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thank you for the invitation to talk
about use and abuse of antibiotics in
neonatology sure
so why should we care about antibiotics
in ethology so as we heard no question
about we have a benefit for the
individual so if you have an infection
and we treat the infection as we heard
from Chris of pure antibiotics is
life-saving we have as well a benefit on
the community level so the benefit is we
can prevent the spread of some of the
infections and as we know things decayed
there is the risk for the community
regarding antibiotic resistance so what
is not so well known but it's coming up
more and more in the last ten years is
there is aware as well a cost on the
individual baby that you're treating
these antibiotics we have the collateral
damage they are doing on the microbiota
and I like to give 23 minutes on this
microbiome because it's very fascinating
if you reading about the microbiome i
probably will change how we are doing
medicine in the next 10-20 years so we
see usually the microbiome as we as
humans are here and they are some
bacteria on the skin in the gut and
they're living with us and the reality
is probably the other way around so we
are living with a community of bacterias
because the bacterial cells are ten
times more than our human cells and in
the genes the factories even around 100
so what happens if you are start with
antibiotic so we start an antibiotic and
the diversity of our bacterial community
is going down this depends on what kind
of antibiotic we are giving and this
depends on how long we are antibiotics
kidding
then after end of treatment there is a
slowly recovery and that diversity is
coming back so we may say as a clinician
at the bedside that's fine we have a
problem for a few days or weeks perhaps
there is a diarrhea but in the end all
is fine
unfortunately we are not ologist so we
are treating our patients in the
variable memorable time so if you look
this is a mouse model where they looked
on the colonization and there is a
impact on the colonization on the immune
system so if you have no colonization of
or if you have a colonization very late
after sometime mouth disease for weeks
we have no idea about this time window
in humans or if you have a conversation
with a low diversity then this my eyes
had a high eg level and they had a trend
to anaphylaxis more this bacteria in the
they interact with our stem cells and
they interact how the Prophet
proliferation of these stem cells
happens so if you are giving antibiotic
then we are intervening in this process
and this maybe is one of the
explanations why giving antibiotics
early in life may have an impact on the
health later in life even more Christian
can't mention that in the morning we
know that the microbiome of the modern
and demand the question if the model is
treated with antibiotics are not has an
impact on the microbiome on the new Nate
and as well for the house later in life
so in summary looking on that on the
literature
these are the diseases that are
currently are associated with antibiotic
treatments early in life we already have
seen this slide by Chris of period with
the antibiotic use and the increased
mortality and chronic lung disease
is and drop disease and of course there
is the questions are baby just thicker
but I think in the end we have to ask
the question and we have to consider
that perhaps the antibiotic itself is
one factor that may be a problem for
mortality and morbidity among and this
infants so to conclude I think everyone
who is prescribing antibiotics should
care about the costs and the benefit of
antibiotics so what we are doing in our
Nick use with antibiotics are we doing
the same know so this is a study from
California they looked in about more
than 100 leak use and they found the 40
fall variation in antibiotic days 40
fall that's that's huge
so there are some units they have very
minimal days and antibiotics and there
are other probably more or less one
hundred percent of the days where
antibiotic days this was independent of
proven infection or neck and it was as
well independent of mortality do we know
what antibiotics we are using or are we
in agreement this is a study from the
Netherlands they looked about ten eq's
and as you can see every color is
another antibiotic class and the picture
is is very cold and at least in the
Netherlands they are not in agreement
but they are giving on their knee cues
how is the situation in Switzerland we
don't know really
we have in the mls data one I came
asking are we giving our tree term
infant below 32 weeks antibiotics for
five days or more without positive
culture and looking on this in 2015 when
the state are true then we have about
three units they are giving more or less
never antibiotics for five days and more
and there are other units are giving
more to third or to have their babies
below 32
weeks antibiotics for five days or more
with negative culture of course we have
to consider that perhaps they have a
different system of culture perhaps
there is a difference in sepsis related
mortality this has to be looked at but i
think it's remarkable and we can
conclude there is a high variability of
antibiotic use in our news so for what
are we using our antibiotics i think
that's similar slides that piece of
clear showed about eighty-nine percent
in this study diseases various study
from the united states were used for
rule out sepsis of culture negative
situations like culture- sepsis
pneumonia so what is about the number
needed to treat with antibiotics to have
a proven infection so i looked in the
literature and they found several
publication wrong from the group from
eric from Luzon they looked on late
preterm babies 222 had an antibiotic
therapy three out of them have the
sepsis so it gives the number of to
treat from 74 in Norway this is the only
published population-based study that I
know regarding antibiotic use in turn
babies they had about 4,000 babies
treated with antibiotics and this was
the lowest number that i found in the
number needed to treat us 44 to have one
proven infection new pins is our
procalcitonin study so far not published
hopefully soon so we had 1740 babies in
Switzerland in the netherlands in Prague
and Canada and we had a number needed to
treat of 64 and then you go now to the
united states that our publication which
number needed to treat from 154 or if
you look on a special situation special
risk situation like Cory immunities
there was the number needed to treat of
138 now of course we can say well but
it's very dangerous to have sexy so we
have to treat very much babies to to
have known
mortality so what about the mortality so
it goes on there are none in the new pin
