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Effectiveness and safety of strategies to optimise antimicrobial use in solid organ transplant recipients. Systematic review and meta-analyses

Abstract

Background: Solid organ transplant recipients (SOTr) are at high risk of infectious complications, and effective antimicrobial stewardship (AMS) programmes need to be developed. We aimed to review the available evidence on the effectiveness and safety of different strategies to optimise antibiotic use in SOTr. Methods: In our systematic review and meta-analyses, we searched MEDLINE (via PubMed), EMBASE, and SCOPUS for original research articles published up to 06 March 2025. Studies with a control group evaluating different strategies to optimise antimicrobial use in adult SOTr were included. The outcomes assessed were mortality, transplant-related complications, infectious outcomes, development of antimicrobial resistance, antimicrobial consumption, hospital related variables, and antimicrobial toxicities. A risk-of-bias assessment was performed using the Cochrane EPOC group's criteria. Data from included studies were pooled in meta-analyses if three or more studies had the same type of intervention and comparison group and reported sufficient data on infection outcomes to be combined. Meta-analyses were performed using a random-effects model and the inverse variance method with the I2 statistic to test for inconsistency between studies. Sensitivity analyses were also evaluated. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PROSPERO ID: CRD42024554606. Findings: Of the 4050 articles identified, 34 studies met the inclusion criteria. Seventeen studies addressed perioperative antimicrobial prophylaxis (seven of which evaluated specifically duration of antimicrobial prophylaxis), two reported information about decolonisation strategies, three addressed duration of antimicrobial treatment as target therapy, one evaluated antibiotic oral step-down strategy, and six reported the impact of AMS implementation approach on SOTr. The other five studies evaluated specific targeted prophylaxis. All the studies had a moderate or high risk of bias. The meta-analysis of three studies on the effect of AMS programmes showed that this intervention may reduce the rate of surgical site infections (OR 0·57, 95% CI 0·35–0·94). For perioperative antimicrobial prophylaxis, the meta-analysis of six trials showed results in favour of prophylaxis in terms of reducing surgical site infections (risk ratio 1·93, 95% CI 1·14–3·27) in kidney SOTr, but prolonging prophylaxis beyond 24 h was not associated with improved SSI rates (RR 0·87, 95% CI 0·51–1·48). Regarding the duration of antimicrobial treatment for uncomplicated graft-related infections (liver and kidney SOTr), the meta-analyses found no difference in terms of recurrence between short and long antimicrobial regimens (0·86, 95% CI 0·55–1·34). The four meta-analyses had low heterogeneity between studies. Interpretation: Strategies to optimise antimicrobial use are safe, with no negative impact on mortality or transplant-related complications, and appear to improve some clinical outcomes in SOTr, particularly when using perioperative antimicrobial prophylaxis in kidney SOTr and when implementing AMS programmes. No difference in the rate of surgical site infection was found between short and extended duration of antimicrobial prophylaxis for kidney and liver SOTr. This suggests that a shorter duration of antimicrobial surgical prophylaxis may be safe for transplant recipients. Short courses of antibiotics were not associated with an increased rate of relapses for uncomplicated graft infections, according to observational studies pooled in our meta-analysis. However, further high-quality clinical trials are needed to better understand the effects of these strategies in SOTr and to design optimal AMS interventions in this population.

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Effectiveness and safety of strategies to optimise antimicrobial use in solid organ transplant recipients. Systematic review and meta-analyses

Author: Paniagua García, María; Guisado Gil, Ana Belén; Molina Gil-Bermejo, José; Peñalva, Germán; Álvarez Marín, Rocío; Pachón Ibáñez, María Eugenia; Cisneros, José Miguel
Publisher: Elsevier
Year: 2025
Source: https://idus.us.es/bitstreams/131181d8-1607-441e-92d8-df794c9b23db/download
E ec i eness and sa e y o s a egies o op imise
an imic obial use in solid o gan ansplan ecipien s.
Sys ema ic e iew and me a-analyses
Ma ía Paniagua-Ga cía,
a
,
b
,
c
,
e
Ana Belén Guisado-Gil,
a
,
b
,
c
,
d
,
e
José Molina Gil-Be mejo,
a
,
b
,
c
,
∗
Ge mán Peñal a,
a
,
b
,
c
Rocío Ál a ez-Ma ín,
a
,
b
,
c
Ma ía Eugenia Pachón-Ibáñez,
a
,
b
,
c
and José Miguel Cisne os
a
,
b
,
c
a
Clinical Uni o In ec ious Diseases, Mic obiology and Pa asi ology, Vi gen del Rocío Uni e si y Hospi al, Se ille, Spain
b
Ins i u e o Biomedicine o Se ille, Vi gen del Rocío Uni e si y Hospi al/CSIC/Uni e si y o Se ille, Se ille, Spain
c
CIBER de En e medades In ecciosas, Ins i u o de Salud Ca los III (CIBERINFEC, ISCIII), Mad id, Spain
d
Depa men o Pha macy, Vi gen del Rocío Uni e si y Hospi al, Se ille, Spain
Summa y
Backg ound Solid o gan ansplan ecipien s (SOT ) a e a high isk o in ec ious complica ions, and e ec i e
an imic obial s ewa dship (AMS) p og ammes need o be de eloped. We aimed o e iew he a ailable e idence on
he e ec i eness and sa e y o di e en s a egies o op imise an ibio ic use in SOT .
Me hods In ou sys ema ic e iew and me a-analyses, we sea ched MEDLINE ( ia PubMed), EMBASE, and SCOPUS
o o iginal esea ch a icles published up o 06 Ma ch 2025.
S udies wi h a con ol g oup e alua ing di e en s a egies o op imise an imic obial use in adul SOT we e included.
The ou comes assessed we e mo ali y, ansplan - ela ed complica ions, in ec ious ou comes, de elopmen o
an imic obial esis ance, an imic obial consump ion, hospi al ela ed a iables, and an imic obial oxici ies. A isk-
o -bias assessmen was pe o med using he Coch ane EPOC g oup’s c i e ia. Da a om included s udies we e
pooled in me a-analyses i h ee o mo e s udies had he same ype o in e en ion and compa ison g oup and
epo ed su icien da a on in ec ion ou comes o be combined. Me a-analyses we e pe o med using a andom-
e ec s model and he in e se a iance me hod wi h he I
2
s a is ic o es o inconsis ency be ween s udies.
Sensi i i y analyses we e also e alua ed. This s udy ollows he P e e ed Repo ing I ems o Sys ema ic Re iews
and Me a-Analyses (PRISMA) guidelines. PROSPERO ID: CRD42024554606.
Findings O he 4050 a icles iden i ied, 34 s udies me he inclusion c i e ia. Se en een s udies add essed pe iop-
e a i e an imic obial p ophylaxis (se en o which e alua ed speci ically du a ion o an imic obial p ophylaxis), wo
epo ed in o ma ion abou decolonisa ion s a egies, h ee add essed du a ion o an imic obial ea men as a ge
he apy, one e alua ed an ibio ic o al s ep-down s a egy, and six epo ed he impac o AMS implemen a ion
app oach on SOT . The o he i e s udies e alua ed speci ic a ge ed p ophylaxis. All he s udies had a mode a e
o high isk o bias. The me a-analysis o h ee s udies on he e ec o AMS p og ammes showed ha his
in e en ion may educe he a e o su gical si e in ec ions (OR 0⋅57, 95% CI 0⋅35–0⋅94). Fo pe iope a i e
an imic obial p ophylaxis, he me a-analysis o six ials showed esul s in a ou o p ophylaxis in e ms o
educing su gical si e in ec ions ( isk a io 1⋅93, 95% CI 1⋅14–3⋅27) in kidney SOT , bu p olonging p ophylaxis
beyond 24 h was no associa ed wi h imp o ed SSI a es (RR 0⋅87, 95% CI 0⋅51–1⋅48). Rega ding he du a ion o
an imic obial ea men o uncomplica ed g a - ela ed in ec ions (li e and kidney SOT ), he me a-analyses
ound no di e ence in e ms o ecu ence be ween sho and long an imic obial egimens (0⋅86, 95% CI
0⋅55–1⋅34). The ou me a-analyses had low he e ogenei y be ween s udies.
In e p e a ion S a egies o op imise an imic obial use a e sa e, wi h no nega i e impac on mo ali y o ansplan -
ela ed complica ions, and appea o imp o e some clinical ou comes in SOT , pa icula ly when using pe iope a i e
an imic obial p ophylaxis in kidney SOT and when implemen ing AMS p og ammes. No di e ence in he a e o
su gical si e in ec ion was ound be ween sho and ex ended du a ion o an imic obial p ophylaxis o kidney and
li e SOT . This sugges s ha a sho e du a ion o an imic obial su gical p ophylaxis may be sa e o ansplan
ecipien s. Sho cou ses o an ibio ics we e no associa ed wi h an inc eased a e o elapses o uncomplica ed
g a in ec ions, acco ding o obse a ional s udies pooled in ou me a-analysis. Howe e , u he high-quali y
*Co esponding au ho . Clinical Uni o In ec ious Diseases, Mic obiology and Pa asi ology, Vi gen del Rocío Uni e si y Hospi al, Se ille, Spain.
E-mail add ess: [email p o ec ed] (J. Molina Gil-Be mejo).
e
These au ho s con ibu ed equally o his wo k.
eClinicalMedicine
2025;85: 103310
Published Online xxx
h ps://doi.o g/10.
1016/j.eclinm.2025.
103310
www. helance .com Vol 85 July, 2025 1
A icles
clinical ials a e needed o be e unde s and he e ec s o hese s a egies in SOT and o design op imal AMS
in e en ions in his popula ion.
