FDA is undertaking a review of active ingredients used in a variety of over-the-counter (OTC) antiseptic rubs and wash products. Health care antiseptics are being evaluated separately from consumer antiseptics because they have different proposed use settings and target populations, and the risks for infection in the different settings varies. More information about both is presented below.
FDA proposed that data was needed from a standard battery of tests that is used to determine the safety of many drugs, including OTC antiseptics. This array of tests has changed over time to incorporate improvements in safety testing. For more specific information on safety tests, please see the final rule on consumer antiseptic washes, the final rule on health care antiseptics, and the final rule on consumer antiseptic rubs.
FDA is not proposing clinical outcome studies for active ingredients when used in health care antiseptics or in consumer antiseptic rub products. FDA is requiring clinical simulation studies for health care antiseptics because of ethical concerns with conducting studies in the health care setting; FDA is requiring the clinical simulation studies for consumer antiseptic rubs because these products are intended for use when soap and water are not available, and so they need not demonstrate clinical effectiveness compared to soap and water. For specific information on the efficacy data requested for health care antiseptics and consumer antiseptic rubs, please see the final rules on health care antiseptics and final rule on consumer antiseptic rubs and their respective dockets.
Antiseptics reduce the number of microorganisms living on the skin, in wounds, and in mucous membranes. They can be particularly useful when an individual needs to cleanse the skin quickly. Many antiseptics are available to buy over-the-counter at pharmacies, making them convenient and easily accessible.
There is also the risk of product contamination from repeated use of topical antiseptics. This can lead to further problems such as localised or systemic infections when the contaminated product is reapplied to open skin, a wound, or a burn.
It is important to note that antiseptics may impair wound healing if they kill skin cells that are involved in the healing process, such as fibroblasts. Routine use of antiseptics for cleansing clean wounds is no longer recommended. Pus and necrotic tissue can also inactivate some antiseptics, reducing their efficacy.
Individuals using antiseptics need to do so correctly. Strong antiseptics should be appropriately diluted before being applied to the skin, as concentrated products may cause chemical burns or severe irritant contact dermatitis. Prolonged contact with dilute antiseptics can also cause erosive contact dermatitis, as described with chlorhexidine-impregnated dressings.
People with allergies of any kind should check with a doctor or pharmacist before using an over-the-counter antiseptic product. Some antiseptics can irritate the skin and cause allergic contact dermatitis.
Both antiseptics and disinfectants contain chemical agents that are sometimes called biocides. Hydrogen peroxide is an example of a common ingredient in both antiseptics and disinfectants. However, antiseptics usually contain lower concentrations of biocides than disinfectants do.
The Food and Drug Administration (FDA) recently banned 24 ingredients in OTC antiseptics, effective December 20, 2018. This is due to concerns about how long these ingredients can remain in the body and a lack of evidence regarding their safety and effectiveness.
Antibacterials include antiseptics that have the proven ability to act against bacteria. Microbicides which destroy virus particles are called viricides or antivirals. Antifungals, also known as antimycotics, are pharmaceutical fungicides used to treat and prevent mycosis (fungal infection).
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.
Whatever the type of microbial cell (or entity), it is probable thatthere is a common sequence of events. This can be envisaged asinteraction of the antiseptic or disinfectant with the cell surfacefollowed by penetration into the cell and action at the target site(s).The nature and composition of the surface vary from one cell type (orentity) to another but can also alter as a result of changes in theenvironment (57, 59). Interaction at the cell surface canproduce a significant effect on viability (e.g. with glutaraldehyde)(374, 421), but most antimicrobial agents appear to beactive intracellularly (428, 451). The outermost layers ofmicrobial cells can thus have a significant effect on theirsusceptibility (or insusceptibility) to antiseptics and disinfectants;it is disappointing how little is known about the passage of theseantimicrobial agents into different types of microorganisms.Potentiation of activity of most biocides may be achieved by the use ofvarious additives, as shown in later parts of this review.
Mycobacteria are generally highly resistant tochlorhexidine (419). Little is known about theuptake of chlorhexidine (and other antiseptics anddisinfectants) by mycobacteria and on the biochemical changes thatoccur in the treated cells. Since the MICs for some mycobacteria are onthe order of those for chlorhexidine-sensitive,gram-positive cocci (48), the inhibitory effects ofchlorhexidine on mycobacteria may not be dissimilar tothose on susceptible bacteria. Mycobacteriumavium-intracellulare is considerably more resistant than othermycobacteria (48).
