Definitions
What is antimicrobial stewardship?
Defined by AVMA as: The actions veterinarians take individually and as a profession to preserve the effectiveness and availability of antimicrobial drugs through conscientious oversight and responsible medical decision-making, while safeguarding animal, public, and environmental health.
Amoxi/clav: drug class, MOA, spectrum, cidal vs static, time vs concentration
- Penicillin
- Amoxi: Cell wall synthesis inhibition; Clavulanic acid: competitively and irreversibly binds to beta lactamases
- Gram positive aerobes, Some gram negative aerobes (E.coli, Klebsiella, Haemophilus), Anaerobes - Not effective against Psuedomonas, Enterobacter, Citrobacter, Serratia
- Cidal, Time
List risk factors for developing an antimicrobial resistant infection
- Tx w/ antimicrobial therapy within the previous 3 months
- Hospitalization for longer than 5 days
- An environment characterized by a high frequency of antimicrobial resistant organisms
- Presence of immunosuppressive disease or therapy
- Evidence that the infection (pneumonia) is related to health care
5yo FS DSH was presented for mucopurulent nasal discharge and sneezing for 5 days duration. Owners recently fostered a kitten. Would you start abx and if so which one?
The Working Group recommends that antimicrobial treatment be considered within the 10-day observation period only if fever, lethargy, or anorexia is present concurrently with mucopurulent nasal discharge. Otherwise most cats w/ URI will be viral and signs self limiting so okay to hold if still eating, drinking, etc
T/F- An MDRO is resistant to three or more antibiotic classes.
True- Per NIH, MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories
What is MIC?
The lowest concentration of an antimicrobial agent that prevents visible growth of a microorganism in an agar or broth dilution susceptibility test
Enrofloxacin: drug class, MOA, spectrum, cidal vs static, time vs concentration
aQFluoroquinolone
MOA: Inhibition of DNA gyrase and topoisomerase IV, prevention of DNA supervoiling and synthesis Active in both stationary and growth phases
Spectrum: Gram positive aerobes, Gram negative aerobes, Pseudomonas (some isolates resistant), Brucella, Mycoplasma, Mycobacterium. Not effective against anaerobes or Streptococci
Cidal
Concentration
What are the four CDC strategies to reduce the incidence of antibiotic resistant microorganisms?
1. timely and appropriate initiation of antibiotics
2. appropriate administration and deescalation of antibiotics
3. data monitoring, transparency, and stewardship infrastructure
4. promoting the development of new antibiotics and new diagnostic tests for resistant bacteria
1yo MN Lab with acute onset of hacking cough and nasal discharge. Would you start abx and if so which one?
The Working Group recommends that antimicrobial treatment be considered within the 10-day observation period only if fever, lethargy, or inappetence is present together with mucopurulent discharges.
If bacterial CIRDC is suspected in dogs with mucopurulent nasal discharge, fever, lethargy, or inappetence but no clinical evidence of pneumonia the Working Group recommends administration of doxycycline empirically for 7–10 days as the first-line antimicrobial
Describe the best approach to deescalation of antimicrobials
A three-pronged approach to deescalation includes narrowing the antibacterial regimen through culture, assessing the susceptibility for dosage determination, and choosing the shortest course of therapy clinically acceptable.
What is a breakpoint and how does this differ from MIC?
• Determined per antibiotic and per bacterial species
• Established concentration (mg/L) of an antibiotic which defines whether a species of bacteria is susceptible or resistant to the antibiotic.
Clinical breakpoints are standardized for a specific organism and each antibiotic tested for that organism, not for an individual patient. On the other hand, the MIC is at the patient level
T/F: Marbofloxacin is a concentration dependent abx
TRUE
Class- Floroquinolone
MOA- Inhibition of DNA gyrase and topoisomerase IV --> prevention of DNA supervoiling and synthesis Active in both stationary and growth phases
Spectrum: Gram positive aerobes, Gram negative aerobes, Pseudomonas (considered the most active fluoroquinolone against Pseud), Brucella, Mycoplasma, Mycobacterium, Not effective against anaerobes or Streptococci
Cidal, concentration
What are the four major mechanisms of antimicrobial resistance?
