Phonophoresis and topical drug delivery

In this study, investigations into phonophoresis were conducted by employing 3 distinct in vitro models. The aim of the first model was to evaluate the effect of ultrasound on the migration rate of different classes of molecules through agar gel. The derived data suggested that small, relatively hydrophobic molecules are more susceptible to ultrasound-enhanced diffusion through the water-filled channels of the agar gel. The application of heat alone increased drug migration by a similar magnitude as the ultrasound, indicating that ultrasonic heating directly increases the thermodynamic potential for diffusion. In the second experimental system, whole rat skin was pre-sonicated and then examined for changes in its barrier properties. At high intensities (1 to 2W cm-2), ultrasonic waves irreversibly compromised the barrier properties of the skin, following the general patterns described in the literature reports. At low intensities (< 1W cm-2), ultrasound discharged sebum from the sebaceous glands so as to fill much of the hair follicle shafts. This entirely novel phenomenon is probably produced by the mechanical effects of the beam. The deposition of sebaceous lipids within the hair follicle shafts can mean that this absorption pathway is blocked for hydrophilic molecules that penetrate via this route. Consequently, this phenomenon can be utilised as a probe to measure the relative follicular contribution to total penetration for these molecules. In the final phonophoresis model, modified Franz cells were employed in order to assess the ultrasound effect on the concurrent transdermal permeation of various molecules through whole rat skin. For the most lipophilic agent tested, the rate-limiting step of absorption was partitioning from the stratum corneum into the viable epidermis. Sonication did not accelerate this step.

Description and critical appraisal of principal components analysis (PCA) methodology applied to pulsed-field gel electrophoresis profiles of methicillin-resistant Staphylococcus aureus isolates

Principal components analysis (PCA) has been described for over 50 years; however, it is rarely applied to the analysis of epidemiological data. In this study PCA was critically appraised in its ability to reveal relationships between pulsed-field gel electrophoresis (PFGE) profiles of methicillin- resistant Staphylococcus aureus (MRSA) in comparison to the more commonly employed cluster analysis and representation by dendrograms. The PFGE type following SmaI chromosomal digest was determined for 44 multidrug-resistant hospital-acquired methicillin-resistant S. aureus (MR-HA-MRSA) isolates, two multidrug-resistant community-acquired MRSA (MR-CA-MRSA), 50 hospital-acquired MRSA (HA-MRSA) isolates (from the University Hospital Birmingham, NHS Trust, UK) and 34 community-acquired MRSA (CA-MRSA) isolates (from general practitioners in Birmingham, UK). Strain relatedness was determined using Dice band-matching with UPGMA clustering and PCA. The results indicated that PCA revealed relationships between MRSA strains, which were more strongly correlated with known epidemiology, most likely because, unlike cluster analysis, PCA does not have the constraint of generating a hierarchic classification. In addition, PCA provides the opportunity for further analysis to identify key polymorphic bands within complex genotypic profiles, which is not always possible with dendrograms. Here we provide a detailed description of a PCA method for the analysis of PFGE profiles to complement further the epidemiological study of infectious disease. © 2005 Elsevier B.V. All rights reserved.

Epidemiology of community-acquired meticillin-resistant Staphylococcus aureus obtained from the UK West Midlands region

Between January 2005 and December 2005, 199 meticillin-resistant Staphylococcus aureus (MRSA) isolates were obtained from nonhospitalised patients presenting skin and soft tissue infections to local general practitioners. The study area incorporated 57 surgeries from three Primary Care Trusts in the Lichfield, Tamworth, Burntwood, North and East Birmingham regions of Central England, UK. Following antibiotic susceptibility testing, pulsed-field gel electrophoresis, Panton-Valentine leukocidin gene detection and SCCmec element assignment, 95% of the isolates were shown to be related to hospital epidemic strains EMRSA-15 and EMRSA-16. In total 87% of the isolate population harboured SCCmec IV, 9% had SCCmec II and 4% were identified as carrying novel SCCmec IIIa-mecI. When mapped to patient home postcode, a diverse distribution of isolates harbouring SCCmec II and SCCmec IV was observed; however, the majority of isolates harbouring SCCmec IIIa-mecI were from patients residing in the north-west of the study region, highlighting a possible localised clonal group. Transmission of MRSA from the hospital setting into the surrounding community population, as demonstrated by this study, warrants the need for targeted patient screening and decolonisation in both the clinical and community environments.