2006-2011年金黄色葡萄球菌耐药性变迁分析

目的 分析我院2006年1月—2011年12月金黄色葡萄球菌的临床分布和耐药性变迁,为临床合理使用抗菌药物提供依据.方法 万古霉素采用E-test法检测最小抑菌浓度(MIC),其余抗菌药物敏感性试验采用纸片扩散法(K-B法),判断标准均按CLSI2011年规定标准判定结果,以WHONET5.4统计软件进行数据分析.结果 共分离出金黄色葡萄球菌3156株,其中耐甲氧西林金黄色葡萄球菌(MRSA)1903株,检出率为60.3％,MRSA检出率呈上升趋势,且随年龄增长而逐渐上升.痰、分泌物为主要标本来源,普外科及ICU病房为金黄色葡萄球菌的主要分离病区.各病区以ICU MRSA检出率最高,为87.4％,其次为普外科和神经外科,分别为85.7％和184.3％.MRSA对除磷霉素、复方磺胺甲嗯唑、克林霉素、红霉素及糖肽类以外的抗菌药物耐药性均在90％以上,MSSA对庆大霉素的耐药率由9.5％上升至16.2％,差异有统计学意义(P＜0.05).复方磺胺甲嗯唑对MRSA和MSSA均保持较好的敏感性,敏感率在80％以上.未发现万古霉素、替考拉宁及利奈唑胺耐药的菌株.结论 6年间金黄色葡萄球菌的耐药率持续保持较高的水平,耐药现象严重,并且MRSA检出率有逐年上升的趋势,临床应合理使用抗菌药物,定期监测其耐药性变迁,避免院内传播.     

耐甲氧西林金黃色葡萄球菌耐药性分析

目的了解耐甲氧西林金黄色葡萄球菌(MRSA)的耐药性情况,为临床合理选用抗生素提供参考和依据。方法参照2009年临床实验室标准化研究所(CLSI)标准,对广东某综合三甲医院2003年1月～2009年6月各种临床标本中分离的188株MRSA,用K-B法对10种抗菌素进行的敏感性检测;微量稀释法对万古霉素、利奈唑烷的敏感性进行检测,统计MIC均值。结果 188株MRSA利奈唑烷、替考拉宁、万古霉素对敏感率均为100.0%,对利奈唑烷和万古霉素的MIC几何均值分别为0.919μg/ml和1.322μg/ml。对氯霉素、利福平的敏感率为71.8%及70.7%,其他被检测的抗菌素的敏感率均低于50.0%。结论 MRSA对利奈唑烷、替考拉宁、万古霉素敏感性高,而对临床常用的其它抗菌药物呈多重耐药性。     

万古霉素与替考拉宁及利奈唑胺对神经外科MRSA感染患者的临床疗效与安全性比较

目的:比较万古霉素与替考拉宁及利奈唑胺对神经外科耐甲氧西林金黄色葡萄球菌(MRSA)感染患者的临床疗效与安全性.方法:选取2015年5月-2020年5月间医院收治的90例神经外科MRSA感染患者资料,将其随机分为万古霉素组、替考拉宁组、利奈唑胺组,每组30例;万古霉素组、替考拉宁组、利奈唑胺组患者分别给予万古霉素、替考拉宁及利奈唑胺治疗,比较3组患者治疗后的总有效率,细菌清除率,以及相关实验室指标即白细胞(WBC)计数、肿瘤坏死因子-α(TNF-α)和C反应蛋白(CRP)水平及其不良反应发生率的差异.结果:万古霉素组、替考拉宁组患者治疗后的总有效率、细菌有效清除率均低于利奈唑胺组(P＜0.05),万古霉素组、替考拉宁组患者治疗后的总有效率、细菌有效清除率经组间比较其差异均无统计学意义(P＞0.05);治疗后,3组患者的WBC计数、TNF-α和CRP水平降低,万古霉素组、替考拉宁组患者的WBC计数、TNF-α和CRP水平均高于利奈唑胺组(P＜ 0.05),万古霉素组、替考拉宁组患者的WBC计数、TNF-α和CRP水平经组间比较其差异均无统计学意义(P＞0.05);3组患者的不良反应发生率经组间比较其差异无统计学意义(P＞0.05).结论:相较于万古霉素和替考拉宁,利奈唑胺对神经外科MRSA感染患者的疗效更为确切,有效促进了细菌清除,改善了机体炎性反应,且安全性较高.     

