利奈唑胺与万古霉素治疗医院获得性耐甲氧西林金黄色葡萄球菌肺炎的疗效比较

目的:比较利奈唑胺与万古霉素治疗医院获得性耐甲氧西林金黄色葡萄球菌(MRSA)肺炎的疗效和安全性。方法:将72例医院获得性MRSA肺炎患者随机均分为两组,利奈唑胺组患者静脉滴注利奈唑胺600 mg,q 12 h;万古霉素组患者静脉滴注万古霉素500 mg,q 8 h。两组患者疗程均为14 d。评价和比较两组患者的临床疗效、细菌学疗效及不良反应情况。结果:利奈唑胺组患者总有效率和细菌清除率显著高于万古霉素组,两组比较差异均有统计学意义(P<0.05),而不良反应发生率与万古霉素组比较差异无统计学意义(P>0.05)。结论:对于医院获得性MRSA肺炎的治疗利奈唑胺总体疗效优于万古霉素,而安全性相似。     

MRSA肺部感染并低蛋白血症患者使用替考拉宁临床研究

目的 探讨替考拉宁对耐甲氧西林金黄色葡萄球菌(MRSA)肺部感染伴低蛋白血症患者的临床疗效。方法 选取2016年1月-2018年6月我院重症监护病房收治的92例MRSA肺部感染患者,将低蛋白血症患者分为两组,A组给予替考拉宁起始6mg/kg q12h,维持6mg/(kg·d)治疗,B组给予起始12mg/kg q12h,维持12mg/(kg·d)治疗,蛋白水平正常者为对照组,给予起始6mg/kg q12h,维持6mg/(kg·d)治疗。分析比较3组患者治疗后的疗效,细菌清除率和不良反应发生率。结果 A组临床有效率、细菌清除率低于对照组,差异均有统计学意义(P<0.05),不良反应率与对照组相当;B组临床有效率、细菌清除率与对照组相当,不良反应率高于对照组,差异有统计学意义(P<0.05)。结论 低蛋白血症患者与蛋白水平正常者相比,替考拉宁的临床疗效明显降低、病原菌清除率降低,通过提高替考拉宁的剂量,临床疗效、病原菌清除率明显提高,但不良反应发生率也伴随升高。     

Nephrotoxicity of teicoplanin in rats

Teicoplanin, a glycopeptide antibiotic, is marketed in a number of European countries and has recently been put on the market in Japan. The spectrum of antibacterial activity of teicoplanin is equivalent or superior to that of vancomycin. The aim of the present study is to examine the nephrotoxicity of teicoplanin compared with vancomycin in rats. Wistar male rats, housed in a light-controlled room at room temperature for 1 week, were used. They were injected with either 15 or 50 mg/kg/day of teicoplanin or 50 or 200 mg/kg/day of vancomycin at 13:00 daily for 14 days. The rats were randomly assigned to groups of five rats each and were housed individually in metabolic cages to collect urine. Urine samples were collected 24 hours prior to the drug treatment and every 24 hours thereafter for 14 days. N-Acetyl-beta-D-glucosaminidase (NAG) activity was determined in the supernatant and expressed in international units per total urine collected for 24 hours. The group which was given vancomycin 200 mg/kg/day had significantly elevated urinary NAG levels compared with the other groups (p < 0.05). No significant differences were observed in the NAG levels in urine among the remaining three groups. These results suggest that the nephrotoxicity of teicoplanin may be only one-fourth that of vancomycin in rats. It appears that by extrapolating the dose amount required for the treatment in humans to rats, the high dose of teicoplanin was set at 50 mg/kg/day and that of vancomycin, 200 mg/kg/day. The recommended dose for teicoplanin will probably be 200 mg/day compared to 2 g/day of vancomycin. If the teicoplanin dose is only one-tenth that of the vancomycin dose, then teicoplanin should be better tolerated than vancomycin in terms of nephrotoxicity.     

