[Effects of application of vancomycin in the early stage of patients with extremely severe burn].

Objective: To evaluate the effects of application of vancomycin in the early stage of patients with extremely severe burn, in order to provide reference to drug for anti-infection treatment in the early stage of patients with extremely severe burn. Methods: Data of 15 patients of Kunshan explosion on August 2nd, 2014, admitted to the Department of Intensive Care in our hospital were retrospectively analyzed. The clinical efficacy of continuously intravenous dripping of vancomycin (combined with imipenem) in the early stage of burns (before and on post burn day 14) was analyzed. (1) The steady state plasma concentration of vancomycin was monitored respectively 30 min before the third, sixth, and tenth medication with direct chemiluminescent imaging method. (2) The distribution of Gram-positive bacteria of patients during hospitalization and their drug resistance to 14 antibiotics commonly used in clinic were analyzed. (3) Serum level of procalcitonin (PCT), white blood cell count, percentage of neutrophils before and after treatment, and efficacy grade of anti-infection treatment in the early stage of burns were analyzed. (4) Serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine before and after treatment, and the adverse effects during medication were analyzed. The WHONET 5.5 statistical software was used to analyze the distribution of Gram-positive bacteria in all the pathogens, and the status of drug resistance of Gram-positive bacteria to 14 antibiotics. Data were processed with Wilcoxon rank sum test. Results: (1) Twenty-nine times of steady state plasma concentration monitoring were performed in the patients in total, with the steady state plasma concentration of vancomycin from 4.3 to 42.1 μg/mL. In the monitoring before third, sixth, and tenth medication, the percentages of result reaching the standard were respectively 1, 3/14, and 2/7. (2) A total of 79 Gram-positive bacteria were isolated, including 49 (62.03%) strains of Staphylococcus aureus, 9 (11.39%) strains of Staphylococcus haemolyticus, 7 (8.86%) strains of Staphylococcus epidermidis, 12 (15.19%) strains of Enterococcus faecium, and 2 (2.53%) strains of Enterococcus faecalis. The above-mentioned Staphylococcus strains were with high drug resistance to antibiotics including penicillins, erythromycin, ciprofloxacin, and low drug resistance to linezolid, teicoplanin, and nitrofurantoin. The above-mentioned Enterococcus strains were with high drug resistance to antibiotics including erythromycin, ciprofloxacin, gentamicin, and low drug resistance to linezolid and teicoplanin. The above-mentioned Staphylococcus strains were all sensitive to vancomycin. Two strains of vancomycin-resistant Enterococcus were detected in the above-mentioned Enterococcus strains. (3) Serum level of PCT, white blood cell count, percentage of neutrophils of patients were (8.1±7.5) ng/mL, (24±10)×10(9)/L, and 0.898±0.029 before treatment, which were significantly higher than (3.0±2.8) ng/mL, (12±5)×10(9)/L, and 0.867±0.016 after treatment (with Z values respectively -2.103, -3.237, and -3.068, P<0.05 or P<0.01). After the early treatment, excellence, progess, and invalid results were achieved in 7, 5, and 3 patients, with the effective percentage of 4/5 in clinic. (4) There were no statistically significant differences in serum levels of AST, ALT, and creatinine of patients between before and after treatment (with Z values respectively-0.057, -1.508, and -1.363, P values above 0.05). Only one patient had liver and renal dysfunction during treatment. Conclusions: The positive and reasonable use of vancomycin can remove most of the Gram-positive bacteria, and control the development of sepsis combined with imipenem in the early stage of patients with extremely severe burn. However, the dose of vancomycin should be individualized and the steady state plasma concentration should be monitored to maintain the blood concentration within the safe and effective range, so as to improve the rational use of vancomycin.目的： 评价特重度烧伤患者早期应用万古霉素的效果，为特重度烧伤患者早期抗感染治疗提供用药参考。 方法： 回顾性分析笔者单位重症医学科在2014年8月2日昆山爆炸事故中收治的15例特重度烧伤患者的资料，对其早期(伤后14 d及其内)使用万古霉素持续静脉滴注(联合亚胺培南)治疗的效果进行统计分析。(1)分别在第3、6、10次给药前30 min采用直接化学发光法监测万古霉素稳态血药浓度。(2)统计患者住院期间检出的革兰阳性菌分布及其对14种常见抗菌药物的耐药性。(3)统计患者治疗前后的血清降钙素原(PCT)、白细胞计数、中性粒细胞，以及烧伤早期抗感染疗效评级。(4)患者治疗前后血清AST、ALT、肌酐水平及治疗期间的不良反应情况。采用WHONET 5.5统计软件分析病原菌中革兰阳性菌分布情况，以及革兰阳性菌对14种常见抗菌药物的耐药情况。对数据行Wilcoxon秩和检验。 结果： (1)本组患者共进行了29次稳态血药浓度监测，万古霉素稳态血药浓度波动于4.3～42.1 μg/mL，在第3、6、10次给药前监测中，稳态血药浓度达标比分别为1、3/14、2/7。(2)共分离到79株革兰阳性菌，其中金黄色葡萄球菌49株，占62.03%；溶血葡萄球菌9株，占11.39%；表皮葡萄球菌7株，占8.86%；屎肠球菌12株，占15.19%；粪肠球菌2株，占2.53%。前述葡萄球菌属细菌对青霉素类抗菌药物、红霉素及环丙沙星耐药率高，对利奈唑胺、替考拉宁及呋喃妥因耐药率低。前述肠球菌属细菌对红霉素、环丙沙星及庆大霉素耐药率高，对利奈唑胺和替考拉宁耐药率低。前述葡萄球菌属细菌对万古霉素均敏感，前述肠球菌属细菌检出2株抗万古霉素肠球菌。(3)本组患者治疗前血清PCT、白细胞计数和中性粒细胞为(8.1±7.5)ng/mL、(24±10)×10(9)/L、0.898±0.029，均明显高于治疗后的(3.0±2.8)ng/mL、(12±5)×10(9)/L、0.867±0.016(Z值分别为－2.103、－3.237、－3.068，P<0.05或P<0.01)。本组患者早期治疗后，显效7例、进步5例、无效3例，临床有效比4/5。(4)本组患者治疗前后AST、ALT、肌酐水平差异无统计学意义(Z值分别为－0.057、－1.508、－1.363，P值均大于0.05)。治疗期间仅有1例患者肝肾功能指标出现了明显异常。 结论： 特重度烧伤患者在烧伤早期积极合理地应用万古霉素清除了大部分革兰阳性菌，联合亚胺培南治疗控制了感染发展，但万古霉素治疗剂量应个体化并注意规律监测稳态血药浓度，根据结果及时用药调整，使其稳态血药浓度维持在有效安全范围内，从而提高万古霉素合理用药水平。.