WO2008133717A2 - Method of controlling the transmission of community-acquired-methicillin-resistant staphylococcus aureus, and preventing or reducing infections caused by the same - Google Patents

Abstract

A method of disrupting the transmission of Community- Acquired Methicillin-Resistant Staphylococcus Aureus (CA-MRSA) using an activated antibacterial composition is disclosed. Methods of reducing and preventing infections caused by CA-MRSA also are disclosed.

Description

METHOD OF CONTROLLING THE TRANSMISSION OF

COMMUNITY-ACQUIRED METHICILLIN-RESISTANT

STAPHYLOCOCCUS AUREUS, AND PREVENTING OR

REDUCING INFECTIONS CAUSED BY THE SAME

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. provisional patent application No.

60/857,447, filed November 7, 2006, incorporated herein by reference.

FIELD OF THE INVENTION

[0002] The present invention relates to a method of disrupting the transmission of

Community-Acquired Methicillin-Resistant Staphylococcus Aureus (CA-MRSA) by contacting a surface with an activated antibacterial composition. The present invention also relates to methods of reducing or preventing infections caused by CA-MRSA. More particularly, the present invention is directed to disrupting the transmission of CA-MRSA from an animate or inanimate surface to an animate surface, and to reducing or preventing infections caused by CA-MRSA, by contacting a surface, such as the skin of a mammal, with an activated antibacterial composition. The activated antibacterial composition provides a substantial reduction in CA-MRSA populations on a surface within one minute of contact with the activated composition and imparts a residual control of CA-MRSA to the surface.

BACKGROUND OF THE INVENTION

[0003] Staphylococcus aureus, or "staph," is a common bacterium found on the skin or in the nose of about 25% of humans. Although staph typically is harmless, in certain instances staph can cause moderate to severe skin infections, such as pimples and boils, which are treatable without antibiotics. Less commonly, staph causes more serious systemic infections requiring hospitalization and the use of antibiotics.

[0004] One strain of staph, known as MRSA (i.e., methicillin-resistant

Staphylococcus aureus), was first identified in 1961 and about 1% of the population is colonized with MRSA. MRSA has established itself as a major hospital pathogen responsible for many nosocomial infections, and is now prevalent in most hospitals. Staph infections, including MRSA infections, most frequently occur in hospitals and healthcare facilities, such as nursing homes and dialysis centers. In these institutions, individuals often have weakened immune systems and are more susceptible to MRSA infections. Healthcare-associated MRSA (i.e., HA-MRSA) infections include surgical wound infections, urinary tract infections, bloodstream infections, and pneumonia, which may require hospitalization and treatment with antibiotics.

[0005J Because of the significant use of antibiotics in the healthcare setting, the

MRSA strain has become resistant to many of the standard antibiotic therapies. MRSA, therefore, is resistant to multiple antibiotics, specifically, all beta-lactams antibiotics, like methicillin, as well as other antibiotics, such as oxacillin, penicillin, and amoxicillin. Vancomycin often is the only drug that successfully treats MRSA infections. MRSA, therefore, is a considerable public health concern.

[0006] A newer form of MRSA infection, known as CA-MRSA (i.e., community- acquired, or community-associated, mefhicillin-resistant Staphylococcus aureus), was first recognized in the 1980s. CA-MRSA is different from HA-MRSA and does not appear to have arisen from HA-MRSA. Whereas HA-MRSA almost always is associated with persons having established risk factors attributed to a prior or ongoing medical treatment, this is not the case with CA-MRSA. In fact, persons suffering from a CA-MRSA infection typically are younger and healthier than persons suffering from an HA-MRSA infection.

[0007] CA-MRSA has appeared with increasing frequency and now is epidemic in certain community populations. It was previously reported that slightly more than 10% of all MRSA infections in the U.S. are CA-MRSA. However, recent reports indicated that many individuals infected with CA-MRSA are infected with a highly virulent new form of CA- MRSA, known as USA300. In particular, the study reports that 249 of 422 emergency room patients tested positive of MRSA, and USA300 was detected in 212 of 218 patient tissue samples that were tested further.

[0008] CA-MRSA causes serious skin and soft tissue infections in otherwise healthy persons who have not been recently hospitalized or undergone invasive medical procedures. CA-MRS A-infected individuals require hospitalization in about one out of five cases. CA- MRSA has been identified most frequently among specific populations, including prisoners, athletes, children, homosexual males, military trainees, Pacific Islanders, Alaskan Natives, and Native Americans.

[0009] CA-MRSA, therefore, poses a new risk to the community at large. This new

CA-MRSA strain is genetically distinguishable from HA-MRSA, and, unlike HA-MRSA, is susceptible to older antibiotic therapies. However, CA-MRSA carries a potent exotoxin, specifically Panton-Valentine leukocidin or PVL, that attacks infection-fighting leukocyte white blood cells and contributes to its virulence. This toxin causes recurrent skin and soft tissue infections. The most serious form of CA-MRSA infection causes necrotizing fascitis, a severe, rapidly-progressing, and life-threatening skin infection or lethal necrotizing pneumonia.

[0010] Treatment of an MRSA skin infection is challenging. For some individuals, skin ointments containing antibiotics, such as mupirocin or fusidic acid, can be used, but resistance to these antibiotics can develop. Beta-lactam antibiotics (e.g., methicillin and oxacillin), which are typically used to treat common staph infections, such as furuncles, abscesses, and cellulites, are ineffective against HA-MRSA. Unlike HA-MRSA, which is resistant to multiple classes of antibiotics (including macrolides, aminoglycosides, fluoroquinolones, tetracyclines, and lincosamides), CA-MRSA is susceptible to several antibiotic classes outside of the beta-lactam group (e.g., clindamycin).

[0011] The transmission of skin MRSA infections most frequently occurs through close, skin-to-skin contact (such as that found in contact sports), through contact with skin wounds of another individual (cuts, abrasions), or through contact with inanimate surfaces on which MRSA can survive for 24 hours or more. MRSA bacteria also can infect healthy, intact skin. Crowded living conditions and poor hygiene also are factors which play a role in the transmission of MRSA, including CA-MRSA.

[0012] Because CA-MRSA can survive on environmental surfaces for several hours after initial contamination, and because infection is readily transmitted by skin-to-skin contact, and by contaminated environmental surface-to-skin contact, a newly contaminated finger then can contaminate another surface. Therefore, CA-MRSA contamination of skin and environmental surfaces should be minimized to reduce the risk of transmitting the infection throughout the general population.

[0013] Currently, the most practical means of preventing or reducing MRSA transmission is through prudent hygiene measures involving hand washing with soap and water or using an alcohol-based hand sanitizer, proper wound care (including proper disposal of bandages), avoiding sharing personal hygiene items (such as towels and razors), and avoiding contact with wounds or bandages of other individuals. Such preventative measures help avoid contracting a CA-MRSA infection and help avoid a recurrence of a CA-MRSA infection. However, to date, even practicing good hygiene measures has not controlled the transmission of CA-MRSA, as evidenced by recently-reported studies.

[0014] It is known that washing body parts (e.g., hand washing) and hard surfaces

(e.g., countertops and sinks) can significantly decrease the population of microorganisms, including pathogens, on the washed surface. Therefore, cleaning skin and other animate and inanimate surfaces to reduce microbial populations is a first defense in removing microbial pathogens from these surfaces, and thereby minimizing the risk of infection.

[0015] Antibacterial personal care compositions also are known in the art. For example, antibacterial cleansing compositions, which typically are used to cleanse the skin and to destroy bacteria and other microorganisms present on the skin, especially the hands, arms, and face of the user, are known.

