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Clinical Aspects of Bacterial Distribution and Antibiotic Resistance in the Reproductive System of Equids

Veterinary Faculty, University of Thessaly, 43100 Karditsa, Greece
Author to whom correspondence should be addressed.
Antibiotics 2023, 12(4), 664;
Received: 19 February 2023 / Revised: 23 March 2023 / Accepted: 27 March 2023 / Published: 28 March 2023
(This article belongs to the Special Issue Antimicrobial Resistance and Zoonoses)


Antibiotic administration is a standard therapeutic practice for the treatment of reproductive disorders of equids. This might lead to undesirable microbial imbalance and could favour the acquisition of antibiotic resistance. Therefore, it is imperative for clinicians to understand patterns of antibiotic resistance when considering and developing treatment regimes. Continued engagement of clinicians with novel alternative approaches to treat reproductive infections would be essential in order to address this rising threat within the One Health perspective. The objectives of the present review were to present the bacterial infections in the reproductive system of equids (horses, donkeys), to upraise the literature related to the issue of antibiotic resistance of bacteria causing these infections and to discuss the topic from a clinical perspective. Initially, the review summarised the various infections of the reproductive system of equids (genital system of females, genital system of males, mammary glands) and the causal bacteria, providing relevant information about horses and donkeys. Subsequently, the clinical therapeutics of these infections were presented, taking into account the significance of antibiotic resistance of bacteria as a limiting factor in treating the infections. Finally, approaches to circumvent antibiotic resistance in clinical settings were summarized. It was concluded that awareness regarding antibiotic resistance in equine reproductive medicine would increase, as we would recognise the multifaceted problem of resistance. Actions and initiatives within the One Health approach, minimizing the potential dissemination of resistant strains to humans and to the environment, with specific applications in medicine of equids should be appropriately instituted internationally.

1. Introduction

Antibiotic resistance poses a significant threat to global health and sustainability, and it is now regarded as a critical One Health issue. Antibiotic-resistant pathogens exist across the animal, human and environment niches [1]. In veterinary medicine, the increasing incidence of antibiotic resistance has been attributed to misuse of these agents and to reduced inflow of new antibiotics [2]. From the discovery of penicillin in 1928 to the ‘golden era of antibiotic discovery’ (in the 1950s to 1970s), antibiotics had been extensively used and have clearly contributed to increasing life expectancy. It is nevertheless noteworthy that in 1942, penicillin-resistant Staphylococcus aureus isolates were recovered, despite the short and limited use of the drug by that time [3]. Since then, various factors, among them, misuse and overuse of antibiotics in humans and animals (e.g., irrational prescription, self-medication, incorrect doses) have contributed to antimicrobial resistance becoming a significant threat in global health [4].
Antibiotic resistance of pathogens is a significant and increasing problem in veterinary medicine [5,6,7]. Comprehensive efforts to control antibiotic resistance of bacterial isolates from animals have been made, given the importance of the problem for animal health itself, as well as the animal–human interactions in a One Health approach [8].
With regard to equine medicine, a large amount of information on the importance of antibiotic-resistant pathogens in horses has been published [6,9,10,11,12,13]. These publications refer to research studies, whilst there is a lack of relevant reviews that would summarise and critically assess relevant studies from a clinician’s viewpoint [14,15,16]. It is also noteworthy that despite the use and importance of donkeys around the world, data regarding their reproductive disorders remain fragmentary [17] and, hence, these animal species have also been included in the present review, which thus refers to equids in a broader context.
The objectives of the present review were to present the bacterial infections in the reproductive system of equids (horses, donkeys), to upraise the literature related to the issue of antibiotic resistance of bacteria causing these infections and to discuss the topic from a clinical perspective.

2. Methodology

This narrative review includes primarily references published in journals cited in the Web of Science database (over 87% of all references cited); papers published in these journals have been refereed. Various search terms have been employed to identify relevant publications (e.g., ‘antibiotic resistance’, ‘antimicrobial resistance’, ‘horse*’, ‘donkey*’, ‘mule*’, ‘equid*’, ‘vaginitis’, ‘metritis’, ‘endometritis’, ‘orchitis’). Subsequently, the full papers have been retrieved through the websites of the respective journals. The papers were evaluated for suitability for citation and were included and cited if within the scope of the review. The remaining literature items refer to books and book chapters, which provide an overview of existing knowledge, theses, official documents of international organisations and information websites.
The median value of the year of publication of the references cited in the review is 2016, with the oldest reference cited date from January 1971 and the most recent one from March 2023, and an interquartile range for the year of publication of the references cited in the review of 12 years.

3. Bacteria in the Reproductive System of Equids

3.1. Bacteria in the Female Reproductive Tract

3.1.1. Vagina

Knowledge of bacteria dominating vaginal microbiota is perennially important to comprehend their role in ascending equine reproductive diseases [18,19,20]. The vaginal vestibule is a major anatomical barrier that contributes to uterine defense against bacteria [21]. In the human reproductive medicine, there is evidence that the normal vaginal microbiome creates an acidic environment due to the dominance of Lactobacillus spp., which protects the reproductive tract from microbial ascension [22]. In contrast, Lactobacillus has been found to be less abundant in the vagina of mares, referring only to 0.18–0.37% of total bacterial numbers in that tissue [21,23]. In a study of healthy mares, in which the vaginal lactic acid bacteria were studied, Lactobacillus equi, L. mucosae, L. pantheris, Enterococcus faecalis and E. faecium predominated among these organisms [23]; the authors postulated that detection of these organisms suggested an intestine–vagina transference [23]. In a more recent study, the core vaginal microbiome of mares included Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria (at phylum level) and Akkermansia spp., Arcanobacterium spp., Campylobacter spp., Corynebacterium spp., Fusobacterium spp., Kiritimatiaellae spp., Porphyromonas spp. and Streptococcus spp. (at the genus level) [21]. No associations were found between the stage of the ovarian cycle and the composition of that microbiome [21]. Other researchers indicated that Escherichia coli predominated in the vagina, a finding that did not differ between mares in which insemination had been performed and unbred control animals [24].
The potential significance of Leptospira spp. should also be considered, as recent findings have indicated colonization of the vagina by L. interrogans serovars Australis and Bratislava of the organism (as shown by the detection of bacterial DNA in samples of vaginal fluid) [25,26]; the infection may lead in subclinical reduced-fertility of the affected mares [27], although results of relevant experimental studies have not provided conclusive evidence [28].
To note that variations in the vaginal microbiota may occur as the result of anatomical malformations (e.g., position and slope of external genitalia), which can lead to various disorders of the vaginal vestibule (e.g., pneumovagina, urovagina), use of irritant chemicals (e.g., antiseptics) during examination of the genital tract or artificial insemination, placement of intra-vaginal devices (for reproductive control), mating, vaginal injury or effects of antibiotics present in semen extenders. The above may lead to disturbance of the normal barrier and an imbalance of the normal vaginal microbiota [29,30].
It is noteworthy that, overall, the proportion of antibiotic-resistant bacteria recovered from the vagina of inseminated mares was higher than that among bacteria isolated from non-inseminated animals. Possibly, this might indicate a link with the exposure to antibiotics present in semen extenders [24].
With regard to female donkeys (jennies), previous studies have reported the recovery of various Gram-positive bacteria (Bacillus spp., Corynebacterium spp., Lactobacillus spp., Staphylococcus spp. and Streptococcus spp.) from vaginal samples collected from healthy animals. Among these, Streptococcus equi subsp. zooepidemicus isolates from individuals with reproductive disorders were found to carry a higher number of virulence factors genes than isolates from clinically healthy jennies [31,32,33]. Recent studies have revealed that the microbiome of the vagina of healthy jennies included mostly the phyla Proteobacteria (most abundant family: Moraxellaceae), Firmicutes (most abundant family: Lactobacillaceae), Bacteroidetes (most abundant family: Sphingobacteriaceae) and Actinobacteria (most abundant family: Corynebacteriaceae) [34].

3.1.2. Uterus

Due to the proximity of the vagina to the uterus, vaginal microbiome studies could help elucidate the relationships between bacterial populations in these two organs. Initial studies on the bacteria present in the uterus of healthy mares included E. coli, Klebsiella spp., Pseudomonas spp., S. equi subsp. zooepidemicus and other Streptococcus spp. [18], organisms that have also been implicated as causal agents of abortions in mares and deaths of newborn foals [19]. More recently, the uterine microbiome of healthy mares has been investigated [35]; the researcher reported that, at phylum level, Bacteroidetes, Firmicutes, Verrucomicrobiota and Fusobacteriota, were more abundant, whilst at genus level, Corynebacterium, Porphyromonas and Streptococcus were more abundant. She also indicated that there were distinct differences to relevant findings in other animal species [35]. Various opportunistic microorganisms, e.g., Enterobacteriaceae, were also detected [35,36].
Endometritis is an important and common equine disorder, of great concern in stud medicine, as it is a primary cause of subfertility in mares [37] and has been diagnosed (in clinical or subclinical form) in 25% to 60% of mares with fertility problems [38,39,40]. It is the result of bacterial infection, precipitated by various factors, e.g., anatomical morphology of the genital tract and the perineal region, management variables and even animal breed [39]. The most commonly isolated bacteria from uterine swabs collected from mares with endometritis include β-haemolytic streptococci, E. coli, Klebsiella spp., Pseudomonas spp. and Staphylococcus aureus [20,41,42,43,44]. Other studies have implicated Actinomyces spp., Bacillus spp., Corynebacterium spp. and Lactobacillus spp. in the aetiology of the infection [38,40,45]. A more recent study highlighted also a potential role for Chlamydia abortus in endometritis [46]. Endometritis has been associated with recovery of bacteria, which are members of the normal microbiota of the uterus, e.g., S. equi subsp. zooepidemicus, from the deeper layers of the organ in long-standing cases of the infection [43,47,48].
Contagious equine metritis caused by the Gram-negative Taylorella equigenitalis is a notifiable venereal disease, associated with subfertility and spontaneous abortions in mares [49,50]. The infection is an officially listed disease by the World Organisation for Animal Health [51]. The infection was first diagnosed during an outbreak of acute metritis that occurred during the breeding season of mares in 1977 in Newmarket, United Kingdom [49] and, since then, it has been diagnosed in over 30 countries worldwide [52,53,54,55,56,57,58]. Since 2015, cases of contagious equine metritis have been confirmed in 17 countries worldwide (Belgium, Czech Republic, Denmark, Finland, France, Germany, Hungary, Poland, Slovenia, Republic of Korea, Republic of South Africa, Spain, Sweden, Switzerland, The Netherlands, United Kingdom and United States of America) [59]. The organism can be transmitted during natural mating or artificial insemination; it has an affinity for localization in the genital system of mares, usually in the clitoral fossa and clitoral sinus and occasionally in the endometrium, where it may also persist [60]. Such atypical infections by T. equigenitalis should be included in the differential diagnosis of equine subfertility, even in cases that the investigated mares had not been exposed to stallions or artificial insemination, of origin from countries where contagious equine metritis is prevalent [61].
During oestrus, when oestrogens dominate the endocrinological pattern, mares would clear bacterial contamination of the genital system efficiently. This is important, because, otherwise, the animals would be susceptible to endometritis. In this respect, many bacteria considered to be non-pathogenic might, nevertheless, cause genital infections. In contrast, mares with anatomical defects (e.g., poor conformation of the perineum, defects in the vestibulo–vaginal seal, cervical stenosis) or animals delaying uterine clearance, compromised immunity and/or exposed to venereal pathogens may fail to clear the bacterial load, as discussed above, which would potentially result in endometritis [30,62].
In sharp contrast to relevant results in mares, investigation of uterine infections of donkeys has been limited [33,34,63]. The uterine microbiome of healthy jennies was found to be composed mainly of the phyla Proteobacteria (most abundant family: Moraxellaceae), Firmicutes (most abundant family: Lactobacillaceae) and Actinobacteria (most abundant family: Corynebacteriaceae) [34]. However, in cases of endometritis, changes were evident in the frequency of abundance at family level, with Enterobacteriaceae, Lactobacillaceae and Sphingomonadaceae being the predominant families [34]. The abundance of the Sphingomonadaceae family has been postulated to be a consequence of using contaminated semen [34].

