多途径联合用药治疗广泛耐药鲍曼不动杆菌颅内感染1例报告并文献复习

目的探讨广泛耐药鲍曼不动杆菌颅内感染的早期诊断及治疗方案。方法分析1例颅脑外伤术后广泛耐药鲍曼不动杆菌颅内感染患者的临床资料;并结合文献复习,分析广泛耐药鲍曼不动杆菌颅内感染的治疗方案。结果本例患者住院过程中,采用二代测序技术及降钙素原检测脑脊液辅助诊断;抗生素使用方案为亚胺培南+替加环素+多粘菌素B静脉注射,以及联合腰大池引流庆大霉素冲洗和多粘菌素B+替加环素鞘内注射。治疗2周后患者颅内感染好转,脑脊液细菌培养阴性。结论对于广泛耐药鲍曼不动杆菌颅内感染,替加环素+多粘菌素B静脉用药,联合腰大池引流庆大霉素冲洗和多粘菌素B+替加环素鞘内注射有较好的治疗效果。     

开颅术后并发泛耐药鲍曼不动杆菌性颅内感染病例报告并文献复习

目的探讨泛耐药鲍曼不动杆菌性颅内感染的治疗方案。方法对1例脑出血术后合并泛耐药鲍曼不动杆菌性颅内感染患者的治疗过程进行回顾分析,重点从药物选择、给药剂量等方面进行药物治疗过程分析。结果通过将抗感染治疗方案调整为替加环素+头孢哌酮舒巴坦+米诺环素静脉给药,联合替加环素鞘内、脑室内给药,患者的颅内感染最终得到有效控制。结论替加环素鞘内及脑室内给药,对泛耐药鲍曼不动杆菌引起的颅内感染可获得较好的治疗效果。     

腰大池引流加鞘内注射治疗泛耐药鲍曼不动杆菌颅内感染的临床疗效分析

目的探讨腰大池引流加鞘内注射治疗泛耐药鲍曼不动杆菌颅内感染的疗效和安全性。方法回顾性分析2018年4月—2019年12月本院神经外科收治的26例泛耐药鲍曼不动杆菌颅内感染患者的临床资料,所有患者均接受腰大池引流及鞘内注射抗生素,观察并记录患者感染指标(体温、颈项强直征、血常规、脑脊液常规及生化、脑脊液细菌培养)变化情况,记录治疗方法并对治疗效果进行分析。结果 24例患者行单纯性腰大池引流,2例患者因腰大池引流管堵塞,重置腰大池引流管并联合侧脑室引流。23例患者在治疗10～34 d内治愈,治愈率为88.46%; 3例患者死亡,死亡率11.54%,死亡时间分别为感染确认后第4天、第7天、第12天。结论对泛耐药鲍曼不动杆菌颅内感染患者应用腰大池引流加鞘内注射治疗是安全有效的,值得临床推广。如发生因脑脊液蛋白含量高导致腰大池引流管堵塞,可联合侧脑室引流并行腰大池-侧脑室方向替加环素溶液持续冲洗。     

替加环素治疗NICU泛耐药鲍曼不动杆菌感染临床分析

目的：研究替加环素在N IC U中呼吸道泛耐药鲍曼不动杆菌感染治疗中的有效性与安全性。方法对2013‐02—2014‐02在我院N IC U中使用替加环素为基础的联合抗生素治疗呼吸道泛耐药鲍曼不动杆菌感染的患者进行疗效及安全性分析。结果9例患者中肺部感染痊愈4例,显效4例,进步1例。出现不良反应经对症处理均有缓解,体现了良好的耐受性。结论替加环素为基础联合抗感染治疗对泛耐药鲍曼不动杆菌安全有效。     

