When Fever Meets Resistance: Mortality Risk Factors in Children With Cancer, Neutropenia and MDR Infections

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Abstract Background Bloodstream and other invasive infections are frequent complications in children with hematologic and oncologic malignancies. Prolonged neutropenia, mucosal barrier injury and intensive antimicrobial exposure favor colonization and infection by multidrug-resistant (MDR) organisms, which may increase morbidity, mortality and healthcare costs. Data on risk factors for death in pediatric oncology patients with fever and neutropenia (FN) due to MDR bacteria remain limited. Methods We performed an analytical case–control study nested in a prospective cohort of pediatric oncology patients with FN at Hospital Infantil de México “Federico Gómez” from March 2015 to September 2017. Children 1–18 years old with cancer, fever and neutropenia were included. Cases were FN episodes with culture-proven MDR infection from a sterile site; controls were FN episodes without MDR isolation. Episodes with incomplete data or ≥2 organisms in the same sterile-site culture were excluded. Demographic, clinical and microbiologic variables were collected at admission (day 1) and day 4 of fever. Infections were classified as microbiologically documented, clinically documented or fever of unknown origin. Descriptive statistics, chi-square or Student’s t tests, and logistic regression were used to identify factors associated with mortality. Results A total of 929 FN episodes were recorded; 56 (6%) had MDR isolates. The most common underlying diagnoses were acute lymphoblastic leukemia (41.1%), rhabdomyosarcoma (10.6%) and acute myeloid leukemia (9.7%). Prior antimicrobial prophylaxis was present in 86.8% of episodes. Mucositis was documented in 9.3%, septic shock in 12.2%, and 4.7% required admission to the pediatric intensive care unit (PICU). Overall mortality was 1.94% (18/929); mortality attributable to MDR infection was 0.86% (8/929), representing 14.0% of MDR episodes. MDR urinary tract infections accounted for 49.1% of MDR infection sites. Bacteremia due to MDR organisms was associated with a higher mortality rate (25.9%) compared with non-MDR bacteremia (3.3%). On multivariable analysis, mucositis, history of endotracheal intubation, PICU stay and septic shock were independently associated with death. Conclusion In this cohort of pediatric oncology patients with FN, MDR infections accounted for a minority of episodes but were associated with substantial mortality, particularly when presenting as bacteremia. Mucositis, prior intubation, PICU admission and septic shock were key risk factors for death. Early recognition and aggressive management of these high-risk features, together with optimized antimicrobial stewardship and infection prevention strategies, are essential to reduce mortality in this vulnerable population.