beta-Lactam antibiotics in respiratory tract infections

beta-Lactam antibiotics have played a major role in the treatment of respiratory infections for many years. The use of the three main groups of beta-lactam antibiotics-penicillins, cephalosporins and non-classical beta-lactams-in respiratory infections is reviewed. Their development and efficacy have more or less kept pace with the changes in microbial resistance, emergence of new pathogens and changes in medical practice. Consequently, beta-lactam agents continue to make a valuable contribution to therapy of respiratory tract infections.     

大环内酯类抗生素在呼吸系统疾病中的应用

大环内酯类抗生素是一类分子结构中含有内酯环的抗菌药物的总称,其作用机制是通过阻断50s核糖体中肽酰转移酶的活性来抑制细菌蛋白质的合成。近年来,14元、15元大环内酯类抗生素的抗炎和免疫调节作用日益受到关注,并且在一些慢性呼吸系统疾病中应用。     

Pharmacodynamics of ceftriaxone and cefixime against community-acquired respiratory tract pathogens

Over the last decade or so there has been a growing interest in routes of antimicrobial administration other than by the conventional intravenous route for institutionalized patients and for some outpatients. Both oral (PO) and intramuscular (IM) routes of administration are less costly than giving antimicrobial agents by vein (IV). In addition, fewer complications such as catheter-related sepsis and phlebitis are associated with non-IV routes of administration. Furthermore, a reduced-dosage, reduced-volume IM administration of ceftriaxone may provide a tolerable route of administration and equivalent bactericidal activities compared with higher dose IV ceftriaxone. The purpose of this study was to determine the time that the drug concentration remained in excess of the minimum inhibitory concentration (MIC) (T>MIC) and the duration of bactericidal activities of ceftriaxone one gram administered IV, ceftriaxone 250 mg given IM and cefixime 400 mg given orally against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in adult volunteers. Single doses of each agent were administered and serum concentrations were collected over the standard dosing period of 24 h for all study regimens. Ceftriaxone, regardless of route of administration and dose, resulted in bactericidal activities and T>MIC for 100% of the dosing period for S. pneumoniae, H. influenzae, and M. catarrhalis. Cefixime maintained at least 50% T>MIC and bactericidal activity against both isolates each of H. influenzae and M. catarrhalis. Against both isolates of S. pneumoniae, cefixime achieved T>MIC for at least 50% of the dosing period, but did not maintain bactericidal activity. Reduced dose ceftriaxone given IM seems to be a viable alternative to ceftriaxone IV if the pathogen, susceptibility and infection site are known. Based on T>MIC exceeding 50% of the dosing interval, cefixime would be considered an effective alternative to IV therapy against common respiratory tract pathogens. Clinical studies need to be conducted to confirm these findings.     

Local treatment of respiratory infections with antibiotics

Local administration of antibiotics for the treatment of respiratory infections has the potential advantage of reduced systemic toxicity and increased drug concentration at the site of infection. This article reviews the basic principles of pulmonary drug delivery using aerosols and the clinical efficacy of local antibiotic therapy of respiratory infections. Clinical studies have been conducted with locally administered aminoglycosides, penicillins, cephalosporins, and polypeptides. The results of these investigations and the pharmacokinetic aspects of pulmonary antibiotic delivery are summarized.     

Nimesulide and antibiotics in the treatment of acute infections of the respiratory tract

Summary

A double-blind, placebo-controlled trial was carried out in 45 hospitalized adult patients requiring antibiotic therapy for acute or chronic respiratory tract infection to compare the effectiveness of antibiotic treatment alone or with the concomitant use of nimesulide, a new non-steroidal anti-inflammatory agent. Patients were allocated at random to receive antibiotic treatment plus either nimesulide (100?mg twice daily) or placebo over a period of 15 to 23 days. The results showed that the patients in the nimesulide group had significantly greater and more rapid improvement in signs and symptoms such as chest pain, cough, oropharyngeal hyperaemia, asthenia, as well as osteoarticular pain in those arthrosis-affected patients, than those treated with antibiotic plus placebo. Treatment was well-tolerated and very few, mild side-effects were reported.     

