Department of Community Health, Kinshasa School of Public Health, Kinshasa, DR Congo.
College of Medicine, University of Ibadan, and University College Hospital, Ibadan, Nigeria.
J Glob Health. 2022 Nov 21;12:04084. doi: 10.7189/jogh.12.04084.
Hospital referral and admission in many- low and middle-income countries are not feasible for many young infants with sepsis/possible serious bacterial infection (PSBI). The effectiveness of simplified antibiotic regimens when referral to a hospital was not feasible has been shown before. We analysed the pooled data from the previous trials to compare the risk of poor clinical outcome for young infants with PSBI with the two regimens containing injectable procaine penicillin and gentamicin with the oral amoxicillin plus gentamicin regimen currently recommended by the World Health Organization (WHO) when referral is not feasible.
Infant records from three individually randomised trials conducted in Africa and Asia were collated in a standard format. All trials enrolled young infants aged 0-59 days with any sign of PSBI (fever, hypothermia, stopped feeding well, movement only when stimulated, or severe chest indrawing). Eligible young infants whose caretakers refused hospital admission and consented were enrolled and randomised to a trial reference arm (arm A: procaine benzylpenicillin and gentamicin) or two experimental arms (arm B: oral amoxicillin and gentamicin or arm C: procaine benzylpenicillin and gentamicin initially, followed by oral amoxicillin). We compared the rate of poor clinical outcomes by day 15 (deaths till day 15, treatment failure by day 8, and relapse between day 9 and 15) in reference arm A with experimental arms and present risk differences with 95% confidence interval (CI), adjusted for trial.
A total of 7617 young infants, randomised to arm A, arm B, or arm C in the three trials, were included in this analysis. Most were 7-59 days old (71%) and predominately males (56%). Slightly over one-fifth of young infants had more than one sign of PSBI at the time of enrolment. Severe chest indrawing (45%), fever (43%), and feeding problems (25%) were the most common signs. Overall, those who received arm B had a lower risk of poor clinical outcome compared to arm A for both per-protocol (risk difference = -2.1%, 95% CI = -3.8%, -0.4%; P = 0.016) and intention-to-treat (risk difference = -1.8%, 95% CI = -3.5%, -0.2%; P = 0.031) analyses. Those who received arm C did not have an increased risk of poor clinical outcome compared to arm A for both per-protocol (risk difference = -1.1%, 95% CI = -2.8%, 0.6%) and intention-to-treat (risk difference = -0.8%, 95% CI = -2.5%, 0.9%) analyses. Overall, those who received arm B had a lower risk of poor clinical outcome compared to the combined arms A and C for both per-protocol (risk difference = -1.6%, 95% CI = -3.5%, -0.1%; P = 0.035) and intention-to-treat (risk difference = -1.4%, 95% CI = -2.8%, -0.1%; P = 0.049) analyses.
Analysis of pooled individual patient-level data from three large trials in Africa and Asia showed that the WHO-recommended simplified antibiotic regimen B (oral amoxicillin and injection gentamicin) was superior to regimen A (injection procaine penicillin and injection gentamicin) and combined arms A and C (injection procaine penicillin and injection gentamicin, followed by oral amoxicillin) in terms of poor clinical outcome for the outpatient treatment of young infants with PSBI when inpatient treatment was not feasible.
AFRINEST study [9] is registered with the Australian New Zealand Clinical Trials Registry: ACTRN12610000286044. SATT Bangladesh study [10] is registered with ClinicalTrials.gov: NCT00844337. SATT Pakistan study [11] is registered at ClinicalTrials.gov: NCT01027429.
在许多低收入和中等收入国家，医院转诊和入院对于许多患有败血症/可能严重细菌感染（PSBI）的婴儿来说并不可行。以前已经证明，在无法转诊到医院的情况下，简化抗生素方案的有效性。我们分析了之前试验的汇总数据，以比较当转诊不可行时，两种方案（包含注射普鲁卡因青霉素和庆大霉素的方案和目前世界卫生组织（WHO）推荐的口服阿莫西林加庆大霉素方案）治疗 PSBI 婴儿的不良临床结局风险。
从非洲和亚洲进行的三项单独随机试验中整理婴儿记录，采用标准格式。所有试验均纳入年龄在 0-59 天、有任何 PSBI 迹象（发热、低体温、停止进食、仅在刺激时活动、或严重胸部凹陷）的婴儿。符合条件的婴儿，如果看护人拒绝入院并同意，将被纳入并随机分配到试验参考臂（臂 A：普鲁卡因苄青霉素和庆大霉素）或两个实验组（臂 B：口服阿莫西林加庆大霉素或臂 C：普鲁卡因苄青霉素和庆大霉素初始，然后口服阿莫西林）。我们比较了参考臂 A 与实验组之间第 15 天的不良临床结局发生率（第 15 天死亡、第 8 天治疗失败、第 9 天至 15 天复发），并呈现了风险差异及其 95%置信区间（CI），经过试验调整。
共有 7617 名婴儿在三项试验中随机分配到臂 A、臂 B 或臂 C，包括在这项分析中。大多数婴儿年龄在 7-59 天之间（71%），且主要为男性（56%）。略多于五分之一的婴儿在入组时具有一种以上 PSBI 迹象。严重胸部凹陷（45%）、发热（43%）和喂养问题（25%）是最常见的迹象。总体而言，与臂 A 相比，接受臂 B 的婴儿不良临床结局的风险较低，无论是按方案（风险差异=-2.1%，95%CI=-3.8%，-0.4%；P=0.016）还是意向治疗（风险差异=-1.8%，95%CI=-3.5%，-0.2%；P=0.031）分析。与臂 A 相比，接受臂 C 的婴儿不良临床结局的风险没有增加，无论是按方案（风险差异=-1.1%，95%CI=-2.8%，0.6%）还是意向治疗（风险差异=-0.8%，95%CI=-2.5%，0.9%）分析。总体而言，与臂 A 和 C 的联合方案相比，接受臂 B 的婴儿不良临床结局的风险较低，无论是按方案（风险差异=-1.6%，95%CI=-3.5%，-0.1%；P=0.035）还是意向治疗（风险差异=-1.4%，95%CI=-2.8%，-0.1%；P=0.049）分析。
对来自非洲和亚洲三项大型试验的个体患者水平数据进行汇总分析表明，与方案 A（注射普鲁卡因青霉素和注射庆大霉素）和联合方案 A 和 C（注射普鲁卡因青霉素和注射庆大霉素，然后口服阿莫西林）相比，世卫组织推荐的简化抗生素方案 B（口服阿莫西林和注射庆大霉素）在无法进行住院治疗时，对门诊治疗 PSBI 婴儿的不良临床结局更有优势。
AFRINEST 研究[9]在澳大利亚新西兰临床试验注册中心注册：ACTRN12610000286044。SATT 孟加拉国研究[10]在 ClinicalTrials.gov 注册：NCT00844337。SATT 巴基斯坦研究[11]在 ClinicalTrials.gov 注册：NCT01027429。
