Dynamics of success and failure in phage and antibiotic therapy in experimental infections

J J Bull¹ , Bruce R Levin² , Terry DeRouin² , Nina Walker² and Craig A Bloch³

¹Section of Integrative Biology and Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712-1023, USA

²Department of Biology, Emory University, Atlanta, GA 30322, USA

³Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48104, USA

author email corresponding author email

BMC Microbiology 2002, 2:35doi:10.1186/1471-2180-2-35


Published:	26 November 2002

Abstract

Background

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.

Results

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.

Conclusions

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.