Funding This s udy was suppo ed by he Ins i u o de Salud Ca los III (ISCIII, e e ence ICI21/00075) and he Cen o
de In es igación Biomédica en de En e medades In ecciosas (CIBERINFEC, CB21/13/00006), ISCIII, Minis e io de
Ciencia e Inno ación.
Copy igh © 2025 The Au ho (s). Published by Else ie L d. This is an open access a icle unde he CC BY-NC-ND
license (h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/).
Keywo ds: Solid o gan ansplan a ion; An imic obial s ewa dship; An ibio ics; Immunosupp ession; An imic obial
esis ance
In oduc ion
Solid o gan ansplan a ion (SOT) has become an
impo an me hod o ea ing end-s age o gan disease.
Imp o emen s in su gical echnique and pos ope a i e
ca e, as well as ad ances in he p e en ion, diagnosis
and ea men o in ec ions, ha e led o a signi ican
imp o emen in quali y o li e and p olonged su i al.
Ne e heless, complex su ge ies, equen exposu e o
an ibio ics, and immunosupp essi e egimens pu solid
o gan ansplan ecipien s (SOT ) a a disp opo ion-
a ely high isk o in ec ion, especially by mul i- esis an
o ganisms (MDRO), which cloud he p ognosis.
1–3
The cu en an imic obial and bac e ial esis ance
c isis
4
has a huge impac on hose mos ulne able o
in ec ion. In a 2018 s udy, da a on an imic obial use in
SOT show ha in sou he n Eu ope, up o 76⋅9% o
pa ien s admi ed o ansplan uni s (solid o gan o
bone ma ow) ecei e an ibio ics, compa ed wi h 66⋅5%
Resea ch in con ex
E idence be o e his s udy
Solid o gan ansplan a ion (SOT) exposes pa ien s o an
inc eased isk o impai ed clinical ou comes ela ed o
inapp op ia e an imic obial ea men and mul id ug
esis an mic oo ganisms. This is why de eloping sa e and
e ec i e an imic obial s ewa dship (AMS) ini ia i es is
especially ele an in his popula ion. SOT pa ien s ha e been
excluded om mos andomised ials ackling c i ical aspec s
o an imic obial op imisa ion (like ea men du a ion), and
only na a i e e iews and call- o-ac ion pape s ha e been
published on his ele an opic.
We conduc ed a li e a u e sea ch o o iginal esea ch a icles
published om incep ion o Ma ch 6, 2025, wi h no
language es ic ions, using MEDLINE, EMBASE and SCOPUS.
Randomised clinical ials, obse a ional analy ical s udies,
quasi-expe imen al, and in e up ed ime se ies analyses wi h
a con ol g oup we e included. Inclusion c i e ia we e based
on he Popula ion, In e en ion, Compa ison, Ou come
(PICO) app oach: (P) Adul SOT pa ien s; (I) Speci ic
in e en ions a ge ing in ec ion p e en ion, indi idual
pa ien ’s ea men op imisa ion, o ans e sal AMS
in e en ions implemen a ion in SOT uni s; (C) Pa ien s o
pe iods wi hou he assessed in e en ion; (O) A leas one
o he ollowing: mo ali y, ansplan - ela ed complica ions,
incidence o in ec ions, an imic obial consump ion,
an imic obial esis ance; hospi al s ay, eadmission a es,
and/o an imic obial oxici ies.
All iden i ied s udies had a mode a e o high isk o bias.
Added alue o his s udy
In his a icle we p esen a sys ema ic e iew wi h se e al
me a-analyses which aim, on one hand, o pool accumula ed
e idence on se e al AMS in e en ions de eloped speci ically
o SOT , and on he o he hand, o map cu en a eas o
unce ain y and p io i y esea ch needs.
S udies iden i ied in his e iew enabled ou me a-analyses
ega ding pe iope a i e p ophylaxis, ea men du a ion o
uncomplica ed g a - ela ed in ec ions and he e ec s o
ans e sal implemen a ion o AMS in SOT uni s.
Acco ding o ou esul s, sho e pe iope a i e an imic obial
p ophylaxis, sho e ea men du a ion o uncomplica ed
g a in ec ions, and he implemen a ion o an AMS
p og ammes in ansplan uni s, may educe an ibio ic
consump ion in hese uni s wi hou impai ing clinical
ou comes o in ec ions, and may help o p e en su gical si e
in ec ions.
Implica ions o all he a ailable e idence
The conclusions o ou sys ema ic e iew and me a-analyses
a e mainly d i en by obse a ional s udies wi h a signi ican
isk o bias, and hus mus be alida ed by u he
andomised ials, which could be suppo ed by he da a
p esen ed in his a icle.
In his e iew we also iden i ied c i ical a eas in u gen need
o e idence. The e is s ill a pauci y o da a o SOT o he
han kidney o li e ecipien s, and also on he
demons a ion o nea clinical bene i s o AMS in e en ions
beyond he educ ion o an ibio ic consump ion, including
imp o ed clinical ou comes and bac e ial esis ance in he
ansplan uni s.
A icles
2 www. helance .com Vol 85 July, 2025
in No h Ame ica.
5
Fu he mo e, in a e ospec i e
s udy o 176 audi s o an ibio ic ea men adequacy in
SOT , mo e han 40% o p esc ip ions we e ound o be
inapp op ia e.
6
These da a show he need o imp o e
he use o an imic obials in SOT , who a e pa icula ly
ulne able o in ec ion as well as d ug in e ac ions and
side e ec s.
In he igh agains an imic obial esis ance, p e-
en i e s a egies play an impo an ole in educing
isk o in ec ion and i s consequences o bo h pa ien
and g a su i al: ac i e su eillance o MDRO ca ie
s a us, a ge ed pe iope a i e an imic obial p ophylaxis,
decolonisa ion s a egies, pos - ansplan an imic obial
p ophylaxis, and ea ly ac i e empi ic ea men .
7
How-
e e , hese p e en i e s a egies should be in eg a ed
wi h an imic obial s ewa dship (AMS) p og ammes,
which aim o op imise clinical ou comes and minimise
he unin ended consequences o an imic obial use,
including oxici y, selec ion o pa hogenic o ganisms
(such as Clos idioides di icile) and he eme gence o
esis ance, as well as o educe cos s wi hou nega i ely
impac ing quali y o ca e.
8
In c oss-sec ional s udies o all hospi alised pa ien s,
AMS in e en ions ha e been shown o imp o e an i-
mic obial use, gene ally by educing consump ion and
mic obiological esis ance and by imp o ing he p e-
sc ibing p o ile, wi h clinical bene i s.
9
Howe e , he
gene alised applica ion o AMS measu es may no be
applicable in SOT , as i does no ake in o accoun all
he ansplan -speci ic a iables ( ime since ansplan ,
ype o immunosupp ession, o gan ansplan ed, in-
ec ions de i ed om dono , polypha macy and d ug
in e ac ions, among o he s).
8,10
In addi ion, he SOT
popula ion is o en unde - ep esen ed in clinical ials
o AMS in e en ions, and guidelines o en do no
p o ide speci ic ecommenda ions. The e a e also ba -
ie s ha hinde implemen a ion o AMS s a egies in
SOT popula ion, such as physician pe cep ions o pa-
ien complexi y, anxie y ega ding disease se e i y, and
a ia ion in hos isk ac o s, such as he le el o
immunosupp ession, ecen su ge y, and he po en ial
o d ug in e ac ions.
11
Gi en he lack o da a, ce ain
issues such as choice o empi ical ea men , du a ion
o ea men , among o he s, a e usually le o he
disc e ion o he ea ing physician.
8,10
Despi e ongoing e o s by solid o gan ansplan
socie ies
8,10
o inco po a e he p inciples o AMS in o
daily p ac ice, he e is s ill li le e idence in his popu-
la ion. Cu en AMS p ac ice guidelines do no add ess
speci ic in e en ions in SOT .
12,13
Howe e , AMS in-
e en ions ha e been shown o be e ec i e and sa e in
o he immunosupp essed popula ions, such as onco-
haema ological pa ien s.
14,15
In ecen yea s, se e al calls
o ac ion ha e been published highligh ing he need o
mul idisciplina y app oaches, including close collabo-
a ion wi h ansplan expe s, and he use o apid and
app op ia e mic obiological diagnos ics o guide
ea men and op imise du a ion.
16–18
Al hough his is a
p io i y opic, o da e only na a i e e iews o AMS in-
e en ions ha e been published, wi h no sys ema ic e-
iew o he a ailable e idence o ou knowledge.
To be e unde s and he exis ing e idence and o
suppo op imal AMS in e en ions in his popula ion,
ou s udy p esen s a sys ema ic e iew and me a-analyses
o s udies epo ing on he e ec i eness and sa e y o
di e en s a egies o op imise an imic obial use in SOT .
Me hods
E hics
The sys ema ic e iew and me a-analyses we e con-
duc ed in acco dance wi h he P e e ed Repo ing
I ems o Sys ema ic Re iews and Me a-Analyses
(PRISMA) guidelines.
19
The e iew p o ocol was egis-
e ed in he In e na ional P ospec i e Regis e o Sys-
ema ic Re iews (PROSPERO) Da abase ( egis a ion
numbe : CRD42024554606).
Sea ch s a egy
We conduc ed an elec onic li e a u e sea ch o o ig-
inal esea ch a icles published om incep ion o 20
May 2024, wi h no language es ic ions, using h ee
heal h da abases: MEDLINE ( ia PubMed), EMBASE,
and SCOPUS. The sea ch ield was he i le and e ms
included bo h MeSH e ms and ee ex (keywo ds,
synonyms and wo d a ia ions) combined wi h Boolean
ope a o s (see Supplemen al Table S1 o he ull sea ch
s a egy). The sea ch s a egy was de eloped o
PubMed and hen adap ed app op ia ely o use in each
da abase. Ci a ions o included e e ences and ele an
sys ema ic e iews we e sea ched o iden i y addi ional
s udies. Email ale s we e c ea ed in he heal h da a-
bases o check o po en ial inclusion o a icles pub-
lished a e he sea ch da e and un il 06 Ma ch 2025.