Comparison of intravitreal vancomycin and daptomycin application in experimental methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis in rabbits

Abstract

Purpose: To compare bactericidal activities of daptomycin and vancomycin in an experimental rabbit model of methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis.

Methods: The right eyes of 19 New Zealand rabbits weighing 2 to 2.5?kg were used. Each eye was inoculated with 1000 colony-forming units (cfu) of MRSA into the vitreous cavity. 24?h after the inoculation, the rabbits were randomly distributed into three groups: control group (n?=?5) was given 0.1?ml of balanced saline solution, daptomycin group 2 (n?=?7) was given 0.2?mg/0.1?ml daptomycin and vancomycin group 3 (n?=?7) was given 1?mg/0.1?ml vancomycin intravitreally. Clinical examination scores were recorded and vitreous aspirates were obtained for microbiological analysis on days 2 and 3 after MRSA inoculation. Rabbits were sacrificed, and the eyes were enucleated for histopathological examination.

Results: There was no difference between the daptomycin group, vancomycin group and control in terms of the clinical grading of endophthalmitis 24?h after the inoculation. In all treatment groups, mean number of cfu and histopathological scores were significantly lower compared to the control group. There was no difference between the daptomycin and vancomycin group in terms of the histopathological and clinical examination scores. Culture negativity achieved on day 3 was 71.4% and 57.1% in the daptomycin treatment group and the vancomycin treatment group, respectively.

Conclusions: Although both daptomycin and vancomycin are effective in treatment of experimental MRSA endophthalmitis, daptomycin has superior bactericidal activity 72?h after inoculation.     

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。     

替考拉宁与万古霉素治疗耐甲氧西林金黄色葡萄球菌肺炎的疗效比较

目的：比较替考拉宁与万古霉素治疗耐甲氧西林金黄色葡萄球菌（ MRSA）肺炎的安全和有效性。方法选取68例MRSA肺炎患者按照随机数字分组法分为两组：观察组34例,采用替考拉宁治疗;对照组34例,采用万古霉素治疗。观察和比较两组的临床疗效、细菌学疗效及不良反应。结果观察组和对照组的临床总有效率分别为82．35％、76．47％,细菌总清除率分别为91．18％、85．29％,两组差异均无统计学意义（均P＞0．05）;观察组出现红斑、皮疹、腹泻各1例,对照组出现肾毒性4例及耳毒性、静脉炎、腹泻各1例,观察组的总不良反应发生率略低于对照组,但差异无统计学意义（P＞0．05）。结论替考拉宁治疗MRSA肺炎的疗效良好、肾损伤较轻,与万古霉素的治疗效果基本相当,值得临床推广和应用。     

氨溴索对肺耐甲氧西林金黄色葡萄球菌感染患者肺部万古霉素浓度的影响

目的:研究氨溴索对肺部耐甲氧西林金黄色葡萄球菌(MRSA)感染患者血液与肺部万古霉素浓度的影响,评价两药联用的合理性。方法:44例肺部MRSA感染患者经纳入后随机分为2组:A组患者入组后即给万古霉素1.0g,ivd,q12h。B组患者入组后即给药万古霉素1.0g,ivd,q12h,联合使用氨溴索60 mg,iv,q12h。于第4个万古霉素给药剂量之前以咳痰或负压吸痰采集痰液样本,同时收集患者血清。采用荧光偏振免疫法(FPIA法)测定万古霉素浓度。结果:A组、B组患者痰液中万古霉素质量浓度分别为(1.8±2.1)μg.mL-1,(3.6±3.1)μg.mL-1,2组差异有显著性(P<0.05);A组、B组患者万古霉素血药质量浓度分为(15.7±2.5)μg.mL-1,(14.7±2.8)μg.mL-1,2组差异无显著性(P>0.05)。结论:万古霉素与氨溴索联合使用可增加肺部MRSA感染患者痰液中万古霉素浓度,不影响血液中万古霉素的浓度。     

Serum and bone concentrations of teicoplanin and vancomycin: study in an animal model

