Antibiotics in Mohs Micrographic Surgery: Strategies for Prophylaxis and Effective Utilization

Function

Antibiotic prophylaxis for MMS is considered for SSI, endocarditis, and prosthetic joint infection prevention. Each of these issues will be discussed and considered separately, but SSI warrants special consideration since dermatologic surgery which does not breach the oral mucosa is unlikely to cause endocarditis or prosthetic joint infection without SSI and subsequent hematogenous dissemination of the bacteria. Due to the low risk of SSI in cutaneous surgery, identifying individuals at increased risk for SSI and subsequent bacterial dissemination is imperative to direct prophylactic therapy.

Surgical site infection is defined by the United States Centers for Disease Control and Prevention (CDC) as an infection of the cutaneous and subcutaneous tissue that occurs within 30 days of the surgery.[7] Regular use of prophylactic antibiotics is not warranted due to the inherent low risk of infection after cutaneous surgery. However, certain endogenous and exogenous risk factors have been shown in the literature to predispose patients to infection after MMS. Some patient-specific risk factors that increase the risk of SSI include diabetes, smoking, elevated body mass index (>25 kg/m), anticoagulation therapy, hypoalbuminemia, nasal Staphylococcus aureus carriage, anatomic site, and age. Exogenous factors that are associated with increased risk of SSI include lack of sterile draping, extended operation duration (>24 min), excision size, hemostasis issues, type of reconstruction (graft versus flap), and healing by secondary intention. A recent study evaluated the effect of mask-wearing during the COVID-19 pandemic on Mohs surgical sites and found an increased risk of SSI with a propensity for gram-negative organism growth compared to matched controls in the pre-COVID-19 pandemic era.[8]

The 2008 JAAD advisory statement reviewed several prospective studies to help guide their recommendations. In a prospective trial to find SSI rate after both MMS and dermatologic surgery that included 5091 lesions on 2424 people, they found certain scenarios to yield an unacceptable SSI rate. The rate of infection of any procedure below the knee, in the groin, wedge excisions, and skin grafts were all over 5%. Thus suggestions are to provide antibiotic prophylaxis in these circumstances.[9] 

Another prospective, multicenter study that included 3491 surgical procedures found infections were more common in flap closures, skin grafts, use of nonsterile gloves after hematoma formation, and those performed on patients with immunosuppression.[10] Finally, they evaluated a trial involving 857 cutaneous surgeries, which found unacceptably high infection rates in patients with diabetes, skin cancer surgeries (compared to benign lesion excisions), and surgical sites of the lower extremities.[11] The consensus statement recommends antibiotics in all these situations, demonstrating a high risk for SSI across multiple publications.[6]

In addition to recognizing the risk factors associated with SSI, the consequences of SSI based on anatomic site should be considered when deciding on antibiotic prophylaxis. Due to the nature of MMS, the surgeries are often on cosmetically sensitive areas, which can require complex closure techniques or skin grafting. An SSI of these areas could cause more distortion or scarring than a simple surgical excision. Therefore, assessing the consequence of poor cosmetic outcomes and any existing risk factors discussed above should be considered and used to assist the Mohs surgeon in risk mitigation and selecting proper candidates and antibiotic regimens for SSIs.

Next, endocarditis prevention will be considered. In the most recent guidelines, the AHA recommended reducing the number of conditions that require preprocedural prophylaxis due to the lack of increased risk of endocarditis in those receiving and not receiving prophylaxis. Some conditions that no longer require antibiotic prophylaxis secondary to these findings include mitral valve prolapse, bicuspid valve disease, calcified aortic stenosis, and several congenital heart conditions (atrial septal defect, ventricular septal defect, and hypertrophic cardiomyopathy).

The conditions for which antibiotic prophylaxis is still indicated are prosthetic heart valves, history of infective endocarditis, cardiac transplant patients with cardiac valvular disease, cardiac valve repairs with prosthetic material or a device that has been repaired within the last six months, unrepaired congenital heart defects and repaired congenital heart defect with residual defect at or adjacent to the site of a prosthetic patch or device.[4] Any patient with the above conditions who undergo perforating dermatologic procedures of the oral mucosa, surgery of non-oral sites that are infected, or sites that are high risk for SSI should receive antibiotic prophylaxis.[6]

The guidelines also identify high-risk groups of orthopedic patients to acquire prosthetic joint infection. These high-risk features include being within two years of a joint replacement, previous joint infection, immunosuppression, insulin-dependent type 1 diabetes, HIV infection, malignancy, malnourishment, and hemophilia. In these high-risk groups, the guidelines recommend antibiotic prophylaxis for perforating dermatologic procedures of the oral mucosa, surgery of infected non-oral sites, or sites at high risk for SSI.[6]

