。分离出的铜绿假单胞菌对亚胺培南和美罗培南的耐药率较高,对环丙沙星等比较敏感;分离出的金黄色葡萄球菌对红霉素和克林霉素耐药率较高,对万古霉素敏感。N分期≥1、美国麻醉医师协会(American Society of Anesthesiologists,ASA)分级≥Ⅱ级、气管切开、住院天数>13 d是患者术后感染的独立危险因素(P<0.05), 据此构建感染风险预测模型的表达式为:预测概率值P=1/(1+e-a),a=-0.803+0.674×(N分期≥1)+0.518×(ASA分级≥Ⅱ级)+0.918×(气管切开)+1.581×(住院天数>13 d),Hosmer-Lemeshow χ2=10.647,P=0.223,提示模型的拟合度较好。模型预测患者术后感染的ROC曲线下面积为0.818,95%CI为0.789~0.846。结论: 口腔鳞状细胞癌修复重建术后感染发生率较高,主要致病菌为革兰阴性菌。多因素Logistic回归分析构建的感染预测模型可以有效预测口腔鳞状细胞癌修复重建术后感染的发生,使临床能够有针对性地采取监测和干预措施,合理使用抗菌药物,有利于预防和减少术后感染。

关键词: 鳞状细胞癌, 口腔外科手术, 病原体, 抗药性, 细菌, 危险因素

Abstract:

Objective: To investigate the characteristics of pathogen infection and to establish a prediction model of infections in oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction. Methods: The retrospective cohort study consisted of 1 596 patients undergoing tumor resection and free flap reconstruction for oral squamous cell carcinoma from January 2018 to December 2020. According to the postoperative infection, the patients were divided into the infected group (n=154) and non-infected group (n=1 442). The characteristics of pathogens were analyzed in the infected patients. The primary outcome variable was postoperative infection, and Logistic regression was used to determine risk factors of the infection. The prediction model was established and the discriminatory accuracy of the model was evaluated using receiver operating characteristic (ROC) curve. Results: Totally 154 cases were infected in the 1 596 cases undergoing surgery with free flap reconstruction, and the infection rate was 9.65%. The most frequent sites of infection were the surgical wound and respiratory tract. A total of 268 pathogens were isolated and cultured, including 240 strains of Gram-negative bacteria, accounting for 89.55%, mainly Pseudomonas aeruginosa and Klebsiella pneumoniae; 23 strains of Gram-positive bacteria, accounting for 8.58%, mainly Enterococcus faecalis and Staphylococcus aureus; and 5 strains of fungi, accounting for 1.87%. The isolated Pseudomonas aeruginosa had high resistant rate to imipenem and meropenem, and was sensitive to antibiotics, such as ciprofloxacin. The isolated Staphylococcus aureus had high resistant rate to erythromycin and clindamycin, and was sensitive to vancomycin. According to the multivariate Logistic analysis, four independent variables were significantly associated with an increased risk of postoperative infection (P<0.05): clinical N category≥1, the American Society of Anesthesiologists (ASA) grade ≥2, tracheotomy and length of hospital stay >13 d. The prediction model was established based on these factors and the expression of the risk prediction model was as follows: predicted probability value P=1/(1+e-a), a=-0.803+0.674×(clinical N category ≥1)+0.518×(the ASA grade ≥2)+0.918×(tracheotomy)+1.581×(length of hospital stay >13 d), Hosmer-Lemeshow χ2=10.647, P=0.223, the degree of fitting of the model was good. The area under the ROC curve was 0.818 and 95%CI of the model for predicting infection was 0.789-0.846. Conclusion: Oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction are prone to have a high incidence of postoperative infection and Gram-negative bacteria are the main pathogens causing an infection. The established prediction model is of good predictive effect. Rational antimicrobial use coupled with awareness of infection control measures is paramount to reduce the incidence of postoperative infection in the oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction.

