The safest antifungal medication for use in breastfeeding mothers is Nystatin.

- Nystatin is a topical antifungal agent that is not significantly absorbed systemically when applied to mucous membranes or skin.
- This makes it safe for breastfeeding mothers, as minimal to no drug passes into breast milk, reducing the risk of exposure to the nursing infant.

In contrast:
- Fluconazole and Itraconazole are systemic azole antifungals that do cross into breast milk and may pose potential risks to the infant. They are generally avoided unless clearly indicated and prescribed with caution.
- Ketoconazole has systemic absorption and potential hepatotoxicity and is not preferred during breastfeeding.

Thus, when antifungal treatment is needed for conditions like oral thrush or localized candidiasis in breastfeeding women, Nystatin remains the first choice due to its safety profile.

Reference: Harrison's Principles of Internal Medicine, 20th Edition, Volume 2, Chapter: Fungal Infections / Page 3215