1
Anaya- BazB, e al. BMJ Open 2020;10:e030608. doi:10.1136/bmjopen-2019-030608
Open access
Sys ema ic li e a u e e iew o he
bu den and ou comes o in ec ions due
o mul id ug- esis an o ganisms in
Eu ope: he ABOUT- MDRO
p ojec p o ocol
Blanca Anaya- Baz,1 Na alia Maldonado,1 Zai a R Palacios- Baena ,1
Vi ginia Palomo,1 Ma ia Dile a Pezzani,2 Sheila Chiesi ,2 Elisa Razzaboni,2
Monica Comp i,2 E elina Tacconelli,2 Jesús Rod iguez- Baño1
To ci e: Anaya- BazB,
MaldonadoN, Palacios-
BaenaZR, e al. Sys ema ic
li e a u e e iew o he bu den
and ou comes o in ec ions due
o mul id ug- esis an o ganisms
in Eu ope: he ABOUT- MDRO
p ojec p o ocol. BMJ Open
2020;10:e030608. doi:10.1136/
bmjopen-2019-030608
►P epublica ion his o y and
addi ional ma e ial o his
pape a e a ailable online. To
iew hese iles, please isi
he jou nal online (h p:// dx. doi.
o g/ 10. 1136/ bmjopen- 2019-
030608).
Recei ed 25 Ma ch 2019
Re ised 25 Sep embe 2019
Accep ed 03 Ma ch 2020
Fo numbe ed a ilia ions see
end o a icle.
Co espondence o
D Jesús Rod iguez- Baño;
jesus b@ us. es
P o ocol
© Au ho (s) (o hei
employe (s)) 2020. Re- use
pe mi ed unde CC BY- NC. No
comme cial e- use. See igh s
and pe missions. Published by
BMJ.
S eng hs and limi a ions o his s udy.
►Da a syn hesis will in ol e collec ion and summa y
o a ailable da a on a es and ou come es ima ions
o di e en ypes o in ec ions caused by p io i ised
an ibio ic- esis an pa hogens, o e all and o spe-
ci ic pa ien popula ions and geog aphical a eas in
Eu ope.
►P e ious da abases o in ec ions and pa hogens
su eillance iden i ied by sys ema ic e iews om
EPI- ne (h ps://epi-ne .eu/) such as Su eillance
Sys ems om Public Heal h Ins i u ions and
Scien i ic Socie ies o An imic obial Resis ance and
Heal hca e- Associa ed In ec ions in Eu ope (doi:
10.1016/j.cmi.2017.07.014) will be a ailable.
►Da a om sou ces o in o ma ion no publicly a ail-
able will be missed. Also, a ailable da a a e ex-
pec ed o be sca ce o some in ec ions. Howe e ,
he s udy will also be use ul o iden i y he gaps in
in o ma ion.
►De ini ions o ou comes and me hodology o
ollow- up o pa ien s may be he e ogeneous ac oss
s udies.
AbS AC
In oduc ion Despi e he inc easing impo ance o
in ec ions due o mul id ug- esis an o ganisms (MDROs),
he e is a lack o comp ehensi e in o ma ion abou
he bu den o disease and ou comes o key in ec ions
caused by hese pa hogens. The aim o he ABOUT- MDRO
(A sys ema ic e iew on he bu den and ou comes o
in ec ions due o mul id ug esi an o ganisms) p ojec is o
p o ide es ima ions o he bu den o some key in ec ions
and hei ou comes caused by he a ge MDROs.
Me hods and analysis A sys ema ic li e a u e sea ch will
be pe o med using MEDLINE/PubMed, Else ie ’s SCOPUS,
Coch ane lib a y, Clinical ials and Web o Science, as well
as he Su eillance Sys ems om Public Heal h Ins i u ions
and Scien i ic Socie ies o An imic obial Resis ance and
Heal hca e- Associa ed In ec ions in Eu ope da abase o
Eu opean su eillance sys ems, o da a on p e alence/
incidence, mo ali y and leng h o s ay o a ge in ec ions
in hospi alised pa ien s (including en ila o - associa ed
pneumonia, hospi al- acqui ed pneumonia, complica ed
in a- abdominal in ec ions, complica ed u ina y ac
in ec ions, skin and so issue in ec ions and bloods eam
in ec ions) and in speci ic popula ions (child en, hospi al
wa ds, neu openic pa ien s) caused by cephalospo in-
esis an o ca bapenem- esis an En e obac e iaceae,
ca bapenem- esis an Pseudomonas ae uginosa and
Acine obac e spp., me hicillin- esis an S aphylococcus
au eus, and ancomycin- esis an En e ococcus spp.
