Therapy for Bacterial Disease

Question 1

What might cause recurrent Staphylococcal pyoderma?

Answer 1

• recurrent vs. persistent
  
  • > 2 weeks <
• inappropriate therapy
  
  • dosage and length
• look for underlying cause
  
  • Demodex
  • allergies
  • endocrine/metabolic
  • immunodeficiency (cats)
  • physical causes (trauma)

Question 2

What is your approach to a recurrent wound or cellulitis?

Answer 2

• best to culture
• systemic therapy based on C&S
• biopsy of intact nodule
• large sample required to culture atypical mycobacteria

Question 3

What cases should be cultured?

Answer 3

• recurrent pyoderma
• pyodermas that fail to respond to initial tx
• deep pyodermas
  
  • chronic recurrent draining tracts
  • cellulitis

Question 4

How should you culture a bacterial skin lesion?

Answer 4

• look for primary lesion
  
  • papule
  • pustule
  • nodule
• avoid secondary lesions, if possible
• avoid ulcerated or opened lesions
• stop abx 3-5d before culture
  
  • if possible - if not alert the laboratory
• pustules - wipe surface w/ alcohol, open and swab
• papules, plaques, nodules or draining tracts - clean surface and biopsy

Question 5

What is the choice of antibiotics determined by?

Answer 5

• empirical or based on susceptibility test
  
  • in vitro vs. in vivo
• safety profile
• concurrent dz
• depth of the infection
• length of the tx
• needs to reach the skin in high concen.
• breed
• age
• constraints of owner

Question 6

What are general rules of therapy for bacterial skin disease?

Answer 6

• use abx with narrow spectrum first
  
  • rapid resistance with some abx
• use abx with less adverse effects
  
  • incr safety
• if many bacteria isolated
  
  • select abx effective against various organisms
  • if not possible, focus on Staph first

Question 7

What are the general rules of antibiotic therapy?

Answer 7

• appropriate length of therapy
  
  • superficial pyoderma
    
    • minimum: 3-4 wks
    • abx continued for a minimum of 7-10d past resolution of C/S
  • deep pyoderma
    
    • minimum: 2-3 mo
    • abx continued for a min of 4 wks past resolution of signs

Question 8

How do you monitor therapy for bacterial disease?

Answer 8

• difficult with deep infections
  
  • rapid initial improvement
  • apparent “plateau” of improvement
  • granulomatous component
  • fibrosis and FB
• topical tx is mandatory
  
  • antibiotic vs. antiseptic

Question 9

What are common reasons for treatment “failure”?

Answer 9

• failure to ID all underlying causes
• wrong abx
• inappropriate dose
• inappropriate length of tx
• concurrent use of steroids
• foreing body rxn

Question 10

What are the first tier antibiotics for pyoderma?

Answer 10

• macrolides/macrolides-like
  
  • erythromycin
  • lincomycin
  • clindamycin
• first generation cephalosporins
• amoxicillin/clavulanic acid
• potentiated sulfonamides

Question 11

What are the second tier antibiotics for pyoderma?

Answer 11

• third generation cephalosporins
  
  • cefpodoxime, cefovecin
• doxycycline and minocycline
• fluoroquinolones
• chloramphenicol
• rifampin
• aminoglycosides
  
  • gentamycin and amikacin

Question 12

What are the third tier antibiotics for pyoderma?

Answer 12

• vancomycin
• linezolid
• teicoplanin

Question 13

Describe beta-lactam antibiotics

Answer 13

• first tier antibiotic
• penicillins
  
  • beta lactamase resistant penicillins
    
    • oxacillin
    • dicloxacillin
    • dafcillin
  • potentiated penicillins
    
    • amoxicillin/clavulanic acid
    • ampicillin/sulbactam
  • cephalosporines

Question 14

What three first tier antibiotics are beta-lactamase susceptible?

