REVIEW ARTICLE

Role of Antiseptics in the Prevention of Surgical Site Infections Kathryn Echols, MD,* Michael Graves, MD,† Keith G. LeBlanc, MD,‡ Sean Marzolf, MD,* and Avis Yount, MD†

BACKGROUND Antiseptics are chemical agents used to reduce the microbial population on the surface of the skin and are used in nearly every surgical procedure today. Despite this, there are currently no definitive guidelines on surgical preoperative antisepsis that indicate a specific regimen based on demonstration of superior efficacy. OBJECTIVE This review serves to examine preoperative antisepsis, including cutaneous bacteriology, preoperative hair removal, preoperative decolonization, surgical attire, and the antiseptic agents themselves. MATERIALS AND METHODS

A review of the literature on surgical antiseptics was performed.

RESULTS Although numerous studies have demonstrated differences in bacterial colonization rates, few well-controlled investigations have demonstrated superiority of a given regimen. The alcohol-based iodophor and chlorhexidine products seem to exhibit greater efficacy than their aqueous counterparts. CONCLUSION More randomized controlled trials will be needed to determine if any specific regimen is most effective. At this point in time, product usage should be based on specific attributes relating to the products, such as iodophors around the eyes and/or ears to avoid irritation and aqueous-based solutions in hair bearing areas because of concern for flammability. Ultimately, it is up to the individual surgeon to tailor the optimal antiseptic regimen for their specific scope of practice. The authors have indicated no significant interest with commercial supporters.

T

he use of antiseptics dates back to the 1840s when Ignaz Semmelweis documented a dramatic reduction in puerperal sepsis associated with the use of appropriate handwashing techniques.1 Antiseptics gained further acclaim when Lister’s use of carbolic acid in the 1870s demonstrated improved infection control and reduction in surgical morbidity.1,2 Since that time, antiseptics have remained an important component of reducing surgical site infections (SSIs), which are defined as any infection occurring at the surgical site within 30 days of the procedure. Despite their importance, there are currently no definitive guidelines on preoperative antiseptic use based on a demonstration of superior

efficacy by any particular agent or regimen.3,4 Preoperative antisepsis involves both scrubbing to remove cutaneous flora physically and chemical killing to minimize the load of resident flora. Clean surgical procedures, defined as those performed after surgical scrubbing with complete sterile technique, have an infection rate of 1% to 4%. Clean– contaminated surgery, in which minor breaks in sterile technique can occur, has an infection rate of 5% to 10%.5 Wounds in office-based cutaneous surgery can be classified as clean or clean–contaminated wounds depending on the procedure type, with infection rates

*Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina; †Section of Dermatology, Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; ‡Total Skin and Beauty Dermatology, Birmingham, Alabama © 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-0512 Dermatol Surg 2015;41:667–676 DOI: 10.1097/DSS.0000000000000375

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ranging from 0.07% to 4.25%.5–8 Recent studies have found similarly low infection rates even without the use of prophylactic antibiotics.9 Additionally, guidelines recommend against the use of topical antimicrobial agents for wound healing by primary intention.10–12 A variety of antiseptics were routinely used in these aforementioned studies. The Surgical Site Bacteriology of the Skin Cutaneous flora includes both resident and transient bacteria. Resident bacteria are located primarily in the superficial epidermal layers. A minority (10%–20%) of resident cutaneous floras are in the deeper layers, particularly the pilosebaceous unit, making them more difficult to eradicate with antiseptic agents.13,14 The majority of these bacteria tend to be nonpathogenic and can prevent colonization of the skin with pathogenic bacteria.15 Resident cutaneous floras are found more commonly in creases and folds, particularly in the intertriginous areas.15 Transient floras are temporary inhabitants acquired by contact that are unable to colonize the skin. They are present superficially, loosely attached, and can be easily removed with scrubbing.4,15 Transient floras are the cause of the majority of postoperative wound infections.16 Both the resident and transient floras are influenced by host factors including sex, age, personal health, nutritional status, and location.17 Staphylococcus aureus is the bacteria most commonly implicated in SSIs. This bacteria usually starts as transient flora and transitions to resident flora with sustained inoculation.15 Increasing incidence of antimicrobial resistance of S. aureus has raised concern for treatment-resistant infections.18 Other common bacteria in SSIs include coagulase-negative Staphylococcus, Enterococcus, Escherichia coli, group A streptococci, and Pseudomonas aeruginosa.4,13,16,19 Hair Removal The 1999 Centers for Disease Control and Prevention (CDC) guidelines strongly discourage hair removal before surgery unless it will interfere with the procedure.

