Conway S P, Brownlee K G, Denton M, Peckham D G
Paediatric and Adult Regional Cystic Fibrosis Centres, St James' and Seacroft University Hospitals, Leeds, UK.
Am J Respir Med. 2003;2(4):321-32. doi: 10.1007/BF03256660.
Respiratory tract infection with eventual respiratory failure is the major cause of morbidity and mortality in cystic fibrosis (CF). Infective exacerbations need to be treated promptly and effectively to minimize potentially accelerated attrition of lung function. The choice of antibiotic depends on in vitro sensitivity patterns. However, physicians treating patients with CF are increasingly faced with infection with multidrug-resistant isolates of Pseudomonas aeruginosa. In addition, innately resistant organisms such as Burkholderia cepacia complex, Stenotrophomonas maltophilia and Achromobacter (Alcaligenes) xylosoxidans are becoming more prevalent. Infection with methicillin-resistant Staphylococcus aureus (MRSA) is also a problem. These changing patterns probably result from greater patient longevity and increased antibiotic use for acute exacerbations and maintenance care. Multidrug-resistant P. aeruginosa infection may be treated successfully by using two antibiotics with different mechanisms of action. In practice antibiotic choices have usually been made on a best-guess basis, but recent research suggests that more directed therapy can be achieved through the application of multiple-combination bactericidal testing (MCBT). Aerosol delivery of tobramycin for inhalation solution achieves high endobronchial concentrations that may overcome bacterial resistance as defined by standard laboratory protocols. Resistance to colistin is rare and this antibiotic should be seen as a valuable second-line drug to be reserved for multidrug-resistant P. aeruginosa. The efficacy of new antibiotic groups such as the macrolides needs to be evaluated.CF units should adopt strict segregation policies to interrupt person-to-person spread of B. cepacia complex. Treatment of panresistant strains is difficult and often arbitrary. Combination antibiotic therapy is recommended, usually tobramycin and high-dose meropenem and/or ceftazidime, but the choice of treatment regimen should always be guided by the clinical response.The clinical significance of S. maltophilia, A. xylosoxidans and MRSA infection in CF lung disease remains uncertain. If patients show clinical decline and are chronically colonized/infected with either of the former two pathogens, treatment is recommended but efficacy data are lacking. There are defined microbiological reasons for attempting eradication of MRSA but there are no proven deleterious effects of this infection on lung function in patients with CF. Various treatment protocols exist but none has been subject to a randomized, controlled trial. Multidrug-resistant microorganisms are an important and growing issue in the care of patients with CF. Each patient infected with such strains should be assessed individually and antibiotic treatment planned according to in vitro sensitivity, patient drug tolerance, and results of in vitro studies which may direct the physician to antibiotic combinations most likely to succeed.
呼吸道感染最终导致呼吸衰竭是囊性纤维化（CF）患者发病和死亡的主要原因。感染性加重需要及时、有效地治疗，以尽量减少肺功能可能加速的衰退。抗生素的选择取决于体外药敏模式。然而，治疗CF患者的医生越来越多地面临铜绿假单胞菌多重耐药菌株感染的问题。此外，洋葱伯克霍尔德菌复合体、嗜麦芽窄食单胞菌和木糖氧化无色杆菌（产碱杆菌）等天然耐药菌正变得越来越普遍。耐甲氧西林金黄色葡萄球菌（MRSA）感染也是一个问题。这些变化模式可能是由于患者寿命延长以及急性加重期和维持治疗中抗生素使用增加所致。多重耐药铜绿假单胞菌感染可通过使用两种作用机制不同的抗生素成功治疗。在实践中，抗生素的选择通常是基于猜测，但最近的研究表明，通过应用多重联合杀菌试验（MCBT）可以实现更有针对性的治疗。妥布霉素吸入溶液的雾化给药可达到较高的支气管内浓度，这可能克服标准实验室方案所定义的细菌耐药性。对黏菌素耐药罕见，这种抗生素应被视为一种有价值的二线药物，留作治疗多重耐药铜绿假单胞菌之用。大环内酯类等新抗生素组的疗效需要评估。CF治疗单位应采取严格的隔离政策，以阻断洋葱伯克霍尔德菌复合体的人际传播。泛耐药菌株的治疗困难且往往随意。建议联合使用抗生素治疗，通常是妥布霉素和高剂量美罗培南和/或头孢他啶，但治疗方案的选择应始终以临床反应为指导。嗜麦芽窄食单胞菌、木糖氧化无色杆菌和MRSA感染在CF肺部疾病中的临床意义仍不确定。如果患者出现临床病情恶化且长期被前两种病原体中的任何一种定植/感染，建议进行治疗，但缺乏疗效数据。有明确的微生物学原因试图根除MRSA，但尚无证据表明这种感染对CF患者的肺功能有有害影响。存在各种治疗方案，但均未进行随机对照试验。多重耐药微生物是CF患者护理中一个重要且日益严重的问题。每例感染此类菌株的患者都应单独评估，并根据体外药敏、患者药物耐受性以及可能指导医生选择最有可能成功的抗生素组合的体外研究结果来规划抗生素治疗。
