Clinical manifestations of sepsis during non-fatal bacteremia in pediatric patients undergoing therapy for acute lymphoblastic leukemia

Background:

Long-term survival from pediatric acute lymphoblastic leukemia (ALL) is now >90%, so non-fatal serious adverse events are increasingly important. Despite data for frequency of bacteremia, severity of sepsis with these events has not been well described.

We aimed to evaluate clinical severity of non-fatal bloodstream infections in children undergoing contemporary therapy for ALL by identifying acute organ dysfunction during each episode.

Methods:

This is a retrospective analysis of a convenience sample of pediatric patients with ALL treated on the St. Jude Children’s Research Hospital Total XV protocol (2000-07) including all patients with non-fatal bacteremia who underwent subsequent neurocognitive assessment. Severe sepsis was defined according to criteria proposed by Goldstein et al. modified for pediatric oncology; episodes not meeting these criteria were assessed for requirement of ‘urgent intervention’ (ICU admission, supplemental oxygen, fluid bolus or diagnosis of septic shock), and number of systems with evidence of sepsis (cardiovascular dysfunction, renal injury, abnormal liver function, coagulopathy, mental status changes, respiratory distress, increased lactate, acidosis).

Results:

There were 81 episodes of bacteremia in 62 patients with a median age of 6 years, including Gram-positive pathogens (n=24), Gram-negative pathogens (n=23), viridans group streptococci (n=7), other Gram positive organisms (n=3), common skin contaminants (n=17), and mixed cultures (n=7). No eligible patients were excluded, but data were incomplete for 11 episodes. Of the 81 episodes, 20 met criteria for ‘severe sepsis’ (24.7%), 5 for ‘urgent intervention’ (6.2%), and 3 for involvement of ≥3 systems (3.7%). Episodes occurred throughout ALL therapy (Fig. 1 shows all episodes during routine treatment)

Conclusion:

Although septic death is uncommon in children with ALL, non-fatal bacteremia is frequent and is often associated with severe sepsis or evidence of acute organ dysfunction (35%). This study has limitations and further studies are needed to assess the impact of bacteremia on long-term neurocognitive or other functioning.

Figure 1. Severity of sepsis in 79 episodes of non-fatal bacteremia during routine therapy for ALL