Dynamics of success and failure in phage and antibiotic therapy in experimental infections.
Dynamics of success and failure in phage and antibiotic therapy in experimental infections.
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DOI：
10.1186/1471-2180-2-35
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发表时间：
2002-11-26
期刊：
影响因子：
4.2
通讯作者：
Bloch, Craig A.
中科院分区：
文献类型：
--
作者：
Bull, J. J.;Levin, Bruce R.;DeRouin, Terry;Walker, Nina;Bloch, Craig A.
1982 年，Smith 和 Huggins 证明，噬菌体在预防小鼠实验性感染荚膜大肠杆菌 (K1) 导致的死亡方面至少与抗生素一样有效。需要 K1 胶囊进行感染的噬菌体比不需要这种胶囊的噬菌体更有效，但噬菌体和抗生素在预防死亡方面的功效均随着感染和治疗之间的时间而下降，在 16 小时内几乎变得无效。我们开发定量微生物学程序，(1) 探索噬菌体和抗生素治疗方案在实验感染中的功效的体内过程（耐药竞争测定或 RCA），以及 (2) 调查噬菌体的体外治疗潜力（噬菌体复制测定或 PRA）。我们通过重复 Smith 和 Huggins 的实验，使用大肠杆菌 K1 小鼠大腿感染模型，并应用噬菌体或链霉素治疗，说明了这些方法的应用和效用。 1) Smith 和 Huggins 噬菌体和抗生素治疗结果在数量和质量上都很稳健。 (2) 我们的 RCA 值反映了不同噬菌体和链霉素在预防死亡方面的微生物功效，并反映了其功效随治疗延迟而下降。这些结果具体表明，细菌在感染期间变得难以治疗。 (3) K1特异性和非特异性噬菌体对肉汤中生长的细菌具有相似的复制率（基于PRA），但K1特异性噬菌体在小鼠血清中具有明显更高的复制率。
In 1982 Smith and Huggins showed that bacteriophages could be at least as effective as antibiotics in preventing mortality from experimental infections with a capsulated E. coli (K1) in mice. Phages that required the K1 capsule for infection were more effective than phages that did not require this capsule, but the efficacies of phages and antibiotics in preventing mortality both declined with time between infection and treatment, becoming virtually ineffective within 16 hours. We develop quantitative microbiological procedures that (1) explore the in vivo processes responsible for the efficacy of phage and antibiotic treatment protocols in experimental infections (the Resistance Competition Assay, or RCA), and (2) survey the therapeutic potential of phages in vitro (the Phage Replication Assay or PRA). We illustrate the application and utility of these methods in a repetition of Smith and Huggins' experiments, using the E. coli K1 mouse thigh infection model, and applying treatments of phages or streptomycin. 1) The Smith and Huggins phage and antibiotic therapy results are quantitatively and qualitatively robust. (2) Our RCA values reflect the microbiological efficacies of the different phages and of streptomycin in preventing mortality, and reflect the decline in their efficacy with a delay in treatment. These results show specifically that bacteria become refractory to treatment over the term of infection. (3) The K1-specific and non-specific phages had similar replication rates on bacteria grown in broth (based on the PRA), but the K1-specific phage had markedly greater replication rates in mouse serum.
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