Soft-tissue infections are common, generally of mild to modest severity, and are easily treated with a variety of agents. An etiologic diagnosis of simple cellulitis is frequently difficult and generally unnecessary for patients with mild signs and symptoms of illness. Clinical assessment of the severity of infection is crucial, and several classification schemes and algorithms have been proposed to guide the clinician . However, most clinical assessments have been developed from either retrospective studies or from an author's own "clinical experience," illustrating the need for prospective studies with defined measurements of severity coupled to management issues and outcomes. Until then, it is the recommendation of this committee that patients with soft-tissue infection accompanied by signs and symptoms of systemic toxicity (e.g., fever or hypothermia, tachycardia [heart rate, >100 beats/min], and hypotension [systolic blood pressure, <90 mm Hg or 20 mm Hg below baseline]) have blood drawn to determine the following laboratory parameters: results of blood culture and drug susceptibility tests, complete blood cell count with differential, and creatinine, bicarbonate, creatine phosphokinase, and C-reactive protein levels. In patients with hypotension and/or an elevated creatinine level, low serum bicarbonate level, elevated creatine phosphokinase level (2-3 times the upper limit of normal), marked left shift, or a C-reactive protein level >13 mg/L, hospitalization should be considered and a definitive etiologic diagnosis pursued aggressively by means of procedures such as Gram stain and culture of needle aspiration or punch biopsy specimens, as well as requests for a surgical consultation for inspection, exploration, and/or drainage. Other clues to potentially severe deep soft-tissue infection include the following: (1) pain disproportionate to the physical findings, (2) violaceous bullae, (3) cutaneous hemorrhage, (4) skin sloughing, (5) skin anesthesia, (6) rapid progression, and (7) gas in the tissue. Unfortunately, these signs and symptoms often appear later in the course of necrotizing infections. In these cases, emergent surgical evaluation is of paramount importance for both diagnostic and therapeutic reasons. Emerging antibiotic resistance among Staphylococcus aureus (methicillin resistance) and Streptococcus pyogenes (erythromycin resistance) are problematic, because both of these organisms are common causes of a variety of skin and soft-tissue infections and because empirical choices of antimicrobials must include agents with activity against resistant strains. Minor skin and soft-tissue infections may be empirically treated with semisynthetic penicillin, first-generation or second-generation oral cephalosporins, macrolides, or clindamycin (A-I); however, 50% of methicillin-resistant S. aureus (MRSA) strains have inducible or constitutive clindamycin resistance  (table 1). Most community-acquired MRSA strains remain susceptible to trimethoprim-sulfamethoxazole and tetracycline, though treatment failure rates of 21% have been reported in some series with doxycycline or minocycline . Therefore, if patients are sent home receiving these regimens, it is prudent to reevaluate them in 24-48 h to verify a clinical response. Progression despite receipt of antibiotics could be due to infection with resistant microbes or because a deeper, more serious infection exists than was previously realized. Patients who present to the hospital with severe infection or whose infection is progressing despite empirical antibiotic therapy should be treated more aggressively, and the treatment strategy should be based upon results of appropriate Gram stain, culture, and drug susceptibility analysis. In the case of S. aureus, the clinician should assume that the organism is resistant, because of the high prevalence of community-associated MRSA strains, and agents effective against MRSA (i.e., vancomycin, linezolid, or daptomycin) should be used (A-I). Stepdown to treatment with other agents, such as tetracycline or trimethoprim-sulfamethoxazole, for MRSA infection may be possible, based on results of susceptibility tests and after an initial clinical response. In the United States, not all laboratories perform susceptibility testing on S. pyogenes. However, the Centers for Disease Control and Prevention has provided national surveillance data that suggest a gradual trend of increasing macrolide resistance of S. pyogenes from 4%-5% in 1996-1998 to 8%-9% in 1999-2001 . Of interest, 99.5% of strains remain susceptible to clindamycin, and 100% are susceptible to penicillin. Impetigo, erysipelas, and cellulitis. Impetigo may be caused by infection with S. aureus and/or S. pyogenes. The decision of how to treat impetigo depends on the number of lesions, their location (face, eyelid, or mouth), and the need to limit spread of infection to others. The best topical agent is mupirocin (A-I), although resistance has been described ; other agents, such as bacitracin and neomycin, are considerably less effective treatments. Patients who have numerous lesions or who are not responding to topical agents should receive oral antimicrobials effective against both S. aureus and S. pyogenes (A-I) (table 2). Although rare in developed countries (<1 case/1,000,000 population per year), glomerulonephritis following streptococcal infection may be a complication of impetigo caused by certain strains of S. pyogenes, but no data demonstrate that treatment of impetigo prevents this sequela. Classically, erysipelas, is a fiery red, tender, painful plaque with well-demarcated edges and is commonly caused by streptococcal species, usually S. pyogenes. Cellulitis may be caused by numerous organisms that are indigenous to the skin or to particular environmental niches. Cellulitis associated with furuncles, carbuncles, or abscesses is usually caused by S. aureus. In contrast, cellulitis that is diffuse or unassociated with a defined portal is most commonly caused by streptococcal species. Important clinical clues to other causes include physical activities, trauma, water contact, and animal, insect, or human bites. In these circumstances appropriate culture material should be obtained, as they should be in patients who do not respond to initial empirical therapy directed against S. aureus and S. pyogenes and in immunocompromised hosts. Unfortunately, aspiration of skin is not helpful in 75%-80% of cases of cellulitis, and results of blood cultures are rarely positive (<5% of cases). Penicillin, given either parenterally or orally depending on clinical severity, is the treatment of choice for erysipelas (A-I). For cellulitis, a penicillinase- resistant semisynthetic penicillin or a first-generation cephalosporin should be selected (A-I), unless streptococci or staphylococci resistant to these agents are common in the community. For penicillin-allergic patients, choices include clindamycin or vancomycin. Lack of clinical response could be due to unusual organisms, resistant strains of staphylococcus or streptococcus, or deeper processes, such as necrotizing fasciitis or myonecