Research progress in mechanisms of drug-resistance of macrolide antibiotics resistance in Mycoplasma pneumoniae
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摘要:
大环内酯类抗生素是治疗儿童肺炎支原体(MP)感染的一线药物，但随着此类药物在临床中的广泛使用，对大环内酯类抗生素耐药的MP菌株检出率迅速增高。耐药机制相关研究中，对药物作用靶点的研究最多见，其中23S rRNA基因突变相关研究尤为广泛和深入。耐药性会影响药物治疗效果，探讨菌株对药物的耐药机制并合理调整药物治疗方案，可获得更好的治疗效果，现将大环内酯类抗生素的作用机制和MP对大环内酯类抗生素的耐药机制综述如下。
Abstract:Macrolide antibiotics are the first-line drugs for the treatment of Mycoplasma pneumoniae (MP)infections in children, but with the increased use of macrolides, the detection rate of resistant strains of MP to macrolides has increased rapidly. Among the studies related to the mechanisms of drug resistance, the study of drug targets has been the most extensive and intensive, with mutations in the 23S rRNA gene being studied most extensively. The emergence of drug resistance affects the therapeutic efficacy of drugs, and the mechanisms of drug resistance need to be explored to adjust the choice of therapeutic agents in order to achieve higher therapeutic efficacy. This paper reviewed the mechanisms of action of macrolides and the mechanisms of resistance to macrolides by MP.
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断指是临床手外科的常见创伤性疾病，通常是因外伤或暴力而致，可导致不同程度神经、血管、肌腱等组织损伤，需及时采取断指再植术治疗[1-2]。既往临床上针对断指患者主要采取缩短指骨断指再植术治疗，虽具有一定疗效，但多数患者术后患指运动能力较差[3-4]。近年来，无缩短断指再植术中吻合血管游离腕横纹复合组织瓣桥修复成为临床关注点，主要是通过切取桡动脉掌浅支营养范围内正中神经手掌支、皮瓣及掌长肌腱，组成复合组织瓣，具有明显优势。本研究选取本院68例断指患者，探讨吻合血管游离腕横纹复合组织瓣桥修复在无缩短断指再植术中的应用效果，报告如下。
1. 资料与方法
1.1 一般资料
选取本院2015年1月—2018年3月断指患者68例，按治疗方案分为2组各34例。对照组女14例，男20例，年龄20~50岁，平均(34.15±9.63)岁，断指发生时间1.5~7.0 h，平均(2.76±0.41) h; 离断手指为环指9例，中指12例，食指13例。观察组女15例，男19例，年龄20~51岁，平均(35.02±10.16)岁，断指发生时间2.0~7.0 h, 平均(2.88±0.45) h; 离断手指为环指8例，中指11例，食指15例。2组性别、断指发生时间、年龄、离断手指等一般资料比较无显著性差异(P>0.05), 具有可比性。本研究符合《世界医学会赫尔辛基宣言》相关要求。纳入标准: 均属于断指患者; 均为单指离断; 均具备断指再植术指征; 患者及家属均知情，签订同意书。排除标准: 不具备断指再植术指征者; 存在手术禁忌者。
1.2 方法
观察组无缩短断指再植术中，采取吻合血管游离腕横纹复合组织瓣桥修复。轴心线选取患侧腕横纹，设计横行皮瓣(呈椭圆形)，尺侧需至腕屈肌肌腱，桡侧需至拇长展肌肌腱，将周围皮肤切开、游离，促使皮下组织充分显露。在显微镜辅助下，对桡动脉掌浅支进行解剖，至远端舟骨结节(2 cm左右)，切取范围3.0 cm×2.5 cm至6.5 cm×2.5 cm, 根据患者断指实际情况进行切取，包括正中神经掌皮支、掌长肌腱，组成复合组织瓣，对断指指骨创面采取游离移植桥接修复措施。吻合复合组织瓣浅、指背静脉，吻合指动脉远近端、桡动脉掌浅支两端。