[0016] Antibacterial compositions are used, for example, in the healthcare industry, food service industry, meat processing industry, and in the private sector by individual consumers. The widespread use of antibacterial compositions indicates the importance consumers place on controlling bacteria and other microorganism populations on skin. It is important, however, that antibacterial compositions provide a rapid reduction in microorganism populations and without problems associated with toxicity and skin irritation. It also is important that the antibacterial composition controls and reduces pathogenic bacteria of particular interest, such as CA-MRSA.

[0017] Most commercial antibacterial compositions, however, generally offer a low to moderate antibacterial activity. Antibacterial activity is assessed against a broad spectrum of microorganisms, including both Gram positive and Gram negative microorganisms. The log reduction, or alternatively the percent reduction, in bacterial populations provided by the antibacterial composition correlates to antibacterial activity. A log reduction of 3-5 is most preferred, a 1-3 reduction is preferred, whereas a log reduction of less than 1 is least preferred, for a particular contact time, generally ranging from 15 seconds to 5 minutes. Thus, a highly preferred antibacterial composition exhibits a 3-5 log reduction against a broad spectrum of microorganisms in a short contact time. Prior disclosures illustrate attempts to provide such antibacterial compositions, which, to date, do not provide the rapid, broad range control of microorganisms desired by consumers.

[0018] Although prior compositions may disclose a substantial reduction in common bacteria dictated by testing in established protocols, it is important that an antibacterial composition also effectively kill hard-to-control bacteria that pose a severe public health threat, such as CA-MRSA. Until recently, antibacterial compositions have been unable to rapidly control hard-to-kill bacteria, such as CA-MRSA, and to provide a residual control of such bacteria,

[0019] In particular, the activated antibacterial compositions typically contain an active antimicrobial agent and one or more of a surfactant, an alcohol, and various other ingredients, for example, dyes, fragrances, pH adjusters, thickeners, skin conditioners, and the like, in an aqueous carrier. Several different classes of antibacterial agents have been used in antibacterial compositions, both cleansing compositions and hand sanitizer gels. Examples of antibacterial agents include a bisguanidine (e.g., chlorhexidine digluconate), diphenyl compounds, benzyl alcohols, trihalocarbanilides, quaternary ammonium compounds, ethoxylated phenols, and phenolic compounds, such as halo-substituted phenolic compounds, like PCMX (i.e., p-chloro-m-xylenol) and triclosan (i.e., 2,4,4'-trichloro-2'- hydroxy-diphenylether). Present-day antimicrobial compositions based on such antibacterial agents exhibit a wide range of antibacterial activity, ranging from low to high, depending on the microorganism to be controlled and the particular antibacterial composition.

[0020] As mentioned above, another class of personal care antimicrobial compositions is the hand sanitizer gels. In hand sanitizer gels, the antimicrobial agent can be one of the above-disclosed antimicrobial agents in addition to an alcohol, typically ethanol, present in such compositions. Hand sanitizer gels are used primarily by medical personnel to disinfect the hands and fingers. A hand sanitizer gel is applied to, and rubbed into, the hands and fingers, and the composition is allowed to evaporate from the skin. Wiping the sanitizing gel from the skin is not necessary because the high alcohol content of hand sanitizer gels leads to a fast and essentially complete evaporation of the sanitizing gel from the skin.

[0021] Although prior antibacterial compositions, including both antibacterial cleansing compositions and hand sanitizer gels, have been designed to control a wide variety of common microorganisms, the control of CA-MRSA has not been fully addressed. For example, U.S. Patent No. 6,022,551 discloses antimicrobial compositions containing an alcohol, a thickener, and an antimicrobial material selected from phenoxyethanol, benzalkonium chloride, benzethonium chloride, and cocophosphatidyl-dimonium chloride. The composition is disclosed as effective against MRSA. [0022] Therefore, a need exists for a method of controlling CA-MRSA and interrupting the transmission of CA-MRSA from an infected surface to a noninfected surface, such as the skin of a mammal. A need also exists for a method of reducing or preventing infections mediated by CA-MRSA. Preferably, the method provides a rapid control of CA- MRSA and imparts a residual control of CA-MRSA to a treated surface. The present invention is directed to providing a heightened and extended level of CA-MRSA control on animate and inanimate surfaces.

SUMMARY OF THE INVENTION

[0023] The present invention relates to a method of interrupting the transmission of

CA-MRSA from an animate or inanimate surface to an animate surface, and particularly to human skin. The present invention also relates to a method of reducing the incidence of infections caused by CA-MRSA. The method provides a rapid and a residual control of CA- MRSA on an animate or inanimate surface.

[0024] Therefore, one aspect of the present invention is to provide a method of disrupting the transmission of CA-MRSA from a first animate or a first inanimate surface to a second animate surface comprising contacting the first animate, first inanimate, or second animate surface with an activated antibacterial composition.

[0025] Another aspect of the present invention is to provide a method of reducing the incidence of infections caused by CA-MRSA by applying an activated antibacterial composition, and preferably an activated triclosan composition, to a surface. The activated antibacterial composition can be a rinse-off product or a leave-on product.

[0026] Still another aspect of the present invention is to provide a method of controlling CA-MRSA comprising contacting a surface with an activated antibacterial cleansing composition or an activated hand sanitizer gel.

[0027] Yet another aspect of the present invention is to provide a method of controlling CA-MRSA by applying an activated antibacterial composition to a surface, wherein a percent saturation of an antibacterial agent in a continuous aqueous phase of the activated composition is at least 25%, and preferably at least 50%, when measured at 25⁰C.

[0028] Yet another aspect of the present invention is to provide a method that achieves a log reduction of at least 2 against CA-MRSA on a surface after 30 seconds of contact with an activated antibacterial composition, like an activated antibacterial cleansing composition or an activated hand sanitizing gel. Another aspect of the present invention is to provide a method of controlling CA-MRSA comprising contacting a surface contaminated with, or potentially being contaminated with, CA-MRSA with an activated antibacterial composition to provide a rapid CA-MRSA kill, e.g., within one minute, and to impart a residual CA-MRSA control to the surface.

[0029] Another aspect of the present invention is to provide a method of controlling or eliminating a population of CA-MRSA on a surface comprising applying an activated antibacterial composition to the surface, said activated composition containing an active antimicrobial agent, a surfactant, water, an optional hydric solvent, and an optional hydrotrope, wherein the antibacterial agent is present in the continuous aqueous phase of the activated composition in an amount of at least 25% of saturation, when measured at 25°C.

[0030] Yet another aspect of the present invention is to provide an activated hand sanitizing gel useful in a method for the control and elimination of CA-MRSA on a surface, said sanitizing gel comprising an active antimicrobial agent, a disinfecting alcohol, a gelling agent, water, and optional hydrotrope, wherein the antimicrobial agent is present in the continuous aqueous phase of the activated sanitizing gel in an amount of at least 25% of saturation, when measured at 25°C.

[0031] A further aspect of the present invention is to provide a method of rapidly reducing CA-MRSA bacterial populations on animal tissue, including human tissue, by contacting the tissue, like the dermis, with an activated antibacterial composition for a sufficient time, such as about 15 seconds to 5 minutes, to reduce a CA-MRSA population to a desired level, and depositing a substantial amount of the antibacterial agent on the tissue to provide a residual antibacterial action against CA-MRSA.

[0032] Yet another aspect of the present invention is to provide a method of interrupting a transmission of CS-MRSA from animate and inanimate surfaces to an animate surface, particularly human skin. Especially provided is a method of interrupting the transmission of CS-MRSA by effectively controlling a CA-MRSA population present on human skin, and continuing to control the CA-MRSA population for a period of about four or more hours, after application of an activated antibacterial composition to the skin.

