Severe Acute Respiratory Failure Associated With Trimethoprim/Sulfamethoxazole Among Adolescent and Young Adults: An Active Comparator-Restricted Disproportionality Analysis From the FDA Adverse Event Reporting System (FAERS) Database
Bibliographic record
Abstract
Background: The US Food and Drug Administration (FDA) has raised concerns about a potential link between trimethoprim/sulfamethoxazole (TMP-SMX) and an increased risk of acute respiratory failure/acute respiratory distress syndrome (ARF/ARDS) in healthy adolescents and young adults. Objective: To assess the association between TMP-SMX and the risk of ARF/ARDS using data from the FDA Adverse Event Reporting System (FAERS). Methods: We analyzed adverse drug events (ADEs) reported in FAERS from January 1, 2004, to December 31, 2023. We focused on reports where TMP-SMX, amoxicillin-clavulanic acid, or azithromycin were the primary suspect drugs for ADEs in individuals aged 10 to 24 years. The outcomes of interest—ARF/ARDS—were identified using MedDRA-preferred terms. We used an active comparator-restricted disproportionality analysis (ACR-DA) to estimate the reporting odds ratio (ROR) and 95% confidence interval (CI), adjusting for age, sex, acne, and urinary tract infections. Bayesian Confidence Propagation Neural Networks (BCPNN) were used to calculate the Information Components (IC 025 ). Due to the amount of missing information, a case-by-case analysis could not be performed. Results: 3171 ICSRs (810 for TMP-SMX, 1617 for azithromycin, and 744 for amoxicillin-clavulanic acid) were included in the study. ACR-DA showed an unadjusted 8-fold increase in the reports of ARF/ARDS with TMP-SMX compared with azithromycin (unadjusted ROR, 7.98; 95% CI, 4.09 to 15.60) and an adjusted 3-fold increase after adjustment for age, sex, acne, and urinary tract infection (adjusted ROR, 2.80; 95% CI, 1.28 to 6.11). BCPNN analysis confirmed significant disproportionality (IC 025 , 0.75). No cases of ARF/ARDS were reported for amoxicillin-clavulanic acid. Conclusion and Relevance: TMP-SMX may increase the risk of ARF/ARDS, requiring further validation in larger pharmacoepidemiological studies. Our findings lay the groundwork for future research to further investigate the safety profile of TMP-SMX in adolescent populations. If confirmed, prescribers should exercise greater caution when prescribing TMP-SMX to adolescents and young adults.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.015 | 0.029 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.004 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".