2010年我院呼吸内科住院患者抗菌药物用药情况分析

目的了解我院呼吸内科住院患者治疗过程中使用抗菌药物的情况。方法通过我院药品信息查询系统查询呼吸内科2010年抗菌药物用药情况,并结合医师工作站,抽取2010年1月1日至12月31日在我院呼吸内科使用过抗菌药物的住院患者125例对其进行回顾性分析。结果我院呼吸内科销售金额、使用数量排名前3位的均为喹诺酮类、碳青霉烯类和青霉素类,且以注射剂型为主,其销售金额占97.06%。125例患者中,中老年患者占绝大部分(78.4%),确诊疾病中肺炎居首位(48.0%),感染菌株以革兰阴性菌为主。呼吸内科使用的抗菌药物以二联用药为主(65.6%)。结论我院抗菌药物使用情况基本合理,但也存在不同程度的问题。     

Delivery of antibiotics to the respiratory tract: an update

The use of inhaled medications for the treatment of pulmonary diseases has become an increasingly popular drug delivery route over the past few decades. This delivery route allows for a drug to be delivered directly to the site of the disease, with a lower dose than more conventional oral or intravenous delivery methods, with reduced systemic absorption and consequently reduced risk of adverse effects. For asthma this delivery route has become the ‘golden standard’ of therapy. It is not unexpected therefore, that there has been great interest in the prospect of using inhaled antibiotics for the treatment of both chronic and recurrent respiratory infections. Since the early 1980s, several investigations have demonstrated that antibiotics could be delivered safely by means of inhalation, using nebulisers as their delivery systems. Lately, antibiotics delivery via inhalation have seen a ‘revival’ in interest and most of these studies have focused on delivering antibiotics to the lungs by means of a dry powder format. This review focuses on recent advances in antibiotic inhalation therapy.     

呼吸科住院患者抗菌药物使用调查

目的了解医院呼吸科抗菌药物应用情况,增强医生合理使用抗菌药物意识,提高用药水平。方法随机抽取2009年2-4月我院呼吸科出院病例188份,将病历基本信息和调查项目填入表格,并将数据分类汇总。结果抗菌药物使用率96.8%,联合用药占28.0%,病原学检测率为57.1%,不合理病例占29.7%。结论我院呼吸科住院患者抗菌药物使用总体上合理,但在个体化给药上应做进一步改进。     

抗生素在严重急性呼吸综合征诊断中作用的探讨

目的探讨抗生素在严重急性呼吸综合征(SARS)诊断中的作用。方法对太原市定点医院的304例住院确诊SARS病例住院前临床症状及抗生素的使用情况进行分析、评价。结果304例SARS患者主要的临床症状有发热298例,占98.0%;咳嗽161例,占53.0%;乏力156例,占51.3%;全身肌肉酸痛95例,占31.3%;咯痰84例,占27.6%;畏寒85例,占27.3%;少数有头痛、咽痛、关节痛、呼吸困难、恶心呕吐、腹痛及腹泻等。77%的SARS患者在入院前使用了抗生素,其中98%治疗效果为无效、差或一般。123例有明确的流行病学接触史,占40.5%。早期白细胞正常或下降的SARS患者有213例,占93.4%。结论SARS患者临床症状以全身症状(如发热、寒战、乏力、肌痛及畏寒)和呼吸道症状(如咳嗽、气促及呼吸困难)为主;多数有明确的流行病学接触史及抗生素治疗史,而且抗生素治疗无效为特征。     

呼吸内科2011年住院患者抗菌药物应用分析

目的 通过了解本院呼吸内科住院患者抗菌药物的应用情况以促进临床抗菌药物的合理应用.方法 通过回顾性调查,随机抽取呼吸内科2011年住院患者病例300份,对其抗菌药物应用情况进行统计、分析.结果 呼吸内科感染性疾病以下呼吸道感染为主(有264例),抗菌药物使用率为99％,其中单联用药209例(占69.67％),二联用药76例(占25.33％),三联用药3例(占1.00％);其中左氧氟沙星的使用频次位居第一;细菌标本送检率57％;患者肝肾功能复检率为28.33％;疾病治愈率为78％.结论 本院呼吸内科抗菌药物使用基本合理,但依然存在个别不合理现象,需继续加强规范临床抗菌药物的应用,促进抗菌药物合理使用.     