[0033] The above and other novel aspects and advantages of the present invention are illustrated in the following, nonlimiting detailed description of the preferred embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0034] Personal care products incorporating an active antibacterial agent have been known for many years. Since the introduction of antibacterial personal care products, many claims have been made that such products provide antibacterial properties. Typically, to be most effective, an antibacterial composition should provide a high log reduction against a broad spectrum of organisms in as short a contact time as possible. It is also important, however, that the antibacterial composition provides a fast and substantial log reduction against difficult-to-control organisms, such as CA-MRSA.

[0035] Commercial liquid antibacterial soap compositions typically provide a poor to marginal time kill efficacy, i.e., rate of killing bacteria. These products especially lack efficacy against Gram negative bacteria, such as E. coli, and a nonexistent to poor efficacy against CA-MRSA. The present invention, therefore, is directed to a method of controlling CA-MRSA comprising contacting a surface with an activated antibacterial composition having an exceptionally high antibacterial efficacy against CA-MRSA, as measured by a rapid kill of CA-MRSA (i.e., time kill). The method also imparts a residual control of CA- MRSA to the treated surface.

[0036] The transmission and spread of CA-MRSA is not fully understood. However, contaminated surfaces and hands are believed to play a major role in the transmission of this bacteria. CA-MRSA also appears well adapted for survival in the community environment and is capable of competing with a diverse population of organisms. Therefore, controlling and disrupting its transmission is a prime public health concern.

[0037] It has been found that controlling a CA-MRSA population on an animate or inanimate surface with an activated antibacterial composition provides an unexpectedly efficacious control of CA-MRSA compared to typical present-day antibacterial compositions. A method wherein a surface contaminated with CA-MRSA, suspected of being contaminated with CA-MRSA, or potentially being contaminated with CA-MRSA is contacted with an activated antibacterial composition provides a dual benefit of interrupting the transmission of CA-MRSA from the surface and reducing or eliminating the CA-MRSA population on the surface, thus preventing or reducing skin or other infections caused by CA-MRSA.

[0038] In accordance with the present method, an activated antibacterial composition is applied to an animate or inanimate surface to provide a rapid and effective control of CA- MRSA, as measured by a time kill test. The treated surface also provides a residual control of CA-MRSA.

[0039] Activated antibacterial compositions useful in the present method are disclosed in U.S. Patent Nos. 6,107,261; 6,136,771; 6,451,748; 6,861,397; and 6,977,082, each incorporated herein by reference. More particularly, an activated antibacterial composition used in the present method is a liquid composition containing an antimicrobial agent, wherein the antimicrobial agent is present in a continuous aqueous phase of the composition in an amount of at least 25%, when measured at 25⁰C.

[0040] An activated antibacterial composition utilized in the present method provides a significantly improved time kill efficacy vs. CA-MRSA compared to prior compositions. This improved time kill efficacy is conveniently correlated to the percent saturation of the active antimicrobial agent in the continuous aqueous phase of the activated composition. The basis of this improved efficacy is the discovery that the antimicrobial efficacy of an active agent can be correlated to the rate at which, and length of time, the agent has access to an active site on the microbe.

[0041] One driving force that determines the rate of antimicrobial agent transport to the site of action is the difference in chemical potential between the site at which the agent acts and the external aqueous phase. Alternatively stated, the microbicidal activity of an active agent is proportional to its thermodynamic activity in the external phase. Accordingly, thermodynamic activity, as opposed to concentration, is an important variable with respect to antimicrobial efficacy. As discussed more fully hereafter, thermodynamic activity is conveniently correlated to the percent saturation of the active antimicrobial agent in the continuous aqueous phase of the composition.

[0042] Many compounds have a solubility limit in aqueous solutions termed the

"saturation concentration," which varies with temperature. Above the saturation concentration, the compound precipitates from solution. Percent saturation is the measured concentration in solution divided by the saturation concentration. The concentration of a compound in aqueous solution can be increased over the saturation concentration in water by the addition of compounds like surfactants. Surfactants not only increase the solubility of compounds in the continuous aqueous phase of the composition, but also form micelles, and can solubilize compounds in the micelles. [0043] The % saturation of an active antimicrobial agent in any composition, including a surfactant-containing composition, ideally can be expressed as:

% saturation=[C/C_s]xl00% wherein C is the concentration of antimicrobial agent in solution in the composition and C_s is the saturation concentration of the antimicrobial agent in the composition at room temperature. It has been theorized that the continuous aqueous phase of a surfactant- containing composition is in equilibrium with the micellar pseudophase of the composition, and further that any dissolved species, such as an antimicrobial active agent, is distributed between the aqueous continuous phase and the micellar pseudophase according to a partition law. Accordingly, the percent saturation, or alternatively the relative thermodynamic activity or relative chemical potential, of an antimicrobial active agent dissolved in a surfactant- containing composition is the same everywhere within the composition. Thus, the terms percent saturation of the antimicrobial agent "in a composition," "in the aqueous continuous phase of a composition," and "in the micellar pseudophase of a composition" are interchangeable.

[0044] Maximum antimicrobial efficacy is achieved when the difference in thermodynamic activities of the active antimicrobial agent between the composition and the target organism is maximized (i.e., when the composition is more "saturated" with the active ingredient). A second factor affecting antimicrobial activity is the total amount of available antimicrobial agent present in the composition, which can be thought of as the "critical dose." It has been found that the total amount of active agent in the continuous aqueous phase of a composition greatly influences the time in which a desired level of antimicrobial efficacy is achieved, given equal thermodynamic activities. Thus, two key factors affecting the antimicrobial efficacy of an active agent in a composition are: (1) its availability, as dictated by its thermodynamic activity, i.e., percent saturation in the continuous aqueous phase of a composition, and (2) the total amount of available active agent in the solution. A third key factor is that amount of time the active agent is allowed to remain in contact with treated surfaces.

[0045] An ingredient in many antimicrobial cleansing compositions is a surfactant, which acts as a solubilizer, cleanser, and foaming agent. Surfactants affect the percent saturation of an antimirobial agent in solution, or more importantly, affect the percent saturation of the active agent in the continuous aqueous phase of the composition. This effect can be explained in the case of a sparingly water-soluble antimicrobial agent in an aqueous surfactant solution, where the active agent is distributed between the aqueous (i.e., continuous) phase and the micellar pseudophase. For antimicrobial agents of exceedingly low solubility in water, such as triclosan, the distribution is shifted strongly toward the micelles (i.e., a vast majority of the triclosan molecules are present in surfactant micelles, as opposed to the aqueous phase).

[0046] The ratio of surfactant-to-antimicrobial agent directly determines the amount of active agent present in the surfactant micelles, which in turn affects the percent saturation of the active agent in the continuous aqueous phase. It has been found that as the surfactant: active agent ratio increases, the number of micelles relative to active molecules also increases, with the micelles being proportionately less saturated with active agent as the ratio increases. Because an active agent in the continuous phase is in equilibrium with active agent in the micellar pseudophase, as the saturation of antibacterial agent in the micellar phase decreases, so does the saturation of the antimicrobial agent in the continuous phase. The converse also is true. Active agent solubilized in the micellar pseudophase is not immediately available to contact the microorganisms, and it is the percent saturation of active agent in the continuous aqueous phase that determines the initial antimicrobial activity of the composition. The active agent present in the surfactant micelles serves as a reservoir of active agent to replenish the continuous aqueous phase as the active agent is depleted, and helps provide a residual antimicrobial activity.

[0047] To summarize, the thermodynamic activity, or percent saturation, of an antimicrobial agent in the continuous aqueous phase of a composition helps drive antimicrobial activity. Further, the total amount of available active agent, and the length of time the active agent remains on the treated surface, determines the ultimate extent of efficacy. In compositions wherein the active agent is solubilized by a surfactant, the active agent present in surfactant micelles is not immediately available for antimicrobial activity. For such compositions, the percent saturation of the active agent in the composition, or alternatively the percent saturation of the active agent in the continuous aqueous phase of the composition, determines initial antimicrobial efficacy.