study we had nonsense related mortality
in Norway there was one baby dying on a
GPS sepsis and in the USA and even by
chorioamnionitis there was a very low
number so in the USA for example you
have to treat more than 11,000 babies to
have one baby will die on sepsis of
course we don't want to have that babies
but at least we have to think about are
these numbers reasonable so i think we
can conclude regarding the start of
therapy we have a high number needed to
treat for proven infection in term at
least interment late preterm babies
what about the duration of antibiotic
therapy again the study from Norway
looking on how long do they treated
their babies for culture prove
insecticide-treated eight days for
culture- sepsis they had a mean six days
for rule out sepsis four days so that
gives an overall duration of antibiotic
therapy for the whole group of four
point eight days
this is a study from the US just babies
with culture negative situations are
with rule out sepsis and they had a mean
duration of 5.3 days in this situation
the range indifferently cues was between
3.2 and 8.6 days
this is a publication of 2016 and not
from to talk two thousand it was also
obvious the sneak us with a higher
number of new bond started on
antibiotics have a significantly longer
course so it's not true that any cues
that started early could say well we
start early but we finish early so we
have a short course at least in this
study this was not true
another study i'm looking on duration
found as well about fifty percent had a
treatment in culture negative situation
for 325 days interesting here to see
babies treated for more or equal five
days in sixty-two percent the reason was
a memoria
I think it's very difficult to diagnose
of ammonia in tree terminator babies I
don't know how they have done it
of course there is nothing mentioned in
this publication so i think we can
conclude that the duration of antibiotic
therapy for suspected infection for
culture- infection is probably often
prolonged so okay now having this these
facts the question is so what is there
anything what what we can do can be make
it better
I come back to the study from lausanne
the study was primary not focused on
duration of antibiotic therapy but they
look that is a laboratory measurement
really helpful regarding the decision to
start antibiotic therapy so they had two
cohorts in the first cohort they had
just the national guidelines and for the
second cohort they made a special policy
how to treat baby and how to do it and
the interestingly point here is looking
on the data they had the duration
without the protocol of 77.5 hours and
in the second period with the protocol
the local they came down to 64.2 hours
comparing these results to Norway in the
normal publication they mentioned that
they didn't have any guidelines
regarding antibiotic therapy
remember we had four point eight days in
the USA in this huge population we had
five point three trays days in the new
pin study we had a protocol as well for
the standard group and our duration of
antibiotic therapy for the whole group
in the standard group was very similar
to the daytime lows on 65 hours we have
to mention this publication because
guidelines and protocols may have
another words affect and perhaps it's
not what we wanted to do so this study
is about the nice guidelines in the UK
probably as you know the nice guidelines
requested or asked to do a CRP with 18
hours after
starting antibiotics and they hoped bcrp
it is possible to shorten the duration
for antibiotic therapy to come down with
lumbar punctures and what happened was
exactly the contrary so the duration of
antibiotic therapy was prolonged stay in
the hospital was prolonged and the
number of long departure longer punches
went up so protocols and guidelines i
think may have a benefit now of course i
have to say something about the PCT p
city is just one out of many biomarkers
and I think one of the important thing
if you're looking on a biomarker we have
to know what are the normal values for
these biomarkers after birth because
probably as well the CRP has some
physiological increase after birth and
not they below
54 below 10 and this is true as well for
the PCT very can see here this is what
we used this increased in the first
three days flag we have a protocol so we
try to say okay rather any risk factors
yes or no whether any clinical symptoms
better some conventional laboratory
findings like a local site opinion or a
CRP above 10 and then we categorize them
and say okay if you have just one point
there is a low-risk we still we had a
medium risk or if you had all three of
them a high-risk and then we have the
culture positive infections and we tried
in the low and the medium risk to do a
PCT guidance trying to shorten
antibiotic therapy and we came down in
the itt analysis to 55 hours and the
per-protocol analyst analysis to 51
hours i think this shows that is
possible to shorten antibiotic therapy
and quite sure it is possible with other
biomarkers I don't think that this is
now a specific PCT thing that is that
you can do this with other biomarkers
and I think the biomarkers just to help
so if you are able to have a short
duration of antibiotic
therapy without any biomarkers that's
fine then probably you don't need them
but if you have doctors who are not able
to make this decision then a biomarker
may help to do it so biomarker guidance
may help to shorten antibiotic therapy
as the last point antibiotic stewardship
as you know this is a big word there is
a recent publication lancet infectious
disease i think this was a NICU in Texas
and they were able with an intervention
to come down on the antibiotic use on
their NICU looking at where was it
possible to come down
it was a total amount of antibiotics and
as you can see here it was especially
possible in the suspected early-onset
senses so the use on this nique you of
antibiotics was focused on early onset
sepsis number two again trustees ammonia
and as you can see the suspected lay
down to Texas and the culture proven
infection they were just a small part of
their antibiotic use and antibiotic
stewardship is if you hear that all of
our thinking about all you need quite a
lot of resources you need the infectious
disease specialist unit isn't that so
the question is it possible to do it not
reason is lower resources so these are
the data from Lucerne end of 2015 and we
had the impression we are using too much
of antibiotics we are we we are using
too much of recognizing of meropenem so
we said let's try to come down on this
and antibiotics so it was possible to
come down reality from seventeen percent
regarding antibiotic days and just
possible in our units to come down mr.