The in o ma ion e ie ed will be abula ed and pooled
es ima es and 95% CIs calcula ed o a es and ou comes,
using andom e ec s models. Rela ionships be ween
a es and ou comes in andomised con ol ials and
epidemiological s udies, and da a o p opo ions and
incidence/p e alence a es will also be analysed. The
in o ma ion collec ed in his s udy will be use ul o
iden i ying gaps in ou knowledge in e ms o incidence/
p e alence and clinical ou comes o in ec ions caused by
MDROs, and o in o ming p io i ies in in ec ion con ol and
he esea ch and design o app op ia e s udies.
E hics and dissemina ion This s udy will be based on
published da a so we did no equi e e hical app o al.
Fo mal consen is no equi ed. The esul s o his e iew
will be epo ed acco ding o he P e e ed Repo ing I ems
o Sys ema ic Re iewand Me a- Analyses s a emen .
Da a will be p esen ed a in e na ional con e ences and
published in pee - e iewed jou nals.
egis a ion de ails PROSPERO (h ps://www. c d. yo k.
ac. uk/ p ospe o/) (CRD42019124185).
In oduC Ion
The wo ldwide sp ead o o ganisms ha a e
esis an o mul iple an ibio ics, gene ally
e e ed o as mul id ug- esis an o gan-
isms (MDRO), has become a public heal h
conce n.1 2 The WHO ecen ly es ablished
a p io i y lis o mic oo ganisms o in o m
esea ch p io i ies o he de elopmen o
new an ibio ics, wi h ca bapenem- esis an
copy igh . on May 19, 2023 a USE/Fac Medicina Biblio eca FME. P o ec ed byh p://bmjopen.bmj.com/BMJ Open: i s published as 10.1136/bmjopen-2019-030608 on 5 May 2020. Downloaded om
2Anaya- BazB, e al. BMJ Open 2020;10:e030608. doi:10.1136/bmjopen-2019-030608
Open access
Acine obac e baumannii (CRAB) and Pseudomonas ae ugi-
nosa, hi d- gene a ion o ca bapenem- esis an En e o-
bac e iaceae, ancomycin- esis an En e ococcus spp. and
me hicillin- esis an S aphylococcus au eus conside ed c i -
ical and o high p io i y.3 The e is also an u gen need o
imp o emen s in su eillance o help op imise empi ical
he apy, d i e an imic obial s ewa dship and in ec ion
con ol measu es, and help in he a ional use o old and
new d ugs agains esis an o ganisms.4
The main sou ces o in o ma ion on a es o in ec ion
caused by MDROs come om egional, na ional o in e -
na ional su eillance sys ems, published epidemiological
s udies and ou b eak epo s. Two da abases de eloped
in he con ex o EPI- NET (epidemiologic Eu opean
ne wo k)/Comba ing Bac e ial Resis ance in Eu ope -
Molecules agains G am- nega i e In ec ions conso ium
iden i ied ele an sou ces o in o ma ion: he SUSPIRE
S udy (Su eillance Sys ems om Public Heal h Ins i u-
ions and Scien i ic Socie ies o An imic obial Resis ance
and Heal hca e- Associa ed In ec ions in Eu ope) ecen ly
mapped all su eillance sys ems wi h publicly a ailable
da a in Eu ope and showed ha , despi e ecen imp o e-
men s and s udies which con ol and s udy his issue, he
a ailable da a s ill emain o be excessi ely he e ogeneous
and sca ce o gene a e an exhaus i e co ela ion and
compa ison wi h publicly a ailable su eillance sys ems
in o ma ion ac oss Eu ope.5 Addi ionally, published
ou b eak epo s we e mapped by he EMBARGO
(EpideMiology and con ol measu es o ou B eaks due o
An ibio ic- Resis an o Ganisms in Eu Ope) S udy.6 While
equen use is made o da a om su eillance sys ems
and s udies p o iding p opo ions o isola es wi h esis-
ance o speci ic an imic obials, comp ehensi e da a on
pa hogen incidence a es and in ec ions a e e y limi ed.