腰穿与腰大池引流结合鞘内注射万古霉素治疗高血压脑出血开颅术后颅内感染的疗效

目的探讨腰穿与腰大池引流结合鞘内注射万古霉素治疗高血压脑出血开颅术后颅内感染的临床效果。方法选取来我院接受治疗的高血压脑出血开颅后颅内感染患者120例,根据治疗方案分为A组与B组,每组60例。A组每隔12h进行腰椎穿刺,放出脑脊液40mL。完毕后在鞘内注射万古霉素与盐水混合液5mL(万古霉素浓度为4mg/mL)。B组每隔12h使用引流管鞘内注射万古霉素,浓度同上。夹闭引流管,2h后打开,然后引流,同时注意每24h视脑脊液压力的引流量控制在100~250mL范围内,引流管留置时间控制在7d内。若拔管后仍未完全控制感染,可根据病情行腰椎穿刺鞘内注射万古霉素。结果 A组治疗前脑脊液金黄色葡萄球菌感染31例,表皮葡萄球菌感染13例,铜绿假单胞菌感染10例,变形菌属感染6例。B组金黄色葡萄球菌感染30例,表皮葡萄球菌感染13例,铜绿假单胞菌感染12例,变形菌属感染5例。A组治愈率为81.67%,B组治愈率为95.00%。A组有效治疗时间为(8.92±1.51)d,疼痛明显占61.67%。B组置管时间为4~6d,有效治疗时间为(6.63±1.26)d,引流管拔出后腰椎穿刺主要药物(1.12±0.29)d,疼痛明显占21.67%。2组均未有癫痫发作及其他严重不良反应。结论腰大池引流结合鞘内注射万古霉素治疗开颅术后颅内感染效果显著,不良反应少,值得推广。     

静脉及鞘内联合用药治疗脑室外引流术后颅内感染

目的评价全身应用头孢吡肟加鞘内注射头孢吡肟及地塞米松治疗脑室外引流术后颅内感染的疗效与安全性。方法脑室外引流术后并发颅内感染患者29名,拔除脑室外引流管后,头孢吡肟2g,静脉点滴,每12小时给药,疗程10￣15d,结合腰穿鞘内给药:头孢吡肟50mg加地塞米松1mg鞘内注射,每天一次。结果该方法临床有效例数为27例,细菌清除例数为27例,不良反应发生例数为2例。结论该方法治疗脑室外引流术后颅内感染疗效确切,不良反应少,值得推荐。     

鞘内阶梯浓度用药治疗术后颅内葡萄球菌感染的临床研究

目的探讨单纯应用万古霉素鞘内阶梯浓度注射对术后颅内葡萄球菌感染的治疗作用。方法31例颅内葡萄球菌感染患者腰穿后鞘内注入生理盐水20ml＋盐酸万古霉素，1次，d，剂量从20mg、40mg、60mg、80mg、100mg、120mg、140mg逐日递增，共7d。在治疗前、后监测患者体温、颅内压、脑脊液常规、生化指标及细菌培养。结果万古霉素鞘内注射治疗前各项指标明显异常，治疗2～3d后逐渐改善，5～7d即出现颅内压降低，体温、脑脊液生化及常规指标趋于正常；治疗前与治疗后3～7d各项指标差异明显（P＜0．05），无并发症发生。结论单纯应用万古霉素鞘内阶梯浓度注射治疗术后颅内葡萄球菌感染疗效显著，操作简便，无毒副作用．是临床治疗颅内感染可行的方法。     

多重耐药鲍曼不动杆菌致颅内感染的治疗及疗效研究

目的 研究多重耐药鲍曼不动杆菌致颅内感染的治疗方法及疗效。方法 20例多重耐药鲍曼不动杆菌致颅内感染患者,行常规脑室及腰大池引流,采用替加环素联合头孢哌酮/舒巴坦抗感染治疗12～42 d。治疗前后观察患者的临床表现,行腰穿脑脊液检查,检测血C反应蛋白(CRP)、降钙素原(PCT)、S-100b蛋白、肿瘤坏死因子(TNF)-α水平。结果 本组患者经抗感染治疗后,痊愈16例、显效4例,脑脊液细胞数、生化指标正常,细菌培养阴性;总有效率100%。治疗1周后的脑脊液白细胞数、多核细胞比、蛋白质含量明显低于治疗前,糖含量高于治疗前;血CRP、PCT、S-100b蛋白、TNF-α水平低于治疗前;差异均有统计学意义(P 0. 01～0. 001)。患者治疗期间肝肾功能、血尿常规正常,未出现白细胞减少、腹泻、抽搐、过敏等不良反应。停用抗感染治疗2个月后随访复查,患者未发生再次感染。结论 多重耐药鲍曼不动杆菌致颅内感染病情重、病死率高,通畅引流,制定合理的治疗方案,选择有效的抗生素,是治疗成功的关键。     

