CHAPTER 4 Bacterial Skin Diseases

Cutaneous bacteriology and normal defense mechanisms

The skin forms a protective barrier without which life would be impossible. The defense has three components: physical, chemical, and microbial (see Chapter 1).^4,⁷

Hair forms the first line of physical defense to protect against the contact of pathogens with the skin. Hair may also harbor bacteria, especially staphylococci. However, the relatively inert stratum corneum forms the basic physical defense layer. Its tightly packed keratinized cells are permeated by an emulsion of sebum, sweat, and intercellular cement substance. The emulsion is concentrated in the outer layers of keratin, where some of the volatile fatty acids vaporize, leaving an impermeable superficial sebaceous crust. Together, the cells and the emulsion function as an effective physical barrier. The emulsion provides a chemical barrier to potential pathogens in addition to its physical properties. Fatty acids, especially linoleic acid, have potent antibacterial properties. Water-soluble substances in the emulsion include inorganic salts and proteins that inhibit bacteria.

The skin is an immune organ that plays an active role in the induction and maintenance of immune responses, which can be beneficial or detrimental (see Chapter 8). Specific components include epidermal Langerhans cells, dermal dendrocytes, keratinocytes, skin-seeking T-lymphocytes, mast cells, and the endothelium of postcapillary venules. Various cytokines, complement, and immunoglobulins are found in the emulsion layer and contribute to the skin’s immunologic function. Many individual components of this complicated system have antimicrobial effects, so the normal skin should be viewed as an organ that is resistant to infection.

The normal skin microflora also contributes to skin defense mechanisms. Bacteria are located in the superficial epidermis and in the infundibulum of the hair follicles, where sweat and sebum provide nutrients. The normal flora is a mixture of bacteria that live in symbiosis, probably exchanging growth factors. The flora may change with different cutaneous environments. These are affected by factors such as heat, pH, salinity, moisture, albumin level, and fatty acid level. The close relationship between the host and the microorganisms enables bacteria to occupy microbial niches and to inhibit colonization by invading organisms. In addition, many bacteria (Bacillus spp., Streptococcus spp., and Staphylococcus spp.) are capable of producing antibiotic substances, and some bacteria can produce enzymes (e.g., β-lactamase) that inhibit antibiotics.

Bacteria cultured from normal skin are called normal inhabitants and are classified as resident or transient, depending on their ability to multiply in that habitat (see Chapter 1). Residents successfully multiply on normal skin, thus forming a permanent population that can be reduced in number by degerming methods, but not eliminated. Transients are cutaneous contaminants acquired from the environment and can be removed by simple hygienic measures.

Studies on the microbial flora of normal equine skin have been strictly qualitative (see Chapter 1). It is clear that skin and hair coats are exceedingly effective environmental samplers, providing a temporary haven and way station for all sorts of organisms. Thus, only repetitive quantitative studies will allow reliable distinction between equine cutaneous residents and transients. Coagulase-negative Staphylococcus sciuri and S. xylosus are frequently isolated from the skin and nostrils of normal horses and may be resident bacteria.^7,^42,^43,⁵⁶

There has been speculation about the means by which only a small number of a vast array of bacteria in the environment are able to colonize or infect the skin. The potent cleaning forces of dilution, washout, drying, and desquamation of surface cells prevent many organisms from colonizing the skin. It is now recognized that bacterial adhesion is a prerequisite to colonization and infection.^4,⁷ Bacterial adhesion is a complex process influenced by both the host and the organism. Bacteria possess surface adhesion molecules, which influence their ability to bind to keratinocytes. For staphylococci, teichoic acid and protein A appear to be most important surface adhesion molecules. These molecules bind to host surface receptors (e.g., fibronectin and vitronectin) to prevent the bacteria from being brushed from the skin. Adhesion is increased with increasing time, temperature, and concentration of bacteria, and in certain diseases. In hyperproliferative disorders, more bacteria adhere to the skin because more binding sites are available. Organisms from the transient group are pathogenic in rare cases. Gram-negative organisms tend to flourish in moist, warm areas and to predominate when medications depress the gram-positive flora.

Anaerobic bacteria are usually abundant in gastrointestinal secretions; therefore, fecal contamination is a cause of soft tissue infections due to these organisms. Anaerobic bacteria isolated from horse infections include Clostridium spp., Bacteroides spp., and Fusobacterium spp. These bacteria are usually found in granulomas, cellulitis, abscesses, fistulae, and other soft tissue wounds.

The numbers of resident bacteria on the skin tend to vary among individuals; some animals have many organisms, whereas others have few. The number per individual may remain constant, unless disturbed by antibacterial treatment or changes in climate. More bacteria are found on the skin in warm, wet weather than in cold, dry weather. Moist, intertriginous areas tend to have large numbers, and individuals with oily skin have higher counts.

Skin infections

The normal skin of healthy individuals is highly resistant to invasion by the wide variety of bacteria to which it is constantly exposed. Pathogenic organisms such as coagulase-positive staphylococci may produce characteristic lesions of folliculitis, furunculosis, and cellulitis in the absence of any obvious impairment of host defenses. However, localized disruption of normal host defenses as produced by maceration (water, friction from skin folds, topical treatments, increased humidity and/or friction associated with tack/blankets/riders), physical trauma (abrasions, cuts, punctures, biting insects and arthropods, scratching, and rubbing), or the introduction of a foreign body (plant awns) may facilitate development of overt infection. Treatment with immunosuppressive agents and immunosuppressive diseases can predispose patients to infections. Widespread bacterial skin infections in a herd of horses were associated with malnutrition and unhygienic environmental conditions.⁴⁰

The host-bacteria relationship in infections of the skin involves three major elements: (1) the pathogenic properties of the organism (particularly the invasive potential and the toxigenic properties), (2) the portal of entry, and (3) the host defense and inflammatory responses to bacterial invasion. Bacterial infection involving the skin may manifest itself in either of two major forms: (1) as a primary cutaneous process, or (2) as a secondary manifestation of infection elsewhere in the body. The cutaneous changes associated with systemic infection are not necessarily suppurative but may represent those of vasculitis or a hypersensitivity response.