Answer 14

• ampicillin
• amoxicillin
• penicillin

Question 15

Describe amoxicillin/clavulanic acid

Answer 15

• broad spectrum
  
  • primarily gram +
• bactericidal
• rapid absorption
• dose: 22 mg/kg q12
• adverse effects: GI

Question 16

Describe Cephalosporins

Answer 16

• broad spectrum bactericidal; work by inhibition of synthesis of bacterial cell wall
• first generations:
  
  • Cephalexin
    
    • used by many as first line antibiotic
    • broad spectrum but primarily gram +
    • resistance increasingly reported
    • t_1/2 = 6.5hrs

Question 17

Describe the adverse effects of cephalexin

Answer 17

• vomiting, diarrhea
• IMHA
• immune mediated thrombocytopenia
• urticaria
• drug eruptions
• rarely: neurotoxicity, neutropenia, interstitial nephritis

Question 18

Describe methicillin resistant staphylococci

Answer 18

• NOT more virulent than MSS
• MORE difficult to treat
• Activation of the gene mecA
  
  • incr penicillin binding protein 2a
  • involved in the synth of peptoglycans in bacterial wall
  • resistance to ALL beta lactams
  • oxacillin = class representative drug for in vitro testing

Question 19

Describe clindamycin

Answer 19

• food does not interfere with absorption
• good penetration in fibrotic tissues
  
  • intracellular accumulation
• greater efficacy than amox/clav. acid
• very well tolerated
  
  • esophageal strictures (cats)
• good choice for methicillin resistant Staph and superficial pyoderma

Question 20

Describe erythromycin

Answer 20

• absorption
  
  • incomplete
  • inactivated by gastric secretions
  • delayed by food admin
• soluble in lipids
  
  • 75% bound; eliminated via excretion in bile
• inhibition of cytochrome P450
  
  • ​drug interactions
• adverse effects: GI
• macrolide; inhibits ribosomal protein synthesis
• bacteriostatic; efficacy is time-dependent
• T_1/2 = 2 hr
• narrow spectrum: ideal for Staph
• effective in 80% cases
• very expensive!

Question 21

Describe lincomycin

Answer 21

• bacteriostatic
• macrolide-like antibiotic
• better absorption and distribution than erythromycin
• give on empty stomach
• rapid resistance (cross-reactive with erythromycin)

Question 22

Describe the clindamycin–macrolide interaction

Answer 22

• macrolide-inducible resistance
  
  • inducible methylase that alters the common ribosomal binding site for macrolides, clindamycin and the group B streptogrammins
    
    • D-test
      
      • Erythomycin and clindamycin

Question 23

Describe potentiated sulfonamides

Answer 23

• work by interfering with synthesis of folic acid
  
  • bacteriocidal
• effective in 50-80% cases
• anti-acids interfere with absorption

Question 24

What are some potential issues with sulfa group antibiotics?

Answer 24

• they are very allergenic and may trigger hypersensitivity reactions
  
  • Type I-III

Question 25

What are some adverse effects of potentiated sulfonamides?

Answer 25

• anemia, leukopenia, thrombocytopenia
• fever
• KCS
• hepatopathy
• nitrous metabolite is cytotoxic
• arthropathy
• cutaneous eruptions
• hypothyroidism
• polymyositis

Question 26

What breeds should you not use potentiated sulfonamides?

Answer 26

• do not use in Dobies and Rotties
  
  • incr risk of arthropathy
  • mechanism unknown
  • possible defect of detoxification

Question 27

Describe silver sulphadiazine

Answer 27

• topical sulfonamide
• broad spectrum
• ideal for Pseudomonas spp.
• 1% for skin
• 0.1% suspension in cases with ruptured ear drum

Question 28

Describe Doxycycline

Answer 28

• 2nd tier antibiotic
• used for resistant cases
• time-dependent cases
• currently very expensive, often substituted with minocycline
• anti-inflammatory properties
• adverse effects:
  
  • vomiting, diarrhea, nausea
  • yellow staining of teeth, esophageal strictures (cats)

