Australasian Journal of Dermatology (2016) 57, 83–91

doi: 10.1111/ajd.12312

REVIEW ARTICLE

Prophylactic antibiotics in dermatological surgery Michael R Lee and Robert Paver Skin and Cancer Foundation, Sydney, New South Wales, Australia

ABSTRACT This is a review of the common pathogens of surgical site infections, antibiotic coverage for particular anatomical sites, mechanisms by which surgical site infections occur and the latest data and recommendations for prophylactic antibiotics in the prevention of surgical site infections, infective endocarditis and haematogenous joint infections. Recent evidencebased guidelines on surgical prophylaxis is for restricted indications and a shorter duration of antibiotic prophylaxis in situations where no clinical benefit of prolonged therapy has been proven, in order to minimise the potential adverse ecological and clinical effects associated with antibiotic therapy. This review recommends the cautious use of prophylactic antibiotics in dermatological surgery to help prevent the growing problem of bacterial resistance as well as other morbidity and health-care costs.

INTRODUCTION Postoperative infections remain a serious concern for the dermatological surgeon. Surgical site and systemic infections lead to associated morbidity and surgical site infections may lead to worse cosmetic results. Many dermatological surgeons regularly prescribe preoperative and postoperative antibiotics in an attempt to prevent surgical site infections and this may lead to increased bacterial resistance, increased morbidity and unnecessary healthcare costs. Infections complicating dermatological surgery are relatively infrequent and when they occur, most are at the surgical site. The incidence of surgical site infections1–7 is variable, depending on the surgical site, the type and length of the procedure, the type of surgical repair, the

Correspondence: Dr Michael R Lee, Skin and Cancer Foundation, 7 Ashley Lane, Westmead, NSW 2145, Australia. Email: [email protected] Michael R Lee, FACD. Robert Paver, FACD. Conflict of interest: none Submitted 14 August 2013; accepted 15 December 2014. © 2015 The Australasian College of Dermatologists

definition used for a surgical site infection, the patient’s medical history and whether prophylactic antibiotics were used. Several studies outlining the rates of surgical site infections are compared in Table 1.1–7 The mechanism by which infective endocarditis and haematogenous joint infections occurs is through bacteraemia. Bacteraemia may occur rarely following dermatological surgery, and the incidence is reassuringly low. In a study of 149 immunocompetent patients with non-infected cutaneous lesions, the incidence of postoperative bacteraemia was reported to be 0.7%.8 The procedures included biopsies, flaps, grafts and micrographically controlled surgery. When assessing the potential value of prophylactic antibiotics one must consider the benefits and the risks, which include adverse events, allergies, the cost to the health-care system and the development of antimicrobial resistance. A study of 142 000 visits to the emergency department for drug-related adverse events demonstrated that 19% were due to antibiotics. One-half of these visits were attributable to penicillins and cephalosporins.9 The prevalence of Clostridium difficile infection is related to total antibiotic usage and, in particular, extended spectrum generation cephalosporins.10 An orthopaedic study demonstrated that three doses of cefuroxime increased the risk of C. difficile diarrhoea (4%) compared with one dose of cefuroxime and gentamicin (2%). Patients with C. difficile infection had a statistically significant increase in antibiotic exposure, inpatient stay, morbidity and mortality.11 Another study demonstrated a significant reduction in C. difficile-associated diarrhoea when the amount of cephalosporins administered was reduced.12 The prevalence of antibiotic resistance is related to the proportion of the population that receives antibiotics and the total antibiotic exposure.10 In a study of coronary artery bypass graft surgery, prolonged antibiotic prophylaxis (>48 h) was associated with an increased risk of acquired antimicrobial resistance (OR 1.6).13 Cardiac patients receiving perioperative vancomycin (one dose preoperatively and two doses postoperatively) were screened for the emergence of vancomycin-resistant Enterococcus colonisation (VRE). No patient was VRE positive at baseline and 4% were positive

Abbreviations: IDSA MRSA VRE

Infectious Diseases Society of America methicillin-resistant Staphylococcus aureus vancomycin-resistant Enterococcus colonisation

693

738

2370

1204

1115

3491

1358

1

2

3

4

5

6

7

Cases (n)

