How and When to Treat Endometritis with Systemic Or Local Antibiotics

REPRODUCTION I

How and When to Treat Endometritis With Systemic or Local Antibiotics

John J. Dascanio, VMD, Diplomate ACT, ABVP (Equine)

Author’s address: Ross University School of Veterinary Medicine, PO Box 334, Basseterre, St. Kitts; e-mail: [email protected]. This paper is adapted with permission from Antibiotics in Mare Reproduction. Clinical Theriogenology 1:2009;411–432. © 2011 AAEP.

1. Introduction cated because investigators have yet to classify The decision to use antibiotics for the treatment of a which organisms may be predisposed to superficial reproductive problem in a mare is not always clear- or more deep seated infections. Chronicity of infec- cut or cookbook. Factors that may influence that tion may certainly predispose to deeper invading decision include current duration of the pathology/ infections. There are also differences between infertility, previous treatment, previous infertility, mares with regard to location within the uterus or previous experience, or even pressure from the endometrium for bacterial infections. Infections may be localized to a specific area of the uterus or owner to get the mare pregnant. may encompass the vast majority of the luminal One of the key factors in treating endometritis is endometrium. accurately diagnosing that a true bacterial infection Antibiotics are used in the mare to treat potential is present. This stems from the potential difficulty or realized reproductive tract infections including in acquiring an accurate diagnostic sample from cul- vaginitis, cervicitis, endometritis, metritis, pyome- ture and/or cytology. Recently, Petersen, from tra, and placentitis. Alternatively, infections may Denmark, described the invasiveness of Streptococ- be associated with or classified as sexually transmit- cus zooepidemicus into the mare’s endometrium, dis- ted diseases, post–mating-induced endometritis, covering on analysis of uterine biopsies that acute or chronic endometritis, abortion-related, Streptococcus was present deep within the endome- and/or bacterial and fungal infections.2 Antibiotics 1 trial tissue. Thus, it is possible to miss a diagnosis are administered either through intravenous/intra- with sampling of the uterine lumen, or, if treatment muscular routes or directly into the reproductive is limited to intra-uterine therapy, the treatment tract lumen. Antibiotics are naturally occurring or course could be unsuccessful, especially if the anti- synthetic substances that inhibit the growth of or biotic did not achieve deep-tissue antibiotic con- kill microorganisms. The definition may be limited centrations adequate to kill the organism. Unfor- to substances affecting bacteria or may also include tunately, there is no immediate answer regarding fungi and protozoa. In this report, antifungals will many bacterial organisms as to where they are lo- be considered part of the antibiotic class.

