奈替米星的临床研究

目的研究来替米星每日1次投药法治疗下呼吸道感染的临床效果、药代动力学、抗生素后效应和药物毒性。方法48例患者分为三组：（1）单一组14例，使用奈替米星，每天总量为6mg·kg-1·h-1；（2）合用组16例，使用头孢唑啉每12小时1次投药3g，奈替米星每天200mg；（3）对照组18例，使用头胞唑啉每12小时投药3g，与阿米卡星每天200mg联合使用，分别观察临床症状、实验室检查及临床疗效；应用荧光偏振分析仪（TDX）药物浓度自动分析仪研究其药代动力学；应用AVANTAGE生物分析仪研究奈替米星抗生素后效应，观察了奈替米星的肾、耳毒性。结果每日1次单用奈替米星组疗效较头抱叹批及阿米卡星组好。平均血药浓度为27．23mg／L谷浓度为0．23mg／L,半数药物消除相时间为5．095小时，药时曲线下面积为70μg·h-1·ml-1。奈替米皇0．5、1及4倍最低抑菌浓度（MIC）对4种细菌均显示不同程度的抗生素后效应。本组研究未发现耳、肾毒性。结论奈替米星每日1次投药法有较高血清浓度，较大药时曲线下面积，作为浓度依赖性杀菌药，此药临床效果较好，而且其抗生素后效应时间较长。     

奈替米星与阿米卡星临床疗效观察

目的以阿米卡星为对照评价奈替米星治疗下呼吸道感染的临床有效性及安全性。方法共人选病例132例，可评价疗效者102例，其中试验组（奈替米星）与对照组（阿米卡星）分别为52例与50例。安全性评价人选病例113例，两组分别为56例与57例。给药方法试验组每次200mg，每日1次，对照组每次200mg，每日2次，两组疗程均为7～14天。结果试验组与对照组的临床有效率分别为84．61％与64．00％，细菌清除率分别为90．91％与66．67％，敏感菌百分率分别为93．18％与71．43％，听力下降发生率分别为1．79％与15．79％。以上结果经统计学处理两组差异有显著性。结论奈替米星为治疗下呼吸道感染的安全、有效的抗菌药物。     

奈替米星治疗消化道感染56例

1996年 6月～ 2 0 0 0年 2月 ,我们应用奈替米星治疗消化道感染 5 6例 ,获得了满意的疗效。现报告如下。一般资料 :本组男 2 9例 ,女 2 7例 ;年龄 16～ 74岁 ,平均41± 15岁。肠道系统感染 2 1例 ,肝脓肿 14例 ,细菌性痢疾 8例 ,急性肠炎 7例 ,伪膜性肠炎 4例 ,肛周化脓性炎症 2例。治疗方法 :轻中度感染用奈替米星 0 .2 g加 5 %葡萄糖液5 0 0 ml静滴 ,每天 1次 ;重度感染静滴奈替米星 0 .3～ 0 .4g/天。疗程为 3～ 2 8天。体质较差者配合支持疗法。肝脓肿配合穿刺引流 ,胆道系统感染均作十二指肠引流 ,肛周化脓炎症配合手术切开引流。结果 …     

法莫替丁治疗消化性溃疡临床分析

近年来，我们采用法莫替丁治疗消化性溃疡病人（PU）54例，与对照组52例病人比较，疗效显著，现报告如下。临床资料：两组病人年龄13～82岁，平均45．8岁，均经纤维胃镜检查确诊。溃疡长径0．3～2cm。两组病人的年龄、病程及临床症状有可比性。治疗方法：两组均系溃疡急性发作病人，入院后均用5％葡萄糖盐液500ml加庆大霉素24万U静滴，每日1次，10天后改为庆大霉素8万U口服，每日3次；有消化道出血者加用止血药。治疗组用法英替丁20mg，加入10％葡萄糖液250ml中静滴，每日2次，10～15天后改法英替丁20mg口服，每日2次，或晚9点顿服40mg。…     

硫氮(艹卓)酮联合左卡尼汀治疗不稳定性心绞痛

为研究硫氮[艹卓]酮联合左卡尼汀治疗不稳定性心绞痛（UAP）的疗效，将60例同期收治的UAP患者随机分为治疗组及对照组各30例，其年龄、性别、病情等无显著差异（P〉0．05）。两组均予阿司匹林、肝紊、辛伐他汀等基础治疗。对照组在此基础上予硝酸甘油10mg＋5％葡萄糖250ml（糖尿病患者用生理盐水）静滴，1次／d；治疗组予硫氮[艹卓]酮30mg、左卡尼汀2．0g分别加入5％葡萄糖250ml（或生理盐水）中静滴，1次／d。两组均连用10d为一疗程。治疗后治疗组症状有效率及心电图有效率（93．3％，70．0％）均显著高于对照组（63．3％，30．3％），P均〈0．01。提示硫氮[艹卓]酮联合左卡尼汀治疗UAP效果确切。     