3.2. Bacteria in the Male Reproductive Tract

The semen of healthy stallions is considered to be bacteria-free, although it may become ‘contaminated’ during its passage through the genital tract at ejaculation [64]. Indeed, in those animals, the penis and the distal part of the urethra are frequently colonised by non-pathogenic bacteria [65,66]. Less frequently, pathogenic bacteria, e.g., E. coli, Kl. pneumoniae, Ps. aeruginosa and S. equi subsp. zooepidemicus may be recovered from those sites, often after mating [67,68]; Cerny et al. [67] indicated that a possibility of bacterial transfer to the stallion’s genital tract during mating could not be excluded.
Other pathogens responsible for infections in the genital tract of stallions include Corynebacterium pseudotuberculosis causing orchitis and epididymitis [69] and Klebsiella pneumoniae causing orchitis, epididymitis and seminal vesiculitis [70].
Leptospira sp. (L. interrogans serovars Bratislava and Copenhageni) was reported in the semen of stallions, which may play a role in sexual transmission of the pathogen [26,71]. The findings suggest that male equids should be confirmed to be Leptospira-free before the mating period, based on results of appropriate tests (e.g., findings of PCR testing in semen samples) [27].
There are limited data about the bacterial populations in male donkeys (jacks). Further to bacteria with confirmed pathogenicity for these animals (S. equi subsp. zooepidemicus, Streptococcus equisimilis and S. aureus), a variety of other organisms have been isolated from clinically healthy animals. These include Gram-positive (Arcanobacterium spp., Bacillus spp., Corynebacterium spp.) and Gram-negative bacteria (Acinetobacter lwoffii, Oligella urethralis, Taylorella asinigenitalis) [72].
T. equigenitalis is an obligate parasite, colonising the surface of the terminal urethra and its fossa in stallions [73], whence it may be transmitted to susceptible mares through direct contact of the semen [74]. It is noteworthy that infected stallions do not mount a humoral immune response and do not show clinical signs of fertility issues [73,75]. T. asinigenitalis is occasionally isolated from the genital tract of male stallions [76], as well as, notably, of jacks [77,78,79,80], and may create diagnostic problems due to identification confusion with T. equigenitalis [76,81,82]. The organism has been found to be pathogenic for mares, transmitted to them from jacks, whilst jennies have been recognised only as carriers [80].

3.3. Bacteria in the Mammary Glands

Bacteria were isolated from milk samples collected from over 40% of clinically healthy mares during the post-foaling period [83]. In general, mammary infections in female equids have been studied significantly less extensively than the respective infections in ruminants [84,85]. In cases of mastitis in mares, most of the bacteria isolated were identified as Streptococcus spp. [86,87], specifically S. equi subsp. zooepidemicus [83]. Other pathogens implicated in mammary infections are Actinobacillus spp., Corynebacterium spp., E. coli, Klebsiella spp., Pseudomonas spp., Rhodococcus equi and Staphylococcus spp. [83,85,88,89].

4. Therapeutics

4.1. General Considerations

In equids, antibiotic administration is important for the treatment of genital infections. Antibiotics are commonly used for the treatment of a variety of infections, including endometritis, metritis, mastitis in female and orchitis and epididymitis in male animals.
Selection of antibiotics must be based on rational principles and decision-making based on up-to-date scientific evidence after taking into consideration the drug, the bacteria involved and the animal. Equine clinicians have to consider a variety of issues in choosing the appropriate antibiotic regime. In most cases, at initiation of treatment, the pathogens involved (confirmed or presumed, as based on clinical findings and results of ancillary tests) in the infection must be taken into account. In a case of a seriously ill or immunocompromised equid patient, a patient with long-standing infection that has already received a broad range of antibiotics or a patient with a history of unsuccessful treatments, precise details are needed to facilitate selection of the optimal antibiotic. In such patients, an array of factors must be evaluated before prescription of the antibiotic.
Among these are results of bacteriological testing, which should include firm identification of causal agents and details of antibiotic susceptibility testing. A frequent reason for possible treatment failure is drug selection pressure, especially when these are ill-chosen and/or administered in suboptimal dose rates. This can lead, additionally to treatment failure, to survival of antibiotic-resistant bacterial populations and induction of antibiotic-resistance mechanisms to other isolates [90]. The recent findings of progressive increase in the MICs (minimum inhibitory concentration) of equine isolates of S. aureus underline the importance of this factor [91]. For β-lactam antibiotics, time necessary to reach concentrations over the MIC in the tissues of hosts is generally long [92]; then, their concentration must always exceed MIC throughout the treatment period for optimal bactericidal effect. In prescribing therapeutic protocols including β-lactam antibiotics, such pharmacodynamic relationships must be taken into account. Hence, for some infections, regimes including β-lactams may require the administration of these drugs up to four times daily [93].
Additionally, clinicians in choosing antibiotic for administration should take into account the One Health perspective and the World Health Organization classification of antibiotics into categories according to level of importance for treatment of human infections: critically important, highly important and important. In that case, possible alternatives should be preferred for administration.
In any case, potential adverse effects of the antibiotic considered for administration should also be taken into account [94]. These generally include patient- or dose-related adverse effects (e.g., nephrotoxicity caused by gentamicin or colitis induced by trimethoprim/sulphadiazine), as well as immunologic effects (e.g., hypersensitivity reactions or anaphylaxis, for example penicillin-induced reactions).
Examples of commonly applied antibiotic administration regimes against reproductive infections of equids are in Table 1 and Table 2.

4.2. Antibiotic Use in Female Genital Infections

Systemic administration of antibiotics, performed in combination with uterine lavage and administration of ecbolic agents, is a commonly accepted therapeutic protocol for endometritis, as it results in higher antibiotic concentrations in uterine fluid compared to intrauterine administration of the antibiotics [107,108]. In pregnant mares, antibiotic diffusion to the uterus is important for selecting the appropriate drug for administration in cases of placentitis [109,110]. Penicillin G and gentamicin [111] and enrofloxacin and trimethoprim–sulphonamides [110,112] have been found to achieve effective antibacterial concentrations in the uterus of mares. For the treatment of uterine infections, clinical studies have indicated that fourth generation cephalosporins, e.g., cefquinome, can have a broad spectrum of antibacterial activity against several uterine pathogens of mares, e.g., E. coli, Pseudomonas spp., Staphylococcus spp., S. equi [113,114,115]. S. equi genital infections do not respond well to trimethoprim–sulphonamide administration, even though the bacteria might have been found to be susceptible to these antimicrobials [116]. Additionally, in cases in which anaerobic bacteria have been isolated from uterine lavage samples, the administration of metronidazole can be considered [117,118].
Antibiotic administration is also recommended, along with non-steroidal anti-inflammatory drugs, in cases of retention of foetal membranes, which is deemed to be an emergency in equine clinical practice [119]. Non-steroidal anti-inflammatory drugs are beneficial as part of supportive treatment of mares with retention of foetal membranes because of their anti-inflammatory, analgesic and antiendotoxic effects. Flunixin meglumine is usually administered to mares post-partum (e.g., in cases of retention of foetal membranes, at a dose rate of 0.25 mg kg−1 thrice daily, intravenously), as it can minimise the adverse haemodynamic effects of endotoxaemia [120].
If intrauterine administration of antibiotics is to be selected, only non-irritating water-soluble antibiotics (e.g., amikacin sulphate, ceftiofur sodium, gentamicin sulphate, penicillin sodium, trimethoprim/sulfamethoxazole, with variations in the available commercial products between countries as per local licencing situation) should be used for successful outcome [38]. Relevant therapeutic protocols depend on the chronicity and severity of the infection and the bacteria involved. It is noted that this route of antibiotic administration can be used only post-partum or during oestrus, i.e., when the cervix is open. In any case, uterine lavage must be performed before infusion of antibiotics.
Uterine lavage by using normal saline after mating is often employed in stud farms because of its ability to increase the tone of uterine muscular layer and its effect in clearing microorganisms, spermatozoa, inflammatory cells and debris from the uterine lumen, as these have been found to contribute to early embryonic death in mares [121]. Use of lactated Ringer’s solution has also been advocated [122], whilst the use of iodine povidone solution has not become widely applied, as it might cause local inflammation [123] and reduced expression of endometrial progesterone receptors, hindering fertility [124].
Accumulation of exudate within the uterine lumen can inactivate or dilute the infused antibiotic [117], thus removal of the exudate would increase antibiotic efficacy. Hence, the possibility of an animal to effectively expel and clear intrauterine fluid has been used to indicate mares, which may show a higher susceptibility to endometritis subsequent to mating [125,126,127]. With regard to the clinical use of specific antibiotics, amikacin is considered to be the antibiotic with the broadest spectrum of activity against uterine pathogens, as well as presenting excellent activity against Ps. aeruginosa [107]. Gentamicin is often used for intrauterine administration; the antibiotic needs to be buffered with bicarbonate before infusion [107]. In cases of administration of penicillin and ampicillin, it should be taken into account that these antibiotics are inactivated in pH ranges below 5.5 or over 8.0 [107]. The use of tetracyclines in horses should be carefully assessed against the possible risk of various important adverse reactions, among them severe colitis [128,129]. Given this, as well as the isolation of tetracycline-resistant pathogens from samples of equine origin, clinicians should carefully consider the use of this antibiotic [130,131]. The use of combinations of antibiotics (i.e., neomycin plus polymyxin B plus crystalline benzylpenicillin) affords a broad-spectrum activity against many common pathogens, as well as specific anaerobe bacteria (e.g., Bacteroides fragilis) and has also been reported for clinical application [107]. However, it is noted that in the European Union that there are no preparations licenced for intrauterine administration to equids, hence clinicians should apply the cascade rule when considering such a therapeutic approach.

4.3. Antibiotic Use in Male Genital Infections

The treatment regime of penile and preputial infections caused by opportunistic pathogens usually consists of using disinfectants, as systemic antibiotic administration is often unrewarding [132]. When artificial insemination is used, penicillin G, streptomycin, amikacin or gentamicin are routinely used in semen extenders [133]. In clinical cases of orchitis or epididymitis, treatment includes the use of systemic antibiotics, based on semen culture and in vitro susceptibility testing of isolated bacteria [134]. In the rare cases of seminal vesiculitis, treatment with systemic antibiotics is considered to be difficult due to the impaired diffusion across mucosal cell borders into the seminal plasma [107]; there is a report in the international literature describing transurethral administration of antibiotics to the seminal vesicle [70]. If local administration is not feasible, then systemic administration needs to be considered; potentially suitable antibiotics for this include macrolides (e.g., erythromycin) and enrofloxacin.

4.4. Antibiotic Use in Mammary Infections

Treatment of equine mastitis should be based on systemic administration of antibiotics [106,135]. Broad-spectrum antimicrobials, e.g., trimethoprim–sulphonamides, can be administered initially until the results of bacterial identification and susceptibility testing become available [106], which would direct appropriate antibiotics for administration. The use of intramammary tubes, which are licenced against bovine mastitis can be considered [103], but their administration may be controversial, as these preparations are not licenced for equids and lack approved withdrawal periods for these species. Anatomical differences between bovine and equine teat and mammary gland may result in incorrect administration of such products and, ultimately, in reduced efficacy [88].

