Skin and soft-tissue infec tions The early clinical presentation of soft-tissue may be deceptive.

JAN PRETORIUS, MB ChB, MMed (Surg), FCS (SA) Critical Care Adjunct Professor, Department of , Medical School, Faculty of Health Sciences, University of Pretoria, and Principal Specialist and Head, Surgical , Steve Biko Academic Hospital, Pretoria Jan Pretorius is chairman of the Multidisciplinary Head and Neck Oncology Unit and of the Critical Care Task Team at the Steve Biko Academic Hospital, Pretoria. Correspondence to: Jan Pretorius ([email protected])

indicating infections extending to the deeper layers of the skin. Definitions and terminology Complicated SSTIs may involve the subcutaneous tissue, deep fascia The skin and its appendages, and the subcutaneous tissue, deep fascia and muscle.1,2 Uncomplicated SSTIs1,2 may be defined as conditions and muscle, can all develop infections under various circumstances. that respond to a course of or to simple drainage. These Patients with skin and soft-tissue infections (SSTIs) often initially include minor , , , furuncles or , present to family physicians. The of SSTIs , limited , and even minor wound infections. 1,2 may overlap, making a comprehensive diagnosis difficult. Early 1,2 Examples of complicated SSTIs are the following: clinical presentation may be deceptively innocent.3 Furthermore, at presentation it is often difficult to assess the depth, severity • infections involving deep skin structures and specific structures or tissues involved. All SSTIs represent a • infections requiring significant surgical intervention, e.g. continuum of symptoms and should be considered collectively: infected burns, major abscesses, infected ulcers, infections in • Erythema, warmth, oedema, skin discoloration and localised diabetics, and deep-space wound infections pain are common presenting signs in the case of superficial, • otherwise uncomplicated infections occurring at anatomical complicated or deep infections. sites (e.g. the rectal area) where the risk of anaerobes and Gram- • Some or all of the following signs are indicative of a necrotising negative pathogens is increased condition affecting deep structures • infections in the presence of significant underlying disease, • when vesicles become manifest e.g. mellitus, peripheral vascular disease, ischaemic ulceration and chronic lymphoedema, that may complicate the • when oedema is tense response to therapy • when is present • where immunosuppression may enable unusual or normally • when pain is extreme non-pathogenic to cause infections or increase the likelihood of developing fulminant infections. • when progresses. SSTIs may also be classified according to the presence or absence of • Failure of an SSTI to respond to antibiotics points to a necrotising necrotic or devitalised tissue. In necrotising soft-tissue infections infection. (NSTIs) the devitalised tissue plays an important role in the • Signs of systemic infection, , tachycardia and pathophysiology of the disease, providing a growth medium for organ dysfunction may indicate toxic (staphylococcal or bacteria and preventing cellular and humoral defence mechanisms streptococcal). from reacting. The acidic pH of such tissue or wounds prevents the antimicrobial agents from being delivered effectively or inactivates It is essential to maintain a high index of suspicion for these these drugs. NSTIs may involve the dermal and subcutaneous infections and be aware of possible presenting features. layers (necrotising cellulitis), fascia (necrotising fasciitis), muscle Recognising the extent of the infection is imperative to ensure ( or myonecrosis) or any combination of these.2 2 prompt and comprehensive therapy. SSTIs may vary from less 4 The cardinal principles of controlling SSTIs are: severe conditions to severe and invasive conditions, which may lead to soft-tissue loss or limb and even death if not • adequate drainage of infected fluid collections managed promptly. Therefore, patients with severe infections need •  of infected, necrotic or devitalised tissue early hospitalisation, surgery and antibiotics. • removal of devices or foreign bodies Early clinical presentation • early, appropriate therapy. may be deceptively innocent. Early aggressive surgery is indicated for both complicated SSTIs and NSTIs after prompt , adjuvant antibiotic therapy and systemic support. Wound bed preparation and wound healing Classification should receive particular attention. SSTIs can be described as localised or spreading – this may be useful when considering surgical treatment. Epidemiology SSTIs can be classified as uncomplicated, referring to infections SSTIs are common bacterial infections seen by family practitioners affecting the superficial layers of the skin, and as complicated, and surgeons. They account for a substantial portion of

June 2010 Vol.28 No.6 CME 265 Skin and soft-tissue infections

