Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns
01 Jul 2017-Clinical Microbiology Reviews (American Society for Microbiology)-Vol. 30, Iss: 3, pp 827-860
TL;DR: A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future.
Abstract: Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future.
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01 Jan 2006
TL;DR: User experience surveys (UESs) are regarded as an important part of the overall performance framework for social care and, providing councils with information about how they might improve services locally, and are required to submit their results to government bodies so that the relative performance of the CSSRs can be judged.
Abstract: For some time now councils with social services responsibilities (CSSRs) have been required to conduct surveys of user’s experience of social services. These have taken place nationally in three-yearly cycles. In 2002/03 the survey was for older people, in 2003/04 it was for younger adults with physical and sensory impairments, and in 2004/05 it was for children. 2005/06 marked the beginning of the second wave of the cycle. The mandate for conducting surveys of user’s experiences and satisfaction with services was first given in the white paper Modern Local Government: in Touch with the People (Department for the Environment, Trade and the Regions, 1998). In 2002 the Office of National Statistics (ONS) and SPRU developed a set of questionnaires for this purpose (Qureshi and Rowlands, 2004). Subsequent national surveys have drawn on this work to identify a set of compulsory questions for each round. User experience surveys (UESs) are regarded as an important part of the overall performance framework for social care and, providing councils with information about how they might improve services locally. Local authorities are required to submit their results to government bodies so that the relative performance of the CSSRs can be judged. This report is composed of five sections. The aims and objectives of the report are outlined in the second section and the method used to gather the data is outlined in section 3. In section 4 we report on the findings from the fieldwork and draw some conclusions and recommendations for the national survey in section 5. The topic guides for the focus groups and interviews are included in the appendices along with a brief discussion of the findings from the focus groups and a copy of the final extended questionnaire.
628 citations
17 Oct 2011
TL;DR: The results of this study indicate that perioperative elimination of nasal carriage using mupirocin nasal ointment significantly reduces the SSI rate in cardiothoracic surgery patients and warrants a prospective, randomized, placebo-controlled efficacy trial.
Abstract: OBJECTIVE
To test the hypothesis that perioperative elimination of nasal carriage of Staphylococcus aureus using mupirocin nasal ointment reduces the surgical-site infection (SSI) rate in cardiothoracic surgery.
DESIGN
Unblinded intervention trial with historical controls.
SETTING
A university hospital, tertiary referral center for cardiothoracic surgery.
PATIENTS
Consecutive patients undergoing cardiothoracic surgery between August 1, 1989, and February 1, 1991 (historical control group), and between March 1, 1991, and August 1, 1992 (intervention group).
RESULTS
The historical control group consisted of 928 patients and the intervention group of 868, of whom 752 actually were treated. The 116 patients who were unintentionally not treated were considered as a concurrent control group. In the intention-to-treat analysis, a significant reduction in SSI rate was observed after the intervention (historical-control group 7.3% and intervention group 2.8%; P < .0001). The SSI rate in the concurrent control group was significantly higher than in the treated group (7.8% and 2.0%, respectively; P = .0023). Resistance of S aureus to mupirocin was not observed.
CONCLUSION
The results of this study indicate that perioperative elimination of nasal carriage using mupirocin nasal ointment significantly reduces the SSI rate in cardiothoracic surgery patients and warrants a prospective, randomized, placebo-controlled efficacy trial. This preventive measure may be beneficial in other categories of surgical patients as well.
234 citations
TL;DR: Preservatives act on several cell targets; however, they might present toxic effects to the consumer, so their use at high concentrations is more effective from the preservation viewpoint, whereas at low concentrations microbial resistance can develop.
Abstract: Cosmetics, like any product containing water and organic/inorganic compounds, require preservation against microbial contamination to guarantee consumer’s safety and to increase their shelf-life. The microbiological safety has as main goal of consumer protection against potentially pathogenic microorganisms, together with the product’s preservation resulting from biological and physicochemical deterioration. This is ensured by chemical, physical, or physicochemical strategies. The most common strategy is based on the application of antimicrobial agents, either by using synthetic or natural compounds, or even multifunctional ingredients. Current validation of a preservation system follow the application of good manufacturing practices (GMPs), the control of the raw material, and the verification of the preservative effect by suitable methodologies, including the challenge test. Among the preservatives described in the positive lists of regulations, there are parabens, isothiasolinone, organic acids, formaldehyde releasers, triclosan, and chlorhexidine. These chemical agents have different mechanisms of antimicrobial action, depending on their chemical structure and functional group’s reactivity. Preservatives act on several cell targets; however, they might present toxic effects to the consumer. Indeed, their use at high concentrations is more effective from the preservation viewpoint being, however, toxic for the consumer, whereas at low concentrations microbial resistance can develop.