万古霉素与替考拉宁及利奈唑胺对神经外科MRSA感染患者的临床疗效与安全性比较

目的:比较万古霉素与替考拉宁及利奈唑胺对神经外科耐甲氧西林金黄色葡萄球菌(MRSA)感染患者的临床疗效与安全性.方法:选取2015年5月-2020年5月间医院收治的90例神经外科MRSA感染患者资料,将其随机分为万古霉素组、替考拉宁组、利奈唑胺组,每组30例;万古霉素组、替考拉宁组、利奈唑胺组患者分别给予万古霉素、替考拉宁及利奈唑胺治疗,比较3组患者治疗后的总有效率,细菌清除率,以及相关实验室指标即白细胞(WBC)计数、肿瘤坏死因子-α(TNF-α)和C反应蛋白(CRP)水平及其不良反应发生率的差异.结果:万古霉素组、替考拉宁组患者治疗后的总有效率、细菌有效清除率均低于利奈唑胺组(P＜0.05),万古霉素组、替考拉宁组患者治疗后的总有效率、细菌有效清除率经组间比较其差异均无统计学意义(P＞0.05);治疗后,3组患者的WBC计数、TNF-α和CRP水平降低,万古霉素组、替考拉宁组患者的WBC计数、TNF-α和CRP水平均高于利奈唑胺组(P＜ 0.05),万古霉素组、替考拉宁组患者的WBC计数、TNF-α和CRP水平经组间比较其差异均无统计学意义(P＞0.05);3组患者的不良反应发生率经组间比较其差异无统计学意义(P＞0.05).结论:相较于万古霉素和替考拉宁,利奈唑胺对神经外科MRSA感染患者的疗效更为确切,有效促进了细菌清除,改善了机体炎性反应,且安全性较高.     

万古霉素联合利奈唑胺体外抑制MRSA活性的探讨

目的:探讨万古霉素联合利奈唑胺体外对耐甲氧西林金黄色葡萄球菌(MRSA)抑菌效应。方法:采用试管二倍稀释法测定万古霉素、利奈唑胺及两者联用时对MRSA抑菌的各自最低抑菌浓度(MIC)值,同时利用棋盘微量稀释法测定不同浓度组合的万古霉素、利奈唑胺抗菌药物对MRSA的最低抑菌浓度,计算相应的联合抑菌指数(FIC)。结果:单用抑制MRSA时,MIC万古霉素为1.563μg/m L,MIC利奈唑胺为0.25μg/m L;当两者联用时,MIC万古霉素、MIC利奈唑胺分别为0.391 0μg/m L、0.312 5μg/m L,联用前后MIC差异有统计学意义(P<0.05),其相应的FIC<0.5。结论:万古霉素与利奈唑胺联用有协同抑菌作用,具有较高的体外抗菌活性,可为有效降低临床细菌耐药率提供新途径。     

利奈唑胺、万古霉素对甲氧西林耐药的金黄色葡萄球菌的防耐药突变体选择浓度的研究

目的：比较利奈唑胺、万古霉素对耐甲氧西林金黄色葡萄球菌的防耐药突变选择能力;研究防耐药突变体选择浓度（MPC）和最低抑菌浓度（MIC）的相关性。方法：采用琼脂微量稀释法测定利奈唑胺、万古霉素对35株耐甲氧西林金黄色葡萄球菌（MRSA）临床分离菌株的MPC和MIC;采用线性回归法比较利奈唑胺、万古霉素对MRSA的MPC和MIC的相关性;结合人体药代动力学数据,预测利夺唑胺、万古霉素对MRSA的防耐药突变体选择能力。结果：利奈唑胺、万古霉素对35株MRSA的MPC90值（抑制90％的细菌发生细菌耐药的最低防耐药突变体选择浓度）分别为16.8μg／mL,选择指数（MPC90／MIC90）均为8。两药对MRSA的MPC和MIC的线性相关系数R^2分别为0．32和0．008。结合两药药代动力学参数,利奈唑胺药物浓度在整个给药间隔落在耐药突变选择窗理论（MSW）中,万古霉素药物浓度在大部分给药间隔落在MPC之上。结论：万古霉素对MRSA的防耐药选择能力强于利奈唑胺;MPC和MIC的相关性差。     