Selec ion c i e ia
Inclusion c i e ia based on he Popula ion, In e en-
ion, Compa ison, Ou come and S udy (PICOS) design
o he sys ema ic e iew and me a-analyses we e adul
(≥18 yea s old) SOT , bo h inpa ien and ou pa ien ,
ega dless o he ime o ansplan a ion. The e alua ed
in e en ions included speci ic an imic obial s a egies
designed o op imise he p e en ion o in ec ions, such
as pe iope a i e an imic obial p ophylaxis (including
e icacy and du a ion), decolonisa ion s a egies and
o he speci ic s a egies o op imising p e en ion.
Speci ic s a egies o op imise an imic obial ea men
we e also e alua ed, including he iming o empi ical
ea men ini ia ion, he choice o empi ical o a ge ed
ea men agen s, de-escala ion, o al s ep-down he apy,
ea men du a ion, and an ibio ic alle gy de-labelling.
O he in e en ions e alua ed we e hose ela ed o
he implemen a ion o speci ic AMS in e en ions,
including educa ional, pe suasi e, es ic i e o
A icles
www. helance .com Vol 85 July, 2025 3
s uc u al app oaches. The compa a o was a con ol
g oup o SOT who did no ecei e he in e en ion
unde e alua ion, o co esponding ime pe iods in
p e-pos s udies. Ou comes included a leas one o
he ollowing, wi h no p ima y ou come equi ed:
ou comes ela ed o e ec i eness, such as global
mo ali y, ansplan - ela ed complica ions (e.g., g a
dys unc ion o ejec ion), in ec ions (including clinical
ailu e, mic obiological ailu e, elapse o ecu ence,
supe in ec ions, and C. di icile in ec ions), an imi-
c obial consump ion, and/o an imic obial esis ance;
and ou comes ela ed o sa e y, such as he need o
hospi alisa ion, p olonged hospi al s ay, need o
ehospi alisa ion, admission o in ensi e ca e uni s
(ICUs), and/o an imic obial oxici ies. Eligible s udy
designs included andomised clinical ials (RCTs),
obse a ional analy ical s udies (coho o case-con ol
s udies), p e-pos s udies, and in e up ed ime se ies
analyses.
We excluded duplica e eco ds using Mendeley,
20
cong ess abs ac s, and s udies assessing unapp o ed
subs ances o subs ances no used in ou ine clinical
p ac ice. T ials ela ed o i al in ec ions (cy omegalo-
i us and BK i us, among o he s) we e excluded, as
hese a e he subjec o mo e ex ensi e s udies
21
and a e
no he subjec o his e iew. We did no include
s udies abou managemen o asymp oma ic bac e iu ia
in kidney ansplan ecipien s, as hese ha e been
add essed in ecen sys ema ic e iews,
22,23
which sug-
ges ha sys ema ic sc eening and ea men o
asymp oma ic bac e iu ia beyond he second mon h
a e ansplan a ion p o ide no appa en bene i
among kidney ansplan ecipien s. An i ungal p o-
phylaxis was also excluded, as ecen sys ema ic e iews
ha e add essed his issue, bo h in he gene al SOT
popula ion and by ype o ansplan , mos commonly
lung
24,25
and li e ,
26,27
bu also hea ansplan a ion.
28
The i les and abs ac s o all iden i ied a icles we e
sc eened o eligibili y by wo independen e iewe s
(MPG and ABGG). I he eligibili y o a s udy was no
mu ually ag eed upon o was no clea om he i le
and abs ac alone, he a icle was included in he ull-
ex e iew s age. Finally, he ull pape s o he p e-
selec ed s udies we e assessed be o e a inal decision on
hei inclusion was made. Any disag eemen s we e
esol ed by consensus o wi h a hi d e iewe (JMC).
Da a ex ac ion
The da a was collec ed in duplica e by wo independen
e iewe s (MPG and ABGG) om a icles selec ed o
inclusion in he e iew. Fo each publica ion, he
ollowing a iables we e eco ded:
- Au ho and yea o publica ion.
- Coun y.
- S udy pe iod.
- S udy design.
- S udy unding: public o p i a e unding, o wi hou
inancial suppo .
- Numbe o hospi als included and mean numbe o
beds.
- Numbe o pa ien s.
- Pa ien ’s cha ac e is ics: age, sex, ype o ansplan ,
immunosupp ession/ ejec ion ea men .
- Time since ansplan (i a ailable).
- Type o in e en ion assessed.
- Type o in ec ion a ge ed by he in e en ion.
- Compa a o g oup: s anda d o ca e o a di e en
in e en ion.
- Du a ion o in e en ion and ou come measu emen
ime ame, in mon hs.
- Le el o compliance wi h he in e en ion:
comple eness and ideli y.
- Ou comes.
Quali y assessmen
The isk o bias o each s udy was assessed by wo in-
dependen au ho s (MPG and ABGG) using he
Coch ane EPOC g oup’s c i e ia. Disc epancies in he
quali y assessmen we e esol ed h ough discussion
wi h a hi d e iewe (JMC) o a i e a a inal desig-
na ion o each domain. Based on he Coch ane EPOC
g oup’s isk o bias ool,
29
s udies we e gi en a sco e o
low, high o unclea isk o bias o he ollowing
c i e ia: andom sequence gene a ion; alloca ion
concealmen ; baseline ou come measu emen s simila ;
baseline cha ac e is ics simila ; incomple e ou come
da a; knowledge o he alloca ed in e en ions
adequa ely p e en ed du ing he s udy; p o ec ion
agains con amina ion; selec i e ou come epo ing;
and o he isks o bias. A summa y o he isk-o -bias
assessmen sco es was assigned o each s udy as ol-
lows: ‘low isk o bias’ when all c i e ia we e sco ed as
‘low’; ‘mode a e isk o bias’ i one c i e ion o wo
c i e ia we e sco ed as ‘unclea ’ o ‘high’; and ‘high isk
o bias’ i mo e han wo c i e ia we e sco ed as ‘un-
clea ’ o ‘high’. REVMAN so wa e Ve sion 5⋅4⋅1 was
used o colla e and p esen he isk-o -bias esul s.
Da a syn hesis and me a-analysis
Fo desc ip i e pu poses, we ex ac ed he da a a ailable
in he included s udies by in e en ion and con ol
g oups. Ra ios o o he s a is ics such as p- alues we e
also ex ac ed whe e a ailable.
We also sough o pool he da a om he a icles
included in he sys ema ic e iews. To do his, we
g ouped ials ha included di e en ypes o SOTs and
he same ype o in e en ion, assuming ha he
e ec i eness o he in e en ions was compa able.
Me a-analyses we e only pe o med i h ee o mo e
s udies wi h simila ypes o in e en ion, con ol
g oups and ou come measu es could be combined. Fo
his pu pose, da a on he p edic ed clinical ou comes
should be epo ed as he numbe o e en s and o al
A icles
4 www. helance .com Vol 85 July, 2025
pa ien s in each a m o , al e na i ely, he di e ence
be ween a ms as he mean and s anda d de ia ion.
Whene e possible, he same ime o ou come assess-
men was de ined o he me a-analyses. I his in o -
ma ion was no a ailable, we used he closes measu e.
In he case o duplica e coho s, p io i y was gi en o
esul s based on la ge sample sizes. I he e was
insu icien o incomple e in o ma ion in he published
ex , missing da a we e eques ed om he s udy au-
ho s. Subg oup analyses, using he same c i e ia as
desc ibed abo e, we e pe o med o analyse he e ec s
o in e en ions in di e en ansplan popula ions
when a su icien numbe o ials we e a ailable.
S a is ics
Me a-analyses we e pe o med using a andom-e ec s
model and he in e se a iance me hod. The odds a-
io (OR) o p e-pos s udies o he isk a io (RR) o
obse a ional s udies and RCTs wi h a 95% con idence
in e al (CI) we e calcula ed based on he epo ed da a.
S udies wi h 0 coun s in a leas one a m ecei ed a
con inui y co ec ion (adding 0⋅5). We used he I
2
es o
assess s a is ical he e ogenei y.
30
A alue o less han
40% ep esen ed low he e ogenei y, a alue be ween
40% and 60% ep esen ed mode a e he e ogenei y, and
a alue o mo e han 60% ep esen ed high he e oge-
nei y. Sensi i i y analyses we e pe o med by emo ing
ials wi h 0 coun s in a leas one a m o ensu e he
obus ness o he esul s. A ixed-e ec s model was also
used o sensi i i y analyses. REVMAN so wa e
Ve sion 5⋅4⋅1 was used o un he me a-analysis, and
he esul s we e p esen ed in o es plo s.
Role o he unding sou ce
This s udy was suppo ed by he Ins i u o de Salud Ca los
III, (ISCIII, e e ence ICI21/00075) and he CIBER de
En e medades In ecciosas (CIBERINFEC, CB21/13/
00006), ISCIII, Minis e io de Ciencia e Inno ación. The
Funde s had no ole in s udy design, da a collec ion, da a
analyses, in e p e a ion, o w i ing o he epo .
Resul s
The elec onic sea ch e u ned 4050 eco ds; 2063 we e
emo ed a e duplica e checking. A u he 1889 pub-
lica ions we e excluded a e i le and abs ac il e ing,
because hey did no mee he eligibili y c i e ia. This
le 98 po en ially ele an s udies ha we e e ie ed in
ull ex : 67 we e excluded be o e da a ex ac ion and 31
me he inclusion c i e ia. Th ee addi ional s udies we e
e ie ed om ci a ions, lea ing 34 included s udies
(Fig. 1).
