MRSA and MRSS in Dogs—Antibiotic Stewardship for Veterinarians

Staphylococcus pseudintermedius is the most common cause of bacterial skin diseases in dogs.  It was “renamed” when advanced identification techniques were used to clarify the differences between S. pseudintermedius and S. intermedius.  Any reference to S. intermedius prior to 2009 should be assumed to be S. pseudintermedius.  S. schleiferi is the second-most common cause of bacterial skin infections. Bacteria began developing strategies to become resistant to antibiotics ever since the initial usage of antibiotics. Basically, bacteria don’t want to die. They have developed many modifications over the past several decades that allow them to become resistant to most antibiotics. New information about the skin microbiome reveals just how complex the normal bacterial skin population really is in humans and animals.1 Any imbalance of this bacterial population or any decrease or alteration of the normal skin barrier function allows an increased risk of a bacterial skin infection. The defect in the skin barrier function that occurs with environmental allergies (Atopic dermatitis) is the most common predisposing factor for bacterial skin disease in dogs. Pruritus leads to self-trauma that leads to epidermal / dermal damage that lead to bacterial skin infections. Repeated courses of antibiotics select for resistant bacteria.2  This selection is particularly true if an inappropriate dose or duration of therapy is used. Antibiotic doses need to be toward the high end of the dosage range and often for longer durations than for other soft tissue infections because there is no blood supply to the epidermis, and only minimal blood supply to the dermis (4% of cardiac output). Sometimes only a couple courses of antibiotic therapy can lead to the development of resistant bacteria. Currently over 50% of cultures taken by dermatologists show methicillin-resistant staph infections (MRSP, MRSS) and approximately half of these bacteria are resistant to all antibiotics except rifampin, amikacin and sometimes chloramphenicol.  Judicious use of antibiotics is more critical now than ever before. Veterinarians need to become more aware of antibiotic stewardship.  In a commentary on antimicrobial stewardship in companion animal practice (JAVMA Vol 246, No. 3; Feb 1, 2015) the AVMA Task Force for Antimicrobial Stewardship in Companion Animal Practice stated:  “It is estimated that 50% of antimicrobials are unnecessarily or inappropriately prescribed in human medicine, and it seems likely that the percentage in companion animal settings is similar.”  While that number may be debated, it is still very thought-provoking.  They also stated “For practicing veterinarians, that means promoting stewardship of antibiotics, reducing the use of antibiotics across the board and seeking alternatives to the use of antibiotics.”  Rather than using antibiotics to “cover” in case of an infection, we need to ask ourselves “Is there a clear indication for antibiotic usage?”   Most sterile soft tissue surgeries do not need post-surgical antibiotic usage.  Can topical antimicrobial therapy be used instead of systemic therapy in a case of focal or intertriginous pyoderma? Skin cytology results can be used to help determine if antibiotics are warranted.  We need to discourage the use of subtherapeutic doses and/or pulse dosing of systemic antibiotics.  Various guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis have been proposed including a three-four tier system recommended by an international group of distinguished veterinarians from various disciplines: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases3

These guidelines are just that—guidelines that need to be massaged and modified based on regional bacterial resistance patterns, practice economics and client compliance issues.  The task of choosing an antibiotic really is much more complicated than we may have previously realized.  I have modified these guidelines to more appropriately fit my patient population from in and around the Philadelphia area as follows:

First line antibiotics in an uncomplicated pyoderma (No Bacterial Culture/Susceptibilty Test required)

Amoxicillin-clavulanic acid (Clavamox), (12.5-25 mg/kg PO BID/TID)
Cephalexin / cefadroxil, (22-33 mg/kg PO BID)
Clindamycin  (5.5-10 mg / kg BID or > 11 mg / kg q 24 h);  Narrow spectrum
Lincomycin (15-25 mg/kg PO BID);  Narrow spectrum
Cefpodoxime proxetil (Simplicef):  Extended spectrum cephalosporin (5-10 mg/kg PO q 24 h)

  • Approved in US for gram negative bacteria (E. coli, Proteus mirabilis)
  • Active drug may not reach large intestine in adequate levels to select for highly resistant
    extended–spectrum B-lactamase (ESBL)-producing E. coli;

Cefovecin (Convenia): (8 mg/kg SQ every 14 days)

  • Exceeds MIC90 of E. coli for 2 days, MIC50 for 6 days →may select for highly resistant
    extended–spectrum B-lactamase (ESBL)-producing E. coli;

Second line antibiotics in a more resistant pyoderma
Based on results of C/S testing→ “Appropriate Antibiotics”
Potentiated Sulfas (1:5 ratio):

