MKSAP primer: Cellulitis, necrotizing fasciitis and toxic shock syndrome
Adapted from ACP's latest Medical Knowledge Self-Assessment Program
Cellulitis
Cellulitis is an inflammation of skin and underlying subcutaneous tissues that may be either infectious or noninfectious. Erysipelas is an acute superficial form of cellulitis that primarily involves the dermal lymphatics. Some of the common and more unusual diseases that may masquerade as infectious cellulitis are listed in Tables 1 and 2. The infectious forms of cellulitis may be caused by various microorganisms. However, group A streptococci (Streptococcus pyogenes), other hemolytic streptococci and Staphylococcus aureus cause most cases of cellulitis in patients seeking medical attention.
Although any anatomic location may be affected, the lower extremities are most often involved. Cellulitis may result from an underlying problem such as trauma causing a break in the skin but may also occur without an obvious cause. As with necrotizing fasciitis and toxic shock syndrome, toxin production by the causative bacteria has a major role in the development of cellulitis.
It has recently been recognized that use of cell wall-active antibiotics such as the ß-lactams (penicillins, cephalosporins and carbapenems) to treat cellulitis may sometimes cause an initial worsening of signs and symptoms before improvement is seen. Patients have also been reported who developed necrotizing fasciitis or toxic shock syndrome after being treated with a ß-lactam for apparently uncomplicated cellulitis. One possible reason is that, upon exposure to bactericidal antibiotics, lysis of the microorganisms leads to rapid release of a bolus of exotoxins that exacerbate the local and systemic effects of the infection.
Clindamycin, an antibiotic that is more likely to be bacteristatic (slowing or stopping the multiplication of the bacteria rather than lysing them), has been shown in vitro to be more effective than ß-lactams in animal models of cellulitis caused by susceptible microorganisms. Evidence is accumulating that this is true in humans as well. A growing number of physicians now treat cellulitis with clindamycin alone or with clindamycin plus vancomycin or an antistaphylococcal ß-lactam such as nafcillin.
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Cellulitis resulting from animal or human bites is more likely to be caused by microorganisms other than group A streptococci or S. aureus. |
Staphylococcus aureus is a common cause of cellulitis, especially in patients with diarrhea, and increasing cases of methicillin-resistant S. aureus (MRSA) are being found in the community. For this reason, vancomycin or the newer antistaphylococcal antibiotics that are effective against MRSA are often included in the initial treatment regimen until the causative microorganisms are identified and their sensitivities are known.
Whether MRSA is more virulent than methicillin-sensitive S. aureus (MSSA) is uncertain. A study of patients with hospital-acquired staphylococcal bloodstream infections reported a statistically significant trend toward MRSA being more virulent than MSSA (mortality rate of 11.8% for MRSA versus 5.1% for MSSA). These results must be replicated in other settings because the differences could be due to differences in patient characteristics, variations in antibiotic treatment or other variables.
Occasional patients develop recurrent cellulitis. This occurs most often on the arms of patients who have had a radical mastectomy with axillary lymph node dissection or on the legs of patients who have had coronary artery bypass graft surgery with saphenous vein harvesting to provide the graft material. Recurrent cellulitis is most often successfully treated with long-term (six months to one year) daily prophylaxis with penicillin V or other antibiotics with good activity against the group A streptococci. An antibiotic with activity against MRSA may rarely be necessary.
Cellulitis resulting from animal or human bites is more likely to be caused by microorganisms other than group A streptococci or S. aureus. Infection due to Pasteurella multocida commonly occurs after cat bites and less commonly after dog bites. Capnocytophaga canimorsus cellulitis may develop after dog bites and less often after cat bites. Human bites may result in cellulitis due to various pathogens, including Eikenella corrodens, Fusobacterium species and others. Human or animal bites may cause S. aureus infection.
Although bite wounds are commonly treated with oral first-generation cephalosporins in emergency department settings, these agents should not be used as primary therapy because many causative microorganisms are resistant to these drugs. A second- or third-generation cephalosporin plus metronidazole, amoxicillin–clavulanate or ampicillin–sulbactam is appropriate for treating most of the common causes of cellulitis following bite wounds. Other regimens can be used for patients who are hypersensitive to penicillins or have other contraindications to use of these drugs. Animal bites that are severe enough for the patient to seek medical care can be treated with amoxicillin–clavulanate or trimethoprim–sulfamethoxazole plus clindamycin orally.
Cellulitis in immunocompromised patients may be due to any of the pathogens already discussed plus a long list of more unusual microorganisms. Mixed infections, especially those due to aerobic and anaerobic bacteria, may cause cellulitis. Cryptococcus neoformans and other fungi may cause cellulitis that closely mimics cellulitis due to group A streptococci. When crepitance or necrosis develops in a patient with cellulitis, the possible progression to necrotizing fasciitis must be considered.
