Meta-Analysis and Systematic Review of Post-Transplant Infection Rates Following Prophylactic and Preemptive Strategies in Solid Organ Transplant Recipients

Purpose : Standard of care to prevent infectious complications post solid organ transplant (SOT) generally involves prophylactic antimicrobial or preemptive monitoring strategies. This systematic review and meta analysis aims to compare rates of common viral and fungal post-SOT infections following either preemptive or prophylactic therapy strategies in kidney, liver, pancreas, lung, and heart SOTs. Methods : Data sources included PubMed, Embase, Medline Complete, Scopus, Web of Science, US National Institutes of Health's ongoing trials registry, Cochrane Library, email listservs, and references of included articles. Studies were considered for inclusion if they involved SOT patients who received an abdominal or thoracic organ, aged over 18 years, and recipients of either prophylaxis or preemptive prevention strategies for a qualifying pathogen within the first year of transplantation. Qualifying organisms included Candida species, Aspergillus species, Zygomycosis (multiple species), Cytomegalovirus (CMV), Herpes Simplex Virus (HSV), and Varicella Zoster Virus (VZV). Data extracted from eligible studies included study methods, prevention strategy used, and development of fungal and/or viral infections. The primary outcome was the odds ratio of opportunistic infections post-SOT when comparing preemptive and prophylactic strategies. Secondary outcomes included time to infection, rates of transplant rejection, rates of antimicrobial adverse events, and mortality rate. Results : 107 studies were extracted and pooled for analysis. Of the 14,464 patients included, 12,194 patients reportedly received prophylactic therapy, while 1,257 patients reportedly received preemptive therapy. Two of the most common infections were more prevalent in patients receiving preemptive therapy, CMV (OR 6.47; 95% CI, 5.72-7.32) and Aspergillus species (OR 2.92; 95% CI 1.99-4.27). Of patients who received preemptive therapy, 59.45% reported an infection with one of the identified study pathogens (n=739) and of patients who received prophylactic therapy, 18.84% reported an infection (n=2,297) (OR 6.32; 95% CI, 5.59-7.14). Patients who received preemptive therapy consistently had an increased odds of infection across all categories, heart transplants (OR 12.73; 95% CI, 8.86-18.30), lung transplants (OR 10.95; 95% CI, 5.35-22.43), liver transplants (OR 4.35; 95% CI, 3.25-5.83), and kidney transplants (OR 2.94; 95% CI, 2.57-3.36). The mortality rate was not significantly different between preemptive and prophylactic therapies (OR 1.57; 95% CI, 0.98-2.53) nor was the rate of adverse effects (OR 1.04; 95% CI, 0.86-1.27). Meta-analysis of infection rates in 14 studies showed that the odds of infection in the preemptive group were 3.84 times that of the prophylactic group (OR 3.84; 95% CI, 2.03-7.26; p < 0.05). Analysis of rejection rates in 8 studies and of mortality rates in 4 studies showed no statistically significant differences. Conclusion : The incidence of infection within the first year of SOT is lower in recipients that receive prophylaxis compared to those that receive preemptive therapy but the rates of mortality and adverse effects were similar.