Teicoplanin and vancomycin are antibiotics widely used in the therapy of bone and joint infections. The aim of this study was to compare bone and serum concentrations of each antibiotic in guinea pigs after administration of 50 mg/kg of teicoplanin or vancomycin by the intravenous route. Serum and bone concentrations were determined immediately before and 0.5, 1, 2, 6, 12 and 24 h after drug administration by means of high performance liquid chromatography. Teicoplanin concentrations were always higher than vancomycin levels. Area under the concentration/time curve was significantly greater for teicoplanin than for vancomycin. In bone, teicoplanin concentration increased up to 6 h, while vancomycin reached its peak after 2 h. Moreover, teicoplanin showed markedly higher levels at 6, 12 and 24 h than vancomycin. In conclusion, the ability of teicoplanin to penetrate bone in greater amount than vancomycin confirms the potential use of teicoplanin in the treatment of bone infections and in the prophylaxis of orthopedic surgery.     

Teicoplanin vs. vancomycin for the treatment of serious infections: a randomised trial

A prospective, randomised study of 56 patients comparing teicoplanin with vancomycin for suspected or proven severe Grampositive infection was conducted. The majority of infections were soft tissue infections (8 teicoplanin; 16 vancomycin) and by chance a significantly higher number of Hickman catheter-related infections occurred in the vancomycin arm (4 vs. 14, P < 0.01). Teicoplanin was administered as a single daily dose of 400 mg iv or im; 5 patients received 200 mg following the initial dose of 400 mg. Vancomycin was given 1 g every 12 h. Fifty-four patients were evaluable for efficacy (26 teicoplanin, 28 vancomycin). Of these, 18 episodes in 17 patients (teicoplanin) and 19 episodes in 18 patients (vancomycin) gave an evaluable clinical response, the success rates being similar (76% teicoplanin; 68% vancomycin). Staphylococcus aureus was the most common pathogen isolated; all pathogens were susceptible to both glycopeptides with MICs < 4 mg/l. Bacteriological elimination rates were similar in both groups (71% teicoplanin; 78% vancomycin). Significantly more patients given vancomycin experienced adverse events (7 teicoplanin; 16 vancomycin; P = 0.03). This caused treatment to be discontinued in 4 cases, compared with only one receiving teicoplanin. The most common vancomycin-related events were histamine-associated reactions (15 patients), including 2 cases of Red Man Syndrome, and nephrotoxicity (5 patients). There were no histamine-mediated events and only one case of nephrotoxicity with teicoplanin. Teicoplanin and vancomycin show similar clinical and bacteriological efficacy and teicoplanin is significantly less toxic and easier to use in patients with severe infection.     

Meningitis due to methicillin-resistant Staphylococcus aureus (MRSA): review of 10 cases

We evaluated retrospectively, 10 MRSA meningitis cases in our hospital that occurred between January 1999 and June 2004. All were post-neurosurgical and were considered to have hospital-acquired meningitis. Fever, leukocytosis, variable conscious levels were the most common findings. Six patients were treated with regimens including teicoplanin, and four with vancomycin. Mean duration of treatment was 23.5+/-18.8 days (range, 3-60 days). One patient died. In cases of MRSA meningitis, intravenous vancomycin is the mainstay of therapy. However, six of these 10 patients were successfully treated with regimens including teicoplanin, suggesting that this agent may be an alternative to vancomycin in the therapy of these cases.     

Ramoplanin versus methicillin-resistant Staphylococcus aureus: in vitro experience

