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Skin and soft tissue infections
SKIN AND SOFT TISSUE INFECTIONS
Skin and soft tissue infections
Key points C
The incidence of severe infections, such as necrotizing fasciitis, appears to be increasing
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Outpatient parenteral antibiotic treatment services are increasingly providing a route for avoiding admission with skin and soft tissue infections (SSTIs)
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New antimicrobials are emerging for use in SSTI
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Antibiotic resistance is an increasing concern in both Grampositive, particularly community-acquired meticillin-resistant Staphylococcus aureus, and Gram-negative organisms
ID Ramsay € ro €k ME To
Abstract Skin and soft tissue infections (SSTIs) range from common superficial skin infections to rare but life-threatening infections such as necrotizing fasciitis. They affect all ages. Predisposing factors include trauma, pre-existing dermatoses, diabetes mellitus and immunosuppression. SSTIs are often caused by organisms that colonize the skin, such as Staphylococcus aureus or group A streptococci, because of a breach in the skin’s integrity. Community-acquired meticillin-resistant S. aureus is increasingly recognized as a cause of SSTI. Treatment is usually with topical or systemic antimicrobials, directed against the suspected organism. Outpatient intravenous antibiotics are increasingly used, and new antimicrobials are emerging for use in these infections. Urgent surgical debridement is sometimes required.
alcoholism, intravenous drug use, peripheral arterial or venous disease, malignancy and immunosuppression. SSTIs can be mild and self-limiting or severe and progressive, leading to tissue necrosis. Clues to potentially severe deep soft tissue infection include pain disproportionate to the physical findings, violaceous bullae, cutaneous haemorrhage, skin sloughing, skin anaesthesia, rapid progression and gas in the tissue. A detailed history is essential to establish a specific diagnosis and should include: onset, duration and progression of symptoms appearance and anatomical distribution of the lesion history of trauma or surgery contact with insects or other animals infectious contacts recent foreign travel pre-existing medical conditions previous antibiotic therapy and allergies. Systemically unwell patients should be admitted to hospital, with blood sampling for full blood count, biochemical profile, inflammatory markers and blood cultures. If the diagnosis of SSTI cannot be made on clinical grounds, investigations such as needle aspiration, punch biopsy or surgical debridement may be necessary.
Keywords Cellulitis; ecthyma; erysipelas; folliculitis; gas gangrene; group A streptococci; impetigo; MRCP; necrotizing fasciitis; skin and soft tissue infection; Staphylococcus aureus
Introduction Skin and soft tissue infections (SSTIs) make up a large proportion of infectious disease presentations to primary and secondary care. Infectious Diseases Society of America guidance1 suggests classification based on three clinical criteria: skin extension (uncomplicated or complicated) rate of progression (acute or chronic) tissue necrosis (necrotizing or non-necrotizing). The US Food and Drug Administration (FDA) has introduced the term ‘acute bacterial skin and soft tissue infection’ to cover lesions >75 cm2. Most SSTIs are caused by Gram-positive organisms, particularly Staphylococcus aureus and b-haemolytic group A streptococci. However, Gram-negative or anaerobic bacteria, viruses, fungi and parasites can be involved.
Antibiotic therapy and antimicrobial resistance Empirical antimicrobial therapy should be directed towards the likely organism(s) and subsequently tailored in the light of microbiological data.2 Worldwide, antimicrobial resistance is of increasing concern, but the prevalence of resistant organisms varies widely, and a knowledge of local epidemiology is vital to inform optimal treatment. Community-acquired meticillin-resistant S. aureus (CAMRSA) is a common cause of SSTI in the USA, and is variably seen across Europe, with a relatively low prevalence in the UK. Vancomycin-intermediate and vancomycin-resistant S. aureus have been sporadically described, particularly in the USA. Multidrug-resistant Gram-negative organisms are increasingly prevalent, particularly in hospital-acquired infections, for example surgical site infections (SSIs). Several new antibiotic agents have emerged.3 These include second-generation lipoglycopeptide antibiotics, for example
Host factors SSTIs can affect any age group, with elderly individuals being at higher risk of severe disease. Conditions predisposing to SSTIs include trauma, pre-existing skin conditions, diabetes mellitus,
ID Ramsay MA BM BCh MRCP is a Specialist Registrar in Infectious Diseases and Microbiology, Addenbrooke’s Hospital, Cambridge, UK. Competing interests: none declared. € ro € k MA PhD FRCP FRCPath is an Honorary Consultant in ME To Infectious Diseases and Microbiology, Department of Medicine, Addenbrooke’s Hospital, Cambridge, UK. Competing interests: none declared.
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bearing site can be affected, but the sites most often involved are the face, scalp, thighs, axillas and inguinal area. Predisposing factors include frequent shaving, pre-existing skin conditions, occlusive clothing/dressings, exposure to hot humid temperatures, diabetes mellitus, obesity, long-term antibiotic or corticosteroid use, and immunosuppression. The most common form of folliculitis is sycosis barbae (barber’s itch), which is caused by S. aureus. Tinea barbae is a fungal folliculitis, caused by dermatophytes, that resembles its bacterial counterpart. Other infectious causes include Enterobacteriaceae (often associated with prolonged antibiotic therapy), P. aeruginosa (associated with hot tubs and wet suits),5 Malassezia furfur, herpes simplex virus, varicella-zoster virus and Demodex mites. Non-infectious causes include eosinophilic folliculitis seen in advanced HIV and malignancy and a self-limiting papulo-pustular follicular eruption that occurs after treatment with epidermal growth factor receptor inhibitors. Antibacterial soaps and good hygiene may be all that is required for recurrent uncomplicated superficial folliculitis. Systemic antibiotics can be required in more severe infection (e.g. oral flucloxacillin for staphylococcal folliculitis; treatment may need to cover MRSA if the patient is colonized). P. folliculitis is usually selflimiting, but oral ciprofloxacin can be given if lesions are persistent or the patient is immunocompromised. Malassezia folliculitis usually responds to topical antifungals (e.g. ketoconazole cream). Herpetic folliculitis responds to oral antivirals (e.g. valaciclovir). Eosinophilic folliculitis may respond to the introduction of antiretroviral therapy in HIV patients or to metronidazole, ultraviolet B phototherapy or itraconazole.
dalbavancin, which has broad Gram-positive cover including MRSA and, in vitro, has activity against organisms with reduced susceptibility to vancomycin. Dalbavancin is amenable for outpatient settings as it is dosed once weekly. Tedizolid is a second-generation oxazolidinone with enhanced activity against staphylococci and enterococci compared with linezolid. The new topical agent retapamulin has activity against both staphylococci (including MRSA) and streptococci, and has been approved by the FDA for treatment of impetigo. In patients who are well enough not to be in hospital with SSTIs but require intravenous antibiotics, outpatient parenteral antibiotic treatment4 services are being used to facilitate earlier discharge or avoid hospital admission. Antibiotics are administered in an outpatient setting, in the patient’s own home or, in some cases, by the patients themselves, after appropriate training.
Impetigo Impetigo is a highly contagious superficial pyogenic infection of the epidermis, typically affecting young children. It is commonly caused by S. aureus or group A streptococci. Two forms are recognized: bullous and non-bullous. Non-bullous impetigo is characterized by coalescing intraepidermal vesicles, often on the face or hands, which rupture to form a golden crust. In bullous impetigo, larger bullae form and rupture, leaving a brown, scaly appearance. Constitutional symptoms are usually absent. Patients often report a history of minor skin trauma, insect bites or pre-existing dermatoses. Impetigo is treated by removing the crusts and applying topical antibiotics, such as mupirocin. Widespread infection responds better to oral or intravenous antibiotics (e.g. flucloxacillin, clindamycin). It can cause outbreaks in households, institutions and sports teams. Affected children should be excluded from school until the lesions have crusted and healed, or for 48 hours after starting antibiotic treatment.
Furuncles and carbuncles Furuncles are subcutaneous boils or abscesses. The usual cause is S. aureus. If several furuncles coalesce, a ‘carbuncle’ is formed (Figure 2). Carbuncles are characterized by inflamed skin with pus draining from several hair follicles and are commonly found on areas of thickened skin such as the nape of the neck, the back and the thighs. Fever and malaise are common. Rarely, recurrent furuncles become a problem. Diabetes mellitus and rare causes of immunodeficiency, such as hyperimmunoglobulin E syndrome (Job’s syndrome) and chronic granulomatous disease, should be considered. Small furuncles can burst and heal spontaneously; larger ones can require incision and drainage. Carbuncles usually require incision and drainage along with systemic antimicrobials (e.g. oral or intravenous flucloxacillin). Patients with recurrent furuncles who do not have underlying immunodeficiency should be considered for staphylococcal decolonization using mupirocin 2% nasal ointment and chlorhexidine gluconate 4% shampoo/ body wash.