1. Reduced permeability (down-regulation of porins in Gram negatives)
2. Active efflux (TetA tetracyclines efflux pump in Enterobacteriaceae)
3. Antimicrobial agent modification (acetylation of chloramphenicol by CAT enzymes)
4. Target modification (peptidoglycan modification in vancomycin-resistant enterococci)
3yo FS mixed K9 presented for hematuria and polakiuria starting this morning. No hx of UTIs. Would you culture? Would you start abx and if so which one?
Per working group- "Aerobic bacterial urine culture is preferred for all cases of suspected bacterial cystitis but empirical therapy in lieu of culture can be justified in dogs with suspected sporadic cystitis, particularly in animals with limited previous antimicrobial exposure and in situations where the likely pathogens and susceptibility patterns are predictable." They do ideally recommend UA though.
Amoxicilin is good first choice- high concentrations achieved in urine. Recommend 3-5 day course (though data is lacking on efficacy of 3 day course).
How long should you wait to start abx in a patient with suspected sepsis?
Don't wait! The 2016 Surviving Sepsis Campaign guidelines recommend that antibiotics be administered within one hour of sepsis diagnosis and that cultures should not delay antibiotic administration for more than 45 minutes. In septic patients, the administration of appropriate antibiotics within one hour can reduce mortality.
Define intrinsic vs extrinsic resistance
Intrinsic resistance- naturally resistant, no need for mutation
Acquired resistance- involves gene mutation
Based on pharmacokinetic and tissue localization studies, doxycycline is highly concentrated in these organs
Ocular (lipid portion of tear film, its a lipophilic drug), kidney, lung, gallbladder, prostate, intestinal tract, myocardium, sinus secretions, tonsil, aqueous humor, and female reproductive tissue
What are three mechanisms of horizontal transfer of genetic material between bacteria?
1. Transformation – uptake of naked DNA present in the environment by naturally competent bacteria
2. Transduction – transfer of DNA from one bacteria to another by bacteriophages
3. Conjugation – transfer of plasmids between bacteria through a mating-like process
An rDVM obtained this UCS on a 2yo MI K9 during wellness exam. What do you recommend?
Source: Urine
Isolate: Enterococcus
Amoxicillin: S, MIC <2
Doxy: S, MIC <0.5
Clavamox: S, MIC <2
Don't treat! This patient is asymptomatic and enterococcus is a known commensal.
What is ISCAID?
The International Society for Companion Animal Infectious Diseases (ISCAID)
"ISCAID members are part of a dynamic group of researchers, clinicians and trainees that are focused on infectious diseases in companion animals. Within human medicine a clinical practice guideline is required to be informed by a systematic review and include recommendations from an expert panel. The following guidelines and consensus statements don’t follow this rigorous methodology but are published by well-established organizations and experts in their respective fields."
What are plasmids?
Plasmids are extrachromasomal self-replicating genetic elements essential for survival that carry genes that impart selective advantage.
This is a major player in the spread of antimicrobial resistance genes
Which commonly used antibiotic can cause olfactory impairment in dogs?
Metronidazole
What are the four classes of mobile genetic elements that move within or between cell genomes?
a. Plasmids
b. Transposons
c. Bacteriophages
d. Self-splicing molecular parasites
T/F- Bacterial pneumonia should be treated with a minimum of 4-6 weeks of antibiotics
False. However we do not have clear cut data to guide us on how long we should treat. The Working Group recommends re-evaluation of animals with pneumonia no later than 10–14 days after starting treatment. At that point, decisions to extend treatment should be based on clinical, hematological, and radiographic findings. We need more studies.
T/F: Screening cultures are a prudent part of antimicrobial stewardship and is gold standard for ensuring judicious antibiotic use
FALSE- Per ACVIM consensus statement, isolation of potential pathogens in the absence of clinical evidence of disease can lead to unnecessary antimicrobial use and might only promote colonization or infection by antimicrobial‐resistant bacteria.