HLH-like Hypersensitivity Reaction Secondary to Prolonged Piperacillin/Tazobactam: A Case Series
Bibliographic record
Abstract
Background Prolonged (>10 days) use of intravenous (IV) piperacillin/tazobactam has been associated with a risk of developing hemophagocytic lymphohistiocytosis (HLH) syndrome. However, clinical and biological descriptions of this rare complication are lacking in the literature, such as management guidelines. Objectives and Methods We describe a series of five children who presented with an HLH-like hypersensitivity reaction after prolonged use of IV piperacillin/tazobactam therapy between February 2024 and October 2024 in a single pediatric tertiary center. Results Five patients aged between 6 and 15 years received IV piperacillin/tazobactam for various bacterial infections. The reaction occurred between 7 and 19 days after the start of therapy. While initial infections were well controlled, all patients presented with a reoccurrence of high fever, malaise, and a maculopapular rash in 4 of them. All developed biological abnormalities with elevated ferritin (range: 913-124895 µg/L), LDH (range: 565-3130 U/L), liver enzymes (ALT range: 113-363 U/L), and severe neutropenia (range: 0.1-0.4 x 109/L). Eosinophils were normal in 4/5 and mildly elevated (0.8 x 109/L) in 1/5. Increased HLADR+ CD8+ T cell frequency was observed in 3/3 patients tested (range: 25-30%). Investigations for classical secondary HLH triggers were negative. Piperacillin/tazobactam discontinuation led to resolution of fever and associated symptoms within 24 hours in all patients. All biological features resolved within a few days. Only one child received a short course of steroids for severe pruritus and myalgia. One patient reported a similar reaction after a previous course of 14 days of piperacillin/tazobactam therapy, 1.5 years earlier. Four patients were evaluated in allergology: 1/4 reacted to intradermal testing for piperacillin/tazobactam. Patch tests and one dose provocation challenge were negative (tested in 4 and 2 patients, respectively). Conclusion We provide further evidence that prolonged use of IV piperacillin/tazobactam may be associated with hypersensitivity reactions reminiscent of HLH (although only 1/5 formally fulfilled HLH-2004 criteria). We propose the term of HLH-like hypersensitivity reactions. Usual allergy testing is not useful to the diagnosis. Spontaneous resolution of symptoms can be expected after discontinuation of piperacillin/tazobactam. Clinicians should be aware of this rare disorder to avoid overtreatment or unnecessary investigations.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.004 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".