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If removal is deemed necessary, the recommendation is that the hair be clipped immediately before the operation, preferably at a level just above the cutaneous surface with minimal, if any, contact with the skin during clipping.3,20 Preoperative shaving has been linked with an increased risk of SSIs. These are thought to be secondary to microabrasions on the cutaneous surface that facilitate postoperative bacterial growth and subsequent infection.13,21 A recent Cochrane review supported the existing CDC guidelines but acknowledged that most of the clinical trials investigating this subject are underpowered and more research is needed.22 Preoperative Decolonization The 1999 CDC guidelines strongly recommend preoperative antiseptic showering, with the use of products containing chlorhexidine gluconate (CHG) to reduce cutaneous bacterial colonization.3 Antiseptic body washes have been studied in a variety of formulations, including 4% CHG wash, 2% CHG impregnated cloths, alcohol-based products, and 10% povidone–iodine (PVP-I) scrub.19,23–27 Numerous studies have demonstrated significantly decreased bacterial colonization rates using these preoperative body washes.23,27–29 However, recent reviews have been unable to show definitive evidence that preoperative showering reduces SSI.30–32 There is increasing evidence that in patients with known carriage of S. aureus, preoperative decolonization may reduce the rate of SSI. It has been shown that nasal carriage of S. aureus is an independent risk factor for the development of SSI in multiple surgical settings, including dermatologic surgery.33–37 Investigations from various surgical disciplines have shown a reduction in SSI to a rate comparable with noncarriers with the use of protocols to identify and decolonize carriers of S. aureus before surgery.38–41 It remains to be seen if these interventions are beneficial in a dermatologic surgery setting, but a recent prospective randomized study demonstrated a significant reduction in SSI after Mohs surgery among nasal S. aureus carriers with the use of a topical decolonization regimen.37 A variety of decolonization protocols have been described, usually consisting of topical agents used

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alone or in combination with oral antibiotics.38,39,41,42 Topical decolonization regimens commonly use a combination of CHG body wash once daily plus intranasal mupirocin ointment twice daily for 5 days before surgery. Cherian and colleagues42 recently reported an unblinded randomized controlled trial, which showed that topical decolonization was superior to prophylactic oral antibiotics at reducing the rate of SSI in 693 patients undergoing Mohs surgery who demonstrated nasal carriage of S. aureus. These results suggest that patients with known S. aureus carriage should be considered for topical decolonization before dermatologic surgical procedures, but more research is needed to confirm the validity of these findings. Surgical Attire Centers for Disease Control and Prevention guidelines state that shoe covers should not be worn for the prevention of SSI, which is supported by a 2003 literature review, which failed to find support for use of shoe covers to prevent SSI.12,43,44 The use of sterile gloves (SG) versus nonsterile gloves (NSG) in Mohs micrographic surgery (MMS) is still a matter of debate. Although studies have demonstrated a statistically significant difference in bacterial load favoring use of SG, the clinical significance of this finding is uncertain.45 A large prospective cohort study of MMS cases demonstrated an absolute risk reduction of 20.47% with the use of SG, but this small risk reduction may not correlate with clinical significance in the setting of overall low infection rates in MMS.46 Furthermore, a more recent study demonstrated that the prevalence of SSI in SG versus NSG was almost identical, and the cost of SG is 3.5 times greater.47 A recent Cochrane review evaluating the use of disposable face masks for preventing SSI in clean surgery identified 3 studies, which demonstrated no statistically significant differences between masked versus unmasked SSI rates; however, because of the small number of trials and limitations of the included studies, it is currently unclear if the use of surgical face masks alters SSI rates.48 Antiseptic Scrubs Adequate surgical antisepsis should remove all transient bacteria from the skin, while minimizing the remaining resident flora residing in the pilosebaceous

units.16 Recommendations have included using a detergent to remove physical debris from the skin, followed by an antiseptic scrub to kill bacteria.15 Scrubbing has been considered to be more important for disinfection than the type of agent used; a 50% reduction in bacteria has been described for every 6 minutes spent scrubbing.15 However, the importance of a full 5-minute scrub in directly preventing SSIs has been challenged and currently is not used by most dermatologic surgeons.49 The ideal antiseptic agent should be capable of killing all bacteria, fungi, viruses, protozoa, and spores present on host skin while remaining nontoxic, hypoallergenic, safe for use in all body regions, and nonabsorbable percutaneously to reduce systemic side effects and toxicity.4 Fast onset of action, continued residual antimicrobial activity, and safety and efficacy with repeated use are also desireable.4 As antiseptics have the risk of bacterial contamination with repeated use from the same receptacle, the ideal agent would be in single-use packets.15 Alcohol Alcohol is effective against Gram-positive and Gramnegative bacteria and many fungi and viruses.4 However, alcohol is not effective against most spores.13 Alcohol has been shown to inactivate HIV in vitro, but this effect was measured after contact times between 2 to 10 minutes.50 Therefore, it should not be relied on for this purpose in normal clinical settings because of its rapid evaporation. Blood and other organic compounds do not affect the antimicrobial action of alcohol.19 Alcohol provides fast acting antisepsis, but its lack of continued antimicrobial effect with drying precludes its stand-alone use.21,51 The utility of alcohol lies in its combination with more persistent antiseptic agents such as iodophors or CHG. These combinations provide more persistent antimicrobial activity that can last for the duration of surgery.21,51 Alcohol also has a role in developing countries where alternative antiseptics may not be available.52 When choosing an alcohol-based regimen, isopropyl alcohol is preferred over ethyl alcohol because of its superior antibacterial spectrum and less volatile nature.13 Alcohol and alcohol-based antiseptics are flammable if the product is still wet on the skin, and there have been

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burns related to fire from electrosurgery after use of alcohol-based antiseptics.53,54 To prevent fires, alcohol should be given adequate time to dry, avoided in hair bearing areas where drying may be impaired, and pooling of the product should be prevented.21,54 Chloroxylenol Chloroxylenol is an antiseptic that is no longer commonly used because of its decreased efficacy in comparison with chlorhexidine and povidone–iodinebased products. One study demonstrated that the number of bacterial colonies after application of chloroxylenol was not statistically significant from the colony count on the skin before antiseptic application.55

heterogeneity in application method exists between studies with a range of time spent scrubbing and variable numbers of applications of PVP-I paint after scrub.4,14,28,49,52,62–69 This regimen of 5-minute scrub followed by painting is not performed by most dermatologic surgeons, as similar efficacy has been observed using the paint-only method.49,66,70 PVP-I should be allowed to dry fully after application for maximal antimicrobial effect.71 Drying time recommendations range from 2 to 20 minutes.67,71,72 A minimum of 2 minutes is recommended because iodophors require approximately 2 minutes of contact time to allow release of free iodine.72 If not removed from the skin, PVP-I can have sustained activity for 1 to 2 hours.15,73 Aqueous-Based Chlorhexidine

Aqueous-Based Iodophors Povidone–iodine (PVP-I), a combination of polyvinylpyrrolidone and iodine, is an iodophor that allows for steady release of iodine in a water-soluble product.2 The bactericidal effect of PVP-I is determined by the concentration of free iodine; a 10% PVP-I formula contains 1% available iodine.2–4 Iodophors are effective against a wide range of microorganisms including Gram-positive and Gramnegative bacteria, some bacterial spores, yeast, other fungal forms, protozoa, and viruses such as HIV, and hepatitis B virus (HBV).2,13,51,56 These are nonirritating to the eyes and mucous membranes, provide visibility to areas covered, and do not readily remove surgical markings.57 However, blood and serum proteins can inactivate PVP-I and prolonged or excessive application can cause systemic toxicity.3,15,51 PVP-I has been documented to cause an iododerma-like reaction and chemical burns.58,59 Anaphylaxis has occurred in patients with a systemic povidone–iodine allergy after topical use; therefore, topical PVP-I is not recommended in those with a history of systemic allergy.59,60 Although impaired wound healing has been demonstrated with direct application of PVP-I into wound beds, this seems not to be significant clinically.2,61 Traditional application involves a 5minute scrub with PVP-I surgical scrub followed by rinsing with sterile gauze saturated with water, then painting of the surgical site with aqueous PVP-I solution as recommended by the manufacturer. However,

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Chlorhexidine gluconate is a bisbiguanide that is bacteriostatic at low concentrations and bactericidal at higher concentrations.74,75 Chlorhexidine gluconate has efficacy against a wide range of Gram-positive and Gram-negative bacteria, many viruses including HIV and HBV, and some fungi.3,13,56,72,76–78 Higher concentrations correlate with lower bacterial load.79 It provides residual antimicrobial action by binding to the stratum corneum and is resistant to removal by alcohol.13 Manufacturer recommendations for application include a 2-minute swab of the surgical site followed by drying with a sterile towel, then an additional 2-minute application followed by towel drying. However, the actual methods used are heterogeneous and include a 5- to 7-minute CHG scrub alone or scrub followed by painting with CHG– alcohol or isopropyl alcohol solution.62,64–67 One source recommended not wiping the area dry of CHG after application to allow its persistent antibacterial effect.79 Drying is recommended before incision, but actual time to allow for adequate drying is rarely cited. Current recommendations include allowing for at least 2 minutes of contact time before surgical incision.79 Chlorhexidine gluconate produces limited irritation to the skin and can be used on the oral mucosa and is not inactivated by blood or other organic material.72 However, CHG is ototoxic and can cause conjunctival irritation.13 It has been reported to cause

