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A mobile colistin resistance gene mcr was first reported in 2016 in China and has since been found with increasing prevalence across South-East Asia. Here we survey the presence of mcr genes in 4907 rectal swabs from mothers and neonates from three hospital sites across Nigeria; a country with limited availability or history of colistin use clinically. Forty mother and seven neonatal swabs carried mcr genes in a range of bacterial species: 46 Enterobacter spp. and single isolates of; Shigella , E. coli and Klebsiella quasipneumoniae . Ninety percent of the genes were mcr-10 ( n  = 45) we also found mcr-1 ( n  = 3) and mcr - 9 ( n  = 1). While the prevalence during this collection (2015-2016) was low, the widespread diversity of mcr -gene type and range of bacterial species in this sentinel population sampling is concerning. It suggests that agricultural colistin use was likely encouraging sustainment of mcr -positive isolates in the community and implementation of medical colistin use will rapidly select and expand resistant isolates. Here, the authors report the results of a BARNARDS sub-study identifying a 1% mobile colistin resistance gene (mcr) carriage rate in around 5000 rectal swabs from mothers and neonates across Nigeria, of which 90% were mcr-10 (mostly Enterobacter spp.) and 10% were mcr-1 and mcr9.

Early development of the microbiome has been shown to affect general health and physical development of the infant and, although some studies have been undertaken in high-income countries, there are few studies from low- and middle-income countries. As part of the BARNARDS study, we examined the rectal microbiota of 2,931 neonates (term used up to 60 d) with clinical signs of sepsis and of 15,217 mothers screening for bla CTX-M-15 , bla NDM , bla KPC and bla OXA-48 -like genes, which were detected in 56.1%, 18.5%, 0% and 4.1% of neonates’ rectal swabs and 47.1%, 4.6%, 0% and 1.6% of mothers’ rectal swabs, respectively. Carbapenemase-positive bacteria were identified by MALDI-TOF MS and showed a high diversity of bacterial species (57 distinct species/genera) which exhibited resistance to most of the antibiotics tested. Escherichia coli , Klebsiella pneumoniae and Enterobacter cloacae / E. cloacae complex, the most commonly found isolates, were subjected to whole-genome sequencing analysis and revealed close relationships between isolates from different samples, suggesting transmission of bacteria between neonates, and between neonates and mothers. Associations between the carriage of antimicrobial resistance genes (ARGs) and healthcare/environmental factors were identified, and the presence of ARGs was a predictor of neonatal sepsis and adverse birth outcomes. Analysis of gut microbiota of mothers and its neonates—as part of the BARNARDS study—reveals associations between β-lactamase gene carriage and neonatal sepsis risk in low-income settings.

Abstract Background Cutaneous plasmacytosis (CP) is a syndrome of multiple cutaneous plasma cell tumors, in the absence of multiple myeloma. Although rare in both humans and dogs, treatment recommendations are usually extrapolated from multiple myeloma protocols. To date, no case series of CP have been described in the veterinary literature. Hypothesis/Objectives To describe clinical presentation, determine treatment response rates and duration, and report overall survival of dogs with CP. Animals Twenty-one client-owned dogs with CP. Methods Medical records of 21 dogs with CP were reviewed. Diagnosis was based on histopathologic evaluation of at least 1 representative cutaneous or subcutaneous lesion in dogs with ≥3 lesions. Dogs with suspicion of multiple myeloma were excluded. Results The most commonly affected breeds were the golden (5/21) and Labrador retriever (3/21). Fourteen of 21 dogs had >10 lesions, with some having >100. Lesions commonly were described as round, raised, pink-to-red, and variably alopecic or ulcerated. The most commonly used drug protocol was combined melphalan and prednisone, with an overall response rate (ORR) of 73.7% (14/19 dogs). Single-agent lomustine was associated with a similar ORR of 71.4% (5/7 dogs). For all treatments combined, the median progression-free interval after the first treatment was 153 days. The median survival time from the first treatment was 542 days. Conclusions and Clinical Importance Alkylating agents were effective in inducing remission of CP; corticosteroids, melphalan, and lomustine were the most commonly used drugs. Survival times were similar to those reported in dogs with multiple myeloma treated with alkylating agents.

Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum β-lactamases ( bla CTX-M-15 ) and carbapenemases ( bla NDM , bla OXA-48 -like and bla KPC ), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae , Enterobacter hormaechei , Acinetobacter baumannii , Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines. In hospitals, surfaces present as a reservoir for bacteria pathogens, potentially leading to nosocomial infections. In this work, authors aim to profile extended-spectrum β lactamase- and carbapenemase-carrying bacterial species colonising neonatal hospital wards and causing neonatal sepsis.

There is a marked paucity in our understanding of the epidemiology of colistin-resistant bacterial pathogens in South Asia. A report by Davies and Walsh (Lancet Infect Dis 18:256–257, https://doi.org/10.1016/S1473-3099(18)30072-0 , 2018) suggests the export of colistin from China to India, Vietnam, and South Korea in 2016 was approximately 1,000 tons and mainly used as a poultry feed additive. A few reports forecast that the prevalence of mcr in humans and livestock will increase in South Asia. Given the high prevalence of bla CTX-M-15 and bla NDM in India, Bangladesh, and Pakistan, colistin has become the invariable option for the management of serious infections, leading to the emergence of mcr -like mechanisms in South Asia. Systematic scrutiny of the prevalence and transmission of mcr variants in South Asia is vital to understanding the drivers of mcr genes and to initiate interventions to overcome colistin resistance. The emergence of mobilized colistin resistance genes ( mcr ) has become a serious concern in clinical practice, compromising treatment options for life-threatening infections. In this study, colistin-resistant Klebsiella pneumoniae harboring mcr-8.1 was recovered from infected patients in the largest public hospital of Bangladesh, with a prevalence of 0.3% (3/1,097). We found mcr-8.1 in an identical highly stable multidrug-resistant IncFIB(pQil) plasmid of ∼113 kb, which belonged to an epidemiologically successful K. pneumoniae clone, ST15. The resistance mechanism was proven to be horizontally transferable, which incurred a fitness cost to the host. The core genome phylogeny suggested the clonal spread of mcr-8.1 in a Bangladeshi hospital. Core genome single-nucleotide polymorphisms among the mcr-8.1 -positive K. pneumoniae isolates ranged from 23 to 110. It has been hypothesized that mcr-8.1 was inserted into IncFIB(pQil) with preexisting resistance loci, bla TEM-1b and bla CTX-M-15 , by IS 903B . Coincidentally, all resistance determinants in the plasmid [ mcr-8.1 , ampC , sul2 , 1d-APH(6) , APH(3′′)-Ib , bla TEM-1b , bla CTX-M-15 ] were bracketed by IS 903B , demonstrating the possibility of intra- and interspecies and intra- and intergenus transposition of entire resistance loci. This is the first report of an mcr -like mechanism from human infections in Bangladesh. However, given the acquisition of mcr-8.1 by a sable conjugative plasmid in a successful high-risk clone of K. pneumoniae ST15, there is a serious risk of dissemination of mcr-8.1 in Bangladesh from 2017 onwards. IMPORTANCE There is a marked paucity in our understanding of the epidemiology of colistin-resistant bacterial pathogens in South Asia. A report by Davies and Walsh (Lancet Infect Dis 18:256–257, https://doi.org/10.1016/S1473-3099(18)30072-0 , 2018) suggests the export of colistin from China to India, Vietnam, and South Korea in 2016 was approximately 1,000 tons and mainly used as a poultry feed additive. A few reports forecast that the prevalence of mcr in humans and livestock will increase in South Asia. Given the high prevalence of bla CTX-M-15 and bla NDM in India, Bangladesh, and Pakistan, colistin has become the invariable option for the management of serious infections, leading to the emergence of mcr -like mechanisms in South Asia. Systematic scrutiny of the prevalence and transmission of mcr variants in South Asia is vital to understanding the drivers of mcr genes and to initiate interventions to overcome colistin resistance.

