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

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). 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