zithromax and Malnutrition

Antibiotics are routinely used as part of the management of severe acute malnutrition and are known to reduce gut microbial diversity in non-malnourished children. We evaluated gut microbiomes in children participating in a randomized controlled trial (RCT) of azithromycin versus amoxicillin for severe acute malnutrition. Three hundred one children aged 6 to 59 months with uncomplicated severe acute malnutrition (mid-upper arm circumference < 11.5 cm and/or weight-for-height Z-score < -3 without clinical complications) were enrolled in a 1:1 RCT of single-dose azithromycin versus a 7-day course of amoxicillin (standard of care). Of these, 109 children were randomly selected for microbiome evaluation at baseline and 8 weeks. Rectal swabs were processed with metagenomic DNA sequencing. We compared alpha diversity (inverse Simpson's index) at 8 weeks and evaluated relative abundance of microbial taxa using DESeq2. Of 109 children enrolled in the microbiome study, 95 were followed at 8 weeks. We found no evidence of a difference in alpha diversity between the azithromycin and amoxicillin groups at 8 weeks controlling for baseline diversity (mean difference -0.6, 95% CI -1.8 to 0.6, P = 0.30). Gut microbiomes did not diversify during the study. Differentially abundant genera at the P < 0.01 level included Salmonella spp. and Shigella spp., both of which were overabundant in the azithromycin compared with amoxicillin groups. We found no evidence to support an overall difference in gut microbiome diversity between azithromycin and amoxicillin among children with uncomplicated severe acute malnutrition, but potentially pathogenic bacteria that can cause invasive diarrhea were more common in the azithromycin group. Trial Registration: ClinicalTrials.gov NCT03568643.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Child; Gastrointestinal Microbiome; Humans; Infant; Malnutrition; Severe Acute Malnutrition

Azithromycin is a promising alternative to amoxicillin in the management of uncomplicated severe acute malnutrition (SAM) as it can be administered as a single dose and has efficacy against several pathogens causing infectious disease and mortality in children under 5. In this pilot trial, we aimed to establish the feasibility of a larger randomized controlled trial and provide preliminary evidence comparing the effect of azithromycin to amoxicillin on weight gain in children with uncomplicated SAM. We enrolled children 6-59 months old with uncomplicated SAM at six healthcare centers in Burkina Faso. Participants were randomized to a single dose of azithromycin or a 7-day course of amoxicillin and followed weekly until nutritional recovery and again at 8 weeks. Apart from antibiotics, participants received standard of care, which includes ready-to-use therapeutic food. Primary feasibility outcomes included enrollment potential, refusals, and loss to follow-up. The primary clinical outcome was weight gain (g/kg/day) over 8 weeks. Outcome assessors were masked. Between June and October 2020, 312 children were screened, 301 were enrolled with zero refusals, and 282 (93.6%) completed the 8-week visit. Average weight gain was 2.5 g/kg/day (standard deviation [SD] 2.0) in the azithromycin group and 2.6 (SD 1.7) in the amoxicillin group (mean difference -0.1, 95% CI -0.5 to 0.3, P = 0.63). Fewer adverse events were reported in the azithromycin group (risk ratio 0.50, 95% CI 0.31-0.82, P = 0.006). With strong enrollment and follow-up, a fully powered trial in this setting is feasible.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Burkina Faso; Child; Child, Preschool; Humans; Infant; Malnutrition; Pilot Projects; Severe Acute Malnutrition; Treatment Outcome; Weight Gain

