Pediatric cancer patients, antibiotics & resistome, Canada
22 stool samples from pediatric leukemia/lymphoma patients in Canada, studied longitudinally for the impact of antibiotic (β-lactam/vancomycin) course number and duration on antibiotic resistance genes. machine-written summary
22 samples · 22 runs · CA · Infant / toddler · 2023 · 1.08 Gbp / sample · cohort Dalhousie pediatric leukemia/lymphoma gut microbio
Checked this project's papers and archive records yourself? Mark it human-verified.
what each source gave
| ✓ Sequence archive | 66 sample values (country, subject id, timepoint) |
| ✓ Abstract / description | 22 sample values (health condition) |
| – Full text | no open-access full text linked |
| – Supplementary tables | no supplementary tables available (or none open access) |
| – External resources | not covered by the external resources we ingest |
| – User contribution | nothing uploaded yet |
| – Human verified | not yet checked by a person · I checked this project — verify it |
intervention — arms not resolved
Antibiotic given as the study intervention (incl. eradication therapy design observational_with_procedure · population other_cancer · Empiric IV β-lactam and/or vancomycin for febrile neutropenia, varying courses/duration
“treated with empiric intravenous antibiotics that include β-lactams and/or vancomycin” — bioproject.description (study level; per-sample arms are in the intervention column below)
longitudinal — not resolved
4 of 14 people sampled more than once (12 samples; median 3, up to 4 per person). Schedule stated by the source: “Repeated stool samples per patient across antibiotic course groupings (no antibiotics, 1-2 courses, 3+ courses) and duration categories; timepoint labels ST01-ST13, SUB-ST.”.
Genera, mean relative abundance over 14 profiled gut samples of this project (Sandpiper SingleM profiles, GTDB R232; low-depth and non-metagenome profiles left out).
| field | samples | coverage | R1 | R2 | R3 | R4 |
|---|---|---|---|---|---|---|
| age_category | 0 | 0% | ||||
| country | 22 | 100% | 22 | |||
| health_condition | 22 | 100% | 22 | |||
| subject_id | 22 | 100% | 22 | |||
| timepoint_label | 22 | 100% | 22 |
- (no title) curated
Archive description
Most children with leukemia and lymphoma experience febrile neutropenia. These are treated with empiric intravenous antibiotics that include β-lactams and/or vancomycin. These are often administered for extended periods, and the effect on the resistome is unknown. We examined the impact of repeated courses and duration of antibiotic use on the resistome of 39 pediatric leukemia and lymphoma patients. Shotgun metagenome sequences from 127 stool samples of pediatric oncology patients were examined for abundance of antibiotic resistance genes (ARGs) in each sample. Abundances were grouped by repeated courses (no antibiotics, 1-2 courses, 3+ courses) and duration (no use, short duration, long and/or mixed duration) of β-lactams, vancomycin and “any antibiotic” use. We assessed changes in both taxonomic composition and prevalence of ARGs among these groups. We found that Bacteroidetes taxa and β-lactam resistance genes decreased, while opportunistic Firmicutes and Proteobacteria taxa, along with multidrug resistance genes, increased with repeated courses and/or duration of antibiotics. Efflux pump related genes predominated (85%) among the increased multidrug genes. While we found β-lactam ARGs present in the resistome, the taxa that appear to contain them were kept in check by antibiotic treatment. Multidrug ARGs, mostly efflux pumps or regulators of efflux pump genes, were associated with opportunistic pathogens, and both increased in the resistome with repeated antibiotic use and/or increased duration. Given the strong association between opportunistic pathogens and multidrug-related efflux pumps, we suggest that drug efflux capacity might allow the opportunistic pathogens to persist or increase despite repeated courses and/or duration of antibiotics. While drug efflux is the most direct explanation, other mechanisms that enhance the ability of opportunistic pathogens to handle environmental stress, or other aspects of the treatment environment, could also contribute to their ability to flourish within the gut during treatment. Persistence of opportunistic pathogens in an already dysbiotic and weakened gastrointestinal tract could increase the likelihood of life-threatening blood borne infections. Of the 39 patients, 59% experienced at least one gastrointestinal or blood infection and 60% of bacteremia’s were bacteria found in stool samples. Antimicrobial stewardship and appropriate use and duration of antibiotics could help reduce morbidity and mortality in this vulnerable population.
How this project entered the registry
Classified as human gut / stool / blood / tissue / internal fluids shotgun DNA metagenome of child and infant / toddler by deterministic_prior with confidence 0.90. Assay shotgun_dna.
- host external_curation.infant_catalog · “infant triage verdict include”
- body site study.description · “sequences from 127 stool samples of pediatric”
- body site external_curation.infant_catalog · “infant triage verdict include (gut/stool scope)”
- body site study.description · “likelihood of life-threatening blood borne infections. Of”
- life stage study.title · “This study examined pediatric patients undergoing treatment”
- life stage study.description · “Most children with leukemia and”
- life stage external_curation.infant_catalog · “infant triage verdict include (0-3 y scope)”
Evidence examples (one per field × route)
| sample | field | value | route | conf. | source | quote |
|---|---|---|---|---|---|---|
| SAMEA112613923 | country | CA | R1 | 0.90 | biosample_attr | Canada |
| SAMEA112613923 | health_condition | other_cancer | R4 | 0.45 | study.description | pediatric leukemia and lymphoma patients |
| SAMEA112613923 | subject_id | MALL-010 | R1 | 0.70 | sample.name_rule:sample_alias | MALL-010-ST13-WGS |
| SAMEA112613923 | timepoint_label | ST13 | R1 | 0.70 | sample.name_rule:sample_alias | MALL-010-ST13-WGS |
Sequencing
22 runs over 22 samples · mean 1.09 Gbp per run (median 1.08 Gbp, total 23.88 Gbp; 22 runs with a base count) · layout SINGLE 22 · platform ILLUMINA 22 · models NextSeq 550 (22) · 64% of runs with a Sandpiper profile · first public 2023-02-13
Authors (7)
MacDonald T first · Dunn KA · MacDonald J · Langille MGI · Van Limbergen JE · Bielawski JP · Kulkarni K last
Downloads
PRJEB59728.csv.gz (1.5 KB) · parquet (69.8 KB) — all 22 samples, every field with route and confidence · PRJEB59728_determinations.csv.gz (1.2 KB) — 88 evidence rows