Clinical use of cefuroxime in paediatric community-acquired pneumonia

Cefuroxime has been recommended as a component of treatment for community-acquired pneumonia (CAP) in guidelines produced by several groups, including the US and British Thoracic Societies. It is effective in vitro against the major bacterial pathogens in CAP but it needs to be given with an agent that is active against Mycoplasma, Chlamydia or Legionella spp. if the presence of any of these organisms is suspected. Cefuroxime penetrates respiratory tissue effectively after either parenteral or oral administration, and it has a pharmacodynamic profile which suggests that adequate cover can be achieved with oral therapy for respiratory pathogens susceptible to cefuroxime concentrations of 4 mg/L or less. This break-point is applicable to oral monotherapy and to sequential therapy regimens for the treatment of pneumonia. Cefuroxime can be used either orally or parenterally and it is approved in many countries for the treatment of adult pneumonia by either route. The oral form, cefuroxime axetil, has been used extensively in the treatment of children aged over 3 months but its use in paediatric pneumonia has not been reviewed. The present review summarises clinical experience in the treatment of bacterial pneumonia, of varying severity, in children. The data show that children with severe pneumonia, including those with pleural effusion or complications, can be treated with a full course of intravenous cefuroxime therapy, whereas hospitalised children whose pneumonia stabilises rapidly after initial intravenous therapy can change to oral cefuroxime axetil after 24 to 72 hours and may be able to return home. Oral cefuroxime axetil was appropriate for patients with milder pneumonia managed either in hospital or at home.     

糖皮质激素在社区获得性肺炎治疗中的应用

社区获得性肺炎是临床常见的疾病,虽然有大量抗生素的开发应用,死亡率却无明显下降。肺炎特别是重症肺炎时患者体内可能发生过度炎性反应,导致糖皮质激素相对不足,因此,其作为辅助治疗的作用逐渐被重视,但疗效仍存在一定争议。多数研究者认为糖皮质激素可减少重症肺炎的并发症、降低死亡率,缩短病程,并且没有发现严重不良反应。然而也有研究结果不支持这一结论。不过,对于存在肾上腺皮质功能不全的肺炎患者,中低剂量糖皮质激素可能是安全有效的。如何确定治疗适应证,如何选择适合的剂型、剂量和疗程需要进一步研究。     

Ceftobiprole medocaril for the treatment of community-acquired pneumonia

Introduction: Ceftobiprole is a novel broad-spectrum cephalosporin with excellent activity against a broad range of pathogens that are important in community-acquired pneumonia (CAP), including drug-resistant pneumococci, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa.

Areas covered: This article reviews the spectrum of activity, the main pharmacological and pharmacodynamic characteristics of ceftobiprole as well its clinical efficacy and safety in the treatment of CAP in adult patients.

Expert opinion: Taking into account that the current treatment guidelines for CAP recommend the use of an adequate empirical therapy to improve its prognosis, ceftobiprole shows a profile of antimicrobial activity that would cover most etiological agents in patients with risk factors for infection caused by multidrug resistant organisms. The results of the pivotal clinical trial of patients hospitalized with CAP treated with ceftobiprole showed a high rate of clinical cure. The clinical tolerance of ceftobiprole in clinical trials was generally very good. These findings make ceftobiprole a good parenteral therapeutic alternative for the empirical treatment of CAP that requires hospitalization, especially in patients with risk factors for CAP caused by resistant microorganisms.     

儿童社区获得性肺炎的临床特点和治疗

目的：探讨儿童社区获得性肺炎的临床特点和治疗预后。方法儿童社区获得性肺炎480例采用抽签成组方法分为治疗组与对照组,各240例,对照组给予头孢曲松钠治疗,治疗组在此基础上加用炎琥宁注射液进行治疗,比较两组的治疗效果。结果治疗组的总有效率为96.7%,对照组总有效率为89.2%,两组比较差异具有统计学意义(P<0.05)。治疗组的咳嗽、啰音、发热消失时间都明显少于对照组,对比差异有统计学意义(P<0.05)。两组治疗前血浆C-反应蛋白(CRP)与白介素(IL-6)值对比,差异无统计学意义(P>0.05),治疗后上述值在组内与组间对比差异均有统计学意义(P<0.05)。结论儿童社区获得性肺炎采用炎琥宁注射液结合抗生素进行治疗能有效提高疗效,缓解临床症状,其作用与降低血浆CRP与IL-6水平有明显相关性。     