© 2015 The Australasian College of Dermatologists

Prospective study

Prospective study

Prospective study

Prospective study

Prospective audit

Prospective randomised trial

Randomised controlled trial

Type of study

Mohs

Excisions with suture, flaps and grafts

Mohs surgery and ‘slow Mohs’

Mohs surgery

Mohs, excisional surgery, biopsy, shave, curettage, snip excision

Mohs surgery

Mohs surgery

Type of procedure

Immunocompromised, diabetics, flaps and grafts Flaps, grafts or procedures on the nose, in the groin or axillae and compromised auricular perichondrium

Nil

Topical decolonisation vs nil topical decolonisation in nasal S. aureus carriers Clinical indication (infective endocarditis, infected lesion), high-risk cases (skin grafts on lower leg, complex procedures on ear and nose) and all Mohs Nil

Topical decolonisation vs oral antibiotics in nasal S. aureus carriers

Use of prophylactic antibiotics

Comparable studies outlining the rate of surgical site infections

Reference

Table 1

Not specified Estimated > 43 (362 flaps + 216 grafts of 1358 procedures)

2

–

–

51

–

50% of nasal S. aureus carriers

Patients prescribed prophylactic oral antibiotics (%)

1

1.9%

1

1

0.5

4 in decolonised group; 11 in non-decolonised group

Overall 6; 0 in decolonised group; 9 in oral antibiotic group

Infection rate (%)

Clean technique for Mohs stages and sterile technique for repair

Clean technique for Mohs stages and repair Sterile technique for first stages and repairs. Clean technique for subsequent stages Variable

Aseptic technique for Mohs repair stage and excisional surgery. Clean technique for Mohs surgical stages and others (shaves and curettes)

Clean technique for Mohs stages and aseptic technique for repair stage Not stated

Sterility of procedure

84 MR Lee et al.

Prophylactic antibiotics

at day 7.14 A study of patients who had free flap reconstructions of head and neck defects compared the acquisition of methicillin-resistant Staphylococcus aureus (MRSA) in those who received 24 h of antibiotics with those who were administered a 5-day course of antibiotics. There were significantly fewer patients with wounds infected with MRSA in the 24-h course group (4/33 compared to 13/31).15 The evidence suggests that inappropriate prolonged postoperative antibiotic exposure contributes to growing antibiotic resistance.

GENERAL PRINCIPLES OF SURGICAL ANTIBIOTIC PROPHYLAXIS Antibiotic prophylaxis should be considered only when there is a significant risk of postoperative infection with significant morbidity. Prophylactic antibiotics should be directed against the bacteria most likely to cause infection and it is not necessary to target all potential pathogens. Regimens that reduce the total number of organisms assist the host’s defences and thus reduce the development of infection. In choosing prophylactic antibiotic(s) the clinician should consider patient’s factors, such as colonisation with a multi-drug resistant organism or whether the patient has had a similar pre-existing infection. The narrowest spectrum antimicrobial should be used to treat the likely pathogen. Surgical antibiotic prophylaxis is not the only strategy to minimise surgical site infections. A holistic approach to the patient, such as maximising the patient’s medical management perioperatively and ensuring that operating staff adhere to strict theatre protocols to minimise crossinfection between staff and patient as well as instrument and operating room contaminants, is required.

PATHOGENS AND ANTIBIOTIC COVERAGE FOR ESTABLISHED SURGICAL SITE INFECTIONS ACCORDING TO ANATOMICAL SITE Normal and transient bacteria vary among the different anatomical sites; thus the selection of an antibiotic, if required, for a surgical site infection should reflect the predominant pathogen at that particular anatomical site. If a diagnosis of a surgical site infection is made, a swab of the wound for microscopy, culture and sensitivities should be performed. Empiric antibiotic therapy should be initiated and modified based on the culture results once they are available.