糖尿病足坏疽创面分离出的164株耐甲氧西林金黄色葡萄球菌耐药性分析

目的 分析糖尿病足坏疽(DFG)创面分离出的耐甲氧西林金黄色葡萄球菌(MRSA)的耐药性,指导临床合理应用抗生素.方法 对空军总医院2008年1月至2011年12月期间610例住院DFG患者创面中分离的411株金黄色葡萄球菌,采用纸片扩散法进行药敏试验,用头孢西丁纸片扩散法筛选MRSA.结果 检出的411株菌株中包括MRSA 164株、甲氧西林敏感金黄色葡萄球菌(MSSA) 247株,除青霉素、红霉素、克林霉素外,MSSA对其他抗生素均有较好的敏感性,而MRSA除对万古霉素、利奈唑胺、替考拉宁、呋喃妥因、氯霉素及复方新诺明敏感外,对其他抗生素均耐药.没有发现对万古霉素及利奈唑胺耐药的菌株.结论 MRSA多重耐药,在DFG患者中应加强对其发生率及耐药率监测,有效地预防及控制其感染.     

利奈唑胺对临床分离阳性球菌的体外敏感性分析

目的:对比利奈唑胺与万古霉素及其他几种常用抗菌药物对临床分离阳性球菌的体外抗菌活性。方法:按照NCCLS(CLSI)2007纸片扩散法操作标准测定利奈唑胺与其他几种常用抗菌药物的体外抗菌活性。结果:本院分离的耐甲氧西林金黄色葡萄球菌(MRSA)比例较高(79.1%),利奈唑胺、万古霉素、替考拉宁的敏感率均达到100%。耐甲氧西林凝固酶阴性葡萄球菌(MRC-NS)的比例较MRSA高(88.9%),利奈唑胺与万古霉素、替考拉宁活性相当,敏感率均为100%。利奈唑胺对粪肠球菌的活性与万古霉素、替考拉宁相当,对屎肠球菌的活性优于万古霉素和替考拉宁(100%,80.4%,78.1%),对青霉素耐药的肺炎链球菌(PRSP)也表现了优越的抗菌活性。结论:对于MRSA、MRCNS、PRSP、粪肠球菌,利奈唑胺与万古霉素、替考拉宁的活性相当,均为100%的敏感率;对屎肠球菌的抗菌活性优于万古霉素和替考拉宁,是治疗多药耐药阳性球菌感染的新型药物。     

利奈唑胺治疗糖肽类药物治疗无效MRSA的感染分析

目的了解利奈唑胺对于治疗糖肽类药物治疗无明显效果的耐甲氧西林金黄色葡萄球菌(MRSA)感染的效果及优点,为临床用药提供参考。方法对2008年2月—2009年7月入住我院ICU并细菌培养为MRSA,且确定为致病菌,给予足够剂量的万古霉素或替考拉宁治疗大于5d无明显效果,后给予利奈唑胺治疗收到满意效果的患者进行回顾性分析。结果所有培养为MRSA的药敏结果均回报对万古霉素、替考拉宁及利奈唑胺敏感。12例患者均根据药敏结果首先选用万古霉素或替考拉宁治疗,疗程均在5d以上,患者血象、体温无明显好转,再次细菌培养仍为MRSA。所有患者给予利奈唑胺治疗后,血象、体温明显好转,再次细菌培养未见细菌生长。4例患者治疗时间超过28d,3例出现三系细胞减低,考虑利奈唑胺致骨髓抑制,停药1周后回复正常。结论利奈唑胺可以做为治疗糖肽类药物初始治疗失败的革兰阳性菌感染的选择用药;疗程超过28d的患者,有出现骨髓抑制等药物相关性副作用的风险,应密切监测血常规。     