emergency department visits and hospital cellular response and lead to admissions. formation or spreading of the infection. These may be extremely potent SSTIs led to 29 820 hospital admissions and cause forms of toxic shock in the UK during 1985, with a mean that may be fatal.1 occupancy of 664 hospital beds each day. A more recent study in the UK indicated that SSTIs account for about 10% of hospital admissions, with a mean length of stay Phy sical examination The following findings are important of 5 days. During 1995, 330 000 hospital 1 1 indicators of severity of infection: admissions for SSTIs were reported. • At the site of infection: Over recent decades physician visits for cellulitis and soft-tissue infections • the type of lesion have increased from 32 to 48 per 1 000 • whether fluctuation (fluid that has to population from 1997 to 2005. Necrotising be drained) is present fasciitis caused by group A streptococci is now endemic in the USA. Of great • whether crepitus is present, indicating concern is that , a gas-forming infection. the predominant cause of cellulitis, and • The size and site of the lesion may abscesses or wound exudates, are becoming indicate the severity of the infection. increasingly resistant to methicillin. Some sites (face, fingers, toes, genitals) and other newer antibiotics Fig. 1. Impetigo (US Department of Health 5 necessitate admission of the patient and are therefore the drugs of choice. This and Human Services). vigilant observation. is true even for community-acquired methicillin-resistant S. aureus (MRSA), • The degree of pain: demonstrating that MRSA is no longer a • pain not in proportion to the pathogen limited to hospitalised patients. appearance of the lesion may indicate a developing necrotising infection

Pathogenesis • loss of skin sensation around a wound The role of the skin as an integral part of may be an indication of dead tissue our host defence mechanisms cannot be • in limbs with peripheral vascular underestimated. Intact skin serves as an disease the pain caused by SSTIs may effective physical barrier to the penetration be masked. of micro-organisms because of the tight junctions between epithelial cells. In • Systemic infection, usually indicated addition, the acidic oily matrix produced by extremes of temperature (<35oC or by the sebaceous glands coats the epithelial >40oC), hypotension, tachycardia and Fig. 2. Facial (CDC/Dr Thomas F cells. Commensal and saprophytic micro- changed levels of consciousness. Sellers/Emory University). organisms of the normal skin flora are interspersed in this matrix cell surface.1 1,6 Bacteria involved are -negative Uncomplicated SSTIs staphylococci, corynebacteria, micrococci, Impetigo (Fig. 1) is a bacterial, diphtheroids and propionibacteria. inflammatory skin disease characterised They augment the defence of the skin by by the appearance of pustules, typically on preventing colonisation and invasion by the face or the extremities. This condition more virulent species. In moist skin areas is common during hot, humid conditions. such as the groin the normal flora may also It is highly communicable and facilitated include Gram-negative enteric bacteria, by overcrowding and poor hygiene. e.g. Escherichia coli. Erysipelas (Fig. 2) is a contagious infection To cause SSTIs invading organisms must of the superficial layers of the skin that Fig. 3. A on the buttock of a dia- penetrate the skin barrier through a breach may extend to the subcutaneous tissue and betic patient (Wikimedia commons). caused by direct trauma or an underlying form vesicles or bullae. The predominant process such as ischaemia. The two most clinical features are sharply demarcated Folliculitis is a purulent inflammation of common pathogens in SSTIs are S. aureus red edges and oedematous, indurated hair follicles. and beta-haemolytic streptococci, e.g. elevation of the affected area. A furuncle or is a painful skin pyogenes. The ability of all dermatitis is infective, with nodule associated with circumscribed micro-organisms to cause SSTIs is related an erythematous-oedematous appearance. inflammation of the corium or dermis and to their toxin production and resistance to subcutaneous tissue, enclosing a central 1 It may occur on the hands of fishmongers host inflammatory reponses. or meat workers and is caused by slough or core. It is caused by bacteria that factors may include secretion Erysipelothrix rhusiopathiae from infected enter the skin through hair follicles. of substances that can induce extensive meat, bone or hides. A carbuncle (Fig. 3) is a necrotising cytokine and chemokine responses in the Cellulitis is a purulent inflammation of infection of skin and subcutaneous tissue, host. They may also deter phagocytosis the loose subcutaneous tissue. The skin is usually caused by staphylococci. Typically, by host scavenger cells or produce warm, diffusely red and swollen. The area it has multiple formed or incipient drainage extracellular toxins that damage the host affected may be extensive and painful. sinuses and an indurated border.

