Quaternary Phosphonium Compounds: An Examination of Non-Nitrogenous Cationic Amphiphiles That Evade Disinfectant Resistance.

Quaternary ammonium compounds (QACs) serve as mainstays in the formulation of disinfectants and antiseptics. However, an over-reliance and misuse of our limited QAC arsenal has driven the development and spread of resistance to these compounds, as well as co-resistance to common antibiotics. Extensive use of these compounds throughout the COVID-19 pandemic thus raises concern for the accelerated proliferation of antimicrobial resistance and demands for next-generation antimicrobials with divergent architectures that may evade resistance. To this end, we endeavored to expand beyond canonical ammonium scaffolds and examine quaternary phosphonium compounds (QPCs). Accordingly, a synthetic and biological investigation into a library of novel QPCs unveiled biscationic QPCs to be effective antimicrobial scaffolds with improved broad-spectrum activities compared to commercial QACs. Notably, a subset of these compounds was found to be less effective against a known QAC-resistant strain of MRSA. Bioinformatic analysis revealed the unique presence of a family of small multiresistant transporter proteins, hypothesized to enable efflux-mediated resistance to QACs and QPCs. Further investigation of this resistance mechanism through efflux-pump inhibition and membrane depolarization assays illustrated the superior ability of P6P-10,10 to perturb the cell membrane and exert the observed broad-spectrum potency compared to its commercial counterparts. Collectively, this work highlights the promise of biscationic phosphonium compounds as next-generation disinfectant molecules with potent bioactivities, thereby laying the foundation for future studies into the synthesis and biological investigation of this nascent antimicrobial class.

Bupropion for postpartum smoking relapse: A remote protocol for a two-arm, double-blind, placebo-controlled randomized clinical trial.

Cigarette smoking among postpartum women remains a significant public health problem despite known health risks to women and their newborns. It is estimated that over 50% of women quit smoking during pregnancy but 90% relapse by one year. Safe and effective postpartum relapse prevention strategies are urgently needed. In an attempt to address this deficit, we will investigate the efficacy of bupropion vs. placebo as a smoking relapse prevention aid in postpartum women. The objective of this paper is to detail an approach to investigate bupropion's efficacy for preventing postpartum smoking relapse among women who quit smoking during pregnancy. Specifically, we designed a two-arm, double-blind, placebo-controlled randomized trial testing the efficacy of bupropion vs. placebo as a relapse prevention tool. Mothers of healthy infants who quit smoking while pregnant will be stratified based on current or past history of major depressive disorder or persistent depressive disorder and randomized to receive either active (bupropion XL 300 mg/day) or placebo medication for 12 weeks. To respond to safety concerns associated with participant and staff exposure to COVID-19, we revised our original protocol and present procedures which allow our trial to be conducted entirely remotely. Primary and secondary outcomes will be assessed at weeks 12, 24, 36 and 52 post-randomization. The primary outcome is 7-day point prevalence abstinence at 24 weeks. Results of this work have the potential to positively impact women and their children by promoting lifelong cessation, eliminating secondhand smoke exposure, and modelling of abstinence to children.