re-enter a log phase of active growth, making posi- tive culture more likely. However, when time is of the essence, proceed with the culture immediately, and notify the laboratory staff of the horse’s antibi- otic regimen and timing of the most recent dose in relation to sample collection. The goal is not simply to identify the pathogens


IN-DEPTH: TRAUMA/WOUND MANAGEMENT Options for Multidrug-Resistant Bacteria


that may be insensitive to the current antibiotic regimen, but to form as complete a picture as possi- ble of the microbial ecology of the wound to formu- late an antibiotic treatment plan that addresses each pathogen and its sensitivities.


Interim Antibiotic Selection


With serious wound infections, interim systemic therapy with an experience-guided (empiric) antibi- otic selection can be critical to a successful outcome while awaiting culture and sensitivity results. Ta- ble 1 lists the common bacteria isolated from various types of wounds in horses47–55 as a basis for empiric antibiotic choices that are most likely to be useful. Unless a specific pathogen with a well-established sensitivity pattern is strongly suspected (e.g., peni- cillin for clostridial myonecrosis), broad-spectrum antibiotic therapy generally is the best approach for interim therapy with serious wound infections. A combination of penicillinG(crystalline or procaine penicillin) and gentamicin is widely used in horses, but for some pathogens penicillin G is best replaced with a synthetic penicillin (e.g., ampicillin) or a cephalosporin (e.g., ceftiofur, cefazolin, cephalo- thin), and amikacin is sometimes a better choice than gentamicin. It is also wise to collect a separate swab or tissue


sample from the wound and perform a Gram stain in-house. This simple procedure provides immedi- ate information that can be very useful in directing interim antibiotic therapy. Table 2 lists some key cytologic features of common equine wound patho- gens, and Table 3 lists likely antibiotic sensitivities for each pathogen based on published studies of various equine populations in North America, Eu- rope, Australia, and New Zealand during the past 20 years.50,53–67


AXIOM IV


Antibiotic sensitivity patterns are quite variable and are always evolving. Sensitivity patterns vary among geographic regions and are heavily influ- enced by the extent of antibiotic use in the particular population of animals and their human caretakers. Pathogens isolated from hospitalized horses or those on farms where antibiotics are frequently used are more likely to show antibiotic resistance than are pathogens isolated from horses at premises on which antibiotic use is less common. Thus, these pub- lished antibiotic sensitivity patterns should be used as a general guide only, to aid in making rational choices for interim therapy, and never as a substi- tute for patient-specific, current bacterial culture and antibiotic sensitivity results.


At the present time, two antibiotic drugs remain in the arsenal for multidrug-resistant bacteria: van- comycin and imipenem. Note, however, that bacte- rial resistance is now documented for both drugs, so they are by no means “silver bullets,” and they will not remain viable options in veterinary or human medicine if they are used indiscriminately. Their use should therefore be reserved for situations in which culture and sensitivity results clearly indicate sensitivity to the particular drug and absence of reasonable alternatives.


Vancomycin


Vancomycin is active against many Gram-positive bacteria, both aerobes and anaerobes, including MRSA and Clostridium difficile. Vancomycin, ei- ther alone or in combination with an aminoglyco- side, is therefore an option for serious infections caused by Staphylococcus sp. or Enterococcus sp. that are resistant to all other available options. The recommended systemic dosage in horses is 7.5


mg/kg every 8 hours, administered in saline by slow IV infusion over 30 minutes.58 For infections confined to the distal limb, vancomycin may be ad- ministered by regional perfusion, either IV or in- traosseous delivery. A vancomycin dosage of 300 mg in 60-mL sterile isotonic saline seems well toler- ated and achieves therapeutic concentrations in the synovial fluid and medullary sinusoidal plasma of the perfused area.68–70 These regional modes of delivery help optimize the treatment of vancomycin- susceptible infections in the distal limb while mini- mizing the cost of treatment, potential for toxicity, and development of bacterial resistance.


Imipenem


by slow IV infusion every 6 to 8 hours.71 Intrasy- novial administration is described in case studies, the dose ranging from 10 to 250 mg.72 Imipenem may also be administered by IV regional perfusion. A dose of 500mg imipenem in 100-mL sterile isotonic saline, delivered into the cephalic or saphenous vein, sustained imipenem concentrations in the metacarpo/ tarsophalangeal joint well above the minimum inhib- itory concentration of most susceptible pathogens for approximately 6 hours.73 Smaller perfusion volumes are also described for IV regional perfusion,72 but the safety of higher imipenem concentrations (solutions 5 mg/mL) have not been established.


Imipenem-cilastatin is active against a wide range of Gram-positive and Gram-negative organisms, both aerobes and anaerobes, including multidrug- resistant enteric pathogens (E. coli, Klebsiella sp., Salmonella sp., etc.), and most strains of P. aerugi- nosa and Bacteroides fragilis. However, it is not effective against MRSA, and resistance is docu- mented for some Enterococcus sp. A recommended dosage in horses is 10–20 mg/kg


AAEP PROCEEDINGS  Vol. 61  2015 21


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