NOTES

24 2011 ր Vol. 57 ր AAEP PROCEEDINGS REPRODUCTION I There are some reviews of the use of antibiotics in participants in the second survey partook in the first mare reproduction.3–5 The choice of antibiotic survey. should be based on culture and sensitivity patterns when possible or based on the most likely organism 3. Results and Discussion when a culture/sensitivity is not possible, such as a Approximately 69% of survey participants stated client refusing the procedures. The most common that the primary way that mares are bred in their bacteria isolated from the mare’s reproductive tract practice is by the use of fresh cooled semen, 27% are are Streptococcus equi, subspecies zooepidemicus bred primarily by natural cover, 3% primarily with (Gram positive), Escherichia coli (Gram negative), frozen semen, and 2% did not provide an answer. Klebsiella pneumonia (Gram negative), Pseudomo- The number of years in practice was: Ͻ5 years, 7%; nas aeruginosa (Gram negative), Staphylococcus 5 to 10 years, 20%; 11 to 15 years, 13%; 16 to 20 aureus (Gram positive), and Bacteroides (Gram years, 18%; Ͼ20 years, 39%; and no answer, 2%. negative, anaerobe).6–11 S. equi subspecies zooepi- The percentage of their practice that was devoted to demicus and E. coli are the number-1 and number-2 equine reproduction was: Ͻ10%, 11%; 10% to 25%, isolates in almost all reports. The most common 21%; 25% to 50%, 18%; 50% to 75%, 15%; Ͼ75%, fungi isolated from the mare’s reproductive tract are 34%; and no answer, 1%. The larger number of Candida spp. and Aspergillus spp.12 practitioners in the Ͼ75% category probably reflects There are many factors that may affect antibiotic the distribution of the survey to two predominately effectiveness/clearance such as overwhelming mi- reproductively oriented listservs (ACT and EqRe- croorganism numbers, presence of uterine fluid/de- pro). Veterinarians from 14 countries participated bris, lack of uterine contractility, use of ecbolics, in the survey, with 70% of respondents practicing in normality of uterine mucocilliary clearance mecha- the United States. nisms, cervical dilation, and dependency of the uter- When asked which bacterial and fungal organ- ine horns.13–16 Disruptions of natural barriers to isms they encountered most, the overwhelming an- infection, such as previous cervical trauma/scarring, swer for bacterial isolates were S. zooepidemicus. vestibulovaginal fold incompetence (windsucker), followed secondarily by E. coli. One practice stated and poor vulvar conformation, may also contribute that they had 80% ␤-hemolytic Streptococcus iso- to continued bacterial/fungal contamination.17 lated from 1400 uterine cultures in their clinic. Intrauterine antibiotic therapy appears to have An antibiotic with both Gram-positive and Gram- decreased in use, probably because of concerns about negative properties may be appropriate for the inducing secondary fungal infections and/or antibi- treatment of uterine infections in those cases with- otic resistance, and as the result of new information out culture. Fungal cultures, from survey results, on the effectiveness of uterine lavage and the use of yielded primarily Candida spp. followed secondarily ecbolics, such as oxytocin and prostaglandins. An- by Aspergillus spp. tibiotic therapies are now more targeted at specific 4. Intrauterine Usage of Antibiotics organisms, are used with more specific disease processes, or are used in conjunction with methods Antibiotics may be placed into the uterus before or to disrupt biofilms or after decreasing bacterial after breeding or in association with treatment of numbers with lavage techniques. This report will suspected or known uterine infections. Dosages for describe the results of an on-line survey of veteri- antibiotics commonly given intrauterine are pre- narians concerning antibiotic use in mare repro- sented in Table 1. Practitioners in the survey duction and will correlate the results to the stated that antibiotics used before breeding were literature. used for mares that were known to be problem breeders, mares that were repeat breeders, mares with uterine fluid before breeding, mares with ex- 2. Materials and Methods cessive uterine edema, mares suspected of having an Two surveys were conducted with regard to the use infection (awaiting culture/cytology results), mares of antibiotics in equine reproduction. The surveys suspected of having an infection (owners decline cul- were initiated to see what is commonly used in prac- ture/cytology), or strictly at the owner’s request. tice versus what is recommended in the literature. Survey participants stated that they used post- Both surveys were sent to the Equine Clinicians breeding antibiotics in situations in which they Network listserv ([email protected]), the knew the mare had previous problems, in mares American Association of Equine Practitioner’s listserv with uterine fluid, in those mares susceptible to (aaep [email protected]), the Equine Repro- post–mating-induced endometritis, in mares bred duction listserv ([email protected]), and late in the breeding season, in mares with previous the American College of Theriogenologists listserv pregnancy loss, or as a routine procedure with a ([email protected]). The first was single dose of antibiotics, especially in natural cover initiated in September 2008 (190 respondents) and situations. A study by Pycock18 found that preg- the second was initiated in March 2009 (109 respon- nancy rates were better after a single dose of anti- dents). The second survey was performed to aug- biotics (with/without oxytocin) after breeding, ment the first survey results. Sixty-one percent of especially in older mares (Ͼ12 years) and mares

