A novel ruthenium-silver based antimicrobial potentiates aminoglycoside activity against Pseudomonas aeruginosa

The rapid dissemination of antibiotic resistance combined with the decline in the discovery of novel antibiotics represents a major challenge for infectious disease control that can only be mitigated by investments in novel treatment strategies. Alternative antimicrobials, including silver, have regained interest due to their diverse mechanisms of inhibiting microbial growth. One such example is AGXX, a broad-spec­trum antimicrobial that produces highly cytotoxic reactive oxygen species (ROS) to inflict extensive macromolecular damage. Due to the connections identified between ROS production and antibiotic lethality, we hypothesized that AGXX could potentially increase the activity of conventional antibiotics. Using the gram-negative pathogen Pseudomonas aeruginosa, we screened possible synergistic effects of AGXX on several antibiotic classes. We found that the combination of AGXX and aminoglycosides tested at sublethal concentrations led to a rapid exponential decrease in bacterial survival and restored the sensitivity of a kanamycin-resistant strain. ROS production contributes significantly to the bactericidal effects of AGXX/aminoglycoside treatments, which is dependent on oxygen availability and can be reduced by the addition of ROS scaveng­ers. Additionally, P. aeruginosa strains deficient in ROS detoxifying/repair genes were more susceptible to AGXX/aminoglycoside treatment. We further demonstrate that this synergistic interaction was associated with a significant increase in outer and inner membrane permeability, resulting in increased antibiotic influx. Our study also revealed that AGXX/aminoglycoside-mediated killing requires an active proton motive force across the bacterial membrane. Overall, our findings provide an understanding of cellular targets that could be inhibited to increase the activity of conventional antimicrobial

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Antimicrobial susceptibility profile of oral and rectal microbiota of non‐human primate species in Ghana: A threat to human health

Abstract Background The potential for the transfer of zoonotic diseases, including bacteria between human and non‐human primates (NHPs), is expected to rise. It is posited that NHPs that live in close contact with humans serve as sentinels and reservoirs for antibiotic‐resistant bacteria. Objectives The objective was to characterize the oral and rectal bacteria in Ghanaian NHPs and profile the antimicrobial susceptibility of the isolated bacteria. Methods Oral and rectal swabs were obtained from 40 immobilized wild and captive NHPs from 7 locations in Ghana. Standard bacteriological procedures were used in the isolation, preliminary identification, automated characterization and antimicrobial susceptibility test (AST) of bacteria using the Vitek 2 Compact system. Results Gram‐negative bacteria dominated isolates from the rectal swabs (n = 76, 85.4%), whereas Gram‐positive bacteria were more common in the oral swabs (n = 41, 82%). Staphylococcus haemolyticus (n = 7, 14%) was the most occurring bacterial species isolated from the oral swabs, whereas Escherichia coli (n = 32, 36%) dominated bacteria isolates from rectal swabs. Enterobacter spp. had the highest (39%) average phenotypic resistance to antimicrobials that were used for AST, whereas a trend of high resistance was recorded against norfloxacin, Ampicillin and Tetracycline in Gram‐negative bacteria. Similarly, among Gram‐positive bacteria, Staphylococcus spp. had the highest (25%) average phenotypic resistance to antimicrobials used for AST, and a trend of high resistance was recorded against penicillin G and oxacillin. Conclusions This study has established that apparently healthy NHPs that live in anthropized environments in Ghana harbour zoonotic and antimicrobial resistant bacteria

Effect of cocoa consumption on postprandial blood pressure in older adults with untreated hypertension: A randomized crossover clinical trial

Abstract Cocoa powder is an important dietary source of flavanols that modulate elevated blood pressure (BP). This study aimed to investigate the acute effects of cocoa beverage co‐consumption with a high‐fat‐high‐salt meal (HFHSM) on postprandial systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate in older adults living with uncontrolled hypertension. The study was a randomized crossover trial and involved older adults (aged 52.50 ± 9.36 years) (n = 28) living with hypertension. Participants, following an overnight fast, consumed either an HFHSM and cocoa beverage comprising 15 g cocoa powder in 250 mL water (HFHSM + CB; intervention) or HFHSM and 250 mL water (HFHSM + W; control). Resting SBP, DBP, and the heart rate of participants were measured at baseline (−5 min and 0 min) and 15, 30, 45, 60, 90, and 120 min following the consumption of either HFHSM + CB or HFHSM + W using an automated BP monitor. Repeated measures linear mixed model was used to compare the effect of cocoa beverage and water on postprandial outcomes over a 2‐h period. A significant reduction (−3.8 ± 0.6 mmHg, p < .05) in resting SBP was observed postprandially following the intake of the HFHSM + CB over the 120‐min period compared to the HFHSM + W. The effect was more prominent during the 90‐ and 120‐min time points of the trial duration. No significant change in the DBP and heart rate following the consumption of HFHSM + CB compared to the HFHSM + W was observed. Cocoa beverage co‐consumption with HFHSM improved postprandial SBP in older adults living with hypertension