莫西沙星治疗国内社区获得性肺炎的Meta分析

目的利用Meta分析方法对莫西沙星治疗国内社区获得性肺炎(CAP)的临床试验进行分析,评价其治疗效果。方法检索2002-2010年在国内生物医学期刊发表的有关莫西沙星治疗社区获得性肺炎的临床研究文献,采用Review Manager 4.2软件对符合条件的文献进行荟萃分析。结果共有19个临床试验纳入本次研究,同质性检验χ2=0.30,P>0.05,故采用固定效应模型进行分析。与对照组比较,莫西沙星治疗社区获得性肺炎总有效率更高,比值比为1.94,95%可信区间为1.32～2.84(P<0.05)。结论临床可选用莫西沙星治疗社区获得性肺炎。     

社区获得性肺炎抗菌药物成本-效果分析

目的 探讨3种抗菌药物治疗社区获得性肺炎的成本-效果.方法 63例社区获得性肺炎随机分为A、B、C组各21例,A组采用头孢哌酮舒巴坦治疗;B组采用阿莫西林舒巴坦治疗;C组采用阿奇霉素治疗.比较各组临床疗效,并进行成本-效果分析.结果 A、B组总有效率高于C组,A组高于B组,差异均有统计学意义(P<0.05).以C组为对照,A组△C/△E为55.0,B组为40.1.结论 阿莫西林舒巴坦为治疗社区获得性肺炎的最佳方案.     

Fluoroquinolones in community-acquired pneumonia: guide to selection and appropriate use

Fluoroquinolone use has dramatically increased since the introduction of the first respiratory fluoroquinolone in the late 1990s. Over a relatively brief period of time, the respiratory fluoroquinolones have supplanted other first-line options as the predominant community-acquired pneumonia (CAP) therapy in hospitals. This article discusses the rise of the fluoroquinolone era, debates the comparative effectiveness of fluoroquinolones for CAP therapy, examines fluoroquinolone resistance and adverse drug reactions, and discusses new trends in pneumonia epidemiology and outcomes assessment. Overall, published data suggest that fluoroquinolone monotherapy is associated with improved patient survival compared with β-lactam monotherapy and similar survival to β-lactam plus macrolide combination therapy. Fluoroquinolone monotherapy may be associated with shorter hospital length of stay compared with β-lactam plus macrolide combination therapy, particularly in severe pneumonia or with high-dose therapy. There is insufficient evidence to conclude that any individual fluoroquinolone therapy is better than another with regards to patient mortality. Fluoroquinolones are generally well tolerated and Streptococcus pneumoniae resistance remains low; however, rare but serious adverse effects have been reported. Some members of the fluoroquinolone class have been removed from the market amidst safety concerns. Pneumonia classifications have changed and antipseudomonal fluoroquinolones may have a role in healthcare-associated pneumonia when administered in combination with other antipseudomonal and anti-methicillin-resistant Staphylococcus aureus therapies.     

Benefit-risk assessment of telithromycin in the treatment of community-acquired pneumonia.

The purpose of this review is to assess the benefits and risks associated with the use of the ketolide antibacterial telithromycin, currently licensed for the treatment of adults with mild to moderate community-acquired pneumonia (CAP). Telithromycin is active against both the major (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) and atypical/intracellular (Chlamydophila pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae) CAP pathogens. It is associated with a low potential to select for resistance and has maintained its in vitro activity against isolates of respiratory pathogens in countries where it has been in clinical use for several years. In randomized clinical trials, telithromycin has demonstrated efficacy comparable to the established antibacterial classes (macrolides, fluoroquinolones and beta-lactams) in the treatment of CAP.The safety profile of telithromycin is broadly similar to that of other antibacterials used to treat CAP. The most common adverse events are gastrointestinal adverse effects and headache; these are generally mild to moderate in severity and reversible. Telithromycin appears to be well tolerated by adult patients in all age groups, including those with co-morbid conditions. In common with other antibacterials, telithromycin has the potential to affect the corrected QT interval; the concomitant use of cisapride or pimozide with telithromycin is contraindicated, while telithromycin should be avoided in patients receiving Class IA or Class III antiarrhythmic drugs. Visual disturbances (usually transient) have occurred in a small proportion of patients treated with telithromycin; it is recommended that activities such as driving are minimized during treatment. Telithromycin is contraindicated in patients with myasthenia gravis. Hepatic dysfunction may occur in some patients taking telithromycin; rare cases of acute hepatic failure and severe liver injury, including deaths, have been reported. As telithromycin is an inhibitor of the cytochrome P450 (CYP) 3A4 system, coadministration of telithromycin with drugs metabolized by this pathway may require dose adjustments (e.g. with benzodiazepines) or a temporary hiatus in the use of the coadministered drug (e.g. HMG-CoA reductase inhibitors) metabolized by CYP3A4. Telithromycin may potentiate the effects of oral anticoagulants; careful monitoring is recommended in patients receiving telithromycin and oral anticoagulants simultaneously.Although serious and sometimes fatal events have occurred in patients receiving telithromycin therapy, current data indicate that telithromycin offers an acceptable benefit risk ratio in the treatment of mild to moderate CAP.     