[0048] The present methods utilize an activated antibacterial composition comprising an antimicrobial agent present in an amount of at least 25% saturation in the continuous aqueous phase of the composition, when measured at 25°C. The activated antibacterial composition provides a rapid and efficient kill of CA-MRSA, and imparts a residual kill of CA-MRSA on both animate and inanimate surfaces treated with an activated antibacterial composition.

[0049] An activated antibacterial composition utilized in the present method of controlling CA-MRSA can be a leave-on or a rinse-off composition. A leave-on composition is exemplified by a hand sanitizing gel, and a rinse-off composition is exemplified by an antibacterial cleansing composition.

[0050] As illustrated in detail below, the present invention is directed to a method of imparting a fast and a residual control of CA-MRSA to treated skin. The present method efficaciously and rapidly disinfects animate and inanimate surfaces that are infected or contaminated with CS-MRSA. The present method also provides a residual effectiveness against CA-MRSA to prevent future CA-MRSA contaminations.

[0051] As used herein, the term "residual efficacy" means leaving a residue or imparting a condition on animate (e.g., skin) or inanimate surfaces that provides significant activity against CA-MRSA for an extended time after application. The method of the present invention provides a rapid and a residual efficacy against CA-MRSA, i.e., preferably a log reduction of at least a log 2, against CA-MRSA, within 30 seconds of contact with an activated antibacterial composition. Activity against CA-MRSA preferably is maintained for at least about 0.5 hour, preferably at least about one hour, and more preferably for at least about two hours, at least about three hours, and at least about four hours after contact with the composition. In some preferred embodiments, activity against CA-MRSA is maintained for about six to about eight hours after contact with the composition.

[0052] The present method can be practiced in vitro and in vivo. In vitro means in or on nonliving things, especially on inanimate objects having hard or soft surfaces located or used where preventing CA-MRSA transmission is desired, most especially on objects that are touched by human hands. In vivo means in or on animate objects, especially on mammalian skin, and particularly on hands.

[0053] An activated antibacterial cleansing composition utilized in the present method comprises (a) about 0.1% to about 10%, by weight, of a phenolic antimicrobial agent; (b) about 0.1% to about 40%, by weight, of a surfactant; (c) 0% to about 30%, by weight, of a hydric solvent; (d) 0% to about 40%, by weight, of a hydrotrope; and (e) water, wherein the antimicrobial agent is present in a continuous aqueous phase of the composition in an amount of at least 25% of saturation concentration, when measured at 25°C (as disclosed in U.S. Patent No. 6,107,261, incorporated herein by reference), and the composition contains at least one of (c) and (d). In preferred embodiments, the activated composition contains both (c) and (d).

[0054] In embodiments wherein the activated antibacterial composition is a hand sanitizing gel, the composition typically contains an antimicrobial agent and a disinfecting alcohol, typically methanol, ethanol, proponal, isopropyl alcohol, or a mixture thereof. Activated hand sanitizer gels are disclosed in U.S. Patent No. 6,136,771, incorporated herein by reference.

[0055] In general, activated hand sanitizer gels typically contain: (a) about 1% to about 75%, by weight, of a disinfecting alcohol, such as ethanol or a combination of lower alcohols, like ethanol and isopropanol, (b) about 0.1% to about 5% of a phenolic antimicrobial agent, (c) water, (d) an optional gelling agent, such as a crosslinked polyacrylate material, and (e) other optional ingredients, such as skin conditioners, fragrances, polyhydric solvents, and the like. The hand sanitizer gel also has a percent saturation of antibacterial agent in the continuous aqueous phase of the composition of at least 25%, when measured at 25°C.

[0056] To achieve the desired CA-MRSA kill in a short contact time, like 15 to 60 seconds, the continuous aqueous phase of the activated composition contains an amount of antimicrobial agent that is at least about 25%, preferably at least about 30%, 40%, or 50%, or at least about 55%, 60%, 65%, or 70%, and more preferably at least about 75%, 80%, 85%, or 90% of the saturation concentration of the antimicrobial agent in water, when measured at room temperature. To achieve the full advantage of the present invention, the continuous aqueous phase is about 95% to 100% saturated with the antimicrobial agent. The method of determining percent saturation of antibacterial agent in the composition is disclosed in U.S. Patent No. 6,107,261, incorporated herein by reference.

[0057] The activated antibacterial composition typically is a mild, and preferably mildly acidic to neutral, composition. Preferred activated antibacterial compositions are disclosed, for example, in U.S. Patent Nos. 6,107,261 and 6,136,771, each incorporated herein by reference. An example of a useful commercial neutral to mildly acidic cleansing composition is Dial Complete, available from The Dial Corporation, Scottsdale, AZ.

[0058] The activated antibacterial composition contains an active antibacterial agent, a surfactant, a hydrotrope, a hydric solvent, a disinfecting alcohol, a gelling agent, and various other optional ingredients, for example, dyes, fragrances, pH adjusters, thickeners, skin conditioners, and the like, in an aqueous and/or alcoholic carrier. An active antimicrobial agent is a phenolic compound, such as halo-substituted phenolic compounds, like PCMX (i.e., p-chloro-m-xylenol) and triclosan (i.e., 2,4,4'-trichloro-2'- hydroxydiphenylether).

[0059] More particularly, an antimicrobial agent can be present in an activated antibacterial composition in an amount of 0.1% to about 10%, and preferably about 0.1% to about 5%, or about 0.1% to about 2%, and more preferably, about 0.3% to about 1%, by weight of the composition.

[0060] Phenolic antimicrobial agents useful in the present invention are exemplified by the following:

[0061] (a) 2-Hydroxydiphenyl compounds

[0062] wherein Y is chlorine or bromine, Z is SO₃H, NO₂, or Ci-C₄ alkyl, r is 0 to 3, o is 0 to 3, p is 0 or 1 , m is 0 or 1 , and n is 0 or 1.

[0063] In preferred embodiments, Y is chlorine or bromine, m is 0, n is 0 or 1, o is 1 or 2, r is 1 or 2, and p is 0.

[0064] In especially preferred embodiments, Y is chlorine, m is 0, n is 0, o is 1, r is 2, and p is 0.

[0065] A particularly useful 2-hydroxydiphenyl compound has a structure:

having the adopted name, triclosan, and available commercially under the tradename IRGASAN DP300, from Ciba Specialty Chemicals Corp., Greensboro, NC. Another useful 2-hydroxydiphenyl compound is 2,2'-dihydroxy-5,5'-dibromo-diphenyl ether. [0066] Phenol derivatives also are useful, for example,

[0067] wherein Ri is hydro, hydroxy, C₁-C₄ alkyl, chloro, nitro, phenyl, or benzyl; R₂ is hydro, hydroxy, Ci-C₆ alkyl, or halo; R₃ is hydro, C₁-C₆ alkyl, hydroxy, chloro, nitro, or a sulfur in the form of an alkali metal salt or ammonium salt; R₄ is hydro or methyl; and R₅ is hydro or nitro. Halo is bromo or, preferably, chloro.

[0068] Specific examples of phenol derivatives include, but are not limited to, chlorophenols (o-, m-, p-), 2,4-dichlorophenol, p-nitrophenol, picric acid, xylenol, p-chloro- m-xylenol, cresols (o-, m-, p-), p-chloro-m-cresol, pyrocatechol, resorcinol, 4-n- hexylresorcinol, pyrogallol, phloroglucin, carvacrol, thymol, p-chlorothymol, o- phenylphenol, o-benzylphenol, p-chloro-o-benzylphenol, phenol, 4-ethylphenol, and 4- phenolsulfonic acid. Other phenol derivatives are listed in U.S. Patent No. 6,436,885, incorporated herein by reference.

