Antiseptic and Antibiotic Stewardship in Dermatologic Surgery: Is Benzoyl Peroxide the Solution?

J Clin Aesthet Dermatol. 2024;17(5):24–28

The human skin is a complex ecosystem which hosts a variety of commensal microbes, including bacteria, fungi, viruses, and mites.¹ If the delicate balance of the skin microbiota is perturbed, infection, dermatoses, and systemic disease may arise.¹ In fact, the location of insult can provide insight into the causal microorganism as the distribution of certain microbes is associated with the topographical physiology of skin.¹ The sebaceous, moist, and dry areas of skin are each characterized by unique microbial niches.^1–3 Bacterial genome sequencing has shown that Propionibacterium species and Staphylococcal species are abundant in sebaceous areas, such as the glabella, back, and nasal creases.² Moist areas, such as the axilla, antecubital fossa, and inguinal crease are dominated by Corynebacterium and Staphylococcal species.^1,2 Dry areas of skin, such as the buttock, volar forearm, and palms are home to a variety of bacterial species, with no one species predominating.² The fungal profile of the skin hinges more on anatomic site.³ It is overall predominated by the Malassezia genus, with some site-specific species.³ 

The viral colonization of the skin is not well understood, however, it is still an integral component of cutaneous health.⁴ The human skin virome is site-specific, and is mostly associated with skin occlusion and exposure features.⁴ A recent skin double stranded DNA virome study employing virus-like particle enrichment found that most of the double stranded DNA genomes which could be identified were a part of the Caudovirales order (bacteriophages). It is important to understand viral colonization of the skin because viruses can contain antibiotic resistance genes which can ultimately affect dermatologic treatment.⁴ 

Microorganisms have been implicated in many dermatologic diseases.¹ As such, a comprehensive understanding of their topographical characteristics can help guide tailored treatment. For example, benzoyl peroxide is commonly prescribed for acne treatment, which is not surprising considering it targets Cutibacterium acnes, formerly known as Propionibacterium, which thrives in sebaceous areas. Understanding the topographic microbial colonization of skin can help tailor anti-microbial treatment to reduce resistance and more accurately target suspected microbes. Since dermatologic surgery tends to be smaller in scope, this targeted approach may be even more favorable and applicable in this field

Skin Antiseptics and Their Role in Dermatologic Surgery

The goal of skin antiseptics is to decrease microbial count on the skin surface prior to disrupting the skin barrier in order to minimize risk of post-operative infection (Table 1) (Figure 1).⁵ Current Centers for Disease Control and World Health Organization guidelines recommend the use of alcohol-based antiseptic solutions for surgical site skin preparation in adults.^5,6 The most commonly used antiseptics are chlorhexidine gluconate (CHG) and povidone-iodine (PVI) in alcoholic solutions, but they exist in aqueous solutions as well.⁵ There is no consensus on optimal concentration of the agents, and various formulations exist on the market.⁵ Alcoholic CHG has been shown to produce better results in surgical site infection prevention.⁷ In fact, a recent network meta-analysis of randomized and observational studies which investigated the comparative efficacy of alcoholic CHG, alcoholic PVI, and aqueous PVI in the prevention of surgical site infection after clean surgery in adults found that alcohol-based CHG was the most effective antiseptic.⁸ In regards to dermatologic surgery, a survey of 168 American College of Mohs Surgeons reported that the most common antiseptic used was 4.0% chlorhexidine gluconate, except when operating on the periocular area, in which 7.5% to 10% PVI was more common.⁹ The 70% isopropyl alcohol was also reported by some practitioners, but not as commonly as the aforementioned agents.⁹ 

Chlorhexidine is a rapid-onset, long-lasting, broad coverage biocide.^10,11 At high concentrations, chlorhexidine kills bacteria through the disruption of the cell membrane and subsequent spillage of internal contents.¹⁰ At low concentrations, it exhibits bacteriostatic action through the suppression of cellular respiration.¹¹ It is used in various concentrations depending on the clinical scenario and can be in an alcohol or aqueous base solution.^10,11 Adverse effects include irritation, and rarely severe allergic reactions.¹¹ Its use is also relatively contraindicated in the periocular or periauricular areas given the potential for keratitis and ototoxicity, respectively.¹⁰

PVI is a rapid-onset, broad coverage iodophor.^10,11 It exists in both aqueous and alcoholic formulations.¹⁰ A concentration of 10% is commonly used in surgical procedures, and unlike chlorhexidine, PVI can be safely used in the periocular area. Iodine’s mechanism of action is not completely understood, but it is considered a strong oxidizing agent which disrupts the microbial cell membrane and integral cellular mechanisms.¹¹ Adverse effects include irritant contact dermatitis with extended exposure and potential for cross-reactivity with other iodide-containing medications.¹⁰

