#90: Outcomes of Gram-negative Bacteremia Managed According to a Risk-based Algorithm (2021)

Abstract Background Management of gram-negative bacteremia (GNB) in children with cancer (CWC) is complicated by increasing rates of antimicrobial resistance. Guidelines for the management of CWC with suspected serious bacterial infections at St. Jude Children’s Research Hospital (SJ) recommend cefepime (CEF) monotherapy for empirical therapy for most patients. Children with evidence of sepsis, recent treatment with CEF or known colonization with a CEF-resistant (CEF-R) organism are initially treated with meropenem and/or amikacin. We compared outcomes of CWC with infections caused by CEF susceptible (CEF-S) and CEF-R bacteria treated according to this algorithm. Methods Demographic information on patients, and clinical and microbiological characteristics of 100 episodes of GNB treated from May 2018 to April 2019 at SJ were retrospectively reviewed. Results Patients’ median age was 8 years; 48% were female. Overall, 46% of patients had leukemia or lymphoma, 40% solid tumors, and 14% were HSCT recipients. Patients were neutropenic [absolute neutrophil count (ANC) &amp;lt;1000] during 70% of episodes and severely neutropenic (ANC &amp;lt;100) in 59%. The most common bacteria identified included E. coli (42%), Ps. aeruginosa (17%), and Klebsiella spp. (10%); 26% of episodes were polymicrobial and 24% of patients had focal infections complicating their bacteremia. Overall, 52% of episodes were caused by CEF-R organisms, including 57% of infections caused by E. coli. Demographic characteristics of CWC with infections caused by CEF-R organisms were similar to those with CEF-S organisms, except that these patients were more likely to have leukemia (adjusted OR 3.6, 95% CI 1.3–9.8) and to have had previous colonization or infection caused by a CEF-R organism (adjusted OR 14.4, 95% CI 2.7–76.0). CWC with infectious caused by CEF-R organisms were more likely to receive intensive care at admission and in the first 3 days of hospitalization than those with CEF-S isolates, but these differences were not statistically significant. The median time to administration of effective antimicrobial therapy was 0.53 hours for episodes caused by CEF-S bacteria and 12.05 hours for episodes caused by CEF-R organisms (P &amp;lt; 0.001), and CEF-R bacteremia was associated with increased time to microbiological resolution (P = 0.002) and a greater likelihood of early modification of treatment because of poor clinical response (5% vs. 14%, P = 0.043). CWC with CEF-R bacteremia had a longer median duration of fever (1 day vs. 2 days, P = 0.015), time to resolution of other signs and symptoms of infection (2 days vs. 4 days, P = 0.005), and median duration of hospitalization (6 vs. 11.5 days, P &amp;lt; 0.001) relative to CEF-S infections. All-cause mortality at hospital discharge and at 30 days was 8% in both CEF-S and CEF-R infections and was associated with the presence of relapsed or refractory malignancy and other significant medical comorbidities. Conclusion Over half of the episodes of GNB in this study were caused by CEF-R organisms. Infection with CEF-R organisms was associated with a delay in the administration of effective therapy and greater morbidity, but not greater mortality. Further studies are warranted to clarify the relationship between antimicrobial resistance, disease severity, treatment, and infection outcomes.