Division of Pediatric Infectious Diseases, Department of Pediatrics, Indiana University Health and Ryan White Center for Pediatric Infectious Diseases & Global Health.
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
J Pediatr Hematol Oncol. 2023 Aug 1;45(6):e702-e709. doi: 10.1097/MPH.0000000000002696. Epub 2023 Jun 26.
There is no practice standard regarding antibiotic duration in children with cancer and unexplained febrile neutropenia (FN). We hypothesized that absolute monocyte count (AMC) and absolute phagocyte count (APC= ANC + AMC + bands) are more sensitive, earlier, and safe markers of antibiotic cessation compared with absolute neutrophil count (ANC).
A retrospective review of FN episodes (FNEs) in pediatric oncology patients was conducted between 2009 and 2016. Included patients were afebrile for 24 hours and without an identified infectious source at antibiotic cessation. Primary endpoints, including recurrent fever, readmission, bloodstream infection, microbiologically documented infection, and adverse outcomes, were assessed 10 days after antibiotic cessation and compared among different bone marrow recovery parameters (ANC, AMC, APC). Secondary endpoints included length of FN stay, antibiotic-free days, and cost.
Three hundred ninety-one FNEs in 235 patients were included. Three groups were compared based on ANC (cells/μL) at the time of antibiotic cessation: < 200 in 102 (26%), 200 to 500 in 111 (28%), and >500 in 178 (46%). No statistically significant differences in primary endpoints were identified among the 3 ANC groups; however, a trend toward unfavorable outcomes in the ANC ≤200 cells/μL group compared with the ANC >200 cells/μL was observed. Primary endpoints based on AMC >100 cells/μL at the time of antibiotic cessation showed statistically significant favorable outcomes compared AMC ≤100 cells/μL (80%, 88%, 90%, 89%, and 93% risk reduction in recurrent fever, readmission, new bloodstream infection, new microbiologically documented infection, and adverse events, respectively). Similar favorable results were seen when APC >300 cells/μL was used as a threshold for antibiotic cessation. The median length of stay for FN if discharged when AMC >100 cells/μL was 3 days shorter and associated with fewer unfavorable outcomes, thus resulting in fewer hospital days, fewer antibiotic days, and decreased cost.
Our results suggest that AMC >100 cells/μL (regardless of ANC) or APC >300 cells/μL may be safe thresholds for empiric antibiotic cessation and result in reduced unfavorable clinical outcomes within 10 days postdischarge, reduced antibiotic days of therapy and reduced health care costs. Further prospective studies are needed to validate AMC as an accurate surrogate marker for antibiotic cessation in FNEs in children with cancer.
对于癌症合并不明原因发热性中性粒细胞减少症（FN）的患儿，抗生素使用时间目前尚无明确的治疗标准。我们假设，与绝对中性粒细胞计数（ANC）相比，绝对单核细胞计数（AMC）和绝对吞噬细胞计数（APC= ANC+AMC+条带）是更敏感、更早且安全的抗生素停药标志物。
对 2009 年至 2016 年间儿科肿瘤患者的 FN 发作（FNEs）进行了回顾性研究。纳入标准为：抗生素停药时体温正常 24 小时且无明确感染源。主要终点包括停药后 10 天内再次发热、再入院、血流感染、微生物学确诊感染和不良结局，并在不同骨髓恢复参数（ANC、AMC、APC）之间进行比较。次要终点包括 FN 持续时间、无抗生素天数和成本。
共纳入 235 例患者的 391 例 FNEs。根据抗生素停药时的 ANC（细胞/μL）将患者分为三组：ANC＜200 细胞/μL 组 102 例（26%）、200~500 细胞/μL 组 111 例（28%）和＞500 细胞/μL 组 178 例（46%）。三组间主要终点无统计学差异；但 ANC≤200 细胞/μL 组与 ANC＞200 细胞/μL 组相比，不良结局的趋势更为明显。抗生素停药时 AMC＞100 细胞/μL 的主要终点显示出统计学上显著的有利结果，与 AMC≤100 细胞/μL 相比，其复发性发热、再入院、新发血流感染、新微生物学确诊感染和不良事件的风险分别降低了 80%、88%、90%、89%和 93%（分别为 80%、88%、90%、89%和 93%）。当 APC＞300 细胞/μL 作为抗生素停药的阈值时，也观察到了类似的有利结果。如果 ANC＞100 细胞/μL 时出院，FN 的中位住院时间缩短 3 天，且不良结局较少，从而减少住院天数、抗生素使用天数和降低医疗费用。需要进一步的前瞻性研究来验证 AMC 作为儿童癌症 FNEs 中抗生素停药的准确替代标志物的准确性。
