Brook I, Ledney G D
Experimental Hematology Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814-5145.
J Antimicrob Chemother. 1994 Feb;33(2):243-52. doi: 10.1093/jac/33.2.243.
The effects on the faecal flora and the efficacies of various antibiotic regimens administered as treatment for a mixed infection caused by Bacteroides fragilis and Escherichia coli in the irradiated host were investigated in a subcutaneous abscess model with C3H/HeN mice which had been exposed to 60Co. The regimens used included imipenem, ofloxacin, metronidazole and the combination of ofloxacin and metronidazole. The incidence of mortality associated with each regimen was as follows: 2 of 20 (10%) mice treated with ofloxacin; 16 of 20 (80%) given metronidazole (P < 0.05 compared with ofloxacin); 8 of 20 (40%) given imipenem (P < 0.05 compared with ofloxacin); 5 of 20 (25%) given the combination of ofloxacin and metronidazole (P = NS compared with ofloxacin); and 15 of 20 (75%) controls given a placebo (P < 0.05 compared with ofloxacin). Compared with the control group, the mean number of lactose-fermenting facultative anaerobes in the faeces of irradiated mice decreased significantly during treatment with either ofloxacin or ofloxacin combined with metronidazole; rose significantly from day 6 during treatment with metronidazole and was similar during treatment with imipenem. The numbers of strict anaerobes fell with all regimens (including the placebo) but, compared with the control group, were significantly higher in the ofloxacin and imipenem groups and significantly lower in the groups which received metronidazole (with or without ofloxacin). Imipenem and the combination of ofloxacin and metronidazole led to significant reductions in the numbers of cfu of both E. coli and B. fragilis in the abscesses compared with the placebo; ofloxacin alone caused a reduction in the number of cfu of E. coli only and metronidazole alone caused a reduction in the number of cfu of B. fragilis only. While the administration of metronidazole had a favourable effect on the B. fragilis component of the localized infection, there was a higher incidence of mortality with this agent, probably because it led to an increase in the number of Enterobacteriaceae in the faeces at the expense of a reduction in the number of strict anaerobes. Antimicrobial agents such as imipenem or the combination of a quinolone, such as ofloxacin, and metronidazole may be used successfully to treat localized infections in the irradiated host while avoiding potentially deleterious increases in the number of facultative anaerobes in the bowel.
在一个皮下脓肿模型中,使用暴露于60Co的C3H/HeN小鼠,研究了各种抗生素治疗方案对脆弱拟杆菌和大肠杆菌引起的混合感染的粪便菌群的影响及其疗效。所用方案包括亚胺培南、氧氟沙星、甲硝唑以及氧氟沙星与甲硝唑的联合用药。与各治疗方案相关的死亡率如下:接受氧氟沙星治疗的20只小鼠中有2只(10%)死亡;给予甲硝唑的20只小鼠中有16只(80%)死亡(与氧氟沙星相比,P<0.05);给予亚胺培南的20只小鼠中有8只(40%)死亡(与氧氟沙星相比,P<0.05);给予氧氟沙星与甲硝唑联合用药的20只小鼠中有5只(25%)死亡(与氧氟沙星相比,P=无显著性差异);给予安慰剂的20只小鼠中有15只(75%)死亡(与氧氟沙星相比,P<0.05)。与对照组相比,在用氧氟沙星或氧氟沙星与甲硝唑联合治疗期间,受辐照小鼠粪便中乳糖发酵兼性厌氧菌的平均数量显著减少;在用甲硝唑治疗期间,从第6天起显著上升,在用亚胺培南治疗期间则相似。所有治疗方案(包括安慰剂)下严格厌氧菌数量均下降,但与对照组相比,氧氟沙星组和亚胺培南组中的严格厌氧菌数量显著更高,而接受甲硝唑(无论是否联用氧氟沙星)治疗的组中严格厌氧菌数量显著更低。与安慰剂相比,亚胺培南以及氧氟沙星与甲硝唑的联合用药使脓肿中大肠杆菌和脆弱拟杆菌的菌落形成单位数量显著减少;单独使用氧氟沙星仅使大肠杆菌的菌落形成单位数量减少,单独使用甲硝唑仅使脆弱拟杆菌的菌落形成单位数量减少。虽然给予甲硝唑对局部感染中的脆弱拟杆菌成分有有利影响,但该药物的死亡率更高,可能是因为它导致粪便中肠杆菌科细菌数量增加,而以严格厌氧菌数量减少为代价。像亚胺培南或喹诺酮类(如氧氟沙星)与甲硝唑的联合用药等抗菌药物可成功用于治疗受辐照宿主的局部感染,同时避免肠道中兼性厌氧菌数量出现潜在有害的增加。