[0069] Additional useful antimicrobial agents are diphenyl compounds, exemplified by

[0070] wherein X is sulfur or a methylene group, R₆ and R'₆ are hydroxy, and R₇, R'₇,

Rg, R'₈, R₉, R'9, Rio, and R'io, independent of one another, are hydro or halo. Specific, nonlimiting examples of diphenyl compounds are hexachlorophene, tetrachlorophene, dichlorophene, 2,3-dihydroxy-5,5'-dichlorodiphenyl sulfide, 2,2'-dihydroxy-3,3',5,5'- tetrachlorodiphenyl sulfide, 2,2'-dihydroxy-3,5¹,5,5',6,6'-hexachlorodiphenyl sulfide, and 3,3'- dibromo-5,5'-dichloro-2,2'-dihydroxydiphenylamine. Other diphenyl compounds are listed in U.S. Patent No. 6,436,885, incorporated herein by reference. [0071] In preferred embodiments, a residual amount of the active antibacterial agent remains on a treated surface, such as the skin, even after an optional rinsing step, in order to impart a residual, or extended, control of CA-MRSA on the treated surface.

[0072] A surfactant is present in an activated antibacterial composition in a sufficient amount to clean the skin, but not in an amount that adversely affects the ability of the antibacterial agent to control CA-MRSA or that provides a harsh composition. The surfactant therefore is present in a sufficient amount such that the % saturation of the phenolic antibacterial agent in the continuous aqueous phase of the composition is at least 25%, when measured at 25⁰C.

[0073] Preferred surfactants that achieve a high level of soil and sebum removal are anionic surfactants, like a C₈-Ci₈ alkyl sulfate, a C₈-Ci₈ fatty acid salt, a C₈-Ci_S alkyl ether sulfate having one or two moles of ethoxylation, a Cs-Ci₈ alkamine oxide, a Cs-Ci₈ alkyl sarcosinate, a Cs-Ci₈ sulfoacetate, a C₈-Ci₈ sulfosuccinate, a C₈-Ci₈ alkyl diphenyl oxide disulfonate, a C₈-Ci₈alkyl carbonate, a C₈-Ci₈ alpha-olefin sulfonate, a methyl ester sulfonate, and mixtures thereof. The surfactant also can be a nonionic or amphoteric surfactant to increase the mildness of the activated composition. Any combination of anionic, nonionic, and amphoteric surfactant also can be used in the activated antibacterial composition, as disclosed in U.S. Patent No. 6,107,621.

[0074] As used herein, the term "hydric solvent" encompasses both disinfecting alcohols and polyhydric solvents. One embodiment of the present invention contains 0% to about 30%, by weight, of a hydric solvent, and 0% to about 30%, by weight, of a hydrotrope, wherein the antibacterial composition contains at least one of the hydric solvent and hydrotrope. Preferred embodiments contain both a hydric solvent and a hydrotrope.

[0075] As defined herein, the term "hydric solvent" is a water-soluble organic compound containing one to six, and typically one to three, hydroxyl groups. The term "hydric solvent" therefore encompasses water-soluble alcohols, diols, triols, and polyols. Specific examples of hydric solvents include, but are not limited to, methanol, ethanol, isopropyl alcohol, n-butanol, n-propyl alcohol, ethylene glycol, propylene glycol, glycerol, diethylene glycol, dipropylene glycol, tripropylene glycol, hexylene glycol, butylene glycol, 1,2,6-hexanetriol, sorbitol, PEG-4, and similar hydroxyl-containing compounds.

[0076] Preferred embodiments contain about 2% to about 20%, by weight, of a hydric solvent and/or about 2% to about 25%, by weight, of a hydrotrope. Most preferred embodiments contain about 5% to about 15%, by weight, of a hydric solvent and/or about 5% to about 20%, by weight, of a hydrotrope.

[0077] Activated hand sanitizer gels used in the present method contain about 1 % to about 75%, by weight, of a disinfecting alcohol. Preferred embodiments of the present invention contain about 2% to about 60%, by weight, of a disinfecting alcohol. Most preferred embodiments contain about 5% to about 40%, by weight, of a disinfecting alcohol. As used herein, the term "disinfecting alcohol" is a water-soluble alcohol containing one to six carbon atoms, i.e., a Ci-βalcohol. Disinfecting alcohols include, but are not limited to, methanol, ethanol, propanol, and isopropyl alcohol.

[0078] A hydrotrope, if present at all, is present in an amount of about 0.1% to about

30%, and preferably about 1% to about 20%, by weight of the activated composition. A hydrotrope is a compound that has an ability to enhance the water solubility of other compounds. A hydrotrope lacks surfactant properties, and typically is a short-chain alkyl aryl sulfonate. Specific examples of hydrotropes include, but are not limited to, sodium cumene sulfonate, ammonium cumene sulfonate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, and xylene sulfonic acid. Other useful hydrotropes include sodium polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl naphthalene sulfonate, sodium camphor sulfonate, and disodium succinate.

[0079] A polyhydric solvent, if present at all, is present in an amount of about 0.1% to about 30%, and preferably about 5% to about 30%, by weight of the activated composition. In contrast to a disinfecting alcohol, a polyhydric solvent contributes minimally, if at all, to the antimicrobial efficacy of the present composition. The term "polyhydric solvent" as used herein is a water-soluble organic compound containing two to six, and typically two or three, hydroxyl groups. The term "water-soluble" means that the polyhydric solvent has a water solubility of at least 0.1 g of polyhydric solvent per 100 g of water at 25°C. There is no upper limit to the water solubility of the polyhydric solvent, e.g., the polyhydric solvent and water can be soluble in all proportions.

[0080] The term polyhydric solvent, therefore, encompasses water-soluble diols, triols, and polyols. Specific examples of hydric solvents include, but are not limited to, ethylene glycol, propylene glycol, glycerol, diethylene glycol, dipropylene glycol, tripropylene glycol, hexylene glycol, butylene glycol, 1 ,2,6-hexanetriol, sorbitol, PEG-4, PPG-9, and similar polyhydroxy compounds.

[0081] In some preferred embodiments, an activated composition contains both a polyhydric solvent and a hydrotrope. In this embodiment, the polyhydric solvent and hydrotrope, independently, can be present in an amount of about 0.1% to about 30%, by weight of the composition.

[0082] An activated antibacterial composition also can contain optional ingredients well known to persons skilled in the art. The optional ingredients are present in a sufficient amount to perform their intended function and not adversely affect the antibacterial efficacy of the activated composition. Classes of optional ingredients include, but are not limited to, dyes, fragrances, pH adjusters, thickeners, viscosity modifiers, buffering agents, foam stabilizers, antioxidants, foam enhancers, chelating agents, opacifiers, and similar classes of optional ingredients known to person skilled in the art. Optional ingredients also include alkanolamides as foam boosters and stabilizers; inorganic phosphates, sulfates, and carbonates as buffering agents; EDTA and phosphates as chelating agents; and acids and bases as pH adjusters.

[0083] Examples of preferred classes of optional basic pH adjusters are ammonia; mono-, di-, and tri-alkyl amines; mono-, di-, and tri-alkanolamines; alkali metal and alkaline earth metal hydroxides; and mixtures thereof. Specific, nonlimiting examples of basic pH adjusters are ammonia; sodium, potassium, and lithium hydroxide; monoethanolamine; triethylamine; isopropanolamine; diethanolamine; and triethanolamine. Examples of preferred classes of optional acidic pH adjusters are the mineral acids. Nonlimiting examples of mineral acids are hydrochloric acid, nitric acid, phosphoric acid, and sulfuric acid.