Innovations for undernourished pregnant women that improve newborn survival and anthropometry are needed to achieve the Sustainable Development Goals 1 and 3. This study tested the hypothesis that a combination of a nutritious supplementary food and several proven chemotherapeutic interventions to control common infections would increase newborn weight and length in undernourished pregnant women.. This was a prospective, randomized, controlled clinical effectiveness trial of a ready-to-use supplementary food (RUSF) plus anti-infective therapies compared to standard therapy in undernourished pregnant women in rural Sierra Leone. Women with a mid-upper arm circumference (MUAC) ≤23.0 cm presenting for antenatal care at one of 43 government health clinics in Western Rural Area and Pujehun districts were eligible for participation. Standard of care included a blended corn/soy flour and intermittent preventive treatment for malaria in pregnancy (IPTp). The intervention replaced the blended flour with RUSF and added azithromycin and testing and treatment for vaginal dysbiosis. Since the study involved different foods and testing procedures for the intervention and control groups, no one except the authors conducting the data analyses were blinded. The primary outcome was birth length. Secondary outcomes included maternal weight gain, birth weight, and neonatal survival. Follow-up continued until 6 months postpartum. Modified intention to treat analyses was undertaken. Participants were enrolled and followed up from February 2017 until February 2020. Of the 1,489 women enrolled, 752 were allocated to the intervention and 737 to the standard of care. The median age of these women was 19.5 years, of which 42% were primigravid. Twenty-nine women receiving the intervention and 42 women receiving the standard of care were lost to follow-up before pregnancy outcomes were obtained. There were 687 singleton live births in the intervention group and 657 in the standard of care group. Newborns receiving the intervention were 0.3 cm longer (95% confidence interval (CI) 0.09 to 0.6; p = 0.007) and weighed 70 g more (95% CI 20 to 120; p = 0.005) than those receiving the standard of care. Those women receiving the intervention had greater weekly weight gain (mean difference 40 g; 95% CI 9.70 to 71.0, p = 0.010) than those receiving the standard of care. There were fewer neonatal deaths in the intervention (n = 13; 1.9%) than in the standard of care (n = 28; 4.3%) group (difference 2.4%; 95% CI 0.3 to 4.4), (HR 0.62 95% CI 0.41 to 0.94, p = 0.026). No differences in adverse events or symptoms between the groups was found, and no serious adverse events occurred. Key limitations of the study are lack of gestational age estimates and unblinded administration of the intervention.. In this study, we observed that the addition of RUSF, azithromycin, more frequent IPTp, and testing/treatment for vaginal dysbiosis in undernourished pregnant women resulted in modest improvements in anthropometric status of mother and child at birth, and a reduction in neonatal death. Implementation of this combined intervention in rural, equatorial Africa may well be an important, practical measure to reduce infant mortality in this context.. ClinicalTrials.gov NCT03079388.

Topics: Adolescent; Adult; Albendazole; Anti-Bacterial Agents; Antiprotozoal Agents; Azithromycin; Dysbiosis; Female; Food Assistance; Humans; Infection Control; Malaria; Malnutrition; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Care; Prospective Studies; Sierra Leone; Vaginal Diseases; Young Adult

World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth.. To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear growth.. The Antibiotics for Children with Diarrhea (ABCD) trial was a multicountry, randomized, double-blind, clinical trial among 8266 high-risk children aged 2 to 23 months presenting with acute nonbloody diarrhea. Participants were recruited between July 1, 2017, and July 10, 2019, from 36 outpatient hospital departments or community health centers in a mixture of urban and rural settings in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania. Each participant was followed up for 180 days. Primary analysis included all randomized participants by intention to treat.. Enrolled children were randomly assigned to receive either oral azithromycin, 10 mg/kg, or placebo once daily for 3 days in addition to standard WHO case management protocols for the management of acute watery diarrhea.. Primary outcomes included all-cause mortality up to 180 days after enrollment and linear growth faltering 90 days after enrollment.. A total of 8266 children (4463 boys [54.0%]; mean [SD] age, 11.6 [5.3] months) were randomized. A total of 20 of 4133 children in the azithromycin group (0.5%) and 28 of 4135 children in the placebo group (0.7%) died (relative risk, 0.72; 95% CI, 0.40-1.27). The mean (SD) change in length-for-age z scores 90 days after enrollment was -0.16 (0.59) in the azithromycin group and -0.19 (0.60) in the placebo group (risk difference, 0.03; 95% CI, 0.01-0.06). Overall mortality was much lower than anticipated, and the trial was stopped for futility at the prespecified interim analysis.. The study did not detect a survival benefit for children from the addition of azithromycin to standard WHO case management of acute watery diarrhea in low-resource settings. There was a small reduction in linear growth faltering in the azithromycin group, although the magnitude of this effect was not likely to be clinically significant. In low-resource settings, expansion of antibiotic use is not warranted. Adherence to current WHO case management protocols for watery diarrhea remains appropriate and should be encouraged.. ClinicalTrials.gov Identifier: NCT03130114.