5. Antibiotic Resistance as a Limiting Factor in Treatment

Antibiotic resistance of bacteria isolated from equine reproductive organs has been reported for animals with fertility problems, as shown in studies performed in various countries in Europe (France [10,130], Germany [136], Italy [42,137], Slovakia [43], Sweden [20], Turkey [138], United Kingdom [139]) and elsewhere (Brazil [140], Canada [141], India [142], United States of America [143]). Antimicrobials are commonly used to treat empirically reproductive disorders. One may suggest that continuing problems are the consequences of inappropriate treatment regimes applied in the animals. The expansion of antibiotic resistance among equids, additionally to the clinical implications for the animals, is also important within the broad concept of One Health as resistant isolates can be transmitted to other animal species and people [144,145]. A diagram of suggested actions in the face of possible antibiotic resistance is shown in Figure 1.
Emergence of methicillin-resistant staphylococci, especially in equine hospitals, is leading to increased monitoring for these bacteria because of the difficulties in their treatment and the importance for public health [6,146,147,148,149]. Methicillin resistance often occurs as the result of carriage of a SCCmec gene cassette [6,150].
Haemolytic and non-haemolytic E. coli isolates recovered from horses were found to be resistant to β-lactams, aminoglycosides, tetracyclines, fluoroquinolones and potentiated sulphonamides [43,151,152,153,154,155,156,157,158]. A common resistance-inducing mechanism in E. coli is the ability to produce extended-spectrum β-lactamases [9,159,160]. β-lactamase producing strains have also been detected in other Enterobacteriacae, e.g., Klebsiella spp., suggesting a spread among different bacterial species, which may complicate antibiotic stewardship decisions [161].
Acinetobacter spp. isolates recovered from jennies were found to possess specific resistance mechanisms, including class 1 integrons that contained multiple aminoglycoside resistance and specific carbapenemase genes [6,162]. It is noted that as carbapenems are considered critically important antibiotics for human medicine [163], their use in equids should be limited strictly to critical cases. Finally, endometritis associated with an antibiotic-resistant isolate of Ps. aeruginosa has been reported in Australia [164].
Another significant issue, of importance in equine clinical work, is the potential role of semen extenders in antibiotic resistance. A recent report indicated that isolates of Acinetobacter spp. and Klebsiella spp. recovered from mares in which artificial insemination was used showed antibiotic resistance more frequently than similar bacteria obtained from non-inseminated animals [68].

6. Approaches to Circumvent Antibiotic Resistance

Failure of equine clinicians to address antibiotic resistance will inevitably generate persistent infections and might result in suboptimal reproductive performance, leading clinicians to face increasing challenges. Any attempt to obviate the excessive and inappropriate use of antibiotics should be encouraged. Moreover, the use of therapeutic protocols that employ other approaches should also be considered (Figure 2).

6.1. Administration of Autologous Plasma

The rationale for treatment with autologous plasma (i.e., plasma with high concentration of thrombocytes with large amount of proteins, resulting in enhancement of an animal’s natural defence response) has been based on the administration of immunoglobulins and complement to support treatment of bacterial endometritis in mares [165]. In an in vitro study, the potential antimicrobial properties of platelet lysate were highlighted against various Gram-positive or -negative bacteria and were found to be concentration-dependent [166]. Under clinical conditions, improvement of fertility of mares with persistent post-breeding endometritis has been reported after administration of autologous plasma [167].

6.2. Administration of Ecbolic Agents

The traditional treatment of many common reproductive disorders in female equids includes the application of uterine lavage and the use of ecbolic agents (or uterotonics), which are pharmacological substances employed for the initiation of contractions or increased tonicity of the uterus, for the induction of parturition and/or for the reduction of post-partum haemorrhage [168], which aim to adjunct uterine clearance, especially in cases of impaired myometrial contractility. Studies have suggested that the above combination can show the same efficacy as antibiotic administrations against post-mating uterine infections in mares [113,126]. Other studies, in which concurrent uterine lavage and administration of prostaglandin F2α was compared to intrauterine administration of penicillin against S. equi subsp. zooepidemicus uterine infection, did not show differences in efficacy between the two regimes [107]. Hence, the author postulated that if treatment with prostaglandin F2α would be initiated early, antibiotic administration may not be necessary [107].
Other ecbolic agents commonly employed include oxytocin or cloprostenol. Oxytocin increases the risk for development of colic-type clinical signs in horses after administration [169,170]. Therefore, as it is often important of using it in emergency reproductive disorders (e.g., retention of foetal membranes), it should be administered at low doses, which minimise that risk [171]. A potential benefit of oxytocin administration after mating or artificial insemination refers to the increase of contractions of uterine muscles to eliminate excessive spermatozoa, as well as bacteria that might have invaded into the uterus at that time. Oxytocin is used because of its contractile action on the myometrium that would accelerate uterine involution and mucosal degeneration [121]. However, at later stages during gestation, the increased uterine contractility may cause adverse effects to the foetus borne, hence caution must be applied when administering to mares the correct oxytocin dose according to specific situations [172].
Moreover, it is noteworthy that, in another study, Li et al. [173] reported that administration of oxytocin and uterine lavage alone may not be as effective as presumed. In their work, these authors indicated that concurrent administration of immunomodulatory agents and blood cell treatments would have better results in the treatment of endometritis caused by streptococci [173].
In any case, the short half-life of oxytocin requires frequent repeated administration, whilst cloprostenol induces uterine contractions of longer duration [114]. As an alternative, the administration of carbetocin, a long-acting oxytocin analogue with a long half-life after intravenous injection, has also been reported [174,175].

6.3. Administration of Immunomodulators

The immune response of the endometrium of mares has been extensively investigated [176,177]. A positive effect of corticosteroid administration on the uterine immune response has been reported in several studies [176,177,178,179], which may ultimately improve fertility of animals. For example, administration of dexamethasone at breeding was found to improve pregnancy rates in mares with a history of post-mating endometritis [180]. Moreover, higher pregnancy rates were recorded in mares with a history of the disorder, after administration of prednisolone at breeding [177].

6.4. Use of Alternative Techniques in Semen Extenders

The addition of antibiotics in semen extenders (as a means to limit bacterial growth and multiplication therein) may trigger changes in susceptibility/resistance patterns of vaginal bacteria, subsequent to the exposure to semen extenders [181]. Hence, alternative therapeutic approaches to conventional antibiotics should be employed for the same objective. For example, the microfiltration of seminal plasma through a syringe prefilter has been found to reduce its bacterial load [182]. In addition, colloid centrifugation has been reported as a simple method to separate spermatozoa from bacteria in an ejaculate [183]. Colloid centrifugation is a semen preparation technique, whereby a sub-population of motile spermatozoa with normal morphology, intact membranes and good chromatin integrity are separated from the ejaculate, including the seminal plasma, by centrifugation through a colloid [183].

6.5. Use of Disinfectant Solutions

Treatment for infections of the genital system of male equids, caused by Ps. aeruginosa or Kl. pneumoniae, can be performed by means of daily application of disinfectant solutions, e.g., iodine-based surgical scrubs, hydrochloric acid diluted solutions or sodium hypochlorite bleach solutions, on the external genitalia of the animals [107].

6.6. Use of Equine Mesenchymal Stem Cells and Antimicrobial Peptides

Studies have discussed the immunomodulatory nature of mesenchymal stem cells and the role of antimicrobial peptides, providing a potential alternative to use of antibiotics, by expressing antibacterial proteins, e.g., lipocalin-2 [184]. Harman et al. [185] have assessed the potential antibacterial activity of these cells and reported that secreted antimicrobial peptides successfully inhibited growth of bacteria isolated from skin wounds of horses.

7. Concluding Remarks: Perspectives and Future Directions

Antibiotic resistance is an important global public health threat [186]. Improving antimicrobial stewardship can be achieved through an array of measures, as well as by means of various approaches to maintain the efficacy of antimicrobials in human, animal and agricultural settings. In this respect, initiatives are being taken by many organisations and authorities, in order to control antibiotic resistance.
Among these, regulatory and voluntary initiatives aim to decrease the dissemination of antibiotic-resistant bacteria to animals, as well as to people, given that recent studies have linked horses as a potential reservoir of a variety of pathogens, which may be transmitted to people [187]. For example, methicillin-resistant S. aureus from infections of horses have been found to disseminate often to veterinarians in Germany [147]; moreover, Albert et al. [145] have recently described the first direct transmission of a mecC-carrying methicillin-resistant S. aureus between a horse and the attending veterinarian. Examples of regulatory interventions taken to control antimicrobial resistance may include strict regulations for licencing, prescribing and marketing of antibiotics [188].
Awareness regarding antibiotic resistance in equine reproductive medicine would increase, as we would recognise the multifaceted problem of resistance. This practice may lead to undesirable microbial imbalance and can favour the acquisition of antibiotic resistance. It is imperative for equine clinicians to understand local patterns of antibiotic resistance when considering and developing treatment regimes [189]. Continued engagement of equine clinicians with the current trends on novel alternative approaches to treat genital infections is essential in order to address this rising threat for the health and welfare of animals, as well as within the One Health perspective.
With regard to work in equids, specific initiatives have been set up. Examples include the BEVA Toolkit in the United Kingdom [190] and the development of a group for equine veterinary work within the European network for the optimum use of antibiotics [191], which aim to guide veterinarians active in equine practice in the correct use of antibiotics. These initiatives show directions for future actions and can be used as examples for furthering such actions internationally within the context of One Health.
This approach, additionally to control of dissemination between animals and people, also involves the monitoring of antibiotic-resistant bacteria or resistance genes to various environmental matrices; these may refer to waste, surface waters, agricultural runoff and water for use in aquaculture, and should not be ignored, further shaping the directions for controlling the problem as much as possible. In recent relevant studies, the environment–animal sharing of resistance has been found to have hindered the impact of interventions for the reduction of antibiotic consumption in animals and to have affected the epidemiology of infections caused by resistant bacteria [192].

Author Contributions

Conceptualization, P.T. and G.C.F.; investigation, P.T.; writing—original draft preparation, P.T.; writing—review and editing, P.T. and G.C.F. All authors have read and agreed to the published version of the manuscript.


This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.