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In general, the dermal layer of the skin Linezolid may be used for hospital- or should provide sufficient cover may become infected (i.e. cellulitis) by health care-associated MRSA (HA- for non-MRSA SSTIs. In serious traumatic injury, surgery or underlying MRSA) infections. infections broad-spectrum skin disease such as psoriasis or peripheral (amoxicillin/clavulanic Simple drainage and wound care should vascular disease. Typical pathogens acid or piperacillin/tazobactam) or suffice for most surgical site infections and that cause cellulitis are S. aureus and carbapenems (ertapenem) provide subcutaneous abscesses. Streptococcus spp. Sometimes Gram- excellent cover for SSTIs. CA- negative bacteria and anaerobes may • Antibiotics are indicated when: MRSA can usually be treated with also be involved.6 Because of the lack of trimethoprim-sulfamethoxazole. • signs of systemic infection are present microbiological technology the aetiology This will also cover Streptococcus (temperature >38oC, tachycardia, can often not be determined. Specimens spp. and Gram-negative organisms leukocytosis) for culture and sensitivity must be taken except Pseudomonas aeruginosa. because at present even community- • >5 cm erythema occurs around the , which will cover Gram- acquired S. aureus infections are often wound positive organisms and anaerobes, resistant to methicillin (CA-MRSA). may also be used. However, in • deep infections with implants or grafts However, outbreaks of CA-MRSA have South Africa, MRSAs encountered are present. not been described in South Africa. are not clone-specific epidemics • For wound infections developing after and may vary in their antimicrobial Infections ‘above the belt’ are more likely clean surgical procedures cefazolin or sensitivity. They may therefore be to be caused by S. aureus, whereas those clindamycin should be sufficient. unpredictable in their response to ‘below the belt’, e.g. perianal abscesses and trimethoprim-sulphamethoxazole. perineal hidradenitis suppurativa, often • For wound infections developing after consist of mixed flora. clean-contaminated surgical procedures • HA-MRSA should be treated with Gram-negative and anaerobic cover vancomycin or linezolid. A new Clinically it is very difficult to distinguish should be provided, e.g. amoxicillin/ drug, tigecycline (a semi-synthetic between streptococcal and staphylococcal clavulanic acid or a fluoroquinolone glycylcycline), also has broad- impetigo and cellulitis. As a microbiological plus clindamycin. spectrum activity against MRSA. diagnosis is often not possible or practical, empiric antibiotic treatment for • Nosocomial infections are often streptococci and staphylococci should be caused by MRSA or mixed flora, commenced. Complicated SSTIs e.g. surgical site infections after These infections differ from uncomplicated intra-abdominal procedures. When infections in that the deeper structures MRSA is suspected, vancomycin or such as muscle and fascia are typically Complicated SSTIs linezolid should be prescribed. When involved. These infections often occur mixed flora are involved, extended- may involve the in immunocompromised or diabetic spectrum penicillins or carbapenems patients. The bacteria involved are subcutaneous are indicated. the same as in superficial infections, tissue, deep fascia although polymicrobial flora occur more Duration of antibiotic therapy: often. These infections are debilitating, and muscle. • Even in the case of deep-seated may be limb threatening or progress to infections antimicrobial therapy should systemic infection, and should be treated not exceed 7 - 10 days. As debridement Treatment immediately. may result in open wounds, dedicated • In general, antibiotics are indicated for wound care will play an important role the treatment of cellulitis. In cases of Treatment in expediting healing. uncomplicated cellulitis outcome after Principles of treatment for patients with 1 5 days of therapy is equivalent to 10 complicated SSTIs are:6 Indications for hospitalisation: days’ treatment. • Early recognition of the need for surgical • severity/size of the infection • Typically, antimicrobial agents include drainage and/or debridement. This may • need for surgical drainage antistaphylococcal penicillins