antibiotica: overleven we de resistentie? · within sciensano a specific mission nsih.be for the...
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Healthcare associated infections & Antimicrobial resistance
Antibiotica:
overleven we de resistentie?
KNOPICS – 7 juni 2019
Within sciensano
a specific mission NSIH.be
For the containment of healthcare-associated infections in hospitals
and nursing homes we provide :
- standardized definitions and tools,
- national reference data on incidence of nosocomial infections and
antimicrobial resistance,
- outbreak support in collaboration with competent authorities.
Enkele gegevens
Enterobacteriaceae
Enterobacteriaceae
Enterobacteriaceae
Enterobacteriaceae
De Pauw et al., 2018
Fonguh Sylvanus, 2016 www.nsih.be
Tabel 5 : Percentage van handhygiënecompliantie volgens de 5 indicaties voor en na campagne op alle betrokken afdelingen (n=136), 2014 - 2015
De 5 indicaties Voor campagne (%)
Na campagne (%)
Verschil (%)
Voor patiëntencontact 58,9 70,6 +11,7
Na patiëntencontact 76,7 84,4 + 7,7
Voor een zuivere of invasieve handeling 61,6 73,7 +12,1
Na blootstelling aan lichaamsvochten of slijmvliezen
79,1 86,9 +7,8
Na contact met de directe patiëntenomgeving 67,6 77,3 +9,7
%=Gemiddeld percentage (hoger gewicht voor instellingen met hoger aantal observaties)
Ziekenhuisbreed
Intensieve zorgen
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
0
20
40
60
80
100
Med
ian
inci
de
nce
of
no
soco
mia
l MR
SAin
acu
te c
are
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spit
als
pe
r 1
00
0 a
dm
issi
on
s
Mea
n h
and
hyg
ien
e co
mp
lian
ce (
%)
Pre campaign Post campaign
MULTIDRUG RESISTANT ORGANISMS
Microorganism Resistance
MRSA Staphylococcus aureus Met(h)icillin
ESBL+ Enterobacteriaceae (E.coli / Klebsiella / …)
3de generation cephalosporins
CPE Enterobacteriaceae Carbapenems
VRE Enterococcus faecalis/faecium Vancomycin
MDR Pseudomonas/Acinetobacter Intrinsic + different classes
CDIF Clostridium difficile Intrinsic (Anaërobic)
Manyother…
e.g. Candida auris Intrinsic antibacterial, multiantifungal resistance
Courtesy: Latour & Jans
MRSA & ESBL in Belgian hospitals
ECDC PPS
ECDC PPS 2011-2012 ECDC PPS 2016-2017
HALT-3
www.ecdc.europa.eu
HALT-1: May-September 2010 HALT-2: April-May 2013 HALT-3: 2016-2017
Active Healthcare associated infection:
AMR (resistant) & AMS (suscept
All infections that met the criteria of an active HAI (associated to a stay in an acute care hospital) had to be included. Th e
following definition of an active HAI was applied: an infection where signs and symptoms were present on the day of the
PPS, or where signs and symptoms were present in the past and the patient was (still) receiving treatment for that infection
on the day of the PPS. The symptoms had to appear on day 3 or later after admission (day of admission = day 1). It could
also be earlier in case the patient was readmitted less than 48 hours after a previous admission to an acute care hospital.
Exceptions to these criteria were also made for SSIs, infections with an invasive device and Clostridium difficile infections. In
case of an active SSI, the onset of the symptoms had to be occurred within 30 days of the operation (or within 90 days in case
of a surgery involving an implant). If an invasive device was placed on day 1 or 2 of the admission, a HAI could emerge before
day 3. Finally, Clostridium difficile infections present on admission (or developped within two days) with an onset less than 28
days after the discharge from an acute care hospital also had to be included (6).