  • TMS (15-30 mg/kg PO BID),
  • Primor (55 mg/kg PO first day, 27.5 mg/kg PO q 24 h)
    Side effects:  Vomiting, diarrhea, immune-mediated joint disease, erythema multiforme→ Avoid in
    Dobermans and Rottweilers
  • Fluoroquinolones (marbofloxacin, enrofloxacin, orbifloxacin, but NOT cipro)
    Known risk factor for selecting for MRSA and ESBL E. coli
  • Enrofloxacin  10-20 mg/kg PO q24h
  • Marbofloxacin  2.75-5.5 mg/kg PO q24h; 5.5 mg/kg for MRSP, Pseudomonas
  • Orbifloxacin  7.5 mg/kg PO q24h
  • Doxycycline hyclate or monohydrate (5-12 mg / kg BID)
    Hyclate oral suspension only lasts 7 days
  • Minocycline (5-10 mg / kg SID / BID)
    Vomiting more common than with doxycycline?

Antibiotics of last resort for MRSP / MRSS:
1)  Chloramphenicol (25-60 mg/kg PO q 8 h +/- food)

  • Side Effects: Vomiting, diarrhea, inappetance
  • Bone marrow suppression
  • Fatal aplastic anemia in humans! (~1:24,000 to 1:40,000 people)
  • Resistance rates are increasing
  • Large dogs may need lower dose (30-40 mg/kg q 8 h?) due to demyelination of
    nerve sheath resulting in temporary or permanent muscle weakness or paresis
  • DO NOT TOUCH! (wear gloves when handling), avoid inhaling; don’t open capsules or
    break tablets; no compounding / liquids?
  • Cytochrome P-450 inhibitor → decreased clearance and metabolism of many other
    drugs  (ketoconazole, ivermectin)

2)  Rifampin (10 mg/kg PO q 24 h or 5 mg/kg PO q 12 h)

  • Induces hepatic enzymes→ increased clearance of antifungals, steroids and digoxin
  • Rapid development of resistance?
    Per Dr. Papich most work supporting rapid resistance development and the
    need for multi-drug therapy was done in mycobacteriosis not pyoderma
  • Is effective as antibiotic monotherapy for Staph pyoderma
  • Bajwa et al, NAVDF 2013, Retrospective study:
    Dose range: 2.9 to 16.5 mg/kg/day
    Adverse drug reactions: 56 patients (16.3%), began after 19-27 days
    Vomiting, anorexia, lethargy, and weight loss
    22% of dogs (20/94) had elevations in ALT
    7 / 344 dogs died (2%) esp if dose was > 10 mg/kg/day
  • Hepatotoxicity (fatal if not caught early!!!) with higher doses
  • Liver enzyme monitoring q 5 days beginning at 14 days of therapy; discontinue if
    increased LE’s!

3)  Amikacin (15 mg/kg SQ q 24 h x 14-60 days)

  • Renal monitoring q 2-4 days:  BUN, Creatinine, Urine Protein:Creatinine ratio, look for urine casts/crystals
  • Give a SQ bolus of fluids, then inject amikacin into the SQ fluid pouch—lessens the pain
    associated with injection and helps flush fluids through the kidneys;

4)  When no antibiotic is effective:

  • Chlorhexidine q 24-48 h
    Whole body (except face) Clorox rinses:  2 oz/gal water q 24-48 h
    Whole body or regional (except face) Clorox sprays: 4 oz/gal water q 24 h

The important points are that we need to accurately diagnose a pyoderma, treat it appropriately and identify and treat the underlying cause to minimize the recurrence and need for antibiotics.
Kevin Shanley, DVM, DACVD

References:
1.  The cutaneous ecosystem: the roles of the skin microbiome in health and its association with inflammatory skin conditions in humans and animals. Hoffman A;  Vet Dermatol 2017; 28: 60-70 See:  http://insights.ovid.com/veterinary-dermatology/vetd/2016/05/001/cutaneousecosystem-roles-skin-microbiome-health/15/01445519

2. Prior antimicrobial use as a risk factor for resistance in selected Staphylococcus pseudintermedius isolates from the skin and ears of dogs.  Vet Dermatol 2016; 27: 468-473 See:  http://onlinelibrary.wiley.com/doi/10.1111/vde.12382/full

3. Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases).  Vet Dermatol 2014; 25: 163-175 (June, 2014);  Hillier A, Lloyd D, Weese S, Blondeau J, Boothe D, Breitschwerdt E, Guardabassi L, Papich M, Rankin S, Turnidge J Sykes J See:  http://onlinelibrary.wiley.com/doi/10.1111/vde.12118/full

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