This is impo an because da a based on p opo ion o
esis an isola es can be misleading i no adequa ely
in e p e ed; o gi e an example, i hospi al A ound wo
ca bapenem- esis an A. baumannii ou o 4 isola es o
his pa hogen in 1 yea , while hospi al B, despi e ha ing
a simila numbe o admissions, ound 20/40, in bo h
cases, he p opo ion is 50%, bu he bu den o in ec-
ion caused by ca bapenem- esis an A. baumannii is
e y di e en . Fu he mo e, he clinical bu den a ies
acco ding o he p edominan in ec ion ype o popula-
ion a ec ed. To ha e such da a a ailable would be o c i -
ical impo ance o in o ming he public, as well as policy
make s, hospi al manage s, esea ch unding bodies and
companies wo king on he de elopmen o diagnos ic
and he apeu ic ools o p io i y esea ch and in ec ion
con ol ac i i ies. The clinical impac o MDRO in ec ions
is usually measu ed using c ude mo ali y and leng h o
o e all hospi al s ay. The s udies a emp ing o es ima e
he a ibu able in luence o an imic obial esis ance on
he ou come o pa ien s a e he e ogeneous in he popu-
la ions included and in he me hodology.7–11
O e all, in iew o he da a p o ided, he main esea ch
ques ion is: Wha is he bu den o in ec ions and esis-
ance caused by MDROs o e all and o speci ic ypes o
in ec ions, mic oo ganisms and pa ien s in he di e en
coun ies/geog aphical a eas/hospi als in Eu ope, and
which is he clinical bu den due o ca bapenem- esis an
Klebsiella pneumoniae, CRAB and ancomycin- esis an
En e ococci (VRE)?
The majo aim o he ABOUT- MDRO p ojec (a sys em-
a ic e iew on he bu den and ou comes o in ec ions due
o MDRO) is o es ima e he bu den o key in ec ions and
hei ou comes caused by a ge MDROs.
ME hodS/dESIgn
design
A sys ema ic e iew o he scien i ic and g ey li e a u e
will be pe o med. The a ge MDROs o his s udy
a e ca bapenem- esis an Acine obac e spp and P. ae ugi-
nosa; cephalospo in- esis an o ca bapenem- esis an
En e obac e iaceae; ancomycin- esis an En e ococcus spp.,
and me hicillin- esis an S. au eus. The a ge in ec ions
include en ila o - associa ed pneumonia and hospi al-
acqui ed pneumonia, complica ed in a- abdominal
in ec ions, complica ed u ina y ac in ec ions, compli-
ca ed skin and skin s uc u e in ec ions, and bloods eam
in ec ions.
Eligibili y c i e ia
S udies will be conside ed o inclusion i p o iding
any o he ollowing, o he a ge in ec ions caused by
he a ge MDROs occu ing in hospi alised pa ien s:
incidence a e, incidence densi y, p e alence, all- cause
mo ali y o leng h o s ay. S udies no p o iding he es i-
ma ions bu o which he nume a o s and denomina o s
o hei calcula ion is a ailable will also be included. All
o he eligibili y c i e ia a e shown in box 1. S udies om
sys ema ic e iews will only be included i he da a om
he indi idual s udies included in hem a e no a ailable.
In o ma ion sou ces
This sys ema ic e iew ollowed he P e e ed Repo ing
I ems o Sys ema ic Re iewand Me a- Analysis P o ocols
guidelines scheme (online supplemen a y igu e S1) and
checklis (online supplemen a y able S1) o me hod-
ology de elopmen and s uc u e esea ch. The ollowing
elec onic da abases will be sea ched: MEDLINE- PubMed,
Coch ane lib a y, SCOPUS and Web o Science. The
upda ed su eillance sys ems da abases o an imic obial-
esis an pa hogens and hospi al- acqui ed in ec ions
om he SUSPIRE p ojec 5 and EPI- NET (h ps:// epi-
ne . eu/) will also be sea ched.
Sea ch s a egy
A comp ehensi e sea ch s a egy will be pe o med o
pee - e iewed li e a u e, wi h no language es ic ions.
The sea ch s a egy will be pe o med using MeSH
(Medical Subjec Headings) e ms and No- MeSH e ms,
selec ed a e pilo ing di e en sea ch s a egies. Finally,
and acco ding o he pilo ing, No- MeSH sea ch e ms
copy igh . on May 19, 2023 a USE/Fac Medicina Biblio eca FME. P o ec ed byh p://bmjopen.bmj.com/BMJ Open: i s published as 10.1136/bmjopen-2019-030608 on 5 May 2020. Downloaded om
3
Anaya- BazB, e al. BMJ Open 2020;10:e030608. doi:10.1136/bmjopen-2019-030608
Open access
box 1 Inclusion c i e ia
►S udy designs: sys ema ic e iews, andomised con olled ials,
non- con olled ials, quasi- expe imen al s udies, coho s udies,
case- con ol s udies, ou b eak epo s, c oss- sec ional s udies and
su eillance epo s.
