Inhibition of the Staphylococcus aureus NADPH-dependent enoyl-acyl carrier protein reductase by triclosan and hexachlorophene.
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Enoyl-acyl carrier protein reductase (FabI) plays a determinant role in completing cycles of elongation in type II fatty acid synthase systems and is an important target for antibacterial drugs. The FabI component of Staphylococcus aureus (saFabI) was identified, and its properties were compared with Escherichia coli FabI (ecFabI). ecFabI and saFabI had similar specific activities, and saFabI expression complemented the E. coli fabI(Ts) mutant, illustrating that the Gram-positive FabI was interchangeable with the Gram-negative FabI enzyme. However, ecFabI was specific for NADH, whereas saFabI exhibited specific and positive cooperative binding of NADPH. Triclosan and hexachlorophene inhibited both ecFabI and saFabI. The triclosan-resistant ecFabI(G93V) protein was also refractory to hexachlorophene inhibition, illustrating that both drugs bind at the FabI active site. Both the introduction of a plasmid expressing the safabI gene or a missense mutation in the chromosomal safabI gene led to triclosan resistance in S. aureus; however, these strains did not exhibit cross-resistance to hexachlorophene. The replacement of the ether linkage in triclosan by a carbon bridge in hexachlorophene prevented the formation of a stable FabI-NAD(P)(+)-drug ternary complex. Thus, the formation of this ternary complex is a key determinant of the antibacterial activity of FabI inhibitors. (+info)
Guideline for Hand Hygiene in Health-Care Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America.
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The Guideline for Hand Hygiene in Health-Care Settings provides health-care workers (HCWs) with a review of data regarding handwashing and hand antisepsis in health-care settings. In addition, it provides specific recommendations to promote improved hand-hygiene practices and reduce transmission ofpathogenic microorganisms to patients and personnel in health-care settings. This report reviews studies published since the 1985 CDC guideline (Garner JS, Favero MS. CDC guideline for handwashing and hospital environmental control, 1985. Infect Control 1986;7:231-43) and the 1995 APIC guideline (Larson EL, APIC Guidelines Committee. APIC guideline for handwashing and hand antisepsis in health care settings. Am J Infect Control 1995;23:251-69) were issued and provides an in-depth review of hand-hygiene practices of HCWs, levels of adherence of personnel to recommended handwashing practices, and factors adversely affecting adherence. New studies of the in vivo efficacy of alcohol-based hand rubs and the low incidence of dermatitis associated with their use are reviewed. Recent studies demonstrating the value of multidisciplinary hand-hygiene promotion programs and the potential role of alcohol-based hand rubs in improving hand-hygiene practices are summarized. Recommendations concerning related issues (e.g., the use of surgical hand antiseptics, hand lotions or creams, and wearing of artificial fingernails) are also included. (+info)
Application of a gloved-hand model for multiparameter measurements of skin-degerming activity.
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The application of an established gloved-hand model to multiparameter measurements of skin-degerming activity is described. In particular, appropriate experimental designs are illustrated which allow characterization of performance of topical skin-cleansing preparations in terms of rapid, sustained, cummulative, and persistent skin-degerming effects on the hand. Single-contact studies were used to define the degerming activity profiles of selected commercial surgical scrub preparations, and to establish the optimal post-treatment sampling interval for individual preparations. Rapid and sustained skin-degerming effects were measured and contrasted. Rapid skin-degerming activity, iodophor preparation. Sustained skin-degerming activity, namely, that occurring on the gloved hand during a postcontact interval, was shown and characterized for two hexachlorophene preparations. Multiple-contact studies with a 3% hexachlorophene preparations were used to illustrate cummulative and persistent skin-degerming effects. Cummulative skin-degerming activity was demonstrated in terms of progressive bacterial reductions after repeated contacts within a single day. Presistent skin-degerming activity was shown in terms of the profile of daily pretreatment bacterial counts after multiple contacts over successive days. Uniformity of treatment response was established for a broad range of pretreatment bacterial counts extending from approximatley log 4 to log 7 per hand. The importance of pretreatment bacterial count measurement and of adequate neutralization of hand extract samples is stressed. A randomized-hand experimental design is discussed relative to its versatility and amenability to statistical analysis. (+info)
ACNE VULGARIS. EVALUATION OF A MEDICATED CLEANSING PAD.