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damage to the corneal epithelium and even lead to permanent corneal opacification.80 A test of rabbit corneas showed 4% chlorhexidine and 4% isopropyl alcohol with detergent to be toxic to the cornea.81 A study of ototoxicity performed on cats showed that application of chlorhexidine (2% and 0.05%) produced damage to the sensory epithelium resulting in a sensorineural hearing loss.82 This effect of chlorhexidine seems to be related to its concentration, and the clinical severity of injury often progresses over several weeks after exposure.83 It has also been shown to erase surgical site markings significantly more than PVP-I.84 Additionally, anaphylaxis has been demonstrated in response to topical application of CHG.85

Chlorhexidine Alcohols The combination of alcohol and CHG benefits from the potency of the alcohol and the persistent activity of the CHG. The mechanism of antimicrobial action of CHG–alcohol is attributed to the combined mechanisms of each of the products. The most popular agent is ChloraPrep (CareFusion, Inc., El Paso, TX), which contains 2% CHG and 70% isopropyl alcohol (CHG-IA), and has a duration of action of 48 hours.88 Chlorhexidine gluconate-IA should be applied for 30 seconds to dry surgical sites and should be allowed to dry for at least 30 seconds. For moist surgical sites such as the inguinal folds, 2-minute application followed by 1-minute drying time is recommended by the manufacturer; however, variable drying times ranging from 3 to 10 minutes were used in clinical studies.84,87

Alcohol-Based Antiseptics Product Comparisons Povidone–Iodine Alcohols Povidone–iodine–ethanol (PVP-I-ethanol or PI-ethanol) has the mechanism of action of PVP-I combined with that of alcohol. The alcohol allows for rapid acting antisepsis of the product, and the combination of alcohol with PVP-I increases the free iodine concentration higher than with PVP-I alone.51 Current available options include DuraPrep (3M Health Care, St. Paul, MN) and Prevail-FX (Cardinal Health, Dublin, OH). DuraPrep is iodine–povacrylex with 0.7% available iodine and 74% isopropyl alcohol by weight (wt/wt) (PI-IA), whereas Prevail-FX is PVP-I and a polymer complex with 0.83% available iodine dissolved in isopropyl alcohol 72.5% (wt/wt) (PVP-IA). Application of both products involves painting a single uniform coat over the operative site; excess product can be removed with absorbent towels or gauze. Both products form a water-resistant (PVP-IA) or water-insoluble (PI-IA) film on the surface of the skin with drying, which contributes to a duration of action of 48 hours or more.73,86 Recommended drying time is at least 2 to 3 minutes, but a longer 5-minute drying time should be considered when electrosurgery will be used to avoid fires.54 Although the film is resistant to removal by saline, which is thought to increase its antimicrobial efficacy, it can be difficult to remove after surgery is complete and may not be practical for brief procedures.16,87

PVP-I seems to have the broadest spectrum of action with excellent coverage of Gram-positive bacteria and good coverage of Gram-negative bacteria, Mycobacterium tuberculosis, fungi, viruses, and spores. Alcohol and CHG have similar spectrums of action, although alcohol is not sporicidal, and CHG has limited activity against the tubercle bacillus and fungi.72 However, it is not clear if these differing spectrums are clinically significant as the vast majority of wound infections are due to bacteria. The small infection rate in clean surgery makes appropriate powering of studies difficult. One study comparing over 1,800 patients using PVP-I versus normal saline had an infection rate of 0%.89 Smaller studies have shown superiority of aqueous- and alcohol-based CHG over PVP-I in reducing both bacterial colony counts and SSIs.62–65,88,90 A recent multicenter prospective cohort study of 20,821 MMS cases found that preoperative use of chlorhexidine was associated with a lower risk for infection.46 However, a 2009 Cochrane review found insufficient evidence in high-quality studies to recommend one antiseptic over another.4 Recent meta-analyses comparing alcohol- and aqueous-based CHG with aqueous PVP-I show superiority for CHG in preventing SSI in a variety of surgical procedures.66,67 These same results have been seen in a meta-analysis on catheter site

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Antiseptic Alcohol

MOA Denatures proteins

Antimicrobial Coverage Gram-positive and Gram-negative bacteria, many fungi, and viruses

