antimicrobial resistance - current threats camilla wiuff november 2010
TRANSCRIPT
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Antimicrobial Resistance - Current Threats
Camilla WiuffNovember 2010
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Antimicrobial resistance - a threat to public health and patient safety• Infections with resistant organisms
are associated with increased morbidity and mortality
• Extended stays in hospitals• Reduced treatment options • Untreatable infections• Increased healthcare costs
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Evolution of antibiotic resistance is a consequence of selective pressure
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Selection for resistance
antibiotic
Antibiotic not effective
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Antibiotic Use
~ 80% of antimicrobial use in humans was for patients in the community
Overview of AntimicrobialUsage and BacterialResistance in Selected Humanand Animal Pathogens in theUK: 2007 – Joint Report
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Use of antibiotics in Scotland 1994-2009
in primary care
SAPG – Report on Antimicrobial Use and Resistance – draft (publication January 2011)
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Qualitative measures of antimicrobial prescribing in hospitals – ESAC Point Prevalence Survey 2009
SAPG – Report on Antimicrobial Use and Resistance – draft (publication January 2011)
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The association between antimicrobial use and resistance is complex and difficult to measure
• Time delay (>1-2 years) between use and the development of resistance
•Co-selection by other antibiotics (due to linked resistance genes)
•Co-selection by metal-ions, disinfectants, other agents/chemicals
•Selection of non-specific resistance mechanisms (e.g. efflux pumps, outer membrane porins)
•Spread of highly resistant (and fit) clones and plasmids
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Association between use and resistance at country level (ESAC and EARSS data)
Penicillin non-susceptible S. pneumoniae
Fluoroquinolone resistant E. coli
Sande-Bruinsma, EID, 14, Nov, 2008
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Gram-negatives
• Penicillinase indentified in the laboratory, 1940
Penicillin entered clinical use
• Penicillinase quickly spread in clinical isolates
Broad-spectrum antibiotics became available in 1950-60’s
• Beta-lactamases with increasing spectrum 1950-1970
Cephalosporins became available in the 1970’s
• Extended spectrum beta-lactamases, ESBLs, 1980-1990 (TEM, SHV, CTX-M, OXA, AmpC)
Carbapenems became available 1985
• 1996 (2003 EU) carbapenemases (KPC, VIM, OXA, NDM-1)
• 2009- carbapenem-non-susceptible Enterobacteriaceae (CSNEs) – “UNTREATABLE”!
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Emerging carbapenem resistance in Gram-negatives
• Significantly limits treatment options for life-threatening infections
• No new drugs are under development for gram-negative infections
• Resistance mechanisms (carbapenemases) are mobile (spread readily via plasmids)
• Co-resistance to other agents is common
• Surveillance, prudent antimicrobial prescribing and infection control are necessary to limit the spread of carbapenemases
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Surveillance of Gram-negatives in Scotland
• The national surveillance is focussed on bacteraemia
• Clinically important infection (high morbidity and mortality)
• All symptomatic patients are sampled and tested
• Resistance data are comparable with European EARS-Net data from 27 countries
• Resistance in bacteraemia isolates is likely to reflect earlier resistance problems in other infections (UTI, GTI, RTI)
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Cases of bacteraemia and ESBLs in Scotland
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E.coli bacteraemia – Scotland 2009
0
10
20
30
40
50
60
70
ampi
cillin
amox
icillin
co-a
mox
iclav
cefu
roxim
ece
ftria
xone
cefo
taxim
ece
ftazid
ime
gent
amici
ncip
roflo
xacin
mer
open
empi
p/ta
zotri
meth
oprim
CRO/CIP
CRO/GEN
% r
esis
tan
ce
2008
2009
SAPG annual AMR report, due Jan 2011
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• Large increase in reporting of bacteraemia to HPS (2008-2009)
• Resistance to all clinically important antibiotics (aminopenicillins, cephalosporins, fluoroquinolones, aminoglycosides)
• No change in %ESBL (~7-8 %)
• Stabilisation in resistance proportions in 2009
• Significant decrease in (%) resistance to 3rd gen. cephalosporins in E. coli
• No carbapenem resistant bacteraemia reported in 2009 (but 10 isolates of other types)
• Are we starting to see an effect of antimicrobial stewardship programmes?
Gram-negative bacteraemia – Trends Scotland
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Multi-drug resistance
MDR: resistant to at least 1 antibiotic in 3 antimicrobial categories
XDR: resistant to all but 2 antimicrobial categories
PDR: resistant to all antimicrobial categories
Magiorakos et al., ECDC, draft definitions, 2010
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ESBL production among cephalosporin resistant bacteraemia isolates
• E. coli7.5% of all E. coli bacteraemia50% of isolates resistant to cefuroxime (2. gen)70% of isolates resistant to ceftriaxone/cefotaxime/ceftazidime
(3. gen)
• K. pneumoniae8.8% of all K. pneumoniae bacteraemia45% of isolates resistant to cefuroxime (2. gen)65% of isolates resistant to ceftriaxone/cefotaxime/ceftazidime
(3. gen)
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Carbapenemases in Scotland in 2009
Isolates characterised by ARMRL, Colindale:• 4 isolates of Pseudomonas aeruginosa (VIM)• 2 Klebsiella pneumoniae (KPC)• 3 Enterobacter (VIM, KPC)• 1 Citrobacter freundii (NDM)
• 4.7% (9/192) of Pseudomonas aeruginosa bacteraemia isolates were resistant to meropenem
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Epidemiology of KPC carbapenemases
• Klebsiella pneumoniae clones of KPC carbapenemases circulating in USA, Israel and Greece
• Sporadic isolations of KPC in South America, Europe, UK
• Further spread in China, Colombia, Puerto Rico
• KPC have been reported in E. coli, Salmonella cubana, Enterobacter, Proteus mirabilis, Citrobacter freundii, Serratia marcescens, P. aeruginosa, Acinetobacter baumannii
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NDM-1 carbapenemases in the UK• Carbapenemase-producers were sporadic in the UK in 2003-2007
• Isolations of carbapenemase-producers increased in the UK 2008-2009
• First NDM-1 isolated in 2008 in the UK
• In 2009, NDM-1 became the predominant carbapenemase in Enterobacteriaceae (44%) in the UK
• 37 isolates of NDM-1 were referred from 25 UK laboratories in 2008-2009 (urines (15), blood (3), burns/wound (4), sputum (2). CL (1), throat (1), unknown (3))
• Average age of UK patients: 60 years (range 1-87) (India: 36 years)
• 17 out of 29 patients with NDM-1 had been in India/Pakistan within the past year (14 had been in hospitals during their travels)
• Most UK carbapenemase-producers concurrently carry additional beta-lactamases (CTXM-15, CMY-4), fluoroquinolone and gentamicin resistance mechanisms
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Carbapenemases - Is there a link to medical tourism?
Kumarasamy,
Lancet Infection, Aug 2010
Clones and plasmids are transported between continents in the human gut flora – most dissemination is undetected!
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Carbapenemases – UK and India
• UK: Non-clonal isolates (NDM-1 on chromosome, variable plasmids, conjugates easily)
• Chennai (South India) : Non-clonal isolates (NDM-1 on plasmids, variation of plasmids, conjugates easily)
• Haryana (North India): Clonal isolates – outbreak?
• There were no genetic links between isolates from India and the UK (possibly due to too few isolates investigated)
• UK is the first Western country to report widespread occurrence of NDM-1
• Most patients in Haryana and Chennai were from community-acquired infections in younger people (mean=36 yrs)
• Non-prescription use of carbapenems in India is of major concern
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Surveillance of carbapenemases in Scotland
• Susceptibility testing in diagnostic laboratories
• Sensitive, reliable and standardised testing methodology is key – automated VITEK systems are part of the Scottish strategy for obtaining high quality data on emerging carbapenem resistance
• Further investigations by ARMRL, Colindale to determine resistance mechanism and subtype
• HPS AMR-alert system that prompts laboratories to unusual susceptibility results (in specific drug-bug combinations) – weekly
• Annual report on resistance in bacteraemia isolates
• Development of national surveillance of resistance in UTI (proportional system)
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Resistance in Gram-positives
• Less of a concern in Scotland at the moment
• Newer antibiotics with activity against Gram-positives are available (linezolid, daptomycin, tigecycline)
• Except for MRSA, resistance rates are generally low among Gram-positive in Scotland
• Gram-positive exhibit a remarkable ability to develop antibiotic resistance through a range of mutational events and gene transfers, followed by spread of successful resistant clones
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Glycopeptide resistance
• Glycopeptides: vancomycin and teicoplanin
• Used for life-threatening Gram-positive infections – last resort drugs
• Vancomycin Resistant Enterococci (VRE) reported in 1987-1988 in UK (high-level resistance, later low-level resistance reported)
• Vancomycin resistance in Enterococcus faecium (VRE) in Scotland - 17% in 2008, 28% in 2009
• In 2008, Ireland, Greece and the UK reported >25% VRE (and increasing trends)
• Enterococci are a common cause of bacteraemia
• Glycopeptide resistance transfer via plasmids to more pathogenic bacteria such as MRSA – is a concern
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Mupirocin
• Mupirocin (pseudomonic acid A) is a topical antibiotic
• Used to treat skin and soft tissue infections
• Used to eradicate staphylococcal nasal carriage in patients pre-operatively
• Used to eradicate MRSA in healthcare facilities
• High-level resistance leads to treatment failure
• It is a concern that the implementation of the national MRSA screening programme will lead to increased mupirocin resistance
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Summary
• Evolution and spread of antibiotic resistance is a consequence of how antibiotics are used and mis-used in humans, animals and the environment.
• Large efforts are going into improving the quality of antimicrobial prescribing and limiting the spread of resistance in NHS Scotland – activities are coordinated by SAPG
• A reduced number of prescriptions was seen in primary care in Scotland in 2009 compared to 2008 (co-amoxiclav, cephalosporins and fluoroquinolones)
• Resistance rates in Gram-negative bacteraemia stabilised in 2009, and cephalosporin resistance decreased.
• Carbapenem (and multidrug) resistance in Gram-negatives (in particular Enterobacteriaceae) is a worldwide threat to public health
• Increasing glycopeptide resistance in Enterococci (e.g. VRE) and increasing mupirocin resistance in S. aureus is causing concern
• Improved quality of antimicrobial prescribing and standardised susceptibility testing are key to monitoring and limiting emerging resistance problems
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The HPS-ISD AMR Team
• Anne Eastaway• Camilla Wiuff • William Malcolm• Julie Wilson• Tracey Cromwell• Marion Bennie • A-Lan Banks• David Henderson• Ernest Amaziro• HPS, ISD, NSS IM&T departments
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"Don't forget to take a handful of our complimentary antibiotics on your way out“
New Yorker Jan 12, 98