Abstract：
OBJECTIVE: Treatment of antibiotic-resistant Gram-positive infections (GPIs), including methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly difficult, particularly in patients with multiple co-morbidities who require antibiotics with greater safety and a consistent pharmacokinetic/pharmacodynamic (PK/PD) profile. Such difficult-to-treat GPIs are often associated with poor outcomes, extended hospital stay and increased expenditure. This can be partly attributed to the limited safety and aberrant PK/PD profile of existing anti-MRSA antibiotics. In this context, intravenous levonadifloxacin and its oral prodrug alalevonadifloxacin are novel anti-MRSA antibiotics that have significant advantages over conventional anti-Gram-positive antibiotics. The purpose of this paper was to generate a consensus on the optimal use of levonadifloxacin and alalevonadifloxacin for tackling resistant Gram-positive infections in patients with multiple co-morbidities.
METHODS: Using a modified Delphi approach that combines critical appraisal of evidence and expert opinion, therapeutic use of levonadifloxacin and alalevonadifloxacin in various clinical scenarios and specific unmet conditions was deliberated. Fifteen expert members from medicine, critical-care, emergency, microbiology, and intensive-care disciplines participated and voted on 11 pre-conceived statements. When there was at least 70 % agreement, a consensus was reached.
RESULTS: Following the voting, agreements were reached on 10 out of the 11 statements. Broadly, a consensus was reached in defining the therapeutic role of levonadifloxacin and alalevonadifloxacin in the treatment of various clinical indications involving resistant Gram-positive pathogens, including MRSA, in patients with co-morbidities, such as co-existing or increased risk for kidney dysfunction or hepatic disease and/or immunosuppression; also, in therapeutically challenging conditions caused by Gram-positive bacteria such as bacteraemia, bone and joint infection, diabetic foot infection, febrile neutropenia, and hospital-acquired pneumonia.
CONCLUSIONS: This consensus supports the therapeutic use of levonadifloxacin and alalevonadifloxacin in the treatment of antibiotic-resistant GPIs, including those caused by MRSA and certain polymicrobial infections, in patients with multiple co-morbidities requiring drug with adequate safety and consistent efficacy.
METHODS: Using a modified Delphi approach that combines critical appraisal of evidence and expert opinion, therapeutic use of levonadifloxacin and alalevonadifloxacin in various clinical scenarios and specific unmet conditions was deliberated. Fifteen expert members from medicine, critical-care, emergency, microbiology, and intensive-care disciplines participated and voted on 11 pre-conceived statements. When there was at least 70 % agreement, a consensus was reached.
RESULTS: Following the voting, agreements were reached on 10 out of the 11 statements. Broadly, a consensus was reached in defining the therapeutic role of levonadifloxacin and alalevonadifloxacin in the treatment of various clinical indications involving resistant Gram-positive pathogens, including MRSA, in patients with co-morbidities, such as co-existing or increased risk for kidney dysfunction or hepatic disease and/or immunosuppression; also, in therapeutically challenging conditions caused by Gram-positive bacteria such as bacteraemia, bone and joint infection, diabetic foot infection, febrile neutropenia, and hospital-acquired pneumonia.
CONCLUSIONS: This consensus supports the therapeutic use of levonadifloxacin and alalevonadifloxacin in the treatment of antibiotic-resistant GPIs, including those caused by MRSA and certain polymicrobial infections, in patients with multiple co-morbidities requiring drug with adequate safety and consistent efficacy.
摘要：
目的：治疗耐药革兰阳性感染（GPIs），包括耐甲氧西林金黄色葡萄球菌（MRSA）变得越来越困难，特别是在有多种合并症的患者中,这些患者需要更高的安全性和一致的药代动力学/药效学(PK/PD)谱的抗生素.这种难以治疗的GPI通常与不良结果相关，延长住院时间和增加支出。这可以部分归因于现有抗MRSA抗生素的有限安全性和异常PK/PD谱。在这种情况下，静脉注射左甲氧氟沙星及其口服前药阿莱文那氟沙星是新型抗MRSA抗生素,与常规抗革兰氏阳性抗生素相比具有显著优势.本文的目的是就左旋纳氟沙星和阿莱文纳氟沙星的最佳使用达成共识，以解决患有多种合并症的患者的耐药性革兰氏阳性感染。
方法：使用改进的Delphi方法，结合了对证据的批判性评估和专家意见，在各种临床情况和特定未满足的条件下，考虑了左旋那氟沙星和阿莱文那氟沙星的治疗用途。来自医学的十五名专家成员，重症监护,紧急情况,微生物学,和重症监护学科参与并对11项预先设想的声明进行了投票。当至少有70%的协议时，达成了共识。
结果：投票后，11项声明中有10项达成协议。广义上,在定义左旋纳氟沙星和阿莱文纳氟沙星在治疗涉及耐药革兰氏阳性病原体的各种临床适应症中的治疗作用方面达成了共识。包括MRSA,在患有合并症的患者中，如共存或增加肾功能障碍或肝病和/或免疫抑制的风险;在由革兰氏阳性细菌引起的治疗挑战性疾病中，例如菌血症，骨和关节感染，糖尿病足感染,发热性中性粒细胞减少症,和医院获得性肺炎。
结论：该共识支持在抗生素耐药GPIs的治疗中使用左旋纳氟沙星和阿莱文纳氟沙星，包括由MRSA和某些多微生物感染引起的，在患有多种合并症的患者中，需要药物具有足够的安全性和一致的疗效。
方法：使用改进的Delphi方法，结合了对证据的批判性评估和专家意见，在各种临床情况和特定未满足的条件下，考虑了左旋那氟沙星和阿莱文那氟沙星的治疗用途。来自医学的十五名专家成员，重症监护,紧急情况,微生物学,和重症监护学科参与并对11项预先设想的声明进行了投票。当至少有70%的协议时，达成了共识。
结果：投票后，11项声明中有10项达成协议。广义上,在定义左旋纳氟沙星和阿莱文纳氟沙星在治疗涉及耐药革兰氏阳性病原体的各种临床适应症中的治疗作用方面达成了共识。包括MRSA,在患有合并症的患者中，如共存或增加肾功能障碍或肝病和/或免疫抑制的风险;在由革兰氏阳性细菌引起的治疗挑战性疾病中，例如菌血症，骨和关节感染，糖尿病足感染,发热性中性粒细胞减少症,和医院获得性肺炎。
结论：该共识支持在抗生素耐药GPIs的治疗中使用左旋纳氟沙星和阿莱文纳氟沙星，包括由MRSA和某些多微生物感染引起的，在患有多种合并症的患者中，需要药物具有足够的安全性和一致的疗效。