►S udies p o iding da a on any o he a ge ed pa ho-
gens: cephalospo in- esis an o ca bapenem- esis an
En e obac e iaceae, ca bapenem- esis an Pseudomonas ae ugino-
sa, ca bapenem- esis an Acine obac e spp., ancomycin- esis an
En e ococcus spp., me hicillin- esis an S aphylococcus au eus.
►S udies p o iding in o ma ion on any o he a ge ed in ec ions:
hospi al- acqui ed pneumonia, en ila o - associa ed pneumonia,
complica ed in a- abdominal in ec ions, complica ed u ina y ac
in ec ions o bloods eam in ec ions.
►Fo da a on he bu den o in ec ions: s udies p o iding es ima es
o da a on he equency o a ge ed in ec ions caused by MDROs,
including a leas one o he ollowing: p e alence, incidence a e
o cumula i e incidence, incidence densi y, pe cen age o esis an
isola es.
►Fo da a on ou comes o in ec ions: s udies p o iding da a on ou -
comes o a ge ed in ec ions caused by MDROs, including a leas
one o he ollowing: mo ali y a es, leng h o s ay.
►Time pe iod and geog aphical scope: Janua y 2005 h ough
Decembe 2018, Eu opean coun ies acco ding o he ESCMID
(Eu opean Socie y o Clinical Mic obiology and In ec ious Diseases)
de ini ion o geog aphical egions (h ps://www.escmid.o g/ ile-
admin/s c/media/PDFs/5P o ession_Ca ee /Pa i y_Commission/
ESCMID_De ini ion_o _Geog aphic_Regions_140703.pd ).
►No age o language es ic ions.
box 2 Keywo d combina ions o sea ch s a egy.
Pa hogens and esis ance e ms
►Ta ge G am nega i es: ‘mul id ug- esis an ’ o ‘MDR’ o
‘ex ensi ely- d ug esis an ’ o ‘XDR’ o ‘cephalospo in- esis ance’
o ‘ex ended- spec um be a- lac amase’ o ‘ESBL’ o ‘CTX- M’ o
‘SHV’ o ‘TEM’ o ‘AmpC’ o ‘imipenem- esis an ’ o ‘me openem-
esis an ’ o e apenem- esis an ’ o ‘ca bapenemase’ o ‘KPC’
o ‘me allo- be a- lac amase’ o ‘NDM’ o ‘VIM’ o ‘IMP’ o ‘oxacil-
linase’ o ‘OXA-48’ o ‘OXA-48- like’ o ‘CRE’ o ‘CPE’ o ‘po in
loss’ AND ‘En e obac e ia’ o ‘En e obac e iaceae’ o ‘Klebsiella’
o ‘coli’ o ‘P o eus’ o ‘Mo ganella’ o ‘Ci obac e ’ o ‘Se a ia’ o
‘En e obac e ’ o ‘Pseudomonas’ o ‘Acine obac e ’
►Ta ge G am posi i es: ‘mul id ug- esis an ’ o ‘MDR’ o ‘ex ensi e-
ly d ug- esis an ’ o ‘XDR’ o ‘me hicillin- esis an ’ o ‘me icillin-
esis an ’ o ‘oxacillin- esis an ’ o ‘ ancomycin- esis an ’ o
‘MRSA’ o ‘VRE’ AND ‘S aphylococcus au eus’ o ‘En e ococcus’ o
‘en e ococci’
And in ec ion ype e ms
►‘bac e emia’ o ‘bloods eam in ec ion’
►‘heal hca e- associa ed pneumonia’ o ‘ en ila o - associa ed pneu-
monia’ o ‘hospi al- acqui ed pneumonia’ o ‘pneumonia’ o ‘ espi a-
o y in ec ions’ o ‘cys ic ib osis’ o ‘b onchiec asis’
►‘u ina y ac in ec ions’ o ‘UTI’ o ‘cys i is’ o ‘pyeloneph i is’ o
‘ca he e - associa ed u ina y ac in ec ions’
►‘in a- abdominal in ec ion’ o ‘pe i oni is’ o ‘cholangi is’ o ‘chole-
cys i is’ o ‘appendici is’ o ‘in a- abdominal abscess’ o ‘IAI’
►‘SSSI’ o ‘skin and skin s uc u es in ec ions’ o ‘su gical si e in ec-
ions’ o ‘celluli is’ o ‘skin and so issue in ec ions’
And bu den o ou come
►Fo bu den o in ec ions: ‘p e alence’ o ‘incidence’ o ‘ a e’ o ‘pe -
cen age o esis ance’ o ‘p opo ion o esis ance’
►Fo ou comes o in ec ions: ‘leng h o s ay’ o ‘mo ali y’ o ‘dea h
a e’ o ‘ a ali y’ o ‘su i al a e’ o ‘dea h’ o ‘dead’ o ‘died’
ha e been de eloped o his s udy using a combina ion
o keywo ds (lis ed in box 2).