  1. Ledingham, K.; Hinchliffe, S.; Jackson, M.; Thomas, F.; Tomson, G. Antibiotic Resistance: Using a Cultural Context of Health Approach to Address A Global Health Challenge; World Health Organization: Copenhagen, Denmark, 2019. [Google Scholar]
  2. World Health Organization. Antibacterial Agents in Clinical Development: An Analysis of the Antibacterial Clinical Development Pipeline, Including Tuberculosis, 2017. Available online: (accessed on 14 March 2023).
  3. Mohr, K.I. History of antibiotics research. Curr. Top. Microbiol. Immunol. 2016, 398, 237–272. [Google Scholar] [PubMed]
  4. World Health Organization. Ten Threats to Global Health in 2019. 2019. Available online: (accessed on 15 March 2023).
  5. Lawhon, S.D.; Taylor, A.; Fajt, V.R. Frequency of resistance in obligate anaerobic bacteria isolated from dogs, cats, and horses to antimicrobial agents. J. Clin. Microbiol. 2013, 51, 3804–3810. [Google Scholar] [CrossRef] [PubMed][Green Version]
  6. Maddox, T.W.; Clegg, P.D.; Williams, N.J.; Pinchbeck, G.L. Antimicrobial resistance in bacteria from horses: Epidemiology of antimicrobial resistance. Equine Vet. J. 2015, 47, 756–765. [Google Scholar] [CrossRef] [PubMed][Green Version]
  7. Christaki, E.; Marcou, M.; Tofarides, A. Antimicrobial resistance in bacteria: Mechanisms, evolution, and persistence. J. Mol. Evol. 2020, 88, 26–40. [Google Scholar] [CrossRef]
  8. Silva, V.; Correia, S.; Rocha, J.; Manaia, C.M.; Silva, A.; García-Díez, J.; Pereira, J.E.; Semedo-Lemsaddek, T.; Igrejas, G.; Poeta, P. Antimicrobial resistance and clonal lineages of Staphylococcus aureus from cattle, their handlers, and their surroundings: A cross-sectional study from the One Health perspective. Microorganisms 2022, 10, 941. [Google Scholar] [CrossRef]
  9. Maddox, T.W.; Clegg, P.D.; Diggle, P.J.; Wedley, A.L.; Dawson, S.; Pinchbeck, G.L.; Williams, N.J. Cross-sectional study of antimicrobial-resistant bacteria in horses. Part 1: Prevalence of antimicrobial-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus. Equine Vet. J. 2012, 44, 289–296. [Google Scholar] [CrossRef]
  10. Adams, R.; Smith, J.; Locke, S.; Phillips, E.; Erol, E.; Carter, C. An epidemiologic study of antimicrobial resistance of Staphylococcus species isolated from equine samples submitted to a diagnostic laboratory. BMC Vet. Res. 2018, 14, 42. [Google Scholar] [CrossRef][Green Version]
  11. Bourély, C.; Cazeau, G.; Jarrige, N.; Haenni, M.; Gay, E.; Leblond, A. Antimicrobial resistance in bacteria isolated from diseased horses in France. Equine Vet. J. 2020, 52, 112–119. [Google Scholar] [CrossRef]
  12. Steinman, A.; Navon-Venezia, S. Antimicrobial resistance in horses. Animals 2020, 10, 1161. [Google Scholar] [CrossRef]
  13. Mitchell, S.; Bull, M.; Muscatello, G.; Chapman, B.; Coleman, N.V. The equine hindgut as a reservoir of mobile genetic elements and antimicrobial resistance genes. Crit. Rev. Microbiol. 2021, 47, 543–561. [Google Scholar] [CrossRef]
  14. Hardefeldt, L.Y.; Bailey, K.E.; Slater, J. Overview of the use of antimicrobial drugs for the treatment of bacterial infections in horses. Equine Vet. Educ. 2021, 33, 602–611. [Google Scholar] [CrossRef]
  15. Isgren, C.M. Improving clinical outcomes via responsible antimicrobial use in horses. Equine Vet. Educ. 2022, 34, 482–492. [Google Scholar] [CrossRef]
  16. Durie, I.; van Galen, G.V. Can the use of antimicrobials in adult equine patients with acute colitis be justified in the era of antimicrobial stewardship? Equine Vet. Educ. 2023, 35, 103–112. [Google Scholar] [CrossRef]
  17. Canisso, I.F.; Morel, M.D.; McDonnell, S. Strategies for the management of donkey jacks in intensive breeding systems. Equine Vet. Educ. 2009, 21, 652–659. [Google Scholar] [CrossRef][Green Version]
  18. Hinrichs, K.; Cummings, M.R.; Sertich, P.L.; Kenney, R.M. Clinical significance of aerobic bacterial flora of the uterus, vagina, vestibule, and clitoral fossa of clinically normal mares. J. Am. Vet. Med. Assoc. 1988, 193, 72–75. [Google Scholar] [PubMed]
  19. Giles, R.C.; Donahue, J.M.; Hong, C.B.; Tuttle, P.A.; Petrites-Murphy, M.B.; Poonacha, K.B.; Roberts, A.W.; Tramontin, R.R.; Smith, B.; Swerczek, T.W. Causes of abortion, stillbirth, and perinatal death in horses: 3527 cases (1986–1991). J. Am. Vet. Med. Assoc. 1993, 203, 1170–1175. [Google Scholar]
  20. Albihn, A.; Båverud, V.; Magnusson, U. Uterine microbiology and antimicrobial susceptibility in isolated bacteria from mares with fertility problems. Acta Vet. Scand. 2003, 44, 121–129. [Google Scholar] [CrossRef]
  21. Barba, M.; Martínez-Boví, R.; Quereda, J.J.; Mocé, M.L.; Plaza-Dávila, M.; Jiménez-Trigos, E.; Gómez-Martín, Á.; González-Torres, P.; Carbonetto, B.; García-Roselló, E. Vaginal microbiota is stable throughout the estrous cycle in arabian mares. Animals 2020, 10, 2020. [Google Scholar] [CrossRef]
  22. Miller, E.A.; Beasley, D.E.; Dunn, R.R.; Archie, E.A. Lactobacilli dominance and vaginal pH: Why is the human vaginal microbiome unique? Front. Microbiol. 2016, 7, 1936. [Google Scholar] [CrossRef][Green Version]
  23. Fraga, M.; Perelmuter, K.; Delucchi, L.; Cidade, E.; Zunino, P. Vaginal lactic acid bacteria in the mare: Evaluation of the probiotic potential of native Lactobacillus spp. and Enterococcus spp. strains. Anton. Leeuw. Int. 2008, 93, 71–78. [Google Scholar] [CrossRef]
  24. Malaluang, P.; Wilén, E.; Frosth, S.; Lindahl, J.; Hansson, I.; Morrell, J.M. Vaginal bacteria in mares and the occurrence of antimicrobial resistance. Microorganisms 2022, 10, 2204. [Google Scholar] [CrossRef]
  25. Hamond, C.; Pinna, A.; Martins, G.; Lilenbaum, W. The role of leptospirosis in reproductive disorders in horses. Trop. Anim. Health Prod. 2014, 46, 1–10. [Google Scholar] [CrossRef]
  26. Hamond, C.; Pestana, C.P.; Rocha-de-Souza, C.M.; Cunha, L.E.R.; Brandão, F.Z.; Medeiros, M.A.; Lilenbaum, W. Presence of leptospires on genital tract of mares with reproductive problems. Vet. Microbiol. 2015, 179, 264–269. [Google Scholar] [CrossRef] [PubMed][Green Version]
  27. Di Azevedo, M.I.N.; Lilenbaum, W. Equine genital leptospirosis: Evidence of an important silent chronic reproductive syndrome. Theriogenology 2022, 192, 81–88. [Google Scholar] [CrossRef]
  28. Zilch, T.J.; Lee, J.J.; Saleem, M.Z.; Zhang, H.; Cortese, V.; Voris, N.; McDonough, S.P.; Divers, T.J.; Chang, Y.F. Equine leptospirosis: Experimental challenge of Leptospira interrogans serovar Bratislava fails to establish infection in naive horses. Equine Vet. J. 2021, 53, 845–854. [Google Scholar] [CrossRef]
  29. Satué, K.; Gardon, J.C. Infection and infertility in mares. In Genital Infections and Infertility; Darwish, A., Ed.; IntechOpen: London, UK, 2016; Available online: (accessed on 15 March 2023).
  30. Malaluang, P.; Wilén, E.; Frosth, S.; Lindahl, J.F.; Hansson, I.; Morrell, J.M. Antimicrobial resistance in vaginal bacteria in inseminated mares. Pathogens 2023, 12, 375. [Google Scholar] [CrossRef]
  31. Maschio, C.; Bussalleu, E.; Miro, J. Preliminary study on the microbiota of the reproductive tract of Catalan jennies. Reprod. Domest. Anim. 2017, 52, 95. [Google Scholar]
  32. Canisso, I.F.; Panzani, D.; Miró, J.; Ellerbrock, R.E. Key aspects of donkey and mule reproduction. Vet. Clin. N. Am. Equine Pract. 2019, 35, 607–642. [Google Scholar] [CrossRef] [PubMed]
  33. Zhao, Y.; Zhu, Y.; Liu, B.; Mi, J.; Li, N.; Zhao, W.; Wu, R.; Holyoak, G.R.; Li, J.; Liu, D.; et al. Antimicrobial susceptibility of bacterial isolates from donkey uterine infections, 2018–2021. Vet. Sci. 2022, 9, 67. [Google Scholar] [CrossRef]
  34. Li, J.; Zhu, Y.; Mi, J.; Zhao, Y.; Holyoak, G.R.; Yi, Z.; Wu, R.; Wang, Z.; Zeng, S. Endometrial and vaginal microbiome in donkeys with and without clinical endometritis. Front. Microbiol. 2022, 13, 884574. [Google Scholar] [CrossRef]
  35. Jones, E. Characterization of the Equine Microbiome during Late Gestation and the Early Postpartum Period, and at Various Times during the Estrous Cycle in Mares Being Bred with Raw or Extended Semen. Master’s Dissertation, Kansas State University, Manhattan, KS, USA, 2019. [Google Scholar]
  36. Husso, A.; Jalanka, J.; Alipour, M.J.; Huhti, P.; Kareskoski, M.; Pessa-Morikawa, T.; Iivanainen, A.; Niku, M. The composition of the perinatal intestinal microbiota in horse. Sci. Rep. 2020, 10, 441. [Google Scholar] [CrossRef] [PubMed][Green Version]
  37. Canisso, I.F.; Stewart, J.; da Silva, M.A.C. Endometritis: Managing persistent post-breeding endometritis. Vet. Clin. N. Am. Equine Pract. 2016, 32, 465–480. [Google Scholar] [CrossRef] [PubMed]
  38. LeBlanc, M.M.; Causey, R.C. Clinical and subclinical endometritis in the mare: Both threats to fertility. Reprod. Domest. Anim. 2009, 44, 10–22. [Google Scholar] [CrossRef] [PubMed]
  39. Rasmussen, C.D.; Petersen, M.R.; Bojesen, A.M.; Pedersen, H.G.; Lehn-Jensen, H.; Christoffersen, M. Equine infectious endometritis—Clinical and subclinical cases. J. Equine Vet. Sci. 2015, 35, 95–104. [Google Scholar] [CrossRef]
  40. Díaz-Bertrana, M.L.; Deleuze, S.; Pitti Rios, L.; Yeste, M.; Morales Fariña, I.; Rivera del Alamo, M.M. Microbial prevalence and antimicrobial sensitivity in equine in field conditions. Animals 2021, 11, 1476. [Google Scholar] [CrossRef] [PubMed]
  41. Szeredi, L.; Tenk, M.; Schiller, I.; Révész, T. Study of the role of Chlamydia, Mycoplasma, Ureoplasma and other microaerophilic and aerobic bacteria in uterine infections of mares with reproductive disorders. Acta Vet. Scand. 2003, 51, 45–52. [Google Scholar]
  42. Frontoso, R.; De Carlo, E.; Pasolini, M.P.; van der Meulen, K.; Pagnini, U.; Iovane, G.; De Martino, L. Retrospective study of bacteria l isolates and their antimicrobial susceptibilities in equine uteri during fertility problems. Res. Vet. Sci. 2008, 84, 1–6. [Google Scholar] [CrossRef]
  43. Benko, T.; Boldizar, M.; Novotny, F.; Hura, V.; Valocky, I.; Dudrikova, K.; Karamanova, M.; Petrovic, V. Incidence of bacterial pathogens in equine uterine swabs, their antibiotic resistance patterns, and selected reproductive indices in English thoroughbred mares during the foal heat cycle. Vet. Med. 2015, 60, 613–620. [Google Scholar] [CrossRef][Green Version]
  44. Canisso, I.F.; Segabinazzi, L.G.; Fedorka, C.E. Persistent breeding-induced endometritis in mares—A multifaceted challenge: From clinical aspects to immunopathogenesis and pathobiology. Int. J. Mol. Sci. 2020, 21, 1432. [Google Scholar] [CrossRef][Green Version]