AAEP PROCEEDINGS ր Vol. 57 ր 2011 25 REPRODUCTION I

Table 1. Intrauterine Antibiotic Dosages

Intrauterine Antibiotics

Antibacterial Antibiotics Antibiotic Dosage Comments Major Bacterial Susceptibility Amikacin 1 to 2 grams Buffer with sodium bicarbonate Gram negative or 150- to 200-mL solution Ampicillin 1 to 3 grams Use soluble product, may be Gram positive and E. coli irritating when concentrated Ceftiofur sodium 1 gram Gram positive and Gram negative Chloramphenicol 2 to 3 grams Can be irritating Gram positive and Gram negative Gentamicin 1 to 3 grams Acidic: Need to dilute and/or Gram negative buffer Neomycin 2 to 4 grams Gram negative Potassium penicillin 5 million international Gram positive units Procaine penicillin 4.5 to 6 million Concern about residue left in Gram positive international units uterus Ticarcillin 3 to 6 grams Infuse with 150- to 200-mL Gram positive, Pseudomonas solution Ticarcillin with 3 to 6 grams ␤-Lactamase inhibitor, infuse Same as ticarcillin plus more Gram clavulanic acid with 150- to 200-mL solution positive (Staph, Bacillus, Enterobacter) Antifungal Antibiotics q 24 Hours for 7 Days Drug Dosage Comment Amphotericin B 100 to 200 mg Polyene, dilute in Ͼ100-mL solution, mix well Clotrimazole 400 to 700 mg Azole, tablets usually crushed and mixed with solution Fluconazole 100 mg Azole, may need to adjust pH to avoid acidic nature Miconazole 500 to 700 mg Azole Nystatin 0.5 to 2.5 million Polyene, Dilute in sterile water, not saline to avoid precipitates, mix well international units

mated at the first postpartum estrus. Some Thor- Forty-three percent of practitioners would in- oughbred farms may routinely use a single post- crease the volume of antibiotic solution infused to breeding antibiotic to limit bacterial contamination between 50 to 100 mL before infusion: 8% used from natural cover.19 whatever volume the antibiotic originally came When asked how many days mares were com- with; 19% added extra volume but kept the total less monly treated with intrauterine antibiotics, the than 50 mL; 11% added extra liquid so that the final responses were: 1 day (12%), 2 days (7%), 3 days volume was Ͼ100 mL; 7% simply added their anti- (50%), 4 days (5%), 5 days (7%), 1 week (1%), other biotic to their lavage solution; 6% did not answer the (13%), and no answer (5%). Those answering question; 8% provided an alternative answer of “other” may treat for 1 to 3 days, 3 to 5 days, number “other,” which included leaving some lavage solution of days would depend on bacteria isolated, number in the uterus and simply adding antibiotics to that, of days would depend on presence of fluid, or would using a 250-mL bottle for infusion with antibiotics never treat a mare intrauterine. It has been rec- added, or using a 10-mL or 20-mL total volume. ommended, based on endometrial biopsy, that treat- The literature has suggested intrauterine infusion ment for mild intrauterine infections be performed volumes ranging from 30 to 200 mL to achieve dis- for 3 days, moderate infections for 5 days, and severe tribution throughout the uterine lumen.3 Six infections for 7 days.13 The determination of how grams of ticarcillin, for instance, has a higher intra- mares fit into these categories may not be clear in uterine concentration over time when a 250-mL vol- practice and would need to be subjectively based on ume is infused rather than a 60-mL volume.20 clinical signs and possible cytologic examination be- With large volumes, however, reflux of fluid back cause biopsy results may not be returned for a num- through the cervix could occur, diminishing the ber of days. It has also been suggested that mares overall dose. A more appropriate recommendation not be treated for more than 2 or 3 days after ovu- may be to maximize the volume of distribution of an lation to decrease possible negative effects on corpus antibiotic while factoring in the relative size and luteum progesterone secretion from prostaglandin position of the uterus. Multiparous mares would released in response to endometrial antibiotic/solu- naturally require more volume of distribution, tion irritation.13 Antibiotics should also not be whereas nulliparous mares should require less. used immediately before breeding because high con- With a dependent uterus, infused fluids tend to pool centrations of antibiotics may negatively affect in the base of the uterine horns, making it difficult to sperm function.13 achieve uniform coverage of the endometrium; con-

