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老年患者下呼吸道感染抗菌药物选择的新进展

New developments in antibacterial choice for lower respiratory tract infections in elderly patients.

作者信息

Ferrara Anna Maria, Fietta Anna Maria

机构信息

Department of Haematological, Pneumological, Cardiovascular Medical and Surgical Sciences, University of Pavia, IRCCS Policlinico San Matteo, Pavia, Italy.

出版信息

Drugs Aging. 2004;21(3):167-86. doi: 10.2165/00002512-200421030-00003.

Abstract

Elderly patients are at increased risk of developing lower respiratory tract infections compared with younger patients. In this population, pneumonia is a serious illness with high rates of hospitalisation and mortality, especially in patients requiring admission to intensive care units (ICUs). A wide range of pathogens may be involved depending on different settings of acquisition and patient's health status. Streptococcus pneumoniae is the most common bacterial isolate in community-acquired pneumonia, followed by Haemophilus influenzae, Moraxella catarrhalis and atypical pathogens such as Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae. However, elderly patients with comorbid illness, who have been recently hospitalised or are residing in a nursing home, may develop severe pneumonia caused by multidrug resistant staphylococci or pneumococci, and enteric Gram-negative bacilli, including Pseudomonas aeruginosa. Moreover, anaerobes may be involved in aspiration pneumonia. Timely and appropriate empiric treatment is required in order to enhance the likelihood of a good clinical outcome, prevent the spread of antibacterial resistance and reduce the economic impact of pneumonia. International guidelines recommend that elderly outpatients and inpatients (not in ICU) should be treated for the most common bacterial pathogens and the possibility of atypical pathogens. The algorithm for therapy is to use either a selected beta-lactam combined with a macrolide (azithromycin or clarithromycin), or to use monotherapy with a new anti-pneumococcal quinolone, such as levofloxacin, gatifloxacin or moxifloxacin. Oral (amoxicillin, amoxicillin/clavulanic acid, cefuroxime axetil) and intravenous (sulbactam/ampicillin, ceftriaxone, cefotaxime) beta-lactams are agents of choice in outpatients and inpatients, respectively. For patients with severe pneumonia or aspiration pneumonia, the specific algorithm is to use either a macrolide or a quinolone in combination with other agents; the nature and the number of which depends on the presence of risk factors for specific pathogens. Despite these recommendations, clinical resolution of pneumonia in the elderly is often delayed with respect to younger patients, suggesting that optimisation of antibacterial therapy is needed. Recently, some new classes of antibacterials, such as ketolides, oxazolidinones and streptogramins, have been developed for the treatment of multidrug resistant Gram-positive infections. However, the efficacy and safety of these agents in the elderly is yet to be clarified. Treatment guidelines should be modified on the basis of local bacteriology and resistance patterns, while dosage and/or administration route of each antibacterial should be optimised on the basis of new insights on pharmacokinetic/pharmacodynamic parameters and drug interactions. These strategies should be able to reduce the occurrence of risk factors for a poor clinical outcome, hospitalisation and death.

摘要

与年轻患者相比,老年患者发生下呼吸道感染的风险更高。在这一人群中,肺炎是一种严重疾病,住院率和死亡率都很高,尤其是在需要入住重症监护病房(ICU)的患者中。根据不同的感染环境和患者的健康状况,可能涉及多种病原体。肺炎链球菌是社区获得性肺炎中最常见的分离细菌,其次是流感嗜血杆菌、卡他莫拉菌以及非典型病原体,如肺炎衣原体、嗜肺军团菌和肺炎支原体。然而,患有合并症、近期住院或住在养老院的老年患者可能会发生由多重耐药葡萄球菌或肺炎球菌以及肠道革兰氏阴性杆菌(包括铜绿假单胞菌)引起的重症肺炎。此外,厌氧菌可能与吸入性肺炎有关。为了提高良好临床结局的可能性、防止抗菌药物耐药性的传播并降低肺炎的经济影响,需要及时且恰当的经验性治疗。国际指南建议,老年门诊患者和住院患者(非ICU患者)应针对最常见的细菌病原体以及非典型病原体感染的可能性进行治疗。治疗方案是使用一种选定的β-内酰胺类药物联合一种大环内酯类药物(阿奇霉素或克拉霉素),或者使用新型抗肺炎球菌喹诺酮类药物进行单药治疗,如左氧氟沙星、加替沙星或莫西沙星。口服(阿莫西林、阿莫西林/克拉维酸、头孢呋辛酯)和静脉注射(舒巴坦/氨苄西林、头孢曲松、头孢噻肟)β-内酰胺类药物分别是门诊患者和住院患者治疗的首选药物。对于重症肺炎或吸入性肺炎患者而言,具体治疗方案是使用一种大环内酯类药物或喹诺酮类药物联合其他药物;联合药物的种类和数量取决于特定病原体危险因素的存在情况。尽管有这些建议,但与年轻患者相比,老年患者肺炎的临床治愈往往延迟,这表明需要优化抗菌治疗。最近,已研发出一些新型抗菌药物,如酮内酯类、恶唑烷酮类和链阳菌素类,用于治疗多重耐药革兰氏阳性菌感染。然而,这些药物在老年人中的疗效和安全性尚待明确。应根据当地的细菌学和耐药模式修改治疗指南,同时应根据对药代动力学/药效学参数和药物相互作用的新认识,优化每种抗菌药物的剂量和/或给药途径。这些策略应能够减少不良临床结局、住院和死亡等危险因素的发生。

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