Skin The primary pathogens on glabrous skin include S. aureus and beta-haemolytic streptococci. Penicillinase resistant antibiotics such as di-flucloxacillin or cephalexin are effective against both organisms. For patients allergic to penicillin and cephalosporins, clindamycin or vancomycin may be administered. If the patient is known to have MRSA then clindamycin, trimethoprim-sulfamethoxazole or doxycycline may be administered. S. epidermidis is part of

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the normal skin flora; however, it is a low-virulence organism that causes disease primarily in immunocompromised patients and in those with implants.16

Oropharynx The primary pathogens arising from the oropharynx are viridans group streptococci and bacteria that are known to cause infective endocarditis. Antibiotics are generally recommended only for oropharyngeal procedures in patients who have an increased risk of infective endocarditis, such as those with prosthetic valves, complicated congenital cardiac abnormalities and high-risk rheumatic heart disease. Where antibiotics are indicated, amoxicillin is the treatment of choice, with clindamycin being a suitable alternative for patients with penicillin allergy.16

Intertriginous sites In addition to S. aureus and beta-haemolytic streptococci, the axillary, groin and perineal areas are also colonised with gram negative bacilli such as Escherichia coli, which may cause surgical site infections. E. coli are usually sensitive to cephalosporins but this is variable.16

Ear S. aureus and beta-haemolytic streptococci are found in the ear and the antibiotic of choice for an infection is the same as for other skin infections. Pseudomonas is a gram negative rod that readily grows in moist areas of the skin and thus is a potential pathogen in the ear and digital spaces. Acute localised otitis externa is usually caused by S. aureus or S. pyogenes and is usually a complication of an infected hair follicle. Acute diffuse otitis externa follows the maceration of the ear canal after water exposure. P. aeruginosa and S. aureus may be implicated in this condition, which is usually treated with a topical combination corticosteroid and antibiotic (framycetin and gramicidin) ear drops. Malignant or necrotising otitis externa is a severe complication of acute otitis externa usually caused by P. aeruginosa and requires the involvement of an infectious disease specialist and aggressive therapy with i.v. antipseudomonal antibiotics such as piperacillin and tazobactam.16

RISK FACTORS FOR SURGICAL SITE INFECTIONS Several patient factors contribute to the development of surgical infections, including related comorbidities, the preoperative state of the skin, bacterial carrier status, and the location and type of surgery. A Queensland study showed that diabetes was significantly correlated with a higher incidence of infection; with an incidence of 18 versus 8% in non-diabetics.17 Skin wound healing has been shown to be worse in smokers than non-smokers and thus results in poorer cosmetic outcomes.18 Tobacco smoking is associated with a higher incidence of postoperative complica© 2015 The Australasian College of Dermatologists

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tions, including wound dehiscence, flap or graft necrosis, prolonged healing time and infections.19 Immunosuppression is a risk factor for surgical site infection following excisions with reconstruction (full thickness skin grafts and flaps) rather than excisions alone.6,20,21 The preoperative state of the skin is an important determinant of surgical site infections. A prospective study demonstrated the risk of surgical site infection was significantly increased for scaly (12%), crusted (18%) and ulcerated (33%) skin surfaces than with with intact surfaces (4%). Older patients were also more likely to have lesions with a broken skin surface.22 Filaggrin mutations are associated with recurrent skin infections in patients with atopic dermatitis due to the impairment of the skin barrier function. In patients with filaggrin mutations there is increased transepidermal water loss and increased pH of the skin mantle, which may facilitate the overgrowth of S. aureus. This was demonstrated in a study of patients with atopic dermatitis who had filaggrin mutations. Compared with those without filaggrin null mutations, patients with atopic dermatitis who had filaggrin null mutations had about sevenfold the risk of more than four episodes of skin infections requiring antibiotics in the previous year.23 A prospective study of dermatology patients who underwent a dermatological procedure (such as elliptical incisions, punch incisions, shave biopsies or curettage and cautery) in the ward demonstrated a higher complication rate (infection and wound dehiscence) than those who had the procedures performed in an outpatient setting (53 vs 17%).20 It is postulated that the dermatology ward inpatients were more likely than their outpatient counterparts to have more widespread skin disease, possibly colonised with S. aureus, to be systemically unwell and to require intensive topical therapy for their underlying dermatoses. There is evidence that nosocomial S. aureus infections originate from patients’ own flora.24 The ecological niche of S. aureus is the anterior nares and 30% of the population is colonised at any given time.25 Nasal carriage of S. aureus is a risk factor for surgical site infections, with carriers having three to sixfold the risk of surgical site infection of noncarriers and low-level carriers.26 A study demonstrated that S. aureus strain isolated from the nares was identical to the infected site in 85%.27 A Western Australian randomised controlled study showed that nasal carriers of S. aureus have a higher risk of surgical site infections, with a relative risk of 3.4 compared to non-carriers.2 Wound location and the type of surgery have been shown to be risk factors for the development of surgical site infections. The Mayo Clinic identifies specific locations and surgical techniques at increased risk for surgical site infection. These include the lower extremities, groin, a wedge excision of the ear or lip, repair with skin flaps of the nose, skin grafts and those with extensive inflammatory disease.28 It is important to recognise that the Mayo Clinic guidelines are based on prospective studies rather than large randomised controlled trials delineating the risk of surgical site infection. A prospective, observational study from Queensland demonstrated that excisions from the lower leg, feet and thighs were independent risk factors for infection. Patients © 2015 The Australasian College of Dermatologists