Topics: Acute Disease; Administration, Oral; Ambulatory Care; Anti-Bacterial Agents; Azithromycin; Child Development; Dehydration; Diarrhea; Double-Blind Method; Drug Administration Schedule; Female; Health Resources; Humans; Infant; Male; Malnutrition; Treatment Outcome

Acute diarrhoea is a common cause of illness and death among children in low- to middle-income settings. World Health Organization guidelines for the clinical management of acute watery diarrhoea in children focus on oral rehydration, supplemental zinc and feeding advice. Routine use of antibiotics is not recommended except when diarrhoea is bloody or cholera is suspected. Young children who are undernourished or have a dehydrating diarrhoea are more susceptible to death at 90 days after onset of diarrhoea. Given the mortality risk associated with diarrhoea in children with malnutrition or dehydrating diarrhoea, expanding the use of antibiotics for this subset of children could be an important intervention to reduce diarrhoea-associated mortality and morbidity. We designed the Antibiotics for Childhood Diarrhoea (ABCD) trial to test this intervention.. ABCD is a double-blind, randomised trial recruiting 11,500 children aged 2-23 months presenting with acute non-bloody diarrhoea who are dehydrated and/or undernourished (i.e. have a high risk for mortality). Enrolled children in Bangladesh, India, Kenya, Malawi, Mali, Pakistan and Tanzania are randomised (1:1) to oral azithromycin 10 mg/kg or placebo once daily for 3 days and followed-up for 180 days. Primary efficacy endpoints are all-cause mortality during the 180 days post-enrolment and change in linear growth 90 days post-enrolment.. Expanding the treatment of acute watery diarrhoea in high-risk children to include an antibiotic may offer an opportunity to reduce deaths. These benefits may result from direct antimicrobial effects on pathogens or other incompletely understood mechanisms including improved nutrition, alterations in immune responsiveness or improved enteric function. The expansion of indications for antibiotic use raises concerns about the emergence of antimicrobial resistance both within treated children and the communities in which they live. ABCD will monitor antimicrobial resistance. The ABCD trial has important policy implications. If the trial shows significant benefits of azithromycin use, this may provide evidence to support reconsideration of antibiotic indications in the present World Health Organization diarrhoea management guidelines. Conversely, if there is no evidence of benefit, these results will support the current avoidance of antibiotics except in dysentery or cholera, thereby avoiding inappropriate use of antibiotics and reaffirming the current guidelines.. Clinicaltrials.gov, NCT03130114. Registered on April 26 2017.

Topics: Africa South of the Sahara; Age Factors; Anti-Bacterial Agents; Asia, Western; Azithromycin; Child Development; Dehydration; Developing Countries; Diarrhea; Double-Blind Method; Female; Humans; Infant; Infant Mortality; Infant Nutrition Disorders; Infant Nutritional Physiological Phenomena; Male; Malnutrition; Multicenter Studies as Topic; Nutritional Status; Organism Hydration Status; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Water-Electrolyte Balance

The aim of this open-label, randomized controlled trial conducted in four African countries (Madagascar, Niger, Central African Republic, and Senegal) is to compare three strategies of renutrition for moderate acute malnutrition (MAM) in children based on modulation of the gut microbiota with enriched flours alone, enriched flours with prebiotics or enriched flours coupled with antibiotic treatment.. To be included, children aged between 6 months and 2 years are preselected based on mid-upper-arm circumference (MUAC) and are included based on a weight-for-height Z-score (WHZ) between - 3 and - 2 standard deviations (SD). As per current protocols, children receive renutrition treatment for 12 weeks and are assessed weekly to determine improvement. The primary endpoint is recovery, defined by a WHZ ≥ - 1.5 SD after 12 weeks of treatment. Data collected include clinical and socioeconomic characteristics, side effects, compliance and tolerance to interventions. Metagenomic analysis of gut microbiota is conducted at inclusion, 3 months, and 6 months. The cognitive development of children is evaluated in Senegal using only the Developmental Milestones Checklist II (DMC II) questionnaire at inclusion and at 3, 6, and 9 months. The data will be correlated with renutrition efficacy and metagenomic data.. This study will provide new insights for the treatment of MAM, as well as original data on the modulation of gut microbiota during the renutrition process to support (or not) the microbiota hypothesis of malnutrition.. ClinicalTrials.gov, ID: NCT03474276 Last update 28 May 2018.

