How and When to Treat Endometritis with Systemic or Local Antibiotics

1. Introduction

The decision to use antibiotics for the treatment of a reproductive problem in a mare is not always clearcut or cookbook. Factors that may influence that decision include current duration of the pathology/ infertility, previous treatment, previous infertility, previous experience, or even pressure from the owner to get the mare pregnant.
      
One of the key factors in treating endometritis is accurately diagnosing that a true bacterial infection is present. This stems from the potential difficulty in acquiring an accurate diagnostic sample from culture and/or cytology. Recently, Petersen, from Denmark, described the invasiveness of Streptococcus zooepidemicus into the mare’s endometrium, discovering on analysis of uterine biopsies that Streptococcus was present deep within the endometrial tissue.¹  Thus, it is possible to miss a diagnosis with sampling of the uterine lumen, or, if treatment is limited to intra-uterine therapy, the treatment course could be unsuccessful, especially if the antibiotic did not achieve deep-tissue antibiotic concentrations adequate to kill the organism. Unfortunately, there is no immediate answer regarding many bacterial organisms as to where they are located because investigators have yet to classify which organisms may be predisposed to superficial or more deep seated infections. Chronicity of infection may certainly predispose to deeper invading infections. There are also differences between mares with regard to location within the uterus or endometrium for bacterial infections. Infections may be localized to a specific area of the uterus or may encompass the vast majority of the luminal endometrium.
     
Antibiotics are used in the mare to treat potential or realized reproductive tract infections including vaginitis, cervicitis, endometritis, metritis, pyometra, and placentitis. Alternatively, infections may be associated with or classified as sexually transmitted diseases, post–mating-induced endometritis, acute or chronic endometritis, abortion-related, and/or bacterial and fungal infections.² Antibiotics are administered either through intravenous/intramuscular routes or directly into the reproductive tract lumen. Antibiotics are naturally occurring or synthetic substances that inhibit the growth of or kill microorganisms. The definition may be limited to substances affecting bacteria or may also include fungi and protozoa. In this report, antifungals will be considered part of the antibiotic class.
     
There are some reviews of the use of antibiotics in mare reproduction.^3–5 The choice of antibiotic should be based on culture and sensitivity patterns when possible or based on the most likely organism when a culture/sensitivity is not possible, such as a client refusing the procedures. The most common bacteria isolated from the mare’s reproductive tract are Streptococcus equi, subspecies zooepidemicus (Gram positive), Escherichia coli (Gram negative), Klebsiella pneumonia (Gram negative), Pseudomonas aeruginosa (Gram negative), Staphylococcus aureus (Gram positive), and Bacteroides (Gram negative, anaerobe).^6-11 S. equi subspecies zooepidemicus and E. coli are the number-1 and number-2 isolates in almost all reports. The most common fungi isolated from the mare’s reproductive tract are Candida spp. and Aspergillus spp.¹²
      
There are many factors that may affect antibiotic effectiveness/clearance such as overwhelming microorganism numbers, presence of uterine fluid/debris, lack of uterine contractility, use of ecbolics, normality of uterine mucocilliary clearance mechanisms, cervical dilation, and dependency of the uterine horns.^13-16 Disruptions of natural barriers to infection, such as previous cervical trauma/scarring, vestibulovaginal fold incompetence (windsucker), and poor vulvar conformation, may also contribute to continued bacterial/fungal contamination.¹⁷ 
      
​​​​​​​Intrauterine antibiotic therapy appears to have decreased in use, probably because of concerns about inducing secondary fungal infections and/or antibiotic resistance, and as the result of new information on the effectiveness of uterine lavage and the use of ecbolics, such as oxytocin and prostaglandins. Antibiotic therapies are now more targeted at specific organisms, are used with more specific disease processes, or are used in conjunction with methods to disrupt biofilms or after decreasing bacterial numbers with lavage techniques. This report will describe the results of an on-line survey of veterinarians concerning antibiotic use in mare reproduction and will correlate the results to the literature.

2. Materials and Methods

Two surveys were conducted with regard to the use of antibiotics in equine reproduction. The surveys were initiated to see what is commonly used in practice versus what is recommended in the literature. Both surveys were sent to the Equine Clinicians Network listserv ([email protected]), the American Association of Equine Practitioner’s listserv (aaep [email protected]), the Equine Reproduction listserv ([email protected]), and the American College of Theriogenologists listserv ([email protected]). The first was initiated in September 2008 (190 respondents) and the second was initiated in March 2009 (109 respondents). The second survey was performed to augment the first survey results. Sixty-one percent of participants in the second survey partook in the first survey.

3. Results and Discussion

Approximately 69% of survey participants stated that the primary way that mares are bred in their practice is by the use of fresh cooled semen, 27% are bred primarily by natural cover, 3% primarily with frozen semen, and 2% did not provide an answer. The number of years in practice was: <5 years, 7%; 5 to 10 years, 20%; 11 to 15 years, 13%; 16 to 20 years, 18%; >20 years, 39%; and no answer, 2%. The percentage of their practice that was devoted to equine reproduction was: <10%, 11%; 10% to 25%, 21%; 25% to 50%, 18%; 50% to 75%, 15%; >75%, 34%; and no answer, 1%. The larger number of practitioners in the >75% category probably reflects the distribution of the survey to two predominately reproductively oriented listservs (ACT and EqRepro). Veterinarians from 14 countries participated in the survey, with 70% of respondents practicing in the United States.

When asked which bacterial and fungal organisms they encountered most, the overwhelming answer for bacterial isolates were S. zooepidemicus.followed secondarily by E. coli. One practice stated that they had 80% ß-hemolytic Streptococcus isolated from 1400 uterine cultures in their clinic. An antibiotic with both Gram-positive and Gram-negative properties may be appropriate for the treatment of uterine infections in those cases without culture. Fungal cultures, from survey results, yielded primarily Candida spp. followed secondarily by Aspergillus spp.

4. Intrauterine Usage of Antibiotics

Antibiotics may be placed into the uterus before or after breeding or in association with treatment of suspected or known uterine infections. Dosages for antibiotics commonly given intrauterine are presented in Table 1. Practitioners in the survey stated that antibiotics used before breeding were used for mares that were known to be problem breeders, mares that were repeat breeders, mares with uterine fluid before breeding, mares with excessive uterine edema, mares suspected of having an infection (awaiting culture/cytology results), mares suspected of having an infection (owners decline culture/cytology), or strictly at the owner’s request. [...]