da a managemen , selec ion p ocess and da a collec ion
p ocess
A wo- s ep selec ion p ocedu e will be ollowed o he
selec ion o s udies. A single e iewe will sc een he
i les and abs ac s o s udies e ie ed du ing he sea ch
s a egy o disca d ineligible s udies (eg, case epo s,
case se ies, basic science s udies). The ull- ex esul s o
po en ially eligible documen s will be uploaded o Zo e o
so wa e; duplica es will be emo ed. Two e iewe s will
assess hese o ele ance agains he p ede ined selec-
ion c i e ia. The e e ence lis o iden i ied a icles will
be sea ched o po en ial addi ional s udies.
The da a will be ex ac ed independen ly by wo
e iewe s using a s anda dised elec onic da a ex ac ion
o m, o be p e iously pilo es ed on a ep esen a i e
sample. Disag eemen s will be esol ed by a hi d e iewe .
Da a ex ac ion om a 10% andom sample o included
a icles will be checked by a hi d e iewe .
da a i ems: p ima y end poin s and o he a iables
The main end poin s o collec will be: (1) Fo bu den
o in ec ions, incidence a e o densi y o in ec ions
(de ined as he numbe o new cases o in ec ion pe 100
hospi alised pa ien s and/o 1000 pa ien - days occu ing
in a speci ic ime pe iod, espec i ely) and p e alence
(de ined as he p opo ion o exis ing cases o in ec ion
pe 100 pa ien s admi ed a a pa icula ime poin ). (2)
Fo clinical ou comes, c ude and in ec ion- a ibu able
mo ali y, and leng h o hospi al s ay (o e all and in in en-
si e ca e uni s). Mo ali y will be collec ed as de ined in
each s udy, bu he p ima y in en ion is o analyse in- hos-
pi al, 14- day, 30- day and 90- day mo ali ies. Also, leng h
o s ay will be collec ed as de ined in he s udies. Da a on
he p opo ion o esis an pa hogens causing he in ec-
ions will also be collec ed i a ailable. We will calcula e
he end poin s e en i no di ec ly p o ided in he a icles,
p o ided he nume a o s and denomina o s a e a ailable.
O he da a o be collec ed a e shown in able 1; o hese,
we will ely on he de ini ions used in he s udies bu will
p o ide desc ip i e in o ma ion abou he de ini ions.
Quali y assessmen
The quali y o he da a e ie ed will be e alua ed by wo
e iewe s using he ollowing c i e ia: (1) The isk o
selec ion bias (low, medium, high) o measu ing bu den
o disease, in e ms o abili y o de ec cases and ep esen-
a i eness o speci ic popula ions. (2) The isk o in o -
ma ion bias (low, medium, high) based on de ini ion o
case, in ec ion ype and mic obiological assessmen . (3)
The quali y o andomised con ol ials will be measu ed
copy igh . on May 19, 2023 a USE/Fac Medicina Biblio eca FME. P o ec ed byh p://bmjopen.bmj.com/BMJ Open: i s published as 10.1136/bmjopen-2019-030608 on 5 May 2020. Downloaded om
4Anaya- BazB, e al. BMJ Open 2020;10:e030608. doi:10.1136/bmjopen-2019-030608
Open access
Table 1 Va iables o be collec ed om included s udies
Co e elemen Va iable
S udy, si e, ime Fi s au ho , i le, coun y, yea (s)
Scope* One hospi al, mul icen e, egion, coun y
Design* Su eillance; andomised ial; coho ; case- con ol
Popula ion* Age: all/child en/adul s
Wa d: all hospi al wa d, speci ic wa ds (ICU, e c)
Speci ic unde lying condi ions: neu openia, dialysis, and so on
In ec ions* HAP/VAP, cUTI, cIAI, cSSSI, BSI (including sou ce)
Mic oo ganism(s)* Gen e and species, pheno ypical esis ance, mechanism(s) o esis ance (i a ailable)
Epidemiological si ua ion* Ou b eak, endemic si ua ion
End poin a iables† Bu den: P e alence, cumula i e incidence, incidence densi y, p opo ion o esis an isola es
Clinical ou comes: all- cause mo ali y, in ec ion- ela ed mo ali y, leng h o hospi al s ay
Mo ali y de ini ions* In- hospi al, ix- day
*As de ined in he a icles.
