Alp Emine, Gozukucuk Suveyda, Canoz Ozlem, Kirmaci Beyhan, Doganay Mehmet
Department of Infectious Diseases, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
BMC Infect Dis. 2004 Oct 18;4:43. doi: 10.1186/1471-2334-4-43.
Methicillin resistant Staphylococcus aureus (MRSA) is the leading pathogenic cause of nosocomial infections, especially in bacteraemia and sepsis. The essential therapy for MRSA infection is glycopeptides. Therapeutic failure can be seen with this therapy and the mortality is still high. The aim of this study was to evaluate the additional effect of G-CSF on the traditional antibiotic treatment in an experimental MRSA sepsis.
Experimental sepsis was performed in mice by intraperitoneal injection of MRSA isolate. Inoculum dose was estimated as 6 x 10(9)ml. Mice were randomised for the study into four group; control group (not receive any therapy), G-CSF group (1000 ng/daily, subcutaneously for 3 d), antibiotic group (vancomycin 25 or 50 mg/kg intraperitoneally every 12 hours for 7 d), and vancomycin+G-CSF group (at the same concentrations and duration). Autopsy was done within one hour after mice died. If mice was still alive at the end of seventh day, they were sacrificed, and autopsy was done. In all groups, the effect of G-CSF therapy on the survival, the number of the MRSA colonies in the lung, liver, heart, spleen, and peritoneal cultures, the histopathology of the lung, liver, heart and spleen was investigated.
One hundred and six mice were used. There were no significant differences in survival rates and bacterial eradication in G-CSF group compared with control group, and also in antibiotic +G-CSF group compared with antibiotic alone group. These parameters were all significantly different in antibiotic alone group compared with control group. Histopathologically, inflammation of the lung and liver were significantly reduced in vancomycin (25 mg/kg)+G-CSF and vancomycin (50 mg/kg)+G-CSF subgroups, respectively (p < 0.01). The histopathological inflammation of the other organs was not significantly different in antibiotic+G-CSF group compared with antibiotic group and, also G-CSF group compared with control group.
G-CSF treatment had no additional effect on survival and bacterial eradication in MRSA sepsis in nonneutropenic mice; and only a little effect on histopathology. G-CSF treatment is very expensive, likewise glycopeptides. The more interest in infection control measures, and prevent the spread of MRSA infections is more rational.
耐甲氧西林金黄色葡萄球菌(MRSA)是医院感染的主要致病原因,尤其是在菌血症和脓毒症中。MRSA感染的基本治疗方法是使用糖肽类药物。这种治疗方法可能会出现治疗失败的情况,且死亡率仍然很高。本研究的目的是评估粒细胞集落刺激因子(G-CSF)在实验性MRSA脓毒症中对传统抗生素治疗的附加作用。
通过腹腔注射MRSA分离株在小鼠中诱导实验性脓毒症。接种剂量估计为6×10⁹/ml。将小鼠随机分为四组进行研究;对照组(不接受任何治疗)、G-CSF组(1000 ng/天,皮下注射3天)、抗生素组(万古霉素25或50 mg/kg,每12小时腹腔注射一次,共7天)以及万古霉素+G-CSF组(相同浓度和持续时间)。在小鼠死亡后1小时内进行尸检。如果小鼠在第7天结束时仍然存活,则将其处死并进行尸检。在所有组中,研究了G-CSF治疗对生存率、肺、肝、心、脾和腹腔培养物中MRSA菌落数量以及肺、肝、心和脾组织病理学的影响。
共使用了106只小鼠。与对照组相比,G-CSF组的生存率和细菌清除率无显著差异,与单独使用抗生素组相比,抗生素+G-CSF组的这些参数也无显著差异。与对照组相比,单独使用抗生素组的所有这些参数均有显著差异。组织病理学上,万古霉素(25 mg/kg)+G-CSF亚组和万古霉素(50 mg/kg)+G-CSF亚组的肺和肝炎症分别显著减轻(p<0.01)。与抗生素组相比,抗生素+G-CSF组其他器官的组织病理学炎症无显著差异,与对照组相比,G-CSF组也无显著差异。
G-CSF治疗对非中性粒细胞减少小鼠的MRSA脓毒症的生存率和细菌清除无附加作用;对组织病理学仅有轻微影响。G-CSF治疗非常昂贵,糖肽类药物也是如此。对感染控制措施给予更多关注并预防MRSA感染的传播更为合理。