重症肺部感染患者肺泡上皮衬液万古霉素渗透性研究

目的对万古霉素在重症肺炎患者的肺组织渗透性进行探索,了解万古霉素在肺组织内分布情况,为研究万古霉素组织浓度与疗效相关性,制订更精准药物治疗方案提供参考。方法选取2016年5月—2017年1月间入住老年重症监护病房(ICU)、因肺部感染使用万古霉素,呼吸衰竭进行机械通气且治疗期间需进行支气管肺泡灌洗治疗患者。万古霉素0.5 g,q8h,持续静脉输注1 h。分别于用药3 d后,于给药间隔内进行一次支气管肺泡灌洗,收集灌洗液和同时期的血液样本,利用液相色谱-串联质谱(LC-MS/MS)法测定万古霉素浓度。同时使用尿素试剂盒对二者中尿素浓度进行测定,以获得灌洗液中药物浓度的稀释倍数,利用Renard公式计算药物在肺组织的渗透性,以渗透率表示。结果纳入符合条件的患者16例,其中男12例,女4例。平均年龄60.94岁,平均急性生理及慢性健康(APACHEⅡ)评分30.31分,主要诊断均为肺部感染,住院期间死亡2例,主要死亡原因为多器官功能衰竭。用药后感染性指标中白细胞(WBC)计数和降钙素原(PCT)差异有统计学意义(P<0.05)。肺泡灌洗操作平均分布在给药间隔内5个采血点,灌洗液回收率为38.83%,尿素在灌洗液中稀释倍数平均为37.34倍(17.8~79倍),肺泡上皮衬液中药物浓度为1.48~10.15μg·mL^-1,万古霉素血清药物浓度为8.71~61.96μg·mL^-1,万古霉素在肺组织渗透率为23.12%。结论万古霉素对重症患者肺部渗透性较低,在血药浓度达标的情况下,感染部位抗菌药物的实际浓度可能并不能达到最佳靶值,可能导致治疗失败。     

高效液相色谱法测定人脑脊液中万古霉素浓度及临床应用

目的：采用HPLC-DAD快速有效地测定人脑脊液中万古霉素浓度,为颅内感染患者鞘内注射调整剂量提供依据。方法：前处理采用乙腈: 6%高氯酸（1∶1,v/v）沉淀萃取,采用Eclipse XDB C18柱（250 mm × 4.6 mm,5 μm）;流动相：A-pH3.2磷酸二氢钾缓冲液,B-乙腈,梯度洗脱;流速：1 mL·min-1;检测波长：236 nm;柱温：30 ℃;进样量：20 μL;二极管阵列检测。内标法定量,去甲万古霉素为内标。结果：万古霉素低、中、高3个浓度（3.125、25、50 mg·L-1）方法的绝对回收率分别为95.4%、97.5%、100.7%,日内精密度RSD小于2.76%,日间精密度RSD小于5.24%,基质效应小于1.08%。结论：本方法准确简便,符合万古霉素药物浓度监测的要求。     

利奈唑胺与万古霉素治疗老年呼吸机相关性肺炎的疗效与安全性研究

目的探讨利奈唑胺与万古霉素治疗老年呼吸机相关性肺炎的疗效与安全性。方法选取我院2015年6月23日~2017年6月24日收治的因呼吸机导致的老年肺炎50例,采用电脑随机抽签的方式把患者分为对照组与观察组,对照组25例患者采用万古霉素进行治疗,观察组25例患者采用利奈唑胺进行治疗,对比两组治疗总有效率、细菌清除率及不良反应发生情况。结果观察组治疗总有效率与细菌清除率分别为92.00%与84.00%,对照组治疗总有效率与细菌清除率分别为68.00%与60.00%,两组比较差异有统计学意义(P0.05);治疗期间两组患者不良反应发生率均为8.00%,差异无统计学意义(P0.05)。结论在老年呼吸机相关性肺炎的治疗中,利奈唑胺的治疗总有效率以及细菌清除率要优于万古霉素,且不良反应少,具有较高的安全性,值得推广。     

肿瘤专科医院66例患者万古霉素使用的专项点评

摘 要 目的：评价肿瘤专科医院万古霉素临床应用情况,促进万古霉素的合理使用。 方法: 收集我院2015年66例使用万古霉素患者病历,对其用药指征、病原学检查、用法用量、用药疗程、联合用药、用药监测、药物利用指数（DUI）等方面进行点评分析。结果: 66例患者中,69.70%的患者万古霉素使用合理,DUI为0.82。不合理用药主要表现为无适应证用药、用法用量不合理、疗程过长或不足、联合用药不合理、预防给药时机不合理。结论:我院万古霉素临床使用基本合理,但仍存在不合理现象,需进一步加强对该药的使用管理及用药监护,促进临床合理用药,保障患者用药安全。     