maximizing and American by around fifty
percent and the mortality at least was
not increasing so I think this shows it
is possible of course it really depends
where you are if you are using your
antibiotics very carefully and very rare
than trouble be this is not possible at
least in our situation
it was possible so antibiotic server
surveillance and stewardship i think in
any form is mandatory for any NICU so my
take-home message in the end is really
this I think when you're prescribe
antibiotics we really have to think
about and they're the mindset that we
probably many of us have you have a baby
and you think well should I start with
antibiotics
there is some risk but the risk is not
that high
perhaps the baby has a little bit of
technique but that's it and then the
mine that all let's give some
antibiotics then we are safe i think
this is probably not true because
probably there is a cost on the
individual health regarding the damage
of the microbiota thank you for your
attention

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Conference program

Welcome Words
M. Roth-Kleiner, R. Arlettaz Mieth
10 Jan. 2017 · 9:33 a.m.
Short Reports Introduction
E. Giannoni, T. Karen, Resp. Lausanne, Zürich
10 Jan. 2017 · 9:38 a.m.
Association of Axonal Injury and Preeclampsia
Katrina Evers, Neonatology UKBB
10 Jan. 2017 · 9:39 a.m.
Q&A - Association of Axonal Injury and Preeclampsia
Katrina Evers, Neonatology UKBB
10 Jan. 2017 · 9:44 a.m.
Retinopathy of Prematurity
Roland Gerull, Bern
10 Jan. 2017 · 9:47 a.m.
Q&A - Retinopathy of Prematurity
Roland Gerull, Bern
10 Jan. 2017 · 9:54 a.m.
Parechovirus Infection: A Rare Cause of Neonatal Encephalitis (in French)
Dr Truant AS, Cheffe de clinique, Néonatologie, CHUV, Lausanne
10 Jan. 2017 · 9:59 a.m.
Q&A - Parechovirus Infection: A Rare Cause of Neonatal Encephalitis
Dr Truant AS, Cheffe de clinique, Néonatologie, CHUV, Lausanne
10 Jan. 2017 · 10:04 a.m.
Genetic Susceptibility to Neonatal Group B Streptococcal Disease
Alessandro Borghesi, Fellay lab, EPFL
10 Jan. 2017 · 10:17 a.m.
Q&A - Genetic Susceptibility to Neonatal Group B Streptococcal Disease
Alessandro Borghesi, Fellay lab, EPFL
10 Jan. 2017 · 10:25 a.m.
Psychomotor Development in Children Prenatally Exposed to Methadone
G. Grand-Guillaume-Perrenoud, Pediatrics, Children's University Hospital Geneva
10 Jan. 2017 · 10:27 a.m.
Q&A - Psychomotor Development in Children Prenatally Exposed to Methadone
G. Grand-Guillaume-Perrenoud, Pediatrics, Children's University Hospital Geneva
10 Jan. 2017 · 10:34 a.m.
Introduction to Christoph Berger's Presentation
C. Kind, R. Gerull, Resp. St.Gallen, Bern
10 Jan. 2017 · 10:37 a.m.
Vertical Infections: An Update
Christoph Berger, Zürich
10 Jan. 2017 · 10:40 a.m.
Q&A - Vertical Infections: An Update
Christoph Berger, Zürich
10 Jan. 2017 · 11:15 a.m.
Introduction to Eric Giannoni's Presentation
R. Pfister, S. Kämpfen, Resp. Geneva, Basel
10 Jan. 2017 · 11:44 a.m.
Sepsis, Antibiotics and Resistances: Where Are We?
Christoph Bührer, Berlin
10 Jan. 2017 · 2:21 p.m.
Use and Abuse of Antibiotics in Neonatology
Martin Stocker, Lucerne
10 Jan. 2017 · 2:50 p.m.
Panel Discussion : Controversies on Use of Antibiotics in Neonatology
Martin Stocker, Christoph Berger, Eric Giannoni, Christoph Bührer
10 Jan. 2017 · 3:10 p.m.
Introduction to Christoph Bührer's Presentation
Romaine Arlettaz Mieth , Neonatologist, Zürich, President of the Organizing Committee
10 Jan. 2017 · 3:47 p.m.
Evidence-Based Haemodynamic Management in Neonatal Sepsis
Christoph Bührer, Berlin
10 Jan. 2017 · 3:48 p.m.
Q&A - Evidence-Based Haemodynamic Management in Neonatal Sepsis
Christoph Bührer, Berlin
10 Jan. 2017 · 4:16 p.m.
SwissNeoDose Project
Marc Pfister, Ped Pharmacology, UKBB
10 Jan. 2017 · 4:20 p.m.