  45. Riddle, W.T.; LeBlanc, M.M.; Stromberg, A.J. Relationships between uterine culture, cytology and pregnancy rates in a Thoroughbred practice. Theriogenology 2007, 68, 395–402. [Google Scholar] [CrossRef]
  46. Nervo, T.; Nebbia, P.; Bertero, A.; Robino, P.; Stella, M.C.; Rota, A.; Appino, S. Chronic endometritis in subfertile mares with presence of chlamydial DNA. J. Equine Vet. Sci. 2019, 73, 91–94. [Google Scholar] [CrossRef]
  47. Pycock, J.F.; Allen, W.E. Inflammatory components in uterine fluid from mares with experimentally induced bacterial endometritis. Equine Vet. J. 1990, 22, 422–425. [Google Scholar] [CrossRef] [PubMed]
  48. Morris, L.H.A.; McCue, P.M.; Aurich, C. Equine endometritis: A review of challenges and new approaches. Reproduction 2020, 160, R95–R110. [Google Scholar] [CrossRef] [PubMed]
  49. Taylor, C.E.D.; Rosenthal, R.O.; Brown, D.F.J.; Lapage, S.P.; Hill, L.R.; Legros, R.M. The causative organism of contagious equine metritis 1977: Proposal for a new species to be known as Haemophilus equigenitalis. Equine Vet. J. 1978, 10, 136–144. [Google Scholar] [CrossRef] [PubMed]
  50. Timoney, P.J. Contagious equine metritis. Comp. Immunol. Microbiol. Infect. Dis. 1996, 19, 199–204. [Google Scholar] [CrossRef] [PubMed][Green Version]
  51. World Organization for Animal Health. Contagious Equine Metritis, 2023. Available online: (accessed on 13 March 2023).
  52. Eaglesome, M.D.; Garcia, M.M. Contagious equine metritis: A review. Can. Vet. J. 1979, 20, 201–206. [Google Scholar]
  53. Timoney, P.J.; Powell, D.G. Contagious equine metritis—Epidemiology and control. J. Equine Vet. Sci. 1988, 8, 42–46. [Google Scholar] [CrossRef]
  54. Breuil, M.F.; Duquesne, F.; Leperchois, E.; Laugier, C.; Ferry, B.; Collin, G.; Petry, S. Contagious equine metritis cases reported in France since 2006. Vet. Rec. 2015, 177, 340. [Google Scholar] [CrossRef]
  55. Luddy, S.; Kutzler, M.A. Contagious equine metritis within the United States: A review of the 2008 outbreak. J. Equine Vet. Sci. 2010, 30, 393–400. [Google Scholar] [CrossRef]
  56. Erdman, M.M.; Creekmore, L.H.; Fox, P.E.; Pelzel, A.M.; Porter-Spalding, B.A.; Aalsburg, A.M.; Cox, L.K.; Morningstar-Shaw, B.R.; Crom, R.L. Diagnostic and epidemiologic analysis of the 2008–2010 investigation of a multi-year outbreak of contagious equine metritis in the United States. Prev. Vet. Med. 2011, 101, 219–228. [Google Scholar] [CrossRef]
  57. Anzai, T.; Kamada, M.; Niwa, H.; Eguchi, M.; Nishi, H. Contagious equine metritis eradicated from Japan. J. Vet. Med. 2012, 74, 519–522. [Google Scholar] [CrossRef] [PubMed][Green Version]
  58. Petry, S.; Breuil, M.F.; Duquesne, F.; Laugier, C. Towards European harmonisation of contagious equine metritis diagnosis through interlaboratory trials. Vet. Rec. 2018, 183, 96. [Google Scholar] [CrossRef] [PubMed]
  59. World Organization for Animal Health. Events Management, 2023. Available online: (accessed on 13 March 2023).
  60. World Organisation for Animal Health (OIE). Chapter 3.5.2 Contagious Equine Metritis, 2018. Available online: (accessed on 25 January 2023).
  61. Katz, J.B.; Evans, L.E.; Hutto, D.L.; Schroeder-Tucker, L.C.; Carew, A.M.; Donahue, J.M.; Hirsh, D.C. Clinical, bacteriologic, serologic, and pathologic features of infections with atypical Taylorella equigenitalis in mares. J. Am. Vet. Med. Assoc. 2000, 216, 1945–1948. [Google Scholar] [CrossRef]
  62. Pasolini, M.P.; Prete, C.D.; Fabri, S.; Auletta, L. Endometritis and infertility in mares—The challenge in the equine breeding industry—A review. In Genital Infections and Infertility; Darwish, A., Ed.; London, UK, 2016; pp. 285–328. [Google Scholar]
  63. Gao, N.; Du, Y.; Zheng, X.; Shu, S.; Suo, J.; Han, M.; Ma, X.; Huang, R.; Peng, W.; Fu, C.; et al. Endometritis in donkeys associated with Streptococcus equi subspecies zooepidemicus infection. Pak. Vet. J. 2020, 40, 537–539. [Google Scholar] [CrossRef]
  64. Al-Kass, Z.; Eriksson, E.; Bagge, E.; Wallgren, M.; Morrell, J.M. Bacteria detected in the genital tract, semen or pre-ejaculatory fluid of Swedish stallions from 2007 to 2017. Acta Vet. Scand. 2019, 61, 25. [Google Scholar] [CrossRef] [PubMed][Green Version]
  65. Rota, A.; Calicchio, E.; Nardoni, S.; Fratini, F.; Ebani, V.V.; Sgorbini, M.; Panzani, D.; Camillo, F.; Mancianti, F. Presence and distribution of fungi and bacteria in the reproductive tract of healthy stallions. Theriogenology 2011, 76, 464–470. [Google Scholar] [CrossRef]
  66. Pasing, S.S.; Aurich, C.; von Lewinski, M.; Wulf, M.; Krüger, M.; Aurich, J.E. Development of the genital microflora in stallions used for artificial insemination throughout the breeding season. Anim. Reprod. Sci. 2013, 139, 53–61. [Google Scholar] [CrossRef]
  67. Cerny, K.L.; Little, T.V.; Scoggin, C.F.; Coleman, R.J.; Troedsson, M.H.; Squires, E.L. Presence of bacteria on the external genitalia of healthy stallions and its transmission to the mare at the time of breeding by live cover. J. Equine Vet. Sci. 2014, 34, 369–374. [Google Scholar] [CrossRef]
  68. Malaluang, P.; Wilén, E.; Lindahl, J.; Hansson, I.; Morrell, J.M. Antimicrobial resistance in equine reproduction. Animals 2021, 11, 3035. [Google Scholar] [CrossRef]
  69. González, M.; Tibary, A.; Sellon, D.C.; Daniels, J. Unilateral orchitis and epididymitis caused by Corynebacterium pseudotuberculosis in a stallion. Equine Vet. Educ. 2008, 20, 30–36. [Google Scholar] [CrossRef]
  70. Pinto, M.R.; Neild, D.M.; Benegas, D.; Vieyra, D.H.; Miragaya, M.H. Successful treatment of seminal vesiculitis with imipenem-cilastatin in a stallion. J. Equine Vet. Sci. 2014, 34, 544–548. [Google Scholar] [CrossRef]
  71. Hamond, C.; Martins, G.; Medeiros, M.A.; Lilenbaum, W. Presence of leptospiral DNA in semen suggests venereal transmission in horses. J. Equine Vet. Sci. 2013, 33, 1157–1159. [Google Scholar] [CrossRef][Green Version]
  72. Carleton, C.L.; Donahue, J.M.; Marteniuk, J.V.; Sells, S.F.; Timoney, P.J. Bacterial and fungal microflora on the external genitalia of male donkeys (Equus asinus). Anim. Reprod. Sci. 2015, 153, 62–68. [Google Scholar] [CrossRef] [PubMed]
  73. Cullinane, A.A.; Barr, B.; Bernard, W.; Duncan, J.L.; Mulcahy, G.; Smith, I.M.; Timoney, J.F. Infectious diseases. In the Equine Manual, 2nd ed.; Higgins, A.J., Snyder, J.R., Eds.; Saunders: Philadelphia, PA, USA, 2006; pp. 1–111. [Google Scholar]
  74. Delerue, M.; Breuil, M.F.; Duquesne, F.; Bayon-Auboyer, M.H.; Amenna-Bernard, N.; Petry, S. Acute endometritis due to Taylorella equigenitalis transmission by insemination of cryopreserved stallion semen. J. Equine Vet. Sci. 2019, 78, 10–13. [Google Scholar] [CrossRef] [PubMed]
  75. Mawhinney, I.; Davis, N.; Carson, T.; Torrens, N.; Wales, A. Screening for Taylorella equigenitalis in equine semen: An exploratory study. J. Equine Vet. Sci. 2022, 119, 104138. [Google Scholar] [CrossRef]
  76. Båverud, V.; Nyström, C.; Johansson, K.E. Isolation and identification of Taylorella asinigenitalis from the genital tract of a stallion, first case of a natural infection. Vet. Microbiol. 2006, 116, 294–300. [Google Scholar] [CrossRef] [PubMed]
  77. Franco, A.; Donati, V.; Troiano, P.; Lorenzetti, R.; Zini, M.; Autorino, G.L.; Petrella, A.; Maggi, A.; Battisti, A. Detection of Taylorella asinigenitalis in donkey jacks in Italy. Vet. Rec. 2009, 165, 540–541. [Google Scholar] [CrossRef] [PubMed]
  78. Meade, B.J.; Timoney, P.J.; Donahue, J.M.; Branscum, A.J.; Ford, R.; Rowe, R. Initial occurrence of Taylorella asinigenitalis and its detection in nurse mares, a stallion and donkeys in Kentucky. Prev. Vet. Med. 2010, 95, 292–296. [Google Scholar] [CrossRef]
  79. Donahue, J.M.; Timoney, P.J.; Carleton, C.L.; Marteniuk, J.V.; Sells, S.F.; Meade, B.J. Prevalence and persistence of Taylorella asinigenitalis in male donkeys. Vet. Microbiol. 2012, 160, 435–442. [Google Scholar] [CrossRef]
  80. Wilsher, S.; Omar, H.; Ismer, A.; Allen, T.; Wernery, U.; Joseph, M.; Mawhinney, I.; Florea, L.; Thurston, L.; Duquesne, F.; et al. A new strain of Taylorella asinigenitalis shows differing pathogenicity in mares and jenny donkeys. Equine Vet. J. 2021, 53, 990–995. [Google Scholar] [CrossRef]
  81. Wakeley, P.R.; Errington, J.; Hannon, S.; Roest, H.I.J.; Carson, T.; Hunt, B.; Sawyer, J.; Heath, P. Development of a real time PCR for the detection of Taylorella equigenitalis directly from genital swabs and discrimination from Taylorella asinigenitalis. Vet. Microbiol. 2006, 118, 247–254. [Google Scholar] [CrossRef] [PubMed]
  82. Dorrego, A.; Herranz, C.; Pérez-Sancho, M.; Camino, E.; Gómez-Arrones, V.; Carrasco, J.J.; De Gabriel-Pérez, J.; Serres, C.; Cruz-López, F. First report and molecular characterisation of cases of natural Taylorella asinigenitalis infection in three donkey breeds in Spain. Vet. Microbiol. 2022, 276, 109604. [Google Scholar] [CrossRef] [PubMed]
  83. Bostedt, H.; Lehmann, B.; Peip, D. The problems of mastitis in mares. Tierarztl. Prax. 1988, 16, 367–371. [Google Scholar]
  84. McGladdery, A.J. Differential diagnosis and treatment of diseases of the equine mammary gland. Equine Vet. Educ. 1998, 10, 266–268. [Google Scholar] [CrossRef]
  85. Smiet, E.; Grinwis, G.C.M.; Van Den Top, J.G.B.; Sloet van Oldruitenborgh-Oosterbaan, M.M. Equine mammary gland disease with a focus on botryomycosis: A review and case study. Equine Vet. Educ. 2012, 24, 357–366. [Google Scholar] [CrossRef]
  86. Brendemuehl, J.P. Mammary gland enlargement in the mare. Equine Vet. Educ. 2008, 20, 8–9. [Google Scholar] [CrossRef]
  87. Böhm, K.H.; Klug, E.; Jacobs, B.J. Mastitis in the mare-a long-term study on the incidence, clinical symptoms, diagnostics, microbiology, therapy and economic importance, as well as recommendations for veterinary practice. Prakt. Tierarzt. 2009, 90, 842–849. [Google Scholar]
  88. McCue, P.M.; Wilson, W.D. Equine mastitis-a review of 28 cases. Equine Vet. J. 1989, 21, 351–353. [Google Scholar] [CrossRef]
  89. Knottenbelt, D.C. The mammary gland. In Equine Stud Farm Medicine and Surgery; Knottenbelt, D.C., LeBlanc, M., Lopate, C., Pascoe, R.R., Eds.; Saunders Elsevier: Edinburgh, UK, 2003; pp. 343–352. [Google Scholar]
  90. Kowalska-Krochmal, B.; Dudek-Wicher, R. The minimum inhibitory concentration of antibiotics: Methods, interpretation, clinical relevance. Pathogens 2021, 10, 165. [Google Scholar] [CrossRef]
  91. Scholtzek, A.D.; Hanke, D.; Walther, B.; Eichhorn, I.; Stöckle, S.D.; Klein, K.-S.; Gehlen, H.; Lübke-Becker, A.; Schwarz, S.; Feßler, A.T. Molecular characterization of Equine Staphylococcus aureus isolates exhibiting reduced oxacillin susceptibility. Toxins 2019, 11, 535. [Google Scholar] [CrossRef][Green Version]
