Protocols for the Treatment of Fungal Endometritis

Fungal endometritis is an uncommon condition in mares, accounting for less than 5% of diagnosed endometritides. Moreover, it is generally accepted that fungal infection is opportunistic, and only becomes established in a chronically disturbed uterine environment, where pneumovagina, persistent or recurrent bacterial endometritis, post-partum necrotic foci and repeated intrauterine antibiotic therapy are the most commonly cited predisposing factors.

Since the exact conditions that permit fungal colonisation of the uterus are unknown, and both the identity of the causal organism and the chronicity of infection appear to influence the likelihood of clearing the infection, there are currently no universal protocols proven to offer a high likelihood of successful resolution. Nevertheless, a study that examined in vitro sensitivity reported nystatin, amphotericin B, ketoconazole and clotrimazole to have the broadest spectrums of activity against fungal pathogens recovered from the uterus of affected mares (>80% of isolates [1]). And, while in vitro sensitivity is no guarantee of in vivo efficacy, a protocol based around a relatively long (>5 days) duration of daily intrauterine infusion with one of the above antimicrobials appears to maximise the likelihood of eliminating the infection.

Alternatively or additionally, intrauterine infusion with nonspecific chemicals such as 2% acetic acid, 1–3% hydrogen peroxide or 10–20% DMSO for 1–3 days appears to offer a reasonable chance of resolution (i.e. approximately 20% of treatment cycles). Irrespective of the intrauterine treatment(s) selected, it is advisable to simultaneously treat against a potential reservoir of infection in the caudal reproductive tract (vagina and clitoral fossa), and to ensure that any (suspected) predispositions (e.g. pneumovagina) are addressed. While systemic administration of antimycotics has also been advocated, it is associated with high costs, long durations of therapy, the risk of significant side effects and poor gastrointestinal availability. While oral fluconazole is considered the most appropriate systemic agent because of its good gastrointestinal availability, even long durations of treatment are associated with a high rate of recrudescence.

Our current first-line fungal endometritis treatment protocol involves a single intrauterine infusion of 2% acetic acid, washed out 5 minutes later with lactated Ringer’s solution, and followed by 6 consecutive days of intrauterine (500 mg once daily) and intravaginal (cream) clotrimazole application. The acetic acid infusion often induces sloughing of the endometrial epithelium and the serosanguineous discharge, if present, is removed by uterine lavage with lactated Ringer’s prior to daily clotrimazole infusion.

Overall, this protocol has yielded promising results with approximately 50% resolution after a single treatment cycle. It is worth noting that resolution of fungal endometritis is often (>40% of successful treatments) followed by a bacterial endometritis (typically Streptococcus equi zooepidemicus) that also requires treatment. If an initial treatment cycle is unsuccessful, the anti-fungal protocol can be repeated at the following oestrus; however, if the owner is not motivated to continue, an extended period of breeding rest after the initial treatment can be surprisingly effective in allowing ‘spontaneous’ re-establishment of a normal uterine environment and clearance of the fungus.

Overall, owners of mares diagnosed with a fungal endometritis need to be warned that resolution can be challenging, particularly if the infection is long-standing, and that the overall costs of treatment can be significant. Moreover, the fungus can induce fibrotic degeneration of the endometrium that may compromise the mare’s subsequent ability to support a pregnancy to term. On the other hand, a recent study reported a 48% pregnancy rate in mares treated for one cycle with intrauterine clotrimazole pessaries on 3 consecutive days [2], suggesting that it is worthwhile at least attempting treatment.

[...]