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目的 研究磺胺嘧啶银(SD-Ag)、莫匹罗星、克霉唑单用或联用对烧伤创面分离的甲氧西林耐药金黄色葡萄球菌(MRSA)的抗菌活性. 方法 收集2011年7-12月笔者单位收治的18例烧伤患者创面分泌物标本,共分离出18株连续、非重复MRSA.采用琼脂稀释的棋盘格法检测SD-Ag、莫匹罗星、克霉唑单用,SD-Ag和莫匹罗星联用,SD-Ag、莫匹罗星和克霉唑联用对MRSA的MIC、对50％菌株的MIC(MIC50)、对90％菌株的MIC(MIC90).检测上述联用药物对MRSA的部分抑菌浓度(FIG)指数以判断抗菌效应,其中FIC指数小于或等于0.5为协同、大于0.5且小于或等于1.0为相加、大于1.0且小于或等于4.0为无关、大于4.O为拮抗,将协同和相加视为有效,无关和拮抗视为无效,计算有效比并与总体比(假设为0)进行比较.对数据行二项分布单侧检验分析. 结果 SD-Ag、莫匹罗星、克霉唑单用对MRSA的MIC分别为8、2、2μg/mL,MIC50分别为8、16、2μg/mL,MIC90分别为16、64、2μg/mL.联合用药中各药物对MRSA的MIC较单用时降低3.1％ ～50.0％.SD-Ag和莫匹罗星联用时SD-Ag、莫匹罗星对MRSA的MIC50均较单用时降低75.0％,MIC90均较单用时降低87.5％；SD-A g、莫匹罗星和克霉唑联用时SD-A g、莫匹罗星和克霉唑对MRSA的MIC50分别较单用时降低75.0％、87.5％和50.0％,MIC90分别较单用时降低87.5％、96.9％和50.0％.SD-Ag和莫匹罗星联用抗菌效果中协同9例、相加7例、无关2例,无拮抗现象；SD-Ag、莫匹罗星和克霉唑联用抗菌效果中相加16例、无关2例,无协同或拮抗现象.2种药物联用或3种药物联用对MRSA的抗菌有效比均明显高于总体比(P值均小于0.01). 结论 对于金黄色葡萄球菌以及金黄色葡萄球菌和真菌混合感染的中、后期烧伤创面,应用较低剂量的SD-Ag或联合应用上述药物既可有效控制感染又可减少药物对创面愈合的不良影响.

Objective To investigate the antibacterial activity of silver sulfadiazine (SD-Ag),mupirocin,and clotrimazole used alone or in combination against methicillin-resistant Staphylococcus aureus (MRSA) isolated from burn wounds.Methods Eighteen MRSA isolates from wound excretion of 18 burn patients hospitalized in our unit from July to December 2011 were collected continuously and non-repetitively.(1) Minimum inhibitory concentration (MIC),50％ MIC (MIC50),and 90％ MIC (MIC90) of SD-Ag,mupirocin,and clotrimazole used alone,those of SD-Ag and mupirocin used in combination,and those of SD-Ag,mupirocin,and clotrimazole used in combination to MRSA were determined by checkerboard agar dilution method.(2) Fractional inhibitory concentration (FIC) index was calculated to determine the combined effect of SD-Ag plus mupirocin,and SD-Ag plus mupirocin and clotrimazole.Synergy with FIC index less than or equal to 0.5 or additivity with FIC index more than 0.5 and less than or equal to 1.0 was regarded as effective,and indifference with FIC index more than 1.0 and less than or equal to 4.0 or antagonism with FIC index more than 4.0 was regarded as ineffective.The effective ratio was compared with overall ratio (assumed as 0) by unilateral binomial distribution test.Results The MIC,MIC50,and MIC90 of SD-Ag,mupirocin,and clotrimazole used alone against 18 MRSA isolates were respectively 8,8,16 μg/mL; 2,16,64 μg/mL; 2,2,2 μg/mL.MIC of antimicrobial agents used in combination decreased from 3.1％ to 50.0％ as compared with that of individual agent used alone.Compared with those of single application of SD-Ag and mupirocin,MICs0 of SD-Ag and that of mupirocin both decreased 75.0％,and MIC90 of them decreased 87.5％ when SD-Ag and mupirocin were used in combination.Compared with those of single application of SD-Ag,mupirocin,and clotrimazole,MIC50 of SD-Ag,mupirocin,and clotrimazole respectively decreased 75.0％,87.5％,and 50.0％ ; MIC90 of them respectively decreased 87.5％,96.9％,and 50.0％ when SD-Ag,mupirocin,and clotrimazole were used in combination.Among the 18 MRSA isolates,the combined effect of SD-Ag and mupirocin was synergic in 9 isolates,additive in 7 isolates,indifferent in 2 isolates,and antagonistic in 0 isolate; the combined effect of SD-Ag,mupirocin,and clotrimazole was additive in 16 isolates,indifferent in 2 isolates,and antagonistic in 0 isolate.There were statistically significant differences between effective ratio and overall ratio of 18 MRSA isolates treated with combined antimicrobial agents (P values all above 0.01).Conclusions For burn wounds at middle and late stages infected with Staphylococcus aureus or Staphylococcus aureus and Fungus,low dose of SD-Ag or combination of above-mentioned antimicrobial agents can effectively control infection and decrease the adverse effect of antimicrobial agents on wound healing.