Results
HAIs = healthcare associated infections; MO = micro-organism; BSI = bloodstream infections, GI= gastro-intestinal, SSI = surgical
site infections, UTI = urinary tract infections
HAIs: main groups / isolated MOs ECDC PPS 2017
Pneumonia
(21.6%)
SSI (16.9%)
UTIs (21.3%)BSI (11.5%)
GI infections
(9.6%)
Top 8 most isolated MOs (% of total HAIs)
Escherichia coli (17.8%)
Staphylococcus aureus (8.9%)
Pseudomonas aeruginosa (5.2%)
Enterococcus faecalis (4.8%)
Klebsiella pneumonia (4.2%)
Enterobacter cloacae (4.2%)
Staphylococcus epidermidis (4.1%)
Clostridium difficile (3.3%)
Point Prevalence Survey – Infections nosocomiales
Belgique 2017
(Vandael et al . , Sciensano 2018 www.nsih.be)
Number (%) of infections by main HAI
group
Patient Specialty
Total Medicine Surgery Intensive care Geriatrics
Pneumonia
Other lower respiratory tract infection
197 (21.6%)
45 (4.9%)
69 (24.6%)
10 (3.6%)
20 (9.1%)
2 (0.9%)
49 (36.3%)
14 (10.4%)
43 (25.9%)
10 (6.0%)
Urinary tract infection 194 (21.3%) 57 (20.3%) 39 (17.8%) 12 (8.9%) 54 (32.5%)
Surgical site infection 154 (16.9%) 16 (5.7%) 95 (43.4%) 15 (11.1%) 5 (3.0%)
Bloodstream infection 105 (11.5%) 40 (14.2%) 21 (9.6%) 24 (17.8%) 15 (0.9%)
Gastro-intestinal infection 87 (9.6%) 32 (11.4%) 15 (6.9%) 9 (6.7%) 22 (13.3%)
Systemic infection 40 (4.4%) 20 (7.1%) 6 (2.7%) 5 (3.7%) 5 (3.0%)
Skin and soft tissue infection 35 (3.8%) 14 (5.0%) 8 (3.7%) 1 (0.7%) 7 (4.2%)
Eye, ear, nose or mouth infection 19 (2.1%) 10 (3.6%) 1 (0.5%) 0 3 (1.8%)
Catheter-related infection 14 (1.5%) 7 (2.5%) 3 (1.4%) 2 (1.5%) 2 (1.2%)
Cardiovascular infection 9 (1.0%) 3 (1.1%) 2 (0.9%) 3 (2.2%) 0
Bone and joint infection 6 (0.7%) 2 (0.7%) 3 (1.4%) 0 0
Central nervous system infection 4 (0.4%) 0 3 (1.4%) 1 (0.7%) 0
Reproductive tract infection 2 (0.2%) 1 (0.4%) 1 (0.5%) 0 0
Specific neonatal cases 0 0 0 0 0
Total 911 281 (30.8%) 219 (24.0%) 135 (14.8%) 166 (18.2%)
Table 5: Distribution of main groups of healthcare-associated infections (HAI), ECDC point prevalence survey (PPS) 2017, BelgiumECDC = European Centre for Disease Prevention and Control
HAI = Healthcare associated infection = nosocomiale = zorggeassocieerde =
zorggerelateerde = zorginfectie ~ ziekenhuisverworven
Focus on ENT (Ear/Nose/Throat) – Belgium
acute care hospitals 2017
ECDC-PPS data 2017 – extra analyses NKO – 20190524 Totaal aantal geïncludeerde patiënten in ECDC-PPS 2017: N=11800 Aantal patiënten met patient specialty SURENT (surgery ear/nose/throat): N=43 (0.36%)
Patiënten met minstens één antimicrobieel middel: N=15 • Indicaties: SP N=4, CAI N=7, HAI N=3, unknown N=1
Patiënten met minstens één HAI: N=3 • UTI, pneumonie, SSI
Voor alle patiënten (N=11800, 4103 AM behandelingen, 911 HAIs) 1. Totaal aantal AM behandelingen met ENT als diagnose: N=75 (1.83%)
1.1. Meest frequent voorgeschreven AM: amoxicilline+clavulaanzuur (J01CR02, N=28), amoxicilline (J01CA04, N=14), fluconazole (J02AC01, N=9)
1.2. Prevalentie patiënten met een AM behandeling met ENT als diagnose: 0.64% (75/11800) 2. Totaal aantal EENT (eye/ear/nose/throat) infecties als HAI: N=19 (2.09%)