不同抗生素治疗下呼吸道感染的效果分析

目的 探讨不同抗生素治疗下呼吸道感染的临床效果.方法 选取本院2010年5月～2012年5月收治的160例下呼吸道感染患者,将其随机分为甲、乙、丙、丁4组,分别采用头孢曲松钠、头孢噻肟钠、阿奇霉素及左氧氟沙星药物治疗,比较4种药物的治疗效果、不良反应发生率及患者的治疗费用.结果 4组患者的治疗效果及不良反应发生率差异无统计学意义（P＞0.05）;甲组及丁组患者治疗成本明显低于乙组及丙组,差异有统计学意义（P＜0.05）.结论 4种药物的临床治疗效果无显著差异,安全性基本一致,头孢曲松钠和左氧氟沙星成本较低,因此在临床治疗时可优先考虑,降低患者的治疗成本.     

呼吸道细菌对抗生素的耐药性与合理使用抗生素

20世纪末,呼吸道病原菌的耐药状况日益受到人们的关注,抗生素的广泛使用,无论其合理或不合理,无论何时何地对何对象使用,均可能诱导细菌耐药.儿童呼吸道感染发病率高,抗生素使用频率相当高,不合理使用抗生素甚至滥用将诱导细菌产生耐药,还可能产生选择性耐药菌,从而引起病程迁延、并发症产生、治疗失败等,也可能使耐药菌扩散,一旦发生在高危病区或高危人群,必将导致严重后果.     

吸入一氧化氮对内毒素诱发犬急性呼吸窘迫综合征的药效和药代动力学特性(英文)

目的:研究犬败血症急性呼吸窘迫综合征时吸入一氧化氮(NO)的药效和药代动力学特点.方法:12只成年犬静脉注射内毒素导致败血症性急性呼吸窘迫综合征,表现为pao_2/F_((io)_2)基线水平(62.5±2.8)kPa下降为(26±4)kPa,kPa,动态顺应性(Cdyn)由(14.8±0.7)下降为(8.6±0.6)mL·kPa~(-1)·kg~(-1).气道死腔由(0.14±0.06)增加到(0.58±0.05),肺内分流由4.7％±1.7％增加到39％±7％,肺血管阻力指数由(16±4)增加至(51±8)kPa·s·L~(-1)·m~(-2)(P<0.05),并伴随大量白细胞肺内集聚和外周循环白细胞减少.动物随机分组给予单纯机械通气或机械通气加吸入NO 0.4-3.2μmol·L~(-1)(10-80 ppm)自疗10 h.结果:NO治疗组比时照组生存率高(4/6比0/6,P<0.05).吸入NO迅速提高血氧分压,降低肺血管阻力,以0.8μmol·L~(-1)(20 ppm)为理想浓度.吸入NO可降低细胞促炎症介质(TNF_(α),IL-8,CD11b)基因表达,且不对肺表面活性物质和肺液吸收产生不良影响.结论:吸入NO对于犬感染性急性肺损伤具有调节肺血管张力和抑制细胞炎症介质表达的双重作用,吸入高浓度NO可导致高铁血红蛋白血症.     

呼吸系统疾病治疗用雾化吸入抗菌药物的研究进展

传统的抗菌药物给药方式(口服或静脉注射)由于药物的理化性质和宿主解剖学特点,感染部位往往达不到有效的抗菌浓度,导致了治疗的失败。雾化吸入疗法因药物直接作用于靶器官,具有起效迅速、疗效佳、全身不良反应少、不需要患者刻意配合等优势,成为治疗呼吸系统相关疾病较为理想的给药方法。目前抗菌药物吸入制剂只有妥布霉素、氨曲南和多黏菌素,正在研制的有环丙沙星、左氧氟沙星、阿米卡星、两性霉素B、万古霉素等。国外在20世纪40年代开始对吸入抗菌药物进行研究,相对国外的研究,国内的相关报道还较少,因此,为给呼吸系统疾病的防治带来临床新路径,对近年来国内外雾化吸入抗菌药物的药效/药动学研究进展进行综述。     