Ecthyma Ecthyma is a form of impetigo that penetrates deeper into the dermis and can scar. It starts as a vesicle and progresses to form a punched-out ulcer surrounded by a violaceous border (Figure 1). Regional lymphadenopathy can be present. Ecthyma often occurs on the legs and is associated with minor trauma, insect bites, eczema, pediculosis, diabetes mellitus and immunodeficiency. Most cases are caused by group A streptococci. A similar lesion called ecthyma gangrenosum is sometimes seen in immunocompromised patients and is usually associated with Pseudomonas aeruginosa bacteraemia, but has been reported rarely with other organisms (e.g. MRSA, Stenotrophomonas maltophilia). Mild cases can be treated with topical mupirocin, and more severe cases with oral penicillin or clindamycin. Debridement of the crusts may be required. Ecthyma gangrenosum should be treated with appropriate parenteral antibiotics, depending on the causative organism.
PantoneValentine leucocidin (PVL) In individuals with recurrent abscesses or furuncles, or where there is a cluster of cases within a household, consideration should be given to detection of PVL-producing S. aureus. The clinical significance of PVL is debated, but current guidelines recommend using two or three agents, for example oral rifampicin, linezolid and intravenous clindamycin, for severe SSTIs caused by PVL-positive strains.
Folliculitis Folliculitis is an inflammation of the hair follicles characterized by clusters of small, erythematous papules or pustules. Any hair-
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SKIN AND SOFT TISSUE INFECTIONS
syndrome, alcohol abuse and immunodeficiency. Erysipelas tends to occur in areas of lymphatic obstruction and, because it also causes lymphatic damage, to recur. Treatment is with intravenous benzylpenicillin; clindamycin can be used in penicillin-allergic patients. Staphylococci are not usually implicated in erysipelas, so anti-staphylococcal therapy (flucloxacillin, vancomycin) is not usually considered necessary unless there are features suggestive of staphylococcal infection (e.g. bullous erysipelas).
Cellulitis Cellulitis is rapidly spreading inflammation of the deep dermis and subcutaneous fat (Figure 4),5 commonly caused by group A streptococci or S. aureus. Soft tissue infection caused by CAMRSA is becoming increasingly common and usually results in skin abscesses. Rarer causes of cellulitis include groups B, C and G streptococci (particularly in lymphatic obstruction), Strep. pneumoniae, Enterobacteriaceae, Pseudomonas spp., Pasteurella multocida (associated with animal contact), Aeromonas hydrophila and Vibrio vulnificus (associated with freshwater and salt water contact, respectively) Brucella spp., Legionella spp. and Neisseria meningitidis. There is often a clear causative injury or breach of the skin (e.g. eczema, tinea infections). Patients with diabetes mellitus are at increased risk of complications, as are those with leg ulcers, lymphoedema, varicose veins or peripheral vascular disease. Cellulitis usually affects the legs and is almost always unilateral. It presents as a red, hot, swollen, tender area that is not as well demarcated or elevated as in erysipelas. Thrombophlebitis, lymphangitis, regional lymphadenopathy and fever are common. Local abscesses can develop, and the overlying skin can become necrotic. The diagnosis of cellulitis is almost entirely clinical; skin swabs are unhelpful and blood cultures, skin biopsies and tissue aspirates are seldom positive. Imaging cannot diagnose cellulitis but can be useful in identifying abscesses or underlying osteomyelitis. Patients with mild cellulitis and no systemic symptoms can be treated with oral flucloxacillin; clindamycin is an alternative in penicillin-allergic patients. In patients with more severe infection or facial or peri-orbital cellulitis, treatment with intravenous antibiotics is usually warranted. If the patient has diabetes mellitus or leg ulcers, Gram-negative organisms and anaerobes are more likely, so intravenous co-amoxiclav can be used instead. In patients who are MRSA-colonized, a glycopeptide should be considered; linezolid and daptomycin are suitable although more expensive alternatives. There is little evidence that MRSA needs to be covered if the cellulitis is community acquired, even in the USA, unless an abscess is present. Analgesia, elevation of the limb and subcutaneous heparin are useful adjunctive measures. A surgical opinion should be sought if there is circumferential cellulitis or necrotic skin. Prophylactic antibiotics (usually penicillin) remain controversial; however, they can be considered in patients with three or four episodes per year. Important non-pharmacological measures include foot care, including treatment of tinea pedis, lymphoedema management and wound care for ulceration.
Figure 1 Ecthyma in an immunocompromised patient.
Figure 2 Carbuncle on the dorsum of the foot.
Erysipelas Erysipelas is a superficial bacterial infection of the dermis, involving the cutaneous lymphatics. It is characterized by abrupt onset of a painful, erythematous, spreading rash with welldemarcated edges (Figure 3). There are often systemic features (e.g. fever, malaise, chills). Most erysipelas infections occur on the lower extremities, with non-group A streptococci being the most common cause. Facial erysipelas is more commonly caused by group A streptococci. Atypical forms, caused by Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, Yersinia enterocolitica, and Moraxella spp., have been described. Predisposing factors include skin conditions (e.g. eczema, dermatophyte infections), venous stasis, paraparesis, diabetes mellitus, nephrotic
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SKIN AND SOFT TISSUE INFECTIONS
The most common sites are the olecranon and pre-patellar bursae. Treatment is with intravenous flucloxacillin, elevation of the limb and, if necessary, aspiration of pus from the affected bursa. In penicillin-allergic or MRSA-colonized patients, a glycopeptide is appropriate. Surgical drainage is rarely required.
Surgical site infections Despite the use of antibiotic prophylaxis, SSIs develop in at least 5% of patients undergoing a surgical procedure, causing significant morbidity. Factors known to contribute to the risk include: host (age, obesity, nutritional status, immune status, perioperative variables such as blood glucose, body temperature and oxygenation) surgical (type of procedure, surgical technique, use of foreign material) microbial (concentration and virulence of organisms, resistance to antimicrobial prophylaxis). SSIs are defined by the US Centers for Disease Control and Prevention as occurring at or near the surgical site within 30 days of operation, or within 1 year if prosthetic material is present. They can be divided into three types: superficial incisional (involving skin or subcutaneous tissues), deep incisional (involving fascia or muscle) and organ/space infection. The infecting organisms are usually the patient’s endogenous flora. S. aureus (including MRSA), coagulase-negative staphylococci and enterococci are the most common organisms. SSIs caused by enterobacteriaceae are becoming increasingly prevalent, particularly after gastrointestinal surgery. Anaerobes and Candida spp. can also be implicated. Polymicrobial infections are more likely in surgery involving a viscus. Early SSIs (in the first 48 hours after surgery) are often caused by Clostridia spp. or streptococci. Most superficial incisional SSIs present within days after surgery, although rarely in the first 48 hours, with fever and local pain, swelling, erythema, tenderness, a purulent discharge or wound dehiscence. These symptoms and signs can be delayed in individuals who are morbidly obese or have multilayer wounds. Ultrasonography or computed tomography (CT) can be required to identify deep incisional infections in patients with clinical evidence of systemic infection but no local signs. Initial management of SSI involves incision and drainage, debridement of necrotic tissue, removal of foreign material and local wound care. Superficial swabs have limited use and can reflect colonizing flora only; therefore deep pus or tissue samples should be sent for microbiological examination. Most superficial SSIs do not require any further therapy. The need for antimicrobial therapy should be guided by clinical findings (e.g. spreading cellulitis, systemic symptoms). The initial choice of antimicrobial agent should be directed towards the most likely organisms, according to the type of operation performed. Treatment can then be tailored in light of microbiological findings. Most incisional SSIs are left open and allowed to heal by secondary intention.
Figure 3 Erysipelas caused by group A Streptococcus.
Figure 4 Cellulitis of the lower limb.
Bursitis Bursitis is an inflammation of a bursa that can be caused by repetitive use, trauma, gout, rheumatoid arthritis or infection (septic bursitis). Septic bursitis occurs from direct inoculation of microorganisms through the skin or spread from adjacent cellulitis; it rarely occurs as a result of haematogenous spread. The predominant cause is S. aureus, followed by streptococci and, rarely, mycobacteria or fungi. Predisposing factors include trauma, skin diseases, diabetes mellitus, alcoholism and corticosteroid therapy. The diagnosis is clinical and based on fever plus swelling, erythema and tenderness over the affected bursa.
