Baby STRENGTH: Eat, Sleep, Console for Infants With Neonatal Abstinence Syndrome.

BACKGROUND: Traditional medication-based management of neonatal abstinence syndrome (NAS) results in long hospitalizations. Nonpharmacologic treatment and using the Eat, Sleep, Console (ESC) model of care have been shown to decrease lengths of stay (LOSs). PURPOSE: To determine whether using the ESC model of care to treat infants with opioid withdrawal resulted in decreased LOSs and number of infants receiving morphine when compared with traditional medication management. METHODS: Retrospective medical review for all patients admitted for NAS 12 months before and 12 months after implementing the ESC model of care. Data collected from electronic health records included demographic data, maternal history, infant LOS, infants receiving morphine, and birth weight/weight on day of life (DOL) 5. Univariate analysis was used to control for demographic data/risk factors. A 2-samples t test was used to compare average LOSs. Chi-square test was used to detect differences in the number of infants receiving morphine. Data were analyzed using SAS 9.4 software. RESULTS: LOS decreased from mean of 17.7 days to a mean of 5.9 days (P < .0001). The number of infants receiving morphine decreased from 20 (58.9%) to 1 (2.7%) (P < .0001). No statistically significant difference was noted in the percentage of weight loss on DOL 5. Data showed an increase in breastfeeding rates from 41.18% to 64.86% (P = .0456). IMPLICATIONS FOR PRACTICE: The ESC model of care decreased infant LOS and the number of morphine doses administered for opioid withdrawal symptoms. Maternal breastfeeding rates increased. IMPLICATIONS FOR RESEARCH: More research is needed to determine long-term neurodevelopmental outcomes of infants managed using ESC principles.

Understanding health professional role integration in complex adaptive systems: a multiple-case study of physician assistants in Ontario, Canada.

BACKGROUND: To meet the complex needs of healthcare delivery, the Ministry of Health and Long Term Care (MOHLTC) introduced Physician Assistants (PAs) into the Ontario health care system in 2006 with the goal of helping to increase access to care, decrease wait times, improve continuity of care and provide a flexible addition to the healthcare workforce. The characterization of healthcare organizations as complex adaptive systems (CAS) may offer insight into the relationships and interactions that optimize and restrict successful PA integration. The aim of this study is to explore the integration of PAs across multiple case settings and to understand the role of PAs within complex adaptive systems. METHODS: An exploratory, multiple-case study was used to examine PA role integration in four settings: family medicine, emergency medicine, general surgery, and inpatient medicine. Interviews were conducted with 46 healthcare providers and administrators across 13 hospitals and 6 family medicine clinics in Ontario, Canada. Analysis was conducted in three phases including an inductive thematic analysis within each of the four cases, a cross-case thematic analysis, and a broader, deductive exploration of cross-case patterns pertaining to specific complexity theory principles of interest. RESULTS: Forty-six health care providers were interviewed across 19 different healthcare sites. Support for PA contributions across various health care settings, the importance of role awareness, supervisory relationship attributes, and role vulnerability are interconnected and dynamic. Findings represent the experiences of PAs and other healthcare providers, and demonstrate how the PAs willingness to work and ability to build relationships allows for the establishment of interprofessional, collaborative, and person-centered care. As a self-organizing agent in complex adaptive systems (i.e., health organizations), PA role exploration revealed patterns of team behavior, non-linear interconnections, open relationships, dynamic systems, and the legacy of role implementation as defined by complexity theory. CONCLUSIONS: By exploring the role of PAs across multiple sites, the complexity theory lens concurrently fosters an awareness of emerging patterns, relationships and non-linear interactions within the defined context of the Ontario healthcare system. By establishing collaborative, interprofessional care models in hospital and community settings, PAs are making a significant contribution to Ontario healthcare settings.

Synthetic sideromycins (skepticism and optimism): selective generation of either broad or narrow spectrum Gram-negative antibiotics.