2.1. Conjunctivitis: N=3, ear mastoid: N=1, oral cavity: N=5, sinusitis: N=4, upper respiratory tract: N=4, not specified: N=2
2.2. Prevalentie patiënten met een EENT infectie als HAI: 0.16% (19/11800)
6.97%
Courtesy Eline Vandael & Katrien Latour
Antimycotic use 2003-2016 Belgium
Hospitals stratified by type
Goemaere et al., Mycosis 2019
Conclusion on ‘PPS Pictures’
HAI prevalence (%) in Belgium• Hospitals: 7.3• LTCFs: 3.5
Estimated number of patients per year with an HAI in Belgium• Hospital: 111 276• LTCFs: 170 090
No decline of HAI occurrence in healthcare facilities Challenge for LTCFs
• Limited resources for infection prevention and control• Home-like facilities
Long term care facilities: residents features
Titre de votre présentation - Oct 2013
Nursing homes characteristics 2015 (n=29) 2011 (n=60)Total n beds 3059 5608Size of NH: mean n beds per NH 105 (41-201) 94 (31-187)
<75 beds 17.2% 36.7%75-150 beds 69.0% 53.3%>150 beds 13.8% 10.0%
NH with high-skilled beds proportion> 65% 37.9% 21.7%
Residents characteristics 2015 (n=1441) 2011 (n=2791)Mean age in years (median) 84.7 (86) 84.8 (86)Male gender 25% 22%Median length of stay in months (IQR) 29 (12-60) 30 (12-61)Stay in a single-bed room 82% 76%Autonomy level
High level of dependency (modified Katz scale C or CD) 49% 45%
Low mobility level (wheelchair or bedridden) 45% 47%Incontinence (urinary or fecal) 62% 57%Disorientation (time or space) 53% 48%
Charlson’s comorbidity index- None or mild (score 0-1) 35% 32%- Moderate (score 2-4) 54% 55%- Severe (score ≥ 5) 12% 13%Previous antibiotic use in the past 3 months 22% 22%Current antibiotic use at the time of the survey 4% 5%Antacid use at the time of screening 45% 33%
Statistically significant (Chi-square test p<0.05) Courtesy Latour Katrien
Total number
of patients
Patients with at least one antimicrobial
N Crude prevalence
(%)
95% CI
Total prevalence 11800 3320 28.1 27.3-29.0
Prevalence by hospital type
Primary 6658 1826 27.4 26.4-28.5
Secondary 2830 793 28.0 26.4-29.7
Tertiary 2312 701 30.3 28.5-32.2
Prevalence by patient
specialty
Medicine 3600 1200 33.3 31.8-34.9
Surgery 2531 916 36.2 34.3-38.1
Intensive care 583 307 52.7 48.6-56.7
Geriatrics 1813 502 27.7 25.6-29.8
Obstetrics/ Maternity 583 73 12.5 9.8-15.2
Healthy neonates 156 3 1.9 0.0-4.1
Neonatology 121 16 13.2 3.1-19.3
Pediatrics 464 153 33.0 28.7-37.3
Psychiatry 823 27 3.3 2.1-4.5
Rehabilitation 903 105 11.6 9.5-13.7
Long-term care 33 8 24.2 9.6-38.9
Mix 28 8 28.6 11.8-45.3
Other 50 2 4.0 0.0-9.4
(Vandael et al., Sciensano 2018 www.nsih.be)
Table 2: Crude prevalence of patients with at least one antimicrobial, ECDC point prevalence survey (PPS) 2017, BelgiumECDC = European Centre for Disease Prevention and Control, CI = confidence interval; N = number of patients with at least one antimicrobial
Point Prevalence Survey – Zorginfecties
België 2017
ESAC-Net: ambulant care 2016
ATC DID in 2015 DID 2016
J01 29.30 27.51
J02+D01BA 3.14 3.11
ESAC-Net: hospitals 2016
ATC DID in 2015 DID 2016
J01 1.67 1.63