Onset

Duration Negatives/Risks Examples

Rapid

Short acting

Not active against bacterial spores Aqueous-based Free iodine oxidizes and iodophors substitutes microbial contents causing protein and DNA damage

Gram-positive and Gram-negative bacteria, yeast, and other fungal forms, protozoa, some viruses (HIV, HBV), and some bacterial spores

Intermediate

Intermediate

Alcohol-based iodophors

Rapid

Alcohol-based CHG

MOA of alcohol combined with that of aqueous CHG

Improved Gram-negative bacterial coverage

Improved Gram-negative bacterial coverage

Isopropyl alcohol

Short duration of action

Ethyl alcohol

Inactivated by blood and serum proteins

$0.03*

Betadine

$0.19*

Hibiclens

$0.31*

DuraPrep

$3.08†

Risk of skin reaction with iodine sensitivity

Aqueous-based Depolarizes bacterial cell walls Gram-positive and Gram-negative CHG and damages the cytoplasmic bacteria, yeasts, some other fungi, membrane, resulting in leakage many viruses, and prevents of cytoplasmic contents outgrowth but not germination of bacterial spores

MOA of alcohol combined with that of aqueous iodophors

1–2 h

High flammability risk

Cost per Application

6h

Prolonged or excessive application can cause systemic toxicity Ototoxic Causes conjunctival irritation Decreased visibility of surgical site markings compared with iodophors

Rapid

48 h

48 h

Skin irritation/ sensitivity related to iodine Film can be difficult to remove Risks of alcohol and CHG

Prevail-Fx ChloraPrep

*Pricing based on estimated volume per application of 15 mL. †Pricing based on application of a single 6 mL DuraPrep applicator. ‡Pricing based on application of a single 3 mL ChloraPrep One Step applicator. MOA, mechanism of action.

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$1.08‡

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TABLE 1. Characteristics of Antiseptic Solutions

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preparation, with less catheter tip positivity and less blood stream infections.91 A recent large study by Darouiche and colleagues63 showed reduction of SSI by 41% with CHG-alcohol compared with aqueous PVPI. However, the perceived efficacy of CHG in skin antisepsis is often based on evidence for the efficacy of CHG-alcohol combination with failure to acknowledge the role of alcohol. A meta-analysis of the role of CHG in skin antisepsis found good evidence favoring CHG-alcohol combinations over aqueous PVP-I, but the superiority was not found to hold against PVP-I plus alcohol or other competitors combined with alcohol.92 In studies comparing PI–alcohol with PVP-I solution alone, there were no statistically significant rates of decreased infection.68,69,93 Chlorhexidine gluconate– alcohol has been shown to be more efficacious than PI– alcohol in decreasing bacterial colony counts after use in concentrations of 0.5%, 2%, and 4%.23,55,62,94 However, a recent large study of general surgery patients comparing PI–alcohol with CHG–alcohol and PVP-I showed a trend toward decreased SSIs in both the PI–alcohol and PVP-I groups when compared with CHG–alcohol.68 Skin irritation potential and product cost must also be taken into account when selecting the appropriate antiseptic. A comparison of 1% CHG–ethanol, 2% CHG–isopropyl alcohol, and 10% PVP-I solution demonstrated a trend of decreased skin irritation potential using 1% CHG–ethanol; larger studies are needed to determine if the difference is significant.95 Regarding cost, an observational study found that PVP-I skin disinfection is associated with systematic adjunctive costs from auxiliary materials and a significantly prolonged drying time compared with CHG leading to increased operating time; these adjunctive costs are considered to be on the same order of magnitude as the disinfectant cost itself.96 These additional costs are an important consideration when making direct per unit product cost comparisons (Table 1).

on demonstration of superior efficacy. Although numerous studies have demonstrated differences in bacterial colonization rates, few well-controlled investigations have demonstrated superiority of a given regimen. The alcohol-based iodophor and CHG products seem to exhibit greater efficacy than their aqueous-based counterparts. More randomized controlled trials will be needed to determine if any specific regimen is most effective. At this point in time, product usage should be based on specific attributes relating to the products, such as iodophors around the eyes and/or ears to avoid irritation and aqueous-based solutions in hair bearing areas because of concern for flammability. Ultimately, it is up to the individual surgeon to tailor the optimal antiseptic regimen for their specific scope of practice.

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Address correspondence and reprint requests to: Kathryn Echols, MD, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, 135 Rutledge Avenue, MSC 578, Charleston, SC 29425, or e-mail: ksfl[email protected]

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Role of antiseptics in the prevention of surgical site infections.

Antiseptics are chemical agents used to reduce the microbial population on the surface of the skin and are used in nearly every surgical procedure tod...
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