The authors have investigated the activity of ramoplanin against 162 isolates of MRSA from some twenty-six countries around the world. MICs were determined by the plate dilution method in isosensitest agar with an inoculum of 10(6) cfu. MBCs were measured by replication, using velvet pads, from MIC plates after 24 h incubation at 37 degrees C. Time-kill curves were determined from viable counts of cultures in Isosensitest broth (inoculum ca. 5.0 x 10(6) cfu/ml) taken at intervals during shaking culture at 37 degrees C for up to 24 h. Ciprofloxacin, mupirocin, rifampicin, teicoplanin and vancomycin were used as comparison compounds. The following MIC90 (MBC90) values (mg/l) were obtained against a selection of 60 strains: ciprofloxacin 0.8 (1.8), mupirocin 0.27 (19.0), ramoplanin 0.5 (1.0), rifampicin 0.007 (0.01), teicoplanin 1.2 (greater than 32) and vancomycin 2.2 (greater than 32.0). In time-kill experiments, ramoplanin at 20 mg/l and ciprofloxacin at 3.0 mg/l produced 99.9% killing in less than 4h. Mupirocin at 4.0 mg/l was only slowly bactericidal. No resistance was found to mupirocin, ramoplanin, teicoplanin or vancomycin in the 162 isolates tested, whereas ca. 20% resistance was found to ciprofloxacin and rifampicin. The absence of resistance, the high intrinsic activity and the rapid bactericidal effect of ramoplanin against this diverse group of MRSA are very encouraging, and suggest that clinical trials are indicated.     

蒙特卡洛模拟评价中国成人持续静脉输注万古霉素治疗开颅术后MRSA脑膜炎感染的给药方案

目的 应用蒙特卡洛模拟(MCs)评价中国成人开颅术后脑膜炎患者持续静脉输注万古霉素(VAN)治疗耐甲氧西林金黄色葡萄球菌(MRSA)感染的给药方案。方法 搜集我国开颅术后脑膜炎感染患者的群体药动学参数，以及成都区域VAN对MRSA的最低抑菌浓度(minimal inhibitory concentration, MIC)值和其分布频率，MCs 10000例次后得到对应的目标获得概率(PTA)与累计反应分数(CFR)。结果 当MIC为0.03mg/L时予1g/d VAN即可达到满意的抗菌活性；当MIC为0.06mg/L时予1.5g/d VAN即可达到满意的抗菌活性；当MIC为0.12mg/L时予3g/d VAN可达到相对满意的抗菌活性(PTA＞90%)；但当MIC为0.25~2mg/L时即使予3g/d也不能达到满意的抗菌活性；各给药方案的CFR均小于90%。结论 开颅术后治疗MRSA脑膜炎感染采用持续静脉输注常规给药剂量(2g/d)的VAN可能偏低，经验性持续静脉输注VAN可考虑联合用药或改用其他给药途径方式。     

盐酸头孢吡肟治疗小儿下呼吸道感染87例疗效观察

目的评价头孢吡肟（Cefepim,FEP）治疗小儿下呼吸道感染的临床疗效。方法87例患者,分成治疗组46例和对照组41例,分别应用头孢吡肟和头孢地嗪,剂量均为50mg/（kg.d）,1次/12h,静脉滴注给药,疗程7～10d。结果头孢吡肟和头孢地嗪临床有效率分别为91.3%、87.8%,细菌清除率分别为91.0%、87.0%,不良反应发生率较低。结论头孢吡肟可作为治疗小儿下呼吸道感染有效和安全的抗生素。     

利奈唑胺与万古霉素对耐甲氧西林金黄色葡萄球菌肺炎的有效性和安全性比较

目的:探讨利奈唑胺和万古霉素对治疗耐甲氧西林金黄色葡萄球菌(MRSA)引起肺炎的有效性和安全性。方法:本研究是前瞻是研究,研究对象为2012年5月-2015年1月在我院院内感染性肺炎成年患者。患者随机分为两组,分别接受利奈唑胺(每12 h 600 mg)和万古霉素(每12 h 15 mg·kg^-1)治疗,疗程7~14 d。治疗过程中根据药物浓度对万古霉素剂量进行调整。观察终点为试验结束(EOS)时患者的临床结果。其他指标还包括治疗结束(EOT)和试验结束(EOS)时意向性治疗(ITT)患者的临床疗效以及符合方案(PP)患者、ITT患者在EOT和EOS时的细菌学结果,评估患者存活率和药物安全性。结果:1184例院内感染性肺炎患者中,ITT患者448例(利奈唑胺组n=224,万古霉素组n=224),PP患者348例(利奈唑胺组n=172,万古霉素组n=176)。PP患者中,95/165例(57.6%)利奈唑胺治疗患者和81/174例(46.6%)万古霉素治疗患者在EOS时成功治愈(95% CI:0.5%~21.6%,P=0.042)。两组患者60 d死亡率(利奈唑胺组10.7%,万古霉素组17.0%)有明显差别,两组不良反应发病率相近,但万古霉素引发的肾脏毒性损伤更为常见(万古霉素组18.2%,利奈唑胺组8.4%)。结论:利奈唑胺治疗MRSA院内感染性肺炎临床预后要明显好于万古霉素,且肾毒性更小。     