166 citations
TL;DR: Intranasal PVP-I significantly improved the efficacy of chlorhexidine wash and was as effective as mupirocin in reducing surgical site infection in orthopedic surgery, making it a useful alternative decolonizing agent for the prevention of S. aureus infections.
Abstract: Nasal decolonization is an integral part of the strategies used to control and prevent the spread of methicillin-resistant Staphylococcus aureus (MRSA) infections The two most commonly used agents for decolonization are intranasal mupirocin 2% ointment and chlorhexidine wash but the increasing emergence of resistance and treatment failure has underscored the need for alternative therapies This article discusses povidone iodine (PVP-I) as an alternative decolonization agent and is based on literature reviewed during an Expert's workshop on resistance and MRSA decolonization When compared to chlorhexidine and mupirocin, respectively, PVP-I 10% and 75% solution had rapid and superior bactericidal activity against MRSA in in vitro and ex vivo studies Notably, PVP-I 10% and 5% solutions were also active against both chlorhexidine-resistant and mupirocin-resistant strains, respectively Unlike chlorhexidine and mupirocin, available reports have not observed a link between PVP-I and the induction of bacterial resistance or cross-resistance to antiseptics and antibiotics These pre-clinical findings also translate into clinical decolonization, where intranasal PVP-I significantly improved the efficacy of chlorhexidine wash and was as effective as mupirocin in reducing surgical site infection (SSI) in orthopedic surgery Overall, these qualities of PVP-I make it a useful alternative decolonizing agent for the prevention of S aureus infections, but additional experimental and clinical data are required to further evaluate the use of PVP-I in this setting
61 citations
Cites background from "Current and Emerging Topical Antiba..."
...However, there are growing concerns about decolonization failures following the emergence of mupirocin (17, 18) and chlorhexidine resistance (18–20)....
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TL;DR: The present review focuses on the current status of delivery agents that use ozonated oils as antimicrobial agents in topical (dermal, skin, and soft tissues) treatments.
Abstract: The search for a wide spectrum of antimicrobial agents that can avoid resistance while maintaining reasonable side effects has led to ozonated oils experiencing an increase in scientific interest and clinical applications. The treatment of vegetable oils with ozone leads to the creation of a reservoir of ozone that slowly releases into the skin thanks to the fact that ozone can be held as ozonides of unsaturated fatty acids. Interest in the use of ozonated oils has meant that several ozonated-vegetable-oil-containing products have been commercialized as cosmetic and pharmaceutical agents, and in innovative textile products with antibacterial activity. New approaches to the delivery of ozonated oils have very recently appeared in an attempt to improve their characteristics and reduce drawbacks, such as an unpleasant odor, high viscosity and undesired effects on skin, including irritation and rashes. The present review focuses on the current status of delivery agents that use ozonated oils as antimicrobial agents in topical (dermal, skin, and soft tissues) treatments. Challenges and future opportunities for these delivery systems will also be discussed.
58 citations
Cites background from "Current and Emerging Topical Antiba..."
...This can be useful as an alternative to contrast the widespread and indiscriminate use of topical agents, particularly mupirocin and fusidic acid, which has led to the emergence of bacterial resistance, predominantly in staphylococci [123]....
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References
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01 Jan 2001
TL;DR: The supplemental information presented in this document is intended for use with the antimicrobial susceptibility testing procedures published in the following Clinical and Laboratory Standards Institute (CLSI)–approved standards.
Abstract: The supplemental information presented in this document is intended for use with the antimicrobial susceptibility testing procedures published in the following Clinical and Laboratory Standards Institute (CLSI)–approved standards: M02-A12—Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard—Twelfth Edition; M07-A10—Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Tenth Edition; and M11-A8—Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard— Eighth Edition. The standards contain information about both disk (M02) and dilution (M07 and M11) test procedures for aerobic and anaerobic bacteria. Clinicians depend heavily on information from the microbiology laboratory for treatment of their seriously ill patients. The clinical importance of antimicrobial susceptibility test results demands that these tests be performed under optimal conditions and that laboratories have the capability to provide results for the newest antimicrobial agents. The tabular information presented here represents the most current information for drug selection, interpretation, and QC using the procedures standardized in the most current editions of M02, M07, and M11. Users should replace the tables published earlier with these new tables. (Changes in the tables since the previous edition appear in boldface type.) Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing. 26th ed. CLSI supplement M100S (ISBN 1-56238-923-8 [Print]; ISBN 1-56238924-6 [Electronic]). Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087 USA, 2016. The data in the interpretive tables in this supplement are valid only if the methodologies in M02-A12—Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard—Twelfth Edition; M07-A10—Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Tenth Edition; and M11-A8—Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard— Eighth Edition are followed.
