Gram‐negative bacteremia in solid organ transplant recipients: Clinical characteristics and outcomes as compared to immunocompetent non‐transplant recipients

Abstract

Background Outcomes from Gram‐negative bacteremia (GNB) in solid organ transplant (SOT) recipients are poorly understood. Methods This is a single center prospective cohort study comparing the clinical characteristics and outcomes of SOT recipients with GNB to immunocompetent non‐SOT patients with GNB between 1/1/2002 through 12/31/2018. Outcomes of interest included incidence of septic shock, respiratory failure, and time to death. A multivariable logistic regression model was used to determine factors associated with incidence of septic shock and respiratory failure. Time to death was evaluated using Cox proportional hazard models. Results A total of 297 SOT and 1245 immunocompetent non‐SOT patients were included. Incidence of septic shock did not significantly differ between the groups (SOT 25.3% vs. non‐SOT 24.6%, p = .8225). Overall survival did not significantly differ by transplant status (30‐day survival: SOT 76%, 95% confidence interval [CI] 70, 92, non‐SOT 74%, 95% CI 71, 77: log rank: p = .76). SOT recipients taking three immunosuppressive medications had significantly lower odds of developing septic shock or respiratory failure requiring intubation and mechanical ventilation than those taking ≤1 agent (shock: adjusted odds ratio [aOR] 0.29, 95% CI 0.09, 0.90, p = .0316; respiratory failure: aOR 0.14, 95% CI: 0.04, 0.49, p = .0020). Conclusions SOT recipients with GNB do not experience higher rates of septic shock, respiratory failure, or mortality than immnon‐SOT recipients with GNB. Among SOT recipients, a greater number of immunosuppressive medications may be associated with improved outcomes during GNB. Future studies are needed to understand the potential relationship between levels of immunosuppression and clinical outcome in SOT recipients with GNB.

Paradoxical outcomes of gram‐negative bloodstream infection in solid organ transplant recipients

“…Although patients receiving intense immune suppressive regimens have an increased risk of GN-BSI, it seems from the current study that they appear less acutely ill when they present with GN-BSI. They are less likely to develop septic shock and respiratory failure, 6 two consistent predictors of mortality in GN-BSI. 7 This is also supported by the previous work by the same authors of reduced levels of chemokines and cytokines in SOT recipients with GN-BSI.…”

“…SOT status has been repeatedly demonstrated to be a good or at least neutral prognostic marker in BSI. 1,3,4,[6][7][8][9] Similarly, two recent large cohorts have demonstrated an association between diabetes mellitus and improved survival in S. aureus BSI. 10,11 Many other studies demonstrated no association between diabetes mellitus and increased mortality in patients with BSI.…”

“…In this issue of Transplant Infectious Diseases, Eichenberger and colleagues validate their previous work in a large single center prospective cohort study of patients with GN-BSI, including 297 SOT and 1245 immune competent non-SOT recipients. 6 There were several key differences in baseline clinical and microbiological characteristics between the two groups. As compared to immune competent non-SOT recipients, SOT recipients were more likely to have hospital-acquired BSI, intra-abdominal and pulmonary source of infection, and BSI due to Pseudomonas aeruginosa, extended-spectrum beta-lactamase (ESBL)producing Enterobacterales, and multi-drug resistant bacteria.…”

“…Many of these variables were previously identified as independent risk factors of increased mortality in GN‐BSI 7,8 . Despite these vast differences favoring immune competent non‐SOT recipients, SOT recipients with GN‐BSI had comparable risk of septic shock, respiratory failure, and mortality 6 . More interestingly, SOT recipients receiving three or more immune suppressive medications had significantly lower incidence of both septic shock and respiratory failure as compared to those taking none or just one immune suppressive agent 6 .…”

“…The current study also brings into question the common practice of reducing immune suppression in transplant patients with BSI. The authors note that there is significant variation in the practice of adjusting or maintaining immune suppression in SOT recipients with BSI and suggest that a randomized clinical trial could be the next step in determining ideal protocols for immune suppression modulation in SOT recipients 6 . While mortality would naturally be the primary outcome of such a study, development of complications should also be examined as a secondary outcome in relation to this variation in practice.…”