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Abstract：
The antibiotic classes that are recommended for tularaemia treatment are the aminoglycosides, the fluoroquinolones and the tetracyclines. However, cure rates vary between 60 and 100% depending on the antibiotic used, the time to appropriate antibiotic therapy setup and its duration, and the presence of complications, such as lymph node suppuration. Thus, antibiotic susceptibility testing (AST) of F. tularensis strains remains of primary importance for detection of the emergence of antibiotic resistances to first-line drugs, and to test new therapeutic alternatives. However, the AST methods reported in the literature were poorly standardized between studies and AST data have not been previously evaluated in a comprehensive and comparative way. The aim of the present review was to summarize experimental data on antibiotic susceptibilities of F. tularensis obtained in acellular media, cell models and animal models since the introduction of fluoroquinolones in the treatment of tularaemia in 1989. We compiled MIC data of 33 antibiotics (including aminoglycosides, fluoroquinolones, tetracyclines, macrolides, β-lactams, chloramphenicol, rifampicin, and linezolid) against 900 F. tularensis strains (504 human strains), including 107 subsp. tularensis (type A), 789 subsp. holarctica (type B) and four subsp. mediasiatica strains, using various AST methods. Specific culture media were identified or confirmed as unsuitable for AST of F. tularensis. Overall, MICs were the lowest for ciprofloxacin (≤ 0.002-0.125 mg/L) and levofloxacin, and ranged from ≤ 0.016 to 2 mg/L for gentamicin, and 0.064 to 4 mg/L for doxycycline. No resistant strain to any of these antibiotics was reported. Fluoroquinolones also exhibited a bactericidal activity against intracellular F. tularensis and lower relapse rates in animal models when compared with the bacteriostatic compound doxycycline. As expected, lower MIC values were found for macrolides against type A and biovar I type B strains, compared to biovar II type B strains. The macrolides were more effective against F. tularensis grown in phagocytic cells than in acellular media.
摘要：
推荐用于图拉血症治疗的抗生素类别是氨基糖苷类，氟喹诺酮类药物和四环素类药物.然而,治愈率在60%到100%之间，取决于所使用的抗生素，适当的抗生素治疗设置的时间及其持续时间，以及并发症的存在，如淋巴结化脓。因此，土拉灵菌株的抗生素敏感性试验（AST）对于检测一线药物的抗生素耐药性的出现仍然至关重要，并测试新的治疗替代方案。然而,文献中报道的AST方法在研究之间的标准化程度很低,而且之前没有对AST数据进行全面和比较的评估.本综述的目的是总结在无细胞培养基中获得的土拉纳氏菌的抗生素敏感性的实验数据，自1989年引入氟喹诺酮类药物治疗图拉血症以来的细胞模型和动物模型。我们收集了33种抗生素（包括氨基糖苷，氟喹诺酮类药物,四环素,大环内酯类,β-内酰胺,氯霉素,利福平,和利奈唑胺）对900个土拉灵菌株（504个人类菌株），包括107个小组。tularensis（A型），789亚科。holarctica（B型）和四个亚种。mediasiatica菌株，使用各种AST方法。特定的培养基被鉴定或确认为不适合于土拉氏菌的AST。总的来说,环丙沙星（≤0.002-0.125mg/L）和左氧氟沙星的MIC最低，庆大霉素的范围为≤0.016至2mg/L，多西环素为0.064至4mg/L。没有报道对这些抗生素中的任何一种具有抗性的菌株。与抑菌化合物多西环素相比，氟喹诺酮类药物还显示出对细胞内杜拉氏菌的杀菌活性，并在动物模型中具有较低的复发率。不出所料,发现大环内酯类药物对A型和BiovarIB型菌株的MIC值较低，与BiovarIIB型菌株相比。大环内酯类抗生素对在吞噬细胞中生长的土拉纳氏菌比在无细胞培养基中生长的土拉纳氏菌更有效。