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Bite infections Bite wounds are usually caused by domestic pets, such as dogs (most common), cats, rabbits, reptiles and, occasionally,
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following a breach of the mucous membranes by surgery or instrumentation. Type II necrotizing fasciitis is typically monomicrobial, and caused by group A streptococci. It can occur in any age group. The cardinal symptom is excruciating pain with minimal cutaneous findings. Initially, there may also be fever, malaise, myalgia and diarrhoea. After 24e48 hours, erythema can develop, the skin can darken to a reddishpurple colour, and bullae can develop. Patients are systemically unwell and can develop streptococcal toxic shock syndrome. CA-MRSA is increasingly recognized as a cause of necrotizing fasciitis in the USA, particularly in IDUs. Other causative agents include V. vulnificus (seawater exposure) and Aeromonas spp (freshwater exposure). Necrotizing fasciitis is a surgical emergency and requires prompt surgical debridement. Intravenous broad-spectrum antibiotics (e.g. piperacillin/tazobactam clindamycin) should be given until microbiological data are available. Clindamycin has a theoretical advantage in that it can interrupt toxin production and reduce systemic toxic effects. Patients often require intensive care. Imaging studies can be helpful for monitoring progress and assessing the need for further surgery, but should not delay initial debridement. Adjunctive therapies such as intravenous immunoglobulin and hyperbaric oxygen have been advocated but lack convincing evidence.
monkeys. It is estimated that 3e18% of dog-bite wounds and 28 e80% of cat-bite wounds become infected, most frequently on the hand. The organisms implicated are usually the oral flora of the biting animal. P. multocida and Pasteurella canis are common, but a wide spectrum of organisms has been isolated from bite wounds (e.g. staphylococci, streptococci, enterococci, Neisseria spp., Haemophilus spp., Eikenella spp., Enterobacteriaceae, Capnocytophaga canimorsus, anaerobes). Bites from marine animals can lead to infection with Vibrio spp. Human bites are the third most common after dogs and cats; around 10e15% become infected, usually with oral flora. Treatment involves wound irrigation, debridement, elevation of the affected part and, if appropriate, tetanus and rabies immunization. Primary wound closure is usually undertaken only for facial wounds. Human and animal bites should be managed with prophylactic antibiotics (e.g. co-amoxiclav), but the risk of blood-borne viral infections should be considered. Recipients of monkey bites should be given prophylactic valaciclovir or aciclovir because of the risk of simian herpesvirus B.
Infections in injection drug-users (IDUs) SSTIs are common in (IDUs) as they often introduce bacteria into normally sterile sites. Because of delays in accessing healthcare, this patient group often presents late and can be poorly adherent to treatment. The most common organism is S. aureus (including MRSA), but oral flora (e.g. a-haemolytic streptococci, Neisseria spp., Haemophilus spp., Eikenella corrodens) can be found in those who lick their needles. Other causes include Strep. pneumoniae, Gram-negative bacteria, Clostridia spp. and fungi. In 2000, a high-fatality outbreak of SSTI occurred in the UK from heroin contaminated with Clostridium novyi. In 2009e2010, >100 cases of cutaneous anthrax, related to contaminated heroin, were reported in IDUs in Scotland. Cellulitis or abscesses can occur at the site of injection and cause considerable soft tissue damage. Injections can also cause intramuscular abscesses (pyomyositis) or necrotizing fasciitis. Complications include bacteraemia, septic arthritis, osteomyelitis and infectious endocarditis. Treatment is with intravenous antibiotics and, usually, surgical drainage or debridement. These patients should be routinely screened for blood-borne virus infections.
Fournier’s gangrene Fournier’s gangrene is a form of necrotizing fasciitis that affects the genital, perineal and perianal regions. Most cases occur in patients aged 30e60 years, and there is a 10:1 male-to-female ratio. Risk factors include advanced age, diabetes mellitus, alcohol abuse, colorectal disease/surgery, malignancy, malnutrition and immunosuppression. Fournier’s gangrene is a polymicrobial infection caused by a mixture of aerobic (e.g. Enterobacteriaceae, streptococci, enterococci, Pseudomonas spp.), and anaerobic (e.g. Bacteroides spp., Clostridium spp.) bacteria. The incidence of MRSA infections appears to be increasing. Rarely, Candida albicans has been implicated. Symptoms usually begin with the insidious onset of pruritus and discomfort in the external genitalia. This is followed by swelling and erythema of the genital/perineal region associated with severe pain and systemic symptoms. Fournier’s gangrene is a surgical emergency that requires prompt surgical debridement and broad-spectrum intravenous antibiotic therapy (e.g. co-amoxiclav, metronidazole, gentamicin). A glycopeptide or other suitable antibiotic should be included if the patient is known or likely to be colonized with MRSA. Consider a tetanus booster if immunization status is unknown e cases of fatal tetanus have been associated with Fournier’s gangrene.
Necrotizing fasciitis Necrotizing fasciitis is an uncommon, severe infection that results in destruction of subcutaneous tissue and fascia. Predisposing factors include diabetes mellitus, alcoholism and injecting drug use. There are two clinical types: Type I necrotizing fasciitis is a mixed infection caused by streptococci, Enterobacteriaceae, Bacteroides spp. and Peptostreptococcus spp. It occurs in middle-aged and elderly individuals, most commonly after surgical procedures, and in patients with diabetes or peripheral vascular disease. Infection usually starts in the feet and progresses rapidly along the fascia into the leg. Clinical presentation is with cellulitis and systemic signs of severe infection. Type I necrotizing fasciitis can also develop in the head and neck
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Gas gangrene Gas gangrene and clostridial myonecrosis are terms used to describe a rare infection caused by toxin-producing clostridia. Clostridium perfringens is the main cause of trauma-related gas
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gangrene. In spontaneous cases, Clostridium septicum is more commonly implicated. Typically, wounds are contaminated with clostridia, which multiply in anaerobic conditions and produce exotoxins that cause tissue damage. Spontaneous cases result from haematogenous spread of clostridia from the gastrointestinal tract, often in the setting of bowel cancer. Clinical features include the sudden onset of pain 6e8 hours after injury. This is followed by increasing pain and tenderness, darkening of the skin to a purplish-red colour, formation of bullae, crepitus, fever, shock, haemolytic anaemia, liver and renal failure. Gas in the soft tissues can be confirmed by plain radiography, CT or magnetic resonance imaging. The diagnosis is confirmed by demonstrating Gram-positive rods in the affected tissue. Management is with aggressive surgical debridement combined with intravenous antibiotics (e.g. piperacillin/tazobactam, clindamycin). Intensive care support and multiple debridements may be required. The use of adjuvant therapies (e.g. hyperbaric oxygen) is controversial.
Tick typhus: is of several types. African tick typhus, caused by Rickettsia conorii and Rickettsia africae, is commonly seen in patients returning from safari in southern Africa. Endemic typhus is caused by Rickettsia typhi and transmitted by the rat flea. Epidemic typhus is caused by Rickettsia prowazekii and transmitted by the human louse. Clinical features include fever, headache, malaise, myalgia, lymphadenopathy and splenomegaly. There may be an eschar at the site of inoculation and a maculopapular rash, although some spotted fevers produce few if any spots. Diagnosis is confirmed serologically. Treatment is with doxycycline. Mycobacterial Leprosy: is caused by infection with Mycobacterium leprae. The spectrum of clinical disease ranges from tuberculoid to lepromatous leprosy. In tuberculoid leprosy, anaesthetic macules or plaques, pigmentary change and thickened peripheral nerves develop. In lepromatous leprosy, macules, papules, nodules and ulceration occur, resulting in collapse of the nasal bones and coarsening of the facial tissues, producing the characteristic ‘leonine’ facies. The diagnosis is confirmed by biopsy and splitskin smears. Treatment is with dapsone, clofazimine and rifampicin.
Uncommon infections Bacterial Anthrax: is caused by Bacillus anthracis and most commonly affects the skin, resulting in a ‘malignant pustule’. Infections occur in abattoir workers and result from inoculation of bacterial spores into skin abrasions caused by handling the hides of infected animals. Recent outbreaks have also been seen in IDUs. After a few days, a papule forms at the site of infection; this develops into a vesicle and ulcerates to form a necrotic centre or eschar. Local oedema, painful regional lymphadenopathy and systemic features are often present. The diagnosis is confirmed by demonstrating Gram-positive bacilli in the ulcer fluid or tissues and by culturing the organism. Penicillin therapy is adequate, although quinolones and tetracyclines are also effective. In some settings, surgical debridement is appropriate.