Microorganisms isolated from an intact lesion such as a pustule are evidence of infection, not colonization. Colonization means that a potential pathogen lives on the skin or in a lesion but that its presence causes no reaction in the host. The problem in evaluating a pyoderma culture is to separate secondary colonization from secondary infection. The presence of many degenerate neutrophils and phagocytosed bacteria is direct evidence of a host reaction and is compatible with infection. Infection can be determined by direct smears of lesion exudates, which may be more informative than cultures.

Staphylococcal organisms, common isolates from skin infections in horses, are not particularly virulent; thus, any skin infection should be considered a sign of some underlying cutaneous, metabolic, or immunologic abnormality. Traditionally, skin infections are classified as either primary or secondary to reflect the absence or the presence of an underlying cause.

Secondary infections are by far the most common and result from some cutaneous, immunologic, or metabolic abnormality. Secondary infections may involve organisms other than staphylococci, tend to respond slowly or poorly to treatment if the underlying problem is ignored, and recur unless the cause is resolved. Virtually any skin condition described in this text can predispose to infection, but allergic, ectoparasitic, seborrheic, or follicular disorders are the most common causes of infection.

Allergic horses are prone to infections because of the damage they do to their skin while itching, the corticosteroids that they often receive, and possibly some immunologic abnormalities associated with their allergic predisposition. When their skin becomes infected, the level of pruritus increases quickly and does not respond well to corticosteroid administration. Antibiotic treatment resolves the lesions of infection and reduces, but does not eliminate, the pruritus.

Seborrheic animals have greatly increased numbers of bacteria on their skin surface, which can colonize an epidermal or follicular defect and cause infection. They also contribute to the alteration of the surface lipid layer to one that can induce inflammation. In this situation, the patches of seborrheic dermatitis cause the animal to itch and induce true infection in these areas. Superficial infections result in significant scaling during their development and resolution. It can sometimes be difficult to decide whether the seborrhea induced the infection or vice versa. Scaling caused by infection decreases quickly with antibiotic therapy. If seborrheic signs are still pronounced after 14-21 days of antibiotic treatment, the animal should be evaluated for an underlying seborrheic disorder.

Follicular inflammation, obstruction, degeneration, or a combination of these predisposes the follicle to bacterial infection. Inflammatory causes are numerous, but dermatophytosis is most commonly implicated. Follicular obstruction occurs as part of generalized seborrhea, in focal seborrheic disorders, follicular dysplasias, and other congenital disorders of the follicle. Follicular degeneration can be caused by all of these conditions, and also by alopecia areata. In cases of follicular infection, examination of skin scrapings, cytology, and evaluations for dermatophytes (e.g., trichogram and fungal culture) are always recommended. After those tests, the skin biopsy is most useful because pathologic changes are too deep to be appreciated with the naked eye. The inflammation associated with the secondary bacterial infection can mask some of the histologic features of the predisposing disease; thus, it is best to resolve the infection first and then perform the skin biopsy.

The most common metabolic cause of skin infection is pituitary pars intermedia dysfunction (hyperadrenocorticism) or inappropriate use of glucocorticoids, but diabetes mellitus, and other systemic metabolic problems must also be considered. These disorders predispose to infection by their impact on the animal’s immune system and the changes they induce in the hair follicle.

Acquired immunodeficiencies are common complications of many serious illnesses. The best-known examples of acquired immunodeficiency disease are associated with viral and protozoal infections.

The classification of primary infection is more problematic. Primary infections are described as those that occur in otherwise healthy skin, are staphylococcal with rare exception, and are cured by appropriate antibiotic therapy. In fact, there is probably no such thing as a “primary” bacterial skin infection. All bacterial skin infections are presumably triggered by something. Perhaps calling such infections “idiopathic” for now is more appropriate. This definition overlooks the tendency for the infection to recur. For instance, a horse is examined for a skin infection, and no historical or physical abnormality to explain the infection is found. Is this a primary infection, an infection secondary to some transient insult to the skin, or an infection secondary to some as yet undefined underlying problem? The key to the primacy of the infection is its tendency to recur. Infections that resolve with no residual skin disease and do not recur with regularity or within a reasonable period (e.g., 3-6 months) could be considered primary infections. If the infection recurs early, the animal has some subclinical skin disease or an immunologic abnormality.

Identification of bacteria from skin lesions may provide important information as to the cause of cutaneous infections, whether primary or secondary to systemic processes. The presence of normal skin flora may confuse interpretation of these studies. All too often, the finding on culture of a potential pathogen, such as a coagulase-positive Staphylococcus sp., is equated with the presence of infection. It is essential to remember that damaged skin provides a medium for proliferation of many bacteria. Only by correlating the clinical appearance of the lesion with cytologic and bacteriologic data can one reach the proper decision concerning the presence of bacterial disease.

Samples of pus or exudates from intact pustules, nodules, abscesses, draining tracts, or ulcers can be smeared on glass slides, air-dried, and stained with new methylene blue, Gram stain, or Diff Quik for light microscopic examination. Important observations to be made include: (1) type(s) of bacteria present (cocci vs. rods; gram-positive or gram-negative), and (2) the associated inflammatory response. Skin contaminants are usually recognized by being extracellular and being often clumped in microcolonies. Pathogenic bacteria are found intracellularly within neutrophils and macrophages. Thus, direct smears often provide the first clue to the specific cause of the infection and also serve as a guide in selecting appropriate culture media and antibiotic therapy.

Because the skin of horses is a veritable cesspool of bacteria, cultures must be carefully taken and interpreted (see Chapter 1). Intact pustules, nodules, and abscesses are preferred lesions for culture and may be aspirated with a needle and syringe or punctured and swabbed with a culturette, after the overlying epithelium has been gently swabbed with alcohol and allowed to air-dry. Cultures of open sores (erosions, ulcers, and sinuses) and exudative surfaces often generate confusing, if not misleading, bacteriologic data.