  92. Berry, A.V.; Kuti, J.L. Pharmacodynamic thresholds for beta-lactam antibiotics: A story of mouse versus man. Front. Pharmacol. 2022, 13, 833189. [Google Scholar] [CrossRef]
  93. Papich, M.G. Antibacterial drug therapy. In Textbook of Veterinary Internal Medicine, 8th ed.; Feldman, E.C., Cote, E., Ettinger, S.J., Eds.; Elsevier: St. Louis, MI, USA, 2017; pp. 683–688. [Google Scholar]
  94. Wilson, W.D.; Magdesian, K.G. Antimicrobial selection for the equine practitioner. Vet. Clin. N. Am. Equine Pract. 2021, 37, 461–494. [Google Scholar] [CrossRef] [PubMed]
  95. Katila, T. Update on endometritis therapy. Pferdeheilkunde Equine Med. 2016, 3, 39–45. [Google Scholar] [CrossRef][Green Version]
  96. Ellerbrock, R.E.; Canisso, I.F.; Roady, P.J.; Rothrock, L.T.; Zhong, L.; Wilkins, P.; Dirikolu, L.; Lima, F.S.; Honoroto, J. Diffusion of enrofloxacin to pregnancy fluids and effects on fetal cartilage after intravenous administration to late pregnant mares. Equine Vet. J. 2019, 51, 544–551. [Google Scholar] [CrossRef][Green Version]
  97. Schoster, A.; Amsler, M.; Kirchgaessner, C.; Saleh, L.; Schwarzwald, C.; Schmitt, S. Gentamicin plasma concentrations in hospitalized horses and retrospective minimal inhibitory concentrations of gram-negative equine pathogens. J. Vet. Emerg. Crit. Care 2021, 31, 323–330. [Google Scholar] [CrossRef]
  98. Beachler, T.M.; Papich, M.G.; Andrews, N.C.; Von Dollen, K.A.; Ellis, K.E.; Withowski, K.; Bailey, C.S. Clinical outcome of transcervical infusion of a combination of procaine penicillin and gentamicin in late-term pregnant mares. J. Equine Vet. Sci. 2021, 106, 103727. [Google Scholar] [CrossRef]
  99. Liepman, R.S.; Swink, J.M.; Habing, G.G.; Boyaka, P.N.; Caddey, B.; Costa, M.; Gomez, D.E.; Toribio, R.E. Effects of intravenous antimicrobial drugs on the equine fecal microbiome. Animals 2022, 12, 1013. [Google Scholar] [CrossRef]
  100. Hardefeldt, L.Y.; Crabb, H.K.; Bailey, K.E.; Gilkerson, J.R.; Billman-Jacobe, H.; Browning, G.F. Antimicrobial dosing for common equine drugs: A content review and practical advice for veterinarians in Australia. Aus. Vet. J. 2019, 97, 103–107. [Google Scholar] [CrossRef]
  101. Ferrer, M.S.; Palomares, R. Aerobic uterine isolates and antimicrobial susceptibility in mares with post-partum metritis. Equine Vet. J. 2018, 50, 202–207. [Google Scholar] [CrossRef] [PubMed]
  102. Davolli, G.M.; Beavers, K.N.; Medina, V.; Sones, J.; Pinto, C.R.; Paccamonti, D.L.; Causey, R.C. Concentrations of sulfadiazine and trimethoprim in blood and endometrium of mares after administration of an oral suspension. J. Equine Vet. Sci. 2018, 67, 27–30. [Google Scholar] [CrossRef]
  103. Perkins, N.R.; Threlfall, W.R. Mastitis in the mare. Equine Vet. Educ. 2002, 5, 99–102. [Google Scholar] [CrossRef]
  104. Mendes, L.C.N.; De Araujo, M.A.; Bovino, F.; Rozza, D.B.; Machado, G.F.; Cadioli, F.A.; Feitosa, F.F.L.; Peiró, J.R. Clinical, histological and immunophenotypic findings in a mare with a mammary lymphoma associated with anaemia and pruritus. Equine Vet. Educ. 2011, 23, 177–183. [Google Scholar] [CrossRef]
  105. Gilday, R.; Lewis, D.; Lohmann, K.L. Mastitis in a neonatal filly. Can. Vet. J. 2015, 56, 63. [Google Scholar]
  106. Canisso, I.F.; Podico, G.; Ellerbrock, R.E. Diagnosis and treatment of mastitis in mares. Equine Vet. Educ. 2021, 33, 320–326. [Google Scholar] [CrossRef]
  107. LeBlanc, M.M. The current status of antibiotic use in equine reproduction. Equine Vet. Educ. 2009, 21, 156–167. [Google Scholar] [CrossRef]
  108. Causey, R.C. Making sense of equine uterine infections: The many faces of physical clearance. Vet. J. 2006, 172, 405–421. [Google Scholar] [CrossRef]
  109. Baggot, J.D.; Giguère, S. Principles of antimicrobial drug bioavailability and disposition. In Antimicrobial Therapy in Veterinary Medicine; Giguère, S., Prescott, J.F., Dowling, P.M., Eds.; John Wiley & Sons: Hoboken, NJ, USA, 2013; pp. 41–77. [Google Scholar]
  110. Pyörälä, S.; Taponen, J.; Katila, T. Use of antimicrobials in the treatment of reproductive diseases in cattle and horses. Reprod. Domest. Anim. 2014, 49, 16–26. [Google Scholar] [CrossRef]
  111. Murchie, T.A.; Macpherson, M.L.; LeBlanc, M.M.; Luznar, S.; Vickroy, T.W. Continuous monitoring of penicillin G and gentamicin in allantoic fluid of pregnant pony mares by in vivo microdialysis. Equine Vet. J. 2006, 38, 520–525. [Google Scholar] [CrossRef]
  112. González, C.; Moreno, L.; Fumuso, E.; García, J.; Rivulgo, M.; Confalonieri, A.; Sparo, M.; Sánchez Bruni, S. Enrofloxacin-based therapeutic strategy for the prevention of endometritis in susceptible mares. J. Vet. Pharmacol. Ther. 2010, 33, 287–294. [Google Scholar] [CrossRef][Green Version]
  113. Thomas, E.; Thomas, V.; Wilhelm, C. Antibacterial activity of cefquinome against equine bacterial pathogens. Vet. Microbiol. 2006, 115, 140–147. [Google Scholar] [CrossRef]
  114. LeBlanc, M.M. Advances in the diagnosis and treatment of chronic infectious and post–mating-induced e in the mare. Reprod. Domest. Anim. 2010, 45, 21–27. [Google Scholar] [CrossRef] [PubMed]
  115. Davis, H.A.; Stanton, M.B.; Thungrat, K.; Boothe, D.M. Uterine bacterial isolates from mares and their resistance to antimicrobials: 8296 cases (2003–2008). J. Am. Vet. Med. Assoc. 2013, 242, 977–983. [Google Scholar] [CrossRef] [PubMed]
  116. Ensink, J.M.; Bosch, G.; Van Duijkeren, E. Clinical efficacy of prophylactic administration of trimethoprim/sulfadiazine in a Streptococcus equi subsp. zooepidemicus infection model in ponies. J. Vet. Pharmacol. Ther. 2005, 28, 45–49. [Google Scholar] [CrossRef]
  117. LeBlanc, M.M. Common peripartum problems in the mare. J. Equine Vet. Sci. 2008, 28, 709–715. [Google Scholar] [CrossRef]
  118. Ricketts, S.W.; Mackintosh, M.E. Role of anaerobic bacteria in equine endometritis. J. Reprod. Fertil. 1987, 35, 343–351. [Google Scholar]
  119. Burden, C.A.; Meijer, M.; Pozor, M.A.; Macpherson, M.L. Fetal membrane removal in the mare: Proactive versus reactive approaches. Vet. Clin. N. Am. Equine Pract. 2019, 35, 289–298. [Google Scholar] [CrossRef]
  120. Canisso, I.F.; Rodriguez, J.S.; Sanz, M.G.; da Silva, M.A.C. A clinical approach to the diagnosis and treatment of retained fetal membranes with an emphasis placed on the critically ill mare. Equine Vet. Sci. 2013, 33, 570–579. [Google Scholar] [CrossRef]
  121. Karam, K.M.; Alebady, A.S.; Alhilfi, H.O.; Al-Delemi, D.H. Comparative study utilizing different post-breeding treatment regimens in cyclic Arabian mares. Vet. World 2021, 14, 2863. [Google Scholar] [CrossRef]
  122. Ravaioli, V.; Raffini, E.; Tamburini, M.; Galletti, G.; Frasnelli, M. Infectious endometritis in mares: Microbiological findings in field samples. J. Equine Vet. Sci. 2022, 112, 103913. [Google Scholar] [CrossRef]
  123. Olsen, L.M.; Al-Bagdadi, F.K.; Richardson, G.F.; Archbald, L.F.; Braun, W.F.; McCoy, D.J.; Godke, R.A.; Titkemeyer, C.W.; Thompson, D.L. A histological study of the effect of saline and povidone-iodine infusions on the equine endometrium. Theriogenology 1992, 37, 1311–1325. [Google Scholar] [CrossRef]
  124. Kalpokas, I.; Perdigón, F.; Rivero, R.; Talmon, M.; Sartore, I.; Viñoles, C. Effect of a povidone-iodine intrauterine infusion on progesterone levels and endometrial steroid receptor expression in mares. Acta Vet. Scand. 2010, 52, 66. [Google Scholar] [CrossRef][Green Version]
  125. LeBlanc, M.M.; Neuwirth, L.; Asbury, A.C.; Tran, T.; Mauragis, D.; Klapstein, E. Scintigraphic measurement of uterine clearance in normal mares and mares with recurrent endometritis. Equine Vet. J. 1994, 26, 109–113. [Google Scholar] [CrossRef] [PubMed]
  126. Troedsson, M.H.; Scott, M.A.; Liu, I.K. Comparative treatment of mares susceptible to chronic uterine infection. Am. J. Vet. Res. 1995, 56, 468–472. [Google Scholar]
  127. Troedsson, M.H.; Desvousges, A.; Macpherson, M.L.; Pozor, M.P. Persistent breeding-induced endometritis. Pferdeheilkunde 2008, 24, 56–60. [Google Scholar] [CrossRef][Green Version]
  128. Andersson, G.; Ekman, L.; Månsson, I.; Persson, S.; Rubarth, S.; Tufvesson, G. Lethal complications following administration of oxytetracycline in the horse. Nord. Vet. Med. 1971, 23, 9–22. [Google Scholar]
  129. Arnold, C.; Pilla, R.; Chaffin, K.; Lidbury, J.; Steiner, J.; Suchodolski, J. Alterations in the fecal microbiome and metabolome of horses with antimicrobial-associated diarrhea compared to antibiotic-treated and non-treated healthy case controls. Animals 2021, 11, 1807. [Google Scholar] [CrossRef]
  130. Léon, A.; Castagnet, S.; Maillard, K.; Paillot, R.; Giard, J.C. Evolution of in vitro antimicrobial susceptibility of equine clinical isolates in France between 2016 and 2019. Anim. Open Access J. 2020, 10, 812. [Google Scholar] [CrossRef]
  131. Ang, L.; Vinderola, G.; Endo, A.; Kantanen, J.; Jingfeng, C.; Binetti, A.; Burns, P.; Qingmiao, S.; Suying, D.; Zujiang, Y.; et al. Gut microbiome characteristics in feral and domesticated horses from different geographic locations. Commun. Biol. 2022, 5, 172. [Google Scholar] [CrossRef] [PubMed]
  132. Samper, J.C.; Tibary, A. Disease transmission in horses. Theriogenology 2006, 66, 551–559. [Google Scholar] [CrossRef] [PubMed]
  133. Varner, D.D.; Schumacher, J.; Blanchard, T.L.; Johnson, L. Diseases and Management of Breeding Stallions; Mosby: St Louis, MI, USA, 1991. [Google Scholar]
  134. Scheeren, V.F.; Sancler-Silva, Y.F.; Ali, H.E.S.; Kastelic, J.P.; Alvarenga, M.A.; Papa, F.O. Update on seminal vesiculitis in stallions. J. Equine Vet. Sci. 2020, 94, 103234. [Google Scholar] [CrossRef]
  135. Motta, R.G.; Ribeiro, M.G.; Langoni, H.; Motta, D.G.; Franco, M.M.J.; Almeida, A.C.S.; Perrotti, I.B.M.; Listoni, F.J.P.; Menozzi, B.D. Study of routine diagnosis methods of mastitis in mares. Arq. Bras. Med. Vet. Zootec. 2011, 63, 1028–1032. [Google Scholar] [CrossRef][Green Version]
  136. Schnepf, A.; Bienert-Zeit, A.; Ertugrul, H.; Wagels, R.; Werner, N.; Hartmann, M.; Feige, K.; Kreienbrock, L. Antimicrobial usage in horses: The use of electronic data, data curation, and first results. Front. Vet. Sci. 2020, 7, 216. [Google Scholar] [CrossRef] [PubMed]
  137. Pisello, L.; Rampacci, E.; Stefanetti, V.; Beccati, F.; Hyatt, D.R.; Passamonti, F. Temporal efficacy of antimicrobials against aerobic bacteria isolated from equine endometritis: An Italian retrospective analysis (2010–2017). Vet. Rec. 2019, 185, 105413. [Google Scholar] [CrossRef][Green Version]