31–64
Fi e au ho s we e con ac ed and h ee o
hem we e able o p o ide he eques ed da a.
Cha ac e is ics o s udies and in e en ions
Table 1 shows he cha ac e is ics o he s udies e alu-
a ed. S udy designs included 10 RCTs,
31–36,41,44,52,53
13 p e-
pos s udies,
37,39,42,43,45,48,49,59–64
and 11 obse a ional
s udies.
38,40,46,47,50,51,54–58
Mos o he s udies ook place in
he USA (n = 12),
31,36,42,44–49,51,58,62
ollowed by Spain
(n = 4),
35,37,61,63
and Ge many (n = 4).
32,43,50,56
Mos s udies
(33/34, 97⋅6%) epo ed he cha ac e is ics o pa ien s
included; howe e , ansplan speci ic de ails (i.e., g a
dis unc ion, ejec ion ea men , dono cha ac e is ics,
e c.) we e only epo ed in hal o he s udies (18/34,
52⋅9%). A o al o 7367 pa ien s we e included in he 34
e alua ed ials (mean numbe was 136⋅50 pa ien s pe
s udy, in e qua ile ange (IQR) 58⋅25–201⋅25). O
hese, 5967 we e SOT , as he s udy by Sha ekhani
e al.
64
also included in o ma ion on 1400 pa ien s on
he wai ing lis o ansplan a ion. In e ms o ype o
o gan ansplan ed, he dis ibu ion was as ollows:
3514 kidney (58⋅9%), 1920 li e (32⋅2%), 381 lung
(6⋅4%), 69 panc eas (1⋅2%), 55 li e -kidney (0⋅9%), 49
kidney-panc eas (0⋅8%), 40 in es inal/mul i isce al
(0⋅7%), 29 hea (0⋅5%), and 15 combined hea -lung
(0⋅3%). Some pa ien s may be included mo e han
once, as some s udies eco ded mo e han one episode
pe pa ien .
58
E alua ed in e en ions we e mul iple. A b ie
desc ip ion o each in e en ion is gi en in Table 2,
oge he wi h da a abou mo ali y, ansplan ela ed
a iables and in ec ions o each included s udy.
Se en een
33,34,36,39,43,44,46,47,51,54,55,57,58,60,61,63,64
epo ed da a
abou mo ali y, and e en i he e alua ed in e en ions
we e di e en , none o hem showed an inc ease in
mo ali y. Da a abou ansplan ela ed complica ions
(which include acu e ejec ion, g a dys unc ion,
dono -de i ed in ec ion, and e u n o dialysis) was e-
po ed in nine s udies
34,36,37,41,43,44,46,47,63
and no di e ence
among con ol and in e en ion g oup was ound. All
s udies excep one
64
epo ed in o ma ion abou inci-
dence o di e en in ec ions a e implemen a ion o a
gi en in e en ion. Mos common epo ed in ec ions
we e su gical si e in ec ions, ollowed by global pos -
ansplan in ec ion, bloods eam in ec ions, u ina y
ac in ec ions and C. di icile in ec ion.
Eigh s udies ga e in o ma ion abou an imic obial
consump ion,
47,57,58,60–64
12 abou an imic obial esis-
ance, and 12 on he ype and du a ion o he hospi al
ca e equi ed (hospi alisa ion, leng h o s ay, o
admission o ICU)
36,43–47,49,55,60,61,63,64
(Supplemen al
Table S2). None o he 34 ials epo ed da a on an i-
mic obial side e ec s.
Li le da a was p o ided on each pa icipa ing cen-
e’s le el o compliance wi h he e alua ed in e en-
ion, and only i e s udies o e ed da a abou
compliance.
41,43,44,47,63
Fou s udies assessed compliance
ela ed o an imic obial p ophylaxis,
41,43,44,47
epo ing
high adhe ence (>80%) in h ee o hem
41,43,44
and
mode a e in ano he s udy (<70%).
47
The o he s udy
63
e alua ed he impac o an AMS p og amme, in
which ecommenda ions we e accep ed in 91⋅7% o
cases.
A icles
www. helance .com Vol 85 July, 2025 5

The compa a o g oup was a iable: in 18 ials he
con ol g oup ecei ed no ea men o in e en ion,
while in 16 ials he in e en ion g oup was compa ed
wi h ano he g oup ha ecei ed a speci ic ea men o
in e en ion acco ding o clinical p ac ice.
Quali y o s udies
Fig. 2 shows he sco es ob ained o each c i e ion o he
Coch ane EPOC g oup’s isk-o -bias ool. The o e all
isk o bias was high o 26 s udies
31–40,42,43,45,46,48,50–59,61,62
and mode a e o eigh ,
38,41,44,47,49,60,63,64
and none o he
s udies we e classi ied as ha ing ‘low isk o bias’.
Supplemen al Figu e S1 shows e iew au ho s’ judge-
men s abou each isk-o -bias i em p esen ed as pe -
cen ages ac oss all included s udies.
All s udies showed simila i ies in he sco es o each
domain. P e-pos s udies and non-RCTs (24/34, 70⋅6%)
we e sco ed as ‘high isk’ o andom sequence gene a-
ion and alloca ion concealmen . Fo RCTs (10/34,
29⋅4%), mos we e conside ed o be a low isk o selec ion
bias, wi h he excep ion o Salehipou e al.,
53
whe e in-
o ma ion on he andomisa ion and alloca ion me hod
was missing. Fo baseline ou comes and cha ac e is ics,
da a om he in e en ion and con ol g oups we e
compa able in 12 s udies (35⋅3%),
30,37–40,47–49,51,54,57,58
and in
he o he s udies s a is ically signi ican di e ences we e
obse ed in he baseline analysis o baseline measu es
we e no pe o med. Missing ou come measu es may
ha e biased he esul s in h ee s udies (8⋅8%).
32,39,51
The
p ima y ou come a iables we e assessed blindly o he
esul s we e objec i e in 12 s udies
(35⋅3%).
45,47,49,51,54,55,57,58,60,62–64
The s udy by Ga cía P ado ME
e al.
37
lacked mo ali y ou comes o he pa ien g oups.
Resul s o speci ic in e en ions
Pe iope a i e an imic obial p ophylaxis
Se en een s udies add essed pe iope a i e an imic o-
bial p ophylaxis, some o which included di e en ypes
o ansplan a ion: mainly enal (n = 12),
31–36,38–43
bu also
li e (n = 4),
37,44,45,47
hepa o enal (n = 2),
37,45
lung (n = 1),
46
and panc eas (n = 1).
36
No a icles abou p ophylaxis in
hea ansplan a ion we e ound. Se en s udies e alu-
a ed du a ion o an imic obial pe iope a i e p ophylaxis
in kidney (n = 3),
41–43
li e (n = 3),
44,45,47
and lung
ansplan a ion (n = 1).
46
The emaining se en s udies
assessed pe iope a i e an ibio ic p ophylaxis e icacy:
se en o hem compa ing an imic obial p ophylaxis
wi h no p ophylaxis in kidney ansplan a ion,
31–35,38,40
one o hem e alua ing he e icacy o addi ion o an-
comycin in kidney and panc eas ansplan ecipien s,
36
one e alua ing he addi ion o gen amicin in kidney
ansplan a ion,
39
and one las s udy in li e ans-
plan a ion compa ing amoxicillin/cla ulana e wi h
ce azolin p ophylaxis.
37
No di e ences ega ding global mo ali y we e e-
po ed in he eigh s udies whe e his a iable was
Fig. 1: PRISMA 2020 low diag am o new sys ema ic e iews which included sea ches o da abases and egis e s only.
A icles
6 www. helance .com Vol 85 July, 2025
S udy ID Coun y Pe iod
(yea s)
Design Numbe o
pa ien s
Type o
ansplan
In e en ion Du a ion
(mon hs) o
assessed
in e en ion
Main ou come assessed
Townsend e al.,
1980
31,
a
Uni ed
S a es
1976–1978 Randomised
clinical ial
37 Kidney Pe iope a i e an ibio ic p ophylaxis 17 Pos - ansplan global
in ec ions
Wilms e al.,
1986
32,
a
Ge many 1982 Randomised
clinical ial
34 Kidney Pe iope a i e an ibio ic p ophylaxis Un il hospi al
discha ge
Pos - ansplan global
in ec ions
E ans e al.,
1988
33,
a
Uni ed
Kingdom
1983 Randomised
clinical ial
46 (34
ansplan
su ge ies)
Kidney Pe iope a i e an ibio ic p ophylaxis 1 SSIs
Cohen e al.,
1988
34,
a
Uni ed
Kingdom
1984–1985 Randomised
clinical ial
53 Kidney Pe iope a i e an ibio ic p ophylaxis 14 days Pos - ansplan global
in ec ions
Robles e al.,
1990
35,
a
Spain 1986–1987 Randomised
clinical ial
60 Kidney Pe iope a i e p ophylaxis 1 SSIs, UTI
P unds ein e al.,
2001
36,
a
Uni ed
S a es
1994–1995 Randomised
clinical ial
112 Kidney, Panc eas Pe iope a i e an ibio ic p ophylaxis 12 Pos - ansplan global
in ec ion, SSIs
Ga cía P ado e al.,
2008
37
Spain 2003–2006 P e-pos
s udy
167 Li e , Li e -
kidney
Pe iope a i e an ibio ic p ophylaxis 12 SSIs
Choi S e al.,
2010
38
Sou h
Ko ea
2006–2008 Re ospec i e
obse a ional
106 Kidney Pe iope a i e an ibio ic p ophylaxis 36 Pos - ansplan global
in ec ions
Abboud e al.,
2013
39
B azil 2009–2011 P e-pos
s udy
45 Kidney Pe iope a i e an ibio ic p ophylaxis 10 Pos - ansplan heal hca e-
associa ed in ec ions
Choi e al.,
2013
40,
a
Sou h
Ko ea
2006–2010 Re ospec i e
obse a ional
174 Kidney Pe iope a i e an ibio ic p ophylaxis 55 Pos - ansplan in ec ion
O lando e al.,
2015
41,
a
I aly 2006–2012 Randomised
clinical ial
205 Kidney Pe iope a i e an ibio ic p ophylaxis
(du a ion)
65 SSIs
Bli en e al.,
2018
42,
a
Uni ed
S a es
2013–2015 P e-pos
s udy
100 Kidney Pe iope a i e an ibio ic p ophylaxis
(du a ion)
32 SSIs
Bachmann el al.
