Royal (Dick) School of Veterinary Studies, Easter Bush Campus, University of Edinburgh, Roslin, UK
We must use antibiotics responsibly to preserve their efficacy and minimise the development and spread of resistance. The key steps in responsible antimicrobial use and stewardship are:
- Ensuring the diagnosis - antimicrobials should not be used speculatively
- Selecting an appropriate antibiotic
- Giving it at the correct dose and frequency to clinical cure
- Managing underlying conditions.
Clinical Diagnosis of Pyoderma
Pyodermas are classified according to their clinical appearance:
1. Seborrhoeic pyoderma (erythema, erosions, exudation without pustules and collarettes): bacterial overgrowth syndrome and intertrigo.
2. Papules, pustules, scaling, focal alopecia: impetigo, bacterial folliculitis and superficial spreading pyoderma.
3. Erosions and/or ulcers: pyotraumatic dermatitis, intertrigo, and mucocutaneous pyoderma.
4. Ulcers and draining sinus tracts: furunculus is (deep pyoderma) and feline chin acne.
5. Nodules and/or regional swelling: abscess, cellulitis and necrotizing fasciitis.
It’s also important to recognise the depth of the infection. Surface and superficial infections are characterised by erythema and pruritus; they do not invade the dermis and often respond to topical therapy. Deep infections show swelling, haemorrhage, draining tracts and pain; they invade the dermis and deeper tissues, and may require prolonged systemic treatment.
Cytology is a simple way to confirm bacterial infection. Techniques include adhesive tape-strips, indirect and direct impression smears, and needle cores and fine needle aspirates. Modified Wright-Giemsa stains such as Rapi-Diff® or Diff-Quik® are quick and easy, and reliably identify inflammatory cells and microorganisms. All bacteria that take up these stains appear blue-purple whether they are gram-positive or gram-negative. Full identification requires further tests and culture.
Neutrophils predominate in most cases. Macrophages and multinucleate giant cells are seen in chronic and/or deep pyoderma, but large numbers (i.e., granulomas or pyo-granulomas) should alter you to the possibility of a mycobacterial or fungal infection. Lymphocytes, plasma cells and eosinophils are seen in most inflammatory reactions.
Bacterial overgrowth syndrome shows large numbers of bacteria with few inflammatory cells. Intracytoplasmic bacteria are a definite indicator of infection, but extracellular bacteria may be contaminants. Staphylococci are large cocci that form pairs, fours or bunched groups. Streptococci, micrococci and enterococci are smaller and form chains or irregular groups. Rod bacteria from the skin include Pseudomonas, Proteus and coliforms. Mycobacteria do not take up Wright-Giemsa stains, but pyogranulomatous inflammation with small rod-shaped vacuoles is suggestive.
Bacterial Culture and Antimicrobial Sensitivity Testing
Bacterial culture and antimicrobial sensitivity testing is not always necessary. Staphylococci have a relatively predictable pattern of antimicrobial sensitivity and empirical treatment is often successful.
Empirical therapy is appropriate:
- Topical therapy
- Life-threatening infections that need immediate treatment
- A first episode of infection
- Animals with no systemic antibiotic therapy within the last 3 months
- Surface or superficial pyodermas
- Cytology consistent with staphylococci
- Antibiotic resistance is unlikely
Culture and antimicrobial sensitivity testing is necessary:
- A life-threatening infection (although immediate therapy is necessary while waiting for results)
- Deep pyoderma
- Inconsistent clinical signs and cytology
- Rod bacteria
- If empirical treatment fails
- If resistance is more likely (e.g., after multiple antibiotic courses, non-healing wounds, or post-operative and other nosocomial infections)
Cytology can be used to determine the most important bacteria if culture detects multiple species with differing antimicrobial sensitivities.
Material for culture can be obtained by a variety of means depending on the type and depth of lesions. Primary lesions should be selected where possible. Alcohol can be used to reduce surface contamination, but this should be allowed to evaporate before the sample is collected. If antibiotic withdrawal isn’t possible prolonged and/or enriched cultures may be necessary and recent therapy should be noted on the submission form.
Understanding Susceptibility and Resistance Breakpoints
Kirby-Bauer tests use antibiotic impregnated paper discs. The zone of inhibition around a disc is compared to agreed susceptibility/resistance breakpoints. The minimum inhibitory concentration (MIC; lowest antibiotic concentration that inhibits growth) is determined in broth culture or using E-strips® and compared to agreed breakpoints to determine susceptibility or resistance.
