Antimicrobial Chemotherapy, 5th Edition
Part 4 - Therapeutic Use of Antimicrobial Agents
Skin and Soft Tissue Infections
At birth the skin of the baby rapidly becomes colonized with bacteria from the mother, other handlers, and the environment. Some of these essentially non-pathogenic microbes, including coryneforms, coagulase-negative staphylococci, micrococci, and propionibacteria become established as the resident flora of the normal skin. In intact skin, these micro-organisms usually prevent potential pathogens such asStaphylococcus aureus and Streptococcus pyogenes (haemolytic streptococci of Lancefield group A) from becoming established. However, if the skin is broken by accidental or surgical trauma, burns, a foreign body, or a primary skin disease (psoriasis, atopic dermatitis), these pathogens may not only become established as resident organisms; they may also give rise to infection of the skin and subcutaneous tissue.
Other bacteria from, for example, faeces or the environment can briefly colonize the skin as transient flora; they are readily removed by washing, whereas resident organisms will persist in moderate numbers despite even the most thorough skin disinfection. If introduced through, for example, a dirty wound or compound fracture, transient micro-organisms can also give rise to skin and soft-tissue infection. Such infections are often polymicrobial (mixed).
The general condition of the patient, including factors such as underlying immunodeficiency, diabetes mellitus, or systemic or topical treatment with corticosteroids, can also predispose to skin infection. Treatment with broad-spectrum antibiotics, which disrupts the resident flora, can give rise to cutaneous candidiasis (thrush). In one of the commonest skin infections—a boil or furuncle—there is usually no evident breach in the skin nor any other predisposing factor.
Many different micro-organisms, including bacteria, fungi, and some viruses, may be involved in skin and soft-tissue infections. However, by far the commonest bacterial causes are Staph. aureus and Str. pyogenes. Thrush is usually caused by the yeast Candida albicans, and cold sores by the virus herpes simplex.
Common clinical presentations
Impetigo consists of discrete purulent lesions on the exposed areas of the body, especially the face and extremities. It is nearly always caused by Str. pyogenes or Staph. aureus. Impetigo is most common in tropical countries but is also prevalent in more temperate zones especially during the summer. It is most common in children aged 2-5 years but can occur in older children or adults. The prevalence is strongly related to personal hygiene and impetigo is much commoner in socially deprived communities.
The lesions of impetigo start with papules that evolve into pustules and then form a characteristic thick crust over 4-7 days. The lesions are sometimes bullous. Antibacterial treatment can be either topical or systemic (Table 23.1).
Such lesions of the skin are by far the commonest bacterial infection in man and include:
- folliculitis (pimples), where the infection is confined to hair follicles and does not involve the surrounding skin or subcutaneous tissue; such infections are usually mild and self-limiting, and do not need medical attention;
- furuncles (boils), where the folliculitis has spread deeper and is surrounded by an area of cellulitis;
- carbuncles, where several furuncles have coalesced and extended into subcutaneous fat to form a large, indurated, painful lesion that contains loculated pus with multiple drainage points.
Antibiotics are rarely required for these lesions unless they are recurrent (Table 23.1). Acne is discussed in Chapter 31 (p. 442).
Cellulitis and erysipelas
These are both diffuse, spreading skin lesions. Cellulitis, which is much more common, occurs in the deeper layers of the skin and subcutaneous tissues. The obviously affected area is red and hot but the demarcation between this and the normal skin is gradual and there is no palpable raised margin. It is more common if there is obstruction to venous or lymphatic drainage or gross obesity, which make the skin more fragile and local host defences less effective. In contrast erysipelas occurs in the superficial layers of the skin, which results in a very clear, abrupt line of demarcation between the affected and normal skin, with a palpable lesion that is raised above the level of the normal skin. Cellulitis may be caused by Str. pyogenes or Staph. aureus, whereas erysipelas is almost always caused by Str. pyogenes.Erysipelas usually occurs on the face or on the legs, whereas cellulitis can occur anywhere on the body although it is commonest on the legs. Both types of lesion are usually preceded by a break in the skin. Methicillin-resistant Staph. aureus (MRSA) is increasingly incriminated in community-acquired cellulitis in some countries.
