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

Effectiveness and safety of strategies to optimise antimicrobial use in solid organ transplant recipients. Systematic review and meta-analyses María Paniagua-García, a , b , c , e Ana Belén Guisado-Gil, a , b , c , d , e José Molina Gil-Bermejo, a , b , c , ∗ Germán Peñalva, a , b , c Rocío Álvarez-Marín, a , b , c María Eugenia Pachón-Ibáñez, a , b , c and José Miguel Cisneros a , b , c a Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Virgen del Rocío University Hospital, Seville, Spain b Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain c CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), Madrid, Spain d Department of Pharmacy, Virgen del Rocío University Hospital, Seville, Spain Summary 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 riskof-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 randomeffects model and the inverse variance method with the I 2 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 transplantrelated 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 *Corresponding author. Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Virgen del Rocío University Hospital, Seville, Spain. E-mail address: [email protected] (J. Molina Gil-Bermejo). e These authors contributed equally to this work. eClinicalMedicine 2025;85: 103310 Published Online xxx https://doi.org/10. 1016/j.eclinm.2025. 103310 www.thelancet.com Vol 85 July, 2025 1 Articles clinical trials are needed to better understand the effects of these strategies in SOTr and to design optimal AMS interventions in this population. Funding This study was supported by the Instituto de Salud Carlos III (ISCIII, reference ICI21/00075) and the Centro de Investigación Biomédica en de Enfermedades Infecciosas (CIBERINFEC, CB21/13/00006), ISCIII, Ministerio de Ciencia e Innovación. Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Keywords: Solid organ transplantation; Antimicrobial stewardship; Antibiotics; Immunosuppression; Antimicrobial resistance Introduction Solid organ transplantation (SOT) has become an important method of treating end-stage organ disease. Improvements in surgical technique and postoperative care, as well as advances in the prevention, diagnosis and treatment of infections, have led to a significant improvement in quality of life and prolonged survival. Nevertheless, complex surgeries, frequent exposure to antibiotics, and immunosuppressive regimens put solid organ transplant recipients (SOTr) at a disproportionately high risk of infection, especially by multi-resistant organisms (MDRO), which cloud the prognosis. 1–3 The current antimicrobial and bacterial resistance crisis 4 has a huge impact on those most vulnerable to infection. In a 2018 study, data on antimicrobial use in SOTr show that in southern Europe, up to 76⋅9% of patients admitted to transplant units (solid organ or bone marrow) receive antibiotics, compared with 66⋅5% Research in context Evidence before this study Solid organ transplantation (SOT) exposes patients to an increased risk of impaired clinical outcomes related to inappropriate antimicrobial treatment and multidrug resistant microorganisms. This is why developing safe and effective antimicrobial stewardship (AMS) initiatives is especially relevant in this population. SOT patients have been excluded from most randomised trials tackling critical aspects of antimicrobial optimisation (like treatment duration), and only narrative reviews and call-to-action papers have been published on this relevant topic. We conducted a literature search for original research articles published from inception to March 6, 2025, with no language restrictions, using MEDLINE, EMBASE and SCOPUS. Randomised clinical trials, observational analytical studies, quasi-experimental, and interrupted time series analyses with a control group were included. Inclusion criteria were based on the Population, Intervention, Comparison, Outcome (PICO) approach: (P) Adult SOT patients; (I) Specific interventions targeting infection prevention, individual patient’s treatment optimisation, or transversal AMS interventions implementation in SOT units; (C) Patients or periods without the assessed intervention; (O) At least one of the following: mortality, transplant-related complications, incidence of infections, antimicrobial consumption, antimicrobial resistance; hospital stay, readmission rates, and/or antimicrobial toxicities. All identified studies had a moderate or high risk of bias. Added value of this study In this article we present a systematic review with several meta-analyses which aim, on one hand, to pool accumulated evidence on several AMS interventions developed specifically for SOTr, and on the other hand, to map current areas of uncertainty and priority research needs. Studies identified in this review enabled four meta-analyses regarding perioperative prophylaxis, treatment duration for uncomplicated graft-related infections and the effects of transversal implementation of AMS in SOT units. According to our results, shorter perioperative antimicrobial prophylaxis, shorter treatment duration for uncomplicated graft infections, and the implementation of an AMS programmes in transplant units, may reduce antibiotic consumption in these units without impairing clinical outcomes of infections, and may help to prevent surgical site infections. Implications of all the available evidence The conclusions of our systematic review and meta-analyses are mainly driven by observational studies with a significant risk of bias, and thus must be validated by further randomised trials, which could be supported by the data presented in this article. In this review we also identified critical areas in urgent need for evidence. There is still a paucity of data for SOTr other than kidney or liver recipients, and also on the demonstration of neat clinical benefits of AMS interventions beyond the reduction of antibiotic consumption, including improved clinical outcomes and bacterial resistance in the transplant units. Articles 2 www.thelancet.com Vol 85 July, 2025 in North America. 5 Furthermore, in a retrospective study of 176 audits of antibiotic treatment adequacy in SOTr, more than 40% of prescriptions were found to be inappropriate. 6 These data show the need to improve the use of antimicrobials in SOTr, who are particularly vulnerable to infection as well as drug interactions and side effects. In the fight against antimicrobial resistance, preventive strategies play an important role in reducing risk of infection and its consequences for both patient and graft survival: active surveillance of MDRO carrier status, targeted perioperative antimicrobial prophylaxis, decolonisation strategies, post-transplant antimicrobial prophylaxis, and early active empiric treatment. 7 However, these preventive strategies should be integrated with antimicrobial stewardship (AMS) programmes, which aim to optimise clinical outcomes and minimise the unintended consequences of antimicrobial use, including toxicity, selection for pathogenic organisms (such as Clostridioides difficile) and the emergence of resistance, as well as to reduce costs without negatively impacting quality of care. 8 In cross-sectional studies of all hospitalised patients, AMS interventions have been shown to improve antimicrobial use, generally by reducing consumption and microbiological resistance and by improving the prescribing profile, with clinical benefits. 