Question 29

Describe Chloramphenicol

Answer 29

• broad spectrum
• bacteriostatic
• works by inhibiting ribosomal protein synthesis
• prescribed more and more frequently
• metabolized by the liver
• AE:
  
  • causes depression of microsomal enzymes
    
    • inhibits the metabolism of other drugs
  • aplastic anemai (irreversible) in owners
  • animals: GI, anorexia, elevated liver enzymes, anemia (reversible), peripheral neuropathy (large breeds)

Question 30

Describe cephalosporins

Answer 30

• third generation
  
  • activity against S. pseudintermedius not superior to 1st generation
  • active against Gram -
  • potential selection for methicillin resistance; very expensive
• e.g. Cefovecin, Cefopodoxime proxetil (Simplicef)

Question 31

Describe fluoroquinolones

Answer 31

• broad spectrum
  
  • gram + and -
• bactericidal
  
  • work by inhibiting DNA gyrase –> DNA replication
• save it for resistant cases and/or gram - !!
• absorption inhibited by anti-acids
  
  • chelates strong cations
• great penetration in tissues
• accumulate in neutrophils and macrophages
• concentration dependent: important to use once daily high dose
• peak concentrations are more important than duration of serum values > MIC

Question 32

What is the aim for the appropriate concentration of an antibiotic?

Answer 32

• try to strive to reach the highest dose possible (above minimum inhibitory concentration and mutant selection window), achieving the mutant prevention concentration
  
  • the risk of selection for resistant mutants is virtually impossible above the MPC

Question 33

What are the adverse effects of fluoroquinolones?

Answer 33

• GI
• neurological
  
  • seizures (very uncommon)
• arthropathy
  
  • stop growing plates
• blindness
  
  • enrofloxacin (cats)

Question 34

Describe enrofloxacin

Answer 34

• bioavailability = 40%
• metabolized into ciprofloxacin
• food administration incr amount of Cipro
• expensive for large dogs

Question 35

Describe marbofloxacin

Answer 35

• Bioavailability: 94%
• T_1/2: 14 hrs
• T_max: 2 hrs
• Wide distribution
• Plasma concentration > MIC for more than 24 hrs

Question 36

Describe Orbifloxacin

Answer 36

• Tmax: 1 hr
• Bioavailbility: 97%
• Cmax in tissues in 6 hrs
• 90% of drug is excreted metabolized in urines

Question 37

Describe Moxifloxacin

Answer 37

• human product
• used in dogs at 8 mg/kg q24h

Question 38

Describe Pradofloxacin (Veraflox)

Answer 38

• 3rd generation enhanced spectrum veterinary antibiotic of the fluoroquinolone class
• labeled for dogs (Europe) and cats (USA)
• extensive ocular safety testing

Question 39

Describe Mupirocin

Answer 39

• bacteriocidal
  
  • binds to tRNA
• excellent for Staph infections
• rare resistance
• minimal systemic absorption

Question 40

Describe Polymixin B

Answer 40

• Used for resistant Pseudomonas spp.
• binds to the cell membrane and alter its structure, making it more permeable
  
  • the resulting water uptake leads to cell death

Question 41

What are the principles of antibiotic use?

Answer 41

1. Full dosage!
2. Adequate time!
3. Treat Staphilococcus
4. Avoid steroids if possible
5. Re-evaluate if not improved

Question 42

What are the considerations you should have for long term antibiotic therapy?

Answer 42

• not recommended
• avoid pulse tx
• consider all triggeringh factors before considering immune stimulation

Question 43

Describe topical therapy

Answer 43

• important adjunct tx
• Chlorhexidine
  
  • mildly irritant
  • bacteriocidal, fungicidal (yeast), virocidal
  • used for whirlpool tx
• Benzoyl peroxide
  
  • excellent for staph infections
  • anti-pruritic, degreasing, keratolytic
    
    • potential irritation and dry skin

Question 44

Describe vetericyn spray

Answer 44

• oxychlorine
• used in humans for MRSA
• two different strengths
• water based
• well tolerated