Gut resistome in ceftriaxone patients, ribaxamase vs placebo
348 longitudinal fecal samples from adult and elderly patients (Bulgaria, Romania, Serbia, Poland, Hungary, USA) treated with ceftriaxone plus ribaxamase or placebo, in an intervention study of antibiotic resistome changes. machine-written summary
349 samples · 349 runs · BG, RO, RS · Adult · 2020 · 7.45 Gbp / sample
Checked this project's papers and archive records yourself? Mark it human-verified.
what each source gave
| ✓ Sequence archive | 2,904 sample values (age, bmi, collection date, country, intervention, intervention detail, sex, subject id) |
| ○ Abstract / description | read; no usable statement |
| ✓ Full text | 1 sample values (collection date) · PMC7383106 |
| ○ Supplementary tables | files read; no table could be matched to the samples |
| – 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 resolved
117 people have samples in more than one arm.
Antibiotic given as the study intervention (incl. eradication therapy Non-antibiotic pharmaceutical given as the study intervention (metformin design randomized_controlled_trial · population gi_infection_or_diarrhoea · Ribaxamase (oral beta-lactamase) vs placebo with IV ceftriaxone
“received concurrent ribaxamase or placebo” — abstract:32801790 (study level; per-sample arms are in the intervention column below)
sex differs between samples of the same subject id (1 subjects, 3 samples) — sex withheld; subject ids shared by samples of both sexes (1 ids, 3 samples) — ids withheld.
The sources disagree on 3 samples. Where two incompatible values exist for one sample (or one person's samples disagree on sex), neither value is published: the field is left empty here, in the sample sheet and in the downloads. Both sides, with their sources, are in gut_metadata_contradictions.parquet of the data package (what counts as a contradiction).
Contradicted values (6)
| sample | field | value | other value | handling |
|---|---|---|---|---|
| SAMN13292910 | sex | female (sequence archive) | subject 514-004: male in 2 samples, female in 1 sample | withheld: neither value published |
| SAMN13293025 | sex | male (sequence archive) | subject 514-004: male in 2 samples, female in 1 sample | withheld: neither value published |
| SAMN13293026 | sex | male (sequence archive) | subject 514-004: male in 2 samples, female in 1 sample | withheld: neither value published |
| SAMN13292910 | subject id | 514-004 | female (sequence archive) | subject id withheld (samples of both sexes share it) |
| SAMN13293025 | subject id | 514-004 | male (sequence archive) | subject id withheld (samples of both sexes share it) |
| SAMN13293026 | subject id | 514-004 | male (sequence archive) | subject id withheld (samples of both sexes share it) |
longitudinal
118 of 119 people sampled more than once (345 samples; median 3, up to 3 per person) · follow-up median 11.0 y (max 11.0 y) · median interval between samples 11.0 y (time from age at collection).
Each row is one person (3 shown of 118); dots are samples at days since that person's first sample.
Genera, mean relative abundance over 306 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 | 349 | 100% | ||||
| country | 349 | 100% | 349 | |||
| health_condition | 0 | 0% | ||||
| subject_id | 346 | 99% | 346 | |||
| age_at_collection_days | 349 | 100% | 349 | |||
| bmi | 349 | 100% | 349 | |||
| collection_date | 349 | 100% | 348 | 1 | ||
| intervention | 349 | 100% | 349 | |||
| timepoint_label | 349 | 100% | 349 | |||
| sex | 346 | 99% | 346 | |||
| intervention_detail | 119 | 34% | 119 |
- Ribaxamase, an Orally Administered β-Lactamase, Diminishes Changes to Acquired Antimicrobial Resistance of the Gut Resistome in Patients Treated with Ceftriaxone. 2020 PMID 32801790 PMC7383106 own_data
Archive description
When β-lactam antibiotics are administered intravenously (IV), a significant portion can be excreted through the bile into the intestine and disrupt the gut microbiome. This can lead to increased susceptibility to certain types of infection, as well as contribute to increase risk of antimicrobial resistance. When given with IV β-lactam antibiotics, Ribaximase degrades excess antibiotics excreted into the upper GI tract before they can disrupt the gut microbiome and alter the resistome.</p><p>During a Phase 2b clinical study, Ribaxamase treatment led to significant reduction in Clostridium difficile infection in patients receiving ceftriaxone. Longitudinal fecal samples (349) were collected from the patients, and the metagenomic content of these samples was sequenced.</p><p>The results of this study found a significant increase in β-lactamase (CfxA) and vancomycin resistance genes (vanD) in placebo-treated vs. ribaxamase-treated patients. We also identified significant correlations between changes in the gut resistome and clinical study parameters including β-lactamase gene frequency and study drug assignment, and efflux pump gene frequency and vancomycin resistance. Taken together, these findings demonstrated that coadministration of ribaxamase with IV β-lactam antibiotics can protect the integrity of the gut resistome and may help limit the emergence of AMR induced by these antibiotics.