If the isolate is susceptible then it is likely that antibiotic levels following systemic administration will exceed the MIC in the target tissue and the infection should respond to treatment. In contrast, if the isolate is resistant it is unlikely that the antibiotic will achieve a therapeutic concentration and the infection is not likely to resolve. Knowing the actual MIC is useful, as antibiotics with MICs close to the break point may need to be given at higher doses to ensure that they achieve therapeutic concentrations in the target tissues.
Breakpoints based on MICs, pharmacokinetics and tissue penetration. They are species specific, and breakpoints established for one species may not be accurate in others. They are also affected by variation in dosing, bioavailability, pharmacokinetics and tissue penetration. Finally, breakpoints are only relevant for systemic therapy and should not be used with topical therapy. The breakpoint does not imply that the bacteria will never respond to the antibiotic, only that systemic treatment will not attain a sufficient concentration at the site of infection. Topical therapy with mg/ml antibiotic concentrations, for example, can overcome apparent resistance.
Why Doesn’t the Clinical Response Match the In Vitro Test?
In vitro susceptibility tests don’t necessarily predict the clinical outcome. Disc diffusion tests may give misleading results - for example beta-lactam and cephalosporin susceptibility or resistance in vitro can be poorly predictive of the presence of meticillin-resistant staphylococci (MRSA/MRSP) or extended spectrum beta-lactamase (ESBL) E. coli and further tests may be necessary. Many MRSA and MRSP isolates exhibit inducible clindamycin resistance in vivo despite apparent in vitro sensitivity. This can be tested for using D-zone tests with erythromycin or PCR. Enrofloxacin is metabolised into ciprofloxacin, and tests based on one drug alone may not accurately predict the outcome. In addition to the MIC, understanding the nature of the infection, the pharmacokinetics of the antibiotic and patient factors will help achieve a successful outcome.
Selecting an Appropriate Antibiotic
It is important to consider whether the infection is deep, severe and/or generalised enough to warrant systemic antibiotics. Topical antimicrobials or topical antibiotics can be effective in surface and superficial infections and some focal deep infections. Effective topical antimicrobials include chlorhexidine, Manuka honey, hypochlorous acid, silver sulfadiazine, mupirocin and fusidic acid. Other antibiotics are also available in topical formulation for eye and ear infections, and injectable preparations can be added to creams and ointments.
First line antibiotics are no less potent than other drugs in the correct circumstances and are appropriate for empirical treatment. They include cefadroxil, cephalexin, clavulanate-amoxicillin, clindamycin and lincomycin. Cefovecin can be considered where administration or compliance may be difficult.
Second line antibiotics should only be used when there is culture evidence that first line drugs will not be effective. These include cefovecin and fluoroquinolones.
Third line antibiotics must only be used where no first or second line antibiotics are effective, and topical antimicrobial therapy is not feasible or effective. These include aminoglycosides, azithromycin, ceftazidime, chloramphenicol, clarithromycin, florphenicol, fosfomycin, piperacillin, rifampin and ticarcillin. Drugs deemed critically important to human health (e.g., vancomycin, teicoplanin, linezolid etc.) should never be used in animals. Some countries prohibit the use of human antibiotics not licensed for animals.
Dose and Duration of Treatment
Treatment should wait until antimicrobial sensitivity test results are available. If immediate treatment is necessary, drug selection should be based on the most likely organisms and their susceptibility, later changing to a higher or lower tier drug as required. Animals should be weighed to allow accurate dosing. Surface and superficial pyodermas typically need 1–3 weeks of treatment. Full resolution of deep pyodermas may take 4–6 weeks or longer. Treatment should continue until clinical cure and normal cytology.
Poor compliance compromises efficacy and encourages resistance. Compliance can be improved by using easy to administer drugs, clear written instructions, and good follow up.
Treatment Failures and Recurrence
Treatment failures can be associated with resistance, poor compliance, inadequate dose and duration, immunosuppressive drugs, and/or poor distribution to the target tissue. However, most recurrent pyodermas involve failure to manage the underling condition. Nevertheless, topical antiseptics or immunostimulants (e.g., Staphage Lysate) can reduce the frequency of relapses.
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2. BSAVA PROTECT antibiotic use guidelines - http://www.bsava.com/Resources/PROTECT.aspx (VIN editor: Link not accessible 1/9/18).
3. International Society for Companion Animal Infectious Diseases - http://www.iscaid.org/.
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