or the necessitate early specialist surgical . Broad-spectrum drugs consultation to ensure adequate source • likelihood of disease progression such as the fluoroquinolones, e.g. control because antibiotic treatment • presence of comorbid conditions moxifloxacin, should be reserved for duration relies on this. organisms resistant to the more narrow- • results of microbiological culture and • Standard of care that includes early, spectrum agents. sensitivity testing appropriate antimicrobial therapy • Broad-spectrum beta-lactams, e.g. combined with drainage or debride- • assessment of the patient’s treatment amoxicillin/clavulanic acid, are ment. Consider where the infection was compliance indicated for animal or human bites acquired because it will determine the • level of support available at home. and intravenous drug users as Gram- choice of antibiotic. The empiric choice negative and anaerobic bacteria are of antibiotic therapy must cover the possibly involved. most likely organisms. Necrotising skin and 6 • The threshold for treatment of MRSA • Community-acquired infections soft-tissue infec tions infections should be low, i.e. if there are mostly due to CA-MRSA, Necrotising infections are fulminant, is no improvement in 72 hours. Out- MSSA and Streptococcus spp. life-threatening forms of complicated patient treatment for suspected CA- Anti-staphylococcal penicillins, SSTIs. They involve the fascia, resulting MRSA may include oral trimethoprim- cephalosporins, or broad-spectrum in of subcutaneous blood sulfamethoxazole or clindamycin. fluoroquinolones, e.g. moxifloxacin, vessels and of the underlying

268 CME June 2010 Vol.28 No.6 Skin and soft-tissue infections tissue. Clinically, this condition should be multiple system organ failure. Fascial at www.whasa.org and Wound Healing suspected when erythema, oedema, skin necrosis and myonecrosis occur, but Southern Africa at www.woundhealingsa. discoloration or bullae are associated with there is no gas in the tissues. co.za. more pain than indicated by signs and Early diagnosis is essential to protect limbs symptoms. This condition may progress References and to save lives. All types of necrotising rapidly to widespread tissue loss. 1. Aldridge KE, Pankey GA, Rodloff AC. Lectures infections should be suspected on clinical in Hospital Infections, part 4: Complicated Skin and Skin Structure Infections. London: Current 1,3 grounds only. An aggressive approach, Classification of necrotising SSTIs e.g. bedside incision, will contribute Medicine Group, 2006. The nomenclature is confusing because to the diagnosis. On incision, there is 2. May AK. Skin and soft tissue infections. Surg these infections often occur along a loss of fascial integrity, lack of Clin N Am 2009; 89: 403-420. continuum. Classically these infections and ‘dishwater fluid’ in the wound. No 3. Majeski JA, John JF, jr. Necrotizing soft tissue are separated into necrotising fasciitis and investigations or preparations should infections: a guide to early diagnosis and initial therapy. South Med J 2003; 96(9): 900-905. myonecrosis: delay operative intervention. Early 4. Marshall JC, Maier RV, Jimenez M, et al. Source • Meleney’s synergistic , caused by specialist surgical consultation for radical, control in the management of severe and S. aureus interacting with microaerophilic repeated debridement takes precedence. : an evidence-based review. Crit streptococci. Surgical patients are at Broad-spectrum antibiotics should be Care Med 2004; 32(11) Suppl: S513-S526. risk and gangrene is observed as slowly administered, as discussed in the previous 5. Eron LJ. Cellulitis and soft tissue infections.Ann expanding ulceration confined to the section. Although antibiotics play an Intern Med 6 January 2009; ITC1-1 – ITC1-16. superficial fascia. adjunctive role to surgery, they should be 6. Hedrick TL, Smith PW, Gazoni LM, Sawyer RG. initiated when a diagnosis has been made. The appropriate use of antibiotics in surgery: a • Clostridial cellulitis, caused by review of surgical infections. Curr Probl Surg perfringens, occurs after local trauma or 3,4,6 2007; 44: 635-675. surgery. Gas is found in the skin, but not Treatment in the fascia. • Timing is critical for successful treatment • Non-clostridial anaerobic cellulitis, – early recognition and aggressive