were excluded from the study if they were already taking oral antibiotics or if topical or oral antibiotics were indicated postoperatively.17 A prospective study of dermatological procedures including elliptical incisions, punch incisions, shave biopsies and curettage and cautery demonstrated a higher rate of wound complications (dehiscence and wound infections) when they were performed below the waist compared with above the waist (48 vs 23% on univariate analysis).20 A prospective study of patients undergoing Mohs micrographic surgery or scalpel-based excisional surgery requiring sutures demonstrated higher surgical site infection rates in the genital area (14%), leg (3%) and hand (3%) versus an overall infection rate of 1%.29 Infection rates of ear surgery have been reported to be as high as 13%, much greater than non-auricular sites. The infection rate of excision at the level of cartilage is much greater (29%) than the infection rate of procedures without cartilage involvement (6%).30 With regard to the type of procedure performed, skin flaps have been demonstrated to have rates of infection ranging from 25 to 3%4 in the absence of antibiotic prophylaxis. Exogenous factors also play a role in the development of surgical site infections. Preoperative preparation such as removal from operating staff of hand jewellery, artificial nails and nail polish is recommended. The National Institute for Health and Clinical Excellence (NICE) guidelines recommend that routine hair removal should be avoided. If the hair has to be removed then using electric clippers with a single-use head on the day of surgery rather than a razor is recommended, as the latter increases the risk of surgical site infection. The operating team should wash their hands prior to the first operation using an antiseptic surgical handwash and ensure that their hands and nails are visibly clean. Before subsequent operations, the hands can be washed with either an alcoholic hand rub or an antiseptic surgical handwash. The skin at the surgical site should be prepared immediately before incision using an antiseptic such as povidone-iodine or chlorhexidine.31 Meticulous haemostasis, surgical technique and the level of training of the dermatological surgeon are important factors in minimising surgical site infections.20 Thus, the dermatological surgeon needs to be aware of such endogenous and exogenous variables when operating and ensure that infection control guidelines are strictly adhered to to prevent nosocomial infections.

WOUND CLASSIFICATION Dermatological wounds can be classified into four categories.32 Class I wounds are clean, non-contaminated, closed by suturing and there are no breaks in aseptic technique. The risk of infection in this class has been reported to be less than 5%. Class II wounds are clean-contaminated wounds, such as those in the oral cavity, axillary or inguinal areas and wounds left to heal by secondary intention. In these wounds the risk of infection has been reported to be less than 10%. Class III wounds are contaminated and are acute, traumatic wounds that are non-purulent or where there are major breaks in the aspetic technique. The risk of

Prophylactic antibiotics

infection in class II wounds has been reported to be 20–30%. Class IV wounds are infected wounds characterised by purulent inflammation, foreign body contamination or devitalised tissue. In these the risk of infection has been reported to be 40%. Both class III and IV wounds warrant antibiotic treatment.32

PROPHYLACTIC ANTIBIOTICS FOR SURGICAL SITE INFECTION The Centre for Disease Control defines a surgical site infection as an infection that occurs after surgery in the part of the body where the surgery took place. Surgical site infections can be superficial infections involving the skin only or more serious infections, which can involve tissues under the skin, other organs, or implanted material. Symptoms include erythema, tenderness and purulent exudate around the surgical site. Several studies outlining the rates of surgical site infections are compared in Table 1.1–7 Minimising the risk of surgical site infections is important as it potentially prevents local consequences such as increased morbidity, the distortion of the normal anatomy and thus a poor cosmetic outcome.