Table 23.1 Most likely bacterial causes and antibacterial treatment for common skin infections
Signs of spreading infection include extension of the line of demarcation, lymphangitis (infection spreading up the lymph vessels with a characteristic thin streak of erythema running up to a lymph node), and painful tender lymph nodes distal to the lesion. Systemic inflammatory response means that the patient has sepsis and is at risk of progressing to severe sepsis or septic shock (see p. 310). Blood cultures should be taken from patients with sepsis arising from cellulitis, as about 50% are positive.
Both cellulitis and erysipelas can be treated with an antistaphylococcal penicillin. In theory erysipelas could be treated with penicillin V, but it is not worth taking the risk that the cause may be Staph. aureus. There is a belief that an antistaphylococcal penicillin should be combined with benzylpenicillin or penicillin V, since the latter are much more active against Str. pyogenes. However, provided antistaphylococcal penicillins are given in adequate dosage they are just as effective alone.
Prevention of recurrent cellulitis requires enhancement of host defences by preventing breaks in the skin (e.g. dry thoroughly between the toes after washing), or wearing compression stockings to reduce oedema. If these measures fail then long-term prophylactic antibiotics are unfortunately not usually effective. It is preferable to give the patient a course of antibiotics to start as soon as symptoms begin.
Necrotizing skin and soft tissue infections
These are rapidly spreading and life-threatening forms of cellulitis that involve the deeper fascial and/or muscle compartments in addition to skin and subcutaneous tissue. Infection usually arises following a break in the skin after trauma or elective surgery. Most cases are caused by Str. pyogenes either alone or in combination with other bacteria, including Staph. aureus, coliform bacilli, and anaerobes. Many variations of nectrotizing skin and soft tissue infections have been described according to the tissues involved, the anatomical site of the infection and the microbial causes but the basic principles of management are the same. The key is early distinction between a cellulitis that will respond to antibacterial treatment and a deeper necrotizing infection that is likely to require surgical debridement as well. The following clinical features indicate the possibility of necrotizing infection:
- severe, constant pain that is disproportionate to the visible inflammation in the skin;
- bullae on the skin, which occur because of occlusion of deep blood vessels that cross the fascia or muscle compartments;
- skin necrosis or bruising;
- gas in the soft tissues detected by palpation or imaging;
- oedema that extends beyond the margin of erythema;
- cutaneous anaesthesia;
- systemic toxicity, manifested by signs of severe sepsis (p. 185);
- rapid spread of infection despite appropriate antibiotic therapy.
Blood cultures are often positive and streptococci can also be isolated from the bullous lesions. The management of these rare conditions is primarily surgical, with radical debridement of all necrotic tissue, intensive life-support therapy, and the treatment of shock. Antimicrobial therapy must be directed against aerobic Gram-positive and Gram-negative bacteria and against anaerobic bacteria until the results of cultures are available. Clindamycin is active against aerobic Gram-positive and anaerobic pathogens, it also suppresses toxin production by group A streptococci and may be superior to penicillins for these infections. A fluoroquinolone should be added initially to treat Gram-negative aerobic pathogens.
Gas gangrene (clostridial myositis) is a life-threatening, invasive infection that can be caused by several species of Clostridium, principallyC. perfringens. These bacteria are part of the normal intestinal flora of man and animals, and clostridial spores are common in soil. Gas gangrene develops when impaired blood supply, tissue necrosis, or the presence of foreign bodies produce a low oxygen tension in the tissues and thus create conditions in which the spores can germinate. Extensive soft-tissue injury contaminated with soil or dirt carries an increased risk of gas gangrene. Gas gangrene may rarely complicate surgical wounds, particularly after intestinal or biliary surgery, or be a complication of septic abortion. Clostridial anaerobic cellulitis occurs under similar circumstances, but exploration of the wound usually reveals that the muscle is spared.