9 However, the generalised application of AMS measures may not be applicable in SOTr, as it does not take into account all the transplant-specific variables (time since transplant, type of immunosuppression, organ transplanted, infections derived from donor, polypharmacy and drug interactions, among others). 8,10 In addition, the SOTr population is often under-represented in clinical trials of AMS interventions, and guidelines often do not provide specific recommendations. There are also barriers that hinder implementation of AMS strategies in SOTr population, such as physician perceptions of patient complexity, anxiety regarding disease severity, and variation in host risk factors, such as the level of immunosuppression, recent surgery, and the potential for drug interactions. 11 Given the lack of data, certain issues such as choice of empirical treatment, duration of treatment, among others, are usually left to the discretion of the treating physician. 8,10 Despite ongoing efforts by solid organ transplant societies 8,10 to incorporate the principles of AMS into daily practice, there is still little evidence in this population. Current AMS practice guidelines do not address specific interventions in SOTr. 12,13 However, AMS interventions have been shown to be effective and safe in other immunosuppressed populations, such as oncohaematological patients. 14,15 In recent years, several calls to action have been published highlighting the need for multidisciplinary approaches, including close collaboration with transplant experts, and the use of rapid and appropriate microbiological diagnostics to guide treatment and optimise duration. 16–18 Although this is a priority topic, to date only narrative reviews of AMS interventions have been published, with no systematic review of the available evidence to our knowledge. To better understand the existing evidence and to support optimal AMS interventions in this population, our study presents a systematic review and meta-analyses of studies reporting on the effectiveness and safety of different strategies to optimise antimicrobial use in SOTr. Methods Ethics The systematic review and meta-analyses were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 19 The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) Database (registration number: CRD42024554606). Search strategy We conducted an electronic literature search for original research articles published from inception to 20 May 2024, with no language restrictions, using three health databases: MEDLINE (via PubMed), EMBASE, and SCOPUS. The search field was the title and terms included both MeSH terms and free text (keywords, synonyms and word variations) combined with Boolean operators (see Supplemental Table S1 for the full search strategy). The search strategy was developed for PubMed and then adapted appropriately for use in each database. Citations of included references and relevant systematic reviews were searched to identify additional studies. Email alerts were created in the health databases to check for potential inclusion of articles published after the search date and until 06 March 2025. Selection criteria Inclusion criteria based on the Population, Intervention, Comparison, Outcome and Study (PICOS) design for the systematic review and meta-analyses were adult (≥18 years old) SOTr, both inpatient and outpatient, regardless of the time of transplantation. The evaluated interventions included specific antimicrobial strategies designed to optimise the prevention of infections, such as perioperative antimicrobial prophylaxis (including efficacy and duration), decolonisation strategies and other specific strategies for optimising prevention. Specific strategies to optimise antimicrobial treatment were also evaluated, including the timing of empirical treatment initiation, the choice of empirical or targeted treatment agents, de-escalation, oral step-down therapy, treatment duration, and antibiotic allergy de-labelling. Other interventions evaluated were those related to the implementation of specific AMS interventions, including educational, persuasive, restrictive or Articles www.thelancet.com Vol 85 July, 2025 3 structural approaches. The comparator was a control group of SOTr who did not receive the intervention under evaluation, or corresponding time periods in pre-post studies. Outcomes included at least one of the following, with no primary outcome required: outcomes related to effectiveness, such as global mortality, transplant-related complications (e.g., graft dysfunction or rejection), infections (including clinical failure, microbiological failure, relapse or recurrence, superinfections, and C. difficile infections), antimicrobial consumption, and/or antimicrobial resistance; and outcomes related to safety, such as the need for hospitalisation, prolonged hospital stay, need for rehospitalisation, admission to intensive care units (ICUs), and/or antimicrobial toxicities. Eligible study designs included randomised clinical trials (RCTs), observational analytical studies (cohort or case-control studies), pre-post studies, and interrupted time series analyses. We excluded duplicate records using Mendeley, 20 congress abstracts, and studies assessing unapproved substances or substances not used in routine clinical practice. Trials related to viral infections (cytomegalovirus and BK virus, among others) were excluded, as these are the subject of more extensive studies 21 and are not the subject of this review. We did not include studies about management of asymptomatic bacteriuria in kidney transplant recipients, as these have been addressed in recent systematic reviews, 22,23 which suggest that systematic screening and treatment of asymptomatic bacteriuria beyond the second month after transplantation provide no apparent benefit among kidney transplant recipients. Antifungal prophylaxis was also excluded, as recent systematic reviews have addressed this issue, both in the general SOTr population and by type of transplant, most commonly lung 24,25 and liver, 26,27 but also heart transplantation. 28 The titles and abstracts of all identified articles were screened for eligibility by two independent reviewers (MPG and ABGG). If the eligibility of a study was not mutually agreed upon or was not clear from the title and abstract alone, the article was included in the fulltext review stage. Finally, the full papers of the preselected studies were assessed before a final decision on their inclusion was made. Any disagreements were resolved by consensus or with a third reviewer (JMC). Data extraction The data was collected in duplicate by two independent reviewers (MPG and ABGG) from articles selected for inclusion in the review. For each publication, the following variables were recorded: - Author and year of publication. - Country. - Study period. - Study design. - Study funding: public or private funding, or without financial support. - Number of hospitals included and mean number of beds. - Number of patients. - Patient’s characteristics: age, sex, type of transplant, immunosuppression/rejection treatment. - Time since transplant (if available). - Type of intervention assessed. - Type of infection targeted by the intervention. - Comparator group: standard of care or a different