When intact, pus-containing lesions are not available for sampling, the culturing of surgical biopsy specimens is preferred. Papules, plaques, nodules, and areas of diffuse swelling may be surgically prepared (e.g., povidone-iodine or chlorhexidine scrub) and punch or excision biopsies taken with aseptic techniques. The epidermis must be removed with a sterile scalpel blade, as topical antiseptics may be retained in this layer and affect culture results. These biopsy specimens can then be delivered to the laboratory in various transport media for culture and antibiotic susceptibility testing.

Treatment of skin infections

Satisfactory resolution of a skin infection necessitates that the cause of the infection be identified and corrected and that the infection receive proper treatment.^4-^8,¹⁷ If the cause of the infection persists, either the response to treatment is poor or the infection recurs shortly after treatment is discontinued. If the cause is resolved but inappropriate treatment for the infection is given, the infection persists and worsens.

Skin infections can be treated topically, systemically, surgically, or by some combination of these. Some equine infections are too widespread or too deep to be resolved with topical treatment alone, but judicious topical therapy can make the patient more comfortable and hasten its response to antibiotics. Topical treatment can take considerable time and effort on the owner’s part and can irritate the skin if the products are too harsh. Surgery alone can be useful with focal lesions or can be performed as an adjunct to other treatments.¹ Management must be individualized.

Topical Treatment

Topical treatments are used to reduce or eliminate the bacterial population in and around an area of infection and to remove tissue debris (see Chapter 3).^2,^6,^7,¹⁰ Debris removal is of paramount importance because it allows direct contact of the active ingredient with the organism and promotes drainage. Agents commonly used include chlorhexidine, povidone-iodine, benzoyl peroxide, and various antibiotics, especially fusidic acid, mupirocin, and bacitracin.

Infections restricted to the skin surface or intact hair follicles may be effectively treated with topical agents alone. When the number of lesions is small and they are confined to a limited area, antiseptics or antibiotics in a cream, ointment, or gel formulation may be sufficient to resolve the infection (see Chapter 3). Benzoyl peroxide gels or antibiotic formulations receive widest use. The benzoyl peroxide gels marketed to veterinarians contain 5% active ingredient, which can be irritating, especially with repeated application. In most instances, antibiotic preparations are nonirritating. In most cases, transdermal absorption of the agent is limited, but frequent application over wide areas should be avoided.

Many potent antibacterial agents are available in topical form (see Chapter 3). The most commonly used are mupirocin, fusidic acid, and silver sulfadiazine (Silvadene).* Neomycin, gentamicin, bacitracin, and polymyxin B can also be effective.⁷ Important considerations for some of these agents are as follows: (1) mupirocin and fusidic acid are more effective than other topical agents for treatment staphylococcal pyodermas; (2) mupirocin has poor activity against gram-negative infections; (3) neomycin has more potential for allergic sensitization than do most topicals, and susceptibility is variable for gram-negative organisms; and (4) polymyxin B and bacitracin in combination may be effective for gram-negative and gram-positive organisms; however, they are rapidly inactivated by purulent exudates and do not penetrate well. Mupirocin 2% ointment is particularly useful because of its ability to penetrate the skin and its very low incidence of adverse reactions.^6,⁷ It is inactivated by exudates and debris, so the surface of lesions must be cleaned prior to application. Silver sulfadiazine 0.1% cream is broad-spectrum, penetrating, and usually well-tolerated.

Often, topical antibiotics are formulated with other ingredients, most commonly glucocorticoids. There are numerous antibiotic-steroid combinations (Gentocin spray, Animax, Panalog). These are occasionally indicated in chronic, dry, lichenified, secondarily infected dermatoses (seborrhea complex and allergic dermatoses) and pyotraumatic dermatitis. Several clinical and bacteriologic trials in humans showed that these antibiotic-steroid combinations were superior to either agent alone.

A 0.4% stannous fluoride (MedEquine) (broad-spectrum antibacterial agent) gel was applied every 24 h for 4 weeks to bacterial folliculitis lesions in horses.²⁰ The study was placebo-controlled and double-blinded. The stannous fluoride was significantly more effective than placebo, and no adverse effects were reported.

Widespread superficial infections are best treated with antibacterial shampoos (see Chapter 3).* The manipulation of the skin during its application and the vehicle of the shampoo removes tissue debris, which allows better contact between the antiseptic and the bacteria. Product selection depends on the preferences of the owner and the clinician and the condition of the animal’s skin. Animals with underlying hypersensitivity disorders or “sensitive” skin should be bathed with nonirritating or minimally irritating agents such as chlorhexidine (see Chapter 3). Benzoyl peroxide products should be reserved for greasy horses or horses with deep crusted infections (see Chapter 3). In this latter group, shampoo selection should be reevaluated in 10-14 days because the skin will be much different then.

Iodophors are popular topical antimicrobial agents in equine practice.^2,^4,^7,¹⁰ Povidone-iodine is available as a 5% solution (Betadine, Purdue Frederick; Poviderm, Vetus; Povidone-Iodine, Equicare), a 5% shampoo (Poviderm, Vetus; Povidone, Butler), and a 10% ointment (Povidone Iodine, First Priority). Polyhydroxydine complex iodine is available as a 1% solution and a 1% spray (Xenodine, V.P.L.). Although these products are excellent antimicrobial agents, their propensity for causing dry, scaly skin and hair coat and irritation, and possible staining of skin and hair coat makes them less desirable than chlorhexidine or benzoyl peroxide.

A thorough bath with a 10-15-min shampoo contact time is indicated at the beginning of treatment. The timing to the next bath depends on the severity of the infection, the cause of the infection, and the speed of the animal’s response to the antibiotics used. Some clinicians request that the client bathe the animal at a set interval, typically every third to seventh day, whereas other clinicians give the client guidelines for when a bath is indicated and let the client decide when to bathe. If the client is not overzealous, the latter method is most appropriate because it treats the animal based on its needs.

