静脉滴注利奈唑胺致白细胞及中性粒细胞减少1例

1例57a女性患者,既往患慢性肾功能衰竭,行持续不卧床腹膜透析治疗。因急性腹膜炎静脉滴注利奈唑胺0.6g,bid。用药2d后,出现白细胞及中性粒细胞减少,WBC2.43×109·L-1,N0。立即停药,给予粒细胞集落刺激因子100μg对症治疗。2d后复查血常规WBC9.10×109·L-1,N41.6%。之后换用其他抗菌药物,未出现白细胞及中性粒细胞减少。     

In vitro activity of moxifloxacin,levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosis

The in vitro activity of moxifloxacin, gatifloxacin, levofloxacin and linezolid was evaluated against 234 strains of Mycobacterium tuberculosis isolated in the Southeast of Spain. All drugs tested showed good activity, with an MIC₉₀ of less than 1 mg/l, and were active against isociacide and rifampicin resistant strains. Three strains were resistant to isoniazid and to the fluoroquinolones, which suggested the existence of mechanisms of resistance not yet described. These new compounds may prove to be therapeutic alternatives for treatment of multi-resistant tuberculosis and further studies should be done to demonstrate their true usefulness.     

利奈唑胺葡萄糖注射液药物利用评价标准的建立及在重症医学科的应用

目的 建立利奈唑胺葡萄糖注射液的药物利用评价（DUE）标准,评价利奈唑胺葡萄糖注射液在重症医学科（ICU）的应用情况,为临床合理用药提供参考。方法 参考药品说明书、抗菌药物临床应用指导原则、相关管理规范,建立利奈唑胺葡萄糖注射液的DUE标准,并对2020年7月至2021年12月合肥市第二人民医院ICU使用利奈唑胺葡萄糖注射液的病历进行回顾性分析。结果 共纳入应用利奈唑胺葡萄糖注射液的病人82例,临床有效率52.44%(43/82)、药品不良反应（ADR）发生率4.88%(4/82),经评估该院ICU的利奈唑胺葡萄糖注射液应用在剂量、处方权限、病程记录、不良反应监测方面均符合评价标准要求,但仍有一些指标存在问题,如经验性用药较多89.02%(73/82)、用药前病原学检查率较低48.78%(40/82)、药物疗程不足45.12%(37/82),主要由病人出院或发生ADR造成。结论 建立的利奈唑胺葡萄糖注射液的DUE标准实用性较强,可及时发现利奈唑胺葡萄糖注射液在使用过程中的问题。     

N-苄氧羰基-3-氟-4-吗啉基苯胺的合成

目的研究新的适合大工业生产的合成N-苄氧羰基-3-氟-4-吗啉基苯胺的方法。方法以3,4-二氟硝基苯和吗啉为原料,经取代,还原,取代三步得到N-苄氧羰基-3-氟-4-吗啉基苯胺。结果通过新的方法成功合成出了N-苄氧羰基-3-氟-4-吗啉基苯胺,总收率达到73％,后处理方便。结论新方法是一种合成N-苄氧羰基-3-氟4-吗啉基苯胺的好方法。     

Efficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven to be caused by methicillin-resistant Staphylococcus aureus

Background

This open-label study compared oral or intravenous linezolid with intravenous vancomycin for treatment of complicated skin and soft-tissue infections (cSSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA).

Methods

Patients with proven MRSA cSSTI were randomized to receive linezolid or vancomycin. Clinical and microbiologic outcomes, duration of antimicrobial therapy, length of hospital stay, and safety were assessed.

Results

In the per-protocol population, the rate of clinical success was similar in linezolid- and vancomycin-treated patients (P = .249). The rate of success was significantly higher in linezolid-treated patients in the modified intent-to-treat population (P = .048). The microbiologic success rate was higher for linezolid at the end of treatment (P < .001) and was similar at the end of the study (P = .127). Patients receiving linezolid had a significantly shorter length of stay and duration of intravenous therapy than patients receiving vancomycin. Both agents were well tolerated. Adverse events were similar to each drug's established safety profile.

Conclusions

Linezolid is an effective alternative to vancomycin for the treatment of cSSTI caused by MRSA.     

