la resistencia bacteriana, necesidad de innovación. dr. ian m. gould
TRANSCRIPT
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Dr. Ian M. Gould Medical Microbiology
Aberdeen Royal Infirmary
Empirical Antibiotic Therapy; a Need for
Innovation
Empirical Antibiotic Therapy; a Need for
Innovation
““At least the waiting lists are improving - I only had At least the waiting lists are improving - I only had to wait one week to get MRSA”to wait one week to get MRSA”
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IF YOU DON’T LOOK PROPERLY,YOU WON’T SEE IT
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How well do you know your enemy: How long have bacteria existed on our planet?How well do you know your enemy: How long have bacteria existed on our planet?
1. 3.5 billion years
2. 1 billion years
3. 500 million years
4. 200 million years
5. 50 million years
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The EnemyMicrobes- Very old- Highly adaptable- Unparalleled ability to survive:
virulence factors, antigenic changes
- Generation time of 20 minutes vs 30 years in man
- Only 10% of cells in/on our bodies are human, the rest are bacteria
Stromatolites are thefossalized remains of a colony or mat ofCyanobacteria that normallyexhibits either a domed or a column-like shape. The oldest known stromatolites occur in rocks in Warrawoona Group of Western Australia and are some 3.4 to 3.5 billion years old. Homo sapiens lived from 250,000 years ago.
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It is time to close the book on infectious diseases, and declare the war against pestilence won
Spellberg B: Dr William H, Stewart: mistaken or maligned?
Clin Infect Dis 2008, 47:294.
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Paradox 1Paradox 1• Antibiotics initially led to poorer
hospital hygiene
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““Haven’t you heard Haven’t you heard – we’ve got MRSA sweeping – we’ve got MRSA sweeping the hospital”the hospital”
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MRSA
Infection Control
MRSA
Infection Control
Just the hands
Frickerson!
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Environmental contaminationEnvironmental contamination
20-50 % antibiotic use in humans not
necessary
40-80% antibiotics used for animals
questionable value
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IntegronIntegronIntegronIntegron
conserved conserved DNADNA 4FQ4FQintegraseintegrasetettetmacrolidemacrolide-lactam-lactampromoterpromoter
Amino-Amino-glycosideglycoside
conserved conserved DNADNA
MULTIPLE ANTIBIOTIC RESISTANT MULTIPLE ANTIBIOTIC RESISTANT DETERMINANTDETERMINANT
GENE CASSETTESGENE CASSETTES
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Paradox 3Paradox 3• Antibiotics increase infections
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Deaths from HAI, USADeaths from HAI, USA
• 1992………..13,300
• 2008……… 100,000Antibiotics and Resistance,(IDSA
website/Researchandmarket.com)
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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
RS
AT
otal ab
. Co
nsu
mp
tion
: DD
D/1000 b
ed d
aysRelationship between % MRSA and antibiotic use.
(3rd GC, FQ, MAC)
Emerg. Inf. Dis 2004, 1432
3rd GC lags = 4 – 7 monthsFQ lags = 4 & 5 monthsMAC lags = 1 – 3 months
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CID 2008:46 (Suppl 1) S25
MA of Risk of C diff v Antibiotic Exposure
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HPS Reported bacteraemiaHPS Reported bacteraemia
0
500
1000
1500
2000
2500
3000
Klebsiella E.coli
2001
2002
2003
2004
2005
2006
2007
2008
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The Antibiotic Resistance Spiral
Adapted from: J. Carlet.
resistance
RESISTANCE
CONCERN
SELECTION
BROAD-SPECTRUMEMPIRIC THERAPY
cross-transmission
dosageduration
new antibiotics(promotion from pharmaceutical
industry)
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Current MDR ConcernsCurrent MDR Concerns
• ESBLS• 16S rRNA Methylase +/- ESBL/MBL. HL res to
all aminoGs, transposon/plasmid born• PMQR +/- ESBL. (Gyr/Topo,efflux and
hydrolysis)• Carbapenemases• Acinetobacter• Burkholderia• Stenotrophomonas
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ESBLsESBLs
• TEM(Temoneira)/SHV(sulhydril) (over 100 in Enterobacteriaceae)
• CTX-M (from Kluyvera spp)
• VEB/PER etc (uncommon in UK)
• OXA(Class D,Turkey)
• IRTs
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Courtesy of D Livermore, HPA
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CarbapenemasesCarbapenemases
• Class A inhib by clavulanate eg KPC (plasmid), SME IMI/NMC-A, GES
• Class B metalloenzymes eg IMP(SE Asia), VIM (Europe) aztreonam susc, plasmid/integron located
• Class C, CMY-10 in an E. aerogenes
• Class D in A. baumannii
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Pseudomonas aeruginosa: proportion of invasive isolates resistant to carbapenems in 2006
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McGowan & Tenover ‘04 Nature Reviews Microbiology 2 251
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SPAIN – EARSS data 2007
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Incidence of inadequate antibiotic therapy in hospitalsIncidence of inadequate antibiotic therapy in hospitals
0
10
20
30
40
50
60
70
Ref (1) Ref (2) Ref (3) Ref (4) Ref (5)
N=147
N =1255
N = 34
n = 146
N = 27
Bloodstream infection
Nosocomial/Ventialor-associated pneumonia
Ibrahim et al Chest 2000; 118:146-155Leibovici et al J Intern Med 1998; 244:379-386Luna et al Chest 1997; 111:676-685.Alvarez-Lerma Inten Care Med 1996; 22:387-394Rello et al Am J Respir Crit Care 1997; 156:196-200
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0
20
40
60
80
100
Ref (1) Ref (2) Ref (3) Ref (4) Ref (5)
Adequate therapy
Inadequate therapy
Bloodstream infections
Nosocomial/Ventilator-associated pneumonia
Influence of inadequate antibiotic therapy on mortality
Ibrahim et al Chest 2000; 118:146-155
Leibovici et al J Intern Med 1998; 244:379-386
Luna et al Chest 1997; 111:676-685.
Alvarez-Lerma Inten Care Med 1996; 22:387-394
Rello et al Am J Respir Crit Care 1997; 156:196-200
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For Septic shock: Each hour delay in antibiotic initiation over the first 6 hours has been shown to
be associated with an average decrease in survival of 7.6%
For Septic shock: Each hour delay in antibiotic initiation over the first 6 hours has been shown to
be associated with an average decrease in survival of 7.6%
Adapted from Kumar A, Critical Care medicine 2006 Vol.34, No 6.
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ViResiST
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ConclusionsConclusions
• Antibiotic resistance is increasing at an unprecedented rate.
• The correct empiric therapy saves lives (not too little) and prevents resistance (not too much)
• Local data is essential to inform local empiric therapy protocols.
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Thanks