耐甲氧西林金黄色葡萄球菌耐药分析

目的了解全院临床科室耐甲氧西林金黄色葡萄球菌(MRSA)耐药情况,为呼吸科临床治疗提供抗菌药选用依据。方法对临床分离的28株金黄色葡萄球菌中耐甲氧西林金黄色葡萄球菌(MRSA)的药物敏感报告单进行耐药分析。结果 28株金黄色葡萄球菌中耐甲氧西林金黄色葡萄球菌(MRSA)的检出率为53.57%,MRSA对18种抗菌药物中种耐药率>63.24%,对青霉素类、头孢菌素类以及红霉素100.0%耐药,MRSA对替考拉宁、利奈唑胺100.0%敏感,检测到1株耐万古霉素金黄色葡萄球菌。结论本研究中我院呼吸科MRSA发生率低于国内平均水平,复方新诺明和氯霉素对其仍较敏感,万古霉素出现耐药菌株,替考拉宁、利奈唑胺仍为首选。     

Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections

BACKGROUND: Vancomycin is commonly used to treat staphylococcal infections, but there has not been a definitive analysis of the pharmacokinetics of this antibacterial in relation to minimum inhibitory concentration (MIC) that could be used to determine a target pharmacodynamic index for treatment optimisation. OBJECTIVE: To clarify relationships between vancomycin dosage, serum concentration, MIC and antimicrobial activity by using data gathered from a therapeutic monitoring environment that observes failures in some cases. METHODS: We investigated all patients with a Staphylococcus aureus lower respiratory tract infection at a 300-bed teaching hospital in the US during a 1-year period. Clinical and pharmacokinetic information was used to determine the following: (i) whether steady-state 24-hour area under the concentration-time curve (AUC24) divided by the MIC (AUC24/MIC) values for vancomycin could be precisely calculated with a software program; (ii) whether the percentage of time vancomycin serum concentrations were above the MIC (%Time>MIC) was an important determinant of vancomycin response; (iii) whether the time to bacterial eradication differed as the AUC24/MIC value increased; (iv) whether the time to bacterial eradication for vancomycin differed compared with other antibacterials at the same AUC24/MIC value; and (v) whether a relationship existed between time to bacterial eradication and time to significant clinical improvement of pneumonia symptoms. RESULTS: The median age of the 108 patients studied was 74 (range 32-93) years. Measured vancomycin AUC24/MIC values were precisely predicted with the A.U.I.C. calculator in a subset of our patients (r2 = 0.935). Clinical and bacteriological response to vancomycin therapy was superior in patients with higher (> or = 400) AUC24/MIC values (p = 0.0046), but no relationship was identified between vancomycin %Time>MIC and infection response. Bacterial eradication of S. aureus (both methicillin-susceptible and methicillin-resistant) occurred more rapidly (p = 0.0402) with vancomycin when a threshold AUC24/MIC value was reached. S. aureus killing rates were slower with vancomycin than with other antistaphylococcal antibacterials (p = 0.002). There was a significant relationship (p < 0.0001) between time to bacterial eradication and the time to substantial improvement in pneumonia score. CONCLUSIONS: Vancomycin AUC24/MIC values predict time-related clinical and bacteriological outcomes for patients with lower respiratory tract infections caused by methicillin-resistant S. aureus.     

Vancomycin MICs of the resistant mutants of S. aureus ATCC43300 vary based on the susceptibility test methods used

Clinical failures with vancomycin against meticillin-resistant Staphylococcus aureus (MRSA) infections have challenged vancomycin's standing as a first-line antimicrobial for these infections. Conventional MIC tests were not predictive of the in vivo therapeutic effect of vancomycin. Thus, we tested the susceptibility for the resistant mutants in the mutant selection window of S. aureus ATCC43300 (a MRSA strain) by three different MIC-testing methods in this paper. The MIC of vancomycin was estimated at 2?μg?ml?1 on the Mueller-Hinton agar (MHA) plate only for the resistant mutant that was selected from the plate of vancomycin concentration 12?μg?ml?1. The obvious changes of susceptibility testing were found between the resistant mutants and S. aureus ATCC43300 on the Brain-Heart Infusion Agar (BHIA) plates. There were subtle changes in the MIC trend within the susceptible range with the result of Etest for the resistant mutants. The susceptibility for the subcultures of resistant mutants would fall back when the external drug environment disappeared. In comparison with the S. aureus ATCC43300, sequence analysis revealed that there were no mutations in the staphylococcal protein A (spa) sequencing of the resistant mutants. The spa tape is t421 for all isolates.     

