PDF(Pubmed)
Abstract：
BACKGROUND: Multiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial pneumonia (NP). The objective of this Bayesian network meta-analysis (NMA) was to compare the efficacy and the safety of different antibiotic treatments for NP.
METHODS: We conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events.
RESULTS: Sixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17-0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19-3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00-2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03-2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02-2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin.
CONCLUSIONS: This network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria. Registration PROSPERO CRD42021226603.
METHODS: We conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events.
RESULTS: Sixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17-0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19-3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00-2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03-2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02-2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin.
CONCLUSIONS: This network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria. Registration PROSPERO CRD42021226603.
摘要：
背景：多项随机对照研究比较了许多抗生素治疗方案，包括新的,最近商业化的抗生素用于治疗医院内肺炎（NP）。此贝叶斯网络荟萃分析（NMA）的目的是比较不同抗生素治疗NP的疗效和安全性。
方法：我们对PubMed进行了系统搜索，Medline,WebofScience,从2000年到2021年的EMBASE和Cochrane图书馆数据库。研究选择包括比较在NP设置中靶向革兰氏阴性杆菌的抗生素的研究。主要终点是28天死亡率。次要结果是临床治愈，微生物治疗和不良事件。
结果：这项分析包括了包括4993名患者的16项研究，比较了13种抗生素治疗方案。死亡率比较的证据水平从非常低到中等。在所有β-内酰胺治疗方案中，28天死亡率没有显着差异。与单独使用静脉注射粘菌素相比，只有美罗培南加雾化粘菌素的组合与死亡率显着降低相关（OR=0.43；95％可信区间[0.17-0.94]），根据纳入的最小试验的结果.头孢他啶的临床失败率高于美罗培南（OR=1.97；95％CrI[1.19-3.45]）或不使用雾化粘菌素（OR=1.40；95％CrI[1.00-2.01]），亚胺酯/西司他丁/来巴坦(OR=1.74;95%CrI[1.03-2.90])和头孢他啶/阿维巴坦(OR=1.48;95%CrI[1.02-2.20])。对于微生物治疗，治疗方案之间没有实质性差异，但头孢洛赞/他唑巴坦优于比较者的可能性最高.在安全分析中，不良事件发生的治疗方法之间没有显着差异，但是急性肾衰竭在接受静脉粘菌素的患者中更为常见。
结论：这项网络荟萃分析表明，大多数抗生素治疗方案，包括新的组合和头孢得洛，在治疗NP中易感革兰氏阴性杆菌方面具有相似的疗效和安全性。对于多药耐药菌引起的NP还需要进一步的研究。注册PROSPEROCRD42021226603。
方法：我们对PubMed进行了系统搜索，Medline,WebofScience,从2000年到2021年的EMBASE和Cochrane图书馆数据库。研究选择包括比较在NP设置中靶向革兰氏阴性杆菌的抗生素的研究。主要终点是28天死亡率。次要结果是临床治愈，微生物治疗和不良事件。
结果：这项分析包括了包括4993名患者的16项研究，比较了13种抗生素治疗方案。死亡率比较的证据水平从非常低到中等。在所有β-内酰胺治疗方案中，28天死亡率没有显着差异。与单独使用静脉注射粘菌素相比，只有美罗培南加雾化粘菌素的组合与死亡率显着降低相关（OR=0.43；95％可信区间[0.17-0.94]），根据纳入的最小试验的结果.头孢他啶的临床失败率高于美罗培南（OR=1.97；95％CrI[1.19-3.45]）或不使用雾化粘菌素（OR=1.40；95％CrI[1.00-2.01]），亚胺酯/西司他丁/来巴坦(OR=1.74;95%CrI[1.03-2.90])和头孢他啶/阿维巴坦(OR=1.48;95%CrI[1.02-2.20])。对于微生物治疗，治疗方案之间没有实质性差异，但头孢洛赞/他唑巴坦优于比较者的可能性最高.在安全分析中，不良事件发生的治疗方法之间没有显着差异，但是急性肾衰竭在接受静脉粘菌素的患者中更为常见。
结论：这项网络荟萃分析表明，大多数抗生素治疗方案，包括新的组合和头孢得洛，在治疗NP中易感革兰氏阴性杆菌方面具有相似的疗效和安全性。对于多药耐药菌引起的NP还需要进一步的研究。注册PROSPEROCRD42021226603。