氦氖激光联合灯盏花素治疗脑梗死疗效观察

将65例脑梗死患者随机分为观察组43例和对照组22例，两组均予常规对症处理，对照组在此基础上予复方丹参液20ml，胞二磷胆碱0．5g加生理盐水500ml静滴（1次／d，10d为一疗程）；观察组予灯盏花素15ml加5％葡萄糖盐水500ml静滴（1次／a，10d为一疗程），同时予氦氖激光血管内放射治疗。观察两组治疗前后血液流变学各项指标和临床疗效。结果观察组治疗后血液流变学指标有显著改善，有效率（93．02％）显著高于对照组（73％），提示灯盏花素联合氦氖激光血管内照射治疗脑梗死效果确切。     

奥曲肽联合奥美拉唑治疗食管胃底静脉曲张出血30例疗效观察

目的观察应用奥曲肽联合奥美拉唑治疗食管、胃底静脉曲张出血的疗效。方法患者分为2组，每组30例，A组予以奥曲肽25mg／h静滴，每日用量600mg；奥美拉唑40mg静脉滴注，每日2次。B组予奥曲肽25mg／h静脉滴注，每日用量600mg。结果两组治疗前基本资料相似，具可比性。止血时间A组（14．2±12．6）h，明显快于B组（21．4±19．6）h（P〈0．05），6、12、24、48、72h止血率A组为50％、70％、80％、86．7％、93．3％，明显高于B组36．7％、53．3％、70％、76．7％、80％，（P〈0．05和0．01）。治疗总有效率：A组为93．3％，明显高于B组80％（P〈0．01）。再出血率：A组10．0％，明显低于B组的23．3％（P〈0．05）。两组均未发生明显不良反应。结论奥曲肽联合奥美拉唑治疗食管胃底静脉曲张出血，疗效可靠值得推广应用。     

奈替米星联合左氧氟沙星治疗耐多药肺结核的临床疗效及安全性

目的探讨奈替米星联合左氧氟沙星治疗耐多药肺结核的临床疗效及其安全性。方法选取成都市传染病医院2014年5月—2017年5月收治的耐多药肺结核患者114例,随机分为对照组和联合组,各57例。对照组患者采用3ZThOED/9ThOD化疗方案,联合组患者给予左氧氟沙星联合奈替米星治疗。比较两组患者的临床疗效及化疗后3、6、9、12个月痰菌阴转情况,并观察患者毒副作用发生情况。结果联合组患者临床疗效优于对照组(P0.05)。联合组患者治疗后3、6、9、12个月痰菌阴转率高于对照组(P0.05)。联合组患者毒副作用发生率低于对照组(P0.05)。结论奈替米星联合左氧氟沙星治疗耐多药肺结核的临床疗效确切,可有效改善患者的临床症状,促进病灶吸收,且安全性好。     

不同剂量氢氯噻嗪联合缬沙坦治疗高血压病合并舒张性心功能不全的临床观察

目的 观察不同剂量氢氯噻嗪联合缬沙坦对高血压病合并舒张性心力衰竭病人心功能的疗效。方法 将87例高血压病合并左室扩大舒张性心力衰竭病人随机分为治疗1组（30例）、治疗2组（30例）、对照组（27例），3组均口服阿司匹林100mg，每日1次，硝酸异山梨醇酯10mg，每日3次。治疗1组加服缬沙坦80mg，每日1次口服，氢氯噻嗪6．25mg，每日1次口服；治疗2组加服缬沙坦80mg，每日1次口服，氢氯噻嗪12．5mg，每日1次口服；对照组加服硝苯地平10mg，每日3次口服；疗程均为6个月。观察血压及超声心动图指标变化。结果 治疗1组、治疗2组反映左室形态的指标及反映左室舒张功能指标有明显改善（P〈0．05），与对照组治疗后比较差异有统计学意义（P〈0．05），3组降压效果无明显差异（P〉0．05），临床疗效评定，治疗1组、治疗2组及对照组总有效率分别为87％、90％和56％，死亡率分别为3．3％、0和14．8％，治疗组与对照组比较有统计学意义（P〈0．01）。结论 不同剂量氢氯噻嗪联合缬沙坦不仅降压，还可改善左室舒张功能，逆转扩大的左心室并明显降低死亡率。     

α硫辛酸联合甲钴胺治疗糖尿病周围神经病变临床研究

将102例2型糖尿病合并周围神经病变患者随机分为治疗组52例和对照组50例。治疗组予硫辛酸600mg静滴,甲钴铵1000p,g静滴;对照组仅予甲钴铵1000μg／d静滴,疗程均14d。结果治疗组显效33例,有效14例,总有效率90．0％;对照组显效19例,有效15例,总有效率68．0％,两组总有效率比较,P〈0．01;两组治疗期间均无明显不良反应。结论硫辛酸联合甲钴胺治疗2型糖尿病性周围神经病疗效确切,且安全性高。     

