It is well established that skin flora plays an essential role in the development of wound infection.⁷,¹⁰,¹⁵,¹⁶,¹⁷ Because an important function of the skin is to serve as a barrier against infection, antiseptic treatment should not be toxic or damaging to the skin,¹⁸ cause skin reactions,¹⁹,²⁰ or interfere with the normal protective function of the skin.¹⁶,¹⁷ Indirect effects such as removal of skin lipids, interference with the “acid mantle,” and excessive drying may result in damage to skin, especially in frequent users of antiseptics such as surgeons and nurses.¹⁶ As assessed by using objective physiologic parameters by Larson et al,²¹,²³ frequent hand washing can cause some damage to the stratum corneum. Such physiologic studies are needed for all antiseptics in addition to assessing efficacy, toxicity, absorption, and inactivation.²⁴,²⁵,²⁶

The skin is a multilayered surface with irregular pits, ridges, and creases covered by cornified epithelial cells that are loosely attached to the deeper cell layers; thus, the skin provides a nesting place for bacterial flora and is also a potential source of airborne particles carrying microorganisms.²⁷ The surface is interrupted by the openings of sweat glands and pilosebaceous units. Because sweat is essentially sterile, slightly acidic, and flows continually,
it keeps the sweat ducts clean of bacteria. In contrast, the ducts of sebaceous glands contain fatty and proteinaceous materials as well as cells, cell detritus, and salts that can serve as nutrients for a number of organisms composing the resident flora. The fat covers the epidermal surface and makes it water repellent. Its composition changes with age and thereby affects the type and quantity of normal flora. Normal flora also differs on various parts of the body surface, depending on the distribution of the skin secretory glands and their activity; the type, size, and density of hair; bacterial adherence; and antimicrobial antagonism.⁶,⁷,⁸,⁹ In addition, certain regions of the body, such as the groin and the paragenital area of women, have extremely high bacterial counts (up to 10⁷ colony-forming units [CFUs]/mL stripping solution).²⁸ Others confirmed Price’s work from 1938 that the resident flora is concentrated mainly around and under fingernails.⁴,²⁹ Unfortunately, whereas it has been established that the subungual space is a significant reservoir of bacteria,³⁰ the routine surgical scrub is often ineffective at reducing the subungual counts to acceptable levels.³¹ Recognizing the subungual space as a good indicator of the efficacy of personnel hand washes and surgical scrubs, new methods were developed for testing antiseptics by assessing the fluid obtained from artificially contaminated hands after scrubbing the subungual space.³²

Many of these earlier studies have been verified in the detailed, molecular analysis of the microbiome on various parts of the skin and the role of resident and transient bacteria as part of a healthy population in comparison to a diseased or unhealthy skin state.³³,³⁴ These studies have verified that the microbial population can highly diverse and variable depending on the person, regional anatomy, environmental factors, and various host factors (eg, immune system, personal hygiene, and genetic factors). The range of microorganisms present is now known to be wider than first observed in traditional microbiological culture methods.⁷,⁸,⁹ The most commonly isolated bacteria included gram-positive, coagulase-negative staphylococci (eg, Staphylococcus epidermidis), Micrococcus, and Actinobacteria (eg, Corynebacterium and Propionibacterium species). Modern molecular techniques allow for the identification of a wider range of bacteria. Skin and mucous membrane bacteria are found to be in four major phyla: Actinobacteria (gram-positive bacteria such as Propionibacterium), Firmicutes (gram-positive bacteria such as Staphylococcus, Bacillus, and Clostridium), Bacteroidetes (gram-negative bacteria such as Bacteroides), and Proteobacteria (gram-negative bacteria such as Escherichia coli and Pseudomonas). The proportions of each of these can vary depending on the area of the skin or mucous membranes. For example, areas with increased moisture can lead to greater proportions of bacteria that grow well under humid conditions, such as gram-negative rods and Staphylococcus aureus, and areas with increased presence of sebaceous glands (eg, the face) see a greater proportion of lipophilic bacteria (eg, Propionibacterium) due to the production of sebum in these areas. In addition to bacteria, other members of the skin flora can include a wide range of resident and transient microorganisms such as fungi, arthropods, and viruses. Of particular note are Malassezia species of fungi and Demodex arthropods (mites) are often considered as resident skin flora.³³,³⁴

