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BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: Single-dose azithromycin does not appear to affect weight and height outcomes when administered during early infancy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03676764.

This paper describes the synthesis and stereochemical determination of Novo29 (clovibactin), a new peptide antibiotic that is related to teixobactin and is active against Gram-positive bacteria. Novo29 is an eight-residue depsipeptide that contains the noncanonical amino acid hydroxyasparagine of hitherto undetermined stereochemistry in a macrolactone ring. The amino acid building blocks Fmoc-(2R,3R)-hydroxyasparagine-OH and Fmoc-(2R,3S)-hydroxyasparagine-OH were synthesized from (R,R)- and (S,S)-diethyl tartrate. Novo29 and epi-Novo29 were then prepared by solid-phase peptide synthesis using these building blocks. Correlation with an authentic sample of Novo29 through 1H NMR spectroscopy, LC-MS, and in vitro antibiotic activity established that Novo29 contains (2R,3R)-hydroxyasparagine. X-ray crystallography reveals that epi-Novo29 adopts an amphiphilic conformation, with a hydrophobic surface and a hydrophilic surface. Four sets of epi-Novo29 molecules pack in the crystal lattice to form a hydrophobic core. The macrolactone ring adopts a conformation in which the main-chain amide NH groups converge to create a cavity, which binds ordered water and acetate anion. The amphiphilic conformation of epi-Novo29 is reminiscent of the amphiphilic conformation adopted by the related antibiotic teixobactin and its derivatives, which contains a hydrophobic surface that interacts with the lipids of the bacterial cell membrane and a hydrophilic surface that interacts with the aqueous environment. Molecular modeling suggests that Novo29 can adopt an amphiphilic conformation similar to teixobactin, suggesting that Novo29 may interact with bacteria in a similar fashion to teixobactin.

As a result of the COVID-19 pandemic, as well as other outbreaks, such as SARS and Ebola, bats are recognized as a critical species for mediating zoonotic infectious disease spillover events. While there is a growing concern of increased antimicrobial resistance (AMR) globally during this pandemic, knowledge of AMR circulating between bats and humans is limited. In this paper, we have reviewed the evidence of AMR in bats and discussed the planetary health aspect of AMR to elucidate how this is associated with the emergence, spread, and persistence of AMR at the human-animal interface. The presence of clinically significant resistant bacteria in bats and wildlife has important implications for zoonotic pandemic surveillance, disease transmission, and treatment modalities. We searched MEDLINE through PubMed and Google Scholar to retrieve relevant studies (n = 38) that provided data on resistant bacteria in bats prior to 30 September 2022. There is substantial variability in the results from studies measuring the prevalence of AMR based on geographic location, bat types, and time. We found all major groups of Gram-positive and Gram-negative bacteria in bats, which are resistant to commonly used antibiotics. The most alarming issue is that recent studies have increasingly identified clinically significant multi-drug resistant bacteria such as Methicillin Resistant Staphylococcus aureus (MRSA), ESBL producing, and Colistin resistant Enterobacterales in samples from bats. This evidence of superbugs abundant in both humans and wild mammals, such as bats, could facilitate a greater understanding of which specific pathways of exposure should be targeted. We believe that these data will also facilitate future pandemic preparedness as well as global AMR containment during pandemic events and beyond.

BackgroundAntibiotics are increasingly used throughout the world in food animal production for controlling and preventing disease and for promoting growth. But this trend also has the potential for promoting antibiotic resistance, which represents a threat to human, animal, and environmental health. The use of antibiotics and the potential effects of antibiotic dependence has often been associated with large-scale food animal production. But rural households also engage in small-scale production, often operating literally in backyards. While some small-scale producers use veterinary antibiotics, many do not. This paper examines knowledge, attitudes, beliefs, and agricultural practices (KAP) that represent an alternative to dependence on antibiotics.MethodsQualitative field research was based on four focus group discussions (FGDs) with non-indigenous backyard food animal producers in four communities near Quito, Ecuador and two FGDs with veterinarians. FGDs were supplemented by structured observations and key informant interviews. They were recorded with digital audio devices and transcriptions were analyzed independently by two researchers using a three-stage coding procedure. Open coding identifies underlying concepts, while axial coding develops categories and properties, and selective coding integrates the information in order to identify the key dimensions of the collective qualitative data.ResultsBackyard food animal producers in the Ecuadorian highlands generally do not use antibiotics while rearing small batches of animals and poultry for predominantly non-commercial household consumption. Instead, they rely on low cost traditional veterinary remedies. These practices are informed by their Andean history of agriculture and a belief system whereby physical activity is a holistic lifestyle through which people maintain their health by participating in the physical and spiritual environment.ConclusionsBackyard food animal producers in the Ecuadorian highlands implement complex strategies based on both economic calculations and sociocultural underpinnings that shape perceptions, attitudes, and practices. They use traditional veterinary remedies in lieu of antibiotics in most cases because limited production of food animals in small spaces contributes to a predictable household food supply, while at the same time conforming to traditional concepts of human and environmental health.

Increasing prevalence of infections caused by antimicrobial-resistant gram-negative bacteria represents a global health crisis, and while several novel therapies that target various aspects of antimicrobial resistance have been introduced in recent years, few are currently approved for children. Ceftazidime-avibactam is a novel β-lactam β-lactamase inhibitor combination approved for adults and children 3 months and older with complicated intra-abdominal infection, and complicated urinary tract infection or hospital-acquired ventilator-associated pneumonia (adults only in the United States) caused by susceptible gram-negative bacteria. Extensive population pharmacokinetic (PK) data sets for ceftazidime and avibactam obtained during the adult clinical development program were used to iteratively select, modify, and validate the approved adult dosage regimen (2,000-500 mg by 2-hour intravenous (IV) infusion every 8 hours (q8h), with adjustments for renal function). Following the completion of one phase I (NCT01893346) and two phase II ceftazidime-avibactam studies (NCT02475733 and NCT02497781) in children, adult PK data sets were updated with pediatric PK data. This paper describes the development of updated combined adult and pediatric population PK models and their application in characterizing the population PK of ceftazidime and avibactam in children, and in dose selection for further pediatric evaluation. The updated models supported the approval of ceftazidime-avibactam pediatric dosage regimens (all by 2-hour IV infusion) of 50-12.5 mg/kg (maximum 2,000-500 mg) q8h for those ≥6 months to 18 years old, and 40-10 mg/kg q8h for those ≥3 to 6 months old with creatinine clearance > 50 mL/min/1.73 m2 .

BackgroundInfectious bacterial diseases exhibiting increasing resistance to antibiotics are a serious global health issue. Bacteriophage therapy is an anti-microbial alternative to treat patients with serious bacterial infections. However, the impacts to the host microbiome in response to clinical use of phage therapy are not well understood.ResultsOur paper demonstrates a largely unchanged microbiota profile during 4 weeks of phage therapy when added to systemic antibiotics in a single patient with Staphylococcus aureus device infection. Metabolomic analyses suggest potential indirect cascading ecological impacts to the host (skin) microbiome. We did not detect genomes of the three phages used to treat the patient in metagenomic samples taken from saliva, stool, and skin; however, phages were detected using endpoint-PCR in patient serum.ConclusionResults from our proof-of-principal study supports the use of bacteriophages as a microbiome-sparing approach to treat bacterial infections. Video abstract.