medical caused by mixed aerobes and anaerobes and surgical therapy are the primary In a nutshell ( spp. and determinants of successful outcome. • Important principles in the prevention spp.). Diabetics are typically affected. The of surgical site infections are good • Early, aggressive surgical debridement, hand hygiene, good surgical technique main clinical feature is gas in the tissues. repeated within 6 - 48 hours in the and appropriate use of perioperative • Gas gangrene, caused by Clostridium operating theatre, is necessary to ascertain antibiotic prophylaxis. spp. (C. perfringens, C. histolyticum, C. that the wound is clean. Source control is • Typical pathogens associated with septicum) may occur after trauma, crush essential. This must be done regardless of cellulitis are S. aureus and Streptococcus injuries, injections or spontaneously in how well the patient is at that time. spp., but may include Gram-negative organisms and anaerobes. oncology patients. It is characterised • Appropriate microbial samples must be • Culture identification of the pathogen by myonecrosis, gas in the tissues and taken. systemic toxicity. produce should point to changing from broad- spectrum antibiotics to more narrow- a variety of toxins. The alpha toxin is • Early, appropriate empiric broad-spect- rum antibiotics should be administered. spectrum regimens to avoid development responsible for rapid tissue necrosis, of resistance. while the others often lead to systemic • Dedicated attention should be given to • Standard of care is antimicrobial therapy toxicity, which may be life threatening. wound healing. with drainage or debridement for patients with complicated . • Necrotising fasciitis type 1. This is • There should be supportive systemic a polymicrobial infection caused by treatment in an ICU. Although • Antibiotics serve an adjunctive role to surgical debridement in necrotising Gram-negative aerobic and controversial, the use of intravenous infections, but should be initiated Gram-positive organisms along with gamma-globulin may be considered. 6 strict anaerobes. Diabetics, patients with immediately on diagnosis. Empiric Hyperbaric should be used after therapy should target the suspected morbid obesity, alcoholics, parenteral surgery for clostridial gangrene. pathogen. drug abusers and those with peripheral • Maintaining a high index of suspicion for vascular disease are at risk. It destroys 1 deep and necrotising infections and an the fat and fascia, sometimes sparing the Other causes of SSTIs awareness of possible presenting features 3-5 skin of the lower extremities, perineum A thorough history must be taken in is essential. and abdominal wall. patients with SSTIs. There is a variety of • Rapid spreading of the infected area, • Necrotising fasciitis type 2 or strepto- infectious agents, other than bacteria, violaceous bullae or reddish-purple coccal gangrene is primarily caused by which may cause infection or play an discoloration of the skin, severe pain, or systemic toxicity suggest necrotising group A beta-haemolytic streptococci important role in the development of infection, e.g. viruses, , animal fasciitis that requires urgent surgical (GAS), also known as S. pyogenes, alone attention.5 or in combination with S. aureus. It may bites, insect bites or stings, tick bites, fungi and injection drug use. • The cardinal principles of source control occur with penetrating injuries, surgery, in SSTIs are:4,5 burns, childbirth, pelvic inflammatory • adequate drainage of infected fluid disease or varicella infections. The collections organism may be very contagious. The Wound healing • meticulous, complete surgical typical appearance of severe local pain Although not the topic of this article, debridement of all infected, necrotic attention to wound healing plays an and rapidly spreading erythema followed or devitalised tissue by necrosis is a result of the streptococcal important role in the recovery of patients • removal of devices or foreign bodies haemolytic toxins, streptolysin O and S, with severe SSTIs. The reader is encouraged which destroy tissue. Three exotoxins are to visit the website of the Wound Healing • early, appropriate antibiotic therapy. also produced, which mediate shock and Association of Southern Africa (WHASA) June 2010 Vol.28 No.6 CME 269