In the case of deep draining infections, the hair in the area must be clipped to prevent the formation of a sealing crust and to allow the topical agents to contact the diseased tissues. Although shampooing is beneficial, soaks are more appropriate at the onset of treatment. Hydrotherapy loosens and removes crusts, decreases the number of surface bacteria, promotes epithelialization, and helps to lessen the discomfort associated with the lesions. With warm-water soaks, the vascular plexus opens, which may allow better distribution of the systemic antibiotic. Antiseptics such as chlorhexidine and povidone-iodine are added for additional antibacterial activity.

If there are draining lesions on a distal limb, the area can be soaked in a bucket. For lesions higher up on the limb, a disposable newborn baby diaper is a useful aid. The outer plastic layer protects the environment while the high absorbency pad holds the soaking solution next to the skin. For these lesions, a hypertonic drawing solution of magnesium sulfate (Epsom salts) (2 tbsp/qt or 30 mL/L of warm water) can be beneficial. Soaks are typically done for 15-20 min, once or twice daily. Because hydrotherapy hydrates the epithelium, excessively soaked skin macerates easily and may become infected more easily. As the antibiotic therapy progresses, drainage should decrease. When drainage is slight after a soak, the frequency of soaking should be decreased or stopped entirely. Typically, soaking is continued for 3-7 days.

Systemic Antibiotics

Systemic antibiotic agents are used for bacterial skin diseases that are not treatable with topical therapy.^2,^4-^10,^17,²¹ Appropriate systemic antibiotic use in the equine presents many challenges. Specific considerations include: poor oral absorption of many drugs; large total dosage and, therefore, high cost; risk of side effects, the most common of which is enterocolitis; extralabel use of drugs due to lack of licensed equine products; and differences in drug disposition in foals versus adults. In addition, there is the concern over development of antimicrobial resistance, which has important implications for both veterinary and human medicine.

Knowledge and understanding of basic pharmacokinetics and pharmacodynamics are essential. In addition, controversies exist regarding the current use of antibiotics, including appropriate selection and use in certain clinical situations. The reader is encouraged to consult available detailed information on these subjects.^4-^6,^8,^17,¹⁸

Proper antibiotic use necessitates that the antibiotic inhibit the specific bacteria, preferably in a bactericidal manner. Bacteriostatic drugs may also be effective as long as the host is not immunocompromised. The antibiotic should be inexpensive, should be easily given (orally [PO], if it is to be prescribed for home use) and absorbed, and should have no adverse effects.

The most important factors influencing the effectiveness of antibiotics are the susceptibility of the bacteria and the distribution to the skin in effective levels of activity at the infection site. Only about 4% of the cardiac output of blood reaches the skin. Although the epidermis is relatively avascular, studies of skin infections showed that the systemic route of therapy is better than the topical route for all but the most superficial infections. The stratum corneum is a major permeability barrier to effective topical drug penetration. These facts led to the inescapable conclusion that the skin is one of the most difficult tissues in which to obtain high antibiotic levels. Factors that may reduce the effectiveness of a therapeutic plan are the following:

1. The organism is resistant to the antibiotic, and because most coagulase-positive staphylococci organisms produce β-lactamase, antibiotics resistant to this substance should be selected.

2. The dosage is inadequate to attain and then maintain inhibitory concentrations in the skin.

3. The organism may be surviving inside macrophages, where it is not exposed to the effect of many antibiotics.

4. The organism is within a necrotic center or protected by a foreign body such as a hair fragment.

5. The organism is walled off by dense scar tissue.

6. The duration of therapy is inadequate to eradicate the infection.

In addition to the susceptibility of the organism, various owner and animal factors enter into the equation during antibiotic selection. Antibiotics are either time-dependent or concentration-dependent in their action. Time-dependent drugs must be given at their specified interval of administration for maximal efficacy. The total dose administered is more important for the concentration-dependent drugs. The route of administration (PO vs. intramuscular [IM]) and frequency of administration (every 8 h vs. every 24 h) are also often important for owner and patient compliance.

The depth of the infection also influences drug selection. Deep infections require protracted courses of treatment, can respond less favorably to certain drugs than more superficial infections, and tend to become fibrotic. Twelve-week courses of antibiotics are not unusual in treating some infections.

Antibiotic selection is not so straightforward when the empirically selected antibiotic is not effective or when the infection recurs shortly after treatment is discontinued. If the empirically selected antibiotic has only good susceptibility, most clinicians empirically select another drug with excellent susceptibility. If this new drug fails to be effective, one must carefully evaluate whether the owner is complying with the treatment regimen and whether the skin is truly infected. If no reason for this poor response can be found, susceptibility testing is mandatory.

If cytologic study shows a mixed infection, susceptibility testing is mandatory because the susceptibility of nonstaphylococcal organisms is not always predictable. If all organisms are susceptible to a safe, reasonably inexpensive drug, that drug should be used. Occasionally, no one drug fits the susceptibility profile of all organisms or the singular drug is too toxic or expensive for long-term use. If the infection contains coagulase-positive staphylococci, as many do, the initial antibiotic selection should be aimed at that organism. Eradication of the staphylococcal component may make the microenvironment unfavorable for the growth of the other organisms. If the antistaphylococcal antibiotic improves but does not resolve the infection, alternative drugs must be used. After an antibiotic has been selected, it should be dispensed at the correct dosage, administered at the appropriate dosage interval, and be used for a sufficient period.

Penicillins

Penicillins are a good choice when bacteria are susceptible (Table 4-1).^2,^4-^10,¹⁷ They are bactericidal, narrow-spectrum, time-dependent, and have a low incidence of severe side effects. They are a common cause of drug-induced urticaria (see Chapter 8), occasional colitis, and rare anaphylaxis and hemolytic anemia. Most streptococci, Corynebacterium pseudotuberculosis, Pasteurella spp., many anaerobes, many actinomycetes (Dermatophilus, Actinomyces), and Actinobacillus spp. are susceptible. Penicillins penetrate poorly into abscesses and necrotic tissue. Most coagulase-positive staphylococci are resistant. Potassium penicillin G seems to be interchangeable with procaine penicillin G. Procaine is eliminated slowly and commonly causes violative residues in race horses and performance horses.⁴