万古霉素治疗耐甲氧西林革兰阳性菌颅内感染的研究

目的比较万古霉素治疗术后耐甲氧西林革兰阳性菌所致颅内感染不同的给药途径,评价其疗效与安全性。方法对颅脑手术后并发甲氧西林耐药革兰阳性菌性颅内感染患者56例,分为3组：（1）静脉给药组：稳可信500mg静滴,q12h;（2）鞘内给药组：通过鞘内注入稳可信0．3mg／（kg·d）＋地塞米松1mg,鞘内注射,q12h;（3）静脉＋鞘内给药组：按以上两种方法联合给药。综合临床症状、体征和脑脊液的转归情况进行评估。结果静脉给药组、鞘内给药组、静脉和鞘内给药组,治愈率分别为26．7％、60．0％和61．9％;细菌清除率分别86．7％、100％和100％,疗程分别为22．8d,15．2d和11．5d。结论万古霉素对术后甲氧西林耐药革兰阳性菌所致颅内感染疗效确切,鞘内给药安全性好,不良反应少,值得推荐在神经外科的应用。     

结核性脑膜炎合并脑结核瘤的临床特点

目的探讨结核性脑膜炎合并脑结核瘤的临床特点。方法回顾性分析7例结核性脑膜炎合并脑结核瘤患者的临床资料。结果 7例患者均有头痛、发热、脑膜刺激征,意识障碍6例,局灶性神经功能损害6例。7例患者CSF检查示颅内压增高4例,降低1例;葡萄糖降低5例;氯降低5例;蛋白增高6例。CSF细胞数增高7例,中性粒细胞比例增高6例。MRI检查显示病灶多分布于环池、鞍上池,丘脑、基底节、额颞叶。经鞘内注射治疗后,5例患者治愈,1例患者好转,1例患者死亡。结论脑结核瘤发生于结核性脑膜炎病程的各个阶段,可以表现为意识障碍及局灶性体征,需及时行MRI检查。规范的全身抗结核治疗联合鞘内注射异烟肼及地塞米松可获得良好预后。     

Analgesic and convulsant effects of guanidinoethylmercaptosuccinic acid (GEMSA)--a potent enkephalin convertase inhibitor

We studied behavioral effects of the intraventricularly and intrathecally administered guanidinoethylmercaptosuccinic acid (GEMSA) - a potent inhibitor of enkephalin convertase. When given intraventricularly in doses of 3 and 6 micrograms, GEMSA elicited analgesia; after doses of 12.5 and 25 micrograms the explosive motor behavior and convulsions occurred. Following the intrathecal administration of GEMSA (12.5, 25 and 50 micrograms), an increase in the tail-flick latency was observed; moreover that drug potentiated analgesic effects of the intrathecally applied Met5-enkephalin-Arg6-Phe7 and Met5-enkephalin-Arg6-Gly7-Leu8. All the above effects of GEMSA were significantly attenuated by naloxone. The rats subjected to chronic pain showed a weaker analgesic response to the intrathecally injected GEMSA. The 3H-GEMSA binding to enkephalin convertase in the spinal cord of these rats produced only a slight increase in KD; besides, no changes in the enzyme activity were observed. The study shows that GEMSA has a potent pharmacological action in the central nervous system. Furthermore, this effect is partly due to the influence of GEMSA on endogenous opioid peptide systems, possibly on proenkephalin A.     

Behavioral change in a cancer patient following intrathecal beta-endorphin administration

A patient with a disseminated malignancy received 3 mg of synthetic beta-endorphin administered intrathecally by lumbar puncture. A marked behavioral syndrome characterized by confusion, hypomanic/manic behavior, and psychosis followed drug administration and persisted for more than 2 days.     