[0084] The activated antibacterial compositions also optionally can contain 0%, or about 0.01%, to about 5%, by weight, and preferably 0.1% to about 3%, by weight, of an gelling agent. The term "gelling agent" as used here and hereafter refers to a compound capable of increasing the viscosity of a water-based composition, or capable of converting a water-based composition to a gel or semisolid. The gelling agent can be organic in nature, for example, a natural gum or a synthetic polymer, or can be inorganic in nature. The activated compositions typically contain a sufficient amount of gelling agent such that the composition is a viscous liquid, gel, or semisolid that can be easily applied to, and rubbed on, the skin or other surface. Persons skilled in the art are aware of the type and amount of gelling agent to include in the composition to provide the desired composition viscosity or consistency.

[0085] Exemplary gelling agents present in an activated antibacterial composition include, but are not limited to,

[0086] The following is a nonlimiting example of an activated composition useful in the present method.

Example 1

[0087] A composition in accordance with the present invention was prepared using the following ingredients in the following weight percentages:

[0088] The composition was prepared by combining the triclosan, propylene glycol, fragrance, and ethanol, and admixing the components until all the triclosan is dissolved, as evidenced by the absence of undissolved solid material. The sodium xylene sulfonate then is added, and the resulting mixture is stirred until the sodium xylene sulfonate is completely dissolved. Finally, the alkyl polyglycoside and water are added, and the mixture again is stirred until homogeneous.

Example 2

[0089] A composition in accordance with the instant invention, was prepared. The composition contained the following components in the indicated weight percentages:

[0090] The composition was prepared by admixing the dipropylene glycol, triclosan, and fragrance until homogeneous (about 5 minutes). After the triclosan was completely dissolved, as evidenced by the absence of undissolved solid material, the sodium xylene sulfonate was added to the solution. The resulting mixture then was stirred to completely dissolve the sodium xylene sulfonate (about 5 minutes). Finally, the ammonium lauryl sulfate and water were added to the resulting solution, and the composition was stirred until homogeneous (about 5 minutes).

Example 3

[0091] A composition in accordance with the present invention, suitable for use as a hand wash, was prepared. The composition comprised the following components at the indicated weight percentages:

[0092] The composition was prepared by first admixing the triclosan and dipropylene glycol until homogeneous (about 5 minutes). After the triclosan was completely dissolved, as evidenced by the absence of the undissolved solid material, the sodium xylene sulfonate was added to the solution. The mixture then was stirred to completely dissolve the sodium xylene sulfonate (about 5 minutes). Finally, the ammonium lauryl sulfate and water were added to the resulting solution, and the composition was stirred until homogeneous (about 5 minutes). The composition had a weight ratio of surfactanttriclosan of 2.5:1 and was at least about 90% saturated with triclosan.

Example 4

[0093] A composition in accordance with the present invention incorporating p- chloro-m-xylene as the active antibacterial ingredient was prepared. The composition contained the following components in the indicated weight percentages:

[0094] The composition was prepared by first combining the PCMX and water, then adding the ammonium lauryl sulfate and mixing the components for such time as to completely admix the components and dissolve the PCMX (about 2 hours). The composition was at least about 90% saturated with PCMX. Example 5

[0095] Compositions of the present invention can contain a wide variety of gelling agents, hydric solvents, and antibacterial active agents, illustrated by the following examples. In Table 1 below, all weight percentages are as active material, except where indicated by a "*," which indicates an "as-is" weight. The composition exhibited acceptable clarity, stability, and performance.

Table 1

a) Dipropylene glycol (DPG), Dow Chemical Co., Midland, Mich., b) p-Chloro-m-xylenol (PCMX), NIPACIDE PX-R, Nipa Inc., Wilmington, Del. (about 100% active), c) Glyceryl polymethacrylate and propylene glycol (LUBRAGEL DV), International Specialty Products, Wayne, NJ. (about 46% active), d) CARBOPOL ULTREZ 10 (ULTREZ 10), crosslinked polyacrylate acid, BF Goodrich Specialty Chemicals, Cleveland, Ohio (about 98% active), e) Isopropanol (IPA), Fisher Scientific, Pittsburgh, PA, 2-Propanol, HPLC Grade A 451-4, f) Liquid Perfume (PF), g) Diisopropylamine, Air Products and Chemicals, Allentown, Pa. (about 100% active) h) Propylene glycol (PG), Dow Chemical Co., USP Grade (active level=99.96%) i) LAPONITE XLG (lithium magnesium silicate, synthetic smectite clay), Southern Clay Products, Gonzales, Tex. (about 99% active), j) CELQUAT CS230M (Polyquaternium 10), National Starch and Chemical Company, Bridgewater, NJ. (about 92% active), k) Tπclosan (TCS), IRGASAN DP-300, Ciba Specialty Chemicals Corp., Greensboro, NC (GC assay on lots used=99.8-99.9% active TCS; mp-56.0-58.0 C),

1) Propylene glycol-9 (PPG-9), Polyglycol P425, Dow Chemical Company, Midland, Michigan (about 100% active) m) Water — distilled or deionized, n) Ethanol (Denatured Ethyl Alcohol 40B), Gold Shield, Hayward, California (about 100% active).

[0096] To demonstrate the new and unexpected results provided by the method of the present invention, the following composition was prepared, and the ability of the composition to control CA-MRSA was determined. The weight percentage listed represents the actual, or active, weight amount of each ingredient present in the composition. The compositions are prepared by blending the ingredients, as understood by those skilled in the art and as described below.

[0097] The following method is used in the testing of the composition:

[0098] a) Determination of Rapid Germicidal (Time Kill) Activity of

Antibacterial Products. The activity of antibacterial compositions is measured by the time kill method, whereby the survival of challenged organisms exposed to an antibacterial test composition is determined as a function of time. In this test, a diluted aliquot of the composition is brought into contact with a known population of test bacteria for a specified time period at a specified temperature. The test composition is neutralized at the end of the time period, which arrests the antibacterial activity of the composition. The percent or, alternatively, log reduction from the original bacteria population is calculated.

[0099] In general, the time kill method is known to those skilled in the art.

[00100] The composition can be tested at any concentration up to 100%. The choice of which concentration to use is at the discretion of the investigator, and suitable concentrations are readily determined by those skilled in the art. For example, viscous samples usually are tested at 50% dilution, whereas nonviscous samples are not diluted. The test sample is placed in a sterile 250 ml beaker equipped with a magnetic stirring bar and the sample volume is brought to 100 ml, if needed, with sterile deionized water. All testing is performed in triplicate, the results are combined, and the average log reduction is reported.

[00101] The choice of contact time period also is at the discretion of the investigator.

Any contact time period can be chosen. Typical contact times range from 15 seconds to 5 minutes, with 30 seconds and 1 minute being typical contact times. The contact temperature also can be any temperature, typically room temperature, i.e., 25 degrees Celsius.

[00102] The bacterial suspension, or test inoculum, is prepared by growing a bacterial culture on any appropriate solid media (e.g., agar). The bacterial population then is washed from the agar with sterile physiological saline and the population of the bacterial suspension is adjusted to about 10⁸ colony forming units per ml (cfu/ml). [00103] The table below lists the test bacterial culture used in the test and includes the name of the bacteria, the ATCC (American Type Culture Collection) identification number, and the abbreviation for the name of the organism used hereafter.