Lupus vulgaris: is a cutaneous infection caused by Mycobacterium tuberculosis. It usually affects the face and neck, and appears as firm, translucent, yellowish-brown ‘apple jelly’ nodules. Untreated lesions spread, leading to disfiguring scarring and contractures. Diagnosis is confirmed by biopsy, which shows tuberculoid granulomas in the mid-dermis. Treatment is with antituberculous chemotherapy. Non-tuberculous mycobacteria: can cause soft tissue infections. Mycobacterium marinum is associated with granulomas, particularly on the hands, in people who handle certain tropical fish. Mycobacterium chelonae infections have been associated with tattoos and with nosocomial infections related to intravenous devices.
Cat-scratch disease: is usually caused by Bartonella henselae. Clinical features include regional lymphadenopathy, fever and a red papule at the inoculation site. Atypical presentations include Parinaud’s ocular glandular syndrome, maculopapular rash, erythema multiforme, erythema nodosum and leukocytoclastic vasculitis. The diagnosis is confirmed serologically and by polymerase chain reaction analysis. Treatment is with azithromycin or doxycycline.
Fungal Eumycetoma (Madura foot): is a chronic subcutaneous fungal infection typically of the foot characterized by lesions, sinus tracts and macroscopic grains. It is caused by a variety of molds and is typically seen in labourers and farmers in subtropical and tropical areas. Filamentous bacteria can cause a similar disease (actinomycetoma). Treatment is with prolonged antifungal therapy. Surgical intervention is sometimes required.
Erysipeloid: is a rare condition is caused by Erysipelothrix rhusiopathiae. It is usually acquired from infected animals and affects veterinary surgeons, farmers and butchers. The organism is inoculated into the skin and causes characteristic dark, purplish lesions with swelling of the digits. Rarely, septicaemia occurs and can be complicated by endocarditis. The condition is treated with penicillin.
Sporotrichosis: is a subacute fungal infection caused by Sporothrix schenkii that is related to soil inoculation into the skin. It is typically seen in gardeners and is treated with antifungals. Parasitic Cutaneous larva migrans: this occurs in returning travellers, particularly those who have visited tropical beaches. It is caused by infection with animal hookworm larvae such as Ancylostoma braziliense, Ancylostoma caninum and Uncinaria stenocephala, and presents as an itchy cluster of lesions or a sinuous track on exposed areas. Treatment is with albendazole.
Erythema chronicum migrans: is the cutaneous manifestation of Lyme disease, which is caused by Borrelia burgdorferi. It is acquired by inoculation from a tick bite. A red, circular lesion develops and spreads from the site of the bite. Other features include fever, malaise and arthralgia. Diagnosis is serological. Treatment is with doxycycline.
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Leishmaniasis: cutaneous leishmaniasis is acquired from a sandfly bite. ‘Old world’ leishmaniasis, caused by Leishmania major, Leishmania tropica and Leishmania aethiopica, is endemic in Africa, Asia, India, the Middle East and the Mediterranean. ‘New world’ leishmaniasis, caused by Leishmania brasiliensis, Leishmania mexicana and Leishmania panamensis, is endemic in Latin America. Clinical presentation is with a crusted sore on the face, hand or leg 6e8 weeks after returning from an endemic area. Diagnosis is clinical and confirmed histologically. Lesions often resolve spontaneously, but some require cryotherapy or treatment with amphotericin or pentamidine. Patients with L. brasiliensis should be given systemic treatment to avoid the possibility of espundia (mucocutaneous disease).
Orf: is an infectious cutaneous lesion caused by a pox virus acquired from sheep. It commonly affects farmers (particularly those who bottle-feed lambs) and veterinary surgeons. A red papule develops, commonly on the sides of the fingers, and grows rapidly, often becoming vesicular, before developing a central necrotic area. Lymphangitis, regional lymphadenopathy and fever are common. Recovery is spontaneous. Ectoparasites Scabies: is a pruritic skin lesion caused by infestation with Sarcoptes scabiei. It is associated with poor socioeconomic conditions and overcrowding. The female mite lays her eggs in a burrow in the stratum corneum, generating a local hypersensitivity reaction; when the eggs hatch, the cycle is repeated. Diagnosis is confirmed by extracting the mite from a burrow. Treatment comprises topical acaricides (e.g. permethrin) and washing of all clothing and linen. All members of the household should be treated at the same time. So-called Norwegian scabies is a severe form with extensive crusting, most commonly seen in HIV infection and best treated with ivermectin. A
Viral Herpes zoster (shingles): is caused by reactivation of varicella-zoster virus infection and characterized by a painful, vesicular eruption in a dermatomal distribution. Risk factors include increasing age, immunosuppression and autoimmune disease. Complications include post-herpetic neuralgia, secondary bacterial skin infection, herpes zoster ophthalmicus, Ramsay Hunt syndrome (herpes zoster oticus) and meningitis. Treatment is with oral valaciclovir (for uncomplicated zoster) or intravenous aciclovir for immunocompromised patients or those with ocular involvement. A vaccine to prevent shingles is available.
KEY REFERENCES 1 Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis 2014; 59: 147e59. 2 Esposito S, Noviello S, Leone S. Epidemiology and microbiology of skin and soft tissue infections. Curr Opin Infect Dis 2016; 29: 109e15. 3 McClain SL, Bohan JG, Stevens DL. Advances in the medical management of skin and soft tissue infections. Br Med J 2016; 355: i6004. 4 Chapman ALN. Outpatient parenteral antimicrobial therapy. Br Med J 2013; 346: f1585. 5 Raff AB, Kroshinsky D. Cellulitis: a review. J Am Med Assoc 2016; 316: 325e37.
Herpetic whitlow: (herpes simplex infection of the skin) occurs as a complication of oral or genital herpes simplex virus infection. It is characterized by a painful, erythematous vesicular or pustular skin lesion. There may be associated fever and lymphadenopathy. The diagnosis is based on exposure history. Herpetic whitlow usually resolves spontaneously in 2e3 weeks, but some recommend treatment with oral aciclovir. Molluscum contagiosum: is a benign condition caused by a pox virus. It usually affects children or immunocompromised individuals. The lesions are most commonly seen on the face and trunk, and are papular with a central punctum.
TEST YOURSELF To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the end of the issue or online here.
Question 1
Which of the following organisms would be of particular concern in this patient? A. Capnocytophaga canimorsus B. Pasteurella canis C. Rabies virus D. Staphylococcus aureus E. Streptococcus pyogenes
A 25-year-old man presented with a 2-day history of a swollen erythematous hand after being bitten by his dog. He had a past medical history of splenectomy following traumatic injury. He had no recent travel outside the UK. On clinical examination, there was a 5 cm, erythematous, swollen area on the back of the right hand.
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SKIN AND SOFT TISSUE INFECTIONS
Question 2
Question 3
A 30-year-old woman presented with a 3-day history of pain and swelling on the left leg. She was an active intravenous drug user with a history of meticillin-resistant S. aureus colonization. On clinical examination, her temperature was 37.0 C, heart rate 88 beats/minute and blood pressure 115/68 mmHg. There was extensive cellulitis of the left leg.
A 55-year-old man became febrile and his laparotomy wound dehisced 4 days after an emergency laparotomy for bowel perforation. He had no known allergies. On clinical examination, his temperature was 38.4 C, heart rate 120 beats/minute, blood pressure 85/55 mmHg and respiratory rate 20/minute. Oxygen saturation on air was 92%.
Which of the following is the most appropriate initial antibiotic management? A. Give intravenous flucloxacillin as an inpatient B. Give intravenous vancomycin as an inpatient C. Give intravenous teicoplanin via an outpatient parenteral antibiotic treatment (OPAT) service D. Give intravenous ceftriaxone via an OPAT service E. Give oral doxycycline as an outpatient
Which of the following empirical antibiotic regimes would be most appropriate? A. Ceftriaxone 2 g once daily i.v. B. Flucloxacillin 1 g four times daily i.v. C. Gentamicin 5 mg/kg once daily i.v. D. Piperacillin/tazobactam 4.5 g 8-hourly i.v. E. Metronidazole 500 mg 8-hourly i.v.