How this project entered the registry
Classified as human gut / stool / blood / tissue / internal fluids shotgun DNA metagenome of adult and elderly by deterministic_prior with confidence 0.90. Assay shotgun_dna.
- host external_curation.infant_catalog · “infant triage reason_code age_adult_only”
- body site study.title · “human gut metagenome Metagenome”
- body site study.description · “bile into the intestine and disrupt the”
- body site study.description · “excreted through the bile into the intestine”
- life stage external_curation.infant_catalog · “infant triage reason_code age_adult_only”
- life stage sample.attr.host_age · “64 (n=216/349)”
Evidence examples (one per field × route)
| sample | field | value | route | conf. | source | quote |
|---|---|---|---|---|---|---|
| SAMN13292712 | age_at_collection_days | 24837.0 | R1 | 0.70 | sample.attr.host_age | 68 |
| SAMN13292959 | age_at_collection_days | 27759.0 | R1 | 0.85 | biosample.attribute:host_age | host_age: 76 |
| SAMN13292712 | bmi | 50.17 | R1 | 0.90 | sample.attr.host_body_mass_index | 50.1657260593031 |
| SAMN13292959 | bmi | 21.97 | R1 | 0.85 | biosample.attribute:host_body_mass_index | host_body_mass_index: 21.9671201814059 |
| SAMN13292712 | collection_date | 2016 | R1 | 0.90 | biosample.attribute:collection_date | 2016 |
| SAMN13292959 | collection_date | 2016-09/2017-09 | R3 | 0.70 | paper.fulltext.methods | from Sept. 2016-Sept. 2017, 862 fecal samples |
| SAMN13292712 | country | US | R1 | 0.90 | sample.attr.geo_loc_name | USA |
| SAMN13292712 | intervention | no_intervention | R1 | 0.90 | biosample.attribute:study_visit | study_visit: Screening |
| SAMN13292713 | intervention | drug_therapy | R1 | 0.85 | biosample.attribute:chem_administration | IV β-lactam antibiotics, SYN-004 |
| SAMN13292959 | intervention | placebo | R1 | 0.85 | biosample.attribute:perturbation | perturbation: Placebo |
| SAMN13292712 | intervention_detail | pre-treatment screening visit | R1 | 0.90 | biosample.attribute:study_visit | study_visit: Screening |
| SAMN13292712 | sex | male | R1 | 0.90 | sample.attr.host_sex | male |
| SAMN13292712 | subject_id | 803-002 | R1 | 0.85 | sample.attr.host_subject_id | 803-002 |
| SAMN13292959 | subject_id | 511-001 | R1 | 0.85 | biosample.attribute:host_subject_id | host_subject_id: 511-001 |
| SAMN13292712 | timepoint_label | Screening | R1 | 0.85 | sample.attr.study_visit | Screening |
| SAMN13292959 | timepoint_label | 4week | R1 | 0.85 | biosample.attribute:study_visit | study_visit: 4week |
Sequencing
349 runs over 349 samples · mean 7.44 Gbp per run (median 7.45 Gbp, total 2,595.24 Gbp; 349 runs with a base count) · layout PAIRED 349 · platform ILLUMINA 349 · models Illumina HiSeq 2000 (349) · 88% of runs with a Sandpiper profile · first public 2020-12-01
Authors (14)
Kokai-Kun JF first · Le C · Trout K · Cope JL · Ajami NJ · Degar AJ · Connelly S last · Tarracchini C first · Lugli GA · Mancabelli L · van Sinderen D · Turroni F · Ventura M · Milani C last
Downloads
PRJNA589866.csv.gz (11.2 KB) · parquet (84.9 KB) — all 349 samples, every field with route and confidence · PRJNA589866_determinations.csv.gz (20.8 KB) — 2,905 evidence rows