intervention. - Duration of intervention and outcome measurement time frame, in months. - Level of compliance with the intervention: completeness and fidelity. - Outcomes. Quality assessment The risk of bias of each study was assessed by two independent authors (MPG and ABGG) using the Cochrane EPOC group’s criteria. Discrepancies in the quality assessment were resolved through discussion with a third reviewer (JMC) to arrive at a final designation for each domain. Based on the Cochrane EPOC group’s risk of bias tool, 29 studies were given a score of low, high or unclear risk of bias for the following criteria: random sequence generation; allocation concealment; baseline outcome measurements similar; baseline characteristics similar; incomplete outcome data; knowledge of the allocated interventions adequately prevented during the study; protection against contamination; selective outcome reporting; and other risks of bias. A summary of the risk-of-bias assessment scores was assigned to each study as follows: ‘low risk of bias’ when all criteria were scored as ‘low’; ‘moderate risk of bias’ if one criterion or two criteria were scored as ‘unclear’ or ‘high’; and ‘high risk of bias’ if more than two criteria were scored as ‘unclear’ or ‘high’. REVMAN software Version 5⋅4⋅1 was used to collate and present the risk-of-bias results. Data synthesis and meta-analysis For descriptive purposes, we extracted the data available in the included studies by intervention and control groups. Ratios or other statistics such as p-values were also extracted where available. We also sought to pool the data from the articles included in the systematic reviews. To do this, we grouped trials that included different types of SOTs and the same type of intervention, assuming that the effectiveness of the interventions was comparable. Meta-analyses were only performed if three or more studies with similar types of intervention, control groups and outcome measures could be combined. For this purpose, data on the predicted clinical outcomes should be reported as the number of events and total Articles 4 www.thelancet.com Vol 85 July, 2025 patients in each arm or, alternatively, the difference between arms as the mean and standard deviation. Whenever possible, the same time of outcome assessment was defined for the meta-analyses. If this information was not available, we used the closest measure. In the case of duplicate cohorts, priority was given to results based on larger sample sizes. If there was insufficient or incomplete information in the published text, missing data were requested from the study authors. Subgroup analyses, using the same criteria as described above, were performed to analyse the effects of interventions in different transplant populations when a sufficient number of trials were available. Statistics Meta-analyses were performed using a random-effects model and the inverse variance method. The odds ratio (OR) for pre-post studies or the risk ratio (RR) for observational studies and RCTs with a 95% confidence interval (CI) were calculated based on the reported data. Studies with 0 counts in at least one arm received a continuity correction (adding 0⋅5). We used the I 2 test to assess statistical heterogeneity. 30 A value of less than 40% represented low heterogeneity, a value between 40% and 60% represented moderate heterogeneity, and a value of more than 60% represented high heterogeneity. Sensitivity analyses were performed by removing trials with 0 counts in at least one arm to ensure the robustness of the results. A fixed-effects model was also used for sensitivity analyses. REVMAN software Version 5⋅4⋅1 was used to run the meta-analysis, and the results were presented in forest plots. Role of the funding source This study was supported by the Instituto de Salud Carlos III, (ISCIII, reference ICI21/00075) and the CIBER de Enfermedades Infecciosas (CIBERINFEC, CB21/13/ 00006), ISCIII, Ministerio de Ciencia e Innovación. The Funders had no role in study design, data collection, data analyses, interpretation, or writing of the report. Results The electronic search returned 4050 records; 2063 were removed after duplicate checking. A further 1889 publications were excluded after title and abstract filtering, because they did not meet the eligibility criteria. This left 98 potentially relevant studies that were retrieved in full text: 67 were excluded before data extraction and 31 met the inclusion criteria. Three additional studies were retrieved from citations, leaving 34 included studies (Fig. 1). 31–64 Five authors were contacted and three of them were able to provide the requested data. Characteristics of studies and interventions Table 1 shows the characteristics of the studies evaluated. Study designs included 10 RCTs, 31–36,41,44,52,53 13 prepost studies, 37,39,42,43,45,48,49,59–64 and 11 observational studies. 38,40,46,47,50,51,54–58 Most of the studies took place in the USA (n = 12), 31,36,42,44–49,51,58,62 followed by Spain (n = 4), 35,37,61,63 and Germany (n = 4). 32,43,50,56 Most studies (33/34, 97⋅6%) reported the characteristics of patients included; however, transplant specific details (i.e., graft disfunction, rejection treatment, donor characteristics, etc.) were only reported in half of the studies (18/34, 52⋅9%). A total of 7367 patients were included in the 34 evaluated trials (mean number was 136⋅50 patients per study, interquartile range (IQR) 58⋅25–201⋅25). Of these, 5967 were SOTr, as the study by Shafekhani et al. 64 also included information on 1400 patients on the waiting list for transplantation. In terms of type of organ transplanted, the distribution was as follows: 3514 kidney (58⋅9%), 1920 liver (32⋅2%), 381 lung (6⋅4%), 69 pancreas (1⋅2%), 55 liver-kidney (0⋅9%), 49 kidney-pancreas (0⋅8%), 40 intestinal/multivisceral (0⋅7%), 29 heart (0⋅5%), and 15 combined heart-lung (0⋅3%). Some patients may be included more than once, as some studies recorded more than one episode per patient. 58 Evaluated interventions were multiple. A brief description of each intervention is given in Table 2, together with data about mortality, transplant related variables and infections for each included study. Seventeen 33,34,36,39,43,44,46,47,51,54,55,57,58,60,61,63,64 reported data about mortality, and even if the evaluated interventions were different, none of them showed an increase in mortality. Data about transplant related complications (which include acute rejection, graft dysfunction, donor-derived infection, and return to dialysis) was reported in nine studies 34,36,37,41,43,44,46,47,63 and no difference among control and intervention group was found. All studies except one 64 reported information about incidence of different infections after implementation of a given intervention. Most common reported infections were surgical site infections, followed by global posttransplant infection, bloodstream infections, urinary tract infections and C. difficile infection. Eight studies gave information about antimicrobial consumption, 47,57,58,60–64 12 about antimicrobial resistance, and 12 on the type and duration of the hospital care required (hospitalisation, length of stay, or admission to ICU) 36,43–47,49,55,60,61,63,64 (Supplemental Table S2). None of the 34 trials reported data on antimicrobial side effects. Little data was provided on each participating centre’s level of compliance with the evaluated intervention, and only five studies offered data about compliance. 