New or repurposed antibiotics are desperately needed since bacterial resistance has risen to essentially all of our current antibiotics, and few new antibiotics have been developed over the last several decades. A primary cause of drug resistance is the overuse of antibiotics that can result in alteration of microbial permeability, alteration of drug target binding sites, induction of enzymes that destroy antibiotics (i.e., ß-lactamases) and even induction of efflux mechanisms. Research efforts are described that are designed to determine if the known critical dependence of iron assimilation by microbes for growth and virulence can be exploited for the development of new approaches to antibiotic therapy. Iron recognition and active transport relies on the biosyntheses and use of microbe-selective iron chelating compounds called siderophores. Several natural siderophore-antibiotic conjugates (sideromycins) have been discovered and studied. The natural sideromycins consist of an iron binding siderophore linked to a warhead that exerts antibiotic activity once assimilated by targeted bacteria. Inspired these natural conjugates, a combination of chemical syntheses, microbiological and biochemical studies have been used to generate semi-synthetic and totally synthetic sideromycin analogs. The results demonstrate that siderophores and analogs can be used for iron transport-mediated drug delivery ("Trojan Horse" antibiotics or sideromycins) and induction of iron limitation/starvation (development of new agents to block iron assimilation). While several examples illustrate that this approach can generate microbe selective antibiotics that are active in vitro, the scope and limitations of this approach, especially related to development of resistance, siderophore based molecular recognition requirements, appropriate linker and drug choices, will be described.

Alternate "Drug" Delivery Utilizing ß-Lactam Cores: Syntheses and Biological Evaluation of ß-Lactams Bearing Isocyanate Precursors.

The synthesis of a small set of ß-lactams containing isocyanate precursors is described. The release of the isocyanate precursor in model hydrolysis experiments was substantiated by trapping experiments, thus confirming that ß-lactams can be designed that are capable of releasing alternatively reactive species. Preliminary biological assessments are also briefly discussed.

Design, syntheses, and anti-tuberculosis activities of conjugates of piperazino-1,3-benzothiazin-4-ones (pBTZs) with 2,7-dimethylimidazo [1,2-a]pyridine-3-carboxylic acids and 7-phenylacetyl cephalosporins.

Tuberculosis (TB) remains one of the most threatening diseases in the world and the need for development of new therapies is dire. Herein we describe the rationale for the design and subsequent syntheses and studies of conjugates between pBTZ and both the imidazopyridine and cephalosporin scaffolds. Overall some compounds exhibited notable anti-TB activity in the range of 2-0.2 µM in the Microplate Alamar Blue (MABA) Assay.

A knowledge translation intervention to enhance clinical application of a virtual reality system in stroke rehabilitation.

BACKGROUND: Despite increasing evidence for the effectiveness of virtual reality (VR)-based therapy in stroke rehabilitation, few knowledge translation (KT) resources exist to support clinical integration. KT interventions addressing known barriers and facilitators to VR use are required. When environmental barriers to VR integration are less amenable to change, KT interventions can target modifiable barriers related to therapist knowledge and skills. METHODS: A multi-faceted KT intervention was designed and implemented to support physical and occupational therapists in two stroke rehabilitation units in acquiring proficiency with use of the Interactive Exercise Rehabilitation System (IREX; GestureTek). The KT intervention consisted of interactive e-learning modules, hands-on workshops and experiential practice. Evaluation included the Assessing Determinants of Prospective Take Up of Virtual Reality (ADOPT-VR) Instrument and self-report confidence ratings of knowledge and skills pre- and post-study. Usability of the IREX was measured with the System Usability Scale (SUS). A focus group gathered therapist experiences. Frequency of IREX use was recorded for 6 months post-study. RESULTS: Eleven therapists delivered a total of 107 sessions of VR-based therapy to 34 clients with stroke. On the ADOPT-VR, significant pre-post improvements in therapist perceived behavioral control (p = 0.003), self-efficacy (p = 0.005) and facilitating conditions (p =0.019) related to VR use were observed. Therapist intention to use VR did not change. Knowledge and skills improved significantly following e-learning completion (p = 0.001) and was sustained 6 months post-study. Below average perceived usability of the IREX (19th percentile) was reported. Lack of time was the most frequently reported barrier to VR use. A decrease in frequency of perceived barriers to VR use was not significant (p = 0.159). Two therapists used the IREX sparingly in the 6 months following the study. Therapists reported that client motivation to engage with VR facilitated IREX use in practice but that environmental and IREX-specific barriers limited use. CONCLUSIONS: Despite increased knowledge and skills in VR use, the KT intervention did not alter the number of perceived barriers to VR use, intention to use or actual use of VR. Poor perceived system usability had an impact on integration of this particular VR system into clinical practice.

PATIENT-REPORTED OUTCOMES IN RARE LYSOSOMAL STORAGE DISEASES: KEY INFORMANT INTERVIEWS AND A SYSTEMATIC REVIEW PROTOCOL.

