Breaking the Barrier

BACKGROUND: Gram-negative bloodstream infections (BSIs) in pediatric hemato-oncology patients, particularly those with neutropenia, are associated with substantial morbidity and mortality. While piperacillin-tazobactam (PTZ) remains a standard empiric therapy, increasing resistance poses a significant clinical challenge. Identifying risk factors for PTZ-resistant (PTZ-R) BSI is crucial for optimizing empiric antibiotic selection and improving clinical outcomes. METHODS: This retrospective study (2015-2024) analyzed pediatric hemato-oncology Gram-negative BSIs at a northern Israeli tertiary center. Using clinical and microbiologic data, we performed univariate and multivariate logistic regression to identify independent predictors of PTZ resistance. RESULTS: Overall, 284 episodes in 162 patients were evaluated for PTZ susceptibility. Seventy (24.6%) episodes in 56 (34.6%) patients were PTZ-R. Mucosal barrier injury laboratory-confirmed BSI (MBI-LCBI) accounted for 46.1% of episodes, central line-associated bloodstream infection for 50% and secondary BSI for 3.9%. MBI-LCBI (68.6% vs. 38.8%, P < 0.001), beta-lactam use within the preceding 30 days (67.2% vs. 43.2%, P < 0.001), and colonization with extended-spectrum beta-lactamases and carbapenemase-producing Enterobacterales (14.3% vs. 5.6%, P = 0.018) were markedly more common among PTZ-R episodes. Additionally, nonlocal residency (5.7% vs. 16.1%, P = 0.014) and hematologic malignancy (85.5% vs. 62.5%, P = 0.003) were significantly more prevalent in patients with PTZ-R episodes. In multivariate analysis, MBI-LCBI (odds ratio 3.1, 95% confidence interval 1.7-6) and recent beta-lactam exposure (odds ratio 2.2, 95% confidence interval 1.2-4.1) were independent predictors of PTZ-R. Thirty-day mortality occurred in 9 (4.2%) cases; all were PTZ sensitive (P = 0.119). CONCLUSIONS: High PTZ-R in pediatric hemato-oncology BSIs is driven by recent beta-lactam use and MBI-LCBI. Identifying these risk factors may support the selection of appropriate empiric therapy for high-risk patients.