高剂量左氧氟沙星治疗呼吸系统感染的安全性与有效性的病例对照分析

目的观察大剂量左氧氟沙星静滴治疗呼吸系统感染的安全性与有效性。方法对70例呼吸道细菌感染患者,分为高剂量左氧氟沙星(可乐必妥)500mg/d一次静脉滴注的治疗组和常规剂量300mg/次每天两次静脉滴注的对照组,疗程5~10天后进行治疗前后两组间的比较。结果治疗组和对照组的临床总有效率分别为93.3%和91.6%,经统计学处理差异无显著性;不良反应发生率治疗组和对照组分别为6.6%和6.1%,两组间无统计学意义;但三日症状缓解率差异有统计学意义,且总疗程治疗组较对照组缩短。结论高剂量左氧氟沙星治疗呼吸道感染疗效良好,副作用较小,不良反应较少,是治疗轻中重度呼吸系统感染较理想的药物。     

甲磺酸帕珠沙星注射液治疗急性细菌感染的疗效研究

目的评价帕珠沙星治疗急性细菌感染的临床疗效和安全性。方法采用随机、双盲、对照试验的方法,治疗组为甲磺酸帕珠沙星注射液,对照组为左氧氟沙星,每组各20例,纳入对象为呼吸道、泌尿道感染,甲磺酸帕珠沙星用量:轻度感染500 mg Qd静滴;中度感染500 mg B id静滴。左氧氟沙星用量:轻度感染200 mg Qd静滴;中度感染200 mg B id静滴。疗程均为7~14 d。结果甲磺酸帕珠沙星的临床治愈率70.0%(14/20),有效率90.0%(18/20),细菌清除率87.5%(14/16);对照组左氧氟沙星分别为65.0%(13/20),90.0%(18/20),86.7%(13/15)。帕珠沙星和左氧氟沙星不良反应发生率均为8.7%。以上结果经统计学处理,差异均无统计学意义(P均>0.05)。结论甲磺酸帕珠沙星是治疗轻中度呼吸道、泌尿道感染有效、安全的抗菌药物。     

Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study.

Linezolid, the first oxazolidinone, is active against gram-positive bacteria, including multidrug-resistant strains. This multinational, randomized, double-blind, controlled trial compared the efficacy, safety, and tolerability of linezolid with vancomycin in the treatment of nosocomial pneumonia. A total of 203 patients received intravenous linezolid, 600 mg twice daily, plus aztreonam, and 193 patients received vancomycin, 1 g intravenously twice daily, plus aztreonam for 7-21 days. Clinical and microbiological outcomes were evaluated at test of cure 12-28 days after treatment. Clinical cure rates (71 [66.4%] of 107 for linezolid vs. 62 [68.1%] of 91 for vancomycin) and microbiological success rates (36 [67.9%] of 53 vs. 28 [71.8%] of 39, respectively) for evaluable patients were equivalent between treatment groups. Eradication rates of methicillin-resistant Staphylococcus aureus and safety evaluations were similar between treatment groups. Resistance to either treatment was not detected. Linezolid is a well-tolerated, effective treatment for adults with gram-positive nosocomial pneumonia.     

左氧氟沙星治疗老年糖尿病合并社区获得性肺炎疗效观察

目的评价左氧氟沙星400mg每天1次治疗老年糖尿病合并社区获得性肺炎的安全性和有效性。方法本研究采用对照研究的方法，实验组采用左氧氟沙星400mg／次，每天1次静脉滴注；对照组采用左氧氟沙星200mg／次，每天2次静脉滴注，总疗程均为10～14d。观察两组治疗老年糖尿病合并社区获得性肺炎的临床疗效和安全性。结果本研究共入选患者74例，可作临床疗效评价患者70例，实验组和对照组分别为36例和34例，实验组和对照组的基本情况、疾病类型、用药天数无显著性差异（P〉0．05）；两组临床有效率、痊愈率、细菌清除率，无统计学差异（P〉0．05）；两组不良反应率亦无显著性差异（P〉0．05）。结论左氧氟沙星400mg每天1次静脉滴注治疗老年糖尿病合并社区获得性肺炎疗效良好，不良反应程度较低，患者可耐受，每天1次给药，方便临床治疗。     

