A honey trap for the treatment of acne: manipulating the follicular microenvironment to control Propionibacterium acnes.

Today, as 40 years ago, we still rely on a limited number of antibiotics and benzoyl peroxide to treat inflammatory acne. An alternative way of suppressing the growth of Propionibacterium acnes is to target the environment in which it thrives. We conjecture that P. acnes colonises a relatively "extreme" habitat especially in relation to the availability of water and possibly related factors such as ionic strength and osmolarity. We hypothesise that the limiting "nutrient" within pilosebaceous follicles is water since native sebum as secreted by the sebaceous gland contains none. An aqueous component must be available within colonised follicles, and water may be a major factor determining which follicles can sustain microbial populations. One way of preventing microbial growth is to reduce the water activity (a w ) of this component with a biocompatible solute of very high water solubility. For the method to work effectively, the solute must be small, easily diffusible, and minimally soluble in sebaceous lipids. Xylose and sucrose, which fulfil these criteria, are nonfermentable by P. acnes and have been used to reduce water activity and hence bacterial colonisation of wounds. A new follicularly targeted topical treatment for acne based on this approach should be well tolerated and highly effective.

Enhanced resistance to erythromycin is conferred by the enterococcal msrC determinant in Staphylococcus aureus.

OBJECTIVES: The msrC gene, found on the chromosome of Enterococcus faecium, shares a high degree of similarity with the staphylococcal erythromycin resistance determinant msr(A). The enterococcal determinant was cloned into Staphylococcus aureus to determine whether msrC could confer antibiotic resistance in staphylococci. METHODS: A shuttle vector comprising pBluescript and pSK265 was used to introduce multiple copies of msrC into S. aureus RN4220. The integration vector pCL84 was employed to insert a single copy of msrC into the S. aureus chromosome. MICs were determined by the broth microdilution method. RESULTS: Expression of msrC from both chromosomal and plasmid loci in erythromycin-susceptible S. aureus RN4220 (MIC 0.25 mg/L) gave rise to enhanced protection against erythromycin, with an MIC of 32-64 mg/L for S. aureus RN4220 containing msrC in multiple copies and an MIC of 16-64 mg/L with msrC inserted as a single copy in the S. aureus chromosome. CONCLUSIONS: MsrC mediates high-level resistance to erythromycin in S. aureus.

Is antibiotic resistance in cutaneous propionibacteria clinically relevant? : implications of resistance for acne patients and prescribers.

It is well recognized that some patients with acne do not respond adequately to antibiotic therapy. It is important to distinguish antibiotic recalcitrant acne which we would suggest represents acne that shows a diminished response to treatment irrespective of the cause as opposed to 'antibiotic-resistant acne' which is acne that is less responsive to treatment as a direct consequence of skin colonization with resistant propionibacteria. Here we show that antibiotic-resistant acne is not just a theoretical possibility but a real phenomenon that could have important consequences for patients and prescribers. The relationship between skin colonization by antibiotic-resistant propionibacteria and treatment outcomes is a complex one that is explained at the follicular level by physiological differences affecting local drug concentrations. A systematic review of the literature on antibiotic-resistant propionibacteria revealed methodological shortcomings in studies of their prevalence and a paucity of evidence on their clinical significance. Despite the elucidation of resistance mechanisms in cutaneous propionibacteria, our continuing inability to distinguish between strains of Propionibacterium acnes means that we still do not fully understand how resistance spreads, although person-to-person transfer is most likely. Finally, we present a decision tree for acne management in an era of prudent antimicrobial prescribing that provides an alternative to existing treatment algorithms by placing topical retinoids and not antibiotics at the cornerstone of acne management.

Msr(A) and related macrolide/streptogramin resistance determinants: incomplete transporters?

The gene msr(A) confers inducible resistance to 14-membered-ring macrolides and type B streptogramins (MS(B) resistance) in staphylococci. The encoded hydrophilic protein (Msr(A)) is 488 amino acids and contains two ATP-binding motifs characteristic of the ABC transporters. The classical organisation of ABC transporters requires interaction between the two cytoplasmically located ATP-binding domains with two hydrophobic domains positioned in the membrane. Msr(A) appears to mediate drug efflux and yet contains no hydrophobic membrane spanning domains. In addition, Msr(A) functions in previously sensitive heterologous hosts such as Staphylococcus aureus in the absence of other plasmid encoded products. Current research on Msr(A) and related determinants in Gram-positive cocci and in antibiotic producing organisms is reviewed. Alternative hypotheses for the mechanism of action of Msr(A) (i.e. active transport vs. ribosomal protection) are discussed. Evidence indicating Msr(A) may have a role in virulence in addition to conferring antibiotic resistance is also considered.

