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Hydroxyurea for Malignant Pertussis in Critically Ill Children
Matthieu Blanc1, Clémence Marais1, Alexandre Debs1
1IHU-PROMETHEUS Comprehensive Sepsis Center and Pediatric Intensive Care, Neonatal Medicine, and Pediatric Emergency Department, AP-HP Paris Saclay University, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
Insights
Hydroxyurea effectively reduces hyperleukocytosis in infants with malignant pertussis, offering a safer alternative to whole blood exchange transfusion. This approach shows promise in improving outcomes for severe Bordetella pertussis infections.
Area of Science:
- Pediatrics
- Infectious Diseases
- Critical Care Medicine
Background:
- Malignant pertussis, a severe form of Bordetella pertussis infection, presents with multi-organ failure and high mortality.
- Hyperleukocytosis is a critical feature of malignant pertussis, demanding immediate intervention.
- Whole blood exchange transfusion is a traditional leukoreduction method but carries significant risks.
Purpose of the Study:
- To evaluate the clinical experience of using hydroxyurea as a pharmacological alternative to whole blood exchange for leukoreduction in infants with malignant pertussis.
- To assess the efficacy and safety of hydroxyurea in managing hyperleukocytosis in this patient population.
Main Methods:
- A prospective case series was conducted in a French pediatric intensive care unit (PICU).
- Critically ill infants (n=27) with severe pertussis were analyzed.
- Treatment strategies included hydroxyurea therapy or whole blood exchange transfusion for managing hyperleukocytosis.
Main Results:
- Twelve infants had malignant pertussis; seven received hydroxyurea and five underwent whole blood exchange.
- Hydroxyurea successfully reduced leukocyte counts within 7 days.
- Overall mortality was 25% (3 of 12 infants), with hydroxyurea demonstrating effective leukoreduction.
Conclusions:
- Hydroxyurea serves as an effective alternative therapy for managing hyperleukocytosis in infants with malignant pertussis.
- This pharmacological approach offers a potentially safer option compared to whole blood exchange transfusion.
- The study highlights hydroxyurea's role in addressing a critical complication of severe pertussis infections.
Objectives:
Malignant pertussis, the most severe manifestation of Bordetella pertussis infection, is characterized by multiple organ failure and a high mortality rate despite advanced intensive care measures. Hyperleukocytosis is the hallmark of malignant pertussis and necessitates urgent and aggressive interventions. Among the therapeutic options, leukoreduction via whole blood exchange (BE) transfusion has been associated with significant procedural risks and potential clinical deterioration. Hydroxyurea was recently proposed as a pharmacological alternative for leukoreduction. This study reports our clinical experience with hydroxyurea as an alternative to BE in managing infants with malignant pertussis admitted to a PICU.
Design:
Prospective case series.
Setting:
A referral PICU in France.
Patients:
Critically ill infants (n = 27) with severe pertussis infection.
Interventions:
Hydroxyurea therapy or BE transfusion.
Measurements And Main Results:
We reviewed all critically ill infants admitted to our unit for severe pertussis between January 2017 and July 2024. The primary outcome was 28-day survival, and the secondary outcome was the efficacy of hydroxyurea on blood leukocyte count reduction. Among the 27 infants admitted for severe pertussis, 12 exhibited features of malignant pertussis. Of these, seven were treated with hydroxyurea and five with BE. The majority of infants were term and under 3 months old. All patients required ventilatory support, with eight on invasive mechanical ventilation and three receiving extracorporeal membrane oxygenation therapy. Overall mortality was three of 12 (25%). Hydroxyurea was administered at a dose of 20 mg/kg/d for a median duration of 12 days. Hyperleukocytosis was successfully reduced within 7 days.
Conclusions:
Hydroxyurea is an alternative therapy for malignant pertussis infection that can efficiently address hyperleukocytosis with limited mortality.
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