A typical spore has a complex structure (29, 151). In brief,the germ cell (protoplast or core) and germ cell wall are surrounded bythe cortex, outside which are the inner and outer spore coats. A thinexosporium may be present in the spores of some species but maysurround just one spore coat. RNA, DNA, and DPA, as well as most of thecalcium, potassium, manganese, and phosphorus, are present in the sporeprotoplast. Also present are large amounts of low-molecular-weightbasic proteins (small acid-soluble spore proteins [SASPs]), which arerapidly degraded during germination. The cortex consists largely ofpeptidoglycan, including a spore-specific muramic lactam. The sporecoats comprise a major portion of the spore. These structures consistlargely of protein, with an alkali-soluble fraction made up of acidicpolypeptides being found in the inner coat and an alkali-resistantfraction associated with the presence of disulfide-rich bonds beingfound in the outer coat. These aspects, especially the roles of thecoat(s) and cortex, are all relevant to the mechanism(s) of resistancepresented by bacterial spores to antiseptics and disinfectants.
Spore coat-less forms, produced by treatment of spores under alkalineconditions with urea plus dithiothreitol plus sodium lauryl sulfate(UDS), have also been of value in estimating the role of the coats inlimiting the access of antiseptics and disinfectants to their targetsites. However, Bloomfield and Arthur (44, 45) andBloomfield (43) showed that this treatment also removes acertain amount of cortex and that the amount of cortex remaining can befurther reduced by the subsequent use of lysozyme. These findingsdemonstrate that the spore coats have an undoubted role in conferringresistance but that the cortex also is an important barrier since (UDSplus lysozyme)-treated spores are much more sensitive to chlorine- andiodine-releasing agents than are UDS-exposed spores.
Two other aspects of spores should be considered: the revival ofinjured spores and the effects of antiseptics and disinfectants ongerminating and outgrowing spores. Although neither aspect is truly aresistance mechanism, each can provide useful information about thesite and mechanism of action of sporicidal agents and about theassociated spore resistance mechanisms and might be of clinicalimportance.
Many years ago, it was proposed (T. H. Shen, cited in reference99) that the resistance of mycobacteria to QACs wasrelated to the lipid content of the cell wall. In support of thiscontention, Mycobacterium phlei, which has a low total celllipid content, was more sensitive than M. tuberculosis,which has a higher lipid content. It was also noted that the resistanceof various species of mycobacteria was related to the content of waxymaterial in the wall. It is now known that because of the highlyhydrophobic nature of the cell wall, hydrophilic biocides are generallyunable to penetrate the mycobacterial cell wall in sufficiently highconcentrations to produce a lethal effect. However, low concentrationsof antiseptics and disinfectants such as chlorhexidine mustpresumably traverse this permeability barrier, because the MICs are ofthe same order as those concentrations inhibiting the growth ofnonmycobacterial strains such as S. aureus, althoughM. avium-intracellulare may be particularly resistant(51, 52). The component(s) of the mycobacterial cell wallresponsible for the high biocide resistance are currently unknown,although some information is available. Inhibitors of cell wallsynthesis increase the susceptibility of M. avium todrugs (391); inhibition of myocide C, arabinogalactan, andmycolic acid biosynthesis enhances drug susceptibility. Treatment ofthis organism withm-fluoro-dl-phenylalanine(m-FL-phe), which inhibits mycocide C synthesis, producessignificant alterations in the outer cell wall layers(106). Ethambutol, an inhibitor of arabinogalactan(391, 501) and phospholipid (461, 462) synthesis,also disorganizes these layers. In addition, ethambutol induces theformation of ghosts without the dissolution of peptidoglycan(391). Methyl-4-(2-octadecylcyclopropen-1-yl) butanoate(MOCB) is a structural analogue of a key precursor in mycolic acidsynthesis. Thus, the effects of MOCB on mycolic acid synthesis andm-FL-phe and ethambutol on outer wall biosynthetic processesleading to changes in cell wall architecture appear to be responsiblefor increasing the intracellular concentration ofchemotherapeutic drugs. These findings support the concept of the cellwall acting as a permeability barrier to these drugs (425).Fewer studies have been made of the mechanisms involved in theresistance of mycobacteria to antiseptics and disinfectants. However,the activity of chlorhexidine and of a QAC, cetylpyridiniumchloride, against M. avium and M. tuberculosiscan be potentiated in the presence of ethambutol (52). Fromthese data, it may be inferred that arabinogalactan is one cell wallcomponent that acts as a permeability barrier tochlorhexidine and QACs. It is not possible, at present, tocomment on other components, since these have yet to be investigated.It would be useful to have information about the uptake into the cellsof these antiseptic agents in the presence and absence of differentcell wall synthesis inhibitors. 2b1af7f3a8