对照组采用传统缩短指骨断指再植术。首先清理断指创面，将断端裸露指骨咬除，进行断指复位，采取内固定措施(钢针)，对损伤肌腱进行修整、缝合。在显微镜辅助下依次吻合断指神经、动静脉。2组均于术后采取抗痉挛、抗凝、抗感染等干预措施，并采取相应康复干预措施。
1.3 观察指标
① 治疗优良率。术后3个月采用Johner-Wuhs法评估，分为优、良、一般、差。优良率=(优+良)/总例数×100%。②康复进程，包括住院时间、康复总时间。③患者对患指外形满意度。采用本院自制量表评估，分为非常满意、满意、尚可、不满意。总满意度=(满意+非常满意)/总例数×100%。④生活质量。2组治疗前、治疗后3个月时采用简明健康状况量表(SF-36)评定，选取生理功能、社会功能、活力、生理职能4个方面，每个方面满分100分，得分越高表示生活质量越好。
1.4 统计学分析
采用SPSS 21.0软件处理数据，计数资料采用[n(%)]表示，行χ2检验，计量资料采用(x±s)表示，行t检验, P < 0.05为差异有统计学意义。
2. 结果
观察组治疗优良率91.18%, 显著高于对照组70.59%(P < 0.05), 见表 1。
表 1 2组治疗优良率比较[n(%)]治疗效果 观察组(n=34) 对照组(n=34) 优 20(58.82) 14(41.18) 良 11(32.35) 10(29.41) 一般 2(5.88) 6(17.65) 差 1(2.94) 4(11.76) 总优良 31(91.18)* 24(70.59) 与对照组比较, *P < 0.05。 观察组住院时间、康复总时间显著短于对照组(P < 0.05), 见表 2。观察组患者对患指外形满意度94.12%, 显著高于对照组73.53%(P < 0.05), 见表 3。观察组治疗后3个月生理功能、社会功能、活力、生理职能评分显著高于对照组(P < 0.05), 见表 4。
表 2 2组康复进程比较(x±s)组别 n 住院时间/d 康复总时间/月 观察组 34 13.81±3.76* 1.63±0.47* 对照组 34 18.35±4.05 2.28±0.34 与对照组比较, *P < 0.05。 表 3 2组患者对患指外形满意度比较[n(%)]满意情况 观察组(n=34) 对照组(n=34) 不满意 1(2.94) 4(11.76) 尚可 1(2.94) 5(14.71) 满意 10(29.41) 12(35.29) 非常满意 22(64.71) 13(38.24) 总满意 32(94.12)* 25(73.53) 与对照组比较, *P < 0.05。 表 4 2组生活质量比较(x±s)分 时点 组别 生理功能 社会功能 活力 生理职能 治疗前 观察组(n=34) 40.06±6.11 46.20±5.32 44.97±5.18 40.25±5.56 对照组(n=34) 40.35±5.79 46.71±6.03 45.01±5.33 40.44±5.37 治疗后3个月 观察组(n=34) 80.39±4.28* 85.14±4.10* 82.19±3.07* 81.01±3.09* 对照组(n=34) 77.20±3.27 80.06±3.86 78.37±4.28 78.96±2.95 与对照组比较, *P < 0.05。 3. 讨论
手部是人体重要部位之一，患者断指后，不仅影响手部精细活动，还对日常生活造成极大影响[5-7]。临床采取断指再植术治疗断指患者的主要目的是恢复手指外形，最大限度地恢复其活动功能[8-9]。由于手指部位解剖结构较为精细、复杂，手术操作难度较大，需采取有效、可靠的断指再植术。
本研究探讨断指患者在无缩短断指再植术中采取吻合血管游离腕横纹复合组织瓣桥修复的效果，结果显示，观察组治疗优良率显著高于对照组，住院时间、康复总时间显著短于对照组(P < 0.05), 表明该方案能提高治疗效果，缩短康复进程。腕横纹复合组织瓣具有供区隐蔽、无毛发、对手部血供影响小等优势，且其皮肤结构、质地接近手指皮肤，加之其位置表浅，血管直径大小符合指动脉静脉口径大小，不仅有助于吻接，恢复浅感觉，还可一次性串联桥接修补，避免操作困难等问题[10-12]。同时，该修复方法可通过复合组织瓣掌长肌腱、正中神经手掌支、动静脉分别吻接伸屈肌腱近远端、指固有神经近远端、指背静脉及指固有动脉近远端等操作，达到促使断指伸、屈指功能、手指感觉恢复及血管循环缺损修复等目的[13-14]。此外，供受区在同一术野，手术操作较为方便，加之桡动脉掌浅支血管解剖组织结构变异少，较为恒定，不仅可缩短手术时间，还可提高手术成功率，在不影响拇指功能的基础上缩短治疗时间[15-17]。本研究结果还显示，观察组患者对患指外形满意度显著高于对照组(P < 0.05)。本研究结果显示，观察组治疗后3个月生理功能、社会功能、活力、生理职能评分显著高于对照组(P < 0.05)。
综上所述，将吻合血管游离腕横纹复合组织瓣桥修复应用于断指患者无缩短断指再植术中，可明显提高治疗优良率，加快康复进程，且患者对患指外形满意度较高，可明显改善生活质量。
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