Key words: Squamous cell carcinoma, Oral surgical procedures, Pathogen, Drug resistance, bacterial, Risk factors

中图分类号: 

  • R782.3

表1

口腔鳞状细胞癌感染患者术后感染部位分布及构成比"

Infection site n Constituent ratio/%
Surgical wound 91 59.09
Respiratory tract 59 38.31
Skin and soft tissue 3 1.95
Urinary tract 1 0.65
Total 154 100.00

表2

口腔鳞状细胞癌感染患者病原菌分布及构成比"

Pathogenic bacteria No. of strains Constituent ratio/%
Gram-negative bacteria
Pseudomonsa aeruginosa 87 32.46
Klebsiella pneumoniae 56 20.90
Enterobacter cloacae 23 8.58
Acinetobacter baumanii 20 7.46
Serratia marcescens 12 4.48
Escherichia coli 12 4.48
Klebsiella oxytoca 7 2.61
Proteus mirabilis 6 2.24
Stenotrophomonas maltophilia 4 1.49
Morganella morganii 3 1.12
Enterobacter aerogenes 3 1.12
Others 7 2.61
Gram-positive bacteria
Enterococcus faecalis 9 3.36
Staphylococcus aureus 8 2.99
Staphylococcus epidermidis 3 1.12
Streptococcus penumoniae 2 0.75
Streptococcus agalactiae 1 0.37
Fungi
Candida albicans 3 1.12
Candida tropicalis 1 0.37
Candida krusei 1 0.37
Total 268 100.00

表3

口腔鳞状细胞癌感染患者主要革兰阴性菌的耐药情况"

Antibacterial drug Pseudomonsa
aeruginosa (n=87)		 Klebsiella
pneumoniae (n=56)		 Enterobacter
cloacae (n=23)		 Acinetobacter
baumanii (n=20)
No. of resistant
strains		 DRR/% No. of resistant
strains		 DRR/% No. of resistant
strains		 DRR/% No. of resistant
strains		 DRR/%
Cephalosporin class
Cefazolin - - 19 33.93 - - - -
Cefoxitin - - 7 12.50 - - - -
Cefuroxime - - 21 37.50 - - - -
Cefoperazone - - 16 28.57 5 21.74 - -
Aztreonam 4 4.60 7 12.50 6 26.09 - -
Cefotaxime - - 17 30.36 7 30.43 0 0
Ceftriaxome - - 17 30.36 6 26.09 0 0
Ceftazidime 3 3.45 4 7.14 7 30.43 0 0
Cefepime 0 0 7 12.50 3 13.04 0 0
Penicillin class
Piperacillin 3 3.45 21 37.50 6 26.09 0 0
Carbapenem class
Imipenem 10 11.49 0 0 0 0 0 0
Meropenem 6 6.90 0 0 0 0 0 0
Cephalosporin-enzyme inhibitors
Ampicillin-sulbactam - - 7 12.50 - - 1 5.00
Piperacillin-tazobactam 4 4.60 1 1.79 1 4.35 0 0
Aminoglycosides class
Gentamicin 2 2.30 11 19.64 3 13.04 0 0
Amikacin 1 1.15 0 0 0 0 0 0
Quinolone class
Levofloxacin 1 1.15 3 5.36 1 4.35 0 0
Ciprofloxacin 0 0 - - - - - -
Sulfa class
Trimethoprim-sulfamethoxazole - - 19 33.93 3 13.04 2 10.00
Tetracycline class
Minocycline - - 13 23.21 1 4.35 1 5.00

表4

口腔鳞状细胞癌感染患者主要革兰阳性菌的耐药情况"

Antibacterial drug Enterococcus faecalis (n=9) Staphylococcus aureus (n=8) Staphylococcus epidermidis (n=3)
No. of resistant strains DRR/% No. of resistant strains DRR/% No. of resistant strains DRR/%
Penicillin 0 0 8 100.00 3 100.00
Cefoxitin - - 1 12.50 3 100.00
Ampicillin 0 0 - - - -
Linezolid 0 0 0 0 0 0
Teicoplanin 0 0 0 0 0 0
Levofloxacin 0 0 2 25.00 1 33.33
Gentamicin - - 0 0 1 33.33
High-dose gentamicin 1 11.11 - - - -
Erythromycin 6 66.67 4 50.00 2 66.67
Clindamycin - - 4 50.00 1 33.33
Trimethoprim-sulfamethoxazole - - 0 0 2 66.67
Minocycline - - 0 0 0 0
Vancomycin 0 0 0 0 0 0

