Musiime Victor, Kiggwe Andrew, Beinomugisha Judith, Kakooza Lawrence, Thembo-Mwesige Josam, Nkinzi Sharafat, Naguti Erusa, Atuhaire Loice, Segawa Ivan, Ssengooba Willy, Mukonzo Jackson K, Babirekere-Iriso Esther, Musoke Philippa
Department of Paediatrics and Child Health, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
Department of Research, Joint Clinical Research Centre, Kampala, Uganda.
Front Pediatr. 2022 Jun 24;10:880355. doi: 10.3389/fped.2022.880355. eCollection 2022.
Children living with HIV (CLHIV) and children who are exposed to HIV but uninfected (CHEU) are at increased risk of developing malnutrition. Severely malnourished children have high mortality rates, but mortality is higher in CLHIV/CHEU. This study aims to investigate whether empiric use of an antibiotic with greater antimicrobial sensitivity (ceftriaxone) than standard-of-care (ampicillin plus gentamicin) will reduce mortality among CLHIV/CHEU admitted with severe acute malnutrition.
This is an open label randomized controlled trial involving 300 children; 76 CLHIV and 224 CHEU. The participants are being randomized to receive 1 week of ceftriaxone ( = 150) or standard-of-care (ampicillin/gentamicin) ( = 150), in addition to other routine care. The trial's primary outcome is in-hospital mortality. Secondary outcomes are: length of hospitalization; weight-for-height, weight-for-age and height-for-age z-scores; and pattern/antimicrobial sensitivity of pathogens. In addition, 280 severely malnourished children of unknown serostatus will be tested for HIV at admission to determine the prevalence and factors associated with HIV-infection. Furthermore, all the CLHIV on LPV/r will each provide sparse pharmacokinetic (PK) samples to evaluate the PK of LPV/r among malnourished children. In this PK sub-study, geometric means of steady-state LPV PK parameters [Area Under the Curve (AUC) , maximum concentration (C) and concentration at 12 h after dose (C)] will be determined. They will then be put in pharmacokinetic-pharmacodynamic (PK-PD) models to determine optimal doses for the study population.
This study will ascertain whether antibiotics with higher sensitivity patterns to common organisms in Uganda and similar settings, will produce better treatment outcomes. The study will also provide insights into the current pattern of organisms isolated from blood cultures and their antimicrobial sensitivities, in this population. In addition, the study will ascertain whether there has been a significant change in the prevalence of HIV-infection among children presenting with severe malnutrition in the WHO recommended option B plus era, while determining the social/structural factors associated with HIV-infection. There will also be an opportunity to study PK parameters of antiretroviral drugs among severely malnourished children which is rarely done, and yet it is very important to understand the dosing requirements of this population.
ClinicalTrials.gov, identifier: NCT05051163.
感染艾滋病毒的儿童（CLHIV）和暴露于艾滋病毒但未感染的儿童（CHEU）发生营养不良的风险增加。严重营养不良的儿童死亡率很高，但CLHIV/CHEU的死亡率更高。本研究旨在调查经验性使用一种抗菌敏感性高于标准治疗药物（氨苄西林加庆大霉素）的抗生素（头孢曲松）是否会降低因严重急性营养不良入院的CLHIV/CHEU的死亡率。
这是一项开放标签随机对照试验，涉及300名儿童；76名CLHIV和224名CHEU。除其他常规护理外，参与者被随机分配接受1周的头孢曲松治疗（n = 150）或标准治疗（氨苄西林/庆大霉素）（n = 150）。试验的主要结局是住院死亡率。次要结局包括：住院时间；身高别体重、年龄别体重和年龄别身高Z评分；以及病原体的类型/抗菌敏感性。此外，280名血清学状态不明的严重营养不良儿童将在入院时进行艾滋病毒检测，以确定艾滋病毒感染的患病率和相关因素。此外，所有接受洛匹那韦/利托那韦（LPV/r）治疗的CLHIV将各自提供少量药代动力学（PK）样本，以评估营养不良儿童中LPV/r的药代动力学。在这项PK子研究中，将确定稳态LPV药代动力学参数的几何平均值[曲线下面积（AUC）、最大浓度（Cmax）和给药后12小时的浓度（C12）]。然后将其纳入药代动力学-药效学（PK-PD）模型，以确定研究人群的最佳剂量。
本研究将确定在乌干达和类似环境中，对常见病原体具有更高敏感性模式的抗生素是否会产生更好的治疗效果。该研究还将深入了解从该人群血培养中分离出的病原体的当前类型及其抗菌敏感性。此外，该研究将确定在世界卫生组织推荐的B+方案时代，患有严重营养不良的儿童中艾滋病毒感染率是否有显著变化，同时确定与艾滋病毒感染相关的社会/结构因素。还将有机会研究严重营养不良儿童中抗逆转录病毒药物的药代动力学参数，这很少有人做，但了解该人群的给药要求非常重要。
ClinicalTrials.gov，标识符：NCT05051163。