26 2011 ր Vol. 57 ր AAEP PROCEEDINGS REPRODUCTION I sequently, systemic antimicrobials may be a good may be lactated Ringers solution, which has a neu- choice in these mares. tral pH. The most common antibiotic in the survey used for Aminoglycosides should not be mixed with ␤-lac- intrauterine treatment before receiving culture/ tam antibiotics. Precipitates may form on combi- antibiotic sensitivity results was ceftiofur (21%), nation, or, more importantly, aminoglycosides may followed by gentamicin (19%), ticarcillin with clavu- cause a nucleophilic opening of the ␤-lactam ring, lanic acid (13%), ampicillin (12%), other (12%), pro- which then combines with an amino group from the caine penicillin (5%), amikacin (5%), potassium aminoglycoside, resulting in a biologically inactive penicillin (3%), and ticarcillin (3%). Nine percent amide.25,26 Although the two drugs are synergistic of survey participants did not answer this question. in controlling Gram-positive (␤-lactams) and Gram- The category “other” included combination of peni- negative (aminoglycosides) infections when given cillin and gentamicin (2%), penicillin and neomycin systemically, it is not completely understood how (2%), ampicillin and gentamicin (1%), oxytetracy- effective they are when placed together into the cline, framomycin, framycetin, cefquinome, cefazo- uterine lumen. In addition, penicillin G (potassium lin, or chloramphenicol. Interestingly, procaine or procaine) is inactivated by acids, so if penicillin penicillin was used even though there are no re- and an aminoglycoside are used together in an un- ported dosages listed in most antibiotic reviews. buffered form, the penicillin may be less effective Some practitioners had concern about residues that because of the low pH environment caused by the may be left within the uterus with the use of the aminoglycoside. From survey results, it appears procaine penicillin suspension. Enrofloxacin has that quite a few practitioners (34%) mix the two been given intrauterine without causing more than classes of drugs together in the same syringe (20%) a moderate inflammatory response,21 but there are or the drugs are given intrauterine at the same time other reports that the basic pH of enrofloxacin is (14%). For maximum effectiveness, mixing these very irritating to the endometrium.13,22 Differ- drugs intrauterine should be discontinued, and the ences in reports may be due to the formulation stud- drugs should be given either systemically or sepa- ied in various countries and dosage; thus, caution rated in time by an unknown number of hours if given intrauterine. It is also not recommended to should still be exerted when considering intrauter- mix the two classes of drugs in lavage solutions. ine enrofloxacin, or, alternatively, systemic enro- Interestingly, there are many semen extenders that floxacin should be used. combine potassium penicillin and amikacin. This If we examine some of the more common antibiot- practice may also result in somewhat diminished ics used in practice, one report found that 19% of antibiotic effectiveness. Conversely, of the amino- ␤-hemolytic Streptococcus (includes S. zooepi- glycosides, gentamicin has a high rate of inactiva- demicus) were susceptible to gentamicin, whereas ␤ 11 tion when mixed with certain -lactams, whereas 96% of E. coli were susceptible. One hundred per- 27 ␤ amikacin is only slightly inactivated. cent of their -hemolytic Streptococcal isolates were When asked about which antifungal intrauterine susceptible to ampicillin and penicillin G, whereas drug they used before receiving culture results, the 86% of E. coli were susceptible to ampicillin. Ceft- majority of practitioners (32%) would not use an iofur was not examined in this study. A separate antifungal drug but instead opted for a betadine study looked at intrauterine ceftiofur in mares, solution lavage, lufenuron, or, less commonly, a di- demonstrating good antimicrobial activity and no lute vinegar lavage. If an antifungal drug was increase in uterine inflammation, through biopsy, 23 used, then the most common responses included clo- over controls. Ticarcillin with clavulanic acid has trimazole (17%), nystatin (11%), miconazole (10%), been examined for intrauterine use and found that fluconazole (8%), and amphotericin B (3%). No an- the clavulanic acid portion does not maintain ade- swer was provided by 19% of the respondents. quate intrauterine concentrations and thus this Only 53% of practitioners submitted fungal cultures formulation may be questionable for intrauterine for sensitivity assay. Not having proper antibiotic 24 use. They also discovered that intrauterine ticar- sensitivity patterns to determine the most appropri- cillin declined rapidly and probably would require ate therapy may explain, in part, why fungal uterine multiple-day dosing for adequate coverage. infections are difficult to treat. The reasons stated Aminoglycosides have an acid pH that will irritate for not submitting fungal cultures for a sensitivity the endometrial lining.4 It is suggested that ami- are length of time to receive result; had success noglycosides be buffered to a more neutral pH, with with iodine lavage; all seem sensitive to amphoteri- an equal volume of 7.5% sodium bicarbonate. For- cin B; inability to obtain fungal sensitivities from ty-three percent of practitioners added sodium bi- the lab; the relative infrequency with which fungal carbonate, whereas 38% increased the volume of infections were encountered precluded sensitivity infusion as a means to moderate the acidic effects, testing; just treated Candida infection with nysta- and 10% did not add anything to the aminoglycoside. tin; or treating appears to work just fine. There are If saline is used to increase the volume of infusion to a number of laboratories that offer fungal sensitivity dilute the effect of a lower pH, it should be noted patterns, including the laboratory at Cornell Uni- that saline has a pH of ϳ5.5. A more suitable diluent versity. There was also concern from practitioners

