dr ian gould 0
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http://cddep.org/sites/default/files/dr_ian_gould_0.pdfTRANSCRIPT
Dr. Ian M. Gould Medical Microbiology
Aberdeen Royal Infirmary
The Many Paradoxes of Antibiotic Use
“At least the waiting lists are improving - I only had to wait one week to get MRSA”
International Society of Chemotherapy
<Infection and Cancer>
www.ischemo.org
Paradox 1 • Antibiotics initially led to poorer
hospital hygiene
Healthcare Environment Inspectorate
Report
“Haven’t you heard – we’ve got MRSA sweeping the hospital”
0
5
10
15
20
25
30
35
Jan-97 Jan-98 Jan-99 Jan-00 Jan-01 Jan-02 Jan-03 Jan-04 Jan-05 Jan-06
%MRSA in hospital clinical specimens. Successful Interventions (Mahamat et al IJAA’07,JHI’11)
Environmental Swabbing (p=0.03)
Bleach (p=0.002)
Hand Gel (p=0.03)
Admission Screen (p<0.01) Stop Bleach (p=0.03)
%M
RSA
in C
linic
al S
peci
men
s
Environmental contamination
20-50 % antibiotic use in humans not
necessary
40-80% antibiotics used for animals
questionable value
Paradox 3 • Antibiotics increase infections
Deaths from HAI, USA
• 1992………..13,300 • 2008……… 100,000 Antibiotics and Resistance,(IDSA website/
Researchandmarket.com)
CID 2008:46 (Suppl 1) S25
MA of Risk of C diff v Antibiotic Exposure
0
5
10
15
20
25
30
35
40
45
500
550
600
650
700
750
800
850
Jan 96 Jan 97 Jan 98 Jan 99 Jan 00
% MRSA
Sum of lagged antimicrobial series
% M
RSA
Total ab. C
onsumption: D
DD
/1000 bed days Relationship between % MRSA and antibiotic use.
(3rd GC, FQ, MAC)
Emerg. Inf. Dis 2004, 1432
3rd GC lags = 4 – 7 months FQ lags = 4 & 5 months MAC lags = 1 – 3 months
MDR K. aerogenes outbreak
Price and Sleigh Lancet 1971
HPS Reported bacteraemia
0
500
1000
1500
2000
2500
3000
Klebsiella E.coli
20012002200320042005200620072008
Paradox 4 Antibiotics can
increase severity of infection
Staphylococcal toxic shock syndrome
Taylor et al, BMJ, 2006
Causes of Increased Transmission,Adherence and Pathogenicity of MRSA when exposed to Antibiotics
§ Biofilm formation § Small colony variants § Efflux § Hypermutation § Skin/RT colonization → transmissibility § Fibrinonectin-binding protein § Toxin production eg ∝, TSST-1 § SOS response → horizontal gene transfer § Phage induction § Quorum sensing § agr expression § Autolysis § Intracellular persistence Dancer JAC ’08 61 246 Gould JAC’08 61 763
A Reasonable Biological Model? (adapt. from Monnet D, 2006)
Poor infection control MRSA colonization pressure MRSA in the environment Length of stay, medical devices Antimicrobial consumption Exposure to fluoroquinolones,
ß-lactams - selection, increased adhesion, increased virulence, patient risk factors, etc.
MRSA negative Colonized Infected
New Bugs, not so new drugs
Paradox 5 No new antibiotics
0
5
10
15
20
1983-1987 1988-1992 1993-1997 1998-2002 2003-06/04
No.
of F
DA
app
rove
d an
tibac
teria
l NM
Es
Adapted from: Nordberg P, et al. Antibacterial drug resistance [background paper].
Priority Medicines for Europe and the World, 2004.
Antibacterial New Molecular Entities (NMEs) Approved by the FDA for Use in the United States,
1983-June 2004 (topical drugs excluded)
R2=0.99 p=0.007
Paradox 6 • Are new antibiotics really the
answer? (can we ever win the war?)
Integron
conserved DNA 4FQ integrase tet macrolide β-lactam promoter
Amino- glycoside
conserved DNA
MULTIPLE ANTIBIOTIC RESISTANT DETERMINANT
GENE CASSETTES
Paradox 7 • Generics and Counterfeits