OBJECTIVES: To investigate the use, challenges and opportunities associated with using patient-reported outcomes (PROs) in studies with patients with rare lysosomal storage diseases (LSDs), we conducted interviews with researchers and health technology assessment (HTA) experts, and developed the methods for a systematic review of the literature. The purpose of the review is to identify the psychometrically sound generic and disease-specific PROs used in studies with patients with five LSDs of interest: Fabry, Gaucher (Type I), Niemann-Pick (Type B) and Pompe diseases, and mucopolysaccharidosis (Types I and II). METHODS: Researchers and HTA experts who responded to an email invitation participated in a telephone interview. We used qualitative content analysis to analyze the anonymized transcripts. We conducted a comprehensive literature search for studies that used PROs to investigate burden of disease or to assess the impact of interventions across the five LSDs of interest. RESULTS: Interviews with seven researchers and six HTA experts representing eight countries revealed five themes. These were: (i) the importance of using psychometrically sound PROs in studies with rare diseases, (ii) the paucity of disease-specific PROs, (iii) the importance of having PRO data for economic analyses, (iv) practical and psychometric limitations of existing PROs, and (v) suggestions for new PROs. The systematic review has been completed. CONCLUSIONS: The interviews highlight current challenges and opportunities experienced by researchers and HTA experts involved in work with rare LSDs. The ongoing systematic review will highlight the experience, opportunities, and limitations of PROs in LSDs and provide suggestions for future research.

Syntheses and evaluation of substituted aromatic hydroxamates and hydroxamic acids that target Mycobacterium tuberculosis.

Tuberculosis (TB) continues to remain one of the most threatening diseases in the world. With the emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) strains, the need to develop new therapies is dire. The syntheses of a focused library of hydroxamates and hydroxamic acids is described, as well as anti-TB activity in the microplate alamar blue assay (MABA). A number of compounds exhibited good activity against Mtb, with notable compounds exhibiting MIC values in the range of 20-0.71 µM. This work suggests that both hydroxamates and their free acids may be incorporated into more complex scaffolds and serve as potential leads for the development of anti-TB agents.

How to succeed in research during medical training: a qualitative study.

PURPOSE: The objective of this study was to examine the characteristics of the medical trainee (resident), the supervisor and the project that contribute to successful completion of resident-led research and publication in a peer-reviewed scientific journal. METHODS: Qualitative, interview-based study of Internal Medicine trainees and their supervisors. All interviewed trainees published at least one first-author research paper based on a project they completed during residency. Thematic analysis was used to explore key themes from interview transcripts. An iterative, team-based approach was used to develop a coding framework, which was then applied to the data and summarized. Six investigators independently reviewed and coded transcripts, discussed the data collectively and developed key themes by consensus. RESULTS: Thirty participants (15 residents and 15 supervisors) were interviewed. Three major themes for successful resident research projects emerged: 1) the resident is the project champion; 2) supervisors ensure feasibility and timeliness of the project; and, 3) limited time is a challenge that can be overcome. Residents were motivated by fellowship aspirations, prioritized the project and were genuinely interested in the content area. Supervisors were responsible for setting deadlines, limiting the scope of the project and ensuring feasibility of the study design. Existing research funds and infrastructure from other projects were frequently used by supervisors to support research done by trainees. CONCLUSIONS: Successful resident-led research projects require leadership and motivation by the resident and engagement, reality-checking and deadline-setting by the supervisor. Responsibilities and expectations in the resident-supervisor relationship should be set early and adequate program resources and funding are required.

Disparities in cancer care: perspectives from the front line.

OBJECTIVE: The purpose of this qualitative study was to investigate how frontline healthcare professionals witness and understand disparity in cancer care. METHOD: Six healthcare providers from a range of care settings, none with < 15 years of frontline experience, engaged with researchers in an iterative process of identifying and reflecting on equity and disparity in cancer care. This knowledge exchange began with formal interviews. Thematic analysis of the interviews form the basis of this article. RESULTS: Participants drew attention to health systems issues, the meaning and experience of discontinuities in care for patients at personal and community levels, and the significance of social supports. Other concerns raised by participants were typical of the literature on healthcare disparities. SIGNIFICANCE OF RESULTS: Providers at the front lines of care offer a rich source of insight into the operation of disparities, pointing to mechanisms rarely identified in traditional quantitative studies. They are also well positioned to advocate for more equitable care at the local level.

Identifying Relevant Content to Inform a Comprehensive Indigenous Health Curriculum: A Scoping Review.