Decolonisation In view of the evidence that nasal carriage of S. aureus is a risk factor for surgical site infections, recent studies have investigated preoperative screening for S. aureus and the prophylactic application of intranasal mupirocin and chlorhexidine washes to reduce the rate of surgical site infections. Screening has also been advocated to both identify candidates for S. aureus decolonisation and to inform optimal antimicrobial prescription for those colonised with MRSA. The data are most compelling in cardiac and orthopaedic surgery patients who were nasal carriers of S. aureus, were decolonised with prophylactic intranasal mupirocin and had lower rates of surgical site infections.33,34 In a randomised, double-blind, placebo-controlled trial of general surgical, gynaecological, neurological and cardiothoracic patients there was no significant difference in the rate of surgical site infections between the intranasal mupirocin and placebo groups (2.3 vs 2.4%). However, of the patients who had S. aureus in their anterior nares, 4% of those who received intranasal mupirocin had nosocomial S. aureus infections versus 8% in those who received placebo.27 This study suggests that topical intranasal mupirocin should be used only in S. aureus carriers and not as a generalised prophylactic measure. A randomised, double-blind, placebo controlled trial of surgical and medical inpatients showed the number of surgical site S. aureus infections acquired in hospital was reduced by screening and decolonising S. aureus nasal carriers on admission.26 In this study, 1251 patients tested positive for S. aureus on polymerase chain reaction and a

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subsequent 918 patients were randomised to either active treatment with mupirocin ointment 2% in combination with chlorhexidine gluconate soap or placebo ointment in combination with placebo soap. Among those randomised, the rate of S. aureus infection was 3% in the mupirocinchlorhexidine group compared with 8% in the placebo group. The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocinchlorhexidine group. The mean hospital stay was also significantly reduced by 2 days in the interventional group. Prophylactic application of intranasal mupirocin and chlorhexidine gluconate washes in reducing the rate of surgical site infections was further highlighted in a Western Australian study.2 In this study of Mohs surgical cases, 738 cases underwent a nasal swab to determine their S. aureus carriage; 203 tested positive for S. aureus. Of the 102 cases that received decolonisation with mupirocin and topical chlorhexidine gluconate wash for 5 days preoperatively, 4% developed a surgical site infection versus 11% of the 101 patients who did not receive decolonisation. In this study, 96% of all cases involved the head and neck, of which 39% involved the nose. Skin flaps and grafts were utilised in 94% of the cases. The authors advocated that an alternative approach would be to screen all patients for nasal carriage of S. aureus in patients undergoing dermatological surgery and to subject them to decolonisation rather than place them on oral systemic prophylactic antibiotics, if indicated. In regard to whether topical or oral antibiotic prophylaxis is superior in the prevention of surgical site infections, a randomised controlled study showed that topical decolonisation resulted in fewer surgical site infections than in patients receiving perioperative oral antibiotics.1 This was a study of Mohs surgical patients who were stratified into nasal carriers or non-carriers of S. aureus, based on a preoperative swab. Nasal carriers were randomised to receive either topical decolonisation with intranasal mupirocin twice daily plus chlorhexidine gluconate body wash for 5 consecutive days before surgery or to oral cephalexin 2 g preoperatively and 1 g postoperatively. The infection rate for the group that had received oral antibiotic prophylaxis was 9% in contrast to 0% in the group who received topical decolonisation. The infection rate was 6% in the non-carrier group. These studies suggest that screening and decolonising S. aureus nasal carriers with topical mupirocin and chlorhexidine washes may reduce the risk of surgical site infections. This raises the question whether all preoperative patients should undergo topical decolonisation, given that S. aureus also resides in areas such as the axillae and groin. We await further studies in this area including a costeffectiveness study in this setting. A concern in the use of mupirocin is the development of resistance. This has been observed when mupirocin has been used for a prolonged period of time as a skin ointment. However, resistance rarely develops when it is used for short periods in the preoperative setting.35 The Australian therapeutic guidelines do not recommend antibiotic prophylaxis for routine sterile dermatological surgery, although it may be indicated in patients who have risk factors (as discussed in the risk factors for surgical site © 2015 The Australasian College of Dermatologists

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88 Table 2

Prophylactic antibiotics for dermatologic surgical procedures.