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Skin and soft tissue infections
Key points C
The incidence of severe infections, such as necrotizing fasciitis, appears to be increasing
C
Outpatient parenteral antibiotic treatment services are increasingly providing a route for avoiding admission with skin and soft tissue infections (SSTIs)
C
New antimicrobials are emerging for use in SSTI
C
Antibiotic resistance is an increasing concern in both Grampositive, particularly community-acquired meticillin-resistant Staphylococcus aureus, and Gram-negative organisms
ID Ramsay € ro €k ME To
Abstract Skin and soft tissue infections (SSTIs) range from common superficial skin infections to rare but life-threatening infections such as necrotizing fasciitis. They affect all ages. Predisposing factors include trauma, pre-existing dermatoses, diabetes mellitus and immunosuppression. SSTIs are often caused by organisms that colonize the skin, such as Staphylococcus aureus or group A streptococci, because of a breach in the skin’s integrity. Community-acquired meticillin-resistant S. aureus is increasingly recognized as a cause of SSTI. Treatment is usually with topical or systemic antimicrobials, directed against the suspected organism. Outpatient intravenous antibiotics are increasingly used, and new antimicrobials are emerging for use in these infections. Urgent surgical debridement is sometimes required.
alcoholism, intravenous drug use, peripheral arterial or venous disease, malignancy and immunosuppression. SSTIs can be mild and self-limiting or severe and progressive, leading to tissue necrosis. Clues to potentially severe deep soft tissue infection include pain disproportionate to the physical findings, violaceous bullae, cutaneous haemorrhage, skin sloughing, skin anaesthesia, rapid progression and gas in the tissue. A detailed history is essential to establish a specific diagnosis and should include: onset, duration and progression of symptoms appearance and anatomical distribution of the lesion history of trauma or surgery contact with insects or other animals infectious contacts recent foreign travel pre-existing medical conditions previous antibiotic therapy and allergies. Systemically unwell patients should be admitted to hospital, with blood sampling for full blood count, biochemical profile, inflammatory markers and blood cultures. If the diagnosis of SSTI cannot be made on clinical grounds, investigations such as needle aspiration, punch biopsy or surgical debridement may be necessary.
Keywords Cellulitis; ecthyma; erysipelas; folliculitis; gas gangrene; group A streptococci; impetigo; MRCP; necrotizing fasciitis; skin and soft tissue infection; Staphylococcus aureus
Introduction Skin and soft tissue infections (SSTIs) make up a large proportion of infectious disease presentations to primary and secondary care. Infectious Diseases Society of America guidance1 suggests classification based on three clinical criteria: skin extension (uncomplicated or complicated) rate of progression (acute or chronic) tissue necrosis (necrotizing or non-necrotizing). The US Food and Drug Administration (FDA) has introduced the term ‘acute bacterial skin and soft tissue infection’ to cover lesions >75 cm2. Most SSTIs are caused by Gram-positive organisms, particularly Staphylococcus aureus and b-haemolytic group A streptococci. However, Gram-negative or anaerobic bacteria, viruses, fungi and parasites can be involved.
Antibiotic therapy and antimicrobial resistance Empirical antimicrobial therapy should be directed towards the likely organism(s) and subsequently tailored in the light of microbiological data.2 Worldwide, antimicrobial resistance is of increasing concern, but the prevalence of resistant organisms varies widely, and a knowledge of local epidemiology is vital to inform optimal treatment. Community-acquired meticillin-resistant S. aureus (CAMRSA) is a common cause of SSTI in the USA, and is variably seen across Europe, with a relatively low prevalence in the UK. Vancomycin-intermediate and vancomycin-resistant S. aureus have been sporadically described, particularly in the USA. Multidrug-resistant Gram-negative organisms are increasingly prevalent, particularly in hospital-acquired infections, for example surgical site infections (SSIs). Several new antibiotic agents have emerged.3 These include second-generation lipoglycopeptide antibiotics, for example
Host factors SSTIs can affect any age group, with elderly individuals being at higher risk of severe disease. Conditions predisposing to SSTIs include trauma, pre-existing skin conditions, diabetes mellitus,
ID Ramsay MA BM BCh MRCP is a Specialist Registrar in Infectious Diseases and Microbiology, Addenbrooke’s Hospital, Cambridge, UK. Competing interests: none declared. € ro € k MA PhD FRCP FRCPath is an Honorary Consultant in ME To Infectious Diseases and Microbiology, Department of Medicine, Addenbrooke’s Hospital, Cambridge, UK. Competing interests: none declared.
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bearing site can be affected, but the sites most often involved are the face, scalp, thighs, axillas and inguinal area. Predisposing factors include frequent shaving, pre-existing skin conditions, occlusive clothing/dressings, exposure to hot humid temperatures, diabetes mellitus, obesity, long-term antibiotic or corticosteroid use, and immunosuppression. The most common form of folliculitis is sycosis barbae (barber’s itch), which is caused by S. aureus. Tinea barbae is a fungal folliculitis, caused by dermatophytes, that resembles its bacterial counterpart. Other infectious causes include Enterobacteriaceae (often associated with prolonged antibiotic therapy), P. aeruginosa (associated with hot tubs and wet suits),5 Malassezia furfur, herpes simplex virus, varicella-zoster virus and Demodex mites. Non-infectious causes include eosinophilic folliculitis seen in advanced HIV and malignancy and a self-limiting papulo-pustular follicular eruption that occurs after treatment with epidermal growth factor receptor inhibitors. Antibacterial soaps and good hygiene may be all that is required for recurrent uncomplicated superficial folliculitis. Systemic antibiotics can be required in more severe infection (e.g. oral flucloxacillin for staphylococcal folliculitis; treatment may need to cover MRSA if the patient is colonized). P. folliculitis is usually selflimiting, but oral ciprofloxacin can be given if lesions are persistent or the patient is immunocompromised. Malassezia folliculitis usually responds to topical antifungals (e.g. ketoconazole cream). Herpetic folliculitis responds to oral antivirals (e.g. valaciclovir). Eosinophilic folliculitis may respond to the introduction of antiretroviral therapy in HIV patients or to metronidazole, ultraviolet B phototherapy or itraconazole.
dalbavancin, which has broad Gram-positive cover including MRSA and, in vitro, has activity against organisms with reduced susceptibility to vancomycin. Dalbavancin is amenable for outpatient settings as it is dosed once weekly. Tedizolid is a second-generation oxazolidinone with enhanced activity against staphylococci and enterococci compared with linezolid. The new topical agent retapamulin has activity against both staphylococci (including MRSA) and streptococci, and has been approved by the FDA for treatment of impetigo. In patients who are well enough not to be in hospital with SSTIs but require intravenous antibiotics, outpatient parenteral antibiotic treatment4 services are being used to facilitate earlier discharge or avoid hospital admission. Antibiotics are administered in an outpatient setting, in the patient’s own home or, in some cases, by the patients themselves, after appropriate training.
Impetigo Impetigo is a highly contagious superficial pyogenic infection of the epidermis, typically affecting young children. It is commonly caused by S. aureus or group A streptococci. Two forms are recognized: bullous and non-bullous. Non-bullous impetigo is characterized by coalescing intraepidermal vesicles, often on the face or hands, which rupture to form a golden crust. In bullous impetigo, larger bullae form and rupture, leaving a brown, scaly appearance. Constitutional symptoms are usually absent. Patients often report a history of minor skin trauma, insect bites or pre-existing dermatoses. Impetigo is treated by removing the crusts and applying topical antibiotics, such as mupirocin. Widespread infection responds better to oral or intravenous antibiotics (e.g. flucloxacillin, clindamycin). It can cause outbreaks in households, institutions and sports teams. Affected children should be excluded from school until the lesions have crusted and healed, or for 48 hours after starting antibiotic treatment.
Furuncles and carbuncles Furuncles are subcutaneous boils or abscesses. The usual cause is S. aureus. If several furuncles coalesce, a ‘carbuncle’ is formed (Figure 2). Carbuncles are characterized by inflamed skin with pus draining from several hair follicles and are commonly found on areas of thickened skin such as the nape of the neck, the back and the thighs. Fever and malaise are common. Rarely, recurrent furuncles become a problem. Diabetes mellitus and rare causes of immunodeficiency, such as hyperimmunoglobulin E syndrome (Job’s syndrome) and chronic granulomatous disease, should be considered. Small furuncles can burst and heal spontaneously; larger ones can require incision and drainage. Carbuncles usually require incision and drainage along with systemic antimicrobials (e.g. oral or intravenous flucloxacillin). Patients with recurrent furuncles who do not have underlying immunodeficiency should be considered for staphylococcal decolonization using mupirocin 2% nasal ointment and chlorhexidine gluconate 4% shampoo/ body wash.