AAEP PROCEEDINGS ր Vol. 57 ր 2011 27 REPRODUCTION I that in vitro sensitivity patterns may not correlate treatment at this time does not have a negative with in vivo effectiveness. It would appear that effect on fertility.34 Most practitioners in the sur- within the group of polyene antifungal antibiotics, vey appeared aware of this, with only 16% of them amphotericin B (96% susceptibility for all fungal placing antibiotics within 4 hours after insemina- organisms) and nystatin (100% susceptibility) are tion. Most practitioners (37%) naturally waited good choices, whereas clotrimazole (80% susceptibil- past 4 hours after breeding as their next examina- ity) or ketoconazole (81% susceptibility) are good tion, and thus treatment of the mare was not until choices when using azole antifungal antibioticsa the next day. Polyene antibiotics are generally considered fungi- cidal, whereas azole antibiotics are fungistatic, un- 5. Systemic Antibiotics less at higher doses. Some practitioners try to The decision to use systemic antibiotics either in avoid intrauterine antifungal treatments with the combination with intrauterine, after intrauterine, or concern that repeated intrauterine treatment may instead of intrauterine antibiotics may be due to make the mare more susceptible to reinfection or personal preference, desire to prolong the treatment prolonged inflammation. An alternative would be period, because the organism is not susceptible to oral antifungals, which may be expensive. nonirritating drugs, or to avoid manual reproductive Lufenuron is a chitin inhibitor that has been used tract manipulations. From the on-line survey, sys- off-label for treatment of fungal intrauterine infec- temic antibiotics are chosen when intrauterine tions at the intrauterine dose of 540 mg of lufenuron treatments go beyond 3 to 5 days, when treating suspension in 60 mL of sterile saline.28 It should mares with metritis, when treating mares with con- be noted that lufenuron affects the wall of growing taminated caudal reproductive tracts, when treating fungi and may not be appropriate for treatment of mares with anatomical defects of the caudal repro- mature infections because chitin is already formed ductive tract, or occasionally when treating mares in fungal cell walls with mature infections. A bet- with fungal infections. It was thought that sys- ter approach may be to treat with an antifungal temic antibiotics negate the need to invade the antibiotic and then, at the end of treatment, place uterus, possibly avoiding the chances of iatrogeni- lufenuron intrauterine to prevent new growth. cally placed bacteria/fungi. The downsides to using The effectiveness of lufenuron still remains in systemic antibiotics are increased costs and incon- question.29,30 venience from having to dose at the animal’s full Uterine lavage with either iodine or vinegar is a body weight, possibly treating multiple times per component of therapy for many veterinarians when day, and potential adverse effects on gastrointesti- treating fungal infections. Forty percent of veteri- nal bacterial flora. A very small number of practi- narians used a dilute iodine solution for lavage (24% tioners thought that it was not good veterinary added iodine to saline, 16% iodine added to lactated practice to place antibiotics intrauterine, since Ringers solution). The percentages of iodine in la- systemic antibiotics work well, do not cause endo- vage solutions in the survey range from 0.02% (2 mL metrial irritation, and do not lead to further of 10% iodine per liter) to 0.5% (50 mL of 10% iodine contamination. per liter). A 0.2% solution of intrauterine iodine Dosages for antibiotics commonly used systemi- has been associated with endometrial inflammation cally are presented in Table 2. Trimethoprim sul- and fibrosis.31 A 0.01% to 0.05% solution of iodine fadiazine, ceftiofur, and a combination of penicillin still maintains antimicrobial activity32 without the and gentamicin were the most common antibiotics associated inflammation and fibrosis.33 This administered from the survey. Trimethoprim sul- equates to 1 to 5 mL of 10% iodine in 1000 mL of famethoxazole (30 mg/kg, per os, q 12 hours) was sterile saline. Practitioners should be cautious of found to provide adequate antibiotic concentrations the higher-concentration intrauterine iodine solu- in fetal tissues in mares with placentitis.35 In a tions. Twenty-two percent of veterinarians used a separate study, ceftiofur dosed at 2 mg/kg q 12 hours dilute vinegar solution (15% of practitioners added intramuscularly did not obtain endometrial tissue vinegar to saline, 7% added it to lactated Ringers levels36; however, it has been suggested as a poten- solution). When using vinegar, saline would be a tial treatment for mares with placentitis.37 High- more appropriate lavage solution if the desire is to er-dosage concentrations (recommended up to 4.4 lavage with a lower pH solution. Addition of 20 mL mg/kg) and/or intravenous treatment could perhaps of white vinegar to 1000 mL of saline (2% v:v solu- result in adequate endometrial levels. In cattle, tion) will reduce the pH from ϳ5.5 to ϳ3, whereas it ceftiofur has achieved in endometrial tissue minimal has little effect on the pH of lactated Ringers inhibitory concentrations after subcutaneous ad- solution. ministration.38 A study by Murchie et al.39 found Intrauterine antibiotics and lavage should be that penicillin G potassium and gentamicin sul- avoided within 4 hours of breeding13 so that sper- phate administered intravenously achieved ade- matozoa are not negatively affected by the drugs/ quate allantoic fluid concentrations in pregnant solutions themselves or the vehicles in which they pony mares. Enrofloxacin has also been used in are delivered. Four hours after insemination, sper- mares with more resistant bacteria.21,40,41 Enro- matozoa are located in the oviduct, and intrauterine floxacin should not be used in pregnant mares