Cefepime

Abstract

Cefepime (Maxipime®, Maxcef®, Cepimax®, Cepimex®, Axepim®¹), a parenteral fourth-generation cephalosporin, is active against many organisms causative in pneumonia. Cefepime has in vitro activity against Gram-positive organisms including Staphylococcus aureus and penicillin-sensitive, -intermediate and -resistant Streptococcus pneumoniae similar to that of cefotaxime and ceftriaxone. Cefepime also has good activity against Gram-negative organisms, including Pseudomonas aeruginosa, similar to that of ceftazidime. Importantly, cefepime is stable against many of the common plasmid- and chromosome-mediated β-lactamases and is a poor inducer of AmpC β-lactamases. As a result, it retains activity against Enterobacteriaceae that are resistant to third-generation cephalosporins, such as derepressed mutants of Enterobacter spp. Cefepime may be hydrolyzed by the extended-spectrum β-lactamases produced by some members of the Enterobacteriaceae, but to a lesser extent than the third-generation cephalosporins.Monotherapy with cefepime 1 or 2g, usually administered intravenously twice daily, was as effective for clinical and bacteriological response as ceftazidime, ceftriaxone or cefotaxime monotherapy (1 or 2g two or three times daily) in a number of randomized, clinical trials in hospitalized adult, or less commonly, pediatric, patients with generally moderate to severe community-acquired or nosocomial pneumonia. More limited data indicated that monotherapy with cefepime 2g three times daily was also as effective in treating patients with nosocomial pneumonia as imipenem/cilostatin 0.5g four times daily, and when combined with amikacin, cefepime was as effective as ceftazidime plus amikacin. Patients with pneumonia who failed to respond to previous antibacterial therapy with penicillins or other cephalosporins responded to treatment with cefepime.Cefepime is generally well tolerated, with a tolerability profile similar to those of other parenteral cephalosporins. In clinical trials, the majority of adverse events experienced by cefepime recipients were mild to moderate and reversible. The most common adverse events with a causal relationship to cefepime reported in clinical trials included rash and diarrhea. Other, less common, adverse events included pruritus, urticaria, nausea, vomiting oral candidiasis, colitis, headache, fever, erythema and vaginitis. Conclusion: Cefepime is an established and generally well tolerated parenteral drug with a broad spectrum of antibacterial activity which, when administered twice daily, provides coverage of most of the pathogens that may be causative in pneumonia. In randomized clinical trials in hospitalized patients with generally moderate to severe community-acquired or nosocomial pneumonia, cefepime monotherapy exhibited good clinical and bacteriological efficacy. Cefepime may become a preferred antibacterial agent for infections caused by Enterobacter spp. With prudent use in order to prevent the emergence of resistant organisms, cefepime will continue to be a suitable option for the empiric treatment of pneumonia.

Antibacterial Activity

Cefepime acts by binding to penicillin-binding proteins and inhibiting the synthesis of the bacterial cell wall. Due to its zwitterionic nature, cefepime can penetrate the porins of the outer membrane of Gram-negative bacteria faster than the third-generation cephalosporins.Cefepime has a broad spectrum of antibacterial activity in vitro. Data from large in vitro or surveillance studies collecting isolates since 1997 have shown that cefepime is active against Gram-positive and Gram-negative bacteria commonly implicated in pneumonia. Using the newly revised US National Committee for Clinical Laboratory Standards cefepime breakpoints for Streptococcus pneumoniae, cefepime is highly active against strains of penicillin-susceptible and -intermediate S. pneumoniae and has good activity against penicillin-resistant strains. Ceftazidime, cefotaxime, ceftriaxone and imipenem were also highly active against penicillin-susceptible strains of S. pneumoniae. Against penicillin-intermediate or -resistant strains, cefepime exhibited similar activity to cefotaxime, ceftriaxone and imipenem, but was more active than ceftazidime. Cefepime shows excellent activity against methicillin-susceptible Staphylococcus aureus, similar to that of cefotaxime, ceftriaxone and imipenem, and better than that of ceftazidime. However, like other β-lactam agents, cefepime is inactive against methicillin-resistant S. aureus.Cefepime has excellent in vitro activity against Escherichia coli, Klebsiella spp., Haemophilus influenzae and Moraxella catarrhalis similar to that of ceftazidime, ceftriaxone, cefotaxime and imipenem. Cefepime has good activity against Enterobacter spp. similar to that of imipenem and better than that of the third-generation cephalosporins. Additionally, cefepime has similar activity against Pseudomonas spp. as ceftazidime and imipenem. Cefepime showed little activity against Stenotrophomonas maltophilia and highly variable activity against Acinetobacter spp., similar to that of the third-generation cephalosporins. Additionally, like the third-generation cephalosporins, cefepime had highly variable activity against anaerobes, such as Bacteroides spp., Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp., Prevotella spp. and Veilonella spp. that are commonly causative pathogens of aspiration pneumonia.Cefepime is stable against the common plasmid-mediated β-lactamases including TEM-1, TEM-2, SHV-1, OXA-2, OXA-3, PSE-1 to PSE-4 and ROB-1 and the chromosomal cephalosporinases K14, P99 and BRO-1. Unlike the third-generation cephalosporins, cefepime does not induce AmpC β-lactamase hyperproduction and has enhanced stability against the AmpC chromosomal β-lactamases produced by Enterobacter spp. and P. aeruginosa. Cefepime has moderate activity against Enterobacteriaceae producing plasmid-mediated AmpC β-lactamases. However, like most β-lactam agents, cefepime may be hydrolyzed by the extended-spectrum β-lactamases, but to a lesser extent than the third-generation cephalosporins.The administration of cefepime (1g twice daily for 5 or 8 days) to a total of 14 healthy men in two studies resulted in few changes to the fecal flora. The total mean counts of bacteria changed only slightly and returned to normal after the cessation of cefepime administration. Clostridium difficile was detected in the feces of one participant in each study; however, neither volunteer experienced diarrhea.Cefepime, like other β-lactam agents, exhibits time-dependent bactericidal activity. A number of studies using pharmacokinetic data from healthy volunteers combined with in vitro data for the inhibition of various bacterial isolates have shown that intermittent doses (1 or 2g twice daily) or continuous infusions (3 or 4g over a 24 hour period) of cefepime were associated with plasma concentrations above the minimum inhibitory concentration required to inhibit the growth of 90% of isolates for a sufficient proportion of the dosage interval for the majority of Enterobacteriaceae, streptococci and staphylococci tested.