TABLE 4-1 Systemic Antibiotics

Trimethoprim-Potentiated Sulfonamides

Trimethoprim-potentiated sulfonamides are effective and popular antibiotics in equine dermatology (see Table 4-1).^2,^4-^10,¹⁷ They are broad-spectrum, bactericidal, concentration-dependent, and generally well-tolerated, but they are a common cause of drug-induced urticaria, erythema multiforme, exfoliative dermatitis, and allergylike pruritus (see Chapters 8 and 9). They are inactivated in abscesses and necrotic tissues. Anemia and/or leukopenia may occasionally be seen in horses treated with long-term trimethoprim-potentiated sulfonamides. Monthly hemograms are recommended during prolonged therapy. Trimethoprim-sulfadiazine (30 mg/kg every 24 h) given PO to healthy horses produced no significant effects on serum concentrations of total and free thyroxine (T4), total and free triiodothyronine (T3), and thyrotropin (TSH).²⁴ Most coagulase-positive staphylococci, streptococci, Dermatophilus congolensis, and many Actinobacillus spp., Rhodococcus equi, and C. pseudotuberculosis are susceptible.

Macrolides

Macrolides are narrow-spectrum, bacteriostatic, concentration-dependent, and have a long postantibiotic effect (see Table 4-1).* They concentrate in phagocytic cells and can be particularly effective for intracellular bacteria and in pyogranulomatous lesions. Most coagulase-positive staphylococci, streptococci, Pasteurella spp., Clostridium spp., Actinobacillus spp., and R. equi are susceptible. Macrolides are not used in adults due to the occurrence of severe and sometimes fatal colitis. In foals, macrolides may produce distress syndromes. Hence, caution is in order when treating foals in hot weather.

Macrolides (erythromycin estolate, clarithromycin) and the macrolide derivative azalides (azithromycin), combined with rifampin, are the treatment of choice for foals with R. equi infections. Clarithromycin is now available as a generic, is cost-effective, is better tolerated than erythromycin, and when combined with rifampin is clinically superior to either erythromycin- or azithromycin-rifampin combinations.²⁸

Fluoroquinolones

Fluoroquinolones are bactericidal, broad-spectrum, concentration-dependent antibiotics with a long postantibiotic effect.^2,^4-^10,¹⁷ They are concentrated intracellularly in phagocytes. Although the pharmacokinetics and pharmacodynamics of a number of fluoroquinolones have been reported in horses (e.g., marbofloxacin, orbifloxacin),^4,^13,^15,²³ only enrofloxacin is widely used in equine dermatology (see Table 4-1).^2,^4-^10,^17,²⁶ Ciprofloxacin is contraindicated in horses due to poor PO absorption and possible severe colitis.

Enrofloxacin and its metabolite, ciprofloxacin, can be detected in equine mane and tail hairs at least 9 months after a 2-week course of treatment.³⁷ Interestingly, concentrations are much higher in black versus white hairs, and enrofloxacin is extensively bound to melanin in vitro.³⁷ Serum concentrations of enrofloxacin may be higher when certain feeds that contain high concentrations of divalent cations (e.g., alfalfa) are withheld pre- and 1-2 h postantibiotic administration.* Coagulase-positive staphylococci, many streptococci, C. pseudotuberculosis, and Actinobacillus spp. are susceptible. Most anaerobes are resistant.^4,^8,¹⁶ Enrofloxacin/β-lactam combinations are synergistic. Enrofloxacin is generally well-tolerated, but is contraindicated in horses less than 2-years old due to chondrotoxicity. Enrofloxacin is administered PO as the bovine injectable (horses object to the taste; rinse mouth with water after dosing) or the canine tablets (crush and mix with feed). When the bovine injectable was compounded in a gel, oral ulcers were seen in about 10% of the horses treated.^11,^16,¹⁷

Rifampin

Rifampin is a bactericidal, narrow-spectrum antibiotic that enters phagocytic cells and is effective for intracellular bacteria and in pyogranulomatous, abscessed, fibrosed lesions.^2,^4-^10,^17,²⁷ Coagulase-positive staphylococci, streptococci, R. equi, C. pseudotuberculosis, and most anaerobes are susceptible. Because resistance to rifampin monotherapy can occur frequently and rapidly, it is usually given in conjunction with other antimicrobial agents (e.g., macrolides, β-lactams, trimethoprim-potentiated sulfonamides). Urine, tears, saliva, sweat, and clothing may be stained red/orange.

Gentamicin

Gentamicin is occasionally used in equine dermatology (see Table 4-1).^2,^4-^10,^17,²⁷ It is bactericidal, broad-spectrum, concentration-dependent, and has an intermediate postantibiotic effect. Gentamicin has poor activity in abscesses and necrotic tissue. Coagulase-positive staphylococci, Pseudomonas spp., Actinobacillus spp., and R. equi are usually susceptible. Anaerobes are not susceptible. The risk for nephrotoxicity increases with prolonged therapy (>7-10 days) and with preexisting renal disease. This risk can be decreased by feeding a high protein, high calcium diet (such as alfalfa).⁴

Cephalosporins

Cephalosporins are excellent broad-spectrum, bactericidal, time-dependent antibiotics with an intermediate postantibiotic effect that are very useful against coagulase-positive staphylococci, streptococci, Pasteurella spp., Salmonella spp., and anaerobes (not Bacteroides spp. and Enterococcus spp.) (see Table 4-1).* They are generally well-tolerated. β-lactams are synergistic with aminoglycosides and fluoroquinolones. Ceftiofur is effective IM, intravenously (IV), and subcutaneously (SQ) (and registered for the horse), and cephalexin is effective PO.

Chloramphenicol

Chloramphenicol is a bacteriostatic, broad-spectrum, concentration-dependent antibiotic with a long postantibiotic effect (see Table 4-1).^2,^4-^6,¹⁷ It has good activity against staphylococci. It is generally well-tolerated. Chloramphenicol is not to be used in food animals, due to a severe, idiosyncratic bone marrow dyscrasia that occurs in humans.