金葡菌细胞壁变化与对万古霉素耐药的关系

目的了解金葡菌细胞壁变化与万古霉素耐药的关系，探讨耐药机制。方法将1株从临床标本中分离的异质性耐万古霉素的金葡菌（h-VRSA）在含有不同浓度的万古霉素培养基上连续诱导转种，用微量肉汤稀释法和菌谱分析法检测其对万古霉素的敏感性；同时采用扫描电镜和透射电镜分别对细胞壁的表面结构和厚度进行摄片观察；用PCR方法检测万古霉素耐药基因（vanA、vanB和vanC）。结果随万古霉素诱导浓度的增加，金葡菌对万古霉素的MIC逐渐增加；菌谱分析显示耐药亚群逐渐增加；电镜摄片可见细胞壁增厚，细胞壁粗糙，有结节状凸起；van基因检测为阴性。结论在万古霉素的选择性压力下金葡菌的耐药性可逐渐增加，细胞壁增厚是金葡菌对万古霉素耐药的重要机制。     

Synergistic effect of rosmarinic acid with antibiotics against Staphylococcus aureus and MRSA

OBJECTIVE To evaluate the synergistic effect of rosmarinic acid(RA)with antibiotics against Staphylococcus aureus(S.aureus)and MRSA and to identify the possible mechanism of action responsible for synergism if any.METHODS The antibacterial activity of Rosmarinic acid was studied for its zone of inhibition by agar well diffusion and MIC determination by liquid broth dilution technique against MRSA and VRSA.The synergistic effect of RA with antibiotics like amoxicillin,ofloxacin and vancomycin was evaluated by Broth checker board method and further confirmed with time kill kinetic studies.Microbial Surface Components Recognizing Adhesive Matrix Molecules(MSCRAMMs)were isolated by protein precipitation technique and its expression was studied by SDS PAGE.Further RA was evaluated for its beta lactamase inhibition property.RESULTS Rosmarinic acid exhibited antibacterial activity against S.aureus and MRSAby showing a MIC value of 0.8mg·mL-1 against S.aureus and 10mg·mL-1 against MRSA.Rosmarinic acid at 1/4X MIC value reduced the MIC of vancomycin,amoxicillin and ofloxacin by 1/4 times against S.aureus.But against MRSA,vancomycin was found to be synergistic.All the synergistic combinations have shown FIC value of 0.5.In order to measure the kinetics of the anti-bacterial activity,the bacterial growth rate with RA,antibiotics and synergistic combinations against S.aureus and MRSA was studied.It is observed that the synergistic combinations showed better time kill kinetics as compared to RA and antibiotics.Further RA could able to destruct the cell surface proteins MSCRAMMs which was studied by SDS PAGE.RA was also found to showβlactamase inhibiting property.CONCLUSION It is concluded that RA possess antibacterial activity but at a very higher concentration(in mg/mL)against S.aureus and MRSA.However it shows synergism with antibiotics and could able to reduce the MIC of antibiotics.Thus RA could be developed as an adjuvant for antibiotics against S.aureus and MRSA caused infections.Further studies are needed to identify the mechanism for its synergism with antibiotics.     

Activity of simulated serum concentrations of daptomycin versus vancomycin during the first 24h of treatment in the presence of physiological albumin concentrations against vancomycin-susceptible, -tolerant or -intermediate-resistant Staphylococcus aureus

In order to determine whether reduced susceptibility or tolerance to vancomycin in Staphylococcus aureus influences the activity of daptomycin by simulating serum concentrations in the first 24h of treatment in the presence of physiological concentrations of human albumin, a computerised pharmacodynamic simulation was performed using Mueller-Hinton broth with 4 g/dL human albumin concentrations. For daptomycin, the media was adjusted to physiological ionised calcium concentrations by adding 100 μg/mL Ca(2+). Protein binding was measured. Six S. aureus isolates were used, comprising one vancomycin-susceptible S. aureus (VSSA), three vancomycin-tolerant strains, one heteroresistant vancomycin-intermediate S. aureus (hVISA) and one homogeneous vancomycin-intermediate S. aureus (VISA). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of daptomycin increased eight times when determined in the presence of albumin (MIC(ALB) and MBC(ALB), respectively). Measured protein binding was 86.6% (C(max)) and 86.5% (C(min)) for daptomycin and 51.6% (C(max)) and 42.2% (C(min)) for vancomycin. Similar values were obtained for fAUC/MIC (where fAUC is the area under the concentration-time curve obtained with extrapolated concentrations using the highest protein binding rate experimentally obtained) and AUC/MIC(ALB) for each antibiotic. Daptomycin showed early (≤ 6 h) bactericidal activity [maximal effect (E(max)) >4 log(10) reductions in initial inocula] against all strains. Vancomycin produced an E(max) of 2.3 log(10) reductions at 8h against the VSSA and reductions ≤1.8 log(10) for the other strains in the 8-24h period. Pharmacodynamic parameters were fAUC/MBC from 8.0 to 15.6 (vancomycin) and from 56.0 to 111.6 (daptomycin) for tolerant strains, and fAUC/MIC of 126.8 and 63.3 for vancomycin and 222.6 and 113.2 for daptomycin against hVISA and VISA strains, respectively. Against the study strains (vancomycin-susceptible, -tolerant, heteroresistant or intermediate), daptomycin, in contrast to vancomycin, exhibited early bactericidal activity despite its high protein binding.     