41,43,44,47,63 Four studies assessed compliance related to antimicrobial prophylaxis, 41,43,44,47 reporting high adherence (>80%) in three of them 41,43,44 and moderate in another study (<70%). 47 The other study 63 evaluated the impact of an AMS programme, in which recommendations were accepted in 91⋅7% of cases. Articles www.thelancet.com Vol 85 July, 2025 5 The comparator group was variable: in 18 trials the control group received no treatment or intervention, while in 16 trials the intervention group was compared with another group that received a specific treatment or intervention according to clinical practice. Quality of studies Fig. 2 shows the scores obtained for each criterion of the Cochrane EPOC group’s risk-of-bias tool. The overall risk of bias was high for 26 studies 31–40,42,43,45,46,48,50–59,61,62 and moderate for eight, 38,41,44,47,49,60,63,64 and none of the studies were classified as having ‘low risk of bias’. Supplemental Figure S1 shows review authors’ judgements about each risk-of-bias item presented as percentages across all included studies. All studies showed similarities in the scores for each domain. Pre-post studies and non-RCTs (24/34, 70⋅6%) were scored as ‘high risk’ for random sequence generation and allocation concealment. For RCTs (10/34, 29⋅4%), most were considered to be at low risk of selection bias, with the exception of Salehipour et al., 53 where information on the randomisation and allocation method was missing. For baseline outcomes and characteristics, data from the intervention and control groups were comparable in 12 studies (35⋅3%), 30,37–40,47–49,51,54,57,58 and in the other studies statistically significant differences were observed in the baseline analysis or baseline measures were not performed. Missing outcome measures may have biased the results in three studies (8⋅8%). 32,39,51 The primary outcome variables were assessed blindly or the results were objective in 12 studies (35⋅3%). 45,47,49,51,54,55,57,58,60,62–64 The study by García Prado ME et al. 37 lacked mortality outcomes for the patient groups. Results of specific interventions Perioperative antimicrobial prophylaxis Seventeen studies addressed perioperative antimicrobial prophylaxis, some of which included different types of transplantation: mainly renal (n = 12), 31–36,38–43 but also liver (n = 4), 37,44,45,47 hepatorenal (n = 2), 37,45 lung (n = 1), 46 and pancreas (n = 1). 36 No articles about prophylaxis in heart transplantation were found. Seven studies evaluated duration of antimicrobial perioperative prophylaxis in kidney (n = 3), 41–43 liver (n = 3), 44,45,47 and lung transplantation (n = 1). 46 The remaining seven studies assessed perioperative antibiotic prophylaxis efficacy: seven of them comparing antimicrobial prophylaxis with no prophylaxis in kidney transplantation, 31–35,38,40 one of them evaluating the efficacy of addition of vancomycin in kidney and pancreas transplant recipients, 36 one evaluating the addition of gentamicin in kidney transplantation, 39 and one last study in liver transplantation comparing amoxicillin/clavulanate with cefazolin prophylaxis. 37 No differences regarding global mortality were reported in the eight studies where this variable was Fig. 1: PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only. Articles 6 www.thelancet.com Vol 85 July, 2025 Study ID Country Period (years) Design Number of patients Type of transplant Intervention Duration (months) of assessed intervention Main outcome assessed Townsend et al., 1980 31, a United States 1976–1978 Randomised clinical trial 37 Kidney Perioperative antibiotic prophylaxis 17 Post-transplant global infections Wilms et al., 1986 32, a Germany 1982 Randomised clinical trial 34 Kidney Perioperative antibiotic prophylaxis Until hospital discharge Post-transplant global infections Evans et al., 1988 33, a United Kingdom 1983 Randomised clinical trial 46 (34 transplant surgeries) Kidney Perioperative antibiotic prophylaxis 1 SSIs Cohen et al., 1988 34, a United Kingdom 1984–1985 Randomised clinical trial 53 Kidney Perioperative antibiotic prophylaxis 14 days Post-transplant global infections Robles et al., 1990 35, a Spain 1986–1987 Randomised clinical trial 60 Kidney Perioperative prophylaxis 1 SSIs, UTI Pfundstein et al., 2001 36, a United States 1994–1995 Randomised clinical trial 112 Kidney, Pancreas Perioperative antibiotic prophylaxis 12 Post-transplant global infection, SSIs García Prado et al., 2008 37 Spain 2003–2006 Pre-post study 167 Liver, Liverkidney Perioperative antibiotic prophylaxis 12 SSIs Choi S et al., 2010 38 South Korea 2006–2008 Retrospective observational 106 Kidney Perioperative antibiotic prophylaxis 36 Post-transplant global infections Abboud et al., 2013 39 Brazil 2009–2011 Pre-post study 45 Kidney Perioperative antibiotic prophylaxis 10 Post-transplant healthcareassociated infections Choi et al., 2013 40, a South Korea 2006–2010 Retrospective observational 174 Kidney Perioperative antibiotic prophylaxis 55 Post-transplant infection Orlando et al., 2015 41, a Italy 2006–2012 Randomised clinical trial 205 Kidney Perioperative antibiotic prophylaxis (duration) 65 SSIs Bliven et al., 2018 42, a United States 2013–2015 Pre-post study 100 Kidney Perioperative antibiotic prophylaxis (duration) 32 SSIs Bachmann el al. 2019 43, a Germany 2014–2017 Pre-post study 212 Kidney Perioperative antibiotic prophylaxis (duration) 21 SSIs Berry et al., 2019 44, a United States 2010–2015 Randomised clinical trial 102 Liver Perioperative antibiotic prophylaxis (duration) 63 SSIs Bandali et al., 2020 45, a United States 2013–2015 Pre-post study 44 Liver, Liverkidney Perioperative antibiotic prophylaxis (duration) 16 Post-transplant global infections Groff et al., 2021 46 United States 2013–2019 Retrospective observational 147 Lung Perioperative antibiotic prophylaxis (duration) 74 Recipient freedom from donor-derived respiratory bacterial infection Yau et al., 2022 47, a United States 2016–2019 Retrospective observational 216 Liver Perioperative antibiotic prophylaxis (duration) 45 DOT after transplant surgery Singh et al., 2006 48 United States 1996–2004 Pre-post study 144 Liver S. aureus screening and decolonisation 48 S. aureus infection or colonisation Lee et al., 2020 49 United States 2014–2016 Pre-post study 121 Kidney Universal postoperative decolonisation 23 Post-transplant global infections Wolters et al., 2014 50 Germany NS Prospective observational 40 Kidney Antimicrobial prophylaxis prior to urinary catheter removal NS UTIs Kohli et al., 2018 51 United States 2008–2015 Retrospective observational 69 Liver Antimicrobial prophylaxis prior to ERCP 24 h within ERCP ERCP related BSIs Salmela et al., 1990 52 Finland 1987–1989 Randomised clinical trial 182 Kidney Perioperative intravesically antibiotic irrigation 24 UTIs, SSIs Salehipour et al., 2009 53 Iran 2006–2007 Randomised clinical trial 200 Kidney Perioperative intravesically antibiotic irrigation 5 UTIs Haja Mydin et al., 2012 54 United Kingdom 2000–2010 Retrospective observational 129 Lung Specific prevention optimisation strategies (Choice of pre-surgical prophylaxis according to microbiological test) 120 Post-lung transplant global infections Avni-Nachman et al., 2021 55, a Israel 2011–2019 Retrospective observational 214 Kidney Duration of treatment (UTI) Not applicable UTIs Ferstl et al., 2022 56, a Germany 2008–2019 Retrospective observational 30 Liver Duration of treatment (cholangitis) Not applicable Acute cholangitis Miwa et al., 2025 57, a Japan 2010–2022 Retrospective observational 91 Liver Duration of treatment (uncomplicated Gram negative-BSI) Not applicable Composite end-pont: 30-day mortality and recurrence of infection or BSI Nussbaum et al., 2024 58 United States 2016–2021 Retrospective observational 147 All types (>65% Kidney) Oral antibiotic step-down therapy Not applicable Uncomplicated gramnegative BSIs (Table 1 continues on next page) Articles www.thelancet.com Vol 85 July, 2025 7 included. 