吸入一氧化氮对内毒素诱发大急性呼吸窘迫综合征的药效和药代动力学特性

AIM: To evaluate pharmacodynamics and pharmacokinetics of inhaled nitric oxide (iNO) in dogs with acute respiratory distress syndrome (ARDS). METHODS: ARDS, induced after iv injection of endotoxin, was evidenced by reduction of paO2/FiO2 from (62.5 +/- 2.8) to (26 +/- 4) kPa and dynamic lung compliance (Cdyn) from (14.8 +/- 0.7) to (8.6 +/- 0.6) mL.kPa-1 . kg-1, increase of dead space (VD/VT) from (0.14 +/- 0.06) to (0.58 +/- 0.05), intrapulmonary shunting (Qs/Qt) from 4.7 % +/- 1.7 % to 39 % +/- 7 %, and pulmonary vascular resistance index (PVRI) from (16 +/- 4) to (51 +/- 8) kPa.s.L-1 . m-2 (all P < 0.05), along with severe intrapulmonary neutrophil recruitment and peripheral neutropenia. The animals were then treated as either a control or an NO group (n = 6 each, iNO 0.4 - 3.2 micromol/L) for another 10 h. RESULTS: More survival was found in NO group (4/6 vs 0/6, P < 0.05). iNO at 0.8, 1.6, and 3.2 micromol/L (20, 40, and 80 ppm) resulted in > 40 % increase of paO2/FiO2 and Cdyn, a reduction of VD/VT to 0.32, Qs/Qt to < 25 %, and PVRI by > 50 % (30.8 kPa . s . L-1 . m-2) compared to the control. Optimal iNO dose was around 0.8 micromol/L as higher methemoglobin (MetHb, > 3 %) was found at higher NO. iNO had no adverse effects on surfactant phospholipids and lung fluid balance, but attenuated expression of tumor necrosis factor alpha,beta2 integrin CD11b, and interleukin-8 mRNA in the lungs by 22 %, 44 %, and 25 %, respectively (P < 0.05). CONCLUSION: Pharmacodynamics of iNO in this model was related to improvement in gas exchange, Cdyn, PVRI, and suppression of proinflammatory cytokine expression in the lungs, and its adverse effect was mainly confined to MetHb at higher NO dose.     

Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections

BACKGROUND: Vancomycin is commonly used to treat staphylococcal infections, but there has not been a definitive analysis of the pharmacokinetics of this antibacterial in relation to minimum inhibitory concentration (MIC) that could be used to determine a target pharmacodynamic index for treatment optimisation. OBJECTIVE: To clarify relationships between vancomycin dosage, serum concentration, MIC and antimicrobial activity by using data gathered from a therapeutic monitoring environment that observes failures in some cases. METHODS: We investigated all patients with a Staphylococcus aureus lower respiratory tract infection at a 300-bed teaching hospital in the US during a 1-year period. Clinical and pharmacokinetic information was used to determine the following: (i) whether steady-state 24-hour area under the concentration-time curve (AUC24) divided by the MIC (AUC24/MIC) values for vancomycin could be precisely calculated with a software program; (ii) whether the percentage of time vancomycin serum concentrations were above the MIC (%Time>MIC) was an important determinant of vancomycin response; (iii) whether the time to bacterial eradication differed as the AUC24/MIC value increased; (iv) whether the time to bacterial eradication for vancomycin differed compared with other antibacterials at the same AUC24/MIC value; and (v) whether a relationship existed between time to bacterial eradication and time to significant clinical improvement of pneumonia symptoms. RESULTS: The median age of the 108 patients studied was 74 (range 32-93) years. Measured vancomycin AUC24/MIC values were precisely predicted with the A.U.I.C. calculator in a subset of our patients (r2 = 0.935). Clinical and bacteriological response to vancomycin therapy was superior in patients with higher (> or = 400) AUC24/MIC values (p = 0.0046), but no relationship was identified between vancomycin %Time>MIC and infection response. Bacterial eradication of S. aureus (both methicillin-susceptible and methicillin-resistant) occurred more rapidly (p = 0.0402) with vancomycin when a threshold AUC24/MIC value was reached. S. aureus killing rates were slower with vancomycin than with other antistaphylococcal antibacterials (p = 0.002). There was a significant relationship (p < 0.0001) between time to bacterial eradication and the time to substantial improvement in pneumonia score. CONCLUSIONS: Vancomycin AUC24/MIC values predict time-related clinical and bacteriological outcomes for patients with lower respiratory tract infections caused by methicillin-resistant S. aureus.