This study was conducted to provide information about the pattern of BSI in pediatric liver and kidney transplant recipients. BSI were common with an incidence rate of 1.91 first BSI per 100 pediatric liver and kidney transplant recipients per month in the first-year post-transplantation. The BSI pathogen composition differed between liver and kidney transplant recipients with bacteria from the Enterobacterales group being more common in kidney transplant recipients whereas Candida spp. and Enterococci spp. only were observed in liver transplant recipients.
No previous studies have reported the IR of BSI in pediatric liver and kidney transplant recipients during the entire first-year post-transplantation. The overall IR of first BSI in the first-year post-transplantation in our study is comparable with data from a nationwide Spanish study of 2935 adult solid organ transplant (SOT) recipients. In this report, the overall IR was 4.8 and 3.0 BSI per 10 000 days post-transplantation in liver and kidney transplant recipients, respectively(18) (corresponding to 1.5-0.9 BSI per 100 recipients per month). Furthermore, a recent study in adult SOT recipients showed that the IR of all infections in liver and kidney transplant recipients was highest during the early post-transplantation period and declined during the first-year post-transplantation(7). We found a similar trend in our cohort with a higher IR in the early post-transplantation period.
With regard to the pathogen composition, we found a higher frequency of BSI with Enterobacterales in kidney transplant recipients than in liver transplant recipients. Similar findings have been reported in adult liver and kidney transplant recipients where Gram-negative bacteria were the major cause of BSI in kidney transplant recipients(7,18,19). We used CDC criteria for BSI which includes bacteria that are normally considered as contaminants including coagulase-negative staphylococci(15). However, there were no BSI due to coagulase-negative staphylococci or other contaminants in our cohort. In contrast, previous studies that used CDC criteria reported as many as 30% of BSI being caused by coagulase-negative staphylococci in pediatric liver transplant recipients(6,9). Furthermore, we found only one case of Staphylococcus aureus which in previous retrospective studies has caused a high proportion of BSI(6,20). However, these studies were conducted in other geographical settings (Japan and the USA) where the antibiotic treatment strategies differ from the Danish approach which may, in part, explain the differences. Other explanations may include differences in surgical techniques, the use of intravenous catheters, and immunosuppression regimens between centers.
In our study, candidemia was rare and only found in liver transplant recipients with an IR of 0.38 fungal BSI per 100 recipients per month in the first-year post-transplantation. This is in line with a study exclusively investigating invasive fungal disease in 584 pediatric SOT recipients that found no invasive fungal disease in the kidney group, while 27.5 invasive fungal diseases per 100 000 patients days (corresponding to 0.85 events per month per 100 recipients) was found in the liver transplant recipients(21). However, this study only investigated invasive fungal disease in the first 180 days post-transplantation, and data for the later post-transplantation periods were not available.
Only one multidrug-resistant organism, an Extended-spectrum-β-lactamase producing E. coli, was observed in our cohort. This is in contrast to a study investigating severe sepsis in 173 pediatric liver transplant recipients reporting that 47.6% of the bacterial infections were with multidrug-resistant organisms(22). However, this study only included a population of highly selected pediatric liver transplant recipients admitted to the pediatric intensive care unit.
Current reviews of BSI in solid organ transplant recipients including liver and kidney transplantation recommend empiric antibiotic treatment of suspected BSI depending on local epidemiology and previous microbiology data. The antibiotic regimens should cover Gram-negative bacteria and, in the case of intravascular catheters, also Gram-positive bacteria(23,24). In our center, the current recommendation for empiric antibiotic treatment of suspected BSI in pediatric liver and kidney transplant recipients is the use of carbapenem. Our findings support the use of empiric carbapenems in pediatric kidney transplant recipients since 88% of the BSI were susceptible to carbapenem. However, for recently transplanted (<12 months) pediatric liver recipients, additional antibiotic coverage for Enterococcus faecium should be considered such as vancomycin or linezolid depending on local resistance patterns and previous history of vancomycin- and/or linezolid resistant enterococci.
Only one among the 15 recipients with a BSI in the first-year post-transplantation died making statistical comparisons in mortality between patients with and without BSI difficult. We found that 8% of the BSI were due to vaccine-preventable pathogens (Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae) highlighting the importance of vaccination prior to transplantation. A recent study of vaccine-preventable infections in 6980 pediatric SOT recipients reported infections with S. pneumoniae in 2% of the recipients and 17 times higher mortality after S. pneumoniae in SOT recipients compared to the general pediatric population(25).
Our study cohort included 68% of all pediatric liver and kidney transplant recipients transplanted in Denmark during the study period(26). Nevertheless, groups were small making extrapolation difficult and highlighting the need for cross-national collaborations. Another limitation to the study is the lack of data on use of immunosuppressants and intravenous catheters as well as lack of information on vaccination status. The strengths of our study include the prospective design with long post-transplantation follow-up. The microbiology database MiBa is nationwide and includes all blood cultures on the recipients sampled in both in- and outpatient facilities as well as in general practice. Furthermore, the Danish Civil Registration System(27) ensures that the vital status is continuously followed for all recipients in the cohort, and we have a near-complete follow-up. Unfortunately, patients migrating and patients from the Faroe Islands and Greenland will be lost to follow-up. However, these patients only represent a small percentage of transplanted children in Denmark. The near-complete follow-up allows us to estimate the IR of BSI in our cohort with a small risk of underestimating the rate.
This study presents incidence rates and pathogen composition for BSI following pediatric liver and kidney transplantation. We found that BSI were common, with an incidence rate of 22.5 first BSI per 100 pediatric liver and kidney transplant recipients in the first-year post-transplantation. The BSI pathogen composition differed between liver and kidney transplant recipients, and the empiric antibiotic treatment should depend on the type of transplanted organ and local epidemiology, including pathogen flora and resistance patterns.