Location or type of surgery

Antibiotic restriction

Antibiotic

High risk for surgical site infection

No penicillin allergy

Di/Flucloxacillin (oral) Cephazolin (IV) Cephalexin (oral) or Cephazolin (IV) excluding immediate hypersensitivity Clindamycin (oral) or vancomycin (IV) for immediate hypersensitivity

Penicillin allergy

Oral (Mayo clinic advisory statement extends this area to the non glabrous oral tissue posterior to the junction where closed lips meet) in patients at high risk for infective endocarditis* and haematogenous joint infection** * Australian therapeutic and Mayo clinic guidelines ** Mayo clinic guidelines

No penicillin allergy Penicillin allergy

Amoxycillin (oral) Ampi/Amoxycillin (IM or IV) Cephalexin (oral) or cephazolin (IM, IV) excluding immediate hypersensitivity Clindamycin (oral or IV) for immediate hypersensitivity

Adult dosage One hour preoperatively 2g 2g 2g 600 mg 15 mg/kg for vancomycin infusion 2g 2g 2g

600 mg

IM = Intramuscular. IV = Intravenous.

infections section) for a postoperative infection (Table 2).36 The Australian therapeutic guidelines recommend screening for S. aureus in patients at high risk of MRSA carriage. It recommends screening in all patients undergoing prosthetic joint, vascular or cardiac surgery and in patients who have recently been hospitalised. It recommends prophylactic intranasal mupirocin and chlorhexidine washes preoperatively for patients colonised with S. aureus, in particular patients undergoing high-risk surgery (prosthetic implantation and cardiothoracic surgery). In high-risk patients, routine decolonisation without screening is an alternative approach.36 The NICE guidelines do not recommend routine antibiotic prophylaxis for clean, uncomplicated non-prosthetic surgery and does not recommend topical mupirocin for nasal decontamination.31 The Scottish Intercollegiate Guidelines Network (SIGN) statement does not recommend antibiotic prophylaxis in patients undergoing clean facial or nasal procedures without an implant. However, it recommends prophylactic intranasal mupirocin for patients undergoing high-risk surgery (cardiothoracic, orthopaedic, neurosurgery and vascular surgery) who are colonised with S. aureus or MRSA.10 Similarly the Infectious Diseases Society of America (IDSA) concludes that antibiotic prophylaxis is not recommended for clean procedures, although the IDSA advocates that patients having a clean procedure with risk factors for a surgical site infection (as discussed in the risk factors for surgical site infections section) should receive antibiotic prophylaxis.37 The use of antibiotics for contaminated, dirty procedures or established infections is classified as treatment, not prophylaxis.

Prophylactic topical antibiotics in the postoperative phase The consequences of the unnecessary and prolonged use of topical antibiotics in postoperative care includes allergic © 2015 The Australasian College of Dermatologists

contact dermatitis, cost to the patient and the health-care system in addition to emerging antibiotic resistance. A recent study showed that prophylactic topical antibiotics continue to be prescribed by dermatologists for postoperative care.38 A prospective randomised controlled study showed that the application of paraffin or mupirocin ointment under a moist occlusive dressing made no difference to infection rates, the pain experienced, wound discomfort or long-term wound aesthetic outcomes compared with no application of the ointment. There was no significant difference in the infection rate between the three comparator groups: 1.4% with no ointment, 1.6% for paraffin and 2.3% for mupirocin (P = 0.49). There were fewer scar complications in the no ointment group (0% versus 0.7% in the paraffin group versus 1.2% in the mupirocin group) largely due to skin necrosis.39 A study of patients undergoing Mohs micrographic auricular surgery showed no statistically significant difference between the use of gentamicin ointment and petrolatum in the prevention of postoperative auricular suppurative chondritis. Eight of the 144 wounds developed suppurative chondritis; four received gentamicin (5%) and four received petrolatum (7%). Twelve of the 144 wounds developed inflammatory chondritis, 10 of which wounds received gentamicin (12%) and two received petrolatum (4%). This may represent allergic contact dermatitis to topical gentamicin.40 In view of the evidence, the authors recommend caution to the dermatological surgeon over the prolonged use of topical antibiotics in postoperative dermatological care. The Australian therapeutic guidelines specifically recommend against the application of topical antibiotics to surgical incisions for the prevention of surgical site infection.36 The NICE guidelines do not recommend topical antibiotics for surgical wounds that are healing by primary intention to reduce the risk of surgical site infection.31 Similarly, IDSA states that the safety and efficacy of topical antibiotics have not been clearly established and thus their routine use is not recommended for surgical procedures.37