Purpose: To identify the entry-level curricular content related to Indigenous health recommended for entry-level physiotherapy (PT) programs in Canada and other similar countries. Methods: Design: Scoping review. Procedures: Four electronic databases were searched using the terms physiotherapy, Indigenous health, entry-level curriculum, and their derivatives. Grey literature sources were hand searched and included Canadian PT professional documents, PT Program websites, Truth and Reconciliation Commission (TRC) sources, and a Google search. Data related to curriculum characteristics, methods of delivery, and barriers and facilitators to implementation were extracted from relevant references. Stakeholders reviewed study findings. Results: Forty-five documents were included. Documents focused on Indigenous peoples in Canada, Aboriginal and Torres Strait Islanders in Australia, and Maori in New Zealand. Canadian PT programs appeared to rely on passive teaching methods while programs in Australia and New Zealand emphasized the importance of partnering and engaging with Indigenous people. Barriers to incorporating indigenous health curriculum included an overcrowded curriculum and difficulty establishing relevance of Indigenous content (i.e., meaning). Conclusions: Similarities and differences were found between curricula content and approaches to teaching IH in Canada and the other countries reviewed. Strategies to promote greater engagement of Indigenous people in the development and teaching of IH is recommended.

Objectif: déterminer le contenu du cursus en santé autochtone recommandé pour les programmes d'entrée en pratique en physiothérapie au Canada et dans des pays semblables. Méthodologie: étude exploratoire. Méthode : les chercheurs ont fouillé quatre bases de données électroniques à l'aide des termes physiotherapy, Indigenous health, entry-level curriculum et leurs dérivés. Ils ont fouillé manuellement les sources de documentation parallèle et y ont inclus des documents professionnels canadiens sur la physiothérapie, les sites Web des programmes de physiothérapie, les sources de la Commission de vérité et réconciliation (CVR) et une recherche dans Google. Les données liées aux caractéristiques du cursus, aux modes de prestation et aux obstacles et incitatifs à la mise en œuvre provenaient de références pertinentes. Les intervenants ont examiné les résultats des études. Résultats: au total, 45 documents ont été retenus. Ils portaient sur les Autochtones du Canada, les Aborigènes et les insulaires du détroit de Torres en Australie et les Maori de la Nouvelle-Zélande. Les programmes de physiothérapie canadiens semblaient reposer sur des méthodes d'enseignement passives, tandis que ceux de l'Australie et de la Nouvelle-Zélande faisaient ressortir l'importance des partenariats et des relations avec les peuples autochtones. Les obstacles à l'intégration du cursus sur la santé autochtone incluaient un cursus surchargé et la difficulté à déterminer la pertinence du contenu sur les Autochtones (c'est-à-dire le sens). Conclusions: les chercheurs ont constaté des similarités et des différences de contenu entre les cursus et les approches d'enseignement de la santé autochtone au Canada et les autres pays analysés. Il est recommandé de trouver des stratégies pour favoriser une plus grande participation des peuples autochtones à la création et à l'enseignement de la santé autochtone.

Thiolates chemically induce redox activation of BTZ043 and related potent nitroaromatic anti-tuberculosis agents.

The development of multidrug resistant (MDR) and extensively drug resistant (XDR) forms of tuberculosis (TB) has stimulated research efforts globally to expand the new drug pipeline. Nitroaromatic compounds, including 1,3-benzothiazin-4-ones (BTZs) and related agents, are a promising new class for the treatment of TB. Research has shown that the nitroso intermediates of BTZs that are generated in vivo cause suicide inhibition of decaprenylphosphoryl-ß-D-ribose 2' oxidase (DprE1), which is responsible for cell wall arabinogalactan biosynthesis. We have designed and synthesized novel anti-TB agents inspired from BTZs and other nitroaromatic compounds. Computational studies indicated that the unsubstituted aromatic carbons of BTZ043 and related nitroaromatic compounds are the most electron-deficient and might be prone to nucleophilic attack. Our chemical studies on BTZ043 and the additional nitroaromatic compounds synthesized by us and others confirmed the postulated reactivity. The results indicate that nucleophiles such as thiolates, cyanide, and hydride induce nonenzymatic reduction of the nitro groups present in these compounds to the corresponding nitroso intermediates by addition at the unsubstituted electron-deficient aromatic carbon present in these compounds. Furthermore, we demonstrate here that these compounds are good candidates for the classical von Richter reaction. These chemical studies offer an alternate hypothesis for the mechanism of action of nitroaromatic anti-TB agents, in that the cysteine thiol(ate) or a hydride source at the active site of DprE1 may trigger the reduction of the nitro groups in a manner similar to the von Richter reaction to the nitroso intermediates, to initiate the inhibition of DprE1.