  138. Goncagül, G.; Seyrek-İntas, K. Antimicrobial susceptibility of bacteria isolated from uteri of Thoroughbred mares with fertility problems. Kafkas Univ. Vet. Fak. Derg. 2013, 19, A105–A109. [Google Scholar] [CrossRef]
  139. Rathbone, P.; Arango-Sabogal, J.C.; De Mestre, A.M.; Scott, C.J. Antimicrobial resistance of endometrial bacterial isolates collected from UK Thoroughbred mares between 2014 and 2020. Vet. Rec. 2023, 192, e2591. [Google Scholar] [CrossRef] [PubMed]
  140. Mota, S.L.; Dos Santos, L.O.; Vidaletti, M.R.; Rodrigues, R.O.; de Menezes Coppola, M.; Mayer, F.Q. Antimicrobial resistance of coagulase-positive Staphylococcus isolated from healthy Crioulo horses and associated risk factors. J. Equine Vet. Sci. 2021, 107, 103779. [Google Scholar] [CrossRef] [PubMed]
  141. Awosile, B.B. Antimicrobial resistance in bacteria isolated from the uteri of horses with endometritis. Vet. Rec. 2019, 185, 596. [Google Scholar] [CrossRef] [PubMed]
  142. Balamurugan, K.; Subapriya, S.; Dinesh, N.M.; Partheban, P. Antibiotic sensitivity test on pathogens causing reproductive tract infection in thoroughbred mares. J. Entomol. Zool. Stud. 2020, 8, 913–915. [Google Scholar]
  143. Trundell, D.A.; Ferris, R.A.; Hennet, M.R.; Wittenburg, L.A.; Gustafson, D.L.; Borlee, B.R.; McCue, P.M. Pharmacokinetics of intrauterine ciprofloxacin in the mare and establishment of minimum inhibitory concentrations for equine uterine bacterial isolates. J. Equine Vet. Sci. 2017, 54, 54–59. [Google Scholar] [CrossRef]
  144. European Food Safety Authority. Scientific Opinion on the assessment of animal diseases caused by bacteria resistant to antimicrobials: Horses. EFSA J. 2021, 19, 7112. [Google Scholar]
  145. Albert, E.; Sahin-Tóth, J.; Horváth, A.; Papp, M.; Biksi, I.; Dobay, O. Genomic evidence for direct transmission of mecC-MRSA between a horse and Its veterinarian. Antibiotics 2023, 12, 408. [Google Scholar] [CrossRef] [PubMed]
  146. Weese, J.S.; Archambault, M.; Willey, B.M.; Dick, H.; Hearn, P.; Kreiswirth, B.N.; Said-Salim, B.; McGeer, A.; Likhoshvay, Y.; Prescott, J.F.; et al. Methicillin-resistant Staphylococcus aureus in horses and horse personnel, 2000–2002. Emerg. Infect. Dis. 2005, 11, 430. [Google Scholar] [CrossRef] [PubMed]
  147. Cuny, C.; Abdelbary, M.M.; Köck, R.; Layer, F.; Scheidemann, W.; Werner, G.; Witte, W. Methicillin-resistant Staphylococcus aureus from infections in horses in Germany are frequent colonizers of veterinarians but rare among MRSA from infections in humans. One Health 2016, 2, 11–17. [Google Scholar] [CrossRef] [PubMed][Green Version]
  148. Mama, O.M.; Gómez, P.; Ruiz-Ripa, L.; Gómez-Sanz, E.; Zarazaga, M.; Torres, C. Antimicrobial resistance, virulence, and genetic lineages of staphylococci from horses destined for human consumption: High detection of S. aureus isolates of lineage ST1640 and those carrying the lukPQ gene. Animals 2019, 9, 900. [Google Scholar] [CrossRef] [PubMed][Green Version]
  149. Marshall, K.; Marsella, R. Evolution of the prevalence of antibiotic resistance to Staphylococcus spp. isolated from horses in Florida over a 10-year period. Vet. Sci. 2023, 10, 71. [Google Scholar] [CrossRef] [PubMed]
  150. Guérin, F.; Fines-Guyon, M.; Meignen, P.; Delente, G.; Fondrinier, C.; Bourdon, N.; Cattoir, V.; Léon, A. Nationwide molecular epidemiology of methicillin-resistant Staphylococcus aureus responsible for horse infections in France. BMC Microbiol. 2017, 17, 104. [Google Scholar] [CrossRef][Green Version]
  151. Anzai, T.; Kamada, M.; Ike, K.; Kanemaru, T.; Kumanomido, T. Drug susceptibility of Escherichia coli isolated from foals with diarrhea and mares with metritis. Bull. Equine Res. Inst. 1987, 24, 42–50. [Google Scholar]
  152. Lavoie, J.P.; Couture, L.; Higgins, R.; Laverty, S. Aerobic bacterial isolates in horses in a university hospital, 1986-1988. Can. Vet. J. 1991, 32, 292. [Google Scholar]
  153. Bucknell, D.G.; Gasser, R.B.; Irving, A.; Whithear, K. Antimicrobial resistance in Salmonella and Escherichia coli isolated from horses. Aust. Vet. J. 1997, 75, 355–356. [Google Scholar] [CrossRef]
  154. Dunowska, M.; Morley, P.S.; Traub-Dargatz, J.L.; Hyatt, D.R.; Dargatz, D.A. Impact of hospitalization and antimicrobial drug administration on antimicrobial susceptibility patterns of commensal Escherichia coli isolated from the feces of horses. J. Am. Vet. Med. Assoc. 2006, 228, 1909–1917. [Google Scholar] [CrossRef]
  155. Vo, A.T.; van Duijkeren, E.; Fluit, A.C.; Gaastra, W. Characteristics of extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates from horses. Vet. Microbiol. 2007, 124, 248–255. [Google Scholar] [CrossRef] [PubMed]
  156. Ahmed, M.O.; Clegg, P.D.; Williams, N.J.; Baptiste, K.E.; Bennett, M. Antimicrobial resistance in equine faecal Escherichia coli isolates from North West England. Ann. Clin. Microbiol. Antimicrob. 2010, 9, 12. [Google Scholar] [CrossRef] [PubMed][Green Version]
  157. Saputra, S.; Jordan, D.; Worthing, K.A.; Norris, J.M.; Wong, H.S.; Abraham, R.; Trott, D.J.; Abraham, S. Antimicrobial resistance in coagulase-positive Staphylococci isolated from companion animals in Australia: A one year study. PLoS ONE 2017, 12, e0176379. [Google Scholar] [CrossRef][Green Version]
  158. Reshadi, P.; Heydari, F.; Ghanbarpour, R.; Bagheri, M.; Jajarmi, M.; Amiri, M.; Alizade, H.; Badouei, M.A.; Sahraei, S.; Adib, N. Molecular characterization and antimicrobial resistance of potentially human-pathogenic Escherichia coli strains isolated from riding horses. BMC Vet. Res. 2021, 17, 131. [Google Scholar] [CrossRef]
  159. Shaikh, S.; Fatima, J.; Shakil, S.; Rizvi, S.M.D.; Kamal, M.A. Antibiotic resistance and extended spectrum beta-lactamases: Types, epidemiology and treatment. Saudi, J. Biol. Sci. 2015, 22, 90–101. [Google Scholar] [CrossRef] [PubMed][Green Version]
  160. Wolny-Koładka, K. Resistance to antibiotics and the occurrence of genes responsible for the development of methicillin resistance in Staphylococcus bacteria isolated from the environment of horse riding centers. J. Equine Vet. Sci. 2018, 61, 65–71. [Google Scholar] [CrossRef]
  161. Tsilipounidaki, K.; Florou, Z.; Skoulakis, A.; Fthenakis, G.C.; Miriagou, V.; Petinaki, E. Diversity of bacterial clones and plasmids of NDM-1 producing Escherichia coli clinical isolates in Central Greece. Microorganisms 2023, 11, 516. [Google Scholar] [CrossRef]
  162. Zordan, S.; Prenger-Berninghoff, E.; Weiss, R.; van der Reijden, T.; van den Broek, P.; Baljer, G.; Dijkshoorn, L. Multidrug-resistant Acinetobacter baumannii in veterinary clinics, Germany. Emerg. Infect. Dis. 2011, 17, 1751. [Google Scholar] [CrossRef]
  163. World Health Organization. Critically Important Antimicrobials for Human Medicine: Categorization for the Development of Risk Management Strategies to Contain Antimicrobial Resistance due to Non-Human Antimicrobial Use: Report of the Second WHO Expert Meeting, 2007. Available online: (accessed on 14 December 2022).
  164. Allen, J.L.; Begg, A.P.; Browning, G.F. Outbreak of equine endometritis caused by a genotypically identical strain of Pseudomonas aeruginosa. J. Vet. Diagn. Investig. 2011, 23, 1236–1239. [Google Scholar] [CrossRef][Green Version]
  165. Asbury, A.C. Uterine defense mechanisms in the mare: The use of intrauterine plasma in the management of endometritis. Theriogenology 1984, 21, 387–393. [Google Scholar] [CrossRef]
  166. Gordon, J.; Álvarez-Narváez, S.; Peroni, J.F. Antimicrobial effects of equine platelet lysate. Front. Vet. Sci. 2021, 8, 703414. [Google Scholar] [CrossRef] [PubMed]
  167. Segabinazzi, L.G.T.M.; Canisso, I.F.; Podico, G.; Cunha, L.L.; Novello, G.; Rosser, M.F.; Loux, S.C.; Lima, F.S.; Alvarenga, M.A. Intrauterine blood plasma platelet-therapy mitigates persistent breeding-induced endometritis, reduces uterine infections, and improves embryo recovery in mares. Antibiotics 2021, 10, 490. [Google Scholar] [CrossRef] [PubMed]
  168. Mousa, H.A.; Blum, J.; Abou El Senoun, G.; Shakur, H.; Alfirevic, Z. Treatment for primary postpartum haemorrhage. Cochrane Database Syst. Rev. 2014, 2014, CD003249. [Google Scholar] [CrossRef] [PubMed]
  169. Sanborn, B.M.; Qian, A.; Ku, C.Y.; Wen, Y.; Anwer, K.; Monga, M.; Singh, S.P. Mechanisms regulating oxytocin receptor coupling to phospholipase C in rat and human myometrium. In Oxytocin: Cellular and Molecular Approaches in Medicine and Research; Ivell, R., Russell, J.A., Eds.; Plenum Press: New York, NY, USA, 1995; pp. 469–479. [Google Scholar]
  170. Meyer, G.A.; Rashmir-Raven, A.; Helms, R.J.; Brashier, M. The effect of oxytocin on contractility of the equine oesophagus: A potential treatment for oesophageal obstruction. Equine Vet. J. 2000, 32, 151–155. [Google Scholar] [CrossRef]
  171. Ishii, M.; Kobayashi, S.; Acosta, T.J.; Miki, W.; Matsui, M.; Yamanoi, T.; Miyake, Y.I.; Miyamoto, A. Effective oxytocin treatment on placental expulsion after foaling in heavy draft mares. J. Vet. Med. Sci. 2009, 71, 293–297. [Google Scholar] [CrossRef][Green Version]
  172. Marcet-Rius, M.; Bienboire-Frosini, C.; Lezama-García, K.; Domínguez-Oliva, A.; Olmos-Hernández, A.; Mora-Medina, P.; Hernández-Ávalos, I.; Casas-Alvarado, A.; Gazzano, A. Clinical experiences and mechanism of action with the use of oxytocin injection at parturition in domestic animals: Effect on the myometrium and fetuses. Animals 2023, 13, 768. [Google Scholar] [CrossRef]
  173. Li, J.; Zhao, Y.; Gao, Y.; Zhu, Y.; Holyoak, G.R.; Zeng, S. Treatments for endometritis in mares caused by Streptococcus equi subspecies zooepidemicus: A structured literature review. J. Equine Vet. Sci. 2021, 102, 103430. [Google Scholar] [CrossRef]
  174. Schramme, A.R.; Pinto, C.R.F.; Davis, J.; Whisnant, C.S.; Whitacre, M.D. Pharmacokinetics of carbetocin, a long-acting oxytocin analogue, following intravenous administration in horses. Equine Vet. J. 2008, 40, 658–661. [Google Scholar] [CrossRef]
  175. Steckler, D.; Naidoo, V.; Gerber, D.; Kähn, W. Ex vivo influence of carbetocin on equine myometrial muscles and comparison with oxytocin. Theriogenology 2012, 78, 502–509. [Google Scholar] [CrossRef][Green Version]
  176. Woodward, E.M.; Christoffersen, M.; Campos, J.; Betancourt, A.; Horohov, D.; Scoggin, K.E.; Squires, E.L.; Troedsson, M.H.T. Endometrial inflammatory markers of the early immune response in mares susceptible or resistant to persistent breeding-induced endometritis. Reproduction 2013, 145, 289–296. [Google Scholar] [CrossRef][Green Version]