†De ini ions in he ex .
. BSI, bloods eam in ec ion; cIAI, complica ed in a- abdominal in ec ion; cSSSI, complica ed skin and skin s uc u e in ec ion; cUTI,
complica ed u ina y ac in ec ion; HAP, hospi al- acqui ed pneumonia; ICU, in ensi e ca e uni ; VAP, en ila o - associa ed pneumonia.
using he E ec i e P ac ice and O ganisa ion o Ca e
Scale, and he quali y o non- andomised con olled ials
wi h he Newcas le- O awa Scale.
da a syn hesis and analysis
The collec ed da a will be summa ised in abula o m,
indica ing he co e cha ac e is ics o su eillance sys ems
and s udies. Fo each pa hogen and ype o in ec ion,
es ima es o a es and ou comes will be p o ided; s a -
i ica ion by geog aphical a ea, ime pe iod, popula ion,
epidemiological si ua ion will be pe o med i possible.
Pooled es ima es o a es and ou comes wi h 95% CIs will
be p o ided; me a- analyses will be pe o med i possible
wi h R s a is ical so wa e (V.3.0.2; R Founda ion o
S a is ical Compu ing, Vienna, Aus ia). The I2 s a is ic
will be used o measu e he he e ogenei y o es ima es
be ween s udies, bu because he e ogenei y is expec ed,
andom- e ec s models will be used. Co ela ions be ween
a es and ou comes in andomised con olled ials
and epidemiological s udies, and da a on p opo ions
and incidence a es will also be analysed. In addi ion, a
desc ip ion o de ini ions o he key a iables used in he
di e en s udies will be p o ided.
Pa ien and public in ol emen isk o bias
Pa ien s o public we e no in ol ed in he sys ema ic
e iew design.
dISCuSSIon
Despi e he epidemiological and clinical impo ance o
in ec ions caused by MDROs, comp ehensi e da a abou
hei bu dens and ou comes a e la gely missing. Mos
in o ma ion seems o come om single- cen e s udies
in he con ex o ou b eaks, o om su eillance da a
lacking pa ien - de i ed denomina o s.
Assessing he bu den o he speci ic ypes o in ec-
ion caused by hese o ganisms is c i ically impo an in
o de o iden i y p io i ies o in ec ion con ol ac i i-
ies and esea ch. Unde s anding he geog aphical and
popula ion- ype a iabili y o he a es is also key o he
design o clinical s udies o e alua e he e icacy and sa e y
o new o old an imic obial d ugs. Se e al ecen s udies
ha e es ima ed he bu den o in ec ion and mo ali y
caused by mul id ug- esis an pa hogens.7 12 Ne e heless,
he es ima es a e based on limi ed and no necessa ily
eliable da a, as has been unde lined.13 14 The he e oge-
nei y o popula ions and he in luence o mul iple highly
in e connec ed a iables (in ec ion ypes, como bidi-
ies, se e i y o illness, app op ia eness o he apy, e c),
as well as s udy design and analysis me hods mean ha
he e alua ion o mo ali y a ibu able o esis ance is
highly a iable.8–11 Sou ce o da a o a es o in ec ions
due o MDRO may be di icul o ind. Da a in he scien-
i ic li e a u e may be limi ed because o publica ion bias,
a ou ing epo ing o ou b eaks o da a om uni e si y
hospi als; he e o e, we will also sea ch he publicly a ail-
able da a om su eillance sys ems p e iously iden i ied
by he SUSPIRE p ojec . Finally, as a as we know, he e
a e no sys ema ic e iews linking incidence a es wi h
ou come o in ec ion.
