# Limited genome evolution of Cryptococcus neoformans following an accidental infection in the research laboratory

## TL;DR

This paper describes four cases of accidental Cryptococcus neoformans infections in a lab and shows that fluconazole treatment was effective, with genome sequencing revealing limited evolution in the fungus.

## Contribution

The study provides updated guidance for handling accidental C. neoformans infections and demonstrates the effectiveness of immediate antifungal therapy.

## Key findings

- Fluconazole therapy successfully treated four accidental C. neoformans infections in laboratory researchers.
- Whole genome sequencing showed limited evolution in the C. neoformans strain over time.
- Prophylactic fluconazole prevented symptoms in three exposed researchers.

## Abstract

Cutaneous infections resulting from accidental exposure to fungal pathogen Cryptococcus neoformans in research laboratories are rarely reported in the literature. To fill a gap in published guidance for handling these situations promptly when they arise, we describe a case report plus three additional examples as a guide to effective resolution.

An immunocompetent laboratory researcher developed primary cutaneous cryptococcosis following accidental infection with Cryptococcus neoformans H99 via a needle scrape that was initially assumed not to have penetrated the skin. On day 8 after the incident, a characteristic nodular erythematous lesion developed on a finger at the exposure site. Antibacterial therapy was initiated for the clinical impression of bacterial cellulitis as clinical tests for cryptococcal serum antigen and cultures of aspirates from the wound site on day 13 after incident were negative. Eight-week fluconazole therapy initiated on day 15 after the incident was curative. Whole genome sequencing of yeast grown from wound exudate collected on day 18 confirmed high sequence similarity to H99 Cryptococcus neoformans var. grubii and sequence divergence from an archived sample isolated from an immunocompromised individual. Three additional cases with potential exposures to C. neoformans in the research lab received prophylactic fluconazole and remained asymptomatic.

In a span of 5 years, four laboratory researchers from two research groups at the same institution sustained accidental exposures to C. neoformans, and all were successfully treated. These cases reinforce and update the recommendations for initiating antifungal therapy immediately after laboratory accidents involving C. neoformans.