Tetracyclines

Tetracyclines are bacteriostatic, broad-spectrum, concentration-dependent antibiotics with a long postantibiotic effect (see Table 4-1).^2,^4-^6,¹⁷ They have variable activity against staphylococci and streptococci. The use of oxytetracycline is controversial, but it is used successfully and increasingly in equine practice (IM use only).^2,^4,¹⁷ Doxycycline is well-absorbed PO, concentrated intracellularly in phagocytic cells, and generally well-tolerated. It is generic and inexpensive. Feed may reduce PO bioavailability.⁶

The most commonly recognized cause of the inability to resolve a skin infection, or of its relapse days after the treatment is discontinued, is an insufficient course of treatment. Although textbooks and clinical experience can suggest appropriate courses of treatment, each animal responds at its own rate and must be treated until its infection is resolved. Resolution means that all lesions have healed both on the surface and in the deeper tissues. Surface healing is easy to determine by visual inspection, but deep healing is much more difficult to assess and necessitates palpation of the lesions and regional lymph nodes.

Intercurrent corticosteroid administration confounds the problem greatly. Corticosteroids decrease visual and palpable inflammation, which is the key sign in determining when an infection is resolved. An inflamed hair follicle is still infected, whereas one that looks and feels normal is probably healed. With concurrent corticosteroid use, it is impossible to determine whether the antibiotic resolved the inflammation, and therefore the infection, or whether the corticosteroid is masking the infection. If an individual animal requires both antibiotics and corticosteroids, the corticosteroid administration should be discontinued at least 7 days before the final evaluation of the infection.

In infections of the intact hair follicle, deep tissues rarely become inflamed enough to be detected by palpation, so infection could still be present when the surface has healed. To prevent relapses because of this inapparent infection, it is recommended that antibiotic treatment be continued for 7-10 days after surface healing. In deeper infections, surface healing is misleading and antibiotic treatment must be continued after the dermal inflammation is gone. Deep lesions always heal on the surface well before the deep infection is resolved. Because some small, nonpalpable nidi of infection can persist even when the tissues feel normal by palpation, antibiotic treatment should be continued for 14-21 days after the tissues return to apparent normalcy. The time to resolution dictates the length of postnormalcy treatment.

Ideally, the clinician should reexamine all animals to determine when true healing has occurred. This is impractical in many instances and is not absolutely necessary in the case of more superficial infections. As long as the owner is an astute observer and treats the animal after clinical normalcy is present, most infections can be resolved without reexamination. Reexamination is mandatory for animals with deep infections. Owners cannot tell when the deep infection is resolved and almost always underestimate the need for antibiotics. Some clinicians schedule examinations every 14 days, whereas other clinicians examine the animal only when the owner reports that the lesions have healed. The approach is individualized for best results.

Deep infections are problematic for both the client and the clinician. With follicular rupture and damage to the dermal tissues, the inflammation tends to be pyogranulomatous and endogenous foreign bodies (keratin, hair shafts, and damaged collagen) are usually found in the dermis. During the first 2-4 weeks of antibiotic treatment, the lesion improves dramatically and then apparently stops responding. If treatment is stopped at this point, any ground gained is lost because it is unlikely that the deep infection is resolved. The rapid initial improvement is due to the resolution of the pyogenic component of the infection, but the granulomatous component remains and responds much more slowly. As long as there is slow, steady improvement, the antibiotic administration should be continued, even if the course of treatment approaches 12 weeks or longer. With long-term treatment, most lesions resolve completely, but the healing of some lesions reaches a certain point and improves no further. In these cases, the tissues never return to palpable normalcy because of resultant fibrosis, the presence of sterile endogenous foreign bodies in the dermis, or walled-off nidi of infection.

Skin biopsies can be both helpful and misleading. If infection is apparent, the need for additional treatment is documented. If no infection is visible, the question remains as to whether some infection is present in areas that do not undergo biopsy. If the lesion does not improve at all with 2-3 weeks of additional antibiotic treatment, one must assume that the infection is resolved and stop treatment. If infection is present, the lesion begins to worsen again in 2-21 days.

Relapses usually occur because the current infection was not treated appropriately or because the underlying cause of the infection was not identified or resolved. The timing to relapse is important. If new lesions appear within 7 days of the termination of treatment, it is likely that the infection was not resolved. More intense treatment is necessary. If the relapse occurs weeks to months after the last treatment, the animal has some underlying problem that must be resolved.

No discussion of antibiotics would be complete without mentioning some of the antiinflammatory and immunomodulatory properties inherent to some of these agents: macrolides (inhibit leukocyte chemotaxis, interleukin (IL)-1, and lymphocyte blastogenesis), trimethoprim (inhibits leukocyte chemotaxis), and fluoroquinolones (inhibit IL-1, leukotriene, and tumor necrosis factor (TNF)-α synthesis; inhibit granulomatous inflammation).⁷ These effects can be beneficial but may also be misleading.

Immunomodulatory Agents (Biologic Response Modifiers)

Recurrent bacterial skin infections in an otherwise healthy horse are rare. Recurrent bacterial dermatoses are usually associated with recurrent or persistent predisposing conditions such as hypersensitivities (atopic, insect, food, contact), ectoparasitisms, environmental triggers (weather, filth, trauma, etc.), and systemic or metabolic disorders.

Horses with recurrent, unexplained skin infections, wherein clinical and laboratory findings are normal when the infections are eliminated with antibiotic therapy, pose a difficult therapeutic problem. Weekly or biweekly antibacterial shampoos and/or rinses may help reduce the frequency of relapses.⁷ If topical treatments are ineffective, and recurrences are not too frequent (e.g., twice or thrice a year), appropriate systemic antibiotic therapy may be satisfactory. More frequent episodes of infection, or inability to use antibiotics, may cause the veterinarian to consider immunomodulatory therapy.