J02+D01BA 0.09 0.08
Antimicrobial consumption
Eline Vandael
AMTABU, WIV-ISP 2014
http://www.medscape.com/viewarticle/868987_print 29/09/2016
http://www.medscape.com/viewarticle/868987_print 29/09/2016
The FDA's Antimicrobial Drugs Advisory Committee (ADMAC) and the Drug
Safety and Risk Management Advisory Committee met jointly to discuss the use
of fluoroquinolone antibacterial drugs for treatment of acute bacterial sinusitis
(ABS), acute bacterial exacerbation of chronic bronchitis in those with chronic
obstructive pulmonary disease (ABECB-COPD), and uncomplicated urinary tract
infection.
Fluoroquinolone labeling currently has warnings about the risks for tendonitis,
tendon rupture, central nervous system effects, peripheral neuropathy,
myasthenia gravis exacerbation, QT prolongation and Torsades de Pointes,
phototoxicity, and hypersensitivity. But panel members called for stronger
wording, with some suggesting the risks be called out with a black box warning.
The panel also voted overwhelmingly that the benefits and risks for the systemic
fluoroquinolone antibacterial drugs do not support the current labeled
indications for the treatment of ABS (unanimous), ABECB-COPD (2 yes, 18
no, 1 abstention), or uncomplicated urinary tract infection (1 yes, 20 no).
Fluoroquinolones currently approved for one or more of these illnesses are
ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, and gemifloxacin.
http://www.medscape.com/viewarticle/854067 - Nov 6 2015
[ I n t e r v e n t i on R e v i e w ] 2 0 1 4 C OC H R A N E
B e t a l a c t a m a nt i b i o t i c m onot he r a py v e r s us be t a
l a c t a m - a mi nog l yc os i de a n t i b i o t i c c ombi na t i on
t he r a py f o r s e ps i s
Duur behandeling lage
urineweginfecties (UWI)
…several studies showed that trimethoprim, pivmecillinam, amoxicillin and certain
cephalosporins are less effective than fluoroquinolones, co-amoxiclav or cotrimoxazole - given
the same treatment duration (Ewer 1988; Gallacher 1986; Hooton 1995; Jonsson 1990). These
findings may explain the better bacterial efficacy of a 3-day course of ofloxacin compared to a 7-
day course with cephalexin (Raz 1996).
Some antibioticsmay not be appropriate for short course treatment (1 to 3 days) for
pharmacokinetic reasons. Several penicillins and cephalosporins have a relatively short half-life
(1 to 2 h in young people, 2 to 4 h in older people), whereas the fluoroquinolones, cotrimoxazole
and fosfomycin have longer half-lives (4 to 12 h, 8 to 13 h, 4 to 50 h respectively) (Compendium
1998; McCue 1992). Indeed, Norrby 1990 has shown in his systematic review, that the optimal
treatment duration for lower, uncomplicatedUTI in women (of all age) depends on the type of
antibiotic: three days for cotrimoxazole and the fluoroquinolones and five days for beta-
lactam antibiotics.
Lutters M, Vogt-Ferrier NB. Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in
elderly women. Cochrane Database of Systematic Reviews 2002, Issue 3. Art. No.: CD001535. DOI: 10.1002/14651858.CD001535.
