Intravenous colistin sulphomethate in acute respiratory exacerbations in adult patients with cystic fibrosis
Intravenous colistin sulphomethate in acute respiratory exacerbations in adult patients with cystic fibrosis
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DOI：
10.1136/thx.52.11.987
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发表时间：
1997-11-01
期刊：
影响因子：
10
通讯作者：
Goldman, MH
中科院分区：
文献类型：
--
作者：
Conway, SP;Pond, HN;Goldman, MH
背景：随着中位存活率的稳步提高，囊性纤维化患者接受了更多的静脉注射抗生素疗程。一些中心采取了定期(每月三次)而不是按需静脉注射抗假单胞菌抗生素的政策。由于抗生素使用的增加，细菌对抗生素产生了更广泛的耐药性。大多数铜绿假单胞菌菌株仍然对粘菌素完全敏感，但由于担心神经毒性和肾脏毒性，它的使用一直受到抵制。为评价粘菌素静脉滴注治疗成人囊性纤维化患者急性呼吸加重的安全性和有效性。方法：慢性铜绿假单胞菌定植的患者随机分为两组，分别接受粘菌素(静脉注射2 MU，TDS)治疗12天或再次使用抗菌药物治疗12天。比较第1天、第5天和第12天的呼吸功能测试的绝对值，以及第1天和第12天的过夜血氧饱和度的绝对值是主要的结果衡量标准。患者的体重、临床和胸片评分，以及炎症的外周血液标志物也被记录在案。每种治疗方案的单独效果是通过临床测量从基线值的变化来评估的。通过测量血清尿素和电解质水平、肌酐清除量和病房尿液检测来监测对肾脏的不良影响。通过直接询问症状监测神经毒性。结果-53例患者，其中18例两次进入研究。两组患者平均1秒用力呼气量(FEV1)、平均用力肺活量(FVC)均显著增加。两组患者的夜间血氧饱和度均无明显升高。所有患者临床症状均有改善。单一治疗组33名患者报告了37个不良神经事件(2个严重)，双重治疗组36个患者报告了37个不良神经事件(无严重)。一名患者因严重虚弱和头晕而退出。在治疗期间或治疗后不久，所有其他不良神经事件都被很好地耐受和解决。两组患者的平均血尿素水平均有显著变化，但只有4名患者的血尿素水平高于正常范围，而双重治疗组的内生肌酐清除量也有显著变化。在24个月的随访中，完成研究的患者没有发现静脉注射粘菌素的长期不良反应。结论静脉注射粘菌素是治疗囊性纤维化患者铜绿假单胞菌相关性肺恶化的有效方法。对每个治疗方案的个体效果的评估表明，当粘菌素与第二种抗生素联合使用时，效果更好，假单胞菌在体外对第二种抗生素表现出敏感性。应监测肾功能的变化。
Background - Patients with cystic fibrosis have received more intravenous antibiotic courses as median survival has steadily increased. A number of centres have adopted a policy of regular (three monthly) rather than on demand intravenous antipseudomonal antibiotics. More widespread bacterial antibiotic resistance has resulted from this increased antibiotic use. Most Pseudomonas aeruginosa strains remain fully sensitive to colistin but its use has been resisted owing to concerns about neurotoxicity and nephrotoxicity. A study was carried out to assess the safety and efficacy of intravenous colistin in the treatment of acute respiratory exacerbations in adult patients with cystic fibrosis.Methods - Patients with chronic Pseudomonas aeruginosa colonisation who presented with protocol defined respiratory tract exacerbations were randomised to receive treatment for 12 days with either colistin (2 MU tds intravenously) alone or with a second anti-pseudomonal antibiotic. Comparisons of the absolute values of respiratory function tests on days 1, 5, and 12 and of overnight oxygen saturation on days 1 and 12 were the primary outcome measures. Patient's weight, clinical and chest radiographic scores, and peripheral blood markers of inflammation were also documented. The effect of each treatment regimen individually was assessed by the change in clinical measurements from baseline values. Adverse renal effects were monitored by measurement of serum levels of urea and electrolytes, creatinine clearance, and ward urine testing. Neurotoxicity was monitored by direct questioning for symptoms.Results - Fifty three patients, 18 of whom entered the study twice, were enrolled. The mean forced expiratory volume in one second (FEV1) increased significantly in both groups, mean forced vital capacity (FVC) only with dual therapy. Both groups showed a non-significant increase in overnight oxygen saturation. All patients showed clinical improvement. Thirty seven adverse neurological events (two severe) were reported in 33 patients in the monotherapy group and 37 (none severe) in 36 patients in the dual therapy group. One patient withdrew because of severe weakness and dizziness. All other adverse neurological events were well tolerated and resolved during or shortly after treatment. Significant changes were seen in mean serum urea levels in both groups, but in only four patients to a level above the normal range, and in creatinine clearance in the dual therapy group. At 24 month follow up no long term adverse consequences from intravenous colistin were found in patients who completed the study.Conclusions - Intravenous colistin is an effective treatment for Pseudomonas aeruginosa associated pulmonary exacerbations in patients with cystic fibrosis. Assessment of the individual effect of each treatment regimen suggests a greater efficacy when colistin is combined with a second antibiotic to which the pseudomonas shows in vitro sensitivity. Changes in renal function should be monitored.