INFECTIOUS DISEASES

Treating Endometritis Fungal

A Closer Look at Difficult to Treat Fungal Endometritis

By Paul Basilio

Fungal endometritis is an important cause of infertility, and it carries a relatively poor breeding prognosis. These cases are often difficult to diagnose and to treat; luckily, they are not nearly as common as their bacterial counterparts, according to Tom Stout, VetMB, PhD, DECAR, a professor in the Department of Clinical Sciences at Utrecht University in the Netherlands.

Fungal endometritis, in essence, is an opportunistic infection. Causal organisms are found commonly in the environment—particularly in feces and on the skin—but the risk of clinical infection is vastly enhanced in mares with a chronically disturbed uterine environment, such as those with pneumovagina, necrotic foci, problematic foaling, and prolonged intrauterine antibiotic therapy.

According to some surveys, fungi account for only about 1% to 7% of all uterine infections. There is, however, a caveat, according to Dr. Stout.

“Do we always check?” He asked during a presentation at the 68th Annual AAEP Convention. “It may be that we’re not always culturing appropriately and picking them all up.”

Many mares with fungal endometritis are barron at the start of the season.

Diagnosis

Typical clinical signs include evidence of uterine inflammation, such as copious uterine fluid and vaginal discharge that can vary in color and consistency. Many mares with fungal endometritis are also barren at the start of the breeding season.

However, “there will be occasions where you see a mare with fungal endometritis that looks pretty normal and healthy,” Dr. Stout said.

Definitive diagnosis involves a combination of cytology and aerobic culture of uterine material obtained through a guarded swab, cytology brush or low-volume uterine lavage.

“You will need to culture [your samples] the right way,” he added. “That will typically involve Sabaraud’s agar or chromogenic agar.”

It’s important to note that a culture should not be declared negative for fungi until 5 days of incubation, as fungi tend to grow at a slower rate than other organisms. For a more rapid diagnosis, Dr. Stout often turns to cytology.

“You’ll pick up neutrophils, and you’ll often see fungal organisms,” he explained. “It can be an extremely useful and quick way of making the diagnosis.”

Rapid typing and identification of the fungus is important for deciding on appropriate treatment. Many laboratories have specialized tests that can also identify fungal pathogens, but that process can take weeks.

“Occasionally, your swab will come back clean, and you may ask yourself why,” Dr. Scott said. “We think it’s because Candida albicans can grow intracellularly, and sometimes it can sit quite deep in the endometrium.”

Endometrial biopsy may also pick up evidence of endometrial fibrosis, which will impact the mare’s fertility prognosis.

Treatment

Fungal endometritis is a tricky infection to resolve, so naturally many different types of treatments have been attempted. The problem, however, is that not many veterinarians or clinics see enough of the cases to create large-scale, controlled clinical trials.

To help weed through the plethora of available choices, Dr. Stout gave a rundown of his typical treatment course.

First, he’ll do a uterine flush with 250 mg of 2% acetic acid. The acid is an irritant and will result in a sloughing of the endometrium.

“Sloughing of the endometrium may help antifungal treatments reach further into the affected tissues to get at that deeper seated fungi,” he explained.

After 5 minutes, he’ll flush out the acid with 3 L of lactated Ringer’s solution. Then, 50 mL of a 10-mg/mL clotrimazole solution is administered by intrauterine infusion for 6 consecutive days. Topical clotrimazole cream is also applied to the vagina and clitoris at the time of infusion.

“If we need to clean the uterus [on subsequent days], I’ll flush with the lactated Ringer’s solution before the clotrimazole administration,” he added. “That can be done daily.”

He explained that this treatment plan clears approximately half of the fungal endometritis cases he sees. It’s not perfect, but that 50% success rate is an improvement over past treatments, Dr. Stout said.

For the other 50% of cases that aren’t cleared, he will switch the clotrimazole to nystatin or amphotericin B.

IS THERE A UTERINE BIOME?

In other structures of the body, such as the gut, excessive antibiotic use can disturb normal commensal flora and create an opening for an opportunistic infection.

“We’ve heard about the possibility of a uterine microbiome, and there have been a few studies that suggest there is a normal bacterial culture within the uterus,” said Tom Stout, VetMB, PhD, DECAR, a professor in the Department of Clinical Sciences at Utrecht University in the Netherlands. “But when we've tried to look, it’s challenging. The uterus of a diestrus mare seems to be sterile.”

He added that some sequencing techniques have found bacteria, but he’s unsure if that can be considered a real microbiome.

“It may be that we just can’t culture them, but I think there’s still a question of how important it is,” he said. “The issue [with fungal endometritis] is that as you put more antimicrobials in the uterus, they’re probably flowing back through the normal flora of the vagina and vestibulum. It may be that the colonization begins there, and then the next time you do something to the uterus, you’ll bring the fungi in.”