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Abstract：
BACKGROUND: In recent years, animal models of bone infections have been used with increased frequency in order to evaluate novel diagnostic and anti-infective technologies, like antibacterial coating of bone implants or local antibiotic carrier products. Therefore, it is highly relevant to evaluate the scientific quality of existing bone infection models.
METHODS: We conducted a systematic review of 316 studies of large non-rodent animal models of bone infection (254 rabbit, 16 pig, 23 dog, 11 goat, and 12 sheep) and extracted data on study design, methodological quality, and postmortem evaluation of infection with respect to reporting and quantification of pathology and microbiology.
RESULTS: The review demonstrated a substantial lack of study-design information, which hampers reproducibility and continuation of the established work. Furthermore, the methodological study quality was found to be low, as the definition of infection, randomization, power analysis, and blinding were only seldomly reported. The use of histology increased in recent years, but a semi-quantitative scoring of the lesions was often missing, i.e. no objective quantification of outcome. Most of the studies focused on whether the inoculated bacteria were present within the bone tissue post mortem or not. However, very often the bacterial burden was not quantified. In many of the models, different antimicrobial interventions were examined and, although antimicrobial effects were commonly described, a lack of complete sterile outcome was observed in many models. On the basis of the systematic review, we established a study template providing a guideline for the standard reporting of animal models of bone infections, including details related to the animal, pathogen, infected animal, and postmortem analysis that are of crucial importance for validation of results and reproducibility.
CONCLUSIONS: As the aim of many bone infection models is to examine the effect of an intervention, the guideline emphasizes the importance of objective quantification of outcome, e.g., blinded quantitative scoring of histological findings and quantification of bacterial burden within tissue and on inserted implants. Less than 5% of the analyzed studies adhered completely to the ideal form presented in the study template.
CONCLUSIONS: Anti-infective interventions must be tested in preclinical animal models before implementation in human patients, and optimal design and validation is essential for a high translational value.
METHODS: We conducted a systematic review of 316 studies of large non-rodent animal models of bone infection (254 rabbit, 16 pig, 23 dog, 11 goat, and 12 sheep) and extracted data on study design, methodological quality, and postmortem evaluation of infection with respect to reporting and quantification of pathology and microbiology.
RESULTS: The review demonstrated a substantial lack of study-design information, which hampers reproducibility and continuation of the established work. Furthermore, the methodological study quality was found to be low, as the definition of infection, randomization, power analysis, and blinding were only seldomly reported. The use of histology increased in recent years, but a semi-quantitative scoring of the lesions was often missing, i.e. no objective quantification of outcome. Most of the studies focused on whether the inoculated bacteria were present within the bone tissue post mortem or not. However, very often the bacterial burden was not quantified. In many of the models, different antimicrobial interventions were examined and, although antimicrobial effects were commonly described, a lack of complete sterile outcome was observed in many models. On the basis of the systematic review, we established a study template providing a guideline for the standard reporting of animal models of bone infections, including details related to the animal, pathogen, infected animal, and postmortem analysis that are of crucial importance for validation of results and reproducibility.
CONCLUSIONS: As the aim of many bone infection models is to examine the effect of an intervention, the guideline emphasizes the importance of objective quantification of outcome, e.g., blinded quantitative scoring of histological findings and quantification of bacterial burden within tissue and on inserted implants. Less than 5% of the analyzed studies adhered completely to the ideal form presented in the study template.
CONCLUSIONS: Anti-infective interventions must be tested in preclinical animal models before implementation in human patients, and optimal design and validation is essential for a high translational value.
摘要：
背景：近年来，骨感染动物模型的使用频率越来越高，以评估新的诊断和抗感染技术，例如骨植入物的抗菌涂层或局部抗生素载体产品。因此,这与评估现有骨感染模型的科学质量高度相关。
方法：我们对骨感染的大型非啮齿动物动物模型的316项研究进行了系统评价（254只兔，16头猪,23狗11只山羊,和12只羊)，并提取了研究设计的数据，方法学质量，以及在病理学和微生物学的报告和量化方面对感染进行验尸评估。
结果：评论显示大量缺乏研究设计信息，这阻碍了既定工作的可重复性和连续性。此外，方法学研究质量较低，作为感染的定义，随机化，功率分析,而致盲的报道很少。近年来组织学的使用有所增加，但是病变的半定量评分经常缺失，即没有客观量化的结果。大多数研究集中在死后骨组织中是否存在接种的细菌。然而,细菌负担通常没有量化。在许多模型中，检查了不同的抗菌干预措施，虽然抗菌作用通常被描述，在许多模型中观察到缺乏完全无菌结局.在系统回顾的基础上,我们建立了一个研究模板，提供骨感染动物模型的标准报告指南，包括与动物有关的细节，病原体,受感染的动物,和验尸分析，对验证结果和可重复性至关重要。
结论：由于许多骨感染模型的目的是检查干预的效果，该指南强调了客观量化结果的重要性，例如，对组织学发现进行盲化定量评分,并对组织内和插入植入物的细菌负荷进行定量.不到5%的分析研究完全遵循研究模板中呈现的理想形式。
结论：在人类患者中实施抗感染干预措施之前，必须在临床前动物模型中进行测试。优化设计和验证对于高平移值至关重要。
方法：我们对骨感染的大型非啮齿动物动物模型的316项研究进行了系统评价（254只兔，16头猪,23狗11只山羊,和12只羊)，并提取了研究设计的数据，方法学质量，以及在病理学和微生物学的报告和量化方面对感染进行验尸评估。
结果：评论显示大量缺乏研究设计信息，这阻碍了既定工作的可重复性和连续性。此外，方法学研究质量较低，作为感染的定义，随机化，功率分析,而致盲的报道很少。近年来组织学的使用有所增加，但是病变的半定量评分经常缺失，即没有客观量化的结果。大多数研究集中在死后骨组织中是否存在接种的细菌。然而,细菌负担通常没有量化。在许多模型中，检查了不同的抗菌干预措施，虽然抗菌作用通常被描述，在许多模型中观察到缺乏完全无菌结局.在系统回顾的基础上,我们建立了一个研究模板，提供骨感染动物模型的标准报告指南，包括与动物有关的细节，病原体,受感染的动物,和验尸分析，对验证结果和可重复性至关重要。
结论：由于许多骨感染模型的目的是检查干预的效果，该指南强调了客观量化结果的重要性，例如，对组织学发现进行盲化定量评分,并对组织内和插入植入物的细菌负荷进行定量.不到5%的分析研究完全遵循研究模板中呈现的理想形式。
结论：在人类患者中实施抗感染干预措施之前，必须在临床前动物模型中进行测试。优化设计和验证对于高平移值至关重要。
