treatment protocol involves a single 250-mL infusion of 2% acetic acid, which is flushed out with 3 L of LRS within 5minutes, followed by intrauterine infusion of 50mL of a 10-mg/mL clotrimazole solution. Clotrima-


zole infusion is repeated for 6 consecutive days, after first removing any accumulated fluid by lavage with LRS, and is combined with daily topical application of clotrimazole cream to the vagina and clitoris. Initial results are promising, and recently, Nielsen et al.2 reported pregnancy in 24/50 mares (48%) treated for fungal endometritis using 3 consecutive days of uter- ine lavage with 0.9% saline followed by the introduc- tion of a 100-mg clotrimazole tablet. In the early 2000s, lufenuron, the benzoylphenyl


urea derivative used for flea control in dogs and cats, was popular for treating fungal endometritis in mares, based on a report of the successful resolution of fungal endometritis in 4 mares treated with a sin- gle intrauterine administration of 540mg of lufe- nuron.15 The rationale for this treatment centered on the factthatlufenuron’s primary anti-insecticidal property is the ability to interfere with chitin biosyn- thesis. Since fungi also incorporate chitin into their cell walls, it was proposed that lufenuron might in- hibit fungal growth. However, fungal endometritis was not cleared in any of 3mares treated with 540mg oflufenuroninthe author’s clinic, and subsequent studies have failed to demonstrate any in vitro anti- fungal activity of lufenuron (e.g., against Aspergillus or Fusarium spp.)16 such that it is unclear whether lufenuron, or other chitin synthesis inhibitors, are effective in the treatment of fungal infections in the uterus ofmares or in other situations. As indicated above, an important adjunct to intrau-


terine antifungal treatment is topical treatment of the vagina and clitoris (e.g., with clotrimazole cream) to remove any reservoir of organisms that might other- wise lead to reinfection. Two further observations worthy ofmention are the following: (1) The clearance of uterine fungal infection has been noted in a handful of mares allowed a prolonged period of breeding rest (months) following apparently unsuccessful antifun- gal treatment. It is possible that a combination of reducing the number of infectious organisms by treat- ment combined with a long period of rest to encourage restoration of the normal vaginal microenvironment was sufficient to facilitate “spontaneous” clearance. (2) Following treatment for fungal endometritis, mares commonly develop bacterial endometritis (62/148: 41%, predominantly Streptococcus equi zooepidemicus).11 Although there is clearly a concern that the bacteria may mask the continuing presence of fungi, the post- treatment streptococcal infection often appears to be an indicator of successful fungal elimination. Moreover, the streptococcal infection is readily resolved by intrau- terine antibiotic treatment, which does not appear to retrigger the fungal infection.


44 2022 / Vol. 68 / AAEP PROCEEDINGS


INFLAMMATION, INFECTION, OR BOTH? ROOT CAUSES OF ENDOMETRITIS 5. Conclusions


Fungal endometritis is an uncommon problem that can be challenging to resolve. At present, a combina- tion of nonspecific therapy with 2% acetic acid or 1% to 3% hydrogen peroxide and/or > 5days intrauterine therapy with a specific antifungal agent (e.g., clotrim- azole, nystatin, or amphotericin B) appears to offer the best chance (20%–50%) of resolving the fungal infection and establishing pregnancy. While contem- poraneous correction of any anatomical abnormalities and treating a potential reservoir of infection in the caudal reproductive tract or correcting any general- ized immune compromisemay reduce the risk of rein- fection, a second estrus may be required to complete elimination of the fungus or to resolve a subsequent bacterial endometritis. Significant improvements in therapy are likely to require a clearer understanding of the conditions that permit the establishment and maintenance of fungal infection in the mare’suterus.


Acknowledgments


Declaration of Ethics The Author has adhered to the Principles of VeterinaryMedical Ethics of the AVMA.


Conflict of Interest The Author has no conflicts of interest.


References


1. Dascanio JJ, Schweizer C, Ley WB. Equine fungal endome- tritis. Equine Vet Educ 2010;13:324–329.


2. Nielsen JM, Fog P, Bojesen AM. Impact of yeast endometri- tis on fertility in the mare. J Equine Vet Sci 2021;99:103409.


3. Pugh DG, Bowen JM, Kloppe LH, et al. Fungal endometritis in mares. Comp Cont Educ Pract Vet 1986;8:S173–S182.


4. Coutinho da Silva MA, Alvarenga MA. Fungal endometritis. In: McKinnon AO, Squires WL, Vaala W, Varner DD, eds. Equine reproduction 2nd ed. Chichester: Wiley-Blackwell, 2011;2643–2651.


5. Malmgren L, Olsson Engvall E, Engvall A, et al. Aerobic bacterial flora of semen and stallion reproductive tract and its relation to fertility under field conditions. Acta Vet Scand 1998;39:173–182.


6. Zafracas AC. Infection of the genital tract in Thoroughbred mares. J Reprod Fert 1975;23:349–351.


7. Troedsson MHT. Diseases of the uterus. In: Robinson N, ed. Current therapy in equine medicine 4th ed. Philadelphia: W.B. Saunders Company, 1997;517–524.


8. Chengappa MM, Maddux RL, Greer SC, et al. Isolation and identification of yeasts and yeast-like organisms from clini- cal sources. J Clin Microbiol 1984;19:427–428.


9. Heil BA, Paccamonti DL, Sones JL. Role for the mammalian female reproductive tract microbiome in pregnancy out- comes. Physiol Genomics 2019;51:390–399.


10. Hurtgen JP, Cummings MR. Diagnosis and treatment of fungal endometritis in mares, in Proceedings. Society for Theriogenology, 1982;82.


11. Stout TAE. Fungal endometritis in the mare. Pferdeheilkunde 2008;24:83–87.


12. Freeman KP, Roszel JF, Slusher SH, et al. Mycotic infec- tions of the equine uterus. Equine Pract 1986;8:34–42.


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