Explore the vast range of titles available.

Substandard and falsified medicines threaten global health and require reliable data and screening technologies to combat their spread. This study examined the quality of 241 samples containing azithromycin, cefixime, esomeprazole and losartan collected from licenced private vendors in the Saptari (121 samples; convenience sampling) and Kathmandu (120 samples; randomised sampling) districts of Nepal. Nearly 10% (24 samples; 95% CI 6.5–14.5) of samples failed pharmacopoeial quality analysis and were classified as ‘substandard’ or ‘probably substandard’. No falsified medicines were identified. Small-scale dissolution acceptance criteria were applied to all 20 three-unit combinations of 213 samples tested in the first stage of the United States Pharmacopoeia dissolution test. Approximately 1% of these results were false positives when compared with the final United States Pharmacopoeia dissolution test results, suggesting the test’s usefulness in encouraging dissolution testing in resource-limited contexts. In the narrow sense of presence/absence, two portable Raman spectrometers reliably detected azithromycin, cefixime and losartan in most samples based on effective methods for detecting falsified medicines; however, none of the substandard samples were identified. The findings suggest that falsified medicines are less prevalent in Nepal and the surrounding region than suggested by regional concerns about Nepal and global concerns about low- and middle-income countries. Nevertheless, the Nepalese government should continue to ensure the quality of all distributed medicines.

The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94–1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. COALITION COVID-19 Brazil and EMS.

In this trial, rural communities in Niger were randomly assigned to distribute azithromycin or placebo to children (1 to 59 months of age) or infants (1 to 11 months). All-cause mortality was reduced in the child-treated group.

In 2023, the World Health Organization (WHO) revised its guidelines for management of severe acute malnutrition (SAM). The revised guidelines include a focus on infants at risk of poor growth and development. The guideline identifies evaluation of routine antibiotics for these infants as a priority research area. We pooled data from two large randomized controlled trials evaluating azithromycin for prevention of infant mortality in Burkina Faso to assess whether azithromycin reduces mortality or wasting in this subgroup. Infants in the two trials were 1-12 weeks of age at enrollment. Infants were considered at risk of poor risk of growth and development per WHO: underweight (weight-for-age Z-score, WAZ < -2), wasted (weight-for-length Z-score, WLZ < -2), or MUAC < 11.0 cm among infants ≥6 weeks of age. Infants were randomized to a single oral (20 mg/kg) dose of azithromycin or matching placebo and were followed until 6 months of age. We evaluated vital status, underweight (WAZ < -2), wasting (WLZ < -2), and stunting (length-for-age Z-score, LAZ) at 6 months among infants at risk of poor growth and development based on WHO single measurement criteria. A total of 54,709 infants were enrolled in the two trials. Of these, 9,728 were at risk of poor growth and development based on baseline WAZ (N = 5,385), WLZ (N = 6,022), or MUAC (N = 1,541). We found no evidence of a difference in mortality (1.3% vs 1.1%, odds ratio, OR, 1.19, 95% confidence interval, CI, 0.82 to 1.72) or wasting (20.6% vs 20.2%, OR 1.03, 95% CI 0.92 to 1.14) at 6 months among infants receiving azithromycin versus placebo. In infants aged 1-12 weeks at risk of poor growth and development, we do not have evidence that single dose azithromycin reduces mortality or improves growth outcomes. ClinicalTrials.gov NCT03682654 and NCT03676764.

Most evidence supporting screening for undernutrition is for children aged 6-59 months. However, the highest risk of mortality and highest incidence of wasting occurs in the first 6 months of life. We evaluated relationships between neonatal anthropometric indicators, including birth weight, weight-for-age -score (WAZ), weight-for-length Z-score (WLZ), length-for-age -score (LAZ) and mid-upper arm circumference (MUAC) and mortality and growth at 6 months of age among infants in Burkina Faso. Data arose from a randomised controlled trial evaluating neonatal azithromycin administration for the prevention of child mortality. We evaluated relationships between baseline anthropometric measures and mortality, wasting (WLZ < -2), stunting (LAZ < -2) and underweight (WAZ < -2) at 6 months of age were estimated using logistic regression models adjusted for the child's age and sex. Five regions of Burkina Faso. Infants aged 8-27 d followed until 6 months of age. Of 21 832 infants enrolled in the trial, 7·9 % were low birth weight (<2500 g), 13·3 % were wasted, 7·7 % were stunted and 7·4 % were underweight at enrolment. All anthropometric deficits were associated with mortality by 6 months of age, with WAZ the strongest predictor (WAZ < -2 to ≥ -3 at enrolment . WAZ ≥ -2: adjusted OR, 3·91, 95 % CI, 2·21, 6·56). Low WAZ was also associated with wasting, stunting, and underweight at 6 months. Interventions for identifying infants at highest risk of mortality and growth failure should consider WAZ as part of their screening protocol.

