Antibiotic Resistance in Global Pediatric Oncology Centers

Antibiotic resistance is one of the major health threats facing global as well as domestic populations, however it is not well characterized in pediatric patients. Pediatric patients receiving cancer-directed therapy have several risk factors implicated in development of antibiotic resistance including multiple courses of antibiotics, repeated exposures to the hospital environment, indwelling devices and chemotherapy-related damage to mucosal barriers. The investigators propose to capitalize upon the unique position of St. Jude Global within the global pediatric oncology community by using its regional alliance network to describe the molecular epidemiology of antibiotic resistance in Gram-negative bacteria in this population.

Primary Objectives

1. Describe the epidemiology and the phenotypic and previously determined molecular determinants of antimicrobial resistance in Gram-negative organisms isolated from pediatric diagnostic specimens in selected Central American and US sites with capacity to treat pediatric cancer
2. Utilize strain typing by whole genome sequencing to describe relatedness between organisms at participating sites

Study Overview

• Status: Completed
• Conditions: Antibiotic Resistant Infection

Detailed Description

Participating clinical microbiology laboratories will flag any Gram-negative bacteria meeting inclusion criteria. Bacteria will be subcultured; one sample will be lysed and shipped to St. Jude; the remaining sample will be stored onsite for the duration of the study. Samples of bacteria from both oncology and non-oncology patients will be included. Whole genome sequencing will be performed on the bacterial samples at St. Jude and the genotypic and phenotypic antimicrobial resistance testing (AST) results compared. Genotypic results will additionally be used to describe phylogenetic relationships and potential transmission events both within and between sites.

Each participating location will collect limited clinical data corresponding to disease and treatment related factors on the affected patient. This will include sociodemographic variables, oncologic diagnosis, treatment phase, presence of a central venous catheter or other foreign body, antibiotic treatment within the past month, and previous history of colonization or infection by a resistant organism.

• Study Type: Observational
• Enrollment (Actual): 560

Contacts and Locations

Study Locations

• El Salvador
  • San Salvador, El Salvador
    • Hospital Nacional de Ninos Benjamin Bloom
• Guatemala
  • Guatemala, Guatemala
    • Unidad Nacional De Oncologia Pediatrica
• Panama
  • Panamá, Panama
    • Hospital del Nino
• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Pediatric (0-18 years of age) patients having a bacteria isolated from a sterile site (blood, cerebrospinal fluid, body fluid) or urine positive for a Gram-negative bacteria nonsusceptible to at least 1 of the following: third generation cephalosporin, fourth generation cephalosporin or carbapenem OR screening positive for carbapenemase or extended spectrum beta lactamase (ESBL) production.

Description

Inclusion Criteria:

• Pediatric (0-18 years of age) patients having a bacteria isolated from a sterile site (blood, cerebrospinal fluid, body fluid) or urine positive for a Gram-negative bacteria nonsusceptible to at least 1 of the following: third generation cephalosporin, fourth generation cephalosporin or carbapenem OR screening positive for carbapenemase or extended spectrum beta lactamase (ESBL) production.

Exclusion Criteria:

• Repeated isolation of the same organism from the same patient within the study period.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patterns of organism and resistance in participating sites	Number of isolated organisms by anatomic site and geographic site	approximately 6 months after completion of data collection
Patterns of organism and resistance in participating sites	Number of antibiotic resistance genes/mutations of interest by geographic site	approximately 6 months after completion of data collection
Patterns of organism and resistance in participating sites	Correlation of known mutations/genes of interest with drug resistance phenotype	approximately 6 months after completion of data collection
Genetic relatedness between bacteria at participating sites	Whole genome sequencing results will be used to describe whether isolated organisms appear to be related phylogenetically.	approximately 6 months after completion of data collection

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Collaborators: Johns Hopkins University; Tarleton State University
• Investigators: Principal Investigator: Sheena Mukkada, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2019
• Primary Completion (Actual): July 29, 2022
• Study Completion (Actual): July 29, 2022

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: October 24, 2018
• First Posted (Actual): October 26, 2018

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Antibiotic Resistance; Pediatric Patients; Gram Negative Bacteria
• Other Study ID Numbers: ARGO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No