脑室-腹腔分流术后颅内感染的处理经验

目的总结脑室-腹腔分流术后颅内感染的临床特点和治疗效果。方法 2003年1月至2009年1月行脑室-腹腔分流术治疗脑积水患者254例,其中11例分流术后并发颅内感染。对颅内感染者在脑脊液细菌培养和药敏试验结果出来前,通过腰椎穿刺置管鞘内注射可在鞘内应用的广谱抗生素,并持续引流感染的脑脊液;细菌培养和药敏试验结果出来后,选用敏感抗生素鞘内注射;10例病情严重者拔除分流装置,行脑室外引流。结果 11例患者,1例经腰椎穿刺置管鞘内注射抗生素后治愈,10例不断调整引流装置同时脑室内注入抗生素后治愈。结论脑脊液脑室外引流、鞘内或脑室内注射抗生素,以及必要时拔除分流装置是治疗脑室-腹腔分流术后颅内感染的主要措施。     

The long-term effects of nefiracetam on learning in older rabbits

Classical conditioning of the nictitating membrane (NM)/eyeblink response has proven utility in the study of age-related memory disorders. The 750 ms delay eyeblink conditioning procedure was used to investigate the magnitude and duration of the nootropic drug nefiracetam's effect on retention and relearning. After administering daily injections of 0 (vehicle), 5, 10, or 15 mg/kg nefiracetam to 34 retired breeder rabbits during 15 days of acquisition, we tested retention and relearning 1, 5, and 12 weeks post-training. Rabbits received no drug after the initial 15 daily injections. Significant relearning was observed in the 10 mg/kg nefiracetam group 1 and 5 weeks after initial acquisition. Differences in tone-alone retention did not achieve statistical significance, although responses were numerically greater in the 10 mg/kg nefiracetam group. The effect of nefiracetam upon the ability of older rabbits to relearn a previously learned task is apparent up to 5 weeks after drug administration. Under normal conditions, a drug is administered continuously. In this experiment, nefiracetam had a significant effect long after drug administration had ceased. Prolonged administration of nefiracetam may have ameliorating effects greater than those observed in only 15 days of drug administration.     

脑室内注射万古霉素治疗术后颅内感染的方法学及药代动力学研究

目的了解脑室内和静脉联合使用万古霉素治疗神经外科术后颅内感染时脑脊液内药代动力学及理化性质变化规律,为建立颅内局部给药方法的标准提供依据。方法选择开颅术后留置术腔/脑室引流管的颅内感染患者10例,万古霉素q12 h静脉给予1 g,持续泵入2 h,同时,经引流管术腔/脑室局部给予10 mg。分别于给药前、后相应时间点采集静脉血及脑脊液标本测定药物浓度及理化性质。结果万古霉素给药开始后1 h血药浓度达到(41.08±15.83)mg/L,48 h谷浓度为(8.10±7.11)mg/L;脑脊液浓度给药后0.25 h为(412.71±464.81)mg/L,48 h谷浓度为(33.62±31.95)mg/L。理化性质无明显变化。结论通过静脉加小剂量脑室给药,可以提高脑脊液万古霉素浓度,可能成为治疗开颅术后严重颅内感染的一种选择,但其安全性、有效性尚需更大规模的研究证实。     

Morphologic image of structures of the limbic system in rats after prolonged administration of antiepileptics

Morphological changes in the anatomical structures of the limbic system induced by phenytoin and ethosuximide administered in effective doses for 1, 3 and 6 months in rats were analyzed. The clinical symptoms consisted of some vegetative and behavioral disorders, mostly transitory. Differences in gain of body weight depending on the sex of the animal and the drug administered were observed. The morphological changes in the parenchymal and mesenchymal nervous tissue elements were not specific with regard to their topography or to the type of pathological process. Some morphological differences depending on the drug and its period of administration were observed only in rats treated for 1 and 3 months. The neuropathological picture in rats treated with both drugs for 6 months showed a great similarity. The pathological process in the ganglionic cells had the character of degeneration. Morphological changes in the myelin sheaths were due to edema which appeared to be vasculogenic and situated in the white matter. Focal and diffuse proliferation of cellular glia appeared after administration of both drugs for 1 and 3 months while in those treated for 6 months the degenerative changes were seen. The anatomo-comparative study of the neuropathological picture in the rats treated with both drugs and the morphological picture of the limbic system structures in patients with chronic epilepsy indicates that the drugs examined could play some role in the pathogenesis of the limbic system lesions encountered in epileptics.     

