Alós J I, García-Peña P, Tamayo J
Servicio de Microbiología, Hospital de Móstoles, Móstoles, Madrid. España.
Rev Esp Quimioter. 2007 Jun;20(2):211-5.
Resistance to fosfomycin develops rapidly in experimental conditions, although despite its frequent use in UTI, resistance in E. coli, the main uropathogen, is very low (1-3%), and has remained so for many years. The objective of this study was to ascertain whether E. coli fosfomycin-resistant strains have less fitness than those that are fosfomycin-sensitive in competing, and would therefore tend to disappear in their competition with fosfomycin-sensitive strains in the absence of antibiotics. Fosfomycin-resistant strains (n=11) with different phenotypes of resistance to other antibiotics were used. All but one were lactose (+). Fosfomycin-susceptible strains (n=15) that had the same phenotypes of resistance to other antibiotics as the resistant strains and which had the opposite pattern of lactose fermentation were also used. Thirty-three (33) competition experiments by pairs of strains were conducted in nutrient broth. Equal amounts of the strains were challenged (approx. 50% and approx. 50%) for 4 days, with a daily change to a new medium. Five differential counts were performed on days 0, 1, 2, 3 and 4. In 20 experiments (60.6%) there was a relative increase in the fosfomycin-sensitive strain. In 6 experiments (18.2%) there was a relative increase in the fosfomycin-resistant strain. In 7 experiments (21.2%), on the fourth day none of the strains reached 60%. When the data of the 26 (20+6) experiments in which there were changes were analyzed by the chi2 test there was a statistically significant difference (p=0.044). Resistance to fosfomycin could entail a biological cost (less fitness) for the majority of the E. coli strains assayed.
在实验条件下，对磷霉素的耐药性发展迅速，尽管其在治疗尿路感染中频繁使用，但主要尿路致病菌大肠杆菌的耐药率非常低（1%-3%），且多年来一直如此。本研究的目的是确定在竞争中，耐磷霉素的大肠杆菌菌株是否比磷霉素敏感菌株适应性更差，因此在无抗生素的情况下，与磷霉素敏感菌株竞争时是否会趋于消失。使用了对其他抗生素具有不同耐药表型的耐磷霉素菌株（n = 11）。除一株外，其余均为乳糖（+）。还使用了对其他抗生素具有与耐药菌株相同耐药表型且乳糖发酵模式相反的磷霉素敏感菌株（n = 15）。在营养肉汤中对菌株进行了33对竞争实验。将等量的菌株（约50%和约50%）接种，培养4天，每天更换新鲜培养基。在第0、1、2、3和4天进行了五次差异计数。在20次实验（60.6%）中，磷霉素敏感菌株相对增加。在6次实验（18.2%）中，耐磷霉素菌株相对增加。在7次实验（21.2%）中，第四天没有菌株达到60%。当用卡方检验分析有变化的26次（20 + 6）实验的数据时，存在统计学显著差异（p = 0.044）。对大多数检测的大肠杆菌菌株而言，对磷霉素的耐药性可能会带来生物学代价（适应性更差）。
