Judicious Use of Florfenicol and other Antibiotics

Lower Snake River Compensation Plan Hatchery Production Planning Meeting

May 15-16, 2012

Judicious Use of AntimicrobialsAVMA AqVMC Guidelines 2002, revised 2004Treat as a Last Resort

Prevention is key: husbandry, biosecurity, nutrition, vaccination, probiotics, minimize stressors

Accurate Disease DiagnosisIf Abx are warranted, determine Abx of

choice of those available.

Judicious Use of AntimicrobialsUse culture and

sensitivityTx 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 AntimicrobialsUse 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 AntimicrobialsAntimicrobials 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 AntimicrobialsChoose 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

1. Pump the antibiotic out of the bacterial cell

2. Degrade the antibiotic with an enzyme

3. Render antibiotic ineffective with an altering enzyme

From Todar’s Online Textbook of Microbiology

How bacteria acquire resistance1. Innate2. Acquired

TransformationTransductionConjugation

Use of Antibiotics: applying a selective pressure for resistance

en.wikipedia.org

From ANTIMICROBIALPHARMACODYNAMICS: CRITICALINTERACTIONS OF ‘BUG AND DRUG’George Drusano Nature 2004

Routes by which antimicrobial resistant bacteria and resistance genes can cycle through human populations, and terrestrial and aquatic systems

Tt

Food, pets, animal

husbandry, leisure

Food, potable

water, fish keeping, bathing, leisure

Irrigation, animal

drinking water,

precipitation, birds

Terrestrial environment

AquaticEnvironment

Sewage effluent, hospital waste, agricultural runoff, direct contact with livestock, humans & wildlife

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 resistanceSchwarz and Chaslus-DancaVeterinary Research 32(2001)221-225

Why feeding fish antibiotics is especially challengingUneven 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 outIn this case, the strains carrying the floR gene were associated with multidrug resistance, with all strains resistant to at least 5 antimicrobialsFlorfenicol 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