Despite the differentiation of transient and resident flora, both types of flora play important roles in the development of health care-acquired infection (HAI). Many transient bacteria are loosely attached to the lipoidal components of the skin and are generally considered easy to remove using mechanical means. Resident flora, on the other hand, is much more difficult to completely remove and are relatively stable in terms of the density and types of organisms; however, the simple historical notion that transient bacteria are bad and resident flora are harmless can no longer be supported. Researchers demonstrated during the S aureus epidemic in the 1950s and 1960s that this pathogen may become part of the resident flora and may even be disbursed in large quantities by shedders.²⁴ Gram-negative bacteria also may lodge persistently, especially in damaged or moist skin.³⁵ Gram-negative bacteria recovered from nurses’ hands after five consecutive hand washings with nonmedicated bar soap and tap water suggests that these organisms, found independently of patient contact, should be considered nontransient (or transitional) flora.³⁶ Regarding skin carriage of gram-negative bacteria, especially in the axilla, groin, and toe webs, it has been emphasized that each patient may carry his or her own environment.⁹,¹⁰ In addition, the skin flora of personnel from different hospital services (eg, dermatology and oncology) can differ in both its composition and its antimicrobial susceptibility.³⁷ Dermatology personnel showed S aureus more frequently, whereas oncology personnel had a significantly higher carriage of gram-negative bacteria, yeast, and multiple antibiotic-resistant Corynebacterium. The isolates from nurses were found to be generally more resistant to many antibiotics, and two-thirds of the oncology nurses had methicillin-resistant staphylococci. These results support more recent studies with skin flora, where the microbial flora can vary depending on environmental factors (such as working locations). Furthermore, it should be reemphasized that there is wide variation in log differences in the density of bacteria across various sites of the body, with relatively low counts on the palm and much higher counts at other sites, such as the axilla and forehead.⁶,⁷,⁸,⁹,¹⁰

Whereas antisepsis can be more or less successful on unbroken skin, its use on exposed or visceral mucosa, open wounds, and burns is more problematic. Side effects that result from increased absorption of the antimicrobial chemical by the tissue and by the reduction of its activity
by blood, exudates, and tissue result in less efficacious antiseptic regimens. Prevention of surgical infection and therapy of local infection are still considered achievable more effectively with systemic antibiotics.¹⁵,³⁸ Although there are many agents that can be specifically applied to wound and burn injuries to decrease infection, it should be emphasized that the primary therapy for prevention of infection in these settings is early mechanical or surgical debridement in association with early skin grafting of burn injuries. Antimicrobial agents, including antiseptics and antibiotics, should only be used in accordance with manufacturers’ label claims, and these can vary regionally. But despite the emphasis on the appropriate use of prophylactic antibiotics to reduce the risk of surgical site infections (SSIs), the parallel use of different antiseptics is recommended to include preoperative bathing (with antimicrobial soaps or antiseptic agents), use of 2% mupirocin ointment in the nares (for decolonization of methicillin-resistant S aureus [MRSA] carriers), surgical site preparation (with an emphasis on the use of alcohols or alcohol/chlorhexidine combinations), surgical hand preparation (uses of antimicrobial soaps or alcohol hand rubs prior to glove donning), and triclosan-containing sutures.¹⁵,³⁸

Since Lister’s³ work, surgeons have been aware that wound infections can be prevented by the topical use of antimicrobial chemicals. Because bacteriologists could demonstrate that bacteria on the skin of surgeons or patients could cause wound infections, hand washing and preoperative surgical scrubbing became part of the system of aseptic surgery introduced since 1882 by Trendelenburg, von Bergmann, and Schimmelbusch in Germany and by Halsted in the United States. Antisepsis and asepsis contributed to the rapid development of surgery, and the advent of antibiotics promised further expansion of the surgical horizons. Despite these advances, the rates of SSIs remain a concern and vary internationally. The SSIs are defined as infections of the incision or organ or space that occur after surgery¹⁵ and usually occurring within 30 days of an operative procedure.³⁸ They can be further subdivided into infections that are limited to the skin and subcutaneous tissue at the site of incision (superficial incisional), including deep soft tissue (eg, muscle and fascia) at the surgical site (deep incisional), and/or any other part of the anatomy that was accessed during the procedure (organ or space SSIs). The SSIs can also be associated with infections that are associated with deep incisional or organ/space infections that occur within 1 year if implant is left in place. The surgical wound can also be classified into four major types that are also associated with increased infection risk due to the level of damage associated at the wound and other factors (Table 43.1).³⁸ The SSIs remain one of the most common HAIs, estimated to comprise 31% of all infections among hospitalized patients. Between 2006 and 2009, SSIs complicated an estimated 1.9% of surgical procedures in the United States. The Centers for Disease Control and Prevention (CDC) HAI prevalence survey found there were an estimated 157 500 SSIs associated with inpatient surgeries in 2011.¹⁵ The SSIs alone can cause serious injury or death at significant cost to patients, families, and health care organizations. A systematic review of the literature on SSI from 1998 to 2014 found the estimated average cost of an SSI ranged between $10 433 and $25 546, which equates to approximately $13 300 to $35 400 in 2019 costs.¹⁵,⁴⁴ In addition, infection remains a further limiting factor of surgical success in certain patients (eg, the obese, diabetics, trauma patients). But, as highlighted earlier,
infections cannot always be controlled by antibiotics alone and are becoming a greater risk with the continuing development of antibiotic-resistant gram-positive (eg, MRSA, vancomycin-resistant Enterococcus [VRE], and various types of mycobacteria) and gram-negative (eg, carbapenem-resistant Enterobacteriaceae) bacteria. Fortunately, the surgical community has retained antisepsis and various usages of biocides as an important component of surgical technique as well as continuing to identify alternatives to antibiotic dependence.¹⁵,³⁸,⁴⁵ Guidelines for the prevention of surgical wound infections in the United States¹⁵ and internationally³⁸ address the continuing need for appropriate surgical antisepsis.