莫西沙星与罗氏芬治疗老年社区获得性肺炎临床疗效比较

目的比较莫西沙星与罗氏芬（头孢曲松钠）治疗老年社区获得性肺炎（CAP）的临床疗效。方法 82例老年CAP患者随机分为观察组（43例）和对照组（39例）。对照组用罗氏芬2.0 g加入250 ml生理盐水中静脉滴注,1次/d。观察组用盐酸莫西沙星氯化钠0.4 g,静脉滴注,1次/d,两组疗程均为7 d。观察两组的治疗情况。结果观察组发热、肺部啰音及胸片炎性影消失时间与对照组比较差异有统计学意义（P〈0.01）,两组咳嗽消失时间比较差异有统计学意义（P〈0.05）。观察组总有效率93.02%明显高于对照组71.79%,差异有统计学意义（P〈0.01）。两组不良反应比较差异无统计学意义（P〉0.05）。结论莫西沙星治疗老年CAP临床疗效优于三代头孢的罗氏芬。     

社区获得性细菌性肺炎治疗药物lefamulin的研究进展

摘要：Lefamulin是首个可以用于治疗全身感染的半合成截短侧耳素类药物。目前,已经完成了lefamulin治疗社区获得性细菌性肺炎(CABP)的Ⅲ期临床试验和急性细菌性皮肤和皮肤结构感染的Ⅱ期临床试验,结果证实了其有效性和安全性,被FDA和EMA批准用于治疗CABP,可经口服和静脉给药。Lefamulin对引起CABP的细菌抗菌谱广,作用机制独特,耐药性出现较慢,与其他抗生素无交叉耐药性。本文从lefamulin的药效学、药动学、临床应用、安全性及耐药机制等方面进行综述,以期为临床合理使用该抗菌素提供理论依据。     

Cost-effective approaches to the treatment of community-acquired pneumonia in the era of resistance

Community-acquired pneumonia (CAP) infects upwards of four million people in the US each year, of which 20% require subsequent hospitalisation. Consequently, it is a large contributor to excessive healthcare resource consumption and cost. Since the aetiology of CAP is not identified in a majority of patients, treatment is often empiric, aimed at the most common causes, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and the atypical pathogens (Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila). A variety of pharmaceutical agents exist for the treatment of CAP, most notably the cephalosporin and penicillin derivatives, the macrolide/azalide antibacterials, the newer tetracyclines, and most recently the respiratory fluoroquinolones. Choosing an agent is usually related to issues such as patient compliance, adverse event profiles, and the presence of resistance. Of these, resistance seems to be the main factor today. S. pneumoniae, the most common cause of CAP, is steadily acquiring resistance to a majority of the currently available antibacterials, thus further increasing costs due to prolonged hospitalisation, treatment of relapses and the use of more expensive antibacterials. Understanding and maximising the pharmacodynamic properties of the available antibacterials will not only prevent the emergence of resistance, thus prolonging their clinical utility, but also reduce the costs associated with treating the infection through rapid symptom improvement and earlier patient discharge. Numerous methods for reducing costs in patients with bacterial infections are documented in the literature and can be applied to CAP. Choosing monotherapy instead of combination therapy can reduce costs associated with the administration of the antibacterial. Agents with longer half-lives allow for once-daily administration, which in turn, leads to improved compliance, successful outcomes, and decreased costs. Administering antibacterials to maximise their pharmacodynamics, such as with continuous infusion of beta-lactams, reduces the amount of drug needed in addition to savings associated with administration and supplies. Finally, transitioning patients to oral therapy as soon as they are clinically stable can significantly reduce the length of hospital stay, which is the major contributing factor of healthcare costs. The use of a clinical pathway in an institution is the most effective way to apply these cost-saving approaches in the treatment of CAP. These pathways should be specific to each institution, thus considering the resistance rates in the area and encouraging the use of the most active, cost-effective agents to produce rapid, positive clinical outcomes.     

