创伤后骨感染患者多次住院细菌谱及耐药性变化规律的研究

Changes of bacterial spectrum and drug resistance in patients with posttraumatic bone infection

目的探讨多次住院后骨感染患者细菌谱及耐药性变化。方法采用回顾性病例系列研究分析沈阳军区总医院2009年1月-2016年12月收治的95例外伤致骨感染患者的临床资料，其中男76例，女34例；年龄17～94岁，平均47岁。取骨创伤感染分泌物、感染骨组织等246个标本做细菌培养及药敏试验，统计全部标本的细菌种类及耐药性数据，并根据住院次数变化分别统计革兰阳性菌与革兰阴性菌的数量及比值变化，记录金黄色葡萄球菌多次住院后耐药性的变化。结果共分离出病原菌110株，混合感染占19％。革兰阳性球菌61株（55．5％），其中金黄色葡萄球菌35株[耐甲氧西林金黄色葡萄球菌株（MRSA）7株]，占革兰阳性球菌株的57％，其余主要的革兰阳性球菌有粪肠球菌、表皮葡萄球菌。革兰阴性杆菌48株（43．6％），其中铜绿假单胞菌12株，占革兰阴性杆菌株的25％；肺炎克雷伯杆菌9株，占革兰阴性杆菌株的19％。金黄色葡萄球菌对青霉素的耐药率达82％。主要的革兰阳性球菌（金黄色葡萄球菌、肠类球菌、表皮葡萄球菌）均对万古霉素及利奈唑胺的敏感性较高。主要的革兰阴性杆菌（铜绿假单胞菌、肺炎克雷伯杆菌、大肠埃希菌、鲍曼不动杆菌）对二代头孢类抗生素耐药性较高，对碳青霉烯类抗生素具有较好的敏感性。95例骨感染患者首次住院时革兰阳性球菌与革兰阴性杆菌检出数量比值为0．98，多次住院后这一比值变为3，数量比值变化差异有统计学意义（P〈0．05）。多次住院后金黄色葡萄球菌对庆大霉素、环丙沙星、左氧氟沙星、四环素等抗生素的耐药性逐渐升高，对青霉素的耐药率甚至高达100％（P〈0．05）；对万古霉素或利奈唑胺敏感性较好。结论骨感染混合感染比较常见，其中金黄色葡萄球菌、粪肠球菌是主要革兰阳性致病菌，铜绿假单胞菌及肺炎克雷伯杆菌为主要的革兰阴性致病菌。多次住院后革兰阳性球菌感染占比增加，成为主要致病菌。治疗多次住院金黄色葡萄球菌感染应避免使用青霉素，慎用庆大霉素、环丙沙星等耐药性较高的抗生素，宜选用较敏感的万古霉素或利奈唑胺。

Objective To investigate the bacterial spectrum and drug resistance of bone infection after multiple hospitalizations. Methods A retrospective case series study was conducted on 95 patients with bone infection due to injuries admitted in the Ceneral Hospital of Shenyang Military Area from January 2009 to December 2016. There were 76 males and 34 females, with an average age of 47 years （range, 17-94 years）. Bacterial culture and drug sensitivity tests were performed in 246specimens of the infection secretions and infected tissues. The bacterial species and drug resistance data of all the specimens were statistically analyzed. The numbers and ratios of Gram-positive bacteria and Gram negative bacteria were counted according to the changes of hospitalization frequency, and the changes of drug resistance of Staphylococcus aureus after repeated hospitalizations were also recorded. Results A total of 110 pathogenic bacteria were isolated, and mixed infection was found in 19% of the bacteria. There were 61 Gram-positive bacteria （55.5%） , including 35 Staphylococcus aureus [ seven methicillin-resistant staphylococcus （MRSA） strains ], accounting for 57% of Gram-positive strains. Other Gram positive bacteria were mainly Enterococcus faecalis and Staphylococcus epidermidis. There were 48 Gram-negative bacteria （43.6%）, including 12 Pseudomonas aeruginosa strains, accounting for 25% of Gram-negative strains, nine Klebsiella pneumoniae strains, accounting for 19% of the Gram- negative strains. Staphylococcus aureus had a resistance rate to penicillin of 82% , and the major Gram positive bacteria （Staphylococcus aureus, Enterococcus faecalis, Staphylococcus epidermidis） were all highly sensitive to vancomycin and linezolid. The major Gram-negative bacteria （Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii） were highly resistant to the second generation of cephalosporins and were sensitive to carbapenem antibiotics. In 95 bone infection patients, the ratio of Gram positive bacteria to Gram negative bacteria increased from 0.98 at the first admission to 3 after repeated hospitalizations, and the ratio change was statistically significant （ P 〈 0.05 ）. After multiple hospitalizations, the drug resistance of Staphylococcus aureus to gentamicin, ciprofloxacin, levofloxacin, and tetracycline increased gradually. The resistance rate to penicillin was even up to 100%. Conclusions The mixed infection of bone infection is common, among which Staphylococcus aureus and Staphylococcus epidermidis are the main Gram-positive pathogenic bacteria, Pseudomonas aeruginosa and Klebsiella pneumoniae are the main Gram negative pathogenic bacteria. The proportion of Gram-positive bacteria infection increased after multiple hospitalizations and became the major pathogenic bacteria. Penicillin should be avoided in the treatment of Staphylococcus aureus infection in multiple hospitalizations, and gentamicin and ciprofloxacin should be used with caution. Vancomycin or linezolid which is more sensitive is a better option.