[00104] The beaker containing the test composition is placed in a water bath (if constant temperature is desired), or placed on a magnetic stirrer (if ambient laboratory temperature is desired). The sample then is inoculated with 1.0 ml of the test bacteria suspension. The inoculum is stirred with the test composition for the predetermined contact time. When the contact time expires, 1.0 ml of the test composition/bacteria mixture is transferred into 9.0 ml of Neutralizer Solution. Decimal dilutions to a countable range then are made. The dilutions can differ for different organisms. Selected dilutions are plated in triplicate on TSA+ plates (TSA+ is Trypticase Soy Agar with Lecithin and Polysorbate 80). The plates then are incubated for 24±2 hours, and the colonies are counted for the number of survivors and the calculation of percent or log reduction. The control count (numbers control) is determined by conducting the procedure as described above with the exception that deionized water is used in place of the test composition. The plate counts are converted to cfu/ml for the numbers control and samples, respectively, by standard microbiological methods.

[00105] The log reduction is calculated using the formula

Log reduction=logi o(numbers controlled)-logio (test sample survivors).

[00106] The following table correlates percent reduction in bacteria population to log reduction:

Example 1

[00107J Activated antibacterial compositions were prepared and tested for an ability to control CA-MRSA. A time kill kinetic study was performed to determine the antibacterial efficacy of the activated triclosan compositions (A and B) against a strain of CA-MRSA. A sample of a leading healthcare personal hand wash product, i.e., Hibiclens containing 4% chlorhexidine gluconate (CHG) (C), and a retail antibacterial soap (Softsoap) containing 0.2% triclosan also were evaluated (D). The data in the following table show a significant reduction in CA-MRSA using the above activated triclosan compositions. These compositions reduced CA-MRSA by greater than 4 log within 30 seconds. The leading hospital product, i.e., Hibiclens, showed a moderate activity, but significantly less than the activated triclosan formula. The nonactivated retail soap containing triclosan failed to show any efficacy against CA-MRSA.

A=Dial Complete with 0.95% triclosan;

B=Dial Complete with 0.57% triclosan;

C=Hibiclens with 4% chlorhexidine gluconate (comparative); and

D=Softsoap with 0.2% triclosan (comparative).

Example 2

[00108] An activated antibacterial composition containing 0.45%, by weight, triclosan was evaluated against CA-MRSA ATCC 33592 using the ASTM Method E-1174-00 Standard Method for the Evaluation of Healthcare Personnel Handwash Formulation. Modifications to this method include the use of a neutralizing buffer to ensure complete inactivation of the active at sampling times.

[00109] In this test, hands of the test subjects were contaminated with a suspension of the marker organism (i.e., CA-MRSA ATCC 33592). The hands were washed with test article, then sampled for recovery of marker organism. LoglO reductions in bacteria population were calculated from the log 10 baseline recovery minus each log 10 treatment wash to reflect the ability of the antibacterial composition to reduce the population of marker organism on the hands.

[00110] Samples were serial diluted using phosphate buffer solution. Dilutions were plated using Tyrptic Soy Agar with lethicin and polysorbate 80. Plates were incubated for 48 hours at 37° C.

[00111] The data shows that an activated antibacterial composition disrupts the transmission of CA-MRSA, (>99.0 %), thereby preventing and mitigating skin or other infections caused by CA-MRSA.

[00112] Activated antimicrobial compositions useful in the present method have several practical forms, including hand cleansers, surgical scrubs, body splashes, antiseptics, disinfectants, hand sanitizer gels, deodorants, and similar personal care products. Additional types of compositions include foamed compositions, such as mousses and the like, and compositions containing organic and inorganic filler materials, such as emulsions, lotions, creams, pastes, and the like. The compositions further can be used on inanimate surfaces, for example, sinks and countertops in hospitals, cruise ships, nursing homes, locker rooms, athletic clubs, military barracks, schools, food service areas, and meat processing plants.

[00113] As discussed above, both animate and inanimate surfaces can be treated in accordance with the method of the present invention. A particularly important surface is mammalian skin, and particularly human skin, to inactivate CA-MRSA, and, in turn, interrupt the transmission of CA-MRSA. However, the present method also is useful in treating inanimate surfaces of all types.

[00114] The present method is useful to treat hard surfaces. As used herein with respect to the surfaces treated by the present compositions, the term "hard" refers to surfaces comprising refractory materials, such as glazed and unglazed tile, brick, porcelain, ceramics, metals, glass, and the like, and also includes wood and hard plastics such as formica, polystyrenes, vinyls, acrylics, polyesters, and the like. Such surfaces are found, for example, in kitchens and bathrooms. A hard surface can be porous or nonporous. [00115] The present method also can be used to treat hard surfaces in processing facilities (such as dairy, brewing, and food processing facilities), healthcare facilities (such as hospitals, clinics, surgical centers, dental offices, and laboratories), long-term healthcare facilities (such as nursing homes), farms, cruise and naval ships, schools, athletic facilities, health clubs, spas, military installations, and private homes.

[00116] The present method can be used to treat environmental surfaces such as floors, walls, ceilings, and drains. The method can be used to treat equipment such as food processing equipment, dairy processing equipment, brewery equipment, and the like. The compositions can be used to treat a variety of surfaces including food contact surfaces in food, dairy, and brewing facilities, countertops, furniture, sinks, telephones, and the like. The method further can be used to treat tools and instruments, such as medical tools and instruments, dental tools and instruments, as well as equipment used in the healthcare industries and institutional kitchens, including knives, wares (such as pots, pans, and dishes, cutting equipment, and the like). Methods of treating hard surfaces are described in U.S. Patent Nos. 5,200,189; 5,314,687; and 5,718,910, the disclosures of which are incorporated herein by reference in their entirety.

[00117] In addition to the hard surfaces, the method can be used to treat textiles, such as clothing, protective clothing, laboratory clothing, surgical clothing, patient clothing, carpets, bedding, towels, linens, and the like.

[00118] In use, the activated antibacterial compositions are applied to contact a target surface. The surface can be animate or inanimate. The compositions can be applied by dipping a surface into the composition, soaking a surface in the composition, or spraying, wiping, brushing, foaming, misting, rolling, pad coating, or fogging the composition onto a surface. The compositions can be applied manually, using equipment, such as a spray bottle, or by machine, such as a spray machine, foam machine, and the like. The compositions also can be used inside a machine, such as a warewashing machine or laundry machine.

[00119] Treatable inanimate surfaces include, but are not limited to, exposed environmental surfaces, such as tables, floors, walls; kitchenwares, including pots, pans, knives, forks, spoons, and plates; food cooking and preparation surfaces, including dishes; food preparation equipment; and tanks, vats, lines, pumps, hoses, and other process equipment. One useful application of the composition is to dairy processing equipment, which is commonly made from glass or stainless steel. Such equipment can be found both in dairy farm installations and in dairy plant installations for the processing of milk, cheese, ice cream, and other dairy products.

[00120] The method of the present invention also can be used in the manufacture of beverages, including fruit juice, dairy products, malt beverages, bottled water products, teas, and soft drinks. The method can be used to treat pumps, lines, tanks, and mixing equipment used in the manufacture of such beverages. The method of the present invention also can be used to treat air filters.

[00121] The method of the present invention also can be used to treat medical carts, medical cages, and other medical instruments, devices, and equipment. Examples of medical apparatus treatable by the present method are disclosed in U.S. Patent No. 6,632,291, incorporated herein by reference.

[00122] For household applications, hand-operated pump-type or pressurized aerosol sprayers can be used. The compositions also can be employed to coat or otherwise treat materials such as sponges, fibrous or nonfibrous web materials, swabs, flexible plastics, textiles, wood, and the like. Generally, the coating process is used to impart prolonged activity against CA-MRSA to a hard porous or nonporous surface by coating said surface with the composition. The activated compositions also can be incorporated into a web material to provide an antimicrobial wiping article. The wiping article can be used to sanitize animate or inanimate surfaces.

