The impact of colonization by multidrug resistant bacteria on graft survival, risk of infection, and mortality in recipients of solid organ transplant: systematic review and meta-analysis

Abstract

Background: The Global increase in colonization by multidrug-resistant (MDR) bacteria poses a significant concern. The precise impact of MDR colonization in solid organ transplant recipients (SOTR) remains not well established.

Objectives: To assess the impact of MDR colonization on SOTR's mortality, infection, or graft loss.

Methods and data sources: Data from PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library, ProQuest Dissertations, Theses Global, and SCOPUS were systematically reviewed, spanning from inception until 20 March 2023. The study protocol was registered with PROSPERO (CRD42022290011) and followed the PRISMA guidelines. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, INTERVENTIONS, AND ASSESSMENT OF RISK OF BIAS: Cohorts and case-control studies that reported on adult SOTR colonized by Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase (ESBL) or carbapenem-resistant Enterobacteriaceae. (CRE), or MDR-pseudomonas, and compared to noncolonized, were included. Two reviewers assessed eligibility, conducted a risk of bias evaluation using the Newcastle-Ottawa Scale, and rated certainty of evidence using the GRADE approach.

Methods of data synthesis: We employed RevMan for a meta-analysis, using random-effects models to compute pooled odds ratios (OR) and 95% confidence intervals (CI). Statistical heterogeneity was determined using the I² statistic.

Results: 15,202 SOTR (33 cohort, six case-control studies) were included, where liver transplant and VRE colonization (25 and 14 studies) were predominant. MDR colonization significantly increased posttransplant 1-year mortality (OR, 2.35; 95% CI, 1.63-3.38) and mixed infections (OR, 10.74; 95% CI, 7.56-12.26) across transplant types (p < 0.001 and I² = 58%), but no detected impact on graft loss (p 0.41, I² = 0). Subgroup analysis indicated a higher association between CRE or ESBL colonization with outcomes (CRE: death OR, 3.94; mixed infections OR, 24.8; ESBL: mixed infections OR, 10.3; no mortality data) compared to MRSA (Death: OR, 2.25; mixed infection: OR, 7.75) or VRE colonization (Death: p 0.20, mixed infections: OR, 5.71).

Conclusions: MDR colonization in SOTR, particularly CRE, is associated with increased mortality. Despite the low certainty of the evidence, actions to prevent MDR colonization in transplant candidates are warranted.

Keywords: Colonization; Infection; MDR; Mortality; Multi drug resistant; Organ; Transplant.