Objective: We described the clinical and laboratory characteristics of acute kidney injury (AKI) in infants with diarrhea. Methods: This medical record analysis was conducted in Dhaka Hospital of the International Centre for Diarrheal Disease Research Bangladesh from January to December 2015. Infants with elevated serum creatinine (>50 µmol/L) constituted cases (n = 146). We randomly selected 150 infants with normal creatinine levels as the controls. Both groups had diarrhea. Events occurring from admission to discharge were analyzed and compared to assess differences in characteristics of the groups. Results: Among the 146 patients with AKI, 130 (89%) were discharged after recovery. Logistic regression analysis, adjusting for potential confounders (such as oral rehydration salt intake at home, convulsions, abnormal mentation, and hypoxemia) showed that infants with AKI were independently associated with hypernatremia (odds ratio (OR) = 8.66, 95% confidence interval (CI) = 3.88–19.22), sepsis (OR = 4.71, 95% CI = 2.07–10.73), and severe dehydration (OR = 3.76, 95% CI = 1.78–7.95). Persistently elevated creatinine was associated with radiological pneumonia (OR = 2.16, 95% CI = 1.09–4.31) and sepsis (OR = 2.24, 95% CI = 1.14–4.40). Conclusion: Dehydration, sepsis, and hypernatremia were found to be associated with AKI in diarrheal infants. After proper correction of dehydration, persistently elevated creatinine could be associated with sepsis and pneumonia.

Children with severe pneumonia in low- and middle-income countries (LMICs) suffer from high rates of treatment failure despite appropriate World Health Organization (WHO)-directed antibiotic treatment. Developing a clinical prediction rule for treatment failure may allow early identification of high-risk patients and timely intervention to decrease mortality. We used data from two separate studies conducted at the Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) to derive and externally validate a clinical prediction rule for treatment failure of children hospitalized with severe pneumonia. The derivation dataset was from a randomized clinical trial conducted from 2018 to 2019, studying children aged 2 to 59 months hospitalized with severe pneumonia as defined by WHO. Treatment failure was defined by the persistence of danger signs at the end of 48 hours of antibiotic treatment or the appearance of any new danger signs within 24 hours of enrollment. We built a random forest model to identify the top predictors. The top six predictors were the presence of grunting, room air saturation, temperature, the presence of lower chest wall indrawing, the presence of respiratory distress, and central cyanosis. Using these six predictors, we created a parsimonious model with a discriminatory performance of 0.691, as measured by area under the receiving operating curve (AUC). We performed external validation using a temporally distinct dataset from a cohort study of 191 similarly aged children with severe acute malnutrition and pneumonia. In external validation, discriminatory performance was maintained with an improved AUC of 0.718. In conclusion, we developed and externally validated a parsimonious six-predictor model using random forest methods to predict treatment failure in young children with severe pneumonia in Bangladesh. These findings can be used to further develop and validate parsimonious and pragmatic prognostic clinical prediction rules for pediatric pneumonia, particularly in LMICs.

The World Health Organization (WHO) recommends intravenous (IV) ampicillin and gentamicin as first-line therapy to treat severe pneumonia in children under five years of age. Ampicillin needs to be administered at a six-hourly interval, which requires frequent nursing intervention and bed occupancy for 5–7 days, limiting its utility in resource-poor settings. We compared the efficacy of IV amoxicillin over IV ampicillin, which is a potential alternative drug in treating severe pneumonia in children between 2–59 months. We conducted an unblinded, randomized, controlled, non-inferiority trial in the Dhaka hospital of icddr,b from 1 January 2018 to 31 October 2019. Children from 2–59 months of age presenting with WHO defined severe pneumonia with respiratory danger signs were randomly assigned 1:1 to either 50 mg/kg ampicillin or 40 mg/kg amoxicillin per day with 7.5 mg/kg gentamicin. The primary outcome was treatment failure as per the standard definition of persistence of danger sign(s) of severe pneumonia beyond 48 h or deterioration within 24 h of therapy initiation. The secondary outcomes were: (i) time required for resolution of danger signs since enrolment, (ii) length of hospital stay, (iii) death during hospitalization, and (iv) rate of nosocomial infections. Among 308 enrolled participants, baseline characteristics were similar among the two groups. Sixty-two (20%) children ended up with treatment failure, 21 (14%) in amoxicillin, and 41 (27%) in ampicillin arm, which is statistically significant (relative risk [RR] 0.51, 95% CI 0.32–0.82; p = 0.004). We reported 14 deaths for serious adverse events, 4 (3%) and 10 (6%) among amoxicillin and ampicillin arm, respectively. IV amoxicillin and IV gentamicin combination is not inferior to combined IV ampicillin and IV gentamicin in treating severe pneumonia in under-five children in Bangladesh. Considering the less frequent dosing and more compliance, IV amoxicillin is a better choice for treating children with severe pneumonia in resource-limited settings.

