Heterogeneous Fenton's-like catalyst potentiation of hydrogen peroxide disinfection: an investigation into mechanisms of action.

AIMS: This study aimed to establish the mechanisms of action (MOA) of a novel surface-functionalized polyacrylonitrile (PAN) catalyst, which was previously shown to have potent antimicrobial activity in conjunction with hydrogen peroxide (H2O2). METHODS AND RESULTS: Bactericidal activity was determined using a disinfectant suspension test. The MOA was investigated by measuring the loss of 260 nm absorbing material, membrane potential, permeability assays, analysis of intra- and extracellular ATP and pH, and tolerance to sodium chloride and bile salts.The catalyst lowered sub-lethal concentrations of H2O2 from 0.2 to 0.09%. H2O2 ± 3 g PAN catalyst significantly (P ≤ 0.05) reduced sodium chloride and bile salt tolerance, suggesting the occurance of sublethal cell membrane damage. The catalyst significantly increased (P ≤ 0.05) N-Phenyl-l-Napthylamine uptake (1.51-fold) and leakage of nucleic acids, demonstrating increased membrane permeability. A significant (P ≤ 0.05) loss of membrane potential (0.015 a.u.), coupled with pertubation of intracellular pH homeostasis and depletion of intracellular ATP, suggests potentiation of H2O2-mediated cell membrane damage. CONCLUSIONS: This is the first study to investigate the catalyst's antimicrobial mechanism of action, with the cytoplasmic membrane being a target for cellular injury.

Priming with biocides: A pathway to antibiotic resistance?

AIMS: To investigate the priming effects of sub-inhibitory concentrations of biocides on antibiotic resistance in bacteria. METHODS AND RESULTS: Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were exposed to sub-inhibitory concentrations of biocides via a gradient plate method. Minimum inhibitory concentration (MIC) and antibiotic susceptibility were determined, and efflux pump inhibitors (thioridazine and chlorpromazine) were used to investigate antibiotic resistance mechanism(s). Escherichia coli displayed a twofold increase in MIC (32-64 mg l-1 ) to H2 O2 which was stable after 15 passages, but lost after 6 weeks, and P. aeruginosa displayed a twofold increase in MIC (64-128 mg l-1 ) to BZK which was also stable for 15 passages. There were no other tolerances observed to biocides in E. coli, P. aeruginosa or S. aureus; however, stable cross-resistance to antibiotics was observed in the absence of a stable increased tolerance to biocides. Sixfold increases in MIC to cephalothin and fourfold to ceftriaxone and ampicillin were observed in hydrogen peroxide primed E. coli. Chlorhexidine primed S. aureus showed a fourfold increase in MIC to oxacillin, and glutaraldehyde-primed P. aeruginosa showed fourfold (sulphatriad) and eightfold (ciprofloxacin) increases in MIC. Thioridazine increased the susceptibility of E. coli to cephalothin and cefoxitin by fourfold and twofold, respectively, and both thioridazine and chlorpromazine increased the susceptibility S. aureus to oxacillin by eightfold and fourfold, respectively. CONCLUSIONS: These findings demonstrate that sub-inhibitory concentrations of biocides can prime bacteria to become resistant to antibiotics even in the absence of stable biocide tolerance and suggests activation of efflux mechanisms may be a contributory factor. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the effects of low-level exposure of biocides (priming) on antibiotic resistance even in the absence of obvious increased biocidal tolerance.

Microneedle Coating Techniques for Transdermal Drug Delivery.

Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates.

New platforms for multi-functional ocular lenses: engineering double-sided functionalized nano-coatings.

A scalable platform to prepare multi-functional ocular lenses is demonstrated. Using rapidly dissolving polyvinylpyrrolidone (PVP) as the active stabilizing matrix, both sides of ocular lenses were coated using a modified scaled-up masking electrohydrodynamic atomization (EHDA) technique (flow rates variable between 5 and 10 µL/min, applied voltage 4-11 kV). Each side was coated (using a specially designed flip-able well) selectively with a pre-determined morphology and model drug substance. PVP nanoparticles (inner side, to be in contact with the cornea, mean size

A fresh look at preoperative body washing.

National guidelines do not support preoperative body washing to reduce surgical site infections, instead recommending bathing or showering with soap. Yet preoperative body washing continues to be widely used in many hospitals across Europe. This paper suggests that existing trials of preoperative body washing, upon which guidelines are based, are dated and proposes a new investigation of preoperative body washing using modern definitions of surgical site infection with standardised patient follow up, modern surgical techniques and well designed trials. This paper provides a critique of existing guidelines and describes a randomised trial with 60 participants to compare the effect of soap and two antiseptic washing products on colony forming units (CFUs) for up to six hours. Chlorhexidine gluconate and octenidine were significantly more effective than soap in reducing CFUs in the underarm, and chlorhexidine was significantly more effective than soap in reducing CFUs in the groin.