Isopropyl alcohol is a fast-acting, short-lived antiseptic which exerts anti-microbial effects through membrane damage and protein denaturation.¹⁰ It is usually combined with water, or as mentioned previously, with other biocides, as this optimizes its anti-microbial activity; the optimal concentration for bactericidal activity is 60 to 90 percent.^10,11 Disadvantages include the potential for irritant contact dermatitis with use, and its flammability which can pose a risk in the presence of electrocautery.¹⁰ 

Antiseptic Stewardship

Antiseptic effects on the cutaneous microbiome have not been consistently characterized in the literature. Although antiseptics are utilized for their broad coverage, their in vivo effects may be less significant than expected.¹² A longitudinal study utilizing 16S ribosomal RNA gene sequencing to investigate “pulse” disturbances to the skin microbiota caused by antiseptics found that the application of these products causes a swift, but transient, depletion of microbial organisms.¹³ Interestingly, the authors found that Propionibacteriaceae is uniquely increased in relative abundance after treatment of the back with antisepsis. The authors surmise that the persistence of Propionibacteriaceae may be due to internal resistance factors specific to the bacteria itself, or due to its presence at deeper skin layers.¹³ In contrast, easily perturbed skin inhabitants occupy more superficial levels of the skin where they are subject to harsher insults.¹³ These findings suggest that bacterial identity influences skin microbiota stability, and this understanding could inform future predictions to treatment response. Furthermore, antiseptics may decrease colonization resistance following treatment, permitting enhanced colonization by S. aureus.¹² Given these findings, the benefit of using antiseptics may be due to their ability to perturb a specific community of superficial microorganisms while leaving deeper residents intact.^12,13 

A study by McNeil et al¹⁴ attempted to characterize chlorhexidine resistance in nosocomial S. aureus isolates from pediatric patients with bacteremia, skin and soft tissue infection, or surgical site infection. Genes encoding efflux pumps associated with an increased minimum concentration of antiseptics, such as qacA/B and smr, were found in almost 45 percent of isolates. Double positive isolates were more likely to cause systemic disease.¹⁴ These isolates were also more likely to be resistant to antibiotics. Isolates positive for both genes required a significantly higher minimum bactericidal concentration than those positive for either gene, or negative for both.¹⁴ Evidence of chlorhexidine resistance has not been consistently reproduced.¹⁵ Of note, many factors may skew microbial communities and subsequent antiseptic effects; however, these findings highlight the potential relationship between antiseptic and antibiotic resistance.

Prophylactic Antibiotics in Dermatologic Surgery and Antibiotic Stewardship

Dermatologic surgery is unique in that it is typically performed in the outpatient setting without stringent protocols on sterile technique and environment.¹⁶ Overall, the incidence of surgical site infection in dermatologic surgery, including Mohs micrographic surgery (MMS), is low even without the use of prophylactic antibiotics or sterile technique.^16–19 A prospective study by Rogers et al¹⁶ sought to evaluate the incidence of surgical site infection following MMS using clean surgical technique during all phases of MMS, this included antiseptic preparation with 4% CHG. Of the 1,204 tumors removed, a surgical site infection rate of 0.91 percent was observed. The rate of infection was highest for skin flaps, and for procedures performed on the trunk.¹⁸ All infection cultures grew S. aureus, which is the most implicated microbe in post-operative dermatologic surgery infections.²⁰ Another prospective study of 5,091 lesions removed by dermatologic surgery found that procedures below the knee or within the groin are significantly more likely to be infected, and thus may benefit from antibiotic prophylaxis.¹⁸. The evidence for the benefit of prophylactic antibiotics in dermatologic surgery is mixed, and while type of procedure or location of procedure may guide the decision process, physicians must evaluate the risk-reward ratio before prescribing prophylactic antibiotics in dermatologic surgery.²¹

Prophylactic antibiotics may be given orally, intravenously, intramuscularly, intraincisionly, or topically.²¹ In a survey of 305 Mohs surgeons, the majority denied routine prescription of oral antibiotics, except in cases of artificial cardiac valves, anogenital procedures, wedge excision of the lip of ear, artificial joint replacement, advanced inflammatory dermatologic disorders, immunosuppression, skin grafts, leg surgery, and nasal flaps.¹⁹ While some of these factors are considered high risk in dermatologic surgery, uncomplicated Mohs surgery, specifically, does not usually require antibiotic prophylaxis.²² High-risk cases in Mohs surgery include patients at high risk for infective endocarditis or systemic total joint infection when the surgical site involves the oral mucosa, infected areas, or patients at high risk due to technique or other factors.²² In cutaneous surgery overall, antibiotic prophylaxis is recommended in certain cases including, but not limited to, in patients with high risk cardiac conditions for endocarditis undergoing surgery in infected skin or oral mucosa, in patients with increased risk of prosthetic total joint infection undergoing surgery on the oral mucosa or on infected skin, in patients undergoing surgery in high-risk areas (e.g., lower extremity or groin) or using high-risk techniques (e.g., wedge excision of lip or ear, nasal skin flaps, and skin grafting), and in patients with advanced inflammatory dermatologic disorders.²² Interestingly, surgeons who recently graduated fellowship were significantly less likely to prescribe prophylactic oral and topical antibiotics.¹⁹ This may be due to increasing awareness and education regarding antibiotic resistance and the importance of antibiotic stewardship. A different survey of 101 Mohs surgeons reported that 75.25 percent of surgeons endorsed routine use of prophylactic antibiotics to decrease the incidence of surgical site infection in any clinical case; of these surgeons, 15.79 percent prescribe only perioperative doses, 22.37 percent use only post-operative antibiotics, and 61.85 percent prescribe both.²³ This depended on the clinical scenario with the highest rate of prescription being for wedge excision of the lip.²³ Evidently, while there may be some trend toward decreased over prescription of antibiotics, the issue persists; the importance of antibiotic stewardship should continue to be investigated in dermatologic surgery.