28 2011 ր Vol. 57 ր AAEP PROCEEDINGS REPRODUCTION I

Table 2. Systemic Antibiotic Dosages

Systemic Antibiotics

Antibacterial Antibiotics Drug Dosage Route, Comment Amikacin 10 mg/kg q 24 h IV or IM Ampicillin 29 mg/kg q 12 to 24 h IV or IM Ceftiofur 2 to 4 mg/kg q 12 to 24 h IV or IM Doxycyline 10 mg/kg q 12 h PO Enroﬂoxacin 5.5 mg/kg q 24 h IV 7.5 mg/kg q 24 h Per os 4.0 mg/kg q 12 h Per os Gentamicin 6.6 mg/kg q 24 h IV or IM Metronidazole 15 to 25 mg/kg PO Oxytetracycline 6.6 mg/kg q 12 h IV, dilute and give slowly Potassium penicillin 22,000 IU/kgq6h IV Procaine penicillin 22,000 IU/kg q 12 h IM, only 10 mL per injection site Trimethoprim sulfa 30 mg/kg q 12 h PO Antifungal Antibiotics Drug Dosage Route Comments Amphotericin B 0.3 to 0.9 mg/kg q 24 to 48 h IV Polyene, Dilute and give slowly Fluconazole 14 mg/kg loading, then 5 mg/kg IV or per os Azole q24h Alternatively, 2 grams q 24 h Itraconazole 5 mg/kg q 12 to 24 h IV or per os Azole, oral suspension more bioavailable than capsules Ketoconazole 20 mg/kg q 12 h in 0.2 N HCl Per nasogastric Azole, irritant if given per os due intubation to low pH; need to place into stomach