33,34,36,39,43,44,46,47 No differences in transplantrelated complications were reported in the eight articles that addressed this issue. 34,36,37,41,43,44,46,47 All the trials looked at infectious complications. None of them showed an increase in infection rates after the intervention, and some even showed significant postintervention benefits. When compared with no prophylaxis, perioperative antimicrobial prophylaxis was shown to significantly decrease the number of total infections in one study, 34 but no differences between the two groups were observed in the other six studies. 31–33,35,38,40 Data from six of these seven studies were pooled in a metaanalysis comparing perioperative antimicrobial prophylaxis vs no prophylaxis and their respective impact on the rate of surgical site infections (SSIs) in kidney recipients. 31–35,40 The study of Choi et al. (2010) 38 was not included, as data was duplicated from Choi et al. (2013). 40 The pooled data from these six studies (Fig. 3A) showed a significant reduction in SSIs, with an RR of 1⋅93 in favour of antimicrobial prophylaxis (95% CI 1⋅14–3⋅27) and low heterogeneity between trials (I 2 0%). These results were consistent with the sensitivity analysis using a fixed-effect model (RR 1⋅93, 95% CI 1⋅14–3⋅27). The Evans et al. 33 study had 0 counts in the prophylaxis group, so the continuity correction was applied by default and a very wide CI (0⋅82–243) was observed. This indicates a very imprecise and potentially biased effect estimate, even though the contribution of this study to the metaanalysis was the lowest (3⋅4%). As a consequence, the results of the sensitivity analysis excluding this study remained unaffected (RR 1⋅80, 95% CI 1⋅05–3⋅07). The addition of gentamicin in kidney transplantation 39 produced no difference in surgical site infections, but a significant decrease was observed in urinary tract infections (UTIs). On the other hand, addition of vancomycin to the standard perioperative prophylaxis in kidney and pancreatic transplantation produced no difference in gram-positive infection rates in both types of transplants. No differences in SSIs or bloodstream infections (BSIs) were found when comparing amoxicillin-clavulanate with cefazolin as prophylaxis in liver transplantation. 37 Regarding duration of presurgical antimicrobial prophylaxis, the seven studies that evaluated this aspect in renal, 41–43 liver 44,45,47 or lung 46 transplant patients concluded that prolonged prophylaxis did not decrease the total number of infections. A metaanalysis of pooled data from six studies 41–45,47 evaluating short (a single presurgical dose 41–44,47 or 24 h 45 ) vs extended prophylaxis (>24 h) on the rate of SSIs was performed (Fig. 3B), both in kidney 41–43 and liver transplant recipients. 44,45,47 The study by Groff was excluded from the meta-analysis as it assessed a different clinical context; prophylaxis duration in lung transplant recipients from culture-positive donors, with donor-derived infections as the primary endpoint, rather than surgical site infections. Given this fundamental difference, it was not considered comparable to the studies included. There were no significant differences in the rate of SSIs when comparing short and extended prophylaxis (RR 0⋅87, 95% CI 0⋅51–1⋅48). The same result was found in the sensitivity analyses using a fixed-effect model. For kidney SOTr, the RR was 1⋅52 (95% CI 0⋅43–5⋅37) with low heterogeneity between studies (I 2 17%), and for liver SOTr, the RR Study ID Country Period (years) Design Number of patients Type of transplant Intervention Duration (months) of assessed intervention Main outcome assessed (Continued from previous page) Frenette et al., 2016 59, a Canada 2010–2014 Pre-post study 1386 Liver, Kidney, Pancreas, Pancreas–kidney AMS intervention + infection control 24 SSIs So et al., 2019 60 Canada 2013–2016 Pre-post study 318 Lung, Kidney, Liver, Kidneypancreas, Heart AMS intervention 12 Post-transplant global infections Fernández et al., 2022 61, a Spain 2016–2019 Pre-post study 76 Liver AMS intervention 12 Colonisation and infection by MDR and XDR bacteria Kueht et al., 2022 62 United States 2016–2019 Pre-post study 172 All types (mainly kidney and liver) AMS intervention 24 C. difficile testing Silva et al., 2023 63, a Spain 2014–2016 Pre-post study 196 Kidney, Kidneypancreas, Liverkidney AMS intervention + infection control 10 Post-transplant global infections Shafiekhani et al., 2023 64 Iran 2020–2021 Pre-post study 2791 All types (mainly kidney and liver) AMS intervention 12 Post-transplant global infections AMS: antimicrobial stewardship; BSIs: bloodstream infections; CDI: Clostridioides difficile infection; DOT: days of antibiotic therapy; ERCP: endoscopic retrograde cholangiography; MDR: multidrugresistant; SSIs: surgical site infections; UTIs: urinary tract infections; XDR: extensively drug-resistant; NS: Not specified. a Studies included in the meta-analyses. Table 1: Characteristics of included studies and interventions assessed. Articles 8 www.thelancet.com Vol 85 July, 2025 Study ID Description of the intervention and control groups Number of patients n (%) Mortality n (%) Transplant related complications n (%) Infections n (%) Perioperative antimicrobial prophylaxis Townsend et al., 1980 31, a Perioperative antibiotic prophylaxis (cefamandole + tobramycin) Control group: no perioperative antibiotic prophylaxis 37 C: 17 INT: 20 – – Infection in the first 7 d after transplantation C: 10 (59); INT: 4 (20) p = 0⋅04 Postoperative wound infection 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 et al., 1986 32, a Perioperative prophylaxis (cephalosporin prophylaxis 2 g pre-transplant and 500 mg at 12, 24, and 38 h hours). Control group: no perioperative antibiotic prophylaxis 34 C: 18 INT: 16 – – Surgical site infections C: 7/18 (38⋅9); INT: 5/16 (31⋅2) NS Evans et al., 1988 33, a Perioperative prophylaxis (amoxicillin-clavulanate 1 gg/200 mg two doses during surgery) Control group: no perioperative antibiotic prophylaxis 46 (34 transplant surgeries) C: 22 INT: 24 2/46 (4⋅3) C: 2 (9⋅1) INT: 0 (0) –Surgical site infections in transplant surgeries C: 4/13 (30⋅8); INT: 0/21 (0) Cohen et al., 1988 34, a Perioperative antibiotic prophylaxis (cefuroxime 750 mg and piperacillin 4 g) Control group: no perioperative antibiotic prophylaxis 53 C: 26 INT: 27 30-day mortality due to infection C: 0; INT: 1 (3⋅7) NS Required dialysis (30 days) C: 11 (42⋅3); INT: 8 (29⋅63) Total number of infections 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 Surgical wound infection 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 et al., 1990 35, a Perioperative prophylaxis with 1 dose of cefotaxime 1 g (arm A), ceftriaxone 1 g (arm B) Control group: no perioperative prophylaxis 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 Pfundstein et al., 2001 36 Addition of vancomycin to perioperative antibiotic prophylaxis Control group: no addition of vancomycin to perioperative antibiotic prophylaxis vancomycin Kidney: 88 C: 45 INT: 43 Pancreas: 24 C: 12 INT: 12 Patient 1-yr survival Kidney: C: 89; INT: 95 NS Pancreas: C: 92; INT: 100 NS Rejection during transplant admission Kidney: C: 24%; INT: 23% NS (p = 0⋅90) Pancreas: C: 42%; INT: 8% NS (p = 0⋅06) Allograft 1-yr survival Kidney: C: 78%; INT: 93% NS (p = 0⋅07) Pancreas: C: 92%; INT: 92 % NS (p = 1⋅00) Gram-positive infection Kidney: C: 22%; INT: 20% NS (p = 0⋅76) Pancreas: C: 50%; INT: 33% NS (p = 0⋅41) García Prado et al., 2008 37 Perioperative antibiotic prophylaxis with amoxicillin/clavulanate Control group: perioperative antibiotic prophylaxis with cefazolin 167 Pre-INT: 94 Post-INT: 73 –Graft survival 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 continues on next page) Articles www.thelancet.com Vol 85 July, 2025 9 patients who switched to oral therapy. No differences in total antibiotic duration were reported. Specific AMS implementation approach Six studies reported the impact of specific AMS implementation approach on SOTr. 59–64 Five of them reported results about implementation of a general AMS programme in different transplant units: one 61 in liver transplant; one 59 in liver, kidney, pancreas, and kidney-pancreas; one 60 in lung, kidney, liver, kidneypancreas, and heart transplant patients; one 63 in kidney, kidney-pancreas, and kidney-liver; and one 64 in all types of transplantation (principally kidney and liver). Finally, one study 62 evaluated an AMS approach prior to ordering C. difficile tests (requiring prescribers to answer a series of short questions within the electronic medical record before ordering C. difficile tests), where all types of transplant were included (mainly kidney and liver). With respect to evaluation of implementation of a general AMS programme in different transplant units, none of the studies showed any difference regarding mortality, one of them reported a decrease in overall SSI rate, 59 another a decrease in UTI and cystitis. 63 One study reported data related to transplantation, 63 with no difference among groups. No other differences in other infection-related variables were described. Antimicrobial consumption was assessed in five studies, 60–64 all of them showing a decrease in overall consumption of antibiotics. Regarding antimicrobial resistance, Silva et al. 63 reported a reduction in the incidence of infections due to AmpC-producing Enterobacterales during the intervention period, after implementation of a joint programme of AMS and hospital-acquired infection control in a kidney, pancreas and liver transplant unit. No differences in episodes due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales or multidrugresistant (MDR) P. aeruginosa were reported. Shafiekhani et al. 64 reported a significant reduction in frequency of patients with methicillin-resistant S. aureus, carbapenem-resistant Enterobacterales, Klebsiella pneumoniae carbapenemase (KPC) isolates and vancomycin-resistant Enterococcus colonisation after the implementation of an AMS programme in a transplant unit. No differences regarding antimicrobial resistance among both intervention and control groups were reported by Fernández et al. 61 The study 62 that evaluated an AMS approach prior to ordering C. difficile tests showed a significant decrease in number of orders for C. difficile toxin, with no differences according to rates of negative C. difficile toxin tests between both groups. Of all the studies, only three reported outcomes homogeneously and provided sufficient information to be included in the meta-analysis. Thus, we were able to pool the data from these three studies to assess the effect of AMS implementation in SOTr on SSI rates. 57,59,61 They were pre-post studies with a moderate to high risk of bias. Fernández et al. 61 and Silva et al. 57 did not find a significant reduction in the number of SSIs as a result of the intervention, in contrast to the study by Frenette et al., 59 where the authors observed a reduction from 15⋅5% to 7⋅5% for SSI rates in SOTr. The pooled data from these studies (Fig. 3D) showed a significant reduction in this outcome, with an OR of 0⋅57 in favour of AMS programmes (95% CI 0⋅35–0⋅94) and low heterogeneity between studies (I 2 21%). These results were consistent with the sensitivity analyses using a fixed-effect model (OR 0⋅54, 95% CI 0⋅36–0⋅81). Discussion SOTr are a fragile population at high risk of infectious complications due to MDRO. Therefore, developing adequate AMS programmes in this setting is an urgent need. 10,18 After searching various databases, a total of 34 publications with a moderate to high risk of bias were included. All were original articles reporting data from controlled clinical trials, pre-post studies or observational studies with a control group that analysed the effect of different types of strategies for optimising antimicrobial use in SOTr on mortality, infectious complications, graft related complications, antimicrobial resistance, antimicrobial consumption, and/or hospitalisation. We would like to highlight some of the most relevant papers published in recent years, grouped together by assessed intervention. Regarding presurgical antimicrobial prophylaxis, we found two recent systematic reviews addressing the issue. A systematic review and meta-analysis 65 performed in 2020, including RCTs and quasi-RCTs assessing the safety and/or efficacy of perioperative antibiotics in SSIs in SOTr, included eight studies (718 randomised participants) with high risk of bias. They concluded that, based on the data available, there is very low certainty evidence to support routine treatment of SOTr with antibiotics to prevent SSIs, so they could not make specific recommendations. In addition, a recent systematic review conducted by Campos-Valera et al., 66 which included eight studies focussing on liver transplant recipients, concluded that the recommendation strength of perioperative liver transplantation antimicrobial prophylaxis was strong for preventing bacterial infections, length of stay (LOS), and mortality, but weak for determining the optimal antibiotic regimen. This review included two non-comparative studies 67,68 and another study 69 addressing targeted prophylaxis against ESBL-producing Enterobacteriaceae-related infection among carriers following liver transplantation. Our search included 17 articles that dealt with perioperative antimicrobial prophylaxis, mainly in kidney and liver transplantation. The search did not identify the optimal antimicrobial regimen for prophylaxis, but it did Articles 16 www.thelancet.com Vol 85 July, 2025 include seven studies that looked at the duration of prophylaxis, and none of these showed differences in infectious complications, graft related complications or increased mortality after a short prophylaxis regimen, even in lung transplantation (<10 days in this case). Based on the results of our meta-analysis, there was no difference in the rate of SSIs between short and extended duration of antimicrobial prophylaxis for kidney and liver SOTr. As regards duration of treatment, our pooled data results from three observational studies suggest that in cases of non-complicated graft infections (primarily urinary, cholangitis, and other intra-abdominal infections) where adequate source control has been achieved, longer regimens of antimicrobial treatments may not have a potential impact in terms of recurrence of the infection. In addition, no studies reported an increase in mortality. The fact that shorter antimicrobial regimens may be sufficient in SOTr, as long as graft infection is not complicated, is consistent with current evidence. 