“ “ Emerging infections, the re-emergence Emerging infections, the re-emergence of infectious diseases previously of infectious diseases previously considered to be under control, and considered to be under control, and the alarming trend of antibiotic the alarming trend of antibiotic resistance….require an immediate and resistance….require an immediate and appropriate response.” appropriate response.” Dr. Gail Cassell, Past President, American Society of Microbiology, May 1994
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“Emerging infections, the re-emergence of infectious diseases previously considered to be under control, and the alarming trend of antibiotic resistance….require.
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““Emerging infections, the re-emergence Emerging infections, the re-emergence of infectious diseases previously of infectious diseases previously
considered to be under control, and considered to be under control, and the alarming trend of antibiotic the alarming trend of antibiotic
resistance….require an immediate and resistance….require an immediate and appropriate response.”appropriate response.”
Dr. Gail Cassell, Past President,
American Society of Microbiology, May 1994
Mechanisms of ResistanceMechanisms of Resistance
• Decreased membrane permeability ( Gram negatives only; also need another mechanism to be significant)
• Enzymatic Inactivation of Antimicrobial
• Target Site Alteration or Bypass
• Efflux Pumps
Mechanisms Of Resistance Mechanisms Of Resistance Expressed In Military TermsExpressed In Military Terms
• Armour
• Antiballistic Missiles
• Diversion & Camouflage
• Hand to Hand Combat
Altered Membrane Permeability
-LactamAntibiotic Porin
OuterMembrane
Protein
InnerMembrane
Penicillins
Adapted from Denver LA, Dermody TS. Arch Intern Med. 1991
-LACTAMASE HYDROLYSIS
Cephalosporins
Action of Aminoglycoside - Inactivating Enzymes
OH OH OH I I I
-OH HO-P-O-P-O-P-O-adenosine II II II O O O
OH OH OH I I I
-O-P-OH HO-P-O-P-O-adenoside II II II O O O phosphorylation
OH OH OH I I I
-O-P-O-adenosine OH-P-O-P-OH II II II O O O adenylation
Longer half-life antibiotics may create a greater windowof opportunity for the development of resistance
Guggenbichler JP, Kastner H Infect Med 14 Suppl C: 17-25 (1997)
Effect of Elimination KineticsEffect of Elimination Kineticson Bacterial Resistanceon Bacterial Resistance
“ I want you to take one of these with water every four years ”
HandwashingHandwashing• The most important method for preventing the spread of infections• ~70% of PRSP in US belong to seven
clonal groups• Antimicrobial handwashing agents - alcohol based handrinses• Wash hands before and after: - all patient contact - contact with infective material
“…“….we have too many illusions .we have too many illusions
that we can… govern… the that we can… govern… the
microbes that remain our microbes that remain our
competitors of last resort for competitors of last resort for
dominion of the planet.”dominion of the planet.”
Lederberg J. JAMA 1988;260:684-5.
“…“….Pitted against microbial .Pitted against microbial