An empiric antibiotic protocol using risk stratification improves antibiotic selection and timing in critically ill children.

RATIONALE: Timely and appropriate empiric antibiotics can improve outcomes in critically ill patients with infection. Evidence and guidelines to guide empiric antibiotic decisions are lacking for critically ill children. OBJECTIVES: To evaluate the impact of an empiric antibiotic protocol on appropriateness of initial antibiotics and time to appropriate antibiotics in critically ill children with suspected infection. METHODS: A computer order entry-based, pediatric intensive care unit-specific, empiric antibiotic protocol including risk stratification for healthcare-associated infections was implemented in a tertiary pediatric intensive care unit. Antibiotic and culture data were evaluated for a total of 556 infectious episodes in 491 patients from 2004 (preprotocol, n = 252) and 2007 (protocol, n = 304) with suspected infection. Antibiotics appropriateness based on risk factors and culture results was assessed, as was time from initial culture to appropriate antibiotics. MEASUREMENTS AND MAIN RESULTS: Patients treated using the protocols were more likely to receive appropriate empiric antibiotics based on risk factors (76 vs. 15%; P < 0.0001) and culture results (89 vs. 64%; P < 0.0001). Patients treated after protocol implementation had a shorter time to appropriate antibiotics (median, 5.9 vs. 9.6 h; P < 0.0001), particularly in those who grew healthcare-associated pathogens (5.8 vs. 24 h; P = 0.0001). No significant baseline characteristic differences were seen. CONCLUSIONS: An empiric antibiotic protocol in the pediatric intensive care unit incorporating risk stratification for healthcare-associated infections resulted in increased appropriateness of empiric antibiotics and in decreased time to appropriate antibiotics in critically ill children with infection.

Timing of correct parenteral antibiotic initiation and outcomes from severe bacterial community-acquired pneumonia in children.

BACKGROUND: The impact of timing of appropriate antibiotic initiation for critically ill children with severe bacterial community-acquired pneumonia (CAP) is unknown. We hypothesized that longer time to initiation of correct parenteral antibiotic would be associated with longer durations of mechanical ventilation, intensive care unit length of stay, and hospital length of stay. METHODS: We retrospectively reviewed medical records of children admitted to Nationwide Children's Hospital between January 2004 and December 2006 with bacterial CAP treated with mechanical ventilation, excluding those with documented viral infection. Time to correct antibiotic was defined as time from presentation to any emergency department to the initiation of a parenteral antibiotic to which cultured pathogens were susceptible. RESULTS: In all, 45 patients, median age 17 months, were identified. Median time to correct antibiotic was 10.3 hours, with 71% of patients receiving correct empiric therapy. After adjusting for severity of illness, longer time to correct antibiotic was independently associated with longer hospital stay (P = 0.007). For the 23 patients in the cohort for whom pneumonia was the primary diagnosis, longer time to correct antibiotic was independently associated with longer durations of mechanical ventilation (P = 0.01), intensive care unit stay (P = 0.001), and hospital stay (P = 0.006). Delays in antibiotic administration as short as 2 to 4 hours were associated with adverse outcomes in this group. CONCLUSIONS: In our critically ill children with severe bacterial CAP, longer delays in receipt of appropriate empiric antibiotics were independently associated with adverse outcomes.

Failure to recover somatotropic axis function is associated with mortality from pediatric sepsis-induced multiple organ dysfunction syndrome.

OBJECTIVES: To describe the associations between mediators of the somatotropic axis and mortality from sepsis-induced multiple organ dysfunction syndrome in children; and to examine the relationship between immune function and the somatotropic axis in this setting. DESIGN: Retrospective study using banked plasma. SETTING: Single mixed surgical/medical intensive care unit at a quaternary level children's hospital. PATIENTS: A total of 24 children (n = 17 survivors, 7 nonsurvivors) with severe sepsis or septic shock and dysfunction of >or=2 organ systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma samples were available from days 3, 7, and 14 of multiple organ dysfunction syndrome. Insulin-like growth factor 1 and insulin-like growth factor binding protein 3 levels were measured by chemiluminescence. Immune function was quantified using previously determined ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha production levels and absolute lymphocyte counts. Insulin-like growth factor 1 levels were lower in nonsurvivors compared with survivors (p = .004) with the greatest difference seen on day 14 (25 [25-69] ng/mL vs. 314 [123-582] ng/mL; p = .038). insulin-like growth factor binding protein 3 levels were reduced similarly over time (p = .019). A drop in plasma insulin-like growth factor binding protein 3 level at any time after day 3 of illness resulted in a 35-fold increased odds of death (odds ratio, 35 [1.6-750]; p = .004). Both ex vivo tumor necrosis factor-alpha and absolute lymphocyte count were reduced in nonsurvivors compared with survivors, but these differences occurred earlier (days 3 and 7). CONCLUSIONS: These data suggest that prolonged reduction of somatotropic axis function is associated with mortality from pediatric sepsis-induced multiple organ dysfunction syndrome. Reductions in innate and adaptive immune function are common in this population and are associated with failure of recovery of the somatotropic axis, although the nature of these relationships remains incompletely understood.