Ecthyma Ecthyma is a form of impetigo that penetrates deeper into the dermis and can scar. It starts as a vesicle and progresses to form a punched-out ulcer surrounded by a violaceous border (Figure 1). Regional lymphadenopathy can be present. Ecthyma often occurs on the legs and is associated with minor trauma, insect bites, eczema, pediculosis, diabetes mellitus and immunodeficiency. Most cases are caused by group A streptococci. A similar lesion called ecthyma gangrenosum is sometimes seen in immunocompromised patients and is usually associated with Pseudomonas aeruginosa bacteraemia, but has been reported rarely with other organisms (e.g. MRSA, Stenotrophomonas maltophilia). Mild cases can be treated with topical mupirocin, and more severe cases with oral penicillin or clindamycin. Debridement of the crusts may be required. Ecthyma gangrenosum should be treated with appropriate parenteral antibiotics, depending on the causative organism.
PantoneValentine leucocidin (PVL) In individuals with recurrent abscesses or furuncles, or where there is a cluster of cases within a household, consideration should be given to detection of PVL-producing S. aureus. The clinical significance of PVL is debated, but current guidelines recommend using two or three agents, for example oral rifampicin, linezolid and intravenous clindamycin, for severe SSTIs caused by PVL-positive strains.
Folliculitis Folliculitis is an inflammation of the hair follicles characterized by clusters of small, erythematous papules or pustules. Any hair-
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syndrome, alcohol abuse and immunodeficiency. Erysipelas tends to occur in areas of lymphatic obstruction and, because it also causes lymphatic damage, to recur. Treatment is with intravenous benzylpenicillin; clindamycin can be used in penicillin-allergic patients. Staphylococci are not usually implicated in erysipelas, so anti-staphylococcal therapy (flucloxacillin, vancomycin) is not usually considered necessary unless there are features suggestive of staphylococcal infection (e.g. bullous erysipelas).
Cellulitis Cellulitis is rapidly spreading inflammation of the deep dermis and subcutaneous fat (Figure 4),5 commonly caused by group A streptococci or S. aureus. Soft tissue infection caused by CAMRSA is becoming increasingly common and usually results in skin abscesses. Rarer causes of cellulitis include groups B, C and G streptococci (particularly in lymphatic obstruction), Strep. pneumoniae, Enterobacteriaceae, Pseudomonas spp., Pasteurella multocida (associated with animal contact), Aeromonas hydrophila and Vibrio vulnificus (associated with freshwater and salt water contact, respectively) Brucella spp., Legionella spp. and Neisseria meningitidis. There is often a clear causative injury or breach of the skin (e.g. eczema, tinea infections). Patients with diabetes mellitus are at increased risk of complications, as are those with leg ulcers, lymphoedema, varicose veins or peripheral vascular disease. Cellulitis usually affects the legs and is almost always unilateral. It presents as a red, hot, swollen, tender area that is not as well demarcated or elevated as in erysipelas. Thrombophlebitis, lymphangitis, regional lymphadenopathy and fever are common. Local abscesses can develop, and the overlying skin can become necrotic. The diagnosis of cellulitis is almost entirely clinical; skin swabs are unhelpful and blood cultures, skin biopsies and tissue aspirates are seldom positive. Imaging cannot diagnose cellulitis but can be useful in identifying abscesses or underlying osteomyelitis. Patients with mild cellulitis and no systemic symptoms can be treated with oral flucloxacillin; clindamycin is an alternative in penicillin-allergic patients. In patients with more severe infection or facial or peri-orbital cellulitis, treatment with intravenous antibiotics is usually warranted. If the patient has diabetes mellitus or leg ulcers, Gram-negative organisms and anaerobes are more likely, so intravenous co-amoxiclav can be used instead. In patients who are MRSA-colonized, a glycopeptide should be considered; linezolid and daptomycin are suitable although more expensive alternatives. There is little evidence that MRSA needs to be covered if the cellulitis is community acquired, even in the USA, unless an abscess is present. Analgesia, elevation of the limb and subcutaneous heparin are useful adjunctive measures. A surgical opinion should be sought if there is circumferential cellulitis or necrotic skin. Prophylactic antibiotics (usually penicillin) remain controversial; however, they can be considered in patients with three or four episodes per year. Important non-pharmacological measures include foot care, including treatment of tinea pedis, lymphoedema management and wound care for ulceration.
Figure 1 Ecthyma in an immunocompromised patient.
Figure 2 Carbuncle on the dorsum of the foot.
Erysipelas Erysipelas is a superficial bacterial infection of the dermis, involving the cutaneous lymphatics. It is characterized by abrupt onset of a painful, erythematous, spreading rash with welldemarcated edges (Figure 3). There are often systemic features (e.g. fever, malaise, chills). Most erysipelas infections occur on the lower extremities, with non-group A streptococci being the most common cause. Facial erysipelas is more commonly caused by group A streptococci. Atypical forms, caused by Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, Yersinia enterocolitica, and Moraxella spp., have been described. Predisposing factors include skin conditions (e.g. eczema, dermatophyte infections), venous stasis, paraparesis, diabetes mellitus, nephrotic
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The most common sites are the olecranon and pre-patellar bursae. Treatment is with intravenous flucloxacillin, elevation of the limb and, if necessary, aspiration of pus from the affected bursa. In penicillin-allergic or MRSA-colonized patients, a glycopeptide is appropriate. Surgical drainage is rarely required.
Surgical site infections Despite the use of antibiotic prophylaxis, SSIs develop in at least 5% of patients undergoing a surgical procedure, causing significant morbidity. Factors known to contribute to the risk include: host (age, obesity, nutritional status, immune status, perioperative variables such as blood glucose, body temperature and oxygenation) surgical (type of procedure, surgical technique, use of foreign material) microbial (concentration and virulence of organisms, resistance to antimicrobial prophylaxis). SSIs are defined by the US Centers for Disease Control and Prevention as occurring at or near the surgical site within 30 days of operation, or within 1 year if prosthetic material is present. They can be divided into three types: superficial incisional (involving skin or subcutaneous tissues), deep incisional (involving fascia or muscle) and organ/space infection. The infecting organisms are usually the patient’s endogenous flora. S. aureus (including MRSA), coagulase-negative staphylococci and enterococci are the most common organisms. SSIs caused by enterobacteriaceae are becoming increasingly prevalent, particularly after gastrointestinal surgery. Anaerobes and Candida spp. can also be implicated. Polymicrobial infections are more likely in surgery involving a viscus. Early SSIs (in the first 48 hours after surgery) are often caused by Clostridia spp. or streptococci. Most superficial incisional SSIs present within days after surgery, although rarely in the first 48 hours, with fever and local pain, swelling, erythema, tenderness, a purulent discharge or wound dehiscence. These symptoms and signs can be delayed in individuals who are morbidly obese or have multilayer wounds. Ultrasonography or computed tomography (CT) can be required to identify deep incisional infections in patients with clinical evidence of systemic infection but no local signs. Initial management of SSI involves incision and drainage, debridement of necrotic tissue, removal of foreign material and local wound care. Superficial swabs have limited use and can reflect colonizing flora only; therefore deep pus or tissue samples should be sent for microbiological examination. Most superficial SSIs do not require any further therapy. The need for antimicrobial therapy should be guided by clinical findings (e.g. spreading cellulitis, systemic symptoms). The initial choice of antimicrobial agent should be directed towards the most likely organisms, according to the type of operation performed. Treatment can then be tailored in light of microbiological findings. Most incisional SSIs are left open and allowed to heal by secondary intention.
Figure 3 Erysipelas caused by group A Streptococcus.
Figure 4 Cellulitis of the lower limb.
Bursitis Bursitis is an inflammation of a bursa that can be caused by repetitive use, trauma, gout, rheumatoid arthritis or infection (septic bursitis). Septic bursitis occurs from direct inoculation of microorganisms through the skin or spread from adjacent cellulitis; it rarely occurs as a result of haematogenous spread. The predominant cause is S. aureus, followed by streptococci and, rarely, mycobacteria or fungi. Predisposing factors include trauma, skin diseases, diabetes mellitus, alcoholism and corticosteroid therapy. The diagnosis is clinical and based on fever plus swelling, erythema and tenderness over the affected bursa.