2019
43,
a
Ge many 2014–2017 P e-pos
s udy
212 Kidney Pe iope a i e an ibio ic p ophylaxis
(du a ion)
21 SSIs
Be y e al.,
2019
44,
a
Uni ed
S a es
2010–2015 Randomised
clinical ial
102 Li e Pe iope a i e an ibio ic p ophylaxis
(du a ion)
63 SSIs
Bandali e al.,
2020
45,
a
Uni ed
S a es
2013–2015 P e-pos
s udy
44 Li e , Li e -
kidney
Pe iope a i e an ibio ic p ophylaxis
(du a ion)
16 Pos - ansplan global
in ec ions
G o e al., 2021
46
Uni ed
S a es
2013–2019 Re ospec i e
obse a ional
147 Lung Pe iope a i e an ibio ic p ophylaxis
(du a ion)
74 Recipien eedom om
dono -de i ed espi a o y
bac e ial in ec ion
Yau e al., 2022
47,
a
Uni ed
S a es
2016–2019 Re ospec i e
obse a ional
216 Li e Pe iope a i e an ibio ic p ophylaxis
(du a ion)
45 DOT a e ansplan su ge y
Singh e al.,
2006
48
Uni ed
S a es
1996–2004 P e-pos
s udy
144 Li e S. au eus sc eening and decolonisa ion 48 S. au eus in ec ion o
colonisa ion
Lee e al., 2020
49
Uni ed
S a es
2014–2016 P e-pos
s udy
121 Kidney Uni e sal pos ope a i e decolonisa ion 23 Pos - ansplan global
in ec ions
Wol e s e al.,
2014
50
Ge many NS P ospec i e
obse a ional
40 Kidney An imic obial p ophylaxis p io o u ina y
ca he e emo al
NS UTIs
Kohli e al., 2018
51
Uni ed
S a es
2008–2015 Re ospec i e
obse a ional
69 Li e An imic obial p ophylaxis p io o ERCP 24 h wi hin ERCP ERCP ela ed BSIs
Salmela e al.,
1990
52
Finland 1987–1989 Randomised
clinical ial
182 Kidney Pe iope a i e in a esically an ibio ic
i iga ion
24 UTIs, SSIs
Salehipou e al.,
2009
53
I an 2006–2007 Randomised
clinical ial
200 Kidney Pe iope a i e in a esically an ibio ic
i iga ion
5 UTIs
Haja Mydin e al.,
2012
54
Uni ed
Kingdom
2000–2010 Re ospec i e
obse a ional
129 Lung Speci ic p e en ion op imisa ion s a egies
(Choice o p e-su gical p ophylaxis acco ding
o mic obiological es )
120 Pos -lung ansplan global
in ec ions
A ni-Nachman
e al., 2021
55,
a
Is ael 2011–2019 Re ospec i e
obse a ional
214 Kidney Du a ion o ea men (UTI) No applicable UTIs
Fe s l e al.,
2022
56,
a
Ge many 2008–2019 Re ospec i e
obse a ional
30 Li e Du a ion o ea men (cholangi is) No applicable Acu e cholangi is
Miwa e al.,
2025
57,
a
Japan 2010–2022 Re ospec i e
obse a ional
91 Li e Du a ion o ea men (uncomplica ed G am
nega i e-BSI)
No applicable Composi e end-pon : 30-day
mo ali y and ecu ence o
in ec ion o BSI
Nussbaum e al.,
2024
58
Uni ed
S a es
2016–2021 Re ospec i e
obse a ional
147 All ypes (>65%
Kidney)
O al an ibio ic s ep-down he apy No applicable Uncomplica ed g am-
nega i e BSIs
(Table 1 con inues on nex page)
A icles
www. helance .com Vol 85 July, 2025 7
included.
33,34,36,39,43,44,46,47
No di e ences in ansplan -
ela ed complica ions we e epo ed in he eigh a i-
cles ha add essed his issue.
34,36,37,41,43,44,46,47
All he ials
looked a in ec ious complica ions. None o hem
showed an inc ease in in ec ion a es a e he in e -
en ion, and some e en showed signi ican pos -
in e en ion bene i s.
When compa ed wi h no p ophylaxis, pe iope a i e
an imic obial p ophylaxis was shown o signi ican ly
dec ease he numbe o o al in ec ions in one s udy,
34
bu no di e ences be ween he wo g oups we e
obse ed in he o he six s udies.
31–33,35,38,40
Da a om
six o hese se en s udies we e pooled in a me a-
analysis compa ing pe iope a i e an imic obial p o-
phylaxis s no p ophylaxis and hei espec i e impac
on he a e o su gical si e in ec ions (SSIs) in kidney
ecipien s.
31–35,40
The s udy o Choi e al. (2010)
38
was
no included, as da a was duplica ed om Choi e al.
(2013).
40
The pooled da a om hese six s udies
(Fig. 3A) showed a signi ican educ ion in SSIs, wi h
an RR o 1⋅93 in a ou o an imic obial p ophylaxis
(95% CI 1⋅14–3⋅27) and low he e ogenei y be ween
ials (I
2
0%). These esul s we e consis en wi h he
sensi i i y analysis using a ixed-e ec model (RR 1⋅93,
95% CI 1⋅14–3⋅27). The E ans e al.
33
s udy had
0 coun s in he p ophylaxis g oup, so he con inui y
co ec ion was applied by de aul and a e y wide CI
(0⋅82–243) was obse ed. This indica es a e y imp e-
cise and po en ially biased e ec es ima e, e en
hough he con ibu ion o his s udy o he me a-
analysis was he lowes (3⋅4%). As a consequence,
he esul s o he sensi i i y analysis excluding his
s udy emained una ec ed (RR 1⋅80, 95% CI
1⋅05–3⋅07).
The addi ion o gen amicin in kidney ans-
plan a ion
39
p oduced no di e ence in su gical si e
in ec ions, bu a signi ican dec ease was obse ed in
u ina y ac in ec ions (UTIs). On he o he hand,
addi ion o ancomycin o he s anda d pe iope a i e
p ophylaxis in kidney and panc ea ic ansplan a ion
p oduced no di e ence in g am-posi i e in ec ion
a es in bo h ypes o ansplan s. No di e ences in
SSIs o bloods eam in ec ions (BSIs) we e ound
when compa ing amoxicillin-cla ulana e wi h ce a-
zolin as p ophylaxis in li e ansplan a ion.
37
Rega ding du a ion o p esu gical an imic obial
p ophylaxis, he se en s udies ha e alua ed his
aspec in enal,
41–43
li e
44,45,47
o lung
46
ansplan pa-
ien s concluded ha p olonged p ophylaxis did no
dec ease he o al numbe o in ec ions. A me a-
analysis o pooled da a om six s udies
41–45,47
e alu-
a ing sho (a single p esu gical dose
41–44,47
o 24 h
45
) s
ex ended p ophylaxis (>24 h) on he a e o SSIs was
pe o med (Fig. 3B), bo h in kidney
41–43
and li e
ansplan ecipien s.
44,45,47
The s udy by G o was
excluded om he me a-analysis as i assessed a
di e en clinical con ex ; p ophylaxis du a ion in lung
ansplan ecipien s om cul u e-posi i e dono s,
wi h dono -de i ed in ec ions as he p ima y endpoin ,
a he han su gical si e in ec ions. Gi en his unda-
men al di e ence, i was no conside ed compa able o
he s udies included. The e we e no signi ican di -
e ences in he a e o SSIs when compa ing sho and
ex ended p ophylaxis (RR 0⋅87, 95% CI 0⋅51–1⋅48).
The same esul was ound in he sensi i i y analyses
using a ixed-e ec model. Fo kidney SOT , he RR
was 1⋅52 (95% CI 0⋅43–5⋅37) wi h low he e ogenei y
be ween s udies (I
2
17%), and o li e SOT , he RR
S udy ID Coun y Pe iod
(yea s)
Design Numbe o
pa ien s
Type o
ansplan
In e en ion Du a ion
(mon hs) o
assessed
in e en ion
Main ou come assessed
(Con inued om p e ious page)
F ene e e al.,
2016
59,
a
Canada 2010–2014 P e-pos
s udy
1386 Li e , Kidney,
Panc eas,
Panc eas–kidney
AMS in e en ion + in ec ion con ol 24 SSIs
So e al., 2019
60
Canada 2013–2016 P e-pos
s udy
318 Lung, Kidney,
Li e , Kidney-
panc eas, Hea
AMS in e en ion 12 Pos - ansplan global
in ec ions
Fe nández e al.,
2022
61,
a
Spain 2016–2019 P e-pos
s udy
76 Li e AMS in e en ion 12 Colonisa ion and in ec ion by
MDR and XDR bac e ia
Kueh e al.,
2022
62
Uni ed
S a es
2016–2019 P e-pos
s udy
172 All ypes (mainly
kidney and li e )
AMS in e en ion 24 C. di icile es ing
Sil a e al.,
2023
63,
a
Spain 2014–2016 P e-pos
s udy
196 Kidney, Kidney-
panc eas, Li e -
kidney
AMS in e en ion + in ec ion con ol 10 Pos - ansplan global
in ec ions
Sha iekhani e al.,
2023
64
I an 2020–2021 P e-pos
s udy
2791 All ypes (mainly
kidney and li e )
AMS in e en ion 12 Pos - ansplan global
in ec ions
AMS: an imic obial s ewa dship; BSIs: bloods eam in ec ions; CDI: Clos idioides di icile in ec ion; DOT: days o an ibio ic he apy; ERCP: endoscopic e og ade cholangiog aphy; MDR: mul id ug-
esis an ; SSIs: su gical si e in ec ions; UTIs: u ina y ac in ec ions; XDR: ex ensi ely d ug- esis an ; NS: No speci ied.
a
S udies included in he me a-analyses.