As outlined separately by the 2007 AHA guidelines and the 2003 ADA and AAOS guidelines, the antibiotic regimens were merged in the 2008 JAAD advisory statement. The purpose of merging the regimens was to simplify the implementation for dermatologic surgeons and was justified by the similarities between the two guidelines and a common underlying mechanism of infection between endocarditis and hematogenous joint infection. These antibiotic regimens apply to both endocarditis and prosthetic joint infection prevention. The AHA recommends administration of the prophylactic antibiotic 30-60 minutes before the procedure, whereas the ADA/AAOS recommends a full 60 minutes. The JAAD advisory statement does not indicate a preference for either time frame.[6]

The suggested prophylaxis regimens for dermatologic surgical procedures that break the oral mucosa or involve infected skin are as follows. For non-oral sites, the suggested antibiotic prophylaxis is cephalexin or dicloxacillin 2 g or either clindamycin 600 mg or azithromycin 500 mg for those patients with a penicillin allergy. If the patient cannot tolerate oral medications, cefazolin or ceftriaxone 1 g may be administered intramuscularly (IM), intravenously (IV), or clindamycin 600 mg IM/IV if the patient is penicillin allergic.

If the skin is infected, the antibiotic should be tailored to the organism’s susceptibilities and the patient’s medication allergies. For those sites that breach the oral mucosa in patients without a penicillin allergy, amoxicillin, 2 g, is recommended. In those patients with a penicillin allergy and surgical breach of the oral mucosa, either clindamycin 600 mg or azithromycin 500 mg is recommended. In patients who cannot tolerate oral medications and the surgery breaches the oral mucosa, cefazolin 1 g IM/IV, ceftriaxone 1 g IM/IV, or ampicillin 2 g IM/IV may be administered. Finally, in those who are penicillin allergic and unable to tolerate oral medications, clindamycin 600 mg IM/IV may be considered.[6]

A study was conducted to investigate whether postoperative antibiotics are linked to a reduced rate of surgical site infections (SSI). However, the study's findings were inconclusive due to limitations such as a small sample size and low infection rates observed during the study.[12] No extensive studies indicate if postoperative antibiotics have a favorable risk-to-benefit ratio. Because of this, postoperative antibiotics should be administered when there is a high risk of SSI based on factors already discussed, or there is clinical suspicion of SSI. If there is suppuration, wound cultures should be obtained before antibiotic administration. The chosen antibiotic should cover organisms most likely to infect the anatomic site and then can be tailored based on culture results and susceptibilities.[13] 

The most common organisms to infect a cutaneous surgical site include Staphylococcus aureus, coagulase-negative staphylococci, enterococci, Escherichia coli, Pseudomonas aeruginosa, and Enterobacter species.[14] Penicillins and cephalosporins are commonly the first-line agents for cutaneous infection. If a methicillin-resistant strain is the suspected pathogen, then a medication that covers methicillin-resistant Staphylococcus aureus (MRSA) should be chosen.[13] The oral medications that cover MRSA strains include tetracycline, trimethoprim-sulfamethoxazole, and clindamycin.[6] 

Finally, the anatomic site should be considered. The bacteria Pseudomonas aeruginosa is a common pathogen of the ear, and second-generation fluoroquinolones are the primary treatment with ciprofloxacin, often the medication of choice to cover this gram-negative organism. The oral cavity harbors many bacterial species, with the most common infecting organisms being Streptococcus viridans and Peptostreptococcus. Any infection near the oral mucosa should be covered with amoxicillin to cover for these pathogens.[13]

Issues of Concern

Ensuring thorough patient medication allergy checks is essential to prevent avoidable adverse events when considering antibiotic prophylaxis or administering antibiotics for suspected or confirmed bacterial infections. Furthermore, prescribers should know about the most frequent and severe adverse events associated with commonly prescribed medications. This enables physicians to educate patients, offer appropriate informed consent, and provide necessary counseling regarding potential risks and benefits.

According to a study by the Centers for Disease Control and Prevention (CDC), antibiotics were responsible for approximately 142,000 emergency room visits between 2004 and 2005. These visits were attributed to adverse events such as allergic reactions, medication errors, and overdoses associated with antibiotic use. This highlights the importance of appropriate antibiotic prescribing, monitoring, and patient education to mitigate potential harm and ensure safe medication practices.[15] This statistic underscores the importance of understanding the most frequent adverse events associated with prescribed medications.

Here is a concise overview of the common and severe adverse events related to the antibiotics mentioned earlier.