IV, intravenous; IM, intramuscular; PO, per os; IU, international units. because of effects on developing cartilage.42 Doxy- contractility. DMSO lavages may be useful to cycline has also been demonstrated to achieve augment antimicrobial tissue penetration and to adequate endometrial concentrations above the disrupt microbial biofilms.45 Acetylcysteine and minimum inhibitory concentration for S. equi sub- kerosene have also been suggested as possible mu- species zooepidemicus.43 colytic agents. Biofilms are aggregates of bacteria Antifungal antibiotics may be administered sys- and/or fungi encased in an adherent polymeric ma- temically. Amphotericin B is fairly caustic as the trix, which may inhibit antibiotic penetration.46–48 result of a low pH and must be given via nasogastric Biofilms have been known to form with Pseudomo- intubation or diluted and given slowly intravenously. nas aeruginosa, E. coli, S. aureus, K. pneumonia, Oral fluconazole has been recommended for treat- and Candida spp.49 ment of Candida spp., whereas oral itraconazole has Tris-EDTA has been demonstrated to act syner- been suggested for treatment of Aspergillus spp.a gistically with antimicrobials by increasing the membrane permeability of bacteria to these drugs.50 6. Uterine Cytology Uterine lavage with Tris-EDTA, either alone or in Uterine cytology was performed in conjunction with combination with antibiotics, should be considered 67% of uterine cultures. This is a relatively easy with resilient infections or in cases with antibiotic- procedure to perform and interpret.44 Sixty-four resistant organisms. percent of practitioners either read their own (56%) or had someone in their practice (8%) read their 8. Conclusions cytologies. By performing this examination “in- Veterinarians should base antibiotic therapy on sen- house, results may be interpreted and therapy insti- sitivity testing. Consideration should be given to tuted without the delay of sending the slides to an antibiotic therapy alternatives such as proper breed- outside laboratory. Only 9% of practitioners, how- ing management, use of uterine lavage, and oxyto- ever, used Gram stain to distinguish Gram-negative cin/prostaglandin treatment. Biofilm formation from Gram-positive bacteria to institute appropriate should be appropriately treated to enable antibiotic antimicrobial therapy. access to bacteria/fungi. With a plan, antibiotic usage can be minimized and treatment success opti- 7. Treatments to Augment Antimicrobial Therapy mized. The main issues identified from the on-line Uterine lavage is recommended to remove uterine survey of veterinarians are the mixing of intrauter- debris and bacteria/fungi and to enhance uterine ine ␤-lactam and aminoglycoside antibiotics, the use

AAEP PROCEEDINGS ր Vol. 57 ր 2011 29 REPRODUCTION I of higher concentrations of iodine solutions intra- 21. Fumuso E, Checura C, Losinno L, et al. Endometrial tissue uterine, the use of lactated Ringers solution with concentrations of enrofloxacin after intrauterine administra- vinegar for uterine lavage, and the treatment of tion to mares. Vet Res Commun 2002;26:371–380. 22. Rodriguez J, Han S, Nielsen S, et al. Effect of intrauterine mares less than 4 hours after breeding with intra- infusion of enrofloxacin on endometrial histology in mares. uterine antibiotics. Consideration should be made Clin Therio 2009;1:553. toward the idea that organisms may develop deep- 23. Bermudez L, Sifontes N, Navarro N, et al. Effects of intra- seated infections within the endometrium, possibly uterine infusion of sodium ceftiofur on the endometrium of making systemic antibiotic administration a better mares, in Proceedings Am Assoc Equine Pract 1995;41:261– 263. choice in chronically infected mares. 24. Van Camp SD, Papich MG, Whitacre MD. Administration of ticarcillin in combination with clavulanic acid intrave- References and Footnote nously and intrauterinely to clinically normal oestrous 1. Petersen MR, Nielsen JM, Lehn-Jensen H, et al. Streptococ- mares. J Vet Pharmacol Ther 2000;23:373–378. cus equi subspecies zooepidemicus resides deep in the chron- 25. Glew RH, Pavuk RA. Stability of gentamicin, tobramycin, ically infected endometrium of mares. Clin Therio 2009;1: and amikacin in combination with four beta-lactam antibiot- 393–409. ics. Antimicrob Agents Chemother 1983;24:474–477. 2. Tibary A, Fite DL. Reproductive Tract Infections. In: Sellon 26. Holt HA, Broughall JM, McCarthy M, et al. 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