Utility of Procalcitonin Levels in Identifying Bacterial Infections in Children With and Without COVID-19

G. Fisler, T. Brandt, G. Ostovar, M. Taylor, S. Shah
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Abstract

Rationale: Elevated procalcitonin levels are associated with increased rates of bacterial infection in children. Observational studies have reported high levels of procalcitonin in COVID-19 and correlated procalcitonin level with illness severity. Data on rates of bacterial coinfections in COVID-19 are sparse;small studies suggest a low coinfection rate. We aim to quantify the positive predictive value (PPV) of procalcitonin in identifying bacterial infection in pediatric patients with and without COVID-19. Methods: A retrospective chart review was performed of 215 pediatric patients age 1 month to 21 years admitted to our tertiary children's hospital between February 1, 2013 and July 15, 2020 who had procalcitonin levels measured within 48 hours of admission. Confirmed bacterial infection was defined as positive blood, urine, or CSF culture, positive endotracheal/sputum culture with significant leukocytosis on gram stain, or CXR consistent with pneumonia. Contaminated blood cultures were excluded. Suspected bacterial infection was defined as either confirmed bacterial infection or administration of therapeutic antibiotics for >48 hours. Results: Of the 215 patients, 73 were PCR and/or antibody positive for SARS-CoV-2 (53% admitted to PICU, 29% required vasoactive medications) and 142 had alternative diagnoses (32% admitted to PICU, 9% required vasoactive medications). Median procalcitonin level was 1.28ng/mL in the COVID-19 cohort and 0.37ng/mL in the control cohort. There were 10 suspected and 5 confirmed bacterial infections in the COVID-19 cohort and 69 suspected and 44 confirmed bacterial infections in the control cohort. Procalcitonin was greater than 1ng/mL in 39 (53%) of COVID-19 subjects and 44 (31%) of control subjects. PPV of procalcitonin level over 1ng/mL for identifying suspected bacterial infection in the COVID-19 cohort was 10% (CI 1-20%) and in the control cohort was 75% (CI 62%-88%). PPV of procalcitonin level over 1ng/mL for identifying confirmed bacterial infection in the COVID-19 cohort was 3% (CI 0%-8%) and in the control cohort was 55% (CI 40%-69%). Conclusions: Our retrospective review demonstrated a low PPV of elevated procalcitonin level above the established threshold of 1ng/mL in identifying either culture-confirmed or suspected bacterial infection in pediatric patients hospitalized with COVID-19. Despite 29% of the COVID-19 cohort requiring vasoactive support, indicating a high pretest probability of bacterial sepsis, procalcitonin performed poorly as a marker of bacterial infection. Our results suggest that COVID-19 infection is associated with an elevated procalcitonin level independent of presence of bacterial infection. Given the importance of antibiotic stewardship, alternative means of identifying bacterial coinfection in COVID-19 are needed.
降钙素原水平在识别COVID-19患儿细菌感染中的应用
理由:降钙素原水平升高与儿童细菌感染率增加有关。观察性研究报告了COVID-19患者降钙素原水平高,降钙素原水平与疾病严重程度相关。关于COVID-19细菌合并感染率的数据很少;小型研究表明合并感染率很低。我们的目的是量化降钙素原在识别儿童COVID-19和非COVID-19患者细菌感染中的阳性预测值(PPV)。方法:回顾性分析2013年2月1日至2020年7月15日在我院三级儿童医院住院的215例1个月至21岁的儿童患者,这些患者在入院48小时内检测降钙素原水平。确诊的细菌感染定义为血液、尿液或脑脊液培养阳性,革兰氏染色显示明显白细胞增多的气管内/痰培养阳性,或与肺炎相符的CXR。排除受污染的血培养物。疑似细菌感染定义为确诊的细菌感染或给予治疗性抗生素48小时。结果:215例患者中,73例SARS-CoV-2 PCR和/或抗体阳性(53%入院PICU, 29%需要血管活性药物治疗),142例有其他诊断(32%入院PICU, 9%需要血管活性药物治疗)。COVID-19组降钙素原水平中位数为1.28ng/mL,对照组为0.37ng/mL。新冠肺炎队列中疑似细菌感染10例,确诊细菌感染5例;对照组中疑似细菌感染69例,确诊细菌感染44例。39例(53%)COVID-19患者和44例(31%)对照患者降钙素原大于1ng/mL。在COVID-19队列中,降钙素原水平超过1ng/mL用于识别疑似细菌感染的PPV为10% (CI 1 ~ 20%),在对照队列中为75% (CI 62% ~ 88%)。降钙素原水平超过1ng/mL对COVID-19确诊细菌感染的PPV为3% (CI 0% ~ 8%),对照组为55% (CI 40% ~ 69%)。结论:我们的回顾性研究表明,在诊断COVID-19住院的儿科患者中,降钙素原水平升高超过1ng/mL的既定阈值可用于鉴定培养确诊或疑似细菌感染。尽管29%的COVID-19队列需要血管活性支持,表明细菌性脓毒症的检测前概率很高,但降钙素原作为细菌感染的标志物表现不佳。我们的研究结果表明,COVID-19感染与降钙素原水平升高相关,与细菌感染的存在无关。鉴于抗生素管理的重要性,需要确定COVID-19细菌合并感染的替代方法。
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