There is growing interest in developing preparations that augment immune defenses to prevent and treat infectious diseases. Immunostimulant preparations produce nonantigen-specific enhancement of cellular and humoral defense mechanisms, presumably through amplification of phagocytosis and intracellular killing by neutrophils and macrophages, antigen presentation, cytotoxic activity of T-lymphocytes and killer cells, cytokine release, and antibody production.^4-^6,^19,²⁵ The effectiveness of such products depends on the horse’s own ability to respond with the production of IL-1, IL-6, IL-15, IL-18, TNF-α, and interferon (IFN). Common systemic reactions to such products include mild fever and depression. In equine medicine, immunostimulant preparations are used predominantly for treatment of chronic respiratory disease and sarcoids (Box 4-1). These preparations are also being used in horses with various dermatoses, infectious and noninfectious, on a completely empirical and anecdotal basis. The authors have used none of these products for treating bacterial dermatoses in horses.

Box 4-1 Immunomodulatory Agents

Bacterial, Viral, and Plant Products

Propionibacterium acnes, inactivated (EqStim): registered for use in equine respiratory disease complex; 1 mL/114 kg every 48-72 h, IV, for 2-3 doses.

Mycobacterial cell wall extracts (Equimune): registered for use in equine respiratory disease complex; 1.5 mL/horse every 1-3 weeks IV.

Parapoxvirus ovis, inactivated (Zylexis): registered for use in upper respiratory EH1 and EH4 infections; 2 mL/horse on day 1, 3, and 10, IM.

Mannan polymer extract of aloe vera (Acemannan Immunostimulant): not registered in horses; serious side effects seen with IV and even intralesional injections.

Echinacea (numerous over-the-counter products for horses): administer PO per manufacturer recommendation.

Chemically Defined Agents

Levamisole (Levasole): not registered in horses; 2 mg/kg every 48 h PO.

IFN-α (Roferon-A; Intron-A): not registered in horses; 50-150 International Units (or 0.1 International Units/kg) every 24 h PO for 5 days.

Autogenous bacterins have been reported to be helpful in recurrent bacterial dermatoses in horses.^2,⁷ All such reports are anecdotal.

Staphylococcal infections

Staphylococcus species are versatile pathogens of animals and humans. The organisms are gram-positive cocci, have a worldwide distribution, are prevalent in nature, and may gain entry to the animal host through any natural orifice and contaminated wounds. Coagulase-positive staphylococci are common equine pathogens.

Prior to 1980, all coagulase-positive staphylococci isolated from horses were identified as Staphylococcus aureus. Currently, three coagulase-positive staphylococci are known to be associated with equine skin infections: S. aureus, S. hyicus subsp. hyicus, and S. delphini.* Prior to 2005, S. intermedius was frequently isolated from equine infections.⁷ Advances in molecular biology have demonstrated that the S. intermedius complex actually includes three organisms: S. intermedius (wild pigeons), S. pseudintermedius (dogs, cats, humans), and S. delphini (horses and domestic pigeons).^36,^47,⁴⁸ It is highly likely that all equine isolates of “S. intermedius” reported prior to 2007 were actually S. delphini.

It is not presently clear whether or not the different staphylococci vary in frequency of isolation from equine pyogenic dermatoses, or are always associated with particular clinical syndromes and epidemiologic scenarios. For instance, some reports state that S. aureus is the major Staphylococcus isolated from equine dermatoses, and that “S. intermedius” (S. delphini) is rarely isolated, while other reports indicate that S. aureus and “S. intermedius” (S. delphini) or S. aureus and S. hyicus are isolated with about equal frequency.⁷

The coagulase-positive staphylococci produce various combinations of enterotoxins (A, B, C, D), protein A, hemolysins, leukocidins, and dermonecrotoxins that may be involved in the pathogenesis of infections.^4,^7,⁸ Protein A and enterotoxin C, in particular, are capable of acting as superantigens (see Chapter 8) and triggering local cutaneous and immunologic responses.³⁶ S. aureus strains isolated from three horses with cellulitis in Japan did not produce enterotoxins A, B, and C.⁷ A S. aureus strain isolated from a horse with cellulitis in Japan produced an exfoliative toxin (“exfoliatin”), which produced generalized exfoliation when injected into 3-day-old mice and 1-day-old chicks.⁷ The toxin was, thus, similar to that associated with so-called staphylococcal scalded skin syndrome in humans. However, the horse from which the exfoliation-producing S. aureus was isolated had no clinical exfoliation. The following is a discussion of some of the clinical syndromes associated with staphylococcal infection in equine dermatology.

Folliculitis and Furunculosis

Staphylococcal folliculitis and furunculosis are usually secondary to cutaneous trauma and various physiologic stresses. Lesions often occur in areas of contact with tack, blankets, abrasive surfaces, or the rider. Folliculitis is an inflammation, with or without infection, of hair follicles. When the inflammatory process breaks through the hair follicles and extends into the surrounding dermis and subcutis, the process is called furunculosis. When multiple areas of furunculosis coalesce, the resultant focal area of induration and fistulous tracts is called a carbuncle (boil).

The primary skin lesion of folliculitis is a follicular papule. Pustules may arise from these papules. However, pustules are rarely seen in bacterial folliculitis. Frequently, one first notices erect hairs over a 2- to 3-mm papule that is more easily felt than seen (Figs. 4-1 and 4-2). Clusters of hairs stick up against the lie of the coat and may be glued together by small crusts. These lesions can regress spontaneously but often progressively enlarge. Some lesions enlarge to 6-10 mm in diameter, develop a central ulcer that discharges a purulent or serosanguineous material, and then become encrusted. The chronic or healing phase is characterized by progressive flattening of the lesion and a static or gradually expanding circular area of alopecia and scaling (Fig. 4-3). Hairs at the periphery of these lesions are often easily epilated. Epidermal collarettes are uncommonly seen (Fig. 4-4). It is extremely important to remember that in the chronic or healing stage, all folliculitides, regardless of cause, are often characterized by circular areas of alopecia and scaling (so-called classic ringworm lesion).

Figure 4-1 Staphylococcal folliculitis on neck. Initial lesions consist of tufted papules.

Figure 4-2 Staphylococcal folliculitis on thorax. Early lesions included tufted to scaly papules (area has been clipped).

Figure 4-3 Staphylococcal folliculitis over thorax. Two annular lesions with varying degrees of alopecia, scaling, erosion, and crusting.