Successful treatment with moxifloxacin of experimental aortic valve endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA)

Moxifloxacin (MXF) is an 8-methoxyquinolone with high activity against Gram-positive bacteria. In an experimental model of aortic valve endocarditis (EAVE), the efficacy of MXF was evaluated against a strain of methicillin-resistant Staphylococcus aureus (MRSA). Rabbits with catheter-induced aortic valve vegetations were randomly assigned to a control group or to groups receiving MXF 20 mg/kg intravenous (i.v.) twice a day (bid) or vancomycin (VAN) 30 mg/kg i.v. bid for a total of eight doses (4 days). Rabbits were sacrificed 15 h after the last dose of antibiotics. In another group, treatment with MXF was extended to 5 days and rabbits were sacrificed 5 days after the last dose (10th dose) of MXF in order to detect possible relapses of endocarditis after the end of treatment (test-of-cure (TOC) study). Both MXF and VAN significantly reduced the bacterial load in vegetations (P < 0.001 vs. controls). All animals in the MXF-TOC group had sterile vegetations. MXF given at a dose of 20 mg/kg i.v. bid for 4 days was equally effective as VAN in the treatment of EAVE due to MRSA. When treatment with MXF was extended to 5 days, the cure rate reached 100% and no relapses of endocarditis were observed.     

蒙特卡洛模拟评价鞘内注射万古霉素治疗耐甲氧西林金黄色葡萄球菌颅内感染的给药方案

目的 应用蒙特卡洛模拟评价万古霉素鞘内注射治疗成人开颅术后耐甲氧西林金黄色葡萄球菌(MRSA)颅内感染的给药方案.方法 查阅有关成都地区万古霉素对MRSA菌株的最低抑菌浓度值(MIC)及其分布频率与中国成人开颅术后脑膜炎感染患者的群体药动学资料,Crystal Ball软件模拟5 000例次后得到相应目标获得概率(PTA)和累计反应分数(CFR).结果 当MIC值分别为0.03、0.06、0.12、0.25、0.50、1、2 mg·L-1时,万古霉素对MRSA的MIC分布频率分别为12.79％、12.79％、12.79％、12.79％、12.79％、29.07％和6.98％.当MIC分别为≤0.25、0.05、1、2mg·L-1时,分别予2.5、5、10、20 mg·d-1即可达到满意的抗菌活性(PTA=100％);鞘内注射10 mg·d-1的给药方案,其CFR大于90％.结论 结合各MIC分布频率与达满意抗菌活性的最低剂量可知,大多数成人开颅术后MRSA颅内感染的患者鞘内注射万古霉素10 mg·d-1时均可达到满意的治疗效果,经验性鞘内注射万古霉素时可考虑10 mg·d-1的给药剂量方案.     