Staff selecting an antiseptic must be familiar with the spectrum of activity and limitations, appropriate use, potential side effects, risk of failures, potential contamination, cost-effectiveness, and, last but not least, the art to motivate people to use these agents correctly.¹⁷,⁴⁶,⁴⁷,⁴⁸,⁴⁹ An initial recommendation of the CDC⁵⁰ that hand washing with plain soap suffices for routine use in hospitals was accepted but with some reservations. The data in laboratory and clinical studies could often be variable, depending on the product formulation, test methods used, and comparisons to controls. The overall evidence of the benefit of antimicrobial soaps in many settings continues to be of some debate. For example, the US Food and Drug Administration (FDA) issued a final ruling in 2016 that over-the-counter (OTC) consumer antiseptic wash products containing certain active ingredients (eg, triclosan and triclocarban) can no longer be marketed due to safety and effectiveness concerns in comparison to regular soap and water but at that time deferred ruling on other biocides such as benzalkonium chloride and chloroxylenol (PCMX).⁵¹ Similarly, for health care antiseptics, such as health care personnel hand washes, health care personnel hand rubs, surgical hand scrubs, surgical hand rubs, and patient antiseptic skin preparations, a range of biocides (particularly including triclosan) could no longer be generally recognized as safe for health care antiseptic use. In addition, they deferred ruling on a further six types of widely used biocides in antiseptic use (benzalkonium chloride, benzethonium chloride, chloroxylenol, alcohol, isopropyl alcohol, and povidone-iodine). Some widely used biocides such as chlorhexidine have a unique situation as they are currently ineligible for evaluation under the FDA’s OTC drug review for use as a health care antiseptic and therefore continue to require approval under a new drug application to the FDA prior to marketing.

But overall, the use of antiseptics (or skin/hand disinfectants) in health care environments continues to be supported by consensus and evidence-based guidelines internationally.¹⁵,¹⁷,³⁸,⁵² But the recommendations have changed depending on the evidence, such as with the emphasis on the use of alcohol-based antiseptics (hand rubs) over antimicrobial soaps (hand washes) than in the past (particularly in the United States, where initial use of various hand rubs was initially low in comparison to other areas such as in Europe; see chapters 19 and 42). These guidelines provide a detailed review of the evidence to support these recommendations and in summary include

Intraoperative irrigation of tissues with an aqueous iodophor solution under restrictive situations, such as of deep or subcutaneous tissues, or in certain situations before wound closure of clean or clean-contaminated wounds.

In addition, it is clear that such products should meet the required efficacy, safety, and registration requirements (as applicable) for the countries in which they are marketed in (eg, under the FDA requirements²⁶ or the European Union Biocidal Product Regulation⁵³ and associated efficacy test standards) (see chapters 61, 62, and 63). These products should also be specifically used in compliance to manufacturer’s instructions and labeled claims.

