Transcript Concerns of antibiotics resistance in Europe

1.2
1
ceftazidime
0.8
M
I
C
fosfomicina
0.6
nitrofurantoina
0.4
ciprofloxacina
0.2
imipenem
0
netilmicina
-0.2
amox+clav
E.Coli
E.Coli
E.Coli
E.Coli
E.Coli
E.Coli
E.Coli
E.Coli
E.Coli
E.coli
amikacina
In European countries, antimicrobial resistance has been
monitored in selected bacteria from humans since 1998
through the European Antimicrobial Resistance Surveillance
System (EARSS)
Funded by the European Commission, EARSS
is an
international network of national surveillance system
intended to collect comparable and reliable resistance data.
The purpose
of EARSS is to document variations in
antimicrobial resistance over time and place and to provide
the basis for the assessment and the effectiveness of
prevention programs and policy decision .
Slovakia
The Question is
Have all microorganisms, responsible
for UTI, become more resistant
Are there any differences between European
Countries
Why has this happened
Are there any solutions
18
Countries
The importance of co-selection is illustrated by sulfamethoxazole resistance in Sweden
an Denmark (16% vs 21%);the frequencies are very similar despite the fact that
sulphonamides were abandoned in Sweden in the 1970s but are still extensively used in
the treatment of UTIs in Denmark. However, trimethoprim is used extensively in
Sweden and co-selects for sulphonamide resistance.
A striking finding in the ECO-SENS
survey is the low incidence of
resistance to agents used only
in lower UTI
Meticillinam
Nitrofurantoin
Fosfomycin
Used for >25 years and exibit equally
low levels of resistance in countries
that have used them extensively and in
countries that have not used them.
The fact that resistance to
gentamicin was almost nonexistent in community E.coli is of
no help in the treatment of UTI,
but
means
that
primary
septicaemia originating from
UTIs with E.coli can be treated as
effectively with gentamicin today
as it was 30 years ago.
Eco-sens project
shows that
resistance to any agent is
associated
with
increased
resistance to all other agents
tested, fosfomycin being the
only exception.
The Question is
Have all microorganisms,
responsible for UTI, become more
resistant
Are there any differences
between European Countries
Why has this happened
Are there any solutions
First
author
Sample size and study
population
Sample
material
Blood
Fluit
n=1,918 E. coli isolates
from hospitalized
bacteremia patients
Urine
Barret
n=962 isolates from
general practice pts
with UTI 65.1% E.coli,
23.4% coliform bacteria
n=11,000 isolates from
hospitalized patients with
E.coli infection
Not stated
n=1,044 E. coli isolates
from
general practice patients
with
symptoms of UTI
Urine
n=395 E. coli isolates from
outpatients with UTI
n=110 E. coli isolates
frominpatients with UTI
Urine
n=37 female outpatients
with
E. coli-caused UTI
Urine
Kresken
Vorland
Huovinen
Brumfitt
First author
Northen
Europe EARSS
Simple size –study
population
Sample
material
Prevalence of
resistance %
UK 2003
Farrel
N=E.coli 1291 isolate from
out and hospitalized pts
8 centers
urine
Amox: 48,7 - Amoxclav: 22SMT:37,7- Cefur:31,4Cipr:4,2
Sweeden
Kronoberg
country 2004
Storby
N=1014 distribution of
Species for two aggregated 4
yperiods (1990–1993 and
1998–2001) in the age groups
0–2 and 18–50 years
urine
2001 Trim: 17 Amp: 28
Fluor
from 0 to 3
Germany
Freiburg
Retrospective
anaysis 2004
Haller
N.636 Strains isolated from in
and outpts with simptoms of
UTI in 2 period (’97-’99-01)
urine
UK (2004)
Ireland
Reynolds
Switzerland
retrospective
study 2005
Fritzsche
UK 2008
Bean
n=495 E. coli isolates
from hospitalized pts
with bacteremia
Pivm, Cefr, Nitr: 0 in 2001
Amp:50,9 - Sxt:37,4
Cec:28,5 -Net:6,6 Caz:17,8 - Cipr:3 - Imp:2,4
Amox: 56.2
Cipr :11.1
Blood
UK 2008
Two study periods
first period from 1980 to 1991
was based on reference
data provided by a previous
urine
95, 32, 29 to Amp,
Amoxclav, Ceph,
31 to at least
two antibiotics; 13 at three
N=11.855
urine
Amp : 55 - TMT :40
Sensitivity %
Isolates of E.coli
from 31 Norwegian
and 31 Russian F
with UTI
three regions
1998–2005, E. coli
Urine
Nor
AMP 0
0
ME
94
90
GENT 100
97
CIPR 100 100
NITR 97
97
SULPH 39
32
TRIM 77
84
Urine
urine
all uropathogens cultured
hospitalised urological
pts. Duplicate isolates
were eliminated
Rus
no general trend of
increase in resistance
the lowest overall
rates of resistance were
found with piperacillin/
tazobactam; CIPR and
TMS showed
the next favourable
overall activity
First
author
Simple size –study
population
n=7,098 E. coli isolates
from 32
hospital laboratories
prospective
crosssectional
study
165 pathogens isolated
from 165 UTI in 131 pts
(lower UTI in 62%).
Mean age was63.7±49.8
months E. coli (87% of
cases)
isolated from pts
with community
acquired UTIs
1998–2001, 54 638
consecutive samples
were analysed.
