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Pearls and Pitfalls of Intrathecal Amphotericin B Therapy for Refractory Coccidioidal Meningitis in Children: An
Sanchi Malhotra1, Kristina Adachi1, Aria Fallah2
1From the Departments of Pediatrics, Division of Infectious Diseases at David Geffen School of Medicine at UCLA.
Introduction:
Incidence of pediatric coccidioidomycosis has risen over the last 20 years, and coccidioidal meningitis is the most severe form of disseminated disease. Intrathecal amphotericin B deoxycholate (IT AmBd) has historically improved outcomes and remains a mainstay of therapy when response to azole therapy is inadequate. However, the dosing, route of administration and duration of therapy in young pediatric patients pose unique challenges due to their anatomy, inability to communicate and the need for hospital-based administration. We present 4 instructive cases over 30 years to provide guidance on the use of IT AmBd.
Methods:
Case information was abstracted from the electronic health record at University of California Los Angeles. Literature review was conducted to look for additional cases on Pubmed with relevant search terms.
Results:
We present 4 cases including 2 patients with successful outcomes and 2 who did not survive. Starting doses, administration routes, complications and neurosurgical challenges are described. Patients had prolonged hospitalizations as the ability to administer outpatient IT amphotericin B was minimal. Therefore, more rapid dose escalation and weaning, with a shorter overall duration of therapy, was needed than described for adults. IT treatment was considered an initial stabilizing measure while attempting to optimize azole monotherapy. Cisternal administration is preferred but remains a logistical challenge.
Conclusion:
Intrathecal AmBd remains an important treatment option in pediatric patients with refractory coccidioidal meningitis; however, due to unique administration, challenges may be more of a temporizing measure rather than definitive prolonged therapy. Further experience and multidisciplinary care are needed to reduce mortality.
Insights
Intrathecal amphotericin B deoxycholate (IT AmBd) is crucial for pediatric coccidioidal meningitis when azoles fail. Unique challenges in pediatric administration require careful management, often as a temporizing measure.
Area of Science:
- Pediatric Infectious Diseases
- Neuroscience
- Mycology
Background:
- Pediatric coccidioidomycosis incidence has increased, with coccidioidal meningitis being the most severe form.
- Intrathecal amphotericin B deoxycholate (IT AmBd) is a key treatment for refractory cases, especially when azole therapy is insufficient.
- Pediatric administration of IT AmBd presents unique challenges regarding dosing, route, and duration.
Purpose of the Study:
- To provide guidance on the use of IT AmBd in young pediatric patients with coccidioidal meningitis.
- To share insights from instructive cases over 30 years to inform clinical practice.
- To address the complexities of IT AmBd administration in pediatric neuroinfections.
Main Methods:
- Retrospective case review of pediatric patients treated with IT AmBd at UCLA.
- Literature search on PubMed for additional relevant cases and treatment strategies.
- Analysis of dosing, administration routes, complications, and outcomes.
Main Results:
- Four cases are presented, with 2 patients experiencing successful outcomes and 2 fatalities.
- Prolonged hospitalizations were common due to limited outpatient IT AmBd administration.
- Faster dose escalation and shorter therapy durations were necessary compared to adults; cisternal administration preferred but challenging.
Conclusions:
- IT AmBd remains vital for pediatric refractory coccidioidal meningitis.
- Administration challenges may position IT AmBd as a temporizing measure rather than definitive therapy.
- Further research and multidisciplinary collaboration are essential to improve outcomes and reduce mortality.
