Antibiotic Resistance and the Future of Antibiotics

36 Pages·2012·1.71 MB·English

Antibiotic Resistance and the Future of Antibiotics
Julian Davies
Forum on Microbial Threats, 20-21 May, 2008
The Global Selection Pressure for Antibiotic Resistance
In the USA alone, more than 25 million pounds of antimicrobials
were manufactured in 2000.
Over a period of 50 years this equates to upwards of
ONE MILLION METRIC TONS
The USA is not the leading producer of antibiotics: Russia,
China, and India each produce larger quantities of these
biologically active agents.
Half or more of the production is for non-human use.
(
It is not possible to obtain accurate figures from manufacturers;
these numbers are based on surveys by various agencies.)
Biochemical Mechanisms of Antibiotic Resistance
2007
Increased efflux* Decreased influx*
Enzymatic inactivation Sequestration
Target modification* Target by-pass
Target repair Target amplification*
Biofilm formation* Intracellular localisation
All of these mechanisms can be acquired
by horizontal gene transfer (* also mutation).
Multi-drug resistance is the rule, rather than the exception.
The Discovery of Transferable Multi-Antibiotic Resistance
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Streptomycins Chloramphenicols Tetracycllines Multidrug Resistance
The Plasmid Meeting
Kavouri 1976
Mortality rates of staphylococcal bacteraemia 1937-2000
Dancer, S. J. J. Antimicrob. Chemother. 2008 61:246-253; doi:10.1093/jac/dkm465
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2001-2002
Endemic Outbreak
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2007
2005
Endemic Outbreak
Where do resistance genes come from?
The Biology of Small Molecules:
Are Antibiotics naturally Antibiotics?
Antibiotic Resistance in the Environment
1972 Identification of ß-lactamases in soil actinomycetes
1974 Identification of aminoglycoside-modifying enzymes in soil
bacteria
2001 Identification of gyrA allelism in soil isolates: "natural"
fluoroquinolone resistance
2004 Resistance genes identified in soil metagenome
2006 The environmental "resistome”: multidrug resistance in soil
isolates
2006 The "intrinsic" resistome of pathogens
2008 The environmental “subsistome”: bacterial degradation of
antibiotics