In this chapter, we use the definitions proposed by the FDA OTC Antimicrobial Panel II⁵⁴ and finalized in 2017 for the use classification of health care antiseptics.²⁶ These are considered drug products that are generally intended for use by health care professionals in a hospital setting or other health care situations outside the hospital. They can include washes that are designed to be applied with water (eg, health care personnel hand washes and surgical hand scrubs) or rubs (or leave-on products) that are applied
and not rinsed off after use (eg, health care personnel hand rubs, surgical hand rubs, and patient antiseptic skin preparations). Overall these include

Patient antiseptic skin preparations (ie, patient preoperative and preinjection skin preparations): fast-acting, broad-spectrum, and persistent antiseptic containing preparation that significantly reduces the number of microorganisms on intact skin. Examples include products used for patient preoperative or preinjection skin preparations.

The antimicrobial ingredients of such preparations were initially placed by the FDA⁵⁴ in three categories: category I, generally recognized as safe and effective and not misbranded; category II, not generally recognized as safe and effective or misbranded; and category III, available data insufficient to classify as safe and effective, and further testing is required. These have now been replaced with products defined as being under monograph conditions (ie, previously considered category I) and nonmonograph conditions (referring to the original categories II and III products). First aid antiseptics are considered separately under a separate monograph.⁵⁵ These regulatory requirements led to many restrictions on the range of biocides that may be used in these products as well as the continuing requirements for new drug applications for the specific use of certain types of biocides (as discussed earlier). Equally in Europe, the range of antimicrobials are restricted based on the environmental safety, antimicrobial effectiveness, and toxicity requirements defined for these types of products.⁵³,⁵⁶ For detailed information on the chemical, antimicrobial, and toxic properties of each active component, the reader is referred to the respective chapter of this book.

For more than 140 years, it has been known that infectious agents can be carried on hands.⁷⁹ Whether acquired from corpses, patients, unclean dressings, or contaminated instruments and surfaces, they can survive as transient flora on the skin for some time, and some may become part of the “nontransient” flora.²⁴,³⁵,³⁶ Hand washing has been accepted for many decades as the most effective way to interrupt the chain of transmission of infection from one person to another. The guidelines for the hand washing and hand antisepsis have evolved over the years since the publication of widely used evidence-based guidelines such as the 1985 CDC Guidelines for Handwashing and Hospital Environment Control.⁸⁰ These include changes in the recommendations in the types and methods of hand antisepsis.¹⁷,⁵² It is practical to consider that the use of soap (antimicrobial or nonantimicrobial) and water is preferred when the hands are visible soiled (such as with blood or other body fluids), but for routine use that convenient use of antimicrobial (usually alcohol-based) hand rubs (that are often preferred) or antimicrobial soap and water can be used. The guidelines specify situations when the use of antiseptic hand rubs or hand washes should be used, to include before and after direct contact with a patient, prior to donning gloves before specific patient procedures (such as catheter insertion), and on contacting patient fluids or inanimate surfaces in close vicinity to a patient (even if not visibly soiled). The methods of handling are equally important to observe. Although deferring to manufacturer’s instructions, the guidelines recommend steps in the use of hand rubs and hand washes, such as prewetting the hands before applying soap, washing for at least 15 seconds, followed by rinsing and drying.¹⁷,⁵² In many clinical situations, washing with plain soap has been recommended for some time unless otherwise indicated.⁸⁰ Unfortunately, such guidelines were often interpreted to mean that antiseptic hand wash agents were to be replaced in all hospital areas with nonmedicated soap. Routine hand washing practices in hospitals already were often less than optimal in frequency, length and technique of washing, and quantity of soap used.⁸¹,⁸²,⁸³,⁸⁴,⁸⁵,⁸⁶ Thus, the removal of antimicrobial soaps with residual activity may have had a negative effect on infection control in some institutions. Several studies demonstrated that hand washing with antiseptic soaps can reduce HAIs.⁷⁰,⁸⁷,⁸⁸,⁸⁹,⁹⁰ Therefore, the guidelines continue to recommend the appropriate use of antiseptics in higher risks situations, including in surgical wards to minimize or eliminate the transient flora acquired from infected patients and reduce the resident flora, which may include gram-positive and gram-negative bacteria.¹⁷,⁵² Hand washing frequency and technique are dependent on many factors such as the motivation of personnel, the selection of an acceptable hand washing agent, and the availability of either sinks for hand washing or dispensers for waterless preparations.¹⁷,⁵²,⁹⁰ Alcohol-based hand rinses are highly efficacious, and such products are recommended as a health care personnel hand wash, particularly when a sink and running water are inaccessible.¹⁷,⁵² Senior clinicians and nurses play important roles both as decision makers and as role models for their associates.