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Article

Phage Therapy Related Microbial Succession Associated with Successful Clinical Outcome for a Recurrent Urinary Tract Infection

1
TAILΦR Labs, Molecular Virology and Microbiology Department, Baylor College of Medicine, Houston, TX 77030, USA
2
Center for Innovative Phage Applications and Therapeutics, Division of Infectious Diseases and Global Public Health, University of California, San Diego, CA 92093, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Jean-Paul Pirnay
Viruses 2021, 13(10), 2049; https://doi.org/10.3390/v13102049
Received: 25 August 2021 / Revised: 28 September 2021 / Accepted: 7 October 2021 / Published: 12 October 2021
(This article belongs to the Special Issue State-of-the-Art Phage Therapy Development in Europe)
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. View Full-Text
Keywords: phage therapy; microbial pathogenesis; UTI; humoral response; comparative genomics phage therapy; microbial pathogenesis; UTI; humoral response; comparative genomics
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MDPI and ACS Style

Terwilliger, A.; Clark, J.; Karris, M.; Hernandez-Santos, H.; Green, S.; Aslam, S.; Maresso, A. Phage Therapy Related Microbial Succession Associated with Successful Clinical Outcome for a Recurrent Urinary Tract Infection. Viruses 2021, 13, 2049. https://doi.org/10.3390/v13102049

AMA Style

Terwilliger A, Clark J, Karris M, Hernandez-Santos H, Green S, Aslam S, Maresso A. Phage Therapy Related Microbial Succession Associated with Successful Clinical Outcome for a Recurrent Urinary Tract Infection. Viruses. 2021; 13(10):2049. https://doi.org/10.3390/v13102049

Chicago/Turabian Style

Terwilliger, Austen, Justin Clark, Maile Karris, Haroldo Hernandez-Santos, Sabrina Green, Saima Aslam, and Anthony Maresso. 2021. "Phage Therapy Related Microbial Succession Associated with Successful Clinical Outcome for a Recurrent Urinary Tract Infection" Viruses 13, no. 10: 2049. https://doi.org/10.3390/v13102049

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