Recurrent ESBL Escherichia coli Urosepsis in a Pediatric Renal Transplant Patient Treated With Antibiotics and Bacteriophage Therapy

Abstract

Introduction: Treating recurrent multidrug resistant (MDR) urosepsis in pediatric transplant recipients can be challenging. Particularly when antibiotics fail to prevent future occurrence and the nidus is seemingly undiscoverable. While there is an increasing amount of data on phage therapy, to our knowledge, there are no published cases involving pediatric renal transplant recipients. Therefore, we present a challenging clinical case in which phage therapy was used in a pediatric renal transplant recipient who developed recurrent MDR urosepsis with an unclear source. Case Presentation: Our patient was a 17-year-old female who initially developed urosepsis caused by extended-spectrum β-lactamase (ESBL) Escherichia coli, while being treated with an immunosuppressant regimen because of kidney rejection secondary to poor immunosuppression therapy compliance. She was admitted to our hospital intermittently for 4 months with 4 episodes of urosepsis caused by ESBL E. coli. She received multiple courses of antibiotics (mainly ertapenem) and underwent a fecal material transplant to eradicate her ESBL E. coli colonized gastrointestinal tract. Because of recurrent development of urosepsis after antibiotic treatment, she later underwent treatment with a phage cocktail consisting of 2 isolate-specific phages. After a prolonged antibiotic course and subsequent 3-week intravenous phage treatment, she had no ESBL E. coli in her urinary cultures for 4 years post-treatment. Discussion: This case highlights the challenges of treating recurrent ESBL E. coli infections in a pediatric renal transplant patient and provides evidence that phage therapy may prove useful in such cases.

Aspects of Phage-Based Vaccines for Protein and Epitope Immunization

“…In addition, phagebank therapy in COVID-19 patients with suspected or proven secondary bacterial infections received FDA approval under the Emergency Use Authorization (EUA) [ 70 ]. Several case reports have described the use of phages to treat persistent bacterial infections after multiple failures of antibiotic treatments [ 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. These studies are encouraging since this could indicate that bacteriophages may be safe in other medical applications, including in phage-based vaccines, without being a risk to people or animals [ 79 ].…”

Phage Therapy in the Management of Urinary Tract Infections: A Comprehensive Systematic Review

“…Only in 3.6% of the articles (2/55) were phages given intravenously, and both were recent case reports. 31 , 32 In one study, bladder instillation was compared with intrarectal or both routes of administration concurrently. 33 Phages were also given topically, via cystostomy, and intravesically with or without vaginal administration.…”

Automating Predictive Phage Therapy Pharmacology

“…These are all as found in situ while treating infections caused by what are typically somewhat uncharacterized bacterial strains and, in many cases, also in combination with antibiotics [ 41 , 57 , 86 , 87 , 88 , 89 ], which can have antagonistic impacts on phage infection abilities [ 41 , 51 , 85 , 90 ]. In particular for the latter, note that of 18 clinical phage therapy studies that I was able to obtain—published in 2023 or, at the time of writing, which are published but still online ahead of print—at least 16 indicate treatments using phages in combination with antibiotics [ 57 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ]. See also [ 109 ], where 79 of the 114 clinical phage treatments reported “were administered in combination with standard-of-care antibiotics”.…”