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Bite infections Bite wounds are usually caused by domestic pets, such as dogs (most common), cats, rabbits, reptiles and, occasionally,
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following a breach of the mucous membranes by surgery or instrumentation. Type II necrotizing fasciitis is typically monomicrobial, and caused by group A streptococci. It can occur in any age group. The cardinal symptom is excruciating pain with minimal cutaneous findings. Initially, there may also be fever, malaise, myalgia and diarrhoea. After 24e48 hours, erythema can develop, the skin can darken to a reddishpurple colour, and bullae can develop. Patients are systemically unwell and can develop streptococcal toxic shock syndrome. CA-MRSA is increasingly recognized as a cause of necrotizing fasciitis in the USA, particularly in IDUs. Other causative agents include V. vulnificus (seawater exposure) and Aeromonas spp (freshwater exposure). Necrotizing fasciitis is a surgical emergency and requires prompt surgical debridement. Intravenous broad-spectrum antibiotics (e.g. piperacillin/tazobactam clindamycin) should be given until microbiological data are available. Clindamycin has a theoretical advantage in that it can interrupt toxin production and reduce systemic toxic effects. Patients often require intensive care. Imaging studies can be helpful for monitoring progress and assessing the need for further surgery, but should not delay initial debridement. Adjunctive therapies such as intravenous immunoglobulin and hyperbaric oxygen have been advocated but lack convincing evidence.
monkeys. It is estimated that 3e18% of dog-bite wounds and 28 e80% of cat-bite wounds become infected, most frequently on the hand. The organisms implicated are usually the oral flora of the biting animal. P. multocida and Pasteurella canis are common, but a wide spectrum of organisms has been isolated from bite wounds (e.g. staphylococci, streptococci, enterococci, Neisseria spp., Haemophilus spp., Eikenella spp., Enterobacteriaceae, Capnocytophaga canimorsus, anaerobes). Bites from marine animals can lead to infection with Vibrio spp. Human bites are the third most common after dogs and cats; around 10e15% become infected, usually with oral flora. Treatment involves wound irrigation, debridement, elevation of the affected part and, if appropriate, tetanus and rabies immunization. Primary wound closure is usually undertaken only for facial wounds. Human and animal bites should be managed with prophylactic antibiotics (e.g. co-amoxiclav), but the risk of blood-borne viral infections should be considered. Recipients of monkey bites should be given prophylactic valaciclovir or aciclovir because of the risk of simian herpesvirus B.
Infections in injection drug-users (IDUs) SSTIs are common in (IDUs) as they often introduce bacteria into normally sterile sites. Because of delays in accessing healthcare, this patient group often presents late and can be poorly adherent to treatment. The most common organism is S. aureus (including MRSA), but oral flora (e.g. a-haemolytic streptococci, Neisseria spp., Haemophilus spp., Eikenella corrodens) can be found in those who lick their needles. Other causes include Strep. pneumoniae, Gram-negative bacteria, Clostridia spp. and fungi. In 2000, a high-fatality outbreak of SSTI occurred in the UK from heroin contaminated with Clostridium novyi. In 2009e2010, >100 cases of cutaneous anthrax, related to contaminated heroin, were reported in IDUs in Scotland. Cellulitis or abscesses can occur at the site of injection and cause considerable soft tissue damage. Injections can also cause intramuscular abscesses (pyomyositis) or necrotizing fasciitis. Complications include bacteraemia, septic arthritis, osteomyelitis and infectious endocarditis. Treatment is with intravenous antibiotics and, usually, surgical drainage or debridement. These patients should be routinely screened for blood-borne virus infections.
Fournier’s gangrene Fournier’s gangrene is a form of necrotizing fasciitis that affects the genital, perineal and perianal regions. Most cases occur in patients aged 30e60 years, and there is a 10:1 male-to-female ratio. Risk factors include advanced age, diabetes mellitus, alcohol abuse, colorectal disease/surgery, malignancy, malnutrition and immunosuppression. Fournier’s gangrene is a polymicrobial infection caused by a mixture of aerobic (e.g. Enterobacteriaceae, streptococci, enterococci, Pseudomonas spp.), and anaerobic (e.g. Bacteroides spp., Clostridium spp.) bacteria. The incidence of MRSA infections appears to be increasing. Rarely, Candida albicans has been implicated. Symptoms usually begin with the insidious onset of pruritus and discomfort in the external genitalia. This is followed by swelling and erythema of the genital/perineal region associated with severe pain and systemic symptoms. Fournier’s gangrene is a surgical emergency that requires prompt surgical debridement and broad-spectrum intravenous antibiotic therapy (e.g. co-amoxiclav, metronidazole, gentamicin). A glycopeptide or other suitable antibiotic should be included if the patient is known or likely to be colonized with MRSA. Consider a tetanus booster if immunization status is unknown e cases of fatal tetanus have been associated with Fournier’s gangrene.
Necrotizing fasciitis Necrotizing fasciitis is an uncommon, severe infection that results in destruction of subcutaneous tissue and fascia. Predisposing factors include diabetes mellitus, alcoholism and injecting drug use. There are two clinical types: Type I necrotizing fasciitis is a mixed infection caused by streptococci, Enterobacteriaceae, Bacteroides spp. and Peptostreptococcus spp. It occurs in middle-aged and elderly individuals, most commonly after surgical procedures, and in patients with diabetes or peripheral vascular disease. Infection usually starts in the feet and progresses rapidly along the fascia into the leg. Clinical presentation is with cellulitis and systemic signs of severe infection. Type I necrotizing fasciitis can also develop in the head and neck
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Gas gangrene Gas gangrene and clostridial myonecrosis are terms used to describe a rare infection caused by toxin-producing clostridia. Clostridium perfringens is the main cause of trauma-related gas
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gangrene. In spontaneous cases, Clostridium septicum is more commonly implicated. Typically, wounds are contaminated with clostridia, which multiply in anaerobic conditions and produce exotoxins that cause tissue damage. Spontaneous cases result from haematogenous spread of clostridia from the gastrointestinal tract, often in the setting of bowel cancer. Clinical features include the sudden onset of pain 6e8 hours after injury. This is followed by increasing pain and tenderness, darkening of the skin to a purplish-red colour, formation of bullae, crepitus, fever, shock, haemolytic anaemia, liver and renal failure. Gas in the soft tissues can be confirmed by plain radiography, CT or magnetic resonance imaging. The diagnosis is confirmed by demonstrating Gram-positive rods in the affected tissue. Management is with aggressive surgical debridement combined with intravenous antibiotics (e.g. piperacillin/tazobactam, clindamycin). Intensive care support and multiple debridements may be required. The use of adjuvant therapies (e.g. hyperbaric oxygen) is controversial.
Tick typhus: is of several types. African tick typhus, caused by Rickettsia conorii and Rickettsia africae, is commonly seen in patients returning from safari in southern Africa. Endemic typhus is caused by Rickettsia typhi and transmitted by the rat flea. Epidemic typhus is caused by Rickettsia prowazekii and transmitted by the human louse. Clinical features include fever, headache, malaise, myalgia, lymphadenopathy and splenomegaly. There may be an eschar at the site of inoculation and a maculopapular rash, although some spotted fevers produce few if any spots. Diagnosis is confirmed serologically. Treatment is with doxycycline. Mycobacterial Leprosy: is caused by infection with Mycobacterium leprae. The spectrum of clinical disease ranges from tuberculoid to lepromatous leprosy. In tuberculoid leprosy, anaesthetic macules or plaques, pigmentary change and thickened peripheral nerves develop. In lepromatous leprosy, macules, papules, nodules and ulceration occur, resulting in collapse of the nasal bones and coarsening of the facial tissues, producing the characteristic ‘leonine’ facies. The diagnosis is confirmed by biopsy and splitskin smears. Treatment is with dapsone, clofazimine and rifampicin.
Uncommon infections Bacterial Anthrax: is caused by Bacillus anthracis and most commonly affects the skin, resulting in a ‘malignant pustule’. Infections occur in abattoir workers and result from inoculation of bacterial spores into skin abrasions caused by handling the hides of infected animals. Recent outbreaks have also been seen in IDUs. After a few days, a papule forms at the site of infection; this develops into a vesicle and ulcerates to form a necrotic centre or eschar. Local oedema, painful regional lymphadenopathy and systemic features are often present. The diagnosis is confirmed by demonstrating Gram-positive bacilli in the ulcer fluid or tissues and by culturing the organism. Penicillin therapy is adequate, although quinolones and tetracyclines are also effective. In some settings, surgical debridement is appropriate.