左氧氟沙星联合万古霉素缩小金黄色葡萄球菌耐药突变选择窗的初步研究

目的:在体外初步探讨联合用药可缩小单药对细菌的耐药突变选择窗(MSW),为临床合理使用现有抗菌药物,防止细菌耐药产生提供理论依据。方法:应用肉汤法富集1010CFU/mL细菌,琼脂平板二倍稀释法测定左氧氟沙星、万古霉素单药和两药联用对金黄色葡萄球菌ATCC29213的最低药物浓度(MPC)和MSW。结果:左氧氟沙星、万古霉素单药对金黄色葡萄球菌ATCC29213的MSW分别为16和64。万古霉素和左氧氟沙星联合用药(1MIC 8MIC,2MIC 4MIC)使左氧氟沙星单药对ATCC29213的MSW缩小2～4倍。左氧氟沙星联合万古霉素用药(1MIC 16MIC,2MIC 8MIC)使万古霉素对ATCC29213的MSW缩小4～8倍。结论:万古霉素和左氧氟沙星联合用药可缩小各自单药对金黄色葡萄球菌ATCC29213的MSW。     

Antimicrobial susceptibility of Gram-positive bacterial isolates from the Asia-Pacific region and an in vitro evaluation of the bactericidal activity of daptomycin, vancomycin, and teicoplanin: a SENTRY Program Report (2003-2004)

Medical centres in eight countries in the Asia-Pacific region provided 2391 isolates for the SENTRY Antimicrobial Surveillance Program during 2003-2004 to determine their susceptibility to several antimicrobial classes, including daptomycin. Daptomycin, vancomycin and teicoplanin minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined for 120 isolates of Staphylococcus aureus, which included wild-type (WT) methicillin-resistant S. aureus (MRSA) and strains with decreased susceptibility to vancomycin (hetero-vancomycin-intermediate S. aureus (hVISA)). Oxacillin-resistant staphylococcal isolates were much less susceptible to the other tested agents compared with oxacillin-susceptible strains. Vancomycin resistance was higher among Enterococcus faecium (10.3%) than Enterococcus faecalis (0.4%), and macrolide resistance was high both for beta-haemolytic (17.7%) and viridans group (48.7%) streptococci. Daptomycin (MIC for 90% of the organisms (MIC(90))=0.5-1mg/L) was two-fold more potent than vancomycin, with >99% susceptibility when tested against staphylococci. All tested isolates of E. faecalis (MIC(90)=2mg/L) and beta-haemolytic streptococci (MIC(90)=0.5mg/L) were susceptible to daptomycin. Daptomycin MIC and MBC values were slightly higher for the hVISA isolates compared with WT-MRSA, with MBC/MIC ratios of only 1-2 for both groups. The MBC/MIC ratio for vancomycin was often greater when tested against these strains, particularly hVISA. In contrast, teicoplanin MBC/MIC ratios were significantly higher, with many of the strains showing values consistent with tolerance (>or=32). Daptomycin was demonstrated to have excellent in vitro activity when tested against Gram-positive isolates collected from Asia-Pacific countries, including hVISA strains.     