Utility of Benzoyl Peroxide in Surgical Site Preparation

Benzoyl peroxide creates reactive oxygen species that associate physically with bacterial components, inflicting a bactericidal effect on microbes, namely gram-positive bacteria such as Staphylococcus, Streptococcus, and C. acnes.^24,25 As such, it is commonly known for its use in acne treatment regimens.²⁴ One of the main advantages of benzoyl peroxide is its very high resistance threshold.²⁴ Due to this high resistance threshold, it is added to acne treatment regimens to prevent or decrease antibiotic resistance.^24,26 We previously discussed the topographical heterogeneity of the skin microbiota, and noted the lipophilic nature of C. acnes, and its ensuing residence in sebaceous areas such as the glabella, back, nasal creases, and shoulder. Indeed, it is a common cause of surgical site infection following orthopedic shoulder surgery.²⁷ Randomized, controlled trials have both demonstrated and refuted the superiority of benzoyl peroxide pre-surgical wash over CHG.^27,28 However, its ability to penetrate sebaceous glands and target C. acnes is an intriguing trait which suggests that its utility might not be limited to orthopedic surgery. 

C. acnes has recently been described as a cause of postoperative infection after dermatologic surgery of the nasal tip; in one case report by Richey et al,²⁵ a patient underwent MMS for infiltrative basal carcinoma on the nasal tip, and within two days, developed new acne-like papules at the surgical site, which were confirmed by culture to be C. acnes. The patient was successfully treated with benzoyl peroxide 4% wash.²⁵ The authors note that this eruption was also likely exacerbated by occlusion from post-operative bandaging and petroleum. They recommended that when operating on sebaceous areas in patients younger than 50 years of age (as they are more likely to be colonized with C. acnes), physicians should consider using 5% benzoyl peroxide preparation.²⁵ This is not the first report of the utility of benzoyl peroxide in treating or preventing dermatologic surgical site infection. Reports of its efficacy within this field date back to the late 1900s.^29,30 A prospective study of 673 patients undergoing surgery for lesions in the centrofacial area evaluated the efficacy of 10% benzoyl peroxide gel used for seven days prior to surgery in diminishing post-operative surgical site infections.²⁹ Of note, all patients were treated immediately before incision with 0.25% benzalkonium chloride in idroalcoholic solution. The results showed a statistically significant decrease in the incidence of surgical site infection between patients treated with benzoyl peroxide and those untreated.²⁹ S. aureus was the main culprit of surgical site infections, and although it is not associated exclusively with sebaceous glands, it is still targeted by benzoyl peroxide.^25,29 Interestingly, the authors note that this may be due to the oxidizing effects of benzoyl peroxide, or due to its desquamation of skin, which eliminates various microbes physically.²⁹ Lynch and Bailin³⁰ describe the efficacy of 10% benzoyl peroxide in fostering wound healing in three patients after MMS surgery to the intergluteal cleft, fourth digit, and upper back, respectively. Overall, benzoyl peroxide appears to be a promising agent for the prevention and treatment of dermatologic surgery site infections. 

Conclusion

Although antiseptics may not cause widespread or long-term disruptions of skin microbiota,^12,13 the potential for reduced colonization resistance following treatment, and the notion that certain taxa members may be more affected by treatment, calls for a concentration on antiseptic stewardship.^12,13 While antiseptic resistance mechanisms have been described, there is no reliable data proving a significant negative impact on clinical outcomes that outweighs the prevention of infection. However, it is possible that the seemingly blanket, broad coverage of antiseptics may be more sophisticated, and some organisms may not be targeted as efficiently as possible. Utilizing our understanding of the topographic distribution of the skin microbiota, it may be more favorable in clean, localized surgical procedures to selectively target common resident skin microorganisms in surgical sites. The use of benzoyl peroxide in sebaceous areas makes use of the topographical heterogeneity of skin and narrows antimicrobial coverage. Given the rising issue of antibiotic resistance and the importance of antibiotic, and possibly antiseptic, stewardship, benzoyl peroxide is a promising pre-surgical preparation agent in dermatologic surgery of sebaceous areas.

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