Prophylactic antibiotics

PROPHYLACTIC ANTIBIOTICS FOR INFECTIVE ENDOCARDITIS AND HAEMATOGENOUS JOINT INFECTION The Australian antibiotic therapeutic guidelines recommend antibiotic prophylaxis for patients with cardiac conditions associated with the highest risk of adverse outcomes from endocarditis if they are undergoing a specified dental or other procedure.36 The high-risk group encompasses those with a prosthetic cardiac valve or prosthetic material used for cardiac valve repair; previous infective endocarditis; rheumatic heart diseases in highrisk patients and congenital heart disease, but only if it involves:(i) unrepaired cyanotic defects including palliative shunts and conduits, (ii) completely repaired defects with prosthetic material or devices, whether placed by surgery or catheter intervention, during the first 6 months after the procedure (after which the prosthetic material is likely to have been endothelialised), (iii) repaired defects with residual defects at or adjacent to the site of a prosthetic patch or device (which inhibits endothelialisation). The American Heart Association does not recommend prophylaxis for cardiac pacemakers and internal defibrillators. The Australian antibiotic therapeutic guidelines recommend amoxicillin 2 g 1 hour prior to undergoing a specified dental procedure that targets viridans streptococci, the primary oral pathogen responsible for infective endocarditis. Patients allergic to penicillin may be prescribed cephalexin 2 g or clindamycin 600 mg (Table 2).36 The Mayo Clinic advisory statement extends this area to oral mucosa (defined as the non-glabrous oral tissue posterior to the junction where closed lips meet).28 No prospective randomised controlled studies exist on the use of prophylactic antibiotics to prevent haematogenous joint infection in patients who have undergone a dermatological procedure. The Australian antibiotic therapeutic guidelines state that for patients with a pre-existing joint prosthesis in situ, there is a risk, though low, that seeding of the prosthetic site, with subsequent infection, can follow an incidental bacteraemia during the surgical procedure. Despite this, neither the indication for prophylaxis nor the choice of antibiotic regimen is altered by the presence of a joint prosthesis for dermatological procedures.36 The American Dental Association, however, in conjunction with the American Academy of Orthopaedic Surgeons, identifies a group of patients who are potentially at high risk of haematogenous joint infection secondary to bacteraemia. These include patients who have received a joint replacement in the preceding 2 years, those with a prior history of prosthetic joint infection; immunocompromised or immunosuppressed patients, including those with rheumatoid arthritis, systemic lupus erythematosus, drug-induced or radiation-induced immunosuppression; HIV infection, malignancy, malnourishment and haemophilia.41 In contrast to the Australian therapeutic guidelines, the Mayo Clinic advisory statement advises that if a high-risk patient

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is undergoing a dermatological procedure that involves or breaches the oral mucosa, a non-infected site that is at high risk for a surgical site infection, then antibiotics are recommended.28 The choices of antibiotics are the same as that for infective endocarditis (Table 2).

