Judicious Use of Florfenicol and other Antibiotics Lower Snake River Compensation Plan Hatchery Production Planning Meeting May 15-16, 2012

Judicious Use of Antimicrobials AVMA AqVMC Guidelines 2002, revised 2004 Treat as a Last Resort Prevention is key: husbandry, biosecurity, nutrition, vaccination, probiotics, minimize stressors Accurate Disease Diagnosis If Abx are warranted, determine Abx of choice of those available.

Judicious Use of Antimicrobials Use culture and sensitivity Tx may be started based on diagnosis and previous sensitivity results if necessary Monitor sensitivity trends over time Lab results can be different than in field

Judicious Use of Antimicrobials Use antimicrobials with narrowest spectrum of activity and known effectiveness in vivo (minimize broad Abx resistance). Antimicrobial use should be optimized using current pharmacological information and principles.

Judicious Use of Antimicrobials Antimicrobials should be used in cases of appropriate clinical indications (for example, not in cases of uncomplicated viral infections). Minimize exposure of bacteria to antimicrobials, treat only until desired clinical response (such as target for mortality rate reduction).

Judicious Use of Antimicrobials Choose antimicrobial drugs of lesser importance in human medicine. Whenever possible, use an antimicrobial that is labeled to treat the condition diagnosed. Do not use antimicrobial drugs prophylactically.

How Bacteria are Able to Avoid Antibiotic Effects Pump the antibiotic out of the bacterial cell Degrade the antibiotic with an enzyme Render antibiotic ineffective with an altering enzyme From Todar’s Online Textbook of Microbiology

How bacteria acquire resistance 1. Innate 2. Acquired Transformation Transduction Conjugation

Use of Antibiotics: applying a selective pressure for resistance From ANTIMICROBIAL PHARMACODYNAMICS: CRITICAL INTERACTIONS OF ‘BUG AND DRUG’ George Drusano Nature 2004 en.wikipedia.org

Routes by which antimicrobial resistant bacteria and resistance genes can cycle through human populations, and terrestrial and aquatic systems Terrestrial environment Food, pets, animal husbandry, leisure Sewage effluent, hospital waste, agricultural runoff, direct contact with livestock, humans & wildlife Food, potable water, fish keeping, bathing, leisure Irrigation, animal drinking water, precipitation, birds Tt Aquatic Environment From Taylor, Aquatic systems: maintain, mixing and mobilizing antimicrobial resistance? Trends in Ecology and Evolution June 2011, Vol 26, No 6

Three key factors with regard to emergence of antimicrobial resistance: “Association of resistance gene(s) with mobile genetic elements Close contact between bacteria in a polymicrobial environment The selective pressure as imposed by the use of antimicrobials” From Use of antimicrobials in veterinary medicine and mechanisms of resistance Schwarz and Chaslus-Danca Veterinary Research 32(2001)221-225

Why feeding fish antibiotics is especially challenging Uneven amount of food (doses), weaker fish eat less aggressively, therefore dose is less. Some antibiotics are excreted largely unchanged and are relatively stable in water Antibiotics settle with particles into the silt below the fish and interact with environmental bacteria

Florfenicol Florfenicol is a fluorinated analog of chloramphenicol approved by the Food and Drug Administration for the treatment of bovine respiratory disease (BRD) pathogens in 1996 Florfenicol binds to the 50S subunit of the bacterial ribosome and disrupts protein synthesis

Aquaflor® Approved for control of mortality in catfish due to enteric septicemia (ESC) associated with Edwardsiella ictaluri in 2005 Approved for treatment of fresh-water salmonids for F. psychrophilum and A. salmonicida in 2007 Approved for the control of mortality in freshwater-reared warmwater finfish due to streptococcal septicemia associated with S. iniae in 2012 Approved for the control of mortality in freshwater-reared finfish due to columnaris disease associated with F. columnare in 2012

Examples of Florfenicol resistance in aquaculture “Detection of the floR Gene in a Diversity of Florfenicol Resistant Gram-Negative Bacilli from Freshwater Salmon Farms in Chile” floR confers antimicrobial resistance to florfenicol and chloramphenicol giving the bacteria the ability to pump the antibiotics out In this case, the strains carrying the floR gene were associated with multidrug resistance, with all strains resistant to at least 5 antimicrobials Florfenicol was licensed for use in aquaculture in Chile in 1994 Zoonoses Public Health (2010) 181-188

Epidemiology of antimicrobial resistance www.IFT.org

Conclusions The epidemiology of antimicrobial resistance is complex Since we do not have all the science to understand the microbial ecology leading to resistance (the complex interactions between antibiotics, bacteria, and the environment) we should be judicious in the use of the few antimicrobials we have available