金黄色葡萄球菌对夫西地酸的体外耐药现状及耐药性改变研究

目的了解金黄色葡萄球菌对夫西地酸的耐药现状及耐药性改变。方法通过琼脂稀释法测定2010年连续收集的260株和2007年收集的220株金黄色葡萄球菌对夫西地酸的MIC值,用K-B纸片法测定这些菌株对万古霉素等7种抗生素的抑菌圈直径。结果 480株金黄色葡萄球菌中对夫西地酸耐药的只有4株,耐药率为0.83%,2007年和2010年收集的菌株对夫西地酸的MIC50均为0.25mg/L,MIC90均为0.5mg/L,纸片法测定结果：所有菌株对万古霉素敏感,2007年的菌株57.8%耐甲氧西林,2010年的菌株76.9%耐甲氧西林。结论夫西地酸对金黄色葡萄球菌的体外抗菌活性很强,而且2007年和2010年菌株的抗菌活性无多大改变。     

利奈唑胺、替考拉宁和万古霉素等抗菌药物对常见需氧革兰阳性球菌的体外抗菌活性

目的评价利奈唑胺、替考拉宁和万古霉素等抗菌药物的体外抗菌活性。方法采用琼脂稀释法对临床收集的132株革兰阳性球菌进行抗菌活性测定,记录其各自的MIC并进行比较。结果利奈唑胺、替考拉宁及万古霉素3药对革兰阳性球菌均有较大抗菌活性,敏感率均为100%,包括其中的耐甲氧西林葡萄球菌和青霉素中介肺炎链球菌均有良好抗菌作用。3药在部分革兰阳性球菌的抗菌作用中与利福平相仿,但比氨基糖苷类抗生素和氟喹诺酮类抗菌药强。在对甲氧西林敏感金葡萄的抗菌活性中,替考拉宁的MIC90均为利奈唑胺和万古霉素的4倍;在对甲氧西林敏感凝固酶阴性葡萄球菌的抗菌活性中,替考拉宁的MIC90分别均为利奈唑胺和万古霉素的8倍;而在青霉素敏感和中介肺炎链球菌的抗菌活性中,替考拉宁的MIC90为利奈唑胺的1/16,为万古霉素的1/8;在肠球菌属的抗菌活性中,万古霉素的MIC90分别为利奈唑胺的2倍,是替考拉宁的4倍和8倍。结论利奈唑胺、替考拉宁以及万古霉素等三药对革兰阳性球菌有较大的抗菌作用,对部分革兰阳性菌的抗菌作用与利福平相仿,但比其他如氨基糖苷类抗生素和氟诺酮类抗菌药更优,是临床革兰阳性球菌严重感染的有效药物。     

Characterisation of laboratory-generated vancomycin intermediate resistant Staphylococcus aureus strains

Vancomycin has been the drug of choice for 30 years for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Emergence of decreased vancomycin susceptibility in MRSA strains presents a significant clinical problem with few therapeutic options. This study was performed to generate and characterise S. aureus strains with reduced susceptibility to vancomycin. Eighteen S. aureus strains were subjected to serial passaging on vancomycin to generate vancomycin intermediate resistant S. aureus (VISA) strains. Minimum inhibitory concentration (MIC) determination was performed for the parent and the passaged cultures with 13 different antibiotics. The strains were tested by the following five methods: simplified population analysis; CDC method; modified vancomycin agar screen; population analysis profile (PAP); and modified population analysis (PAP-area under the curve (AUC) ratio). Phenotypic changes such as doubling time, synergy with beta-lactam antibiotics and effect on norA efflux pumps were also studied for these strains. The result indicated that 8 VISA mutants (vancomycin MICs, 8-16 microg/mL) were generated in vitro from the 18 S. aureus strains. The CDC and modified agar methods proved to be the most sensitive and specific methods for detection of VISA strains. The PAP for all the VISA strains ranged from 12 microg/mL to > 16 microg/mL, with a PAP-AUC ratio of > 1.3. All mutants showed increased doubling time compared with their parent isolate. Synergism of the vancomycin and beta-lactam combinations was observed for all methicillin-resistant mutants. Upon acquisition of vancomycin resistance, a few mutants showed decreased oxacillin resistance. Two VISA strains were chosen for molecular characterisation of the mecA gene and one mutant showed genotypic changes with deletion of mecA. Loss of norA efflux pumps leading to fluoroquinolone sensitivity was also observed in four mutants.