Diergeneeskunde België
37
Persoons et al., 2012 Callens et al., 2012 Catry et al., under revision Pardon et al., 2012
0
100
200
300
400
500
600
poultry pigs dairy cattle beef cattle veal calves
Tre
atm
en
t in
cid
en
ce o
n U
DD
(an
imal
s/1
00
0 d
aily
tr
eae
d)
Antimicrobial use in livestock in Belgium
Courtesy: B. Pardon, UGent
According to type of hospitals
• Competent authorities
Outbreak
Surveillance & notification
• experts
Outbreak support
Reference
lab
WIV
ISP
Extra cost MDRO
(hospital ES, 2005-2012)
A total of 571 admissions with bacteremia matched the inclusion criteria and 82,022 were
included in the control group. The mean cost was € 25,891 for admissions with bacteremia
and € 6,750 for those without bacteremia
Ligduur en opnames,
Maasstadt, NL
43Remark: For confidentiality reasons, the locations of the bullets representing
individual hospitals do not correspond to the real location of the hospitals in the
province.
Entérobactéries productrices de carbapénémases (CPE) à partir de prélèvementscliniques: par type de carbapénémase et par province:
2012 - 2014
CPE en MRS (2015):
1 seul porteur (OXA-
48)
dans une MRS
Vlaanderen:
OXA-48 = 95% de tous
les CPE
Wallonie:
KPC = 49%
OXA-48= 39%
Bruxelles:
OXA-48: 64%
KPC: 18%
NDM: 10%
VIM: 6%
Surveillances
&
FEEDBACK
MRSA
Campaigns
IndicatorsICU & SSI
Blood stream
infections
C. difficile
Gram -
BeH-SAC
Rectangle = mandatory
VRE
Burden = ‘Zorglast voor de maatschappij’
PLOS Medicine, 2016
We estimated that 2,609,911 new cases of HAI occur every year in the European Union and European Economic Area (EU/EEA). The
cumulative burden of the six HAIs was estimated at 501 DALYs per 100,000 general population each year in EU/EEA. HAP and HA
primary BSI were associated with the highest burden and represented more than 60% of the total burden, with 169 and 145 DALYs per
100,000 total population, respectively. HA UTI, SSI, HA CDI, and HA primary BSI ranked as the third to sixth syndromes in terms of
burden of disease. HAP and HA primary BSI were associated with the highest burden because of their high severity. The cumulative
burden of the six HAIs was higher than the total burden of all other 32 communicable diseases included in the BCoDE 2009±2013
study. The main limitations of the study are the variability in the parameter estimates, in particular the disease models' case fatalities, and
the use of the Rhame and Sudderth formula for estimating incident number of cases from prevalence data.
PLOS Medicine | DOI:10.1371/journal.pmed.1002150 October 18, 2016
Newsflash – 2019 Sciensano
Assessment of the burden of antimicrobial resistance in Europe & Belgium Catry B., Vandael E., Latour K., Mertens K, Devleesschauwer B. A recent international study estimated the burden of disease of antimicrobial resistance, for the first time at EU/EEA level and applying the Disability adjusted life years (DALY) methodology. Data from both the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections and antimicrobial use (ECDC PPS, 2011-2012) and data from the eight bacterial species frequently isolated from blood or cerebrospinal fluid (invasive isolates) reported to the European antimicrobial resistance surveillance network (EARS-Net 2015) were combined. Remind that this approach is an underestimation of the total burden for the community at large, since for this analysis only the predominant types of healthcare associated infections (ca 88%) and only acute care hospitals were included. Throughout Europe, this study concluded that an estimated number of 33 000 casualties are annually attributed to antimicrobial resistance. For Belgium, this number has been estimated at 530 deaths annually. Among these, 240 and 70 could be attributed to third-generation cephalosporin resistant Escherichia coli and Klebsiella pneumoniae (excluding those resistant to colistin and/or