New evidence suggests that mass drug administration of azithromycin (MDAA) can significantly reduce childhood mortality in high-burden, low-resource settings, yet the World Health Organization's (WHO) 2020 guidelines take a cautious approach due to concerns about antimicrobial resistance (AMR).While the WHO guidelines cite ethical principles, they insufficiently address key considerations, such as intergenerational justice, equitable burden sharing, and the structural determinants of health that shape infectious disease vulnerability.Global AMR policy often prioritizes conservation over access in ways that disproportionately burden low-income countries, despite high-income countries also bearing significant responsibility for the emergence and spread of AMR.A balanced ethical framework is needed: one that explicitly integrates contextual values, including justice across generations, historical inequities, and community input under uncertainty.Revised WHO guidelines that expand eligibility for MDAA based on context-specific criteria, establish thresholds for mortality and resistance monitoring, and encourage global investment in sustainable health systems and antibiotic access, may better align with the WHO's own principles on equity, human rights, and social determinants of health in the development of guidelines.

We use machine learning to identify innovative strategies to target azithromycin to the children with watery diarrhea who are most likely to benefit. Using data from a randomized trial of azithromycin for watery diarrhea (NCT03130114), we develop personalized treatment rules given sets of diagnostic, child, and clinical characteristics, employing a robust ensemble machine learning-based procedure. This procedure estimates the child-level expected benefit for a given set of covariates by combining predictions from a library of statistical models. For each rule, we estimate the proportion treated under the rule and the average benefits of treatment. Among 6692 children, treatment under the most comprehensive rule is recommended on average for one third of children. The risk of diarrhea on day 3 is 10.1% lower (95% CI: 5.4, 14.9) with azithromycin compared to placebo among children recommended for treatment (NNT: 10). For day 90 re-hospitalization and death, risk is 2.4% lower (95% CI: 0.6, 4.1; NNT: 42). While pathogen diagnostics are strong determinants of azithromycin effects on diarrhea duration, host characteristics may better predict benefits for re-hospitalization or death. This suggests that targeting antibiotic treatment for severe outcomes among children with watery diarrhea may be possible without access to pathogen diagnostics. Pathogen diagnostics are strong determinants of azithromycin effects on diarrhea duration, but host factors may better predict benefits for severe outcomes. In this work, authors utilise a machine learning-based approach to evaluate personalized rules for the decision to treat watery diarrhea with azithromycin.

Antibiotic use during early infancy has been linked to childhood obesity in high-income countries. We evaluated whether a single oral dose of azithromycin administered during infant-well visits led to changes in infant growth outcomes at 6 months of age in a setting with a high prevalence of undernutrition in rural Burkina Faso. Infants were enrolled from September 25, 2019, until October 22, 2022, in a randomized controlled trial designed to evaluate the efficacy of a single oral dose of azithromycin (20 mg/kg) compared to placebo when administered during well-child visits for prevention of infant mortality. The trial found no evidence of a difference in the primary endpoint. This paper presents prespecified secondary anthropometric endpoints including weight gain (g/day), height change (mm/day), weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and mid-upper arm circumference (MUAC). Infants were eligible for the trial if they were between 5 and 12 weeks of age, able to orally feed, and their families were planning to remain in the study area for the duration of the study. Anthropometric measurements were collected at enrollment (5 to 12 weeks of age) and 6 months of age. Among 32,877 infants enrolled in the trial, 27,298 (83%) were followed and had valid anthropometric measurements at 6 months of age. We found no evidence of a difference in weight gain (mean difference 0.03 g/day, 95% confidence interval (CI) -0.12 to 0.18), height change (mean difference 0.004 mm/day, 95% CI -0.05 to 0.06), WAZ (mean difference -0.004 SD, 95% CI -0.03 to 0.02), WLZ (mean difference 0.001 SD, 95% CI -0.03 to 0.03), LAZ (mean difference -0.005 SD, 95% CI -0.03 to 0.02), or MUAC (mean difference 0.01 cm, 95% CI -0.01 to 0.04). The primary limitation of the trial was that measurements were only collected at enrollment and 6 months of age, precluding assessment of shorter-term or long-term changes in growth. Single-dose azithromycin does not appear to affect weight and height outcomes when administered during early infancy. ClinicalTrials.gov NCT03676764.

Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38 . Registered on 22 April 2020

HIV-associated chronic lung disease (HCLD) accounts for over 50% of deaths in children living with HIV. Azithromycin reduces the risk of respiratory exacerbations in children with HCLD, but its impact on respiratory pathogens and Streptococcus pneumoniae serotypes in HCLD remains partially understood. We investigated the impact of azithromycin on the prevalence and density of respiratory microbes in children enrolled in the BREATHE randomized controlled trial. Nasopharyngeal swabs collected from 287 participants at baseline, 48 and 72 weeks were analysed using nanofluidic qPCR testing for 94 S. pneumoniae serotypes, 12 bacterial species, and eight respiratory viruses. No differences were observed between microbial colonisation in the azithromycin and placebo groups at baseline or 72 weeks. At 48 weeks, overall bacterial colonisation was significantly lower in the azithromycin group compared to placebo (adjusted Odd Ratio [aOR]: 0.45, 95% CI 0.25-0.82; p =0.008), with reduced colonisation of S. pneumoniae (aOR: 0.37; 95% CI: 0.24-0.71; p =0.003) and non-typeable Haemophilus influenzae (aOR: 0.29; 95% CI: 0.14-0.61; p =0.001). The 13-valent pneumococcal conjugate vaccine serotypes (19F and 23F) and non-vaccine type (15A/F) were most commonly observed in both groups at all time points. Findings suggest that azithromycin reduces nasopharyngeal colonisation of certain bacteria in HCLD during treatment but has no long-lasting effects after treatment cessation. Trial registration: The BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112, registered date: 24/04/2015).