Pharmacokinetic Properties

The absorption kinetics of cefepime are linear over the 0.25–2g dose range. After intravenous administration, maximum cefepime plasma or serum concentrations (C_max) were 16–133 mg/L over the 0.25–2g dose range, whereas the same doses of cefepime administered via intramuscular injection achieved C_max values of 8–58 mg/L in healthy volunteers. The absorption of intramuscular cefepime (0.25–2g) was rapid, as the time to C_max was reached after 1.00–1.58 hours. The bioavailability of intramuscular cefepime was approximately 100% in healthy volunteers. There was no accumulation of cefepime after multiple intravenous or intramuscular administration to individuals with normal renal function.The plasma protein binding of cefepime is relatively low (14–19% in healthy adult volunteers). Cefepime has been shown to penetrate bronchial mucosa and lung tissue. The volume of distribution at steady-state was not dependent on the dose and ranged from 16–19L in healthy adult volunteers.Cefepime undergoes minimal metabolism and is primarily eliminated as unchanged drug by the kidneys. The total clearance (CL_T) and renal clearance (CL_R) of cefepime are independent of the administered dose, but are directly proportional to the rate of creatinine clearance. After a single intravenous or intramuscular injection of cefepime (0.25–2g), CL_T and CL_R ranged from 7.32–9.12 L/h (122–152 mL/min) and 5.4–8.28 L/h (90–138 mL/min), respectively. The mean elimination half-life (t1/2) of cefepime is independent of the dose and after intravenous or intramuscular administration of cefepime (0.25–2g) in healthy adults was about 2–2.4 hours.The pharmacokinetics of cefepime were not significantly affected by acute respiratory illness. The elimination kinetics of cefepime in healthy elderly volunteers with normal renal function for their age differed from those of younger volunteers but this was not clinically significant. The pharmacokinetics of cefepime in children and adolescents were similar to those previously determined for healthy adults.As cefepime is eliminated by the kidneys, patients with renal impairment have slower elimination kinetics than healthy volunteers. In a study in patients with varying degrees of renal impairment, the CL_T and CL_R decreased and the t1/2 increased with decreasing renal function. Studies in patients with renal failure have shown that hemodialysis, hemofiltration and continuous renal replacement therapies effectively eliminate cefepime. The pharmacokinetics of cefepime in individuals with hepatic impairment are not appreciably different from those in healthy volunteers.