We expec some di icul ies in ou s udy and acknowl-
edge some limi a ions. The da a o some pa hogens and
in ec ions may be sca ce and some imes based on special
epidemiological si ua ions; we would y o s a i y he da a
acco ding o he epidemiological si ua ions bu his may
be di icul . The s udies and su eillance sys ems may also
be he e ogeneous in he popula ion s udies, designs and
quali y. Howe e , iden i ying gaps in knowledge will also
be impo an o u u e s udies. De ini ions o ou comes,
and me hods o assessing hem may be he e ogeneous.
copy igh . on May 19, 2023 a USE/Fac Medicina Biblio eca FME. P o ec ed byh p://bmjopen.bmj.com/BMJ Open: i s published as 10.1136/bmjopen-2019-030608 on 5 May 2020. Downloaded om
5
Anaya- BazB, e al. BMJ Open 2020;10:e030608. doi:10.1136/bmjopen-2019-030608
Open access
We will also p o ide desc ip i e da a abou his which may
be use ul o u u e s udies.
In summa y, he aim o he ABOUT- MDRO p ojec is
o p o ide pooled es ima es o a ge MDRO bu dens
and ou comes ha a e as speci ic as possible o di e en
se ings and popula ions as a ool o help policy make s
and esea che s es ablish p io i ies and design be e
s udies o use in he igh agains an imic obial esis-
ance. The s udy will also summa ise g ey li e a u e da a
in o de o assess he clinical bu den o MDRO in ec ions
a he Eu opean le el. These esul s will also be in o ma-
i e o he e icien design o andomised clinical ials.
Au ho a ilia ions
1Unidad Clínica de En e medades In ecciosas, Mic obiología y Medicina P e en i a,
Hospi al Uni e si a io Vi gen Maca ena / Depa amen o de Medicina, Uni e sidad de
Se illa / Ins i u o de Biomedicina de Se illa (IBiS), Se illa, Spain
2Di isione di Mala ie In e i e, Dipa imen o di Diagnos ica e Sani à Pubblica,
Ospedale Policlinico Bo go Roma, Ve ona, I aly
Con ibu o s JR- B and ET concei ed he s udy. JR- B led he de elopmen o
he p o ocol, p o ided supe ision and men o ship o BA- B who w o e he i s
d a , and de eloped pa o he sea ch s a egy, and coo dina ed and in eg a ed
ideas and commen s om ZRP- B, NM and VP. The o he coau ho s MDP, SC, ER,
MC de eloped he clinical ou comes pa o he s udy p o ocol. All he au ho s
con ibu ed o he selec ion o a iables and he es o he p o ocol sec ions.
Funding The ABOUT- MDRO S udy is pa o he COMBACTE- MAGNET p ojec
(Comba ing Bac e ial Resis ance in Eu ope - Molecules agains G am- nega i e
In ec ions), Inno a i e Medicines Ini ia i e (IMI), Eu opean Union's Se en h
F amewo k P og amme (FP7/2007-2013) and EFPIA companies’ in- kind
con ibu ion, G an ag eemen 115737. ZRP- B and JR- B ecei ed unding o
esea ch om Plan Nacional de I+D+i 2013‐2016 and he Ins i u o de Salud
Ca los III, Subdi ección Gene al de Redes y Cen os de In es igación Coope a i a,
Minis e io de Economía, Indus ia y Compe i i idad, Spanish Ne wo k o Resea ch
in In ec ious Diseases (REIPI RD16/0016/0001), co- inanced by he Eu opean
De elopmen Regional Fund 'A way o achie e Eu ope', Ope a i e P og amme
In elligen G ow h 2014‐2020.
Compe ing in e es s ZRP- B ecei ed hono a ia o educa ional alks by Gilead.
JR- B ecei ed hono a ia o acc edi ed educa ional ac i i ies unded by Me ck
h ough un es ic ed g an s. All o he au ho s decla e ha hey ha e no con lic s o
in e es .
Pa ien and public in ol emen Pa ien s and/o he public we e no in ol ed in
he design, o conduc , o epo ing, o dissemina ion plans o his esea ch.
Pa ien consen o publica ion No equi ed.
P o enance and pee e iew No commissioned; ex e nally pee e iewed.
da a a ailabili y s a emen The e a e no da a in his wo k.
open access This is an open access a icle dis ibu ed in acco dance wi h he
C ea i e Commons A ibu ion Non Comme cial (CC BY- NC 4.0) license, which
pe mi s o he s o dis ibu e, emix, adap , build upon his wo k non- comme cially,
and license hei de i a i e wo ks on di e en e ms, p o ided he o iginal wo k is
p ope ly ci ed, app op ia e c edi is gi en, any changes made indica ed, and he use
is non- comme cial. See:h p:// c ea i ecommons. o g/ licenses/ by- nc/ 4. 0/.
o CId ids
Zai a RPalacios- Baena h p:// o cid. o g/ 0000- 0002- 1713- 6807
SheilaChiesi h p:// o cid. o g/ 0000- 0002- 0108- 0722
EFE EnCES
1 Eu opean Commission. Ac ion plan agains he ising h ea s om
an imic obial esis ance. In: Communica ion om he Commission o
he Eu opean Pa liamen and he Council. 15. B ussels, 2011.