  177. Troedsson, M.H.; Nielsen, J.M. Non-antibiotic treatment of equine endometritis. Pferdeheilkunde 2018, 34, 17–22. [Google Scholar] [CrossRef][Green Version]
  178. Christoffersen, M.; Woodward, E.M.; Bojesen, A.M.; Petersen, M.R.; Squires, E.L.; Lehn-Jensen, H.; Troedsson, M.H.T. Effect of immunomodulatory therapy on the endometrial inflammatory response to induced infectious endometritis in susceptible mares. Theriogenology 2012, 78, 991–1004. [Google Scholar] [CrossRef]
  179. Arlas, T.R.; Wolf, C.A.; Petrucci, B.P.L.; Estanislau, J.F.; Gregory, R.M.; Jobim, M.I.M.; Mattos, R.C. Proteomics of endometrial fluid after dexamethasone treatment in mares susceptible to endometritis. Theriogenology 2015, 84, 617–623. [Google Scholar] [CrossRef] [PubMed][Green Version]
  180. Bucca, S.; Carli, A.; Buckley, T.; Dolci, G.; Fogarty, U. The use of dexamethasone administered to mares at breeding time in the modulation of persistent mating induced endometritis. Theriogenology 2008, 70, 1093–1100. [Google Scholar] [CrossRef]
  181. Morrell, J.M.; Wallgren, M. Alternatives to antibiotics in semen extenders: A review. Pathogens 2014, 3, 934–946. [Google Scholar] [CrossRef] [PubMed][Green Version]
  182. Barone, F.; Ventrella, D.; Zannoni, A.; Forni, M.; Bacci, M.L. Can microfiltered seminal plasma preserve the morphofunctional characteristics of porcine spermatozoa in the absence of antibiotics? A preliminary study. Reprod. Domest. Anim. 2016, 51, 604–610. [Google Scholar] [CrossRef] [PubMed]
  183. Morrell, J.M.; Kumaresan, A.; Johannisson, A. Practical implications of sperm selection techniques for improving reproduction. Anim. Reprod. 2017, 14, 572–580. [Google Scholar] [CrossRef]
  184. Cortés-Araya, Y.; Amilon, K.; Rink, B.E.; Black, G.; Lisowski, Z.; Donadeu, F.X.; Esteves, C.L. Comparison of antibacterial and immunological properties of mesenchymal stem/stromal cells from equine bone marrow, endometrium, and adipose tissue. Stem Cells Dev. 2018, 27, 1518–1525. [Google Scholar] [CrossRef] [PubMed]
  185. Harman, R.M.; Yang, S.; He, M.K.; Van de Walle, G.R. Antimicrobial peptides secreted by equine mesenchymal stromal cells inhibit the growth of bacteria commonly found in skin wounds. Stem Cell Res. Ther. 2017, 8, 157. [Google Scholar] [CrossRef][Green Version]
  186. Anon. Antimicrobial resistance: A top ten global public health threat. eClinicalMedicine 2021, 41, 101221. [Google Scholar] [CrossRef]
  187. Islam, M.Z.; Espinosa-Gongora, C.; Damborg, P.; Sieber, R.N.; Munk, R.; Husted, L.; Moodley, A.; Skov, R.; Larsen, J.; Guardabassi, L. Horses in Denmark are a reservoir of diverse clones of methicillin-resistant and -susceptible Staphylococcus aureus. Front. Microbiol. 2017, 8, 54. [Google Scholar] [CrossRef] [PubMed][Green Version]
  188. Velazquez-Meza, M.E.; Galarde-López, M.; Carrillo-Quiróz, B.; Alpuche-Aranda, C.M. Antimicrobial resistance: One Health approach. Vet. World 2022, 15, 743–749. [Google Scholar] [CrossRef] [PubMed]
  189. Guardabassi, L.; Jensen, L.B.; Kruse, H. Guide to Antimicrobial Use in Animals; John Wiley & Sons: Hoboken, NJ, USA, 2012. [Google Scholar]
  190. British Equine Veterinary Association. Protect Me Toolkit. 2020. Available online: (accessed on 14 March 2023).
  191. European Network for Optimisation of Veterinary Antimicrobial Treatment. COST Action CA18217-ENOVAT, 2019. Available online: (accessed on 14 March 2023).
  192. Lepper, H.C.; Woolhouse, M.E.J.; van Bunnik, B.A.D. The role of the environment in dynamics of antibiotic resistance in humans and animals: A modelling study. Antibiotics 2022, 11, 1361. [Google Scholar] [CrossRef] [PubMed]
Figure 1. Diagram of suggested actions in the face of possible antibiotic resistance in reproductive infections of equids (created with, accessed 14 March 2023).
Figure 1. Diagram of suggested actions in the face of possible antibiotic resistance in reproductive infections of equids (created with, accessed 14 March 2023).
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Figure 2. Approaches other than administration of antibiotics that can be employed to circumvent antibiotic resistance in reproductive medicine of equids (created with; accessed 14 March 2023).
Figure 2. Approaches other than administration of antibiotics that can be employed to circumvent antibiotic resistance in reproductive medicine of equids (created with; accessed 14 March 2023).
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Table 1. Examples of commonly applied antibiotic administration regimes in cases of genital infections of equids.
Table 1. Examples of commonly applied antibiotic administration regimes in cases of genital infections of equids.
(Dose Rate)
Route of AdministrationComments
Amikacin sulphate
(10 mg kg−1 per 24 h)
(intravenous (i.v.) or intramuscular (i.m.)
Good efficacy against uterine infections caused by Gram −ve bacteria. Resistance by staphylococci and streptococci. Inactivation in purulent material. Recommendation for administration in infections caused by gentamicin-resistant bacteria. Nephrotoxicity.
Amikacin sulphate
(2 g)
IntrauterineBuffering with bicarbonate or dilution with large volume of normal saline.
Ampicillin sodium
(20 mg kg−1, per 6–8 h)
Systemic (i.v. or i.m.)Improved efficacy over penicillin against Gram −ve bacteria.
(1 g)
IntrauterineEffective against Gram +ve bacteria.
(22,000 IU kg−1 per 4–6 h)
Systemic (i.v.)Antibiotic of choice against streptococcal infections. Excellent efficacy against anaerobes (except Bacteroides spp.). Possibility for combination with aminoglycosides for broad spectrum coverage.
BenzylpenicillinIntrauterineInactivation in solutions with pH < 5.5 or pH > 8.0. No mixing with gentamicin, sulphonamides or sodium bicarbonate. Use should be guided by bacteriological culture, cytology or ultrasonographic findings.
Ceftiofur sodium or ceftiofur crystalline free acid
(1.1–2.2 mg kg−1 per 12 h)
Systematic (i.v. or i.m.)Avoidance of use, in alignment with recommendations for keeping 3rd generation cephalosporins (e.g., ceftiofur) as reserve drugs [95]. Possible swelling at injection site.
(5–7.5 mg kg−1)
Systemic (i.v.) or per osBroad spectrum activity. Avoidance of use, in alignment with recommendations for keeping 3rd generation fluoroquinolones as reserve drugs. Use only based on results of bacterial culture and susceptibility testing. Generally, avoidance of use in horses < 4 years of age and during pregnancy. Synergism with β-lactams and aminoglycosides. Intrauterine administration of the licenced product for administration to cattle: not recommended (association with development of necrosis) [96].
(adult animals: 6.6 mg kg−1 per 24 h)
Systemic (i.v.)Potential development of nephrotoxicity or ototoxicity. Development of muscular discomfort after intramuscular administration [97].
(1–2 g)
IntrauterineIrritation to endometrium or induction of depigmentation of vulvar skin if administered without buffering (performed with an equal volume of 7.5% sodium bicarbonate and dilution into 200 mL normal saline). Recommendation for administration in infections by Gram −ve bacteria. Inactivation by purulent material. Synergistic action with drugs that interfere with cell wall synthesis, e.g., penicillin [98].
(6.6 mg kg−1 per 12 h)
Systemic (slow i.v.)Broad-spectrum antibacterial activity. Good spectrum of activity against anaerobic bacteria, but variable against Bacteroides spp. and Clostridium spp. Adverse effects: hypotension and collapse after rapid intravenous administration, renal tubular necrosis after administration of high doses, colitis and irritation after extravascular administration [99].
Procaine penicillin (20,000–25,000 IU kg−1)Systemic (i.m.)Efficacy against infections by β-haemolytic streptococci, anaerobic organisms (bar Bacteroides fragilis) and some Gram −ve bacteria (e.g., Actinobacillus spp. and Pasteurella spp.). Time dependent action. Long-acting formulations inappropriate for horses. Adverse effects: possibly hypersensitivity reactions (urticaria, anaphylaxis, immune mediated haemolytic anaemia) [100].
Procaine penicillin
(1.2 g)
(30 mg kg−1 per 12 h)
Systemic (slow i.v.) or per osInactivation in purulent material [101]. Concurrent administration of penicillin can act antagonistically to sulphonamides. Drugs are irritant if administered intramuscularly or by the intrauterine route [102].
Table 2. Examples of commonly applied antibiotic administration regimes in cases of mammary infections of equids.
Table 2. Examples of commonly applied antibiotic administration regimes in cases of mammary infections of equids.
(Dose Rate)
Route of AdministrationComments
AmoxicillinIntramammaryAdministration of products for intramammary administration licenced for cattle under provisions for ‘off-label’ use. Choice should depend on the results of culture and sensitivity examinations.
Administration of ‘dry cow’ products may provide long-standing antibiotic activity after the end of therapeutic administration [88,103].
Ceftiofur crystallineSystemicEmpirical treatment regime with questionable efficacy [96].
IntramammaryAdministration of products for intramammary administration licenced for cattle under provisions for ‘off-label’ use. Choice should depend on the results of culture and sensitivity examinations.
CefquinomeIntramammaryAdministration of products for intramammary administration licenced for cattle under provisions for ‘off-label’ use. Choice should depend on the results of culture and sensitivity examinations.
GentamycinIntramammaryIntramammary administration of a product available in pharmaceutical form for injectable administration [104].
(30 mg kg−1)
Per osEmpirical treatment regime, often used until results of bacteriological examinations (bacterial identification and sensitivity testing) become available [105,106].
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Tyrnenopoulou, P.; Fthenakis, G.C. Clinical Aspects of Bacterial Distribution and Antibiotic Resistance in the Reproductive System of Equids. Antibiotics 2023, 12, 664.

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Tyrnenopoulou P, Fthenakis GC. Clinical Aspects of Bacterial Distribution and Antibiotic Resistance in the Reproductive System of Equids. Antibiotics. 2023; 12(4):664.

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Tyrnenopoulou, Panagiota, and George C. Fthenakis. 2023. "Clinical Aspects of Bacterial Distribution and Antibiotic Resistance in the Reproductive System of Equids" Antibiotics 12, no. 4: 664.

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