Therapeutic Efficacy

In randomized, generally nonblind trials, cefepime monotherapy was as effective as monotherapy with ceftazidime or ceftriaxone in adult patients with community-acquired (CAP). In clinically evaluable patients with CAP treated with cefepime (1 or 2g twice daily), clinical response rates (resolution or improvement) at the end of therapy ranged from 79–95% of patients and were generally similar to those achieved in the recipients of comparator drugs (1 or 2g two or three times daily; range 73–98% of patients). Bacteriological eradication rates (complete or presumed) in cefepime recipients (91–100% of patients or isolated pathogens) were similar to those achieved with ceftazidime and ceftriaxone (97–100% of patients or isolated pathogens).Similarly, in patients with CAP or nosocomial pneumonia (hospital-acquired pneumonia; HAP) or pneumonia of unspecified origin, cefepime monotherapy (1 or 2g twice daily) provided similar clinical efficacy to monotherapy with ceftazidime (1 or 2g two or three times daily) [58–90% vs 60–94% of patients] or cefotaxime (2g three times daily) [92% and 98% vs 86% and 93% of patients]. Cefepime recipients also achieved similar bacteriological eradication rates to those receiving ceftazidime (85–97% vs 73–97% of pathogens) or cefotaxime (100% vs 93% of patients with bacterial eradication and 95% of pathogens eradicated).Cefepime monotherapy (2g three times daily) produced a similar satisfactory response rate to (59% vs 57% of patients), and a slightly higher bacteriological eradication rate (52% vs 44%) than, imipenem/cilastatin 0.5g four times daily for patients with nosocomial pneumonia admitted to the ICU.In three randomized, comparative clinical trials in pediatric patients with CAP or HAP, monotherapy with cefepime (50 mg/kg/dose two to three times daily) was as effective as ceftazidime (50 mg/kg/dose three times daily) and appeared as effective as cefotaxime (30 mg/kg/dose four times daily) or cefuroxime (100 mg/kg/day in three divided doses), although the latter two comparisons involved ≤10 patients per treatment group. Additionally, in a randomized, double-blind trial in elderly patients with CAP, cefepime 2g twice daily produced a similar clinical (79% vs 75% of patients) and bacteriological response (94% vs 100% of patients) to ceftriaxone (1g twice daily).Cefepime monotherapy also proved clinically effective as a therapy for adult patients with pneumonia who had failed to respond to previous antibacterial therapy with penicillins or other cephalosporins (clinical response rate 70.1%). Cefepime achieved a satisfactory bacteriological response in 87.9% of patients with pneumonia who failed to respond to previous treatment with penicillins and in 78.6% in those previously treated with other cephalosporins.Cefepime was an effective treatment when used as part of a combination regimen with amikacin in ventilated patients with HAP. The cefepime (2g twice daily) plus amikacin (7.5 mg/kg twice daily) regimen was as effective as ceftazidime (2g three times daily) plus amikacin (7.5 mg/kg twice daily), with a clinical cure rate of approximately 68% of patients for the per-protocol analysis in both treatment groups and bacteriological eradication in 86.5% vs 89.3% of microbiologically evaluable patients.

Tolerability

In clinical trials, intravenous or intramuscular cefepime was generally well tolerated in hospitalized patients with pneumonia. The majority of adverse events were mild to moderate in intensity and reversible upon discontinuation of treatment.In a pooled analysis of patients with pneumonia, urinary tract infections and other serious infections, the most common adverse events that occurred during treatment with cefepime were rash and diarrhea. Other less common adverse events probably related to cefepime included pruritus, urticaria, nausea, vomiting, oral candidiasis, colitis, headache, fever, erythema and vaginitis.Comparative clinical trials in adults with pneumonia have indicated that cefepime 1 or 2g twice daily has a similar tolerability profile to that of ceftazidime, ceftriaxone and cefotaxime (1 or 2g twice or three times daily) with no significant difference in the incidence, type or severity of adverse events. The percentage of patients with HAP admitted to the ICU receiving cefepime 2g three times daily that experienced adverse events was also similar to the percentage of patients receiving imipenem 0.5g four times daily.Pediatric patients with pneumonia treated with cefepime 50 mg/kg/dose three times daily experienced a similar number, type and severity of adverse events as those receiving the same dose of ceftazidime three times daily. According to pooled tolerability data from pediatric patients, the most commonly reported adverse events in cefepime recipients were fever, diarrhea and rash.Cefepime has been associated with rare instances of neurotoxicity, including encephalopathy, myoclonus and seizures in postmarketing experience. Most episodes occurred in patients with renal impairment who received doses of cefepime greater than those recommended by the manufacturer.

Pharmacoeconomic Considerations

Two cost analyses in patients with HAP or various bacterial infections, using similar acquisition costs for cefepime and ceftazidime, found that the institutional costs associated with cefepime therapy appear less than those of ceftazidime although no statistics were given in one model. When other factors (such as the cost of concomitant antibacterial agents, agents used to treat clinical failures, the preparation costs, and any medications used to treat adverse events) were considered, costs associated with cefepime therapy were significantly lower than those associated with ceftazidime treatment in one model, but not in the other.