Topics: Acute Disease; Africa; Age Factors; Albendazole; Anti-Bacterial Agents; Antiparasitic Agents; Azithromycin; Child Development; Child, Preschool; Female; Flour; Food, Fortified; Gastrointestinal Microbiome; Humans; Infant; Infant Nutrition Disorders; Infant Nutritional Physiological Phenomena; Male; Malnutrition; Multicenter Studies as Topic; Nutritional Status; Prebiotics; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome

Malaria and malnutrition remain major problems in Sahel countries, especially in young children. The direct effect of malnutrition on malaria remains poorly understood, and may have important implications for malaria control. In this study, nutritional status and the association between malnutrition and subsequent incidence of symptomatic malaria were examined in children in Burkina Faso and Mali who received either azithromycin or placebo, alongside seasonal malaria chemoprevention.. Mid-upper arm circumference (MUAC) was measured in all 20,185 children who attended a screening visit prior to the malaria transmission season in 2015. Prior to the 2016 malaria season, weight, height and MUAC were measured among 4149 randomly selected children. Height-for-age, weight-for-age, weight-for-height, and MUAC-for-age were calculated as indicators of nutritional status. Malaria incidence was measured during the following rainy seasons. Multivariable random effects Poisson models were created for each nutritional indicator to study the effect of malnutrition on clinical malaria incidence for each country.. In both 2015 and 2016, nutritional status prior to the malaria season was poor. The most prevalent form of malnutrition in Burkina Faso was being underweight (30.5%; 95% CI 28.6-32.6), whereas in Mali stunting was most prevalent (27.5%; 95% CI 25.6-29.5). In 2016, clinical malaria incidence was 675 per 1000 person-years (95% CI 613-744) in Burkina Faso, and 1245 per 1000 person-years (95% CI 1152-1347) in Mali. There was some evidence that severe stunting was associated with lower incidence of malaria in Mali (RR 0.81; 95% CI 0.64-1.02; p = 0.08), but this association was not seen in Burkina Faso. Being moderately underweight tended to be associated with higher incidence of clinical malaria in Burkina Faso (RR 1.27; 95% CI 0.98-1.64; p = 0.07), while this was the case in Mali for moderate wasting (RR 1.27; 95% CI 0.98-1.64; p = 0.07). However, these associations were not observed in severely affected children, nor consistent between countries. MUAC-for-age was not associated with malaria risk.. Both malnutrition and malaria were common in the study areas, high despite high coverage of seasonal malaria chemoprevention and long-lasting insecticidal nets. However, no strong or consistent evidence was found for an association between any of the nutritional indicators and the subsequent incidence of clinical malaria.

Topics: Antimalarials; Azithromycin; Burkina Faso; Child, Preschool; Female; Humans; Incidence; Infant; Malaria; Male; Mali; Malnutrition; Nutritional Status; Seasons

In Papua New Guinea, intermittent preventive treatment with sulphadoxine-pyrimethamine and azithromycin (SPAZ-IPTp) increased birthweight despite limited impact on malaria and sexually transmitted infections. To explore possible nutrition-related mechanisms, we evaluated associations between gestational weight gain (GWG), enrolment body mass index (BMI) and mid-upper arm circumference (MUAC), and birthweight. We investigated whether the increase in birthweight associated with SPAZ-IPTp may partly be driven by a treatment effect on GWG. The mean GWG rate was 393 g/week (SD 250; n = 948). A 100 g/week increase in GWG was associated with a 14 g (95% CI 2.6, 25.4) increase in birthweight (P = 0.016). Enrolment BMI and MUAC also positively correlated with birthweight. SPAZ-IPTp was associated with increased GWG [58 g/week (26, 900), P < 0.001, n = 948] and with increased birthweight [48 g, 95% CI (8, 880), P = 0.019] when all eligible women were considered (n = 1947). Inclusion of GWG reduced the birthweight coefficient associated with SPAZ-IPTp by 18% from 44 to 36 g (n = 948), although SPAZ-IPTp was not significantly associated with birthweight among women for whom GWG data were available (P = 0.13, n = 948). One month post-partum, fewer women who had received SPAZ-IPTp had a low post-partum BMI (<18.5 kg m(-2) ) [adjusted risk ratio: 0.55 (95% CI 0.36, 0.82), P = 0.004] and their babies had a reduced risk of wasting [risk ratio 0.39 (95% CI 0.21, 0.72), P = 0.003]. SPAZ-IPTp increased GWG, which could explain its impact on birthweight and maternal post-partum BMI. Future trials of SPAZ-IPTp must incorporate detailed anthropometric evaluations to investigate mechanisms of effects on maternal and child health.

Topics: Adolescent; Antimalarials; Azithromycin; Birth Weight; Body Mass Index; Drug Combinations; Female; Follow-Up Studies; Humans; Infant, Low Birth Weight; Linear Models; Malnutrition; Maternal Exposure; Multivariate Analysis; Nutritional Status; Papua New Guinea; Pregnancy; Pyrimethamine; Risk Factors; Socioeconomic Factors; Sulfadoxine; Weight Gain