TIMING AND DURATION OF PROPHYLACTIC ANTIBIOTICS To be successful prophylaxis requires the delivery of the antibiotic to the surgical site prior to contamination. Therefore, prophylactic antibiotics should be administered at a time that will produce serum and tissue concentrations exceeding the minimum inhibitory concentration of likely pathogens for the duration of the operation. A prospective study of patients undergoing clean or clean-contaminated surgery (gynaecological, gastrointestinal and orthopaedic) demonstrated that the preoperative administration of antibiotics within 2 h before surgical incision decreased the risk of surgical site infection to 1%, compared with 4% for those administered antibiotics 2–24 h prior to surgical incision and 3% for any postoperative administration.42 A case-controlled study of patients undergoing orthopaedic surgery showed that the timing of preoperative antibiotic prophylaxis was an independent risk factor for surgical site infection. The rate of surgical site infection was higher in those receiving antibiotic prophylaxis more than 60 min before incision (OR 2.2) or after incision (OR 4.4) than in those who received antibiotic prophylaxis within 60 min before the incision.43 Other large-scale studies of general surgical, cardiac, orthopaedic and gynaecological patients showed there was a lower risk of surgical site infection with shorter times between the administration of the antibiotic prophylactic and the skin incision.44,45 Intraoperative redosing is required to ensure adequate serum and tissue concentrations of the antibiotic if the duration of surgery exceeds two half-lives of the antibiotic.37 This may be important in complex Mohs micrographic surgery where wounds may be open for an extended period of time. For many dermatological procedures performed in the office, this is not a concern. A single preoperative dose of antibiotic is a sufficient prophylaxis and evidence suggests there is no additional benefit from a prolonged postoperative antibiotic administration greater than 24 h. The prevalence of antibiotic resistance is related to the proportion of the population that receives antibiotics and the total antibiotic exposure.10 In a study of coronary artery bypass graft surgery, prolonged antibiotic prophylaxis (> 48 h) instead of a shorter duration of prophylaxis (< 48 h) failed to reduce the risk of surgical site infection. Prolonged prophylaxis was also associated with an increased risk of acquired antimicrobial resistance (OR 1.6).13 A study of cardiac patients receiving perioperative vancomycin (one dose preoperatively and two doses postoperatively) were screened for the emergence of VRE colonisation. No patient was VRE-positive at baseline and 4% were positive at day 7.14 A study of patients who had free flap reconstructions of head and © 2015 The Australasian College of Dermatologists

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neck defects compared the acquisition of MRSA in those who received 24 h of antibiotics with those who were administered a 5-day course of antibiotics. There were significantly fewer patients with wounds infected with MRSA in the 24-h course group (4/33 compared to 13/31).15 The evidence suggests that inappropriate, prolonged postoperative antibiotic exposure increases the risk of postoperative infection caused by multi-resistant microorganisms and other complications such as Clostridium difficile infection. The Australian therapeutic guidelines recommend that preoperative antibiotics should be administered within the 60 min before surgical incision with the exception of i.v. vancomycin: 15–30 min before surgical incision is optimal. Where an infusion is required, administration should ideally be finished before surgical incision. Intraoperative redosing is required only if the duration of surgery exceeds two half-lives of the antibiotic. Postoperative prophylactic antibiotics are not recommended. The continuation of antibiotics while waiting for noninfected skin grafts or flaps to epithelialise is not recommended.36 The NICE guidelines recommend a single prophylactic antibiotic dose up to 2 h preoperatively and the administration of a repeat dose of antibiotic prophylaxis only when the operation is longer than the half-life of the antibiotic.31 The SIGN guidelines recommend using a single dose of prophylactic antibiotic with a long enough half-life to achieve activity throughout the operation, within 60 min before the skin is incised and as close as possible to the time of incision.10 Similarly, the IDSA guidelines recommend a single preoperative prophylactic dose within 60 min before surgical incision and intraoperative redosing is required only if the duration of surgery exceeds two half-lives of the antibiotic. The postoperative duration of antimicrobial prophylaxis should be limited to less than 24 h, regardless of the presence of indwelling catheters or surgical drains.37

CONCLUSION One must consider the benefits and risks of prescribing antibiotics, which include adverse events, allergies, costs to the health-care system and antimicrobial resistance. Recent evidence-based guidelines on surgical prophylaxis recommend no antibiotic prophylaxis for clean, uncomplicated dermatological surgery. When risk factors for a surgical site are present a single preoperative dose is recommended. There is no evidence for using topical antibiotics postoperatively, with the risk of allergic contact dermatitis. The evidence-based guidelines recommend more restricted indications for and a shorter duration of antibiotic prophylaxis in situations where no clinical benefit of prolonged therapy has been proven. This will help minimise the adverse clinical effects and the rise in antimicrobial resistance that compromises the effectiveness of our current armamentarium of antibiotics. This review recommends the cautious use of prophylactic antibiotics in dermatological surgery to help prevent the growing problem of bacterial resistance as well as other morbidity and health-care costs. © 2015 The Australasian College of Dermatologists

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