carbapenem), respectively, and 133 to MRSA (methicillin resistant Staphylococcus aureus). Further actions should focus on a reduction of inappropriate antimicrobial consumption and adequate preventive measures including hand hygiene and other infection control policies. Further reading: https://ecdc.europa.eu/en/news-events/33000-people-die-every-year-due-infections-
antibiotic-resistant-bacteria The article is available here: www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30605-
4/fulltext
C. difficile
Valencia et al., 2016, in preparation - WIV
Figuur 1Non-pediatric antimicrobial use in the community in Daily Defined Doses per 1000 inhabitant days. Belgium 2007-2013
Incidence of Clostridium difficile infections
in acute care hospitals, Belgium 2008-2016
50* Hospital associated CDI: onset of symptoms 2 days or more after admission in the declaring
hospital *Acute care hospitals: average length of stay <14 days,
0.00
0.50
1.00
1.50
2.00
2.50
2008 2009 2010 2011 2012 2013 2014 2015 2016
N/1
00
0
ad
mis
sio
ns
Total
Hospital-associated
Faecal Microbiota Transplantation by Colonoscopy vs. Vancomycin for the Treatment of
Recurrent Clostridium Difficile Infection
G. Cammarota; L. et al. Aliment Pharmacol Ther. 2015;41(9):835-843.
Background Faecal microbiota transplantation (FMT) from healthy donors is considered an
effective treatment against recurrent Clostridium difficile infection.
Aim To study the effect of FMT via colonoscopy in patients with recurrent C. difficile infection
compared to the standard vancomycin regimen.
Methods In an open-label, randomised clinical trial, we assigned subjects with recurrent C.
difficile infection to receive: FMT, short regimen of vancomycin (125 mg four times a day for 3
days), followed by one or more infusions of faeces via colonoscopy; or vancomycin,
vancomycin 125 mg four times daily for 10 days, followed by 125–500 mg/day every 2–3 days
for at least 3 weeks. The latter treatment did not include performing colonoscopy. The primary
end point was the resolution of diarrhoea related to C. difficile infection 10 weeks after the end
of treatments.
Results The study was stopped after a 1-year interim analysis. Eighteen of the 20 patients
(90%) treated by FMT exhibited resolution of C. difficile-associated diarrhoea. In FMT, five
of the seven patients with pseudomembranous colitis reported a resolution of diarrhoea.
Resolution of C. difficile infection occurred in 5 of the 19 (26%) patients in vancomycin (P <
0.0001). No significant adverse events were observed in either of the study groups.
Conclusions Faecal microbiota transplantation using colonoscopy to infuse faeces was
significantly more effective than vancomycin regimen for the treatment of recurrent C. difficile
infection. The delivery of donor faeces via colonoscopy has the potential to optimise the
treatment strategy in patients with pseudomembranous colitis.
Transplantation in
our socio-economical perspective
Indication AB*
AB treatment
Dysbacteriosis*
Diagnosis Clostridium difficile*
Treatment: tox B antibodies
Transplantation*
300 euro : p.o.
1000 euro : endoscope
Aliment Pharmacol Ther. 2017;46(5):479-493.
Slotbeschouwingen
Intrinsieke resistentie en verworven resistentie accumuleert in het enorme
microbioom van het spijsverteringsstelsel. De huid is controleerbaar.
• Verworven resistentie is te ‘duiden’
(530 slachtoffers in acute ziekenhuizen).
• Antibioticum - gevoeligheid en intrinsieke resistentie is een geruisloos
taboe
(2000-2500 slachtoffer in acute ziekenhuizen).
Toekomst is afstappen van lange combi-therapiën, met uitgesteld voorschrift
en duidelijke informatie naar patiënt of familie.
• Acknowledgements:
• The NSIH team, ECDC, BAPCOC
• The labs, NRCs & hospitals & nursing homes
Slides available on: www.nsih.be