10.765 E. coli and other
coliforms were
isolated, of which 5043
(46.8%) were
duplicates.
Sample
material
blood
urine
Amp 59,9 Cipr 19,3 -17,2
2001
21,1 (2003) Cotr 32,6
Amp 74,2 Cotr 61,3
Gent 12,9 Cipr 10,4
Ceftr 10,2
Nitr 5,8
Amik 4,3
1998 – 2001
urine
Amp 74,3
Cef 27,1
Ctx 13,5
Atm 1,7
Nal 19,4
Ofx 7,3
Smt 54,6
Amik 42,0
Cotr 19,3
Imp 16,3
Gent 9
Norf 12,1
Cipt 10,1
Chl 17,4
The Question is
Have all microorganisms, responsible for
UTI, become more resistant
Are there any differences between
European Countries
Why has this happened
Are there any solutions
•urinary malformations
•history of UTI
•presence of urinary catheter
•hospitalization within the last year
•recent treatment with antibiotics
•prophylactic antibiotics exsposure
•the emergence of mutations
Mutation as a cause of antibiotic resistance has the greatest clinical
impact on particular antibiotic classes or in particular bacterial
pathogens.
However, it can also alter the way in which resistance genes are
expressed and, in the longer term, can play a significant role in the
evolution and diversification of acquired determinants.
There is clear potential for mutational resistance to emerge,
including resistance to agents not yet licensed for clinical use, and
this aspect should be investigated during the development process of
new compounds.
Such studies may help to inform the choice of suitable dosing
regimens for agents awaiting a licence, in order to better prevent
the emergence of resistance.
The lack of fimbrial antigens, like the absence of VF
traits, is irreversible but would be adapted to an
appropriate contex in which bacteria, without particular
damage and through avoidance of host defenses,
achieve new niches where they colonize or cause chronic
infections, spreading possible resistance.
In the study of
Ansoy
the gene combinations
aer,afaI
and sfa + pap increased resistance to
tobramycin by between 10% and 87%, wilst for other
gene combinations 100% sensitivity to this antibiotic
was noted.
A similar situation was also observed with
ceftriaxone and ciprofloxacin, where with most
gene combinations nearly 100% sensitivity was
observed against these antibiotics.
The association of ampicillin resistance and
decreased susceptibility to third-generation
cephalosporins with resistance to other non-βlactam antibiotics
(co-trimoxazole, ciprofloxacin, gentamicin) is
the cause of multidrug resistance in nearly 14%
of strains.
This multidrug resistance has important
implications for the empirical therapy of
infection caused by E.Coli.
Ciproflaxicin demonstraded the most
complete in vitro coverage amongst the
antimicrobials
tested
and
hence
emphasizing its great utility as a choice
for empiric therapy of UTI in the UK.
Physicians electing to treat febrile UTI orally
should
use
second
or
third-generation
cephalosporins in order to avoid treatment failure
caused by antimicrobial resistance.
Using ceftriaxone as a marker, third-generation
cephalosporins were found to be fully susceptible.
Antibiotic use is not monitored in Russia, but a
comparatively low level of antibiotics use has been
reported.
Consumption of antibiotics in Norway remains low.
The
high
rates
of
sensitivity
to
antimicrobial agents that were found may
be explained by the low consumption of
antibiotics, resulting in low selection
pressure.
In Bosnia and Erzegovina the intensive usage of
ampicillin and co-trimoxazole during the war period
might have contributed to their high resistance rates.
Similar situation was reported in Serbia.
In poor and underdeveloped countries, where health
organizations donate large amounts of antibiotics to treat
many diseases, overall prevalence of antimicrobial
resistance was notably high, reflecting irrational and
inordinate use of antimicrobial agents.
The Question is
Have all microorganisms, responsible for
UTI, become more resistant
Are there any differences between
European Countries
Why has this happened
Are there any solutions
The major recommendations were as follows:
(i) Increased efforts are needed to reduce the spread
of resistant strains both in the environment and in
hospitals—these include improved hygiene and
decreased use of some antimicrobials.
(ii) Surveillance of resistance is a key factor and
improved technology (e.g. IT systems) is needed to
improve the potential for surveillance data to inform
clinical practice.
(iii) Rapid, sensitive and specific diagnostics are urgently
needed and the issue of reimbursement needs to be
addressed.
(iv) More accurate estimates of the cost-efficacy of
using anti-infectives and diagnostics are urgently
needed.
(v) Vaccine technology is available but is underused for
the prevention of bacterial infections, particularly
those caused by organisms resistant to antimicrobials.
(vi) Incentives are required to encourage large
pharmaceutical
companies
to
partner
small
biotechnology companies, which are more innovative
and have the potential to deliver the new drugs,
diagnostics and vaccines.
This study revealed no obvious trend in the prevalence of drug –
resistant community-acquired UTI in single community.
Prevalence at any time was influenced by a small number of E.coli
clonal groupes.
This observation suggests that the introduction of strains that
are drug resistant into a community plays a greater role in
changing the prevalence of drug-resistant UTI than does the
drug use or prescribing habits in that community..
Prudent prescribing, establishment and use of infection
control guidelines, local monitoring of resistance and
longitudinal surveillance studies are necessary to
minimized and monitor the development of resistance.