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Baytril Max. Resistance development Mutant Prevention Concentration (MPC). Resistance. Mutation. Selection. Genetic transfer. Mutation. Frecuency : 10 -8 to 10 -10. The possibility of having a mutation is between 100 to 10 000 millions; it is very low. Bacterial selection.
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Baytril Max Resistance development Mutant Prevention Concentration (MPC)
Resistance Mutation • Selection • Genetic transfer
Mutation Frecuency : 10-8to 10 -10 The possibility of having a mutation is between 100 to 10 000 millions; it is very low
Bacterial selection • Bacterial selection is related with the use of antibacterials; after having mutant bacteria. • It cannot be avoided
Mutants to: Te, Ge, Am Te Sensitive population Am Ge Mutants are not detected in the sensitive bacterial population……unless
Tetracycline treatment ( example) Selected mutants Te Am Ge Sensitives Te resitant population could be selected
Genetic transfer Resistant bacteria can transmit genetic information encoding resistance to other living bacteria; by: • Transformation • Transduction ( bacteriophages- virus-) • Conjugation ( mating, plasmids)
Transformation From: http://www.learner.org/courses/biology/images/archive/detail/1854_d.jpg
Transduction: bacteriophages ( virus ) From: http://www.bio.miami.edu/~cmallery/150/gene/c7.18.16general.jpg
Conjugation: bacterial „mating“ From: Image from Wikipedia.org under the item ‘Bacterial conjugation’
Susceptibility monitoring • There is no resistance to fluoroquinolones plasmid mediated • Genetic mutation is of low frequency
MPC Mutant Prevention Concentration: How to delay the resistance
Selective Amplification of Resistant Mutants at MIC Time 20 000 in 1 billion MIC 2 in 1 billion Weaning, Shipment 200 in 1 billion Immunocompromised state Prior Infection Weather Prior antibiotic exposure Acute infections/failed therapy Other stressors Potential Clearance Healthy immune system Immune Threshold Breached Hansen & Blondeau 2002; Blondeau et al 2004
If an antibacterial has this curve, possibility of selection of mutants is high Blondeau et al, J. Chemo, 2004
Inhibition of colony formation with increasing drug concentrations (Wetzstein, 2000) Inoculum: 4 x 109 CFUs per plate ~ 2700 CFUs 190 CFUs no CFUs 11 CFUs
Selective Amplification of Resistant Mutants at MPC Time MPC Colonization or New Infection 2 in 1 billion Weaning, Shipment Normal flora Immunocompromised state Prior Infection Weather Prior antibiotic exposure Acute infections/failed therapy Other stressors Potential Clearance Healthy immune system Immune Threshold Breached Hansen & Blondeau 2002; Blondeau et al, 2004
Program in EU: Resistance Monitoring
How is the situation of resistant isolates after 20 years of use in countries with responsible use policies? Last report in Germany Shows bacterial isolations from cattle with low resistance rate: Pasteurella spp: < 5% Manhaemia spp: <5% S. aureus (mastitis): < 5% Salmonella spp: < 5% E. coli: 27% In the case of E. coli Enro resistance rate is higher; but Ampicillin has 72% of resitance and tetracyclines 67%
Bayer Animal Health endorses the responsible use of antimicrobial products in veterinary medicine