Bacteriophage compositions and methods for treatment of bacterial infections

Inventors

Maresso, Anthony • Ramig, Robert • Green, Sabrina • Terwilliger, Austen • Salazar, Keiko • Clark, Justin R. • Trautner, Barbara

Assignees

Baylor College of Medicine • US Department of Veterans Affairs

Abstract

Disclosed are compositions, devices, kits, and methods for treatment of Enterobacteriaceae infection. Aspects of the present disclosure are directed to bacteriophage compositions comprising one or more of ES17, ES19, HP3, HP3.1, and HP3.2. Certain aspects of the disclosure are directed to compositions comprising (a) bacteriophage ES17 or bacteriophage ES19, (b) bacteriophage HP3, and (c) bacteriophage HP3.1. Also disclosed are compositions comprising bacteriophage HP 3.2. Further disclosed are devices and kits comprising such compositions and methods for use of such compositions in treatment and prevention of pathogenic E. coli infection.

Core Innovation

The invention relates to bacteriophage compositions, kits, devices, and methods for the treatment or prevention of Enterobacteriaceae infections, specifically pathogenic Escherichia coli (E. coli) infections, including multidrug-resistant (MDR) and extraintestinal pathogenic E. coli (ExPEC). The disclosed compositions comprise one or more bacteriophages selected from ES17, ES19, HP3, HP3.1, and HP3.2, which can be combined in various arrangements including a composition of bacteriophage ES17 or ES19, bacteriophage HP3, and bacteriophage HP3.1, or compositions comprising bacteriophage HP3.2 alone or in combination with others. The invention further includes devices and kits containing such compositions and methods for administering these bacteriophage compositions to treat or prevent E. coli infections.

The problem addressed is the urgent threat posed by multidrug-resistant bacterial infections caused by Enterobacteriaceae, including ExPEC strains of E. coli, which cause serious illnesses like urinary tract infections, bacteremia, sepsis, and neonatal meningitis. Antibiotic resistance has rendered many infections untreatable with current drugs and the antibiotic development pipeline is slow, while resistant strains rapidly evolve. Bacteriophage therapy presents a promising approach due to phage specificity, safety, and capacity to infect MDR strains, however, prior phage therapies are limited by the emergence of phage-resistant bacteria and inefficacy in certain environments like the gastrointestinal tract.

The invention discloses novel bacteriophage compositions that include phages like ES17, which possess enhanced activity in mucin-rich environments such as the intestinal tract, overcoming the inhibitory effect of mucin found in the gastrointestinal environment that limits the effectiveness of prior phage HP3. The methods provide for administration of these phage compositions alone or upon devices, to effectively target and reduce E. coli infections, including MDR strains and various infection sites such as urinary tract, bloodstream, gut, and other organs. The compositions can be formulated in liquid or solid pharmaceutically acceptable preparations and can be used prophylactically or therapeutically in immunosuppressed individuals or those at higher risk of E. coli infection.

Claims Coverage

The patent claims encompass compositions, devices, and methods involving bacteriophage combinations for treating E. coli infections. There are multiple inventive features related to specific phage compositions, device integration, and treatment methods.

The claims cover compositions of specific bacteriophage combinations with optional metals, formulations, devices incorporating these compositions, and methods of administering these compositions for treating or preventing diverse pathogenic E. coli infections, including in immunocompromised individuals and multiple infection sites.

Stated Advantages

Documented Applications