17,824 citations
TL;DR: Known mechanisms of microbial resistance (both intrinsic and acquired) to biocides are reviewed, with emphasis on the clinical implications of these reports.
Abstract: Antiseptics and disinfectants are extensively used in hospitals and other health care settings for a variety of topical and hard-surface applications A wide variety of active chemical agents (biocides) are found in these products, many of which have been used for hundreds of years, including alcohols, phenols, iodine, and chlorine Most of these active agents demonstrate broad-spectrum antimicrobial activity; however, little is known about the mode of action of these agents in comparison to antibiotics This review considers what is known about the mode of action and spectrum of activity of antiseptics and disinfectants The widespread use of these products has prompted some speculation on the development of microbial resistance, in particular whether antibiotic resistance is induced by antiseptics or disinfectants Known mechanisms of microbial resistance (both intrinsic and acquired) to biocides are reviewed, with emphasis on the clinical implications of these reports
4,243 citations
"Current and Emerging Topical Antiba..." refers background in this paper
...DNA, and protein synthesis pathways, disruption of cellular homeostasis, and a loss of cellular integrity, which ultimately lead to a loss of viability (201)....
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...but may be related to protein denaturation (201) or to inhibition and uncoupling of...
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...Like chlorine, iodine is a powerful oxidizing agent that can quickly penetrate the cell membrane (201)....
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...isopropyl alcohol, and n-propanol are most commonly used as biocides (201)....
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...Chlorhexidine can also be impregnated into wound dressings (199) and central line catheters (200) and is generally regarded as an extremely safe topical agent (201)....
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TL;DR: The “Guideline for Prevention of Surgical Site Infection, 1999” presents the Centers for Disease Control and Prevention's recommendations for the prevention of surgical site infections (SSIs), formerly called surgical wound infections, and replaces previous guidelines.
Abstract: The “Guideline for Prevention of Surgical Site Infection, 1999” presents the Centers for Disease Control and Prevention (CDC)'s recommendations for the prevention of surgical site infections (SSIs), formerly called surgical wound infections. This two-part guideline updates and replaces previous guidelines.Part I, “Surgical Site Infection: An Overview,” describes the epidemiology, definitions, microbiology, pathogenesis, and surveillance of SSIs. Included is a detailed discussion of the pre-, intra-, and postoperative issues relevant to SSI genesis.
4,059 citations
TL;DR: Improved outcomes for severely burned patients have been attributed to medical advances in fluid resuscitation, nutritional support, pulmonary and burn wound care, and infection control practices.
Abstract: Burns are one of the most common and devastating forms of trauma. Patients with serious thermal injury require immediate specialized care in order to minimize morbidity and mortality. Significant thermal injuries induce a state of immunosuppression that predisposes burn patients to infectious complications. A current summary of the classifications of burn wound infections, including their diagnosis, treatment, and prevention, is given. Early excision of the eschar has substantially decreased the incidence of invasive burn wound infection and secondary sepsis, but most deaths in severely burn-injured patients are still due to burn wound sepsis or complications due to inhalation injury. Burn patients are also at risk for developing sepsis secondary to pneumonia, catheter-related infections, and suppurative thrombophlebitis. The introduction of silver-impregnated devices (e.g., central lines and Foley urinary catheters) may reduce the incidence of nosocomial infections due to prolonged placement of these devices. Improved outcomes for severely burned patients have been attributed to medical advances in fluid resuscitation, nutritional support, pulmonary and burn wound care, and infection control practices.
1,627 citations
"Current and Emerging Topical Antiba..." refers background in this paper
...storm” for colonization and proliferation of microbes (36, 37)....
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TL;DR: An in vitro Fenton system was established that generates DNA strand breaks and inactivates bacteriophage and that also reproduces the suppression of DNA damage by high concentrations of peroxide.
Abstract: Exposure of Escherichia coli to low concentrations of hydrogen peroxide results in DNA damage that causes mutagenesis and kills the bacteria, whereas higher concentrations of peroxide reduce the amount of such damage. Earlier studies indicated that the direct DNA oxidant is a derivative of hydrogen peroxide whose formation is dependent on cell metabolism. The generation of this oxidant depends on the availability of both reducing equivalents and an iron species, which together mediate a Fenton reaction in which ferrous iron reduces hydrogen peroxide to a reactive radical. An in vitro Fenton system was established that generates DNA strand breaks and inactivates bacteriophage and that also reproduces the suppression of DNA damage by high concentrations of peroxide. The direct DNA oxidant both in vivo and in this in vitro system exhibits reactivity unlike that of a free hydroxyl radical and may instead be a ferryl radical.
1,488 citations
"Current and Emerging Topical Antiba..." refers background in this paper
...in the formation of lesions and nicks in cellular DNA, the cleavage of nucleic acid and protein backbones, and subsequent damage to the cell membrane (293, 294)....
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