Epidemiology and Clinical Outcomes of Multidrug-resistant, Gram-negative Bloodstream Infections in a European Tertiary Pediatric Hospital During a 12-month Period

Background: Bloodstream infections caused by multidrug-resistant, Gram-negative (MDRGN) bacteria represent a significant cause of morbidity and mortality. Prompt diagnosis and appropriate empiric treatment are the most important determinants of patient outcome. The objective of our study was to assess the epidemiology and clinical outcome of MDRGN sepsis in a tertiary-care pediatric hospital during a 12-month period. Methods: It was a retrospective, observational study of MDRGN bacteremia including all patients <18 years of age, hospitalized during 2011, with documented bacteremia caused by Enterobacteriaceae or non-fermentative bacteria. Results: Overall, 136 blood cultures in 119 patients were included. The median age of patients was 1.1 years; 86.3% of patients had an underlying disease. The cumulative incidence of Gram-negative bloodstream infections was 5.4/1000 hospital admissions and the infection rate was 0.65/1000 hospital days. Most frequently isolated strains were Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa; 67.6% of infections were hospital acquired. The percentage of multidrug-resistant (MDR) organisms among isolated species was 39%. The crude rate of mortality was 16% and sepsis-related mortality was 9.2%. The mortality rate among patients with an antibiotic-resistant isolate was 22.6%. Factors significantly associated with sepsis-related mortality were antibiotic resistance (odds ratio: 4.26, 95% confidence interval: 1.07-16.9) and hospital acquisition of infection (odds ratio: 1.13, 95% confidence interval: 1.05-1.22). Conclusions: This study demonstrates the high mortality of -hospital-acquired MDRGN bacteremia in children. International networks focusing on clinical management and outcomes of MDRGN in children are required. Study of novel antibiotics active against Gram-negative bacteria should include children early in the clinical trial development programs.