ICU患者万古霉素血药浓度监测与个体化给药方案调整

摘 要 目的：临床药师通过万古霉素血药浓度监测结果,参与制定个体化给药方案。 方法: 监测特殊群体患者万古霉素的血药浓度,根据监测结果以及患者的临床表现,设计个体化给药方案。 结果: 临床药师通过个体化给药方案的调整,提高了疗效,并减少了不良反应的发生,提高了临床合理用药水平。 结论: 临床药师通过个体化的精准药学的实践,更好地服务于临床,为患者提供安全合理的药学服务。     

Glycopeptides and nephrotoxicity

Infections due to Gram-positive bacteria have become an increasing problem in the ICU. Furthermore, multidrug resistance among Gram-positive pathogens is increasingly recognized. Empirical therapy with antibiotic regimens that are effective against Gram-positive pathogens is often required in the ICU. Many critically ill patients in the ICU have multiorgan system failure, including acute renal failure, which further impedes optimal antimicrobial therapy. In this communication, the use of glycopeptides in the ICU is briefly reviewed, and the occurrence of associated nephrotoxicity during therapy with vancomycin or teicoplanin, alone or in combination with an aminoglycoside, is examined. Finally, existing recommendations regarding the dose regimens of these agents in patients with renal impairment are evaluated, and guide-lines for optimizing glycopeptide therapy through improved pharmacokinetic monitoring are presented.     

Effect of selective antimicrobial therapy on plaque and gingivitis in the dog

Abstract. The present investigation was performed to assess the effect of selective antibiotic therapy on developing plaque and gingivitis in dogs, which at the start of the study had normal gingiva. Fifteen beagle dogs were used. Throughout the entire observation period the animals were fed a diet which favored plaque accumulation. A baseline examination involved assessments of plaque, gingivitis and gingival exudate. The subgingival bacterial flora was assessed by dark-field microscopy. Subsequently the teeth of the right jaws were allowed to accumulate plaque. A careful tooth-cleaning program was maintained in the left jaws. Plaque and gingivitis assessments were repeated and subgingival plaque sampled in the right jaws after 14 and 28 days. On experimental day 28 the second part of the study was initiated. The dogs were randomly distributed into three groups of five animals each. A new baseline examination was performed in the left jaws, after which all tooth cleanings were terminated. During the subsequent 28 days each group of dogs was treated with one of three antimicrobial compounds (vancomycin, metronidazole or clindamycin). Examinations were repeated after 14 and 28 days.
The results demonstrated that systemic administration of antimicrobial substances can reduce the rate of plaque formation, change the composition of the developing subgingival microbiota and prevent (or retard) the onset of gingivitis. A comparison of the ability of the three compounds to prevent the formation of a "gingivitis-inducing" plaque revealed that metronidazole and clindamycin were markedly more effective than vancomycin. In fact, in dogs receiving metronidazole and clindamycin treatment, the initiation of gingivitis was almost entirely prevented during the 28 days of treatment.     

Vancomycin-resistant enterococcal meningitis treated with intrathecal streptomycin

Enterococcal meningitis is a rare complication of neurosurgical procedures. We present a patient who developed vancomycin-resistant enterococcal ventriculitis - meningitis after a brain tumor resection and ventriculoperitoneal shunt placement, treated successfully with intrathecal streptomycin through bilateral cerebrospinal fluid drainage catheters in addition to systemic antibiotics. This is the first report of such treatment for this resistant organism.     

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.     

Focal injection of vancomycin combined with surgical debridement–dermatoplasty in the treatment of pseudo-epitheliomatous granuloma

Background

Pseudo-epitheliomatous granuloma (PEG) can occur in some small skin wounds with secondary infections resulting from improper treatments. It is difficult to heal and can easily relapse.

Objectives

This study explores the clinical and pathological characteristics of PEG and effective treatments.

Patients and methods

Tissue specimens of PEG obtained from 11 patients (age range: 2–67 years) were sent for microbial examination and histological observation. The local lesions were treated by focal injection of vancomycin combined with surgical debridement–dermatoplasty.

Results

The diagnosis of PEG was based on histological examination, which revealed long epithelial peduncle encapsulated granulation tissue-like honeycomb in which more vessels, macrophages, lymphocytes and mast cells and less extracellular matrix were distributed. Bacteria such as Staphylococcus aureus, Bacillus pyocyaneus, ethylene-type Streptococcus, stool Streptococcus and F-citric acid Bacillus were found in the microbial culture of the specimens. They were tolerant to celbenin but sensitive to vancomycin. PEG could be cured by focal application of vancomycin combined with free skin or skin flap after thorough debridement. The relapse of PEG could be prevented by the therapy.

Conclusion

Focal injection of vancomycin combined with surgical debridement–dermatoplasty is an effective therapy for PEG.