Table 1: Cha ac e is ics o included s udies and in e en ions assessed.
A icles
8 www. helance .com Vol 85 July, 2025
S udy ID Desc ip ion o he in e en ion and con ol
g oups
Numbe o pa ien s
n (%)
Mo ali y
n (%)
T ansplan ela ed
complica ions
n (%)
In ec ions n (%)
Pe iope a i e an imic obial p ophylaxis
Townsend
e al., 1980
31,
a
Pe iope a i e an ibio ic p ophylaxis
(ce amandole + ob amycin)
Con ol g oup: no pe iope a i e an ibio ic
p ophylaxis
37
C: 17
INT: 20
– – In ec ion in he i s 7 d a e ansplan a ion
C: 10 (59); INT: 4 (20)
p = 0⋅04
Pos ope a i e wound in ec ion
C: 5 (29⋅4); INT: 3 (15) NS (p = 0⋅51)
UTIs
C: 14 (82⋅35); INT: 12 (60) NS (p = 0⋅26)
BSIs
C: 3 (17⋅65); INT: 2 (10) NS (p = 0⋅84)
Wilms e al.,
1986
32,
a
Pe iope a i e p ophylaxis (cephalospo in p ophylaxis
2 g p e- ansplan and 500 mg a 12, 24, and 38 h
hou s).
Con ol g oup: no pe iope a i e an ibio ic
p ophylaxis
34
C: 18
INT: 16
– – Su gical si e in ec ions
C: 7/18 (38⋅9); INT: 5/16 (31⋅2) NS
E ans e al.,
1988
33,
a
Pe iope a i e p ophylaxis (amoxicillin-cla ulana e
1 gg/200 mg wo doses du ing su ge y)
Con ol g oup: no pe iope a i e an ibio ic
p ophylaxis
46 (34 ansplan
su ge ies)
C: 22
INT: 24
2/46 (4⋅3)
C: 2 (9⋅1)
INT: 0 (0)
–Su gical si e in ec ions in ansplan su ge ies
C: 4/13 (30⋅8); INT: 0/21 (0)
Cohen e al.,
1988
34,
a
Pe iope a i e an ibio ic p ophylaxis (ce u oxime
750 mg and pipe acillin 4 g)
Con ol g oup: no pe iope a i e an ibio ic
p ophylaxis
53
C: 26
INT: 27
30-day
mo ali y due
o in ec ion
C: 0; INT: 1
(3⋅7) NS
Requi ed dialysis
(30 days)
C: 11 (42⋅3); INT: 8
(29⋅63)
To al numbe o in ec ions
0–14 days:
C: 30 (115⋅38); INT: 24 (88⋅9)
0–5 days:
C: 11 (42⋅31); INT: 3 (11⋅1) p = 0⋅04
Su gical wound in ec ion
0–14 days:
C: 11 (3⋅85); INT: 4 (14⋅8)
0–5 days:
C 5 (19⋅2); INT: 1 (3⋅7) p = 0⋅027
UTIs
0–14 days:
C: 18 (69⋅2); INT: 19 (70⋅4)
0–5 days:
C: 5 (19⋅2); INT: 2 (7⋅41)
Robles e al.,
1990
35,
a
Pe iope a i e p ophylaxis wi h 1 dose o ce o axime
1 g (a m A), ce iaxone 1 g (a m B)
Con ol g oup: no pe iope a i e p ophylaxis
60
C: 20
INT: 40 (20 + 20)
– – SSI
C: 2/20 (10); INT: 3/40 (7⋅5) NS
UTI
C: 7/20 (35); INT: 12/40 (30) NS
P unds ein
e al., 2001
36
Addi ion o ancomycin o pe iope a i e an ibio ic
p ophylaxis
Con ol g oup: no addi ion o ancomycin o
pe iope a i e an ibio ic p ophylaxis ancomycin
Kidney: 88
C: 45
INT: 43
Panc eas: 24
C: 12
INT: 12
Pa ien 1-y
su i al
Kidney:
C: 89; INT: 95
NS
Panc eas:
C: 92; INT: 100
NS
Rejec ion du ing
ansplan
admission
Kidney:
C: 24%; INT: 23%
NS (p = 0⋅90)
Panc eas:
C: 42%; INT: 8% NS
(p = 0⋅06)
Allog a 1-y
su i al
Kidney:
C: 78%; INT: 93%
NS (p = 0⋅07)
Panc eas:
C: 92%; INT: 92 %
NS (p = 1⋅00)
G am-posi i e in ec ion
Kidney:
C: 22%; INT: 20% NS (p = 0⋅76)
Panc eas:
C: 50%; INT: 33% NS (p = 0⋅41)
Ga cía P ado
e al., 2008
37
Pe iope a i e an ibio ic p ophylaxis wi h
amoxicillin/cla ulana e
Con ol g oup: pe iope a i e an ibio ic p ophylaxis
wi h ce azolin
167
P e-INT: 94
Pos -INT: 73
–G a su i al 30
days
C: 89 (92⋅6); INT:
66 (90⋅4) NS
(p = 0⋅41)
SSIs
C: 34 (36⋅2); INT: 22 (30⋅1) NS
BSIs
C: 4 (4⋅3); INT: 5 (6⋅8) NS (p = 0⋅35)
(Table 2 con inues on nex page)
A icles
www. helance .com Vol 85 July, 2025 9
pa ien s who swi ched o o al he apy. No di e ences in
o al an ibio ic du a ion we e epo ed.
Speci ic AMS implemen a ion app oach
Six s udies epo ed he impac o speci ic AMS
implemen a ion app oach on SOT .
59–64
Fi e o hem
epo ed esul s abou implemen a ion o a gene al
AMS p og amme in di e en ansplan uni s: one
61
in
li e ansplan ; one
59
in li e , kidney, panc eas, and
kidney-panc eas; one
60
in lung, kidney, li e , kidney-
panc eas, and hea ansplan pa ien s; one
63
in kid-
ney, kidney-panc eas, and kidney-li e ; and one
64
in all
ypes o ansplan a ion (p incipally kidney and li e ).
Finally, one s udy
62
e alua ed an AMS app oach p io o
o de ing C. di icile es s ( equi ing p esc ibe s o
answe a se ies o sho ques ions wi hin he elec onic
medical eco d be o e o de ing C. di icile es s), whe e
all ypes o ansplan we e included (mainly kidney and
li e ).
Wi h espec o e alua ion o implemen a ion o a
gene al AMS p og amme in di e en ansplan uni s,
none o he s udies showed any di e ence ega ding
mo ali y, one o hem epo ed a dec ease in o e all
SSI a e,
59
ano he a dec ease in UTI and cys i is.
63
One
s udy epo ed da a ela ed o ansplan a ion,
63
wi h no
di e ence among g oups. No o he di e ences in o he
in ec ion- ela ed a iables we e desc ibed.
An imic obial consump ion was assessed in i e
s udies,
60–64
all o hem showing a dec ease in o e all
consump ion o an ibio ics. Rega ding an imic obial
esis ance, Sil a e al.
63
epo ed a educ ion in he
incidence o in ec ions due o AmpC-p oducing En e -
obac e ales du ing he in e en ion pe iod, a e
implemen a ion o a join p og amme o AMS and
hospi al-acqui ed in ec ion con ol in a kidney,
panc eas and li e ansplan uni . No di e ences in
episodes due o ex ended-spec um be a-lac amase
(ESBL)-p oducing En e obac e ales o mul id ug-
esis an (MDR) P. ae uginosa we e epo ed.
Sha iekhani e al.
64
epo ed a signi ican educ ion in
equency o pa ien s wi h me hicillin- esis an
S. au eus, ca bapenem- esis an En e obac e ales, Kleb-
siella pneumoniae ca bapenemase (KPC) isola es and
ancomycin- esis an En e ococcus colonisa ion a e he
implemen a ion o an AMS p og amme in a ansplan
uni . No di e ences ega ding an imic obial esis ance
among bo h in e en ion and con ol g oups we e e-
po ed by Fe nández e al.
61
The s udy
62
ha e alua ed an AMS app oach p io o
o de ing C. di icile es s showed a signi ican dec ease
in numbe o o de s o C. di icile oxin, wi h no di -
e ences acco ding o a es o nega i e C. di icile oxin
es s be ween bo h g oups.
O all he s udies, only h ee epo ed ou comes
homogeneously and p o ided su icien in o ma ion o
be included in he me a-analysis. Thus, we we e able o
pool he da a om hese h ee s udies o assess he
e ec o AMS implemen a ion in SOT on SSI
a es.
57,59,61
They we e p e-pos s udies wi h a mode a e
o high isk o bias. Fe nández e al.
61
and Sil a e al.
57
did no ind a signi ican educ ion in he numbe o
SSIs as a esul o he in e en ion, in con as o he
s udy by F ene e e al.,
59
whe e he au ho s obse ed a
educ ion om 15⋅5% o 7⋅5% o SSI a es in SOT .