[00123] The present invention, therefore, encompasses applying an effective amount of an activated antimicrobial composition onto inanimate surfaces, such as household surfaces, e.g., countertops, kitchen surfaces, food preparing surfaces (cutting boards, dishes, pots and pans, and the like); major household appliances, e.g., refrigerators, freezers, washing machines, automatic dryers, ovens, microwave ovens, and dishwashers; cabinets; walls; floors; bathroom surfaces, shower curtains, garbage cans, and/or recycling bins, and the like.

[00124] In one embodiment of the present invention, a person suffering from a CA-

MRSA infection, or who is likely to be exposed to other individuals suffering from a CA- MRSA infection, can apply an activated antimicrobial composition to his or her hands. This application kills the CA-MRSA present on the hands. The applied composition, either rinsed off or allowed to remain on the hands, preferably provides a residual activity against CA- MRSA. CA-MRSA, therefore, is not transmitted to noninfected individuals via hand-to-hand transmission. The amount of the composition applied, the frequency of application, and the period of use will vary depending upon the level of disinfection desired, e.g., the degree of microbial contamination and/or skin soiling.

[00125] The activated antimicrobial compositions provide the advantages of a substantial CA-MRSA control in short contact times. The short contact time for a substantial log reduction of CA-MRSA is important in view of the typical 15 to 60 second time frame used to sanitize the skin and inanimate surfaces. The composition preferably imparts a residual activity against CA-MRSA to the contacted surface.

[00126] The present compositions are effective in short contact time because the antimicrobial agent is present in the aqueous continuous phase of the composition, as opposed to surfactant micelles. The antimicrobial agent, therefore, is available to immediately begin reducing CA-MRSA populations, and further is available to deposit on the skin to provide a residual efficacy against CA-MRSA. In addition, because the antimicrobial agent is in solution as opposed to surfactant micelles, the absolute amount of antimicrobial agent in the composition can be reduced without adversely affecting efficacy, and the antimicrobial agent is not rinsed from the skin with the surfactant prior to performing its antimicrobial function.

[00127] Obviously, many modifications and variations of the invention as hereinbefore set forth can be made without departing from the spirit and scope thereof, and, therefore, only such limitations should be imposed as are indicated by the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A method of reducing a population of community- acquired methicillin- resistant Staphylococcus aureus (CA-MRSA) on an animate or inanimate surface comprising contacting the surface with an activated antibacterial composition capable of achieving a log reduction of at least 2 against a CA-MRSA after 30 seconds of contact.

2. The method of claim 1 wherein the activated antibacterial composition comprises:

(a) about 0.1% to about 10%, by weight, of a phenolic antimicrobial agent;

(b) about 0.1% to about 40%, by weight, of a surfactant;

(c) 0% to about 30%, by weight, of a hydric solvent;

(d) 0% to about 40%, by weight, of a hydrotrope; and

(e) water, wherein the antimicrobial agent is present in a continuous aqueous phase of the composition in an amount of at least 25% of saturation concentration, when measured at 25°C, and the composition contains at least one of (c) and (d).

3. The method of claim 1 wherein the activated antibacterial composition comprises:

(a) about 0.1% to about 5%, of a phenolic antimicrobial agent;

(b) about 1% to about 75% of a disinfecting alcohol;

(c) 0% to about 3%, by weight, of a gelling agent; and

(d) water, wherein the antimicrobial agent is present in a continuous aqueous phase of the composition in an amount of at least 25% of saturation concentration, when measured at

25°C.

4. The method of claim 3 wherein the activated composition further comprises a surfactant.

5. The method of claim 2 or 4 wherein the surfactant comprises an anionic surfactant, a nonionic surfactant, an amphoteric surfactant, or a mixture thereof.

6. The method of claim 2 or 3 wherein the antimicrobial agent is present in the composition in an amount of at least 50% of saturation concentration, when measured at

25°C.

7. The method of claim 2 or 3 wherein the antimicrobial agent is present in an amount of at least 75% of saturation concentration.

8. The method of claim 2 or 3 wherein the antimicrobial agent is present in an amount of at least 95% of saturation concentration.

9. The method of claim 2 wherein the activated composition comprises both a hydric solvent and a hydrotrope.

10. The method of claim 2 or 3 wherein the composition comprises about 0.01% to about 2%, by weight, of the phenolic antimicrobial agent, said phenolic antimicrobial agent selected from the group consisting of:

(a) a 2-hydroxydiphenyl compound having the structure

.

wherein Y is chlorine or bromine, Z is SO₃H, NO₂, or C₁-C₄ alkyl, r is 0 to 3, o is 0 to 3, p is 0 or 1, m is 0 or 1, and n is 0 or 1;

(b) a phenol derivative having the structure

wherein Ri is hydro, hydroxy, Cj -C₄ alkyl, chloro, nitro, phenyl, or benzyl, R₂ is hydro, hydroxy, Ci-C₆ alkyl, or halo, R3 is hydro, Ci-C₆ alkyl, hydroxy, chloro, nitro, or a sulfur in the form of an alkali metal salt or ammonium salt, R₄ is hydro or methyl, and R₅ is hydro or nitro;

(c) a diphenyl compound having the structure

wherein X is sulfur or a methylene group, R₆ and R'₆ are hydroxy, and R₇, RV, Rs, R'g, R₉, R'₉, Rio, and R'jo, independent of one another, are hydro or halo; and

(d) mixtures thereof.

11. The method of claim 2 or 3 wherein the antimicrobial agent comprises triclosan, p-chloro-m-xylenol, or a mixture thereof.

12. The method of claim 3 wherein the disinfecting alcohol is present in the composition in an amount of about 2% to about 60%, by weight, and wherein the disinfecting alcohol comprises at least one Ci -₆ alcohol.

13. The method of claim 12 wherein the disinfecting alcohol is selected from the group consisting of methanol, ethanol, isopropyl alcohol, n-butanol, n-propyl alcohol, and mixtures thereof.

14. The method of claim 2 wherein the hydric solvent comprises an alcohol, a diol, a triol, or mixtures thereof.

15. The composition of claim 2 wherein the hydric solvent comprises methanol, ethanol, isopropyl alcohol, n-butanol, n-propyl alcohol, ethylene glycol, propylene glycol, glycerol, diethylene glycol, dipropylene glycol, tripropylene glycol, hexylene glycol, butylenes glycol, 1 ,2,6-hexanetriol, sorbitol, PEG-4, PPG-9, or mixtures thereof.

16. The method of claim 2 wherein the hydrotrope is selected from the group consisting of sodium cumene sulfonate, ammonium cumene sulfonate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, xylene sulfonic acid, sodium polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl naphthalene sulfonate, disodium succinate, and mixtures thereof.

17. The method of claim 1 further comprising a step of rinsing the activated composition from the surface.

18. The method of claim 1 wherein the activated composition is allowed to remain on the surface.

19. The method of claim 1 wherein the animate surface is a skin of a mammal.

20. The method of claim 19 wherein the skin has a log reduction against a CA-MRSA of at least 2.5 about five hours after contact with the composition.

21. The method of claim 1 wherein the activated composition imparts a residual activity against CA-MRSA to the surface.

22. A method of reducing the incidence of a CA-MRSA infection in a human population comprising contacting skin of one or more human with an activated antimicrobial composition capable of achieving a log reduction of at least 2 against a CA-MRSA after 30 seconds of contact.

23. The method of claim 22 wherein the activated composition is applied prior to the human being exposed to CA-MRSA.

24. The method of claim 22 wherein the activated composition is applied multiple times within a twenty-four-hour period.

25. The method of claim 22 wherein the composition is rinsed from the skin.

26. The method of claim 22 wherein the composition is allowed to dry and remain on the skin.