Azithromycin extended release: a review of its use in the treatment of acute bacterial sinusitis and community-acquired pneumonia in the US

Azithromycin is a macrolide antibacterial agent. The novel microspheres oral extended-release formulation (Zmax) is the first antibacterial drug approved in the US for administration as a single dose in adult patients with mild to moderate acute bacterial sinusitis (ABS) or community-acquired pneumonia (CAP). It has a broad spectrum of in vitro antibacterial activity against Gram-positive, Gram-negative and atypical pathogens that cause ABS and CAP infections (including Streptococcus pneumoniae), and achieves good tissue penetration. Azithromycin extended release is an effective and generally well tolerated treatment in patients with ABS or CAP. The clinical cure rates of a single 2.0 g dose of azithromycin extended release were noninferior to those obtained with a 10-day regimen of levofloxacin in patients with ABS, and with 7-day regimens of clarithromycin extended release or levofloxacin in patients with CAP. With a pharmacodynamic and pharmacokinetic profile well suited to administration as a single-dose regimen that may offer the advantage of improved compliance and convenience compared with once-daily longer-course regimens, azithromycin extended release is a new option in the empirical treatment of adult patients with mild or moderate ABS or CAP in the US.     

社区获得性肺炎抗菌药物成本-效果分析

目的探讨3种抗菌药物治疗社区获得性肺炎的成本-效果。方法 63例社区获得性肺炎随机分为A、B、C组各21例,A组采用头孢哌酮舒巴坦治疗;B组采用阿莫西林舒巴坦治疗;C组采用阿奇霉素治疗。比较各组临床疗效,并进行成本-效果分析。结果 A、B组总有效率高于C组,A组高于B组,差异均有统计学意义(P<0.05)。以C组为对照,A组△C/△E为55.0,B组为40.1。结论阿莫西林舒巴坦为治疗社区获得性肺炎的最佳方案。     

60例新生儿呼吸机相关肺炎病原培养和药敏分析

目的:分析新生儿呼吸机相关肺炎(vAP)的病原和药敏试验结果.方法:对60例VAP患儿在撤机时无菌操作下留取气管导管末端分泌物进行细菌培养并作药敏试验.结果:60例标本检出50株病原菌,阳性率83.3%,病原菌前5位依次是大肠埃希菌、恶臭假单胞菌、铜绿假单胞菌、肺炎克雷伯菌、表皮葡萄球菌;革兰阴性杆菌40例(80.0%),革兰阳性球菌6例(12.0%),真菌2例(4.0%).革兰阴性杆菌敏感药物前5位依次是亚胺培南/西司他丁(泰能)、环丙沙星、克林霉素、头孢他啶、头孢哌酮 舒巴坦,表皮葡萄球菌对万古霉素敏感,对其余大部分抗生素均耐药.结论:VAP致病菌主要是耐药性条件致病菌,综合防治至关重要.     

口服加替沙星治疗社区获得性肺炎的临床观察

目的:观察口服加替沙星在治疗轻、中度社区获得性肺炎中的临床疗效和安全性。方法:选择轻、中度社区获得性肺炎患者41例,分两组。加替沙星组21例口服加替沙星7-14天(加替沙星400mg,Qd),对照组20例静脉点滴头孢三嗪7-14天(0.9%生理盐水100ml+头孢三嗪2g,静脉滴注,Qd),治疗前后给予血常规、肝肾功能、血糖、电解质、胸片、痰液细菌培养等检查。疗程结束作疗效及细菌清除率评价。结果:两组患者治疗前的基本情况无显著性差异(P>0.05),加替沙星组和对照组治疗有效率均为90%左右。加替沙星组痊愈率和病原茵清除率分别为57.1%和86.7%。对照组痊愈率和病原菌清除率分别为60%和92.3%。但统计学分析差异无显著性(P>0.05)。加替沙星组治疗前后肝肾功能、血糖、淀粉酶无显著性差异(P>0.05)。结论:口服加替沙星治疗轻、中度社区获得性肺炎,疗效可靠、安全性较好。     