Iron transport-mediated drug delivery: practical syntheses and in vitro antibacterial studies of tris-catecholate siderophore-aminopenicillin conjugates reveals selectively potent antipseudomonal activity.

An artificial tris-catecolate siderophore with a tripodal backbone and its conjugates with ampicillin and amoxicillin were synthesized. Both conjugates exhibited significantly enhanced in vitro antibacterial activities against Gram-negative species compared to the parent drugs, especially against Pseudomonas aeruginosa . The conjugates appeared to be assimilated by an induced bacterial iron transport process as their activities were inversely related to iron concentration. The easily synthesized tris-catecolate siderophore has great potential for future development of various drug conjugates to target antibiotic-resistant Gram-negative bacteria.

Portfolios with Evidence of Reflective Practice Required by Regulatory Bodies: An Integrative Review.

Purpose: Regulatory bodies impose continuing professional development (CPD) requirements on health care professionals (HCPs) as a condition for license revalidation. Many regulatory bodies require annual evidence of CPD activities that are informed by reflective practices, guided by learning plans, and compiled into a portfolio. The purpose of this integrative review is to summarize the literature discussing how regulatory bodies use portfolios with evidence of reflection for licensure renewal. Method: We reviewed English-language articles published until May 2020 discussing evidence of CPD and reflective practice in portfolios in the context of licensure renewal. Results: We located 17 articles for the review. None reported or measured outcomes beyond submission of reflective evidence. Sixteen articles (93%) included information about passive learning resources that regulatory bodies provided to help guide HCPs' reflective learning activities. HCPs' feedback about using reflective learning activities indicated mixed opinions about their utility. Conclusions: Few publications reported how jurisdictions expected HCPs to provide evidence of reflective practices for licensure renewal. None of the regulatory bodies required evidence regarding the impact of reflective practice on patient or organizational outcomes. HCPs reported both benefits and challenges of a mandated reflective process.

Objectif : les organismes de réglementation imposent des exigences de perfectionnement professionnel continu (PPC) aux professionnels de la santé (PdS) afin qu'ils puissent renouveler leur permis. Bon nombre exigent des preuves annuelles d'activités de PPC éclairées par des pratiques réflexives, orientées par des plans d'apprentissage et compilées dans un portfolio. La présente analyse intégrative vise à résumer les publications qui expliquent l'utilisation que font les organismes de réglementation des portfolios contenant des preuves de pratiques réflexives dans le processus de renouvellement des permis. Méthodologie : articles de langue anglaise publiés jusqu'en mai 2020 sur des portfolios contenant des preuves de PPC et de pratiques réflexives pour renouveler le permis. Résultats : les chercheurs ont extrait 17 articles. Aucun ne portait sur les résultats mesurés après la soumission des preuves réflexives. Au total, 16 articles (93 %) contenaient de l'information sur les ressources d'apprentissage passif que les organismes de réglementation fournissaient pour contribuer à orienter les activités d'apprentissage réflexif des PdS. Les commentaires des PdS sur les activités de pratique réflexive faisaient foi d'avis mitigés quant à leur utilité. Conclusions : Peu de publications indiquaient la manière dont les régions sociosanitaires voulaient recevoir les preuves de pratiques réflexives des PdS en vue du renouvellement du permis. Aucun organisme de réglementation n'avait besoin de données probantes sur les répercussions de la pratique réflexive pour le patient ou sur les résultats organisationnels. Selon les PdS, le processus réflexif obligatoire comportait à la fois des avantages et des inconvénients.

Remediation Programs for Regulated Health Care Professionals: A Scoping Review.

PURPOSE: Clinical competence is essential for providing safe, competent care and is regularly assessed to ensure health care practitioners maintain competence. When deficiencies in competence are identified, practitioners may undergo remediation. However, there is limited evidence regarding the effectiveness of remediation programs. The purpose of this review is to examine the purpose, format, and outcomes of remediation programs for regulated health care practitioners. METHODS: All six stages of the scoping review process as recommended by Levac et al were undertaken. A search was conducted within MEDLINE, Embase, CINAHL, ERIC, gray literature databases, and websites of Canadian provincial regulatory bodies. Emails were sent to Registrars of Canadian regulatory bodies to supplement data gathered from their websites. RESULTS: A total of 14 programs were identified, primarily for physicians (n = 8). Reasons for remediation varied widely, with some programs identifying multiple reasons for referral such as deficiencies in recordkeeping (n = 7) and clinical skills (n = 6). Most programs (n = 9) were individualized to address specific deficiencies in competence. The process of remediation followed three stages: (1) assessment, (2) active remediation, and (3) reassessment. Most programs (n = 12) reported that remediation was effective in improving competence. CONCLUSIONS: Regulatory bodies should consider implementing individualized remediation programs to ensure that clinicians' deficiencies in competence are addressed effectively. Further research is indicated, using reliable and valid outcome measures to assess competence immediately after remediation programs and beyond.

