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

Bull, James J.; Levin, Bruce R.; Derouin, T.; Walker, Nina; Bloch, Craig A.

doi:10.1186/1471-2180-2-35

Cited by 101 publications

(45 citation statements)

References 36 publications

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“…Smith et al, using a model of E. coli K1 septicemia, found only one natural phage, among 15 phages active in vitro, that cured 100% of animals at 8 h postinfection. However, when the treatment was delayed to 16 h postinfection, all animals died (7,40). This underlines the remarkable in vivo activity of EC200 PP .…”

Section: Discussionmentioning

confidence: 81%

Efficacy of Bacteriophage Therapy in Experimental Sepsis and Meningitis Caused by a Clone O25b:H4-ST131 Escherichia coli Strain Producing CTX-M-15

Pouillot

Chomton

Blois

et al. 2012

Antimicrob Agents Chemother

120

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bWe evaluated phage therapy in experimental infections due to S242, a fatal neonatal meningitis Escherichia coli strain belonging to the worldwide-distributed O25b:H4-ST131 clone that produces extended-spectrum beta-lactamase CTX-M-15. A lytic phage, EC200 PP , active against S242, was isolated from environmental water. After determining in vitro and ex vivo stabilities and pharmacokinetic properties of EC200 PP in rat pups, we assessed the therapeutic efficacy of a single dose of 10 8 PFU using models of sepsis and meningitis in which fatality was 100%. EC200 PP was partially neutralized by human serum. In contrast to the high concentration of phage in the spleen and the kidney, low titers in urine and the central nervous system were observed. Nevertheless, in the sepsis model, EC200 PP administered 7 h or 24 h postinfection resulted in 100% and 50% pup survival, respectively. In the meningitis model, EC200PP administered 1 h or 7 h postinfection rescued 100% of the animals. The most delayed treatments were associated with the selection of phage-resistant S242 mutants. However, a representative mutant was highly sensitive to killing serum activity and avirulent in an animal model. EC200PP is a potential therapeutic agent for sepsis and meningitis caused by the widespread E. coli O25:H4-ST131 multidrug-resistant clone.

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Section: Discussionmentioning

confidence: 81%

Efficacy of Bacteriophage Therapy in Experimental Sepsis and Meningitis Caused by a Clone O25b:H4-ST131 Escherichia coli Strain Producing CTX-M-15

Pouillot

Chomton

Blois

et al. 2012

Antimicrob Agents Chemother

120

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“…Phages with high in vitro lytic activity were also the most effective in conferring protection in vivo. The results of Smith and Huggins were reproduced recently (Bull et al, 2002).…”

Section: Animal Studiesmentioning

confidence: 81%

Phage therapy: the Escherichia coli experience

2005

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Phages have been proposed as natural antimicrobial agents to fight bacterial infections in humans, in animals or in crops of agricultural importance. Phages have also been discussed as hygiene measures in food production facilities and hospitals. These proposals have a long history, but are currently going through a kind of renaissance as documented by a spate of recent reviews. This review discusses the potential of phage therapy with a specific example, namely Escherichia coli.

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“…The propagation of phage in a mammalian host is bacterial density dependent5960. The density of bacteria may in turn be dependent on their intrinsic virulence; thus, more virulent ExPEC strains that invade the blood and grow to high levels may be more susceptible to phage.…”

Section: Discussionmentioning

confidence: 99%

Bacteriophages from ExPEC Reservoirs Kill Pandemic Multidrug-Resistant Strains of Clonal Group ST131 in Animal Models of Bacteremia

Green

Kaelber

et al. 2017

Sci Rep

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Multi-drug resistant (MDR) enteric bacteria are of increasing global concern. A clonal group, Escherichia coli sequence type (ST) 131, harbors both MDR and a deadly complement of virulence factors. Patients with an immunocompromised system are at high risk of infections with these E. coli and there is strong epidemiologic evidence that the human intestinal tract, as well as household pets, may be a reservoir. Here, we examine if phages are an effective treatment strategy against this clonal group in murine models of bacteremia that recapitulate clinical infections. Bacteriophages isolated from known E. coli reservoirs lyse a diverse array of MDR ST131 clinical isolates. Phage HP3 reduced E. coli levels and improved health scores for mice infected with two distinct ST131 strains. Efficacy was correlated to in vitro lysis ability by the infecting phage and the level of virulence of the E. coli strain. Importantly, it is also demonstrated that E. coli bacteremia initiated from translocation across the intestinal tract in an immunocompromised host is substantially reduced after phage treatment. This study demonstrates that phage, isolated from the environment and with little experimental manipulation, can be effective in combating even the most serious of infections by E. coli “superbugs”.

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

Cited by 101 publications

References 36 publications

Efficacy of Bacteriophage Therapy in Experimental Sepsis and Meningitis Caused by a Clone O25b:H4-ST131 Escherichia coli Strain Producing CTX-M-15

Efficacy of Bacteriophage Therapy in Experimental Sepsis and Meningitis Caused by a Clone O25b:H4-ST131 Escherichia coli Strain Producing CTX-M-15

Phage therapy: the Escherichia coli experience

Bacteriophages from ExPEC Reservoirs Kill Pandemic Multidrug-Resistant Strains of Clonal Group ST131 in Animal Models of Bacteremia

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