帕珠沙星治疗泌尿生殖系统感染的疗效观察

目的:评价帕珠沙星治疗泌尿生殖系统感染的临床疗效和安全性。方法:采用病例对照研究的方法将84例泌尿生殖系统感染患者随机分为两组,治疗组45例,给予帕珠沙星300 mg,ivd,q12h;对照组39例,给予左氧氟沙星200 mg,ivd,q12 h;疗程均为7-14 d。结果:治疗组和对照组的临床有效率分别为91．1％和89．7％(P>0．05),细菌清除率分别为92．2％和90.2％(P>0．05);不良反应发生率分别为8．9％和7．7％(P>0．05),两组间差别均无统计学意义。结论:帕珠沙星是治疗泌尿生殖系统感染安全有效的药物。     

莫西沙星对224株肠球菌的体外抗菌活性研究

目的观察莫西沙星对224株肠球菌的体外抗菌活性。方法采用二倍琼脂稀释法对224株肠球菌进行体外抗菌实验．并与意大利Aventis公司生产的替考拉宁和Lilly公司生产的万古霉素进行抗菌效果对比。结果莫西沙星的抗菌效果较好，对169株粪肠球菌和51株屎肠球菌的MIC90均为4mg／L，替考拉宁和万古霉素对169株粪肠球菌的MIC90分别为1、2mg／L；对51株屎肠球菌的MIC90分别为0．5和2mg／L。结论莫西沙星对224株肠球菌的抗菌效果较好，肠球菌对莫西沙星的敏感率均为76．34％。莫西沙星的抗菌效果低于替考拉宁和万古霉素。     

Cost analysis of 2 empiric antibacterial regimens containing glycopeptides for the treatment of febrile neutropenia in patients with acute leukaemia.

OBJECTIVE: Patients with cancer-associated neutropenia are at high risk of developing severe infections which can be fatal if treatment is not promptly administered. For this reason, fever is treated as soon as possible with broad spectrum antibacterial therapy. The objective of this study was to conduct a cost analysis in Italy comparing 2 empiric glycoprotein-containing antibacterial regimens for the treatment of febrile neutropenia in patients with acute leukaemia. DESIGN AND SETTING: A retrospective cost analysis was conducted, using the records of 527 febrile neutropenic patients with acute leukaemia who participated in an 18-month multicentre (29 Italian haematological units) randomised trial during 1991. All patients received either of the following 2 empiric intravenous regimens, each containing 3 antibacterial agents: ceftazidime (2 g, 3 times daily) and amikacin (15 mg/kg/day, in 3 separate doses) plus teicoplanin (6 mg/kg, in a single dose) or vancomycin (30 mg/kg/day, in 2 separate doses). Economic analyses were carried out from a hospital perspective. Only the direct costs per patient, i.e. mean antibacterial treatment and management cost, mean overall treatment failure cost and mean cost of adverse effects, were included. MAIN OUTCOME MEASURES AND RESULTS: No differences were found in the clinical response, defined as the improvement in the rate of fever or infection (if documented), between the 2 regimens. However, tolerability, defined as the incidence of adverse effects probably or definitely related to the assigned treatment, was reported to be better with the teicoplanin-rather than the vancomycin-containing regimen. CONCLUSIONS: Thus retrospective cost analysis showed that despite the higher acquisition cost of teicoplanin relative to vancomycin, the lower incidence of adverse effects associated with teicoplanin and its ease of administration (single daily dose) resulted in equivalent overall treatment costs between teicoplanin- and vancomycin containing regimens.     

利奈唑胺与替考拉宁治疗革兰阳性球菌感染的疗效比较

目的:比较利奈唑胺与替考拉宁治疗革兰阳性球菌感染患者的疗效和安全性。方法:采取回顾性研究,选取确诊的革兰阳性球菌感染住院患者100例,分为2组,利奈唑胺组(50例)给予注射用利奈唑胺600mg/次,q12h,静脉滴入,治疗时间7～28d;替考拉宁组(50例)给予注射用替考拉宁400mg/次,qd,静脉滴入,治疗时间7～28d。比较2组的疗效和不良反应。结果:利奈唑胺组有效率96%,病原菌清除率80%,总不良反应发生率16%;替考拉宁组有效率84%,病原菌清除率68%,总不良反应发生率12%。2组有效率和病原菌清除率差异均有统计学意义(P<0.05)。结论:对革兰阳性球菌感染的治疗,利奈唑胺有效性优于替考拉宁。