Figure 4-4 Staphylococcal folliculitis on brisket. Two annular lesions with epidermal collarettes.

Some lesions progress to furunculosis. This stage is distinguished by varying combinations of nodules, draining tracts, ulcers, and crusts (Figs. 4-5–4-7). Large lesions are often associated with severe inflammatory edema and may assume an edematous plaque or urticarial appearance. Cellulitis may occur. Lymphatic engorgement may lead to the development of “runners” on the body wall radiating away from lesions. Scarring, leukoderma, and leukotrichia may follow.

Figure 4-5 Staphylococcal folliculitis and furunculosis on flank. Tufted and crusted papules (folliculitis) and a large painful nodule (furunculosis).

Figure 4-6 Staphylococcal furunculosis on shoulder. Multiple draining tracts.

Figure 4-7 Staphylococcal furunculosis involving periocular area. Coalescent papules, nodules, crusts, and draining tracts.

Staphylococcal folliculitis and furunculosis (acne, heat rash, summer rash, summer scab, sweating eczema of the saddle region, sweat spots, saddle scab, saddle boils) are common.* Bacterial folliculitis (cocci phagocytosed by neutrophils seen on cytology, cultures usually not done) accounts for 11.8% of the equine dermatology cases seen at the CUHA. No age, breed, or sex predilections are evident. Most cases begin in spring and early summer. This period coincides with shedding, clipping, heavy riding and work schedules, higher environmental temperature and humidity, and increased insect population densities. Poorly groomed horses may be at risk. Lesions can, of course, occur at any time of year, and on any part of the body, reflecting the many predisposing causes (hypersensitivities, ectoparasites, trauma, filth, etc.).

Skin lesions initially affect the saddle and tack areas in about 90% of cases (Figs. 4-8–4-10). Hence, the sides of the neck, saddle region, rump, and shoulders are commonly affected. The superficial lesions of folliculitis are usually asymptomatic, while the deep lesions of furunculosis are often painful. Neither condition is commonly pruritic. If triggering factors are not recognized and eliminated, recurrences are common.

Figure 4-8 Staphylococcal folliculitis in saddle area. Multiple tufted-to-crusted papules.

Figure 4-9 Staphylococcal folliculitis in saddle area. Annular areas of alopecia, scaling, and crusting.

Figure 4-10 Same horse as in Fig. 4-9. Areas have been clipped to expose annular areas of alopecia and thick white scale-crust.

Although all coagulase-positive staphylococci have been isolated from folliculitis-furunculosis lesions, there is conflicting information as to which species is most common. Some clinicians indicate that S. aureus is most common, while others find S. hyicus subsp. hyicus most common.⁷

Pastern Folliculitis and Furunculosis

Bacterial infections may uncommonly be restricted to the caudal aspect of the pastern and fetlock regions, with involvement of one or more limbs (Fig. 4-11).^2,^7,^9,¹⁰ This disorder must be considered in the differential diagnosis of “grease heel” or “scratches” (see Pastern Dermatitis, Chapter 15). Bacterial infections may, of course, be superimposed on other dermatoses of the pastern (vasculitis, dermatophytosis, dermatophilosis, chorioptic mange, contact dermatitis, etc.). Although all coagulase-positive staphylococci have been isolated from pastern folliculitis—sometimes more than one species simultaneously—there is conflicting information concerning the most commonly isolated species. A Japanese study found that S. aureus was most commonly isolated, while a Belgian study found S. hyicus subsp. hyicus most commonly.⁷ Infections were produced in normal horses by scarifying skin and applying S. hyicus inocula from clinical cases.

Figure 4-11 Staphylococcal pastern folliculitis and furunculosis. Coalescent areas of alopecia, exudation, and crusting.

(Courtesy W. McMullen.)

Tail Pyoderma

So-called tail pyoderma—actually folliculitis and furunculosis of the tail (Figs. 4-12 and 4-13)—usually follows the cutaneous trauma produced by tail rubbing provoked by insect-bite hypersensitivity, atopic dermatitis, food allergy, chorioptic mange, psoroptic mange, pediculosis, oxyuriasis, and behavioral abnormalities (vice).⁷

Figure 4-12 Staphylococcal tail pyoderma. Large alopecic, ulcerated pyogranuloma.

Figure 4-13 Staphylococcal tail pyoderma. Alopecia, pyogranulomatous dermatitis, and crusting.

(Courtesy W. McMullen.)

Cellulitis

Cellulitis (phlegmon) is a severe, deep diffuse suppurative infection wherein the process spreads through the dermis and subcutis along the tissue planes. The infection may extend to the skin surface, producing draining tracts. There may be extensive edema and swelling. The overlying skin may be friable, darkly discolored, and devitalized. Affected tissues may slough, leaving large ulcers. Many cases of leg cellulitis do not have a history of recent trauma (penetrating wound, surgical incision, injections), and are termed “primary” (idiopathic).^9,^29,³⁸ Coagulase-positive staphylococci are isolated in greater than 80% of the cases.^7,^29,³⁸ Streptococcus spp., E. coli, Enterobacter spp., and others are isolated much less commonly.

There are no apparent age or sex predilections, but Thoroughbreds and race horses account for the majority of reported cases.^7,^9,^29,³⁸ Animals typically develop acute swelling and lameness of one leg, and hind legs are affected more commonly. Most horses are febrile, and leukocytosis, neutrophilia, and hyperfibrinogenemia are common. Many horses develop laminitis in the contralateral leg.

Diagnosis is based on history, physical examination, and culture. Ultrasonographic imaging supports the clinical diagnosis and may provide useful information on the presence of fluid pockets than could be aspirated or surgically drained.^29,³⁸ Treatment needs to be instituted early and aggressively. Initial antimicrobial treatment often includes an IV β-lactam and aminoglycoside.^29,³⁸

Up to 25% of the horses with leg cellulitis are euthanized (necrosis and sloughing of tissue; severe laminitis).^7,^29,³⁸ Where follow-up information was available, 69% and 77% of discharged horses were being used for their intended or original use or were sound, respectively.²⁹ Recurrence of cellulitis occurred in 23% of discharged horses.

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