The pooled da a om hese s udies (Fig. 3D) showed a
signi ican educ ion in his ou come, wi h an OR o
0⋅57 in a ou o AMS p og ammes (95% CI 0⋅35–0⋅94)
and low he e ogenei y be ween s udies (I
2
21%). These
esul s we e consis en wi h he sensi i i y analyses
using a ixed-e ec model (OR 0⋅54, 95% CI 0⋅36–0⋅81).
Discussion
SOT a e a agile popula ion a high isk o in ec ious
complica ions due o MDRO. The e o e, de eloping
adequa e AMS p og ammes in his se ing is an u gen
need.
10,18
A e sea ching a ious da abases, a o al o 34
publica ions wi h a mode a e o high isk o bias we e
included. All we e o iginal a icles epo ing da a om
con olled clinical ials, p e-pos s udies o obse a-
ional s udies wi h a con ol g oup ha analysed he
e ec o di e en ypes o s a egies o op imising
an imic obial use in SOT on mo ali y, in ec ious
complica ions, g a ela ed complica ions, an imic o-
bial esis ance, an imic obial consump ion, and/o
hospi alisa ion. We would like o highligh some o he
mos ele an pape s published in ecen yea s, g ouped
oge he by assessed in e en ion.
Rega ding p esu gical an imic obial p ophylaxis, we
ound wo ecen sys ema ic e iews add essing he
issue. A sys ema ic e iew and me a-analysis
65
pe -
o med in 2020, including RCTs and quasi-RCTs
assessing he sa e y and/o e icacy o pe iope a i e
an ibio ics in SSIs in SOT , included eigh s udies (718
andomised pa icipan s) wi h high isk o bias. They
concluded ha , based on he da a a ailable, he e is e y
low ce ain y e idence o suppo ou ine ea men o
SOT wi h an ibio ics o p e en SSIs, so hey could no
make speci ic ecommenda ions. In addi ion, a ecen
sys ema ic e iew conduc ed by Campos-Vale a e al.,
66
which included eigh s udies ocussing on li e ans-
plan ecipien s, concluded ha he ecommenda ion
s eng h o pe iope a i e li e ansplan a ion an imi-
c obial p ophylaxis was s ong o p e en ing bac e ial
in ec ions, leng h o s ay (LOS), and mo ali y, bu weak
o de e mining he op imal an ibio ic egimen. This
e iew included wo non-compa a i e s udies
67,68
and
ano he s udy
69
add essing a ge ed p ophylaxis agains
ESBL-p oducing En e obac e iaceae- ela ed in ec ion
among ca ie s ollowing li e ansplan a ion. Ou
sea ch included 17 a icles ha deal wi h pe iope a i e
an imic obial p ophylaxis, mainly in kidney and li e
ansplan a ion. The sea ch did no iden i y he op imal
an imic obial egimen o p ophylaxis, bu i did
A icles
16 www. helance .com Vol 85 July, 2025

include se en s udies ha looked a he du a ion o
p ophylaxis, and none o hese showed di e ences in
in ec ious complica ions, g a ela ed complica ions o
inc eased mo ali y a e a sho p ophylaxis egimen,
e en in lung ansplan a ion (<10 days in his case).
Based on he esul s o ou me a-analysis, he e was no
di e ence in he a e o SSIs be ween sho and
ex ended du a ion o an imic obial p ophylaxis o
kidney and li e SOT .
As ega ds du a ion o ea men , ou pooled da a
esul s om h ee obse a ional s udies sugges ha
in cases o non-complica ed g a in ec ions (p ima ily
u ina y, cholangi is, and o he in a-abdominal in-
ec ions) whe e adequa e sou ce con ol has been
achie ed, longe egimens o an imic obial ea men s
may no ha e a po en ial impac in e ms o ecu ence
o he in ec ion. In addi ion, no s udies epo ed an
inc ease in mo ali y. The ac ha sho e an imic o-
bial egimens may be su icien in SOT , as long as
g a in ec ion is no complica ed, is consis en wi h
cu en e idence.
70
Un o una ely, SOT ha e been
excluded om mos ials o ea men du a ion. Da a
om his me a-analysis may allow hem o be included
in u u e andomised ials o inally answe his
ques ion.
O he i e ials ha looked a he implemen a ion
o a speci ic AMS app oach in di e en ansplan
uni s,
59–61,63,64
no ansplan - ela ed complica ions we e
obse ed a e AMS in e en ion, sugges ing ha AMS
p og ammes in he SOT popula ion a e sa e. In addi-
ion, he use o AMS can educe SSI a es by hal , ac-
co ding o he esul s o ou me a-analysis. Howe e ,
his esul is based on h ee p e-pos s udies, mainly
d i en by he s udy by F ene e e al.,
59
so i will be
necessa y o con i m his inding wi h highe -quali y
s udies.
Fo he o he ypes o in e en ions e alua ed, we
did no ind su icien e idence o make a ecommen-
da ion. Mainly o al s ep-down he apy
71
may bene i
SOT , al hough we did no ind enough e idence o
ully suppo his claim. O he in e en ions, such as
pe iope a i e in a esical an ibio ic i iga ion
52,53
and
an imic obial p ophylaxis p io o ERCP in li e ans-
plan a ion,
51
do no appea o be e ec i e in he kidney
and li e ansplan popula ions, espec i ely.
E en i ou sea ch s a egy did no e eal any s udies
on he ole o empi ical ea men , we would like o
highligh wo e ospec i e s udies ha e alua ed his
issue bu we e no included in ou sys ema ic e iew
because o hei design: Lupei e al.
72
and Hamandi
e al.
73
Bo h epo a signi ican ly highe mo ali y a e
in SOT pa ien s whose an imic obial empi ical an i-
mic obial ea men was inadequa e. Al hough we do
no ha e any s udies wi h a con ol g oup e alua ing
empi ical ea men , hese wo s udies sugges he
impo ance o choosing he igh egimen ea ly in he
cou se o in ec ion in SOT .
Nei he did ou sea ch s a egy ind any s udies on
alse-an ibio ic alle gy de-labelling. Howe e , he e a e
some obse a ional s udies
74,75
sugges ing wo se ou -
comes associa ed wi h SOT pa ien s wi h a alse an i-
bio ic alle gy label, including highe C. di icile a es and
g a ailu e. E en in he absence o compa a i e
s udies, his shows he need o p omo e mul idisci-
plina y in e en ions aiming a emo ing in alid alle gy
labels p io o ansplan .
The esul s p esen ed in his sys ema ic e iew a e
in line wi h he a ailable published e idence, hus
showing he need o e alua e he impac o AMS in-
e en ions on SOT by conduc ing u he highe -
quali y s udies,
10,18
mainly in ypes o ansplan o he
han kidney and li e . Some AMS s a egies wi h
p o en bene i s o SOT ha e demons a ed he use-
ulness o ea ing asymp oma ic bac e iu ia beyond
wo mon hs a e kidney ansplan a ion o p e en
UTIs, and he e icacy o an i ungal p ophylaxis o
p e en in asi e ungal in ec ion among li e ans-
plan ecipien s. Howe e , hanks o his sys ema ic
e iew, we we e able o iden i y some a eas o de ici
ha u gen ly need de elopmen and esea ch in he
SOT popula ion: an imic obial p ophylaxis (mainly i s
e icacy and du a ion in o he ypes o SOTs di e en o
kidney) and du a ion o ea men in g a - ela ed in-
ec ions. E icacy o an i ungal p ophylaxis o p e en
mould in ec ions in lung ansplan and e icacy o
ea ing asymp oma ic bac e iu ia in ea ly kidney
ansplan ecipien s also need o be de eloped. O he
a eas, such as he use ulness o de-escala ion, o al
ansi ion and mislabelling o an ibio ic alle gies, also
need u u e esea ch, e en i hey can be in e ed om
da a om he gene al popula ion. Also, none o he
included s udies epo ed in o ma ion abou
an imic obial- ela ed oxici y, which is an in e es ing
a iable o collec in u u e s udies. A summa y o he
cu en e idence and p oposed u u e esea ch needs is
p esen ed in Table 3.
Based on he in e p e a ions o he indings o each
o he e alua ed s udies, we can es ablish some c i e ia
o he design o u u e AMS in e en ions in SOT
popula ion, including bo h gene al and speci ic cha -
ac e is ics, o ensu e ha hese p og ammes a e mo e
e ec i e. I is essen ial ha we di ide he in e en ions
acco ding o ype o ansplan , hea , lung, panc eas,
and in es inal ansplan a ion being he a eas whe e we
ha e mo e unce ain y. I is also impo an o de e -
mine ansplan ela ed a iables in each s udy, bo h as
baseline a iables ( ype o immunosupp ession, ea -
men o ejec ion, e c.) and ou comes. In addi ion, we
belie e ha i is impo an o highligh he need o
include SOT popula ion in clinical ials ela ed o
AMS in e en ions, om which hey a e adi ionally
excluded.
In e ms o ou comes, ou me a-analyses we e
pe o med: one assessing he impac o an AMS
A icles
www. helance .com Vol 85 July, 2025 17
app oach in hospi alised SOT , showing i s possible
bene i s; wo me a-analyses o an imic obial p ophy-
laxis in SOT su ge y (li e and kidney), whe e su gical
p ophylaxis was ound o educe su gical si e in ec-
ion a es in SOT pa ien s, bu no addi ional bene i
was ound o ex ended p ophylaxis; and one assess-
ing non-complica ed g a in ec ions, whe e no di -
e ences we e ound in e ms o ecu ence o
in ec ion when compa ing sho and ex ended ea -
men du a ions.
Fu u e s udies o an imic obial op imisa ion in
SOT should include a iables such as mo ali y,
ansplan - ela ed complica ions, de elopmen o an i-
mic obial esis ance, an imic obial consump ion and
hospi al- ela ed ou comes in a s anda dised way o
allow pooled analysis.