Selective molecular sequestration with concurrent natural product functionalization and derivatization: from crude natural product extracts to a single natural product derivative in one step.

A resin-bound nitroso compound sequestered a single unexpected component from crude plant seed extracts. Several plants, including Piper nigrum, Eugenia caryophyllata, and Pimenta dioica, were extracted with organic solvent in the presence of a nitroso-containing resin. The nitroso resin selectively sequestered a single compound, ß-caryophyllene, via a chemo- and regioselective ene reaction. The ene product was released from the resin, and proper selection of the solid-phase linker and cleavage cocktail allowed concomitant further transformation of the primary ene product to a novel functionalized polycycle. Preliminary studies indicate that the new hydroxylamine-containing natural product derivatives have antibiotic activity.

Syntheses and studies of amamistatin B analogs reveals that anticancer activity is relatively independent of stereochemistry, ester or amide linkage and select replacement of one of the metal chelating groups.

A series of analogs of the amamistatin natural products was designed and synthesized to facilitate additional anticancer structure-activity relationships. The results indicate that the anticancer activity is relatively independent of stereochemistry, ester or amide linkage and replacement of the oxazoline/oxazole based iron-binding group with a catechol.

Conjugation of Aztreonam, a Synthetic Monocyclic ß-Lactam Antibiotic, to a Siderophore Mimetic Significantly Expands Activity Against Gram-Negative Bacteria.

Monocyclic ß-lactams with antibiotic activity were first synthesized more than 40 years ago. Extensive early structure-activity relationship (SAR) studies, especially in the 1980s, emphasized the need for heteroatom activation of monocyclic ß-lactams and led to studies of oxamazins, monobactams, monosulfactams, and monocarbams with various side chains and peripheral substitution that revealed potent activity against select strains of Gram-negative bacteria. Aztreonam, still the only clinically used monobactam, has notable activity against many Gram-negative bacteria but limited activity against some of the most problematic multidrug resistant (MDR) strains of Pseudomonas aeruginosa and Acinetobacter baumannii. Herein, we report that extension of the side chain of aztreonam is tolerated and especially that coupling of the side chain free acid with a bis-catechol siderophore mimetic significantly improves activity against the MDR strains of Gram-negative bacteria that are of most significant concern.

Hydride-induced Meisenheimer complex formation reflects activity of nitro aromatic anti-tuberculosis compounds.

The formation efficiency of hydride-induced Meisenheimer complexes of nitroaromatic compounds is consistent with their anti-TB activities exemplied by MDL860 and benzothiazol N-oxide (BTO) analogs. Herein we report that nitro cyano phenoxybenzenes (MDL860 and analogs) reacted slowly and incompletely which reflected their moderate anti-TB activity, in contrast to the instantaneous reaction of BTO derivatives to quantitatively generate Meisenheimer complexes which corresponded to their enhanced anti-TB activity. These results were corroborated by mycobacterial and radiolabelling studies that confirmed inhibition of the DprE1 enzyme by BTO derivatives but not MDL860 analogs.

Antibiotic repurposing: bis-catechol- and mixed ligand (bis-catechol-mono-hydroxamate)-teicoplanin conjugates are active against multidrug resistant Acinetobacter baumannii.

Antibiotics that are normally used to treat infections caused by Gram-positive bacteria might be made effective against Gram-negative bacterial infections, if they can circumvent permeability barriers and antibiotic deactivation processes associated with Gram-negative bacteria. Herein we report syntheses of bis-catechol-teicoplanin and mixed ligand catechol-hydroxamate-teicoplanin conjugates. Antibacterial activity assays revealed that conjugation of teicoplanin, which is only known to be active against Gram-positive bacteria, to the siderophore mimics induced potent activity against multidrug resistant strains of select Gram-negative bacteria (Acinetobacter baumannii) while retaining moderate activity against Gram-positive bacteria (Staphylococcus aureus).