HLH-like Hypersensitivity Reaction Secondary to Prolonged Piperacillin/Tazobactam: A Case Series
Why this work is in the frame
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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.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it