2 The bac e ial challenge: ime o eac . ECDC/EMEA join echnical
epo . EMEA Doc. Re . EMEA/576176/2009. S ockholm, Sep embe
2009.ISBN 978-92-9193-193-4. A ailable: h ps:// ecdc. eu opa. eu/
si es/ po al/ iles/ media/ en/ publica ions/ Publica ions/ 0909_ TER_ The_
Bac e ial_ Challenge_ Time_ o_ Reac . pd [Accessed Ma ch 2019].
3 Tacconelli E, Ca a a E, Sa oldi A, e al. Disco e y, esea ch,
and de elopmen o new an ibio ics: he who p io i y lis o
an ibio ic- esis an bac e ia and ube culosis. Lance In ec Dis
2018;18:318–27.
4 Tacconelli E, Si akis F, Ha ba h S, e al. Su eillance o con ol o
an imic obial esis ance. Lance In ec Dis 2018;18:e99–106.
5 Núñez- Núñez M, Na a o MD, Palomo V, e al. The me hodology o
su eillance o an imic obial esis ance and heal hca e- associa ed
in ec ions in Eu ope (SUSPIRE): a sys ema ic e iew o publicly
a ailable in o ma ion. Clin Mic obiol In ec 2018;24:105–9.
6 Babu Rajend an N, Glads one BP, Rod íguez- Baño J, e al.
Epidemiology and con ol measu es o ou B eaks due o
an ibio ic- esis an o Ganisms in Eu ope (emba go): a sys ema ic
e iew p o ocol 6A Be yl P, Vilken T, Be nha d a, Tacconelli
E. epidemiological di e ences in con olling he sp eading o
ca bapenem- esis an bac e ial s ains in hospi alized pa ien s.
ECCMID 2016 Ams e dam, O386 (o al p esen a ion).. BMJ Open
2017;7:e013634..
7 O’Neill J. An imic obial esis ance: ackling a c isis o he heal h and
weal h o na ions. A ailable: h ps://am e iew. o g/ si es/ de aul / iles/
AMR% 20Re iew % 20Pape % 20% 20Tackling% 20a% 20c isis%
20 o % 20 he% 20heal h% 20and% 20weal h% 20o % 20na ions_ 1. pd
8 Zeng X, Zhang Y, Kwong JSW, e al. The me hodological quali y
assessmen ools o p eclinical and clinical s udies, sys ema ic
e iew and me a- analysis, and clinical p ac ice guideline: a
sys ema ic e iew. J E id Based Med 2015;8:2–10.
9 Va dakas KZ, Ra ailidis PI, Kons an elias AA, e al. P edic o s o
mo ali y in pa ien s wi h in ec ions due o mul i- d ug esis an g am
nega i e bac e ia: he s udy, he pa ien , he bug o he d ug? J In ec
2013;66:401–14.
10 Naylo NR, A un R, Zhu N, e al. Es ima ing he bu den o
an imic obial esis ance: a sys ema ic li e a u e e iew. An imic ob
Resis In ec Con ol 2018;7:58.
11 E ans SR, Ha is AD. Me hods and issues in s udies o C e. Vi ulence
2017;8:453–9.
12 Cassini A, Högbe g LD, Plachou as D, e al. A ibu able dea hs and
disabili y- adjus ed li e- yea s caused by in ec ions wi h an ibio ic-
esis an bac e ia in he EU and he Eu opean economic a ea in
2015: a popula ion- le el modelling analysis. Lance In ec Dis
2019;19:56–66.
13 de K ake MEA, S ewa dson AJ, Ha ba h S. Will 10 million people
die a yea due o an imic obial esis ance by 2050? PLoS Med
2016;13:e1002184.
14 Tacconelli E, Pezzani MD. Public heal h bu den o an imic obial
esis ance in Eu ope. Lance In ec Dis 2019;19:4–6.
copy igh . on May 19, 2023 a USE/Fac Medicina Biblio eca FME. P o ec ed byh p://bmjopen.bmj.com/BMJ Open: i s published as 10.1136/bmjopen-2019-030608 on 5 May 2020. Downloaded om