A clinical diagnosis is made on the basis of palpable (crepitus) or radiological signs of a spreading, gas-producing infection in a toxic patient with the above risk factors. Immediate and extensive surgical excision of all involved tissues and the removal of any foreign body are essential, and may mean hysterectomy (after septic abortion), excision of subcutaneous tissue and muscle of the abdominal wall, or even amputation of a limb. Parenteral benzylpenicillin should also be given promptly in high dosage. For patients allergic to penicillin, metronidazole may be used. Despite these desperate and mutilating measures, the mortality remains high.
Cellulitis following animal or human bites
Infections following animal bites are polymicrobial, often include anaerobic bacteria and unusual organisms such as Pasteurella multocida, a human pathogen that is part of the normal oral flora of cats. Human bites are often associated with greater damage to the skin and soft tissues and are also polymicrobial with aerobic and anaerobic bacteria. Co-amoxiclav is an effective treatment for all these infections (Table 23.1).
Diabetic foot infections
Infections of the feet are particularly common in diabetics because several important host defences, including circulation and sensation, are compromised. This enables minor injuries to progress to advanced stages of infection rapidly and with very few symptoms. Consequently it is vital to educate patients with diabetes about how to avoid trauma to the feet and how to recognize infection early. Patients with diabetes also have impaired healing so that chronic ulcers are common.
Chronic ulcers without spreading cellulitis do not require antibiotic treatment, even if there is some purulence in the exudate as this simply indicates bacterial colonization of the ulcer. If there is cellulitis spreading up to 2 cm from the margin of the ulcer the infection is likely to respond to oral antibiotics, but if the infection spreads more widely or is associated with signs of sepsis then referral to hospital for intravenous treatment should be considered. Taking swabs from chronic ulcers is not helpful because they will be colonized with possibly harmless bacteria; even if infection is present the bacteria cultured are not always the ones that are responsible. Meaningful cultures can be obtained only by debriding the ulcer and then obtaining tissue specimens from the base of the lesion by curettage (scrapings with a sterile blade). Empirical treatment should cover both aerobic and anaerobic pathogens (Table 23.1).
Because of the combination of impaired circulation and sensation diabetic foot infections are particularly likely to progress to osteomyelitis because they may be present for weeks before the patient seeks medical attention. Osteomyelitis should be considered as a potential complication of any deep or extensive ulcer, especially if it is overlying a bony prominence or contains visible bone particles. Management of osteomyelitis is considered in Chapter 24.
Toxic shock syndrome
Certain phage types of Staph. aureus and Str. pyogenes produce toxins that cause a multisystem disease characterized by the sudden onset of fever, myalgia, vomiting, diarrhoea, hypotension, and an erythematous rash: the toxic shock syndrome. Staphylococcal toxic shock syndrome was originally thought to affect only menstruating women who used a particular type of tampon, it is now known to be a rare sequel of any type of staphylococcal infection. An antistaphylococcal penicillin (e.g. flucloxacillin) or clindamycin should be given, but antibiotic therapy is secondary to systemic support. Clinical results with intravenous immunoglobulin are inconsistent, probably because different batches of immunoglobulin contain variable quantities of neutralizing antibodies to some of these toxins.
Viral infections of the skin, such as herpes simplex and varicella zoster, are discussed in Chapter 27. Superficial fungal infections usually respond to topical therapy (Chapter 31), although dermatophyte infections of finger- or toenails may require oral treatment with terbinafine for up to 3 months, or with griseofulvin for a year or more. These agents are deposited in newly formed keratin and the prolonged treatment is needed to allow healthy nail to replace the diseased tissue. Even so, treatment of chronic infections of toenails may be unsuccessful, although terbinafine is more reliable in this respect than griseofulvin.
Lipsky BA, Berendt AR, Deery HG, Embil JM, Joseph WS, Karchmer AW, LeFrock JL, Lew DP, Mader JT, Norden C, Tan JS. Diagnosis and treatment of diabetic foot infections. Clinical Infectious Diseases 2004; 39:885-910.
Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger P, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan EL, Montoya JG, Wade JC. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clinical Infectious Diseases 2005; 41:1373-1406.