Evidence map›Paper›PMID 40660905›Full record

ReviewThe Journal of antimicrobial chemotherapy2025

Trimethoprim/sulfamethoxazole and risk of haemophagocytic lymphohistiocytosis (HLH): a literature review and disproportionality analysis using individual case safety reports from FAERS.

Rinko Lau, Hasti Sadeghi, Fatemeh Ahmadi, Niaz Chalabianloo, Rebecca Preyra, Mohammad Ali Omrani, Flory T Muanda

Abstract readReviewCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Review in The Journal of antimicrobial chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Rinko LauDepartment of Physiology and Pharmacology, Western University, London, ON, Canada.
Hasti SadeghiDepartment of Biology, Western University, London, ON, Canada.
Fatemeh AhmadiDepartment of Epidemiology and Biostatistics, Western University, London, ON, Canada.
Niaz ChalabianlooDepartment of Physiology and Pharmacology, Western University, London, ON, Canada.
Rebecca PreyraDepartment of Physiology and Pharmacology, Western University, London, ON, Canada.
Mohammad Ali OmraniDepartment of Physiology and Pharmacology, Western University, London, ON, Canada.ORCID 0000-0001-6847-0699
Flory T MuandaDepartment of Physiology and Pharmacology, Western University, London, ON, Canada.ORCID 0000-0003-4682-6564

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThis study aimed to review existing literature regarding the association between haemophagocytic lymphohistiocytosis (HLH) and trimethoprim/sulfamethoxazole and examine the risk of HLH using data from the FDA Adverse Event Reporting System (FAERS).

methodsWe conducted a literature review to identify studies investigating the link between trimethoprim/sulfamethoxazole and HLH. Additionally, we performed an active-comparator restricted disproportionality analysis (ACR-DA) in FAERS (2004Q1-2023Q4) for trimethoprim/sulfamethoxazole compared to amoxicillin/clavulanate and azithromycin. We calculated reporting odds ratios (ROR), adjusted ROR (accounting for age category and indications for respiratory and urinary tract infections), proportional reporting ratios and information components (IC25), to identify potential safety signals for HLH.

resultsOur literature review identified five case reports of HLH linked to trimethoprim/sulfamethoxazole, showing a male predominance of 80% and a median age of 39 years. Symptoms appeared 2 to 14 days after initiating treatment, with fever being the first symptom reported in all patients. The disproportionality analysis indicated that reports of HLH associated with trimethoprim/sulfamethoxazole were approximately 3 to 14 times more frequent than those for amoxicillin/clavulanate (ROR, 3.08; 95% CI, 1.67-5.68) and azithromycin (ROR, 13.89; 95% CI, 5.88-32.82), with most reports submitted by other healthcare professionals.

conclusionsTrimethoprim/sulfamethoxazole may be linked to an increased risk of HLH. Further pharmacoepidemiologic research is necessary to confirm these findings and inform the safe clinical use of trimethoprim/sulfamethoxazole.

Indexed as

Adverse Drug Reaction Reporting SystemsAnti-Bacterial AgentsLymphohistiocytosis, HemophagocyticTrimethoprim, Sulfamethoxazole Drug CombinationAdultAmoxicillin-Potassium Clavulanate CombinationAzithromycinFemaleHumansMaleUnited StatesAmoxicillin-Potassium Clavulanate CombinationAnti-Bacterial AgentsAzithromycinTrimethoprim, Sulfamethoxazole Drug Combination

Identifiers

PMID40660905
PMCPMC12404721

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.