Background: Pneumonia causes about 0.9 million deaths worldwide each year. The World Health Organization (WHO) guidelines for the standard management of severe pneumonia requires parenteral ampicillin every 6 hours and once-daily parenteral gentamicin for 5 to 7 days. Although this treatment has contributed to the reduction of mortality, it requires nursing interventions every 6 hours for 7 days. Further intervention trials should be conducted to search for alternate antibiotics with better adherence, reduced cost, and reduced hospital stay. Parenteral amoxicillin is an effective alternative to ampicillin, as it has a longer half-life and broader coverage. Objective: The aim of this clinical trial is to compare the efficacy of a dose of injectable amoxicillin every 12 hours plus a once-daily dose of injectable gentamicin with a dose of injectable ampicillin every 6 hours plus a once-daily dose of injectable gentamicin in children hospitalized for severe pneumonia. Methods: This randomized, controlled, open-label, noninferiority trial is being conducted in Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh. A sample size of 308 children with severe pneumonia will give adequate power to this study. Children aged 2 to 59 months are randomized to either intravenous ampicillin or intravenous amoxicillin, plus intravenous gentamicin in both study arms. The monitoring of the patients is carried out according to the WHO protocol for the treatment of severe pneumonia. The primary objective is the rate of treatment failure, defined by the persistence of danger signs of severe pneumonia beyond 48 hours or deterioration within 24 hours of initiation of the therapy. The secondary objectives are (1) improvement in or the resolution of danger signs since enrollment, (2) length of hospital stay, (3) death during hospitalization, and (4) rate of nosocomial infections. Results: Enrollment in the study started on January 1, 2018, and ended on October 31, 2019. Data entry and analysis are in progress. Findings from the study are expected to be disseminated in October 2020. Conclusions: Our study's findings will improve compliance with the use of antibiotics that require less frequent doses for the treatment of severe pneumonia. Trial Registration: ClinicalTrials.gov NCT03369093; https://clinicaltrials.gov/ct2/show/NCT03369093 International Registered Report Identifier (IRRID): DERR1-10.2196/17735

Sepsis is the leading cause of child mortality worldwide and is responsible for over 60% of all paediatric deaths [1]. It is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. It encompasses a continuum that ranges from sepsis to severe sepsis, septic shock, multiple organ dysfunction syndrome and death [1–7]. […]

: Children with malnutrition present with aberrant laboratory parameters. This study aimed to identify high-risk diarrheal children with varied nutritional status. The data were obtained from the electronic database of Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh from 2019 to 2021. Among 1,068 children under 5 years of age with diarrhea, 177 (14%) had severe acute malnutrition (SAM; weight-for-length/height Z score < −3), 239 children (17%) had severe stunting (SS; length/height-for-age Z score < −3), and 652 did not have malnutrition (weight-for-length/height and weight-for-age and length/height-for-age Z score > −2). We independently assessed the relationship of nutritional profiles with each clinical and laboratory parameter. After adjustment for age and sex in the multiple regression model, hyponatremia (adjusted odds ratio [aOR] = 2.37 [95% CI: 1.52–3.68]; P < 0.001) and dehydration (aOR = 2.42 [95% CI: 1.67–3.52]; P < 0.001) were independently associated with SAM compared with children without malnutrition. In comparison to non-malnutrition, SS was less likely to be associated with acute watery diarrhea (aOR = 0.66 [95% CI: 0.47–0.92]; P = 0.014) but was significantly associated with anemia (aOR = 2.18 [95% CI: 1.57–3.02]; P < 0.001) and thrombocytosis (aOR = 2.43 [95% CI: 1.78–3.32]; P < 0.001). The presence of hypernatremia was substantially lower in children with SAM (aOR = 0.38 [95% CI: 0.22–0.65]; P < 0.001) or SS (aOR = 0.56 [95% CI: 0.35–0.88]; P = 0.012) than in children without malnutrition. Severe stunting was less likely to be associated with dehydration (aOR = 0.44 [95% CI: 0.29–0.67]; P < 0.001) in contrast to SAM. Therefore, children hospitalized with diarrhea may have different clinical and laboratory manifestations depending on their nutritional status and may require differential treatment.