Many oral antibiotics administered for cutaneous infection and prophylaxis, especially penicillins and cephalosporins, have the common adverse effects of gastrointestinal upset, such as nausea and diarrhea. In addition, both medication classes have been associated with hypersensitivity reactions, and the more severe acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN), and anaphylaxis.[16] 

Studies suggest that the cross-reactivity between penicillins and cephalosporins in patients with penicillin allergies is relatively low, with estimates indicating that no more than 2% of patients allergic to penicillins will experience cross-reactivity with cephalosporins. It is worth noting that early perceptions of high cross-reactivity were inflated due to the contamination of early cephalosporin preparations with penicillin.[16] Amoxicillin, frequently prescribed for oral mucosal breaches, is associated with low rates of adverse effects, with the most common being diarrhea when used in combination with clavulanate. However, statistics from the Allergy Vigilance Network of Europe indicate that penicillins, cephalosporins, and amoxicillin collectively accounted for 42.6% of reported anaphylactic reactions between 2002 and 2010.[17]

Azithromycin and clindamycin are recommended as second-line agents for prophylaxis of cutaneous infection in patients with penicillin allergies. Azithromycin belongs to the macrolide class of antibiotics and is associated with common adverse effects such as hypersensitivity reactions and photosensitivity. However, it is essential to note that azithromycin can also cause more severe adverse effects, including QT prolongation and a rare arrhythmia called torsades de pointes. Careful monitoring and appropriate patient selection are essential when using these antibiotics as alternatives to penicillin in allergic patients.[18] Clindamycin, a lincosamide antibiotic, is known to have a higher incidence of adverse effects such as rashes and diarrhea. However, a more severe adverse effect associated with clindamycin use is the development of pseudomembranous colitis, which occurs in approximately 2% of individuals who receive this medication. Cases of pseudomembranous colitis can occur up to 6 weeks after completing therapy, highlighting the importance of monitoring patients closely even after treatment completion.[19] Ciprofloxacin is a second-generation fluoroquinolone often prescribed to cover Pseudomonas infection of the ear and is associated with tendonitis and tendon rupture.[20]

Rise in Antimicrobial Resistance and Healthcare Spending

Two other issues of concern include the rise in antimicrobial resistance and healthcare spending. Antimicrobial resistance is an increasing concern worldwide, and studies have shown an increase in MRSA. Rising healthcare costs in the United States have also been a recent concern. According to a 2019 study published in JAMA, healthcare spending wastage was estimated to range from 760 to 935 billion dollars annually, accounting for approximately 25% of total healthcare spending.[21] Active participation in the prudent prescription of antibiotics plays a significant role in antimicrobial stewardship efforts and helps reduce unnecessary healthcare expenditures.

Clinical Significance

SSI rates after MMS can vary depending on factors such as the anatomic site, closure method, and other variables. However, these rates are generally low, typically ranging from around 1.4% to 2.7%.[1]

Rates of endocarditis and prosthetic joint infection are even lower. A survey was sent to the American College of Mohs Surgery members in 2012. With 230 respondents, there were no reports of infective endocarditis following a cutaneous surgery and only one report of prosthetic joint infection. The prosthetic joint infection reportedly occurred following a skin infection of a biopsy site that subsequently seeded the knee joint.[22] In addition, the rate of bacteremia after cutaneous surgery is around 0.7% which is lower than the higher end of positive blood cultures (2.1%) found in healthy patients.[23] 

This study concluded that cutaneous surgeons overuse antibiotics for prophylaxis of endocarditis and prosthetic joint infection based on the current guidelines.[22] This highlights the variability in practice between surgeons and the need to focus on best practices to avoid adverse effects, adding to unnecessary healthcare spending and increasing antimicrobial resistance, as outlined above.

Other Issues

Wound care post-MMS varies widely among Mohs surgeons. Topical antibiotics have not shown benefit in MMS wounds closed by primary intention and have been shown to have a risk of contact allergy.[24] Research has demonstrated that petrolatum or topical silicone usage on clean dermatologic wounds does not demonstrate an increased infection rate compared to wounds in which topical antibiotics were applied.[25] Given the risk of contact dermatitis with some topical antibiotics and no infection rates with petrolatum, topical antibiotics use should be carefully considered in MMS surgical sites.

Some patients are chronic carriers of Staphylococcal aureus in their nares and present with recurrent MRSA infections. Although mupirocin has been useful in preventing staphylococcal nasal carriage in patients, it has not been demonstrated to prevent SSI when administered preoperatively.[26] Despite this information, some studies have recommended treating patients with nasal mupirocin if their nasal culture-confirmed Staphylococcus aureus growth, and they have recurrent MRSA infections.[27]

Enhancing Healthcare Team Outcomes

In the context of Mohs micrographic surgery, the responsibility for implementing appropriate antibiotics lies with the Mohs surgeon, but the support of an interprofessional team is crucial for optimal patient care. Nurses and medical assistants play a critical role by ensuring updated allergy information, making recommendations to clinicians based on their observations, and educating patients on medication administration. Pharmacists, on the other hand, contribute by preventing adverse drug interactions, suggesting alternative medications, counseling patients on proper administration, and providing antibiotic coverage information to the surgeon, thereby improving antibiotic effectiveness and helping to prevent antibiotic resistance.

While randomized controlled trials evaluating community pharmacist services in preventing adverse drug effects have shown mixed results, it is important to acknowledge that all members of the interprofessional healthcare team have a vital role in ensuring the appropriate and safe use of antibiotics in the context of Mohs micrographic surgery. Collaborative efforts among team members contribute to optimal patient outcomes.[28] [Level 1]