# P-1724. Cryptococcus neoformans var. grubii infection due to medical cannabis consumption

## TL;DR

This study shows that medical cannabis can be a source of dangerous fungal infections, like cryptococcosis, in immunocompromised patients.

## Contribution

The first definitive evidence linking a specific invasive fungal infection to a pathogen in medical cannabis.

## Key findings

- Cryptococcus neoformans var. grubii was isolated from a patient's body and from cannabis flower they consumed.
- Cannabis products were heavily contaminated with multiple fungi, including Aspergillus and Fusarium species.
- The size of cryptococcal conidia may lead to upper airway deposition, causing infection.

## Abstract

Backgound. Cannabis can be contaminated with fungi and bacteria. Cannabis use is associated with invasive fungal infections (IFIs; aspergillosis in particular) in case reports and epidemioloic studies. However, precise sources of these IFIs, whether directly from cannabis or other environmental foci, have not been validated.

Methods. We recovered C. neoformans var. grubii from cerebrospinal fluid (CSF) and larynx of a patient (pt) receiving chemotherapy for multiple myeloma. The pt provided dried ground cannabis flowers (Sativa and hybrid), cannabis vape (distillate) and cannabis wax that were purchased legally from different dispensaries. We cultured samples on maltose yeast extract agar (MEA) and Sabouraud plates or in maltose yeast extract broth (MEB). Strains underwent Illumina whole genome sequencing.

Results. Moulds were cultured readily from all 4 cannabis products (Aspergillus fumigatus, A. flavus, A. niger, Fusarium spp, Penicillium spp). After adding a sonication step and isolating mould colonies early to prevent overgrowth, we cultivated 2 C. neoformans var. grubii colonies from hybrid flower (but not other products) on MEA and in MEB. Strains from larynx, CSF, flower-MEA and flower-MEB were indistinguishable by core genome SNP phylogeny, but they differed significantly from a reference strain and a strain from another pt. Therefore, C. neoformans var. grubii from cannabis flower was the cause of cryptococcosis. Disseminated cryptococcois likely originated from inhalation of conidia and laryngeal infection. Crypotococcal conidia are larger than those of Aspergillus (4-6 µm, up to 100 µm with enlarged capsule vs. 2-3.5 µm), which may have prediposed to upper airway deposition. We are currently performing metagenomic sequencing of DNA from cannabis products to determine the full spectrum of fungal contamination.

Conclusions. This is the first study to definitively link IFI or bacterial infection to a pathogen in medical cannabis used by the pt. Our data prove that cannabis consumption is a risk for IFI, as long postulated. There are no U.S. federal guidelines for development, medical use or quality testing of cannabis. Better regulation of medical cannabis is needed, as are rigorous clinical studies of efficacy and complications.

Cornelius J. Clancy, MD, Merck: Grant/Research Support|Shionogi: Advisor/Consultant M Hong Nguyen, MD, Basilea: Advisor/Consultant|BioMerieux: Grant/Research Support|Melinta: Grant/Research Support|Pulmocide: Advisor/Consultant|Pulmocide: Grant/Research Support