Background/Objectives: Infections caused by Legionella species are primarily associated with Legionella pneumophila, but non-pneumophila species are increasingly implicated in human disease. Despite this, antimicrobial susceptibility testing (AST) data for non-pneumophila species remain scarce, and standardised testing protocols or resistance thresholds have not been established. This study aimed to address this gap by evaluating and comparing AST performance for non-pneumophila Legionella species relative to L. pneumophila using three methodologies. Methods: AST was conducted on 89 Legionella isolates using LASARUS agar dilution, buffered yeast extract broth microdilution (BYE-BMD), and BCYE-α agar dilution, against ampicillin, azithromycin, chloramphenicol, doxycycline, levofloxacin, and rifampicin. Growth performance and minimum inhibitory concentrations (MICs) were assessed after a 96 h incubation. Results: MIC profiles were obtained using LASARUS and BYE-BMD for 53.9% and 93.3% of isolates, respectively. While L. pneumophila reached sufficient turbidity in BYE-BMD after a 48 h incubation, non-pneumophila species required an extended incubation (72–96 h). Non-pneumophila species displayed broader MIC ranges against azithromycin (0.016–1 mg/L) and levofloxacin (0.016–0.25 mg/L), but a narrower rifampicin range (≤0.0005–0.032 mg/L) relative to L. pneumophila. L. longbeachae exhibited a higher MIC50 for rifampicin despite overlapping susceptibility ranges across all species (0.001–0.016 mg/L). Conclusions: This study demonstrates species-specific differences in Legionella susceptibility and highlights the limitations in extrapolating L. pneumophila-based AST data. Azithromycin MICs in non-pneumophila species exceeded those of L. pneumophila, raising clinical concern. While BYE-BMD was the most effective method for MIC determination, three species required BCYE-α due to poor growth. These findings support developing standardised, species-specific AST protocols and thresholds amid rising macrolide resistance and the increasing detection of non-pneumophila infections.

People lie, and some research suggests that over 90% of people lie at least once a week ([@ref34]). More specifically, sales and marketing professionals are seen as more likely liars (e.g., [@ref15]), leading to ever-greater skepticism on the part of customers. Other than some recent work in marketing regarding marketplace deception ([@ref4]; [@ref35]), little has been done to understand the impact of different kinds of lies on a buyer’s relationship commitment. Applying Bok’s (1999) theories related to lies, this paper investigates how deceit has been viewed in marketing and sales, provides a theoretical model for how the lies of a salesperson might impact a customer’s relationship commitment, and presents a brief study on the impact that lies might have on buyer’s relationship commitment. Results show that even though the truth is always better than a lie, different lies - independent of their direct impact on the buyer - can have varying amounts of impact on relationship commitment.

Hospitalisation and routine antibiotic treatment are recommended for children with complicated severe acute malnutrition (SAM) but this may exacerbate antimicrobial resistance. Here, we investigate carriage of Gram-negative bacteria in children under five years of age receiving treatment for SAM in Niger, comparing the frequency of colonisation with bacteria carrying resistance genes at admission, during hospital stay and at discharge. E. coli isolates carrying a bla NDM-5 gene were selected for whole-genome sequencing. Rectal colonisation with bacteria carrying ß-lactamase genes is high, with 76% (n = 1042/1371) of children harbouring bacteria carrying a bla CTXM-1 -group gene and 25% (n = 338/1371) carrying a bla NDM-5 gene. Over two-thirds of children who did not carry bacteria with a carbapenemase gene at admission are colonised with bacteria carrying a carbapenemase gene at discharge (n = 503/729, 69%). E. coli ST167 carrying bla NDM-5 gene is recovered from 11% (n = 144/1371) of children. Here we highlight infection control and bacterial AMR transmission concerns amongst a vulnerable population in need of medical treatment. Hospital treatment for children with severe malnutrition may facilitate antibiotic resistance. Here, using rectal swabs from 1,371 children receiving treatment for severe acute malnutrition in Niger, the authors identify high rates of bacteria carrying carbapenemase genes, highlighting the urgent need to prioritize infection control.

