Abstract：
BACKGROUND: Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial.
OBJECTIVE: To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection.
METHODS: A systematic review and individual patient data meta-analysis.
METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023.
METHODS: (a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis.
METHODS: SOT recipients.
METHODS: TMP-SMX prophylaxis versus no prophylaxis.
UNASSIGNED: Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies.
UNASSIGNED: For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS: Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100).
CONCLUSIONS: In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.
OBJECTIVE: To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection.
METHODS: A systematic review and individual patient data meta-analysis.
METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023.
METHODS: (a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis.
METHODS: SOT recipients.
METHODS: TMP-SMX prophylaxis versus no prophylaxis.
UNASSIGNED: Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies.
UNASSIGNED: For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS: Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100).
CONCLUSIONS: In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.
摘要：
背景：甲氧苄啶-磺胺甲恶唑（TMP-SMX）预防是否可以预防实体器官移植受体（SOT）的诺卡心症存在争议。
目的：评估TMP-SMX在预防SOT术后诺卡心病中的作用，它的剂量-反应关系，它对预防播散性诺卡尼病的作用，以及突破性感染时TMP-SMX耐药的风险。
方法：系统评价和个体患者数据荟萃分析。
方法：MEDLINE，Embase,Cochrane中央控制试验登记册,Cochrane系统评价数据库，WebofScience核心合集,和Scopus至2023年9月19日。
方法：（i）有和没有TMP-SMX预防的SOT接受者之间的诺卡心病风险，或（ii）足够的细节来确定突破性诺卡尼病的TMP-SMX耐药率。
方法：SOT接受者。
方法：TMP-SMX预防与不预防。
■用于比较研究的ROBINS-E；用于非比较研究的专用工具。
■对于我们的主要结果(即，为了确定TMP-SMX对诺卡尼病风险的影响)，使用一步混合效应回归模型来估计结局与暴露之间的关联.使用单变量和多变量无条件回归模型来调整潜在的混杂效应。使用等级方法评估证据的确定性。
结果：获得了来自三项病例对照研究的个体数据（260例SOT受者，519个未感染的对照）。TMP-SMX预防与显著降低的诺卡心症风险独立相关(校正OR=0.3,95%CI0.18-0.52,证据的中度确定性)。与诺卡心病风险增加独立相关的变量是年龄较大，目前使用皮质类固醇，钙调磷酸酶抑制剂浓度高，近期急性排斥反应,较低的淋巴细胞计数，心脏移植。突破性感染（66/260，25％）通常对TMP-SMX敏感（合并比例98％，95%CI92-100）。
结论：在SOT接受者中，TMP-SMX预防可能会降低诺卡心病的风险。在突破性感染的情况下，耐药性似乎并不常见。
目的：评估TMP-SMX在预防SOT术后诺卡心病中的作用，它的剂量-反应关系，它对预防播散性诺卡尼病的作用，以及突破性感染时TMP-SMX耐药的风险。
方法：系统评价和个体患者数据荟萃分析。
方法：MEDLINE，Embase,Cochrane中央控制试验登记册,Cochrane系统评价数据库，WebofScience核心合集,和Scopus至2023年9月19日。
方法：（i）有和没有TMP-SMX预防的SOT接受者之间的诺卡心病风险，或（ii）足够的细节来确定突破性诺卡尼病的TMP-SMX耐药率。
方法：SOT接受者。
方法：TMP-SMX预防与不预防。
■用于比较研究的ROBINS-E；用于非比较研究的专用工具。
■对于我们的主要结果(即，为了确定TMP-SMX对诺卡尼病风险的影响)，使用一步混合效应回归模型来估计结局与暴露之间的关联.使用单变量和多变量无条件回归模型来调整潜在的混杂效应。使用等级方法评估证据的确定性。
结果：获得了来自三项病例对照研究的个体数据（260例SOT受者，519个未感染的对照）。TMP-SMX预防与显著降低的诺卡心症风险独立相关(校正OR=0.3,95%CI0.18-0.52,证据的中度确定性)。与诺卡心病风险增加独立相关的变量是年龄较大，目前使用皮质类固醇，钙调磷酸酶抑制剂浓度高，近期急性排斥反应,较低的淋巴细胞计数，心脏移植。突破性感染（66/260，25％）通常对TMP-SMX敏感（合并比例98％，95%CI92-100）。
结论：在SOT接受者中，TMP-SMX预防可能会降低诺卡心病的风险。在突破性感染的情况下，耐药性似乎并不常见。