This s udy has se e al limi a ions. Fi s , he sea ch
ield was he i le because he wide ange o e ms
included in he sea ch s a egy made he ini ial sea ch
including he abs ac ields un easible. To o se his
disad an age, ci a ions o included e e ences and
ele an sys ema ic e iews we e sea ched o iden i y
addi ional s udies. Second, he low quali y o he s udies
included in he sys ema ic e iew makes i di icul o
d aw i m conclusions abou he e ec s o AMS in-
e en ions in SOT . Also, he he e ogenei y o in-
e en ions included in he e iew inc eases he
di icul y o unde s anding he e ec o each o hem.
Thi d, as he me a-analysis on an imic obial p ophy-
laxis is based on a icles ha in some cases we e pub-
lished mo e han 20 yea s ago, he esul s should be
aken wi h cau ion. The same applies o he me a-
analysis on he e ec o AMS in SSIs, whe e he e-
sul s a e mainly d i en by he s udy by F ene e e al.
59
wi h a la ge numbe o pa ien s e alua ed, bu which is
olde han he o he wo s udies.
AMS in e en ions A ailable s udies Resul s P oposed u u e esea ch
p io i y
a
An imic obial p ophylaxis in e en ions
E icacy o pe iope a i e an ibio ic
p ophylaxis o p e en SSIs in KT
su ge y
To al s udies: 6 A dec ease in SSIs was shown in pa ien s who ecei ed an imic obial p ophylaxis in
ansplan su ge ies, a ou ing an imic obial p ophylaxis
Low
RCTs: 5
To al pa ien s: 390
Sho ening pe iope a i e an ibio ic
p ophylaxis <24 h
To al s udies: 6 No di e ences in SSIs we e ound compa ing sho and ex ended su gical
an imic obial p ophylaxis in kidney and li e ansplan ecipien s
Low o KT and LT
High o lung, hea ,
mul i isce al/in es inal, and
combined ansplan
RCTs: 2
To al pa ien s: 839
E icacy o an i ungal p ophylaxis o
p e en mould in ec ions in lung
ansplan
24,25
To al s udies: 28 No e idence o bene i o an i ungal p ophylaxis s no p ophylaxis, uni e sal
p ophylaxis s p e-emp i e ea men , o p olonged (>6 mon hs) p ophylaxis s <6
mon hs based mainly on obse a ional, high isk o bias s udies.
High
RCTs: 1
To al pa ien s: 4538
E icacy o an i ungal p ophylaxis o
p e en IFI in LT
26,27
To al s udies: 15 Consis en e idence ac oss RCTs on he bene i o an i ungal p ophylaxis s placebo
o p e en IFIs in high- isk LT. No p o en bene i o o he an i ungals o e
luconazole.
Low
RCT: 15
To al pa ien s: 1853
T ea ing asymp oma ic bac e iu ia in
KT
22,23
To al s udies: 9 No clinical bene i s p o ed o ea ing asymp oma ic bac e iu ia in KT beyond 2
mon hs a e ansplan a ion
Low o la e KT
High o ea ly KT
RCTs: 5
To al pa ien s: 959
An ibio ic ea men op imisa ion in e en ions
Sho ening ea men du a ion o
g a in ec ions
To al s udies: 3 No clinical bene i s p o ed o ea men s >10 days s sho e cou ses o 6–10 days
o non-complica ed g a in ec ions
High
RCTs: 0
To al pa ien s: 335
Sa e y and iming o o al swi ch To al s udies: 1 No di e ences in clinical ou comes o a e o pa ien s wi h BSIs which needed o
es a i ea men o he index in ec ion be ween ully-i ea men s and o al
ansi ions
High
RCTs: 0
To al pa ien s: 162
Assessing he impac o AMS p og ams in SOT uni s
Reducing an ibio ic consump ion To al s udies: 2 All a ailable s udies showed dec eased an ibio ic consump ion a e AMS
implemen a ion
Low
RCTs: 0
Reducing mo ali y, eadmissions, LOS To al s udies: 6 No clinical ou come bene i s ha e been p o ed o AMS in e en ions High
RCTs: 0
Reducing incidence o in ec ions To al s udies: 3 Signi ican educ ion in SSIs a e implemen ing combined AMS + in ec ion con ol
in e en ions in SOT uni s
Mode a e
RCTs: 0
Reducing bac e ial esis ance To al s udies: 3 Limi ed e idence om non-con olled ials showing educ ions in he incidence o
some speci ic MDRO
High
RCTs: 0
Compa ing e ec i eness o di e en
in e en ions o implemen a ion
s a egies
To al s udies: 0 No e idence on which in e en ions and implemen a ion s a egies a e mo e
e ec i e in SOT uni s
High
RCTs: 0
AMS: An imic obial s ewa dship; KT: Kidney ansplan ; LT: Li e ansplan ; IFI: In asi e ungal in ec ion; RCT: Randomised con olled ial; BSIs: Bloods eam in ec ion; SOT: Solid o gan ansplan ; LOS:
Leng h o hospi al s ay; SSIs: Su gical si e in ec ions: MDRO: Mul id ug esis an o ganisms. This able has been elabo a ed acco ding o he da a p oduced by his sys ema ic e iew combined wi h
ecen ly published e iews on speci ic opics.
a
Ranking c i e ia o u u e esea ch p io i y: High p io i y: No a ailable o only low-quali y s udies o a equen clinical p oblem. Mode a e p io i y:
Some mode a e quali y s udies al eady a ailable o in equen clinical p oblems. Low p io i y: High quali y s udies al eady a ailable.
Table 3: Cu en e idence summa y and p oposed u u e esea ch needs.
A icles
18 www. helance .com Vol 85 July, 2025
We should also emphasise ha he ield o solid
o gan ansplan a ion is ela i ely young compa ed o
o he ields o medicine, as is an imic obial s ewa d-
ship, so mo e s udies need o be ca ied ou . I should
be aken in o accoun ha pa ien olumes a y be-
ween cen es and ac oss he wo ld, and ha con-
duc ing p ospec i e RCTs speci ically on in ec ious
diseases and an imic obial s ewa dship has limi a ions
in en olmen o achie e sample sizes wi h su icien
powe . Finally, an imic obial use and ailo ed in-
e en ions also depend on local epidemiology, which
may limi he ex apola ion o local esul s o he global
communi y.
We conclude ha , al hough he a ailable e idence
on he impac o AMS in e en ions in he SOT
popula ion is sca ce and o low quali y, some s a e-
gies, such as sho e pe iope a i e an imic obial p o-
phylaxis, sho e ea men du a ion o g a - ela ed
in ec ions and uncomplica ed g am-nega i e BSI in
li e and kidney ansplan ecipien s, and he
implemen a ion o an AMS p og amme in ansplan
uni s, appea o imp o e an imic obial use wi hou
inc easing in ec ion complica ions. Ou pooled da a
om he me a-analyses showed no bene i om p o-
longed an imic obial su gical p ophylaxis in li e and
kidney ansplan ecipien s, and a possible bene icial
e ec on SSIs when an AMS app oach is imple-
men ed in hospi alised SOT pa ien s. Fu he mo e,
sys ema ic e iew o a ailable e idence ound no e i-
dence o inc easing mo ali y, g a - ela ed complica-
ions, inc easing hospi al admissions o an imic obial
esis ance when AMS measu es a e implemen ed.
While he e is no compelling e idence agains , he e
a e, on he con a y, well-g ounded easons in a ou
o implemen ing s a egies o op imise an ibio ic use
and AMS p og ammes in he SOT popula ion,
designed o achie e he bes possible esul s in hese
se ings. This s udy has iden i ied he a eas o AMS
esea ch in SOT ha equi e he highes p io i y,
hose wi h he lowes le el o e idence, and hose
whe e he le el o knowledge is su icien as o be
applied.
Con ibu o s
MPG, ABGG, JMGB, GP, RAM, MEPI, JMC designed he s udy. MPG
and ABGG de eloped he sea ch s a egy wi h eedback om JMGB,
GP, and JMC. MPG and ABGG sc eened and selec ed s udies. MPG
and ABGG ex ac ed he da a and p epa ed he da a o analysis. JMC,
GP, and JMGB had access o and e i ied he s udy da a. ABGG ana-
lysed he da a. MPG w o e he i s d a o he manusc ip , and all
au ho s c i ically e ised he manusc ip . All au ho s had ull access o
all he da a in he s udy and had inal esponsibili y o he decision o
submi o publica ion. All au ho s ead and app o ed he inal e sion
o he manusc ip .
Da a sha ing s a emen
The s udy p o ocol is a ailable a PROSPERO (CRD42024554606). The
da ase s gene a ed and analysed in his me a-analysis a e published in
he Appendix. Addi ional in o ma ion collec ed om s udies is a ailable
om he co esponding au ho on easonable eques .
Decla a ion o in e es s
MPG is suppo ed by he Subp og ama Río Ho ega, 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 Ciencia, Inno ación y Uni e sidades, Spain
(CM23/00078). ABGG is suppo ed by he Subp og ama Juan Rodés,
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 Ciencia, Inno ación, y
Uni e sidades, Spain (JR21/00017). GP epo s g an s om he Cen o
de In es igación Biomédica en Red (CIBER), Ins i u o de Salud Ca los
III, Spanish Go e nmen , co- inanced by he Eu opean De elopmen
Regional Fund (A Way o Achie e Eu ope), Mad id, Spain. MEPI is a
esea che belonging o he p og am “Nicolás Mona des” (C1-0038-
2019), Se icio Andaluz de Salud, Jun a de Andalucía, Spain.
Acknowledgemen s
N/A.
Appendix A. Supplemen a y da a
Supplemen a y da a ela ed o his a icle can be ound a h ps://doi.
o g/10.1016/j.eclinm.2025.103310.
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