Accumulation of misfolded and mistrafficked rhodopsin on the endoplasmic reticulum of photoreceptor cells has a pivotal role in the pathogenesis of retinitis pigmentosa and a subset of Leber’s congenital amaurosis. One potential strategy to reduce rhodopsin misfolding and aggregation in these conditions is to use opsin-binding compounds as chemical chaperones for opsin. Such molecules have previously shown the ability to aid rhodopsin folding and proper trafficking to the outer cell membranes of photoreceptors. As means to identify novel chemical chaperones for rhodopsin, a structure-based virtual screening of commercially available drug-like compounds (300,000) was performed on the main binding site of the visual pigment chromophore, the 11-cis-retinal. The best 24 virtual hits were examined for their ability to compete for the chromophore-binding site of opsin. Among these, four small molecules demonstrated the ability to reduce the rate constant for the formation of the 9-cis-retinal-rhodopsin complex, while five molecules surprisingly enhanced the formation of this complex. Compound 7, 13, 20 and 23 showed a weak but detectable increase in the trafficking of the P23H mutant, widely used as a model for both retinitis pigmentosa and Leber’s congenital amaurosis, from the ER to the cell membrane. The compounds did not show any relevant cytotoxicity in two different human cell lines, with the only exception of 13. Based on the structures of these active compounds, a series of in silico studies gave important insights on the potential structural features required for a molecule to act either as chemical chaperone or as stabiliser of the 11-cis-retinal-rhodopsin complex. Thus, this study revealed a series of small molecules that represent a solid foundation for the future development of novel therapeutics against these severe inherited blinding diseases.

Background The burden of antibiotic resistant infection is mainly felt in low-to-middle income countries, where the rate of antimicrobial resistance is largely under-surveyed and under huge pressure from unregulated, disparate and often self-guided access to antimicrobials. Nosocomial infections from hospital environments have been shown to be a particularly prevalent source of multi-drug resistant strains, yet surveillance of hospital environmental contamination is often not investigated. Methods The study was prospective, observational and cross-sectional, sampling 231 high and low touch surfaces from 15th March to 13th April 2021, from five wards in the Cape Coast Teaching Hospital, Ghana. Microbial growth in the presence of vancomycin and either meropenem or cefotaxime was examined and bacterial species were identified by MALDI-TOF. The presence of common extended-spectrum β-lactamases (ESBL) and carbapenemase antimicrobial resistance genes (ARG) were identified through PCR screening, which were confirmed by phenotypic antimicrobial susceptibility determination. Isolates positive for carbapenem resistance genes were sequenced using a multi-platform approach. Results We recovered microbial growth from 99% of swabs (n = 229/231) plated on agar in the absence of antimicrobials. Multiple sites were found to be colonised with resistant bacteria throughout the hospital setting. Bacteria with multi-drug resistance and ARG of concern were isolated from high and low touch points with evidence of strain dissemination throughout the environment. A total of 21 differing species of bacteria carrying ARG were isolated. The high prevalence of Acinetobacter baumannii carrying bla NDM-1 observed was further characterised by whole genome sequencing and phylogenetic analysis to determine the relationship between resistant strains found in different wards. Conclusion Evidence of multiple clonal incursions of MDR bacteria of high sepsis risk were found in two separate wards for a regional hospital in Ghana. The prevalence of multiple bla NDM carrying species in combination with combinations of ESBLs was particularly concerning and unexpected in Africa. We also identify strains carrying tet (X3), bla VIM-5 or bla DIM-1 showing a high diversity of carbapenamases present as a reservoir in a hospital setting. Findings of multi-drug resistant bacteria from multiple environmental sites throughout the hospital will inform future IPC practices and aid research prioritisation for AMR in Ghana.