Low permeability across the outer membrane is a major reason why most antibiotics are ineffective against Gram-negative bacteria. Agents that permeabilize the outer membrane are typically toxic at their effective concentrations. Here, we report the development of a broad-spectrum homodimeric tobramycin adjuvant that is nontoxic and more potent than the gold standard permeabilizing agent, polymyxin B nonapeptide. In pilot studies, the adjuvant confers potent bactericidal activity on novobiocin against Gram-negative bacteria, including carbapenem-resistant and colistin-resistant strains bearing plasmid-borne mcr-1 genes. Resistance development to the combination was significantly reduced, relative to novobiocin alone, and there was no induction of cross-resistance to other antibiotics, including the gyrase-acting fluoroquinolones. Tobramycin homodimer may allow the use of lower doses of novobiocin, overcoming its twin problem of efficacy and toxicity.

No abstract

Hypertonic saline (HTS) is a commonly administered agent for intracranial pressure (ICP) control in traumatic brain injury (TBI). The literature on its use is mainly in moderate/severe TBI where invasive ICP monitoring is present. The role of HTS in patients with moderate TBI (mTBI) outside of the intensive care unit (ICU) setting remains unclear. The goal of this scoping review was to provide an overview of the available literature on HTS administration in patients with mTBI without ICP monitoring, assessing its impact on outcome and transitions in care. We performed a scoping systematic review of the literature of MEDLINE, Embase, Scopus, BIOSIS, and the Cochrane Databases from inception to July 31, 2020. We searched for those published articles documenting the administration of HTS in patients with mTBI with recorded functional outcome or transitions in hospital care. A two-step review process was conducted in accordance with methodology outlined in the Cochrane Handbook for Systematic Reviews of Interventions . There were many studies with combined moderate/severe TBI populations. However, most failed to document subgroup analysis for patients with mTBI. Our search strategy identified only one study that documented the administration of HTS in mTBI in which subgroup analysis for mTBI and outcomes were provided. This retrospective cohort study assessed patients with mTBI who did/did not receive prophylactic HTS, finding that those not receiving HTS demonstrated a deterioration in Glasgow Coma Scale (GCS) score in the first 48 h. However, the HTS group did demonstrate a trend to longer hospital stay and pneumonia. Our scoping review identified a significant gap in knowledge surrounding the use of HTS for patients with mTBI without invasive ICP monitoring. The limited identified literature suggests prophylactic administration prevents clinical deterioration, although this is based on a single study with data available for mTBI sub-analysis. Further studies on HTS in non-monitored patients with mTBI are required.

Radiographic reporting in adolescent idiopathic scoliosis:Is there a discrepancy comparing radiologists' reports and surgeons' assessments? Karamjot Sidhu,