颅内感染病原菌的构成及耐药性分析

目的 分析颅内感染的致病菌分布及耐药性,为临床治疗提供参考。方法 对2016年1月至2018年4月收集的13 712例脑脊液样本培养结果进行回顾性分析。结果 共有877例颅内感染,感染率为6.40%。革兰阳性菌占81.64%,其中耐甲氧西林凝固酶阴性葡萄球菌占46.86%,甲氧西林敏感凝固酶阴性葡萄球菌占18.70%,对替加环素、万古霉素及利奈唑胺敏感;革兰阴性菌占18.36%,其中鲍曼不动杆菌表现出广泛耐药性,肺炎克雷伯菌对碳青霉烯类及酶抑制剂类药物敏感。结论 颅内感染以革兰阳性菌为主,对替加环素、万古霉素及利奈唑胺敏感;革兰阴性菌中鲍曼不动杆菌多数耐药。     

Analgesis and convulsant effects of guanidinoethylmercaptosuccinic acid (GEMSA) — A potent enkephalin convertase inhibitor

We studied behavioral effects of the intraventricularly and intrathecally administered guanidinoethylmercaptosuccinic acid (GEMSA) — a potent inhibitor of enkephalin convertase. When given intraventricularly in doses of 3 and 6 μg, GEMSA elicited analgesia; after doses of 12.5 and 25 μg the explosive motor behavior and convulsions occurred. Following the intrathecal administration of GEMSA (12.5, 25 and 50 μg), an increase in the tail-flick latency was observed; moreover that drug potentiated analgesic effects of the intrathecally applied Met⁵-enkephalin-Arg⁶-Phe⁷ and Met⁵-enkephalin-Arg⁶-Gly⁷-Leu⁸. All the above effects of GEMSA were significantly attenuated by naloxone. The rats subjected to chronic pain showed a weaker analgesic response to the intrathecally injected GEMSA. The ³H-GEMSA binding to enkephalin convertase in the spinal cord of these rats produced only a slight increase in K_D; besides, no changes in the enzyme activity were observed. The study shows that GEMSA has a potent pharmacological action in the central nervous system. Furthermore, this effect is partly due to the influence of GEMSA on endogenous opioid peptide systems, possibly on proenkephalin A.     

Continuous intrathecal administration of morphine via an osmotic minipump in the rat

Morphine HCl dissolved in artificial CSF or artificial CSF were administered intrathecally on the dorsum of the lumbar enlargement in rats via ALZET® osmotic minipumps delivering 0.5 μl/h for 14 days. Significant analgesia as assessed by the hot plate test was observed for 3 days after the start of drug administration for both morphine and CSF. No analgesia was found in rats where the catheter was located away from the dorsum of the lumbar enlargement.     

Evaluation of NK and LAK cell activities in neoplastic patients during treatment with morphine.

The cytotoxic activity of Natural Killer (NK) and Lymphokine Activated Killer (LAK) cells in neoplastic patients with or without antalgic treatment was studied. NK cell activity was found reduced in untreated neoplastic patients when compared to healthy subjects. The atalgic treatment with morphine (orally or intrathecally administered) was able to significantly reduce the mean values of NK cell activity found in cancer patients. In three patients the cytotoxicity of NK cells significantly decreased during transfer from oral to intrathecal administration of morphine. In contrast to the NK cell function, the development of LAK cell activity significantly increased in neoplastic patients when compared to healthy controls. Further increments were obtained during treatment with morphine. The oral treatment with morphine was able to determine a higher induction of LAK cells than the intrathecal administration of the drug. Besides providing new knowledge on the effect of morphine on immune system our findings suggest that, in order to include neoplastic patients in clinical trials of adoptive immunotherapy with LAK cells and interleukin-2 (IL-2), the antalgic therapy with oral administration of morphine may represent a better solution than the intrathecal administration of the drug.