从社区获得性肺炎经验性抗生素治疗方案看药学服务的重要性

目的：探讨对临床医师进行药学服务的必要性。方法：收集从2000年5月～2002年5月接受呼吸科医师和内科医师抗生素治疗社区获得性肺炎(CAP)的门诊病历426例。统计和分析首选抗生素种类和每日给药次数，并与我国《社区获得性肺炎诊断和治疗指南》进行对比。结果：呼吸科医师和内科医师治疗CAP的抗生素选择与《社区获得性肺炎诊断和治疗指南》有差距，以内科医师较为明显，表现为过多使用第三代头孢菌素，大环内酯类使用偏低，首选氨基糖苷类依然存在，且时间依赖型抗生素每日给药次数不合理。结论：为经济、合理、安全和有效使用药物，对临床医师开展药学服务指导十分重要。     

台州地区肺炎支原体肺炎患儿诱导痰细菌培养及药敏分析

目的了解肺炎支原体肺炎患儿合并细菌感染的致病菌及耐药情况。方法对408例确诊为肺炎支原体肺炎的患儿痰标本进行培养及药敏试验。结果 408例标本检出致病菌203株,其中革兰阴性菌154株（75.9%）、革兰阳性菌28株（13.8%）、真菌19株（9.4%）。主要致病菌依次为肺炎克雷伯菌75株（36.9%）、大肠埃希菌53株（26.1%）、金黄色葡萄球菌18株（8.9%）、产气肠杆菌10株（4.9%）、铜绿假单胞菌8株（4.0%）。结论肺炎支原体肺炎患儿合并细菌感染的病原菌以革兰阴性菌为主,不同的细菌对常用的抗生素存在不同程度的耐药,临床上应针对非典型病原体使用抗生素的同时合理使用其它抗生素。     

社区获得性呼吸道感染患者肺炎支原体IgM抗体检测结果分析

目的：探讨肺炎支原体（Mp）感染与患者性别、年龄及季节的关系。方法：对本院1335例社区获得性呼吸道感染患者血清标本,应用Serodia-MycoⅡ试剂盒检测Mp-IgM抗体,分析其与患者性别、年龄及季节的关系。结果：1335例患者中Mp-IgM抗体检出阳性者36例,阳性率为2.70%。其中0～20岁组发病率最高,不同性别和各季节阳性率差异无统计学意义。结论：肺炎支原体是青少年社区获得性呼吸道感染的常见病原体,应用Serodia-MycoⅡ试剂盒检测Mp-IgM抗体具有操作简便、敏感度高等优点,有重要的临床应用价值。     

International guidelines for the treatment of community-acquired pneumonia in adults: the role of macrolides

The significance of community-acquired pneumonia (CAP) has led to the publication of guidelines from numerous international organisations. Because the macrolide class of antimicrobials is active against most of the key pathogens associated with CAP, agents from this class are commonly included in recommendations from these guidelines. However, there are differences among the various guidelines concerning the positioning of the macrolides for empirical therapy. An important factor concerning the use of macrolides for CAP is the emergence of resistance of Streptococcus pneumoniae over the past decade. The rate of S. pneumoniae resistance to macrolides ranges from 4 to 70% of strains in worldwide surveillance studies. The most common mechanisms of resistance include methylation of a ribosomal target encoded by the erm gene and efflux of the macrolides by a cell membrane protein transporter, encoded by the mef gene. S. pneumoniae strains with the mef gene are resistant at a lower level (with minimum inhibitory concentration [MIC] values generally 1-16 microg/ml) than erm resistant strains; and it is possible that such strains may be inhibited if sufficiently high levels of macrolide can be obtained at the infected site. Currently mef-associated resistance predominates in North America, whereas erm predominates in Europe. Until recently, reports of failure of treatment of CAP with macrolides has been rare, particularly for patients with low-risk for drug-resistant strains. However, since 2000, several patients treated with an oral macrolide who have subsequently required admission to the hospital for macrolide-resistant S. pneumoniae (MRSP) bacteraemia have been reported in the literature. Major issues, which are fundamental to the use of the macrolides as recommended in the various guidelines, include the importance of providing therapy for 'atypical' pathogens and the clinical significance of MRSP. Presently, the macrolides are more prominently recommended in the North American guidelines than in other parts of the world. The difference in the emphasis placed on the importance of the atypical pathogens as well as the expression of MRSP in North America compared with Europe partly explains this variance.