70 Unfortunately, SOTr have been excluded from most trials of treatment duration. Data from this meta-analysis may allow them to be included in future randomised trials to finally answer this question. Of the five trials that looked at the implementation of a specific AMS approach in different transplant units, 59–61,63,64 no transplant-related complications were observed after AMS intervention, suggesting that AMS programmes in the SOTr population are safe. In addition, the use of AMS can reduce SSI rates by half, according to the results of our meta-analysis. However, this result is based on three pre-post studies, mainly driven by the study by Frenette et al., 59 so it will be necessary to confirm this finding with higher-quality studies. For the other types of interventions evaluated, we did not find sufficient evidence to make a recommendation. Mainly oral step-down therapy 71 may benefit SOTr, although we did not find enough evidence to fully support this claim. Other interventions, such as perioperative intravesical antibiotic irrigation 52,53 and antimicrobial prophylaxis prior to ERCP in liver transplantation, 51 do not appear to be effective in the kidney and liver transplant populations, respectively. Even if our search strategy did not reveal any studies on the role of empirical treatment, we would like to highlight two retrospective studies that evaluated this issue but were not included in our systematic review because of their design: Lupei et al. 72 and Hamandi et al. 73 Both report a significantly higher mortality rate in SOTr patients whose antimicrobial empirical antimicrobial treatment was inadequate. Although we do not have any studies with a control group evaluating empirical treatment, these two studies suggest the importance of choosing the right regimen early in the course of infection in SOTr. Neither did our search strategy find any studies on false-antibiotic allergy de-labelling. However, there are some observational studies 74,75 suggesting worse outcomes associated with SOTr patients with a false antibiotic allergy label, including higher C. difficile rates and graft failure. Even in the absence of comparative studies, this shows the need to promote multidisciplinary interventions aiming at removing invalid allergy labels prior to transplant. The results presented in this systematic review are in line with the available published evidence, thus showing the need to evaluate the impact of AMS interventions on SOTr by conducting further higherquality studies, 10,18 mainly in types of transplant other than kidney and liver. Some AMS strategies with proven benefits for SOTr have demonstrated the usefulness of treating asymptomatic bacteriuria beyond two months after kidney transplantation to prevent UTIs, and the efficacy of antifungal prophylaxis to prevent invasive fungal infection among liver transplant recipients. However, thanks to this systematic review, we were able to identify some areas of deficit that urgently need development and research in the SOT population: antimicrobial prophylaxis (mainly its efficacy and duration in other types of SOTs different to kidney) and duration of treatment in graft-related infections. Efficacy of antifungal prophylaxis to prevent mould infections in lung transplant and efficacy of treating asymptomatic bacteriuria in early kidney transplant recipients also need to be developed. Other areas, such as the usefulness of de-escalation, oral transition and mislabelling of antibiotic allergies, also need future research, even if they can be inferred from data from the general population. Also, none of the included studies reported information about antimicrobial-related toxicity, which is an interesting variable to collect in future studies. A summary of the current evidence and proposed future research needs is presented in Table 3. Based on the interpretations of the findings of each of the evaluated studies, we can establish some criteria for the design of future AMS interventions in SOTr population, including both general and specific characteristics, to ensure that these programmes are more effective. It is essential that we divide the interventions according to type of transplant, heart, lung, pancreas, and intestinal transplantation being the areas where we have more uncertainty. It is also important to determine transplant related variables in each study, both as baseline variables (type of immunosuppression, treatment of rejection, etc.) and outcomes. In addition, we believe that it is important to highlight the need to include SOTr population in clinical trials related to AMS interventions, from which they are traditionally excluded. In terms of outcomes, four meta-analyses were performed: one assessing the impact of an AMS Articles www.thelancet.com Vol 85 July, 2025 17 approach in hospitalised SOTr, showing its possible benefits; two meta-analyses of antimicrobial prophylaxis in SOT surgery (liver and kidney), where surgical prophylaxis was found to reduce surgical site infection rates in SOT patients, but no additional benefit was found for extended prophylaxis; and one assessing non-complicated graft infections, where no differences were found in terms of recurrence of infection when comparing short and extended treatment durations. Future studies of antimicrobial optimisation in SOTr should include variables such as mortality, transplant-related complications, development of antimicrobial resistance, antimicrobial consumption and hospital-related outcomes in a standardised way to allow pooled analysis. This study has several limitations. First, the search field was the title because the wide range of terms included in the search strategy made the initial search including the abstract fields unfeasible. To offset this disadvantage, citations of included references and relevant systematic reviews were searched to identify additional studies. Second, the low quality of the studies included in the systematic review makes it difficult to draw firm conclusions about the effects of AMS interventions in SOTr. Also, the heterogeneity of interventions included in the review increases the difficulty of understanding the effect of each of them. Third, as the meta-analysis on antimicrobial prophylaxis is based on articles that in some cases were published more than 20 years ago, the results should be taken with caution. The same applies to the metaanalysis on the effect of AMS in SSIs, where the results are mainly driven by the study by Frenette et al. 59 with a large number of patients evaluated, but which is older than the other two studies. AMS interventions Available studies Results Proposed future research priority a Antimicrobial prophylaxis interventions Efficacy of perioperative antibiotic prophylaxis to prevent SSIs in KT surgery Total studies: 6 A decrease in SSIs was shown