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Using the technique of simultaneous, symmetrical paired comparisons, a medicated cleansing pad that can be easily used at work or at school as an adjunctive in the treatment of acne vulgaris was evaluated.The experimental pads were significantly beneficial in reducing skin oiliness and in clinical improvement of the acne. Response to standard acne therapy was faster when the pads were used adjunctively, although the significant results seen initially tended to even out as therapy continued. Use of the medicated pads produced no untoward side effects and were well accepted by patients. (+info)
INFECTION AND HEALING IN SUPERFICIAL WOUNDS. A COMPARATIVE CLINICAL STUDY OF TOPICAL TREATMENT METHODS.
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The comparative value of nitrofurazone-hydrocortisone cream, of saline solution soaks and of a dry method of care in preventing or curing surface infections was studied in 86 patients. Of a total of 117 discrete lesions treated, 59 were infected, most of these being chronically infected decubital ulcers in paraplegic patients. The other lesions were burns, avulsive and wringer injuries, orthopedic surgical wounds and various abrasions. Excellent results were obtained with the nitrofurazone-hydrocortisone cream in infected lesions: infection rapidly cleared in all 37 lesions treated although only 29 healed completely and promptly. Five lesions were improved, and in three instances healing was unduly delayed. Among 22 infected lesions treated twice daily with saline solution soaks, only five were cured, two improved, seven had delayed healing, and eight had no improvement. In the non-infected wounds, saline soaks or plain dry care after surgical debridement and hexachlorophene cleansing gave results generally more comparable to those obtained in similar cases treated with the nitrofurazone-hydrocortisone cream. (+info)
Prediction of mechanisms of action of antibacterial compounds by gene expression profiling.
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We have generated a database of expression profiles carrying the transcriptional responses of the model organism Bacillus subtilis following treatment with 37 well-characterized antibacterial compounds of different classes. The database was used to build a predictor for the assignment of the mechanisms of action (MoAs) of antibacterial compounds by the use of support vector machines. This predictor was able to correctly classify the MoA class for most compounds tested. Furthermore, we provide evidence that the in vivo MoA of hexachlorophene does not match the MoA predicted from in vitro data, a situation frequently faced in drug discovery. A database of this kind may facilitate the prioritization of novel antibacterial entities in drug discovery programs. Potential applications and limitations are discussed. (+info)
Recurring methicillin-resistant Staphylococcus aureus infections in a football team.
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An outbreak of community-associated methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI) occurred in a college football team from August to September 2003. Eleven case-players were identified, and boils were the most common sign. Linemen had the highest attack rate (18%). Among 99 (93% of team) players with cultured specimens, 8 (8%) had positive MRSA nasal cultures. All available case-players' MRSA isolates characterized had the community-associated pulsed-field type USA300. A case-control study found that sharing bars of soap and having preexisting cuts or abrasions were associated with infection. A carrier-control study found that having a locker near a teammate with an SSTI, sharing towels, and living on campus were associated with nasal carriage. Successful outbreak control measures included daily hexachlorophene showers and hygiene education. (+info)
Hexachlorophene inhibits Wnt/beta-catenin pathway by promoting Siah-mediated beta-catenin degradation.
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Aberrant activation of Wnt/beta-catenin signaling and subsequent up-regulation of beta-catenin response transcription (CRT) is a critical event in the development of human colon cancer. Thus, Wnt/beta-catenin signaling is an attractive target for the development of anticancer therapeutics. In this study, we identified hexachlorophene as an inhibitor of Wnt/beta-catenin signaling from cell-based small-molecule screening. Hexachlorophene antagonized CRT that was stimulated by Wnt3a-conditioned medium by promoting the degradation of beta-catenin. This degradation pathway is Siah-1 and adenomatous polyposis colidependent, but glycogen synthase kinase-3beta and F-box beta-transducin repeat-containing protein-independent. In addition, hexachlorophene represses the expression of cyclin D1, which is a known beta-catenin target gene, and inhibits the growth of colon cancer cells. Our findings suggest that hexachlorophene attenuates Wnt/beta-catenin signaling through the Siah-1-mediated beta-catenin degradation. (+info)