万古霉素和利奈唑胺对耐甲氧西林金黄色葡萄球菌防耐药变异浓度的测定

目的检测万古霉素和利奈唑胺对MRSA的抗菌活性及两种药物对其耐药突变株的选择能力。方法按照美国临床实验室标准研究院推荐的琼脂平板二倍稀释法测定万古霉素和利奈唑胺对临床分离的122株MRSA的最低抑菌浓度（MIC）;平板稀释法测定二者对MRSA的防耐药变异浓度（MPC）。结果万古霉素对122株MRSA的MICrang为0.5～4.0μg/ml,MIC50为1.0μg/ml,MIC90为2.0μg/ml,MPC90为22.4μg/ml,选择指数为11.2;利奈唑胺对122株MRSA的MICrang为1.0～4.0μg/ml,MIC50和MIC90均为2.0μg/ml,MPC90为5.6μg/ml;选择指数为2.8。结论万古霉素和利奈唑胺对MRSA的抗菌活性均较好,作用于MRSA均不容易筛选出耐药突变株;利奈唑胺限制MRSA耐药突变菌株的选择能力强于万古霉素,较万古霉素更不容易筛选出耐药突变株。     

Pharmacokinetically-based prediction of the effects of antibiotic combinations on resistant Staphylococcus aureus mutants: in vitro model studies with linezolid and rifampicin

To explore if combinations of linezolid (L) with rifampicin (R) are able to restrict Staphylococcus aureus resistance, the enrichment of L- and R-resistant mutants was studied in an in vitro dynamic model. L- and R-resistant mutants were enriched in all single drug treatments. In contrast, L-resistant mutants were not enriched and R-resistant mutants were similar to baseline amounts with only minimal regrowth at the end of the combination treatments. These effects appear to be explained by lowering the mutant prevention concentration (MPC) for L+R combinations (MPC_L+R) compared to the MPCs of L and R alone (MPC_L and MPC_R) and thereby the longer times above MPC_L+R (73–100% of the dosing interval for L and 42–58% for R) compared to the times above MPC_L (0–44%) and MPC_R (0%). These findings provide an opportunity to predict the selection of S. aureus resistance in L+R treatments using MPC_L+Rs.     

利奈唑胺治疗广泛耐药结核研究进展

我国是全球耐多药结核病严重流行国家之一。广泛耐药结核(XDR-TB)是最为严重的一种耐药结核病,疗效差、病死率高。利奈唑胺是噁唑烷酮类抗菌药物,研究证实其对XDR-TB治疗有效。本文通过对耐药结核的流行病学、耐药机制以及利奈唑胺的抗菌机制、治疗XDR-TB的疗效和不良反应等方面对利奈唑胺治疗XDR-TB的研究进展进行简要综述。     

几种常用抗MRSA药物在老年患者肺部感染中的疗效比较

目的观察和比较利奈唑胺、替考拉宁、夫西地酸、万古霉素治疗老年患者肺部耐甲氧西林金黄色葡萄球菌(MRSA)感染的临床疗效及安全性。方法选取我院2008年1月—2012年7月间肺部MRSA感染的老年住院患者132例,分成四组:A组(利奈唑胺组)29例,B组(替考拉宁组)34例,C组(夫西地酸组)32例,D组(万古霉素组)37例,对其临床疗效、细菌清除率、不良反应进行临床对比分析。结果临床有效率:A组86.21%、B组73.53%、C组62.50%、D组83.78%,C组分别与A、D两组比较,有统计学差异(P<0.05);细菌清除率方面:A组89.66%、B组70.59%、C组65.63%、D组89.19%,C组分别与A、D两组比较,有统计学差异(P<0.05);总不良反应发生率方面:A组34.48%、B组35.29%、C组25.00%、D组48.65%,C组显著优于D组(P<0.05)。结论对于MRSA肺部感染的老年患者,利奈唑胺、万古霉素疗效显著优于夫西地酸;而夫西地酸在安全性方面更具优势,此类患者应采用个体化治疗方案。     

利奈唑胺治疗非结核性分枝杆菌肺病1例报道

目的 观察含利奈唑胺治疗方案对非结核性分枝杆菌肺病的临床疗效、长疗程用药的安全性及不良反应.方法 对1例确诊为高度耐药脓肿型分枝杆菌属感染的非结核性分枝杆菌肺病患者,根据药敏使用含利奈唑胺方案治疗后的临床资料进行回顾性分析,观察患者临床症状、细菌学改善、影像学表现和不良反应,并结合文献进行复习.结果 患者接受利奈唑胺600 mg每日1次静脉滴注联用克拉霉素及阿米卡星的治疗,利奈唑胺使用长达24周,临床症状缓解,肺部阴影吸收,右主支气管狭窄改善,痰非结核性分枝杆菌转阴.结论 利奈唑胺具有抗非结核性分枝杆菌作用,与克拉霉素阿米卡星联用收到明显效果,未发现明显不良反应.