Lupus vulgaris: is a cutaneous infection caused by Mycobacterium tuberculosis. It usually affects the face and neck, and appears as firm, translucent, yellowish-brown ‘apple jelly’ nodules. Untreated lesions spread, leading to disfiguring scarring and contractures. Diagnosis is confirmed by biopsy, which shows tuberculoid granulomas in the mid-dermis. Treatment is with antituberculous chemotherapy. Non-tuberculous mycobacteria: can cause soft tissue infections. Mycobacterium marinum is associated with granulomas, particularly on the hands, in people who handle certain tropical fish. Mycobacterium chelonae infections have been associated with tattoos and with nosocomial infections related to intravenous devices.
Cat-scratch disease: is usually caused by Bartonella henselae. Clinical features include regional lymphadenopathy, fever and a red papule at the inoculation site. Atypical presentations include Parinaud’s ocular glandular syndrome, maculopapular rash, erythema multiforme, erythema nodosum and leukocytoclastic vasculitis. The diagnosis is confirmed serologically and by polymerase chain reaction analysis. Treatment is with azithromycin or doxycycline.
Fungal Eumycetoma (Madura foot): is a chronic subcutaneous fungal infection typically of the foot characterized by lesions, sinus tracts and macroscopic grains. It is caused by a variety of molds and is typically seen in labourers and farmers in subtropical and tropical areas. Filamentous bacteria can cause a similar disease (actinomycetoma). Treatment is with prolonged antifungal therapy. Surgical intervention is sometimes required.
Erysipeloid: is a rare condition is caused by Erysipelothrix rhusiopathiae. It is usually acquired from infected animals and affects veterinary surgeons, farmers and butchers. The organism is inoculated into the skin and causes characteristic dark, purplish lesions with swelling of the digits. Rarely, septicaemia occurs and can be complicated by endocarditis. The condition is treated with penicillin.
Sporotrichosis: is a subacute fungal infection caused by Sporothrix schenkii that is related to soil inoculation into the skin. It is typically seen in gardeners and is treated with antifungals. Parasitic Cutaneous larva migrans: this occurs in returning travellers, particularly those who have visited tropical beaches. It is caused by infection with animal hookworm larvae such as Ancylostoma braziliense, Ancylostoma caninum and Uncinaria stenocephala, and presents as an itchy cluster of lesions or a sinuous track on exposed areas. Treatment is with albendazole.
Erythema chronicum migrans: is the cutaneous manifestation of Lyme disease, which is caused by Borrelia burgdorferi. It is acquired by inoculation from a tick bite. A red, circular lesion develops and spreads from the site of the bite. Other features include fever, malaise and arthralgia. Diagnosis is serological. Treatment is with doxycycline.
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SKIN AND SOFT TISSUE INFECTIONS
Leishmaniasis: cutaneous leishmaniasis is acquired from a sandfly bite. ‘Old world’ leishmaniasis, caused by Leishmania major, Leishmania tropica and Leishmania aethiopica, is endemic in Africa, Asia, India, the Middle East and the Mediterranean. ‘New world’ leishmaniasis, caused by Leishmania brasiliensis, Leishmania mexicana and Leishmania panamensis, is endemic in Latin America. Clinical presentation is with a crusted sore on the face, hand or leg 6e8 weeks after returning from an endemic area. Diagnosis is clinical and confirmed histologically. Lesions often resolve spontaneously, but some require cryotherapy or treatment with amphotericin or pentamidine. Patients with L. brasiliensis should be given systemic treatment to avoid the possibility of espundia (mucocutaneous disease).
Orf: is an infectious cutaneous lesion caused by a pox virus acquired from sheep. It commonly affects farmers (particularly those who bottle-feed lambs) and veterinary surgeons. A red papule develops, commonly on the sides of the fingers, and grows rapidly, often becoming vesicular, before developing a central necrotic area. Lymphangitis, regional lymphadenopathy and fever are common. Recovery is spontaneous. Ectoparasites Scabies: is a pruritic skin lesion caused by infestation with Sarcoptes scabiei. It is associated with poor socioeconomic conditions and overcrowding. The female mite lays her eggs in a burrow in the stratum corneum, generating a local hypersensitivity reaction; when the eggs hatch, the cycle is repeated. Diagnosis is confirmed by extracting the mite from a burrow. Treatment comprises topical acaricides (e.g. permethrin) and washing of all clothing and linen. All members of the household should be treated at the same time. So-called Norwegian scabies is a severe form with extensive crusting, most commonly seen in HIV infection and best treated with ivermectin. A
Viral Herpes zoster (shingles): is caused by reactivation of varicella-zoster virus infection and characterized by a painful, vesicular eruption in a dermatomal distribution. Risk factors include increasing age, immunosuppression and autoimmune disease. Complications include post-herpetic neuralgia, secondary bacterial skin infection, herpes zoster ophthalmicus, Ramsay Hunt syndrome (herpes zoster oticus) and meningitis. Treatment is with oral valaciclovir (for uncomplicated zoster) or intravenous aciclovir for immunocompromised patients or those with ocular involvement. A vaccine to prevent shingles is available.
KEY REFERENCES 1 Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis 2014; 59: 147e59. 2 Esposito S, Noviello S, Leone S. Epidemiology and microbiology of skin and soft tissue infections. Curr Opin Infect Dis 2016; 29: 109e15. 3 McClain SL, Bohan JG, Stevens DL. Advances in the medical management of skin and soft tissue infections. Br Med J 2016; 355: i6004. 4 Chapman ALN. Outpatient parenteral antimicrobial therapy. Br Med J 2013; 346: f1585. 5 Raff AB, Kroshinsky D. Cellulitis: a review. J Am Med Assoc 2016; 316: 325e37.
Herpetic whitlow: (herpes simplex infection of the skin) occurs as a complication of oral or genital herpes simplex virus infection. It is characterized by a painful, erythematous vesicular or pustular skin lesion. There may be associated fever and lymphadenopathy. The diagnosis is based on exposure history. Herpetic whitlow usually resolves spontaneously in 2e3 weeks, but some recommend treatment with oral aciclovir. Molluscum contagiosum: is a benign condition caused by a pox virus. It usually affects children or immunocompromised individuals. The lesions are most commonly seen on the face and trunk, and are papular with a central punctum.
TEST YOURSELF To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the end of the issue or online here.
Question 1
Which of the following organisms would be of particular concern in this patient? A. Capnocytophaga canimorsus B. Pasteurella canis C. Rabies virus D. Staphylococcus aureus E. Streptococcus pyogenes
A 25-year-old man presented with a 2-day history of a swollen erythematous hand after being bitten by his dog. He had a past medical history of splenectomy following traumatic injury. He had no recent travel outside the UK. On clinical examination, there was a 5 cm, erythematous, swollen area on the back of the right hand.
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SKIN AND SOFT TISSUE INFECTIONS
Question 2
Question 3
A 30-year-old woman presented with a 3-day history of pain and swelling on the left leg. She was an active intravenous drug user with a history of meticillin-resistant S. aureus colonization. On clinical examination, her temperature was 37.0 C, heart rate 88 beats/minute and blood pressure 115/68 mmHg. There was extensive cellulitis of the left leg.
A 55-year-old man became febrile and his laparotomy wound dehisced 4 days after an emergency laparotomy for bowel perforation. He had no known allergies. On clinical examination, his temperature was 38.4 C, heart rate 120 beats/minute, blood pressure 85/55 mmHg and respiratory rate 20/minute. Oxygen saturation on air was 92%.
Which of the following is the most appropriate initial antibiotic management? A. Give intravenous flucloxacillin as an inpatient B. Give intravenous vancomycin as an inpatient C. Give intravenous teicoplanin via an outpatient parenteral antibiotic treatment (OPAT) service D. Give intravenous ceftriaxone via an OPAT service E. Give oral doxycycline as an outpatient
Which of the following empirical antibiotic regimes would be most appropriate? A. Ceftriaxone 2 g once daily i.v. B. Flucloxacillin 1 g four times daily i.v. C. Gentamicin 5 mg/kg once daily i.v. D. Piperacillin/tazobactam 4.5 g 8-hourly i.v. E. Metronidazole 500 mg 8-hourly i.v.
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Please cite this article in press as: Ramsay ID, T€ or€ ok ME, Skin and soft tissue infections, Medicine (2017), http://dx.doi.org/10.1016/ j.mpmed.2017.08.008