Dosage and Administration

In countries other than the US, cefepime is indicated for the treatment of mild to very severe pneumonia in adults and children (aged ≥1 month). The recommended dosage of cefepime for adult or pediatric patients more than 40kg with mild to moderate pneumonia is 1g twice daily administered by intramuscular injection or intravenous infusion (dependent on the severity of infection) for 7–10 days. For adult or pediatric patients more than 40kg with severe to very severe pneumonia the recommended dosage of cefepime is 2g twice or three times daily via intravenous infusion (again, dependent on the severity of infection) for 7–10 days. For pediatric patients (aged >2 months and up to 40kg in bodyweight), with bacterial pneumonia, the recommended dosage is 50 mg/kg/dose twice daily for 10 days; however, for more severe infections, a dosage interval of 8 hours can be used. Experience of the efficacy and tolerability of cefepime is limited in pediatric patients aged <2 months; however, pharmacokinetic modelling suggests that a dose of 30 mg/kg/dose twice daily or three times daily may be considered in these patients.In the US, cefepime is approved for the treatment of moderate to severe pneumonia caused by S. pneumoniae, P. aeruginosa, K. pneumoniae or Enterobacter spp. in adults or children (aged >2 months). The recommended dosage of cefepime for adult patients with moderate to severe pneumonia in the US is 1 or 2g administered intravenously for 10 days. For children (≤40kg in bodyweight), the recommended dosage is 50mg/kg/dose twice daily administered by intravenous infusion for 10 days.No dosage modifications are recommended for the elderly or patients with hepatic dysfunction; however, the dose or frequency of administration of cefepime should be adjusted for patients with renal impairment or those receiving renal dialysis.Cefepime should not be directly mixed with other antibacterial agents. If other antibacterial agents are to be used in a combination regimen they should be administered separately.

     

Linezolid versus ceftriaxone/cefpodoxime in patients hospitalized for the treatment of Streptococcus pneumoniae pneumonia

Intravenous (i.v.) to oral linezolid (600 mg twice daily for both, with optional aztreonam) and a cephalosporin regimen (i.v. ceftriaxone 1 g twice daily followed by oral cefpodoxime 200 mg twice daily) were compared for the treatment of community-acquired pneumonia (CAP), with emphasis on patients with Streptococcus pneumoniae. This multicenter, randomized, open-label trial was conducted in 27 countries in 6 continents. Efficacy was assessed 12-28 d following treatment. Clinical and laboratory safety assessments were evaluated; isolates for microbiologic assessments were identified primarily by sputum or blood culture. In all treated patients (linezolid, n = 381; ceftriaxone/cefpodoxime, n = 366), linezolid had a higher clinical cure rate than ceftriaxone/cefpodoxime (83.0% vs. 76.4%, respectively; p = 0.040). S. pneumoniae was isolated in 73.2% (186/254) of patients at baseline, with similar eradication rates in the linezolid and ceftriaxone/cefpodoxime groups (88.7% vs. 89.9%, respectively; p = 0.830). Linezolid had a superior clinical cure rate (93.1% vs. 68.2%; p = 0.021) in patients with S. pneumoniae bacteremia. Logistic regression analyses revealed that linezolid-treated patients with bacteremia, pleural effusion, cardiac comorbidities, diabetes or abnormal white blood cell counts had significantly better outcomes than cephalosporin-treated patients. Both regimens were well tolerated, although the incidence of drug-related adverse events was higher in the linezolid group than in the ceftriaxone/cefpodoxime group (21.3% vs. 11.2%, respectively; p = 0.0002). In summary, empiric i.v./oral linezolid was more effective than ceftriaxone/cefpodoxime in patients hospitalized with CAP, with comparable cure rates in S. pneumoniae pneumonia and higher cure rates in pneumonia complicated by bacteremia.     

美罗培南静脉注射联合吸入对老年VAP的临床疗效

目的 探讨美罗培南静脉注射联合吸入对老年VAP （呼吸机相关性肺炎）的疗效.方法 将78例VAP患者随机分成两组,分别为观察组38例和对照组40例.对照组每日静脉注射美罗培南3次（每次500 mg）.给予观察组每日静脉注射两次美罗培南（每次500 mg）,同时每日进行4次美罗培南雾化吸入进行治疗（10 mg/次,用2 ml生理盐水稀释）;以上两组均连续治疗10 d后,观察各组疗效.结果 观察组的总有效率为86.84%,对照组的总有效率为77.50%,观察组的疗效优于对照组（P〈0.05）,且不良反应的发生率也比对照组低（P〈0.05）.结论 美罗培南静脉注射联合吸入治疗老年呼吸机相关性肺炎疗效好,使用药量少,不良反应轻,值得进一步推广.     

Bactericidal activity of antibiotics alone and in combination against Enterococcus faecalis in a pharmacodynamic model.

We evaluated the bactericidal kinetics of teicoplanin, mezlocillin, netilmicin, and ciprofloxacin alone and in dual combinations against strains of Enterococcus faecalis susceptible or resistant to ampicillin in a pharmacodynamic model reproducing in bacterial culture in active human plasma or Mueller-Hinton broth the serum kinetics of these antibiotics in humans. Killing was not different in cultures grown in plasma and those grown in broth. Antibiotics used alone had no or low bactericidal activity except for high-dose ciprofloxacin (600 mg intravenously [iv] twice daily or 750 mg orally twice daily), which achieved a 3- to 4-log reduction in colony-forming units (cfu). Netilmicin was equally active at 6 mg/kg once a day or 2 mg/kg three times daily in all combinations. No major increase in bactericidal activity was detected in any combination that included mezlocillin. Maximal synergistic killing was observed for the combination of teicoplanin plus netilmicin (both at three-times daily and once-daily dosing), which sterilized the bacterial cultures (initial inoculum, 10(6) cfu/mL). Combinations of ciprofloxacin at 600 mg iv twice daily and 750 mg orally twice daily plus either teicoplanin or netilmicin were less synergistic but equally effective in total killing as a result of the high bactericidal activity of ciprofloxacin alone.     

Cefepime: a review of its use in the management of hospitalized patients with pneumonia

Cefepime (Maxipime), Maxcef, Cepimax, Cepimex, Axepim, a parenteral fourth-generation cephalosporin, is active against many organisms causative in pneumonia. Cefepime has in vitro activity against Gram-positive organisms including Staphylococcus aureus and penicillin-sensitive, -intermediate and -resistant Streptococcus pneumoniae similar to that of cefotaxime and ceftriaxone. Cefepime also has good activity against Gram-negative organisms, including Pseudomonas aeruginosa, similar to that of ceftazidime. Importantly, cefepime is stable against many of the common plasmid- and chromosome-mediated beta-lactamases and is a poor inducer of AmpC beta-lactamases. As a result, it retains activity against Enterobacteriaceae that are resistant to third-generation cephalosporins, such as derepressed mutants of Enterobacter spp. Cefepime may be hydrolyzed by the extended-spectrum beta-lactamases produced by some members of the Enterobacteriaceae, but to a lesser extent than the third-generation cephalosporins. Monotherapy with cefepime 1 or 2g, usually administered intravenously twice daily, was as effective for clinical and bacteriological response as ceftazidime, ceftriaxone or cefotaxime monotherapy (1 or 2g two or three times daily) in a number of randomized, clinical trials in hospitalized adult, or less commonly, pediatric, patients with generally moderate to severe community-acquired or nosocomial pneumonia. More limited data indicated that monotherapy with cefepime 2g three times daily was also as effective in treating patients with nosocomial pneumonia as imipenem/cilostatin 0.5g four times daily, and when combined with amikacin, cefepime was as effective as ceftazidime plus amikacin. Patients with pneumonia who failed to respond to previous antibacterial therapy with penicillins or other cephalosporins responded to treatment with cefepime. Cefepime is generally well tolerated, with a tolerability profile similar to those of other parenteral cephalosporins. In clinical trials, the majority of adverse events experienced by cefepime recipients were mild to moderate and reversible. The most common adverse events with a causal relationship to cefepime reported in clinical trials included rash and diarrhea. Other, less common, adverse events included pruritus, urticaria, nausea, vomiting oral candidiasis, colitis, headache, fever, erythema and vaginitis. CONCLUSION: Cefepime is an established and generally well tolerated parenteral drug with a broad spectrum of antibacterial activity which, when administered twice daily, provides coverage of most of the pathogens that may be causative in pneumonia. In randomized clinical trials in hospitalized patients with generally moderate to severe community-acquired or nosocomial pneumonia, cefepime monotherapy exhibited good clinical and bacteriological efficacy. Cefepime may become a preferred antibacterial agent for infections caused by Enterobacter spp. With prudent use in order to prevent the emergence of resistant organisms, cefepime will continue to be a suitable option for the empiric treatment of pneumonia.     

替吉奥联合紫杉醇周疗对晚期老年胃癌患者的临床疗效评价

目的评价替吉奥(S-1)联合紫杉醇周疗治疗晚期老年胃癌患者的近期疗效及毒副反应物。方法将广西横县人民医院确诊的38例晚期老年胃癌患者随机分为2组,治疗组20例,采用紫杉醇联合替吉奥化疗:紫杉醇60 mg/m2,第1、8、15 d用药,替吉奥胶囊80 mg/m2,2次/d,连续口服14 d,28 d为1个周期;对照组18例,采用FP方案:顺铂15 mg/m2,第1~5天静点,5-Fu 750mg/m2,第1~5天静点,28 d为1个周期。两组患者至少治疗2个周期后评价其疗效及毒副反应。结果治疗组与对照组的有效率(RR)、疾病控制率(DCR)、1年生存率分别为40.0%、75.0%、55.0%和22.2%、50.0%、38.9%,差异无统计学意义(P0.05);治疗组患者KPS改善情况优于对照组(P0.05);治疗组的胃肠道反应及Ⅲ~Ⅳ度骨髓抑制明显低于对照组(P0.05)。结论替吉奥口服联合紫杉醇周疗方案化疗有效率高,老年患者耐受性好,是老年晚期胃癌患者值得选择的化疗方案。