TY - JOUR
T1 - Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients
T2 - systematic review and individual patient data meta-analysis
AU - Passerini, Matteo
AU - Nayfeh, Tarek
AU - Yetmar, Zachary A.
AU - Coussement, Julien
AU - Goodlet, Kellie J.
AU - Lebeaux, David
AU - Gori, Andrea
AU - Mahmood, Maryam
AU - Temesgen, Zelalem
AU - Murad, Mohammad H.
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2024/2
Y1 - 2024/2
N2 - Background: Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. Objectives: 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. Data sources: 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. Study eligibility criteria: (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. Participants: SOT recipients. Intervention: TMP-SMX prophylaxis versus no prophylaxis. Assessment of risk of bias: Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies. Methods of data synthesis: 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.
AB - Background: Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. Objectives: 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. Data sources: 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. Study eligibility criteria: (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. Participants: SOT recipients. Intervention: TMP-SMX prophylaxis versus no prophylaxis. Assessment of risk of bias: Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies. Methods of data synthesis: 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.
KW - Infections in immunosuppressed
KW - Nocardiosis
KW - Prophylaxis
KW - SOT
KW - Systematic review
UR - http://www.scopus.com/inward/record.url?scp=85176143800&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85176143800&partnerID=8YFLogxK
U2 - 10.1016/j.cmi.2023.10.008
DO - 10.1016/j.cmi.2023.10.008
M3 - Review article
C2 - 37865337
AN - SCOPUS:85176143800
SN - 1198-743X
VL - 30
SP - 170
EP - 177
JO - Clinical Microbiology and Infection
JF - Clinical Microbiology and Infection
IS - 2
ER -