Correlation between enterococcal biofilm formation in vitro and medical-device-related infection potential in vivo.

Hospital-acquired infections caused by enterococci have increased dramatically since the 1970s. Many nosocomial enterococcal bloodstream infections are associated with medical devices such as central venous catheters. The ability to form biofilm on medical devices is a potential virulence trait that may allow enterococci to cause infections in the expanding population of patients managed with such devices. In this study, the hypothesis that increased ability to form biofilm in vitro is associated with medical-device-related infection in vivo was tested. A microplate assay was employed to assess biofilm-forming characteristics of enterococci in 0.9 % (w/v) sodium chloride, an oligotrophic environment, and BHI, a nutrient-rich environment. Results were compared in isolates from different sources of infection. One hundred and nine enterococcal bloodstream isolates were assayed. Biofilm formation on microplates was demonstrated by all Enterococcus faecalis isolates and 16/38 (42 %) Enterococcus faecium isolates. E. faecalis isolates produced significantly more biofilm than E. faecium isolates in both media (P < 0.0001, Mann-Whitney U test). E. faecalis isolates from intravascular-catheter-related bloodstream infections (CRBSIs) produced significantly more biofilm than non-CRBSI isolates (P < 0.0001), or isolates of uncertain clinical significance (P < 0.0001). Biofilm formed by E. faecium isolates was not significantly affected by culture medium and did not differ between isolates from the different clinical categories. In conclusion, there was significantly more biofilm formed by E. faecalis isolates causing CRBSI compared with isolates from other types of infection or from isolates of uncertain clinical significance. The ability of E. faecalis isolates to form biofilm in vitro appears to be a marker of a virulence trait that enhances the ability of isolates to cause CRBSI.

Staphylococcal resistance revisited: community-acquired methicillin resistant Staphylococcus aureus--an emerging problem for the management of skin and soft tissue infections.

PURPOSE OF REVIEW: In the community non-localized or deep staphylococcal skin and soft tissue infections are typically managed with beta-lactamase stable penicillins. The aims of this review are (1) to evaluate the evidence for the emergence of new strains of community-acquired methicillin resistant Staphylococcus aureus (MRSA), (2) to identify the reasons for their significant association with cutaneous infections, and (3) to consider how they arose and how big a threat they pose to the management of such infections outside hospitals. RECENT FINDINGS: MRSA are emerging as significant community pathogens, especially in previously healthy children with no recognizable risk factors, and are predominantly associated with skin and soft tissue infections (especially abscesses and cellulitis). When present, risk factors are generally similar to those for infection with methicillin susceptible S. aureus. The MRSA isolates associated with such infections may not be entirely 'new', but could represent the displacement of some hospital clones (e.g. EMRSA-15 or variants thereof) to the community as well as the de-novo generation of novel MRSA clones by multiple horizontal transmissions of the mecA gene into methicillin susceptible S. aureus with different genetic backgrounds, some of which are already circulating globally. Community-acquired MRSA from diverse locations are non multiresistant and almost always contain the novel type IV SCCmec commonly found in coagulase-negative staphylococci, but also in hospital-associated gentamicin susceptible MRSA from France, the paediatric clone and in EMRSA-15. SUMMARY: More local data on CA-MRSA infections are needed so that dermatologists and community physicians can assess the risk of such infections amongst their patients and avoid the inappropriate administration of beta-lactams. No simple change in prescribing practices will entirely alleviate selective pressure for the spread of community-acquired MRSA and not exacerbate resistance in pyogenic streptococci, commonly found together with S. aureus in skin and soft tissue infections. The importance of hygiene in preventing the spread of community-acquired MRSA in the community must be reemphasized.

Detection of transposon Tn5432-mediated macrolide-lincosamide-streptogramin B (MLSB) resistance in cutaneous propionibacteria from six European cities.

Forty-five cutaneous propionibacterial isolates from six European cities were found to be highly resistant to all macrolide-lincosamide-streptogramin B antibiotics, including the ketolide telithromycin. This contrasts with previously documented phenotypes associated with 23S rRNA mutations. Sequencing of the resistance determinant showed it to be erm(X) of corynebacterial origin located on the composite transposon Tn5432.