表5

口腔鳞状细胞癌患者术后感染的单因素和多因素Logistic回归分析"

Variables Postoperative infection Univariate analysis Multivariate analysis
Yes No
n % n % OR 95%CI P OR 95%CI P
Gender
Male 116 75.3 892 61.9 1.88 1.3-2.8 0.001
Female 38 24.7 550 38.1
Age/years
>60 65 42.2 696 48.3 0.78 0.6-1.1 0.153
≤60 89 57.8 746 51.7
BMI/(kg/m2)
≤23 53 34.4 339 23.5 1.71 1.2-2.4 0.003
>23 101 65.6 1 103 76.5
Clinical T category
T3-T4 120 77.9 603 41.8 4.91 3.3-7.3 <0.001
T1-T2 34 22.1 839 58.2
Clinical N category
N+ 100 64.9 495 34.3 3.54 2.5-5.0 <0.001 1.961 1.3-2.9 0.001
N0 54 35.1 947 65.7
ASA score
≥Ⅱ 132 85.7 1 086 75.3 1.97 1.2-3.1 0.005 1.679 1.0-2.8 0.043
<Ⅱ 22 14.3 356 24.7
Preoperative WBC count
>6.3×109/L 94 61.0 697 48.3 1.68 1.2-2.4 0.003
≤6.3×109/L 60 39.0 745 51.7
Preoperative serum Alb/(g/L)
≤41 98 63.6 757 52.5 1.58 1.1-2.2 0.009
>41 56 36.4 685 47.5
Diabetes mellitus
Yes 25 16.2 184 12.8 1.33 0.8-2.1 0.226
No 129 83.8 1 258 87.2
Hypertension
Yes 52 33.8 431 29.9 1.20 0.8-1.7 0.320
No 102 66.2 1 011 70.1
Tumor diameter/cm
>3 106 68.8 533 37.0 3.77 2.6-5.4 <0.001
≤3 48 31.2 909 63.0
Bone resection
Yes 116 75.3 803 55.7 2.43 1.7-3.5 <0.001
No 38 24.7 638 44.3
Type of free-flap reconstruction
Osseous 47 30.5 251 17.4 2.08 1.4-3.0 <0.001
Non-osseous 107 69.5 1 191 82.6
Neck dissection
Bilateral 54 35.1 251 17.4 2.56 1.8-3.7 <0.001
Ipsilateral 100 64.9 1 190 82.6
Titanium plate reconstruction
Yes 83 53.9 442 30.7 2.65 1.9-3.7 <0.001
No 71 46.1 1 000 69.3
Tracheotomy
Yes 126 81.8 569 39.5 6.89 4.5-10.5 <0.001 2.503 1.5-4.1 <0.001
No 28 18.2 871 60.5
Operative duration/min
>260 125 81.2 667 46.3 5.01 3.3-7.6 <0.001
≤260 29 18.8 775 53.7
Blood loss/mL
>200 109 70.8 555 38.5 3.87 2.7-5.6 <0.001
≤200 45 29.2 887 61.5
Length of hospital stay/d
>13 135 87.7 596 41.3 10.09 6.2-16.5 <0.001 4.862 2.9-8.3 <0.001
≤13 19 12.3 846 58.7

表6

口腔鳞状细胞癌患者修复重建术后感染的风险预测模型"

Characteristic β SE Wald OR 95%CI P
Clinical N category 0.674 0.195 11.963 1.961 1.339-2.873 0.001
ASA score 0.518 0.256 4.088 1.679 1.016-2.773 0.043
Tracheotomy 0.918 0.257 12.782 2.503 1.514-4.140 <0.001
Length of hospital stay 1.581 0.270 34.194 4.862 2.862-8.261 <0.001

图1

口腔鳞状细胞癌患者修复重建术后感染风险预测模型的ROC曲线"

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ISSN 1671-167X
CN 11-4691/R
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