Necrotizing fasciitis
Necrotizing fasciitis is an infection of fascial planes that results in the death of affected tissues. Although infection usually occurs in fascia deep in subcutaneous tissues, any anatomic area may be affected. Adjacent muscle or other tissue may be involved as the process spreads. Necrotizing fasciitis is almost always accompanied by significant systemic signs and symptoms, such as fever, malaise and leukocytosis.
Common causative microorganisms are group A streptococci and other hemolytic streptococci (e.g., groups B, C and G), S. aureus, Clostridium perfringens, Clostridium septicum, other clostridia and mixed infections with aerobic gram-negative bacilli and gram-positive or gram-negative anaerobic bacteria. More unusual pathogens, such as Vibrio vulnificus, Flavobacterium odoratum and other gram-negative microorganisms, may be causative in specific situations. Necrotizing fasciitis may also evolve from cutaneous ulcers, such as diabetic or decubitus ulcers.
The causative microorganism cannot be determined from clinical findings alone. Cultures of blood or affected tissue must be done to identify the pathogen. Gram stains will often provide valuable clues to the diagnosis by suggesting streptococcal, staphylococcal or mixed bacteria, but culture results are required to identify the exact species and to determine antibiotic sensitivities.
Although the diagnosis (but not the causative pathogen) can sometimes be made on clinical grounds alone, additional information is often required to establish a definitive diagnosis. MRI scans, CT scans or biopsy results are often needed not only to define the process but also to provide precise anatomic localization. The finding of gas in tissue planes or the presence of edema, enhancement or inflammatory stranding on CT or MRI scans provides critical information early in the course of the illness. Frozen-section biopsies of suspected areas can be done when necessary. The usefulness of obtaining blood cultures cannot be overemphasized, as cultures are frequently positive in patients with necrotizing fasciitis, and culture results are highly relevant in almost every case.
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Treatment of necrotizing fasciitis requires appropriate antibiotic therapy and aggressive surgical debridement to lay open all involved fascial planes. |
The history may provide clues to involvement of unusual microorganisms. For example, if necrotizing fasciitis occurs after a cut or puncture and immersion in warm salt water, infection with V. vulnificus is likely. A recent outbreak of necrotizing fasciitis caused by Clostridium sordellii has been described in "black tar heroin" users. The mortality rate in this group was 38%. The batch of heroin causing this outbreak was contaminated with C. sordellii, and other heroin batches have been reported that were contaminated with other bacteria.
Treatment of necrotizing fasciitis requires appropriate antibiotic therapy and aggressive surgical debridement to lay open all involved fascial planes. Empiric antibiotic therapy will almost always include drugs effective against hemolytic streptococci, S. aureus and anaerobic bacteria.
Because of the increasing prevalence of MRSA in the community, vancomycin or other drugs effective against MRSA should be used for antistaphylococcal therapy. Early administration of clindamycin is also advisable. Initial treatment of V. vulnificus infection should include a tetracycline or third-generation cephalosporin.
Toxic shock syndrome
Toxic shock syndrome is characterized by fever, nausea, vomiting, diarrhea, hypotension and a rash that often leads to peeling of the skin. Any combination of these findings may occur, although the presence of hypotension is required for the definition of toxic shock syndrome. In its severe form, toxic shock syndrome may progress to multiorgan system failure and death. S. aureus and group A streptococci are the usual causative microorganisms. Groups B, C, G and F streptococci, as well as various other bacteria, have also been implicated.
The disease is caused by bacterial exotoxins that act as superantigens and other bacterial components. Superantigens are able to crosslink T-cell receptors with class II major histocompatibility complex (MHC) molecules on antigen-presenting cells in the absence of specific antigens. This results in activation of huge numbers of T cells (up to 40% of cells), whereas antigenic stimulation results in activation of less than 0.01% of T cells. The extensive activation results in an outpouring of cytokines that causes the severe systemic inflammatory response that is the hallmark of toxic shock syndrome.
Another causative mechanism involving group A streptococci has recently been elucidated. M protein, a cell-wall constituent of the streptococcus, is shed from the organism in tissues and in the bloodstream. The M protein forms aggregates with fibrinogen. These aggregates, in turn, activate polymorphonuclear leukocytes after binding to ß2 integrins on their surface. The leukocytes then release heparin-binding protein and various other cellular components that damage the vascular endothelium, which causes increased vascular permeability and a hypercoagulable state. This process, along with the release of other toxins, results in streptococcal toxic shock syndrome.
As with treatment of cellulitis and necrotizing fasciitis, treatment of toxic shock syndrome should include clindamycin in the initial antibiotic regimen because of its greater ability to reduce the production and release of toxins and also to reduce the shedding of M protein compared with vancomycin and the ß-lactam antibiotics.
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.
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