We rationally designed a bacteriophage cocktail to treat a 56-year-old male
liver transplant patient with complex, recurrent prostate and
urinary tract infections caused by an extended-spectrum
beta-lactamase (ESBL)-producing Escherichia coli (E. coli) (UCS1). We screened our library for phages that killed UCS1, with four promising candidates chosen for their virulence,
mucolytic properties, and ability to reduce bacterial resistance. The patient received 2 weeks of intravenous phage cocktail with concomitant
ertapenem for 6 weeks. Weekly serum and urine samples were collected to track the patient's response. The patient tolerated the
phage therapy without any adverse events with symptom resolution. The neutralization of the phage activity occurred with sera collected 1 to 4 weeks after the first phage treatment. This was consistent with immunoassays that detected the upregulation of immune stimulatory analytes. The patient developed asymptomatic recurrent
bacteriuria 6 and 11 weeks following the end of
phage therapy-a condition that did not require
antibiotic treatment. The
bacteriuria was caused by a sister strain of E. coli (UCS1.1) that remained susceptible to the original phage cocktail and possessed putative mutations in the
proteins involved in adhesion and invasion compared to UCS1. This study highlights the utility of rationally designed phage cocktails with
antibiotics at controlling E. coli
infection and suggests that microbial succession, without complete eradication, may produce desirable clinical outcomes.