Ehl S, Gering B, Bartmann P, Högel J, Pohlandt F
University of Ulm, Department of Pediatrics, Germany.
Pediatrics. 1997 Feb;99(2):216-21. doi: 10.1542/peds.99.2.216.
To determine whether C-reactive protein (CRP) can be used as a parameter to identify the time point when antibiotic treatment can safely be discontinued in a defined major subgroup of neonates treated for suspected bacterial infection.
One hundred seventy-six newborns with birth weights of greater than 1500 g and without central lines and mechanical ventilation who had suspected bacterial infection were enrolled in a prospective study.
Tertiary care neonatal reference center.
Serum concentrations of CRP were determined 24 to 48 hours after the first dose of antibiotics. If CRP levels were less than 10 mg/L, infants were considered unlikely to be infected, and the antibiotic treatment was stopped using CRP as the single decision criterion in 84 of 94 newborns (group 1). Infants with CRP levels of 10 mg/L or greater were considered likely to be infected and randomized to two study groups. In 38 of 39 neonates (group 2a), CRP was determined daily, and antibiotic therapy was discontinued as soon as CRP returned to less than 10 mg/L. Forty-three neonates with likely infection (group 2b) were treated for at least 5 days, and relapse rates of bacterial infections were compared between groups 2a and 2b.
The primary outcome variable of the study was the number of infectious relapses of the primary infection. This was assessed by the need for a second course of antibiotics within 4 weeks of the first one. The value of CRP for guiding treatment duration was determined by calculating the negative predictive value of CRP with respect to further treatment in study groups 1 and 2a. Treatment durations and relapse incidence in the two groups of neonates with likely infection (groups 2a and 2b) were compared.
Within the 4-week follow-up period, one infant in group 1 and no infant in group 2a received a second course of antibiotics for bacterial infection. CRP levels of less than 10 mg/L determined later than 24 hours after beginning the antibiotic treatment thus correctly identified 120 of 121 infants as not needing further antibiotics. This corresponds to a negative predictive value with respect to further treatment of 99% (95% confidence interval, 95.4% to 99.9%). The mean treatment duration was 3.7 (median, 4; range, 3 to 6) days in the CRP-guided group and 5.5 (median, 5; range, 5 to 7) days in the at least 5-day study group. In the latter group, one infant was treated for a potential relapse, and one infant was treated for a likely relapse. The low relapse rates in both treatment groups are a preliminary indication that relapses may not occur more frequently if patients are treated until CRP is negative rather than for a 5-day or longer treatment period.
We conclude that CRP could be a key parameter for individually guiding the duration of antibiotic treatment in a major subgroup of newborns with suspected bacterial infection. This approach would allow considerably shorter courses of antibiotic therapy.
确定C反应蛋白（CRP）是否可作为一个参数，用以识别在疑似细菌感染的特定主要亚组新生儿中，抗生素治疗可安全停药的时间点。
176例出生体重超过1500g、无中心静脉导管且未接受机械通气的疑似细菌感染新生儿纳入一项前瞻性研究。
三级医疗新生儿参考中心。
在首剂抗生素使用后24至48小时测定血清CRP浓度。若CRP水平低于10mg/L，则认为婴儿感染可能性不大，94例新生儿中的84例（第1组）以CRP作为唯一决策标准停用抗生素治疗。CRP水平为10mg/L或更高的婴儿被认为可能感染，并随机分为两个研究组。在39例新生儿中的38例（第2a组）中，每天测定CRP，一旦CRP降至低于10mg/L即停用抗生素治疗。43例可能感染的新生儿（第2b组）接受至少5天的治疗，比较第2a组和第2b组细菌感染的复发率。
研究的主要观察变量为原发性感染的感染复发次数。通过在首次使用抗生素后4周内是否需要第二疗程抗生素进行评估。通过计算第1组和第2a组中CRP对于指导治疗持续时间的阴性预测值，确定CRP指导治疗持续时间的价值。比较两组可能感染的新生儿（第2a组和第2b组）的治疗持续时间和复发发生率。
在4周随访期内，第1组1例婴儿和第2a组无婴儿因细菌感染接受第二疗程抗生素治疗。在开始抗生素治疗24小时后测定的CRP水平低于10mg/L，正确识别了121例婴儿中的120例无需进一步使用抗生素。这对应于进一步治疗的阴性预测值为99%（95%置信区间，95.4%至99.9%）。CRP指导组的平均治疗持续时间为3.7天（中位数，4天；范围，3至6天），至少5天研究组为5.5天（中位数，5天；范围，5至7天）。在后一组中，1例婴儿因潜在复发接受治疗，1例婴儿因可能复发接受治疗。两个治疗组的低复发率初步表明，如果患者接受治疗直至CRP转阴而非治疗5天或更长时间，复发可能不会更频繁发生。
我们得出结论，CRP可能是个别指导疑似细菌感染的主要亚组新生儿抗生素治疗持续时间的关键参数。这种方法将使抗生素治疗疗程大幅缩短。