in patients who received antimicrobial prophylaxis in transplant surgeries, favouring antimicrobial prophylaxis Low RCTs: 5 Total patients: 390 Shortening perioperative antibiotic prophylaxis <24 h Total studies: 6 No differences in SSIs were found comparing short and extended surgical antimicrobial prophylaxis in kidney and liver transplant recipients Low for KT and LT High for lung, heart, multivisceral/intestinal, and combined transplant RCTs: 2 Total patients: 839 Efficacy of antifungal prophylaxis to prevent mould infections in lung transplant 24,25 Total studies: 28 No evidence of benefit for antifungal prophylaxis vs no prophylaxis, universal prophylaxis vs pre-emptive treatment, or prolonged (>6 months) prophylaxis vs <6 months based mainly on observational, high risk of bias studies. High RCTs: 1 Total patients: 4538 Efficacy of antifungal prophylaxis to prevent IFI in LT 26,27 Total studies: 15 Consistent evidence across RCTs on the benefit of antifungal prophylaxis vs placebo to prevent IFIs in high-risk LT. No proven benefit for other antifungals over fluconazole. Low RCT: 15 Total patients: 1853 Treating asymptomatic bacteriuria in KT 22,23 Total studies: 9 No clinical benefits proved for treating asymptomatic bacteriuria in KT beyond 2 months after transplantation Low for late KT High for early KT RCTs: 5 Total patients: 959 Antibiotic treatment optimisation interventions Shortening treatment duration for graft infections Total studies: 3 No clinical benefits proved for treatments >10 days vs shorter courses of 6–10 days for non-complicated graft infections High RCTs: 0 Total patients: 335 Safety and timing of oral switch Total studies: 1 No differences in clinical outcomes or rate of patients with BSIs which needed to restart iv treatment for the index infection between fully-iv treatments and oral transitions High RCTs: 0 Total patients: 162 Assessing the impact of AMS programs in SOT units Reducing antibiotic consumption Total studies: 2 All available studies showed decreased antibiotic consumption after AMS implementation Low RCTs: 0 Reducing mortality, readmissions, LOS Total studies: 6 No clinical outcome benefits have been proved for AMS interventions High RCTs: 0 Reducing incidence of infections Total studies: 3 Significant reduction in SSIs after implementing combined AMS + infection control interventions in SOT units Moderate RCTs: 0 Reducing bacterial resistance Total studies: 3 Limited evidence from non-controlled trials showing reductions in the incidence of some specific MDRO High RCTs: 0 Comparing effectiveness of different interventions or implementation strategies Total studies: 0 No evidence on which interventions and implementation strategies are more effective in SOT units High RCTs: 0 AMS: Antimicrobial stewardship; KT: Kidney transplant; LT: Liver transplant; IFI: Invasive fungal infection; RCT: Randomised controlled trial; BSIs: Bloodstream infection; SOT: Solid organ transplant; LOS: Length of hospital stay; SSIs: Surgical site infections: MDRO: Multidrug resistant organisms. This table has been elaborated according to the data produced by this systematic review combined with recently published reviews on specific topics. a Ranking criteria for future research priority: High priority: Not available or only low-quality studies for a frequent clinical problem. Moderate priority: Some moderate quality studies already available or infrequent clinical problems. Low priority: High quality studies already available. Table 3: Current evidence summary and proposed future research needs. Articles 18 www.thelancet.com Vol 85 July, 2025 We should also emphasise that the field of solid organ transplantation is relatively young compared to other fields of medicine, as is antimicrobial stewardship, so more studies need to be carried out. It should be taken into account that patient volumes vary between centres and across the world, and that conducting prospective RCTs specifically on infectious diseases and antimicrobial stewardship has limitations in enrolment to achieve sample sizes with sufficient power. Finally, antimicrobial use and tailored interventions also depend on local epidemiology, which may limit the extrapolation of local results to the global community. We conclude that, although the available evidence on the impact of AMS interventions in the SOTr population is scarce and of low quality, some strategies, such as shorter perioperative antimicrobial prophylaxis, shorter treatment duration for graft-related infections and uncomplicated gram-negative BSI in liver and kidney transplant recipients, and the implementation of an AMS programme in transplant units, appear to improve antimicrobial use without increasing infection complications. Our pooled data from the meta-analyses showed no benefit from prolonged antimicrobial surgical prophylaxis in liver and kidney transplant recipients, and a possible beneficial effect on SSIs when an AMS approach is implemented in hospitalised SOTr patients. Furthermore, systematic review of available evidence found no evidence of increasing mortality, graft-related complications, increasing hospital admissions or antimicrobial resistance when AMS measures are implemented. While there is no compelling evidence against, there are, on the contrary, well-grounded reasons in favour of implementing strategies to optimise antibiotic use and AMS programmes in the SOTr population, designed to achieve the best possible results in these settings. This study has identified the areas of AMS research in SOTr that require the highest priority, those with the lowest level of evidence, and those where the level of knowledge is sufficient as to be applied. Contributors MPG, ABGG, JMGB, GP, RAM, MEPI, JMC designed the study. MPG and ABGG developed the search strategy with feedback from JMGB, GP, and JMC. MPG and ABGG screened and selected studies. MPG and ABGG extracted the data and prepared the data for analysis. JMC, GP, and JMGB had access to and verified the study data. ABGG analysed the data. MPG wrote the first draft of the manuscript, and all authors critically revised the manuscript. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. All authors read and approved the final version of the manuscript. Data sharing statement The study protocol is available at PROSPERO (CRD42024554606). The datasets generated and analysed in this meta-analysis are published in the Appendix. Additional information collected from studies is available from the corresponding author on reasonable request. Declaration of interests MPG is supported by the Subprograma Río Hortega, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain (CM23/00078). ABGG is supported by the Subprograma Juan Rodés, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación, y Universidades, Spain (JR21/00017). GP reports grants from the Centro de Investigación Biomédica en Red (CIBER), Instituto de Salud Carlos III, Spanish Government, co-financed by the European Development Regional Fund (A Way to Achieve Europe), Madrid, Spain. MEPI is a researcher belonging to the program “Nicolás Monardes” (C1-00382019), Servicio Andaluz de Salud, Junta de Andalucía, Spain. Acknowledgements N/A. Appendix A. Supplementary data Supplementary data related to this article can be found at https://doi. org/10.1016/j.eclinm.2025.103310. 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