Paniagua-García María, Guisado-Gil Ana Belén, Molina Gil-Bermejo José, Peñalva Germán, Álvarez-Marín Rocío, Pachón-Ibáñez María Eugenia, Cisneros José Miguel
Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Virgen del Rocío University Hospital, Seville, Spain.
Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
EClinicalMedicine. 2025 Jul 3;85:103310. doi: 10.1016/j.eclinm.2025.103310. eCollection 2025 Jul.
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.
In our systematic review and meta-analyses, we searched MEDLINE (via PubMed), EMBASE, and SCOPUS for original research articles published up to 06 March 2025.Studies with a control group evaluating different strategies to optimise antimicrobial use in adult SOTr were included. The outcomes assessed were mortality, transplant-related complications, infectious outcomes, development of antimicrobial resistance, antimicrobial consumption, hospital related variables, and antimicrobial toxicities. A risk-of-bias assessment was performed using the Cochrane EPOC group's criteria. Data from included studies were pooled in meta-analyses if three or more studies had the same type of intervention and comparison group and reported sufficient data on infection outcomes to be combined. Meta-analyses were performed using a random-effects model and the inverse variance method with the I 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.
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.
Strategies to optimise antimicrobial use are safe, with no negative impact on mortality or transplant-related complications, and appear to improve some clinical outcomes in SOTr, particularly when using perioperative antimicrobial prophylaxis in kidney SOTr and when implementing AMS programmes. No difference in the rate of surgical site infection was found between short and extended duration of antimicrobial prophylaxis for kidney and liver SOTr. This suggests that a shorter duration of antimicrobial surgical prophylaxis may be safe for transplant recipients. Short courses of antibiotics were not associated with an increased rate of relapses for uncomplicated graft infections, according to observational studies pooled in our meta-analysis. However, further high-quality clinical trials are needed to better understand the effects of these strategies in SOTr and to design optimal AMS interventions in this population.
This study was supported by the (ISCIII, reference ICI21/00075) and the Centro de Investigación Biomédica en (CIBERINFEC, CB21/13/00006), ISCIII, .
实体器官移植受者（SOTr）发生感染并发症的风险很高，因此需要制定有效的抗菌药物管理（AMS）计划。我们旨在综述不同策略优化SOTr抗生素使用的有效性和安全性的现有证据。
在我们的系统评价和荟萃分析中，我们检索了MEDLINE（通过PubMed）、EMBASE和SCOPUS，以获取截至2025年3月6日发表的原始研究文章。纳入了有对照组的研究，这些研究评估了优化成人SOTr抗菌药物使用的不同策略。评估的结局包括死亡率、移植相关并发症、感染结局、抗菌药物耐药性的发展、抗菌药物消耗、医院相关变量以及抗菌药物毒性。使用Cochrane EPOC小组的标准进行偏倚风险评估。如果三项或更多研究具有相同类型的干预措施和比较组，并报告了足够的感染结局数据以进行合并，则将纳入研究的数据汇总到荟萃分析中。使用随机效应模型和逆方差方法进行荟萃分析，并使用I统计量检验研究之间的不一致性。还进行了敏感性分析。本研究遵循系统评价和荟萃分析的首选报告项目（PRISMA）指南。PROSPERO注册号：CRD42024554606。
在识别出的4050篇文章中，34项研究符合纳入标准。17项研究涉及围手术期抗菌药物预防（其中7项专门评估了抗菌药物预防的持续时间），2项报告了关于去定植策略的信息，3项涉及作为目标治疗的抗菌药物治疗持续时间，1项评估了抗生素口服降阶梯策略，6项报告了AMS实施方法对SOTr的影响。其他5项研究评估了特定的靶向预防。所有研究都有中度或高度偏倚风险。对三项关于AMS计划效果的研究进行的荟萃分析表明，这种干预可能会降低手术部位感染率（OR 0.57，95%CI 0.35 - 0.94）。对于围手术期抗菌药物预防，六项试验的荟萃分析表明，在肾脏SOTr中，预防在降低手术部位感染方面有效果（风险比1.93，95%CI 1.14 - 3.27），但将预防时间延长超过24小时与改善手术部位感染率无关（RR 0.87，95%CI 0.51 - 1.48）。关于单纯性移植相关感染（肝脏和肾脏SOTr）的抗菌药物治疗持续时间，荟萃分析发现短疗程和长疗程抗菌方案在复发方面没有差异（0.86，95%CI 0.55 - 1.34）。这四项荟萃分析在研究之间具有低异质性。
优化抗菌药物使用的策略是安全的，对死亡率或移植相关并发症没有负面影响，并似乎能改善SOTr的一些临床结局，特别是在肾脏SOTr中使用围手术期抗菌药物预防和实施AMS计划时。对于肾脏和肝脏SOTr，抗菌药物预防时间短和长在手术部位感染率上没有差异。这表明较短的抗菌药物手术预防时间对移植受者可能是安全的。根据我们荟萃分析中汇总的观察性研究，短疗程抗生素与单纯性移植感染的复发率增加无关。然而，需要进一步的高质量临床试验来更好地了解这些策略在SOTr中的效果，并为该人群设计最佳的AMS干预措施。
本研究由（西班牙国家卫生系统研究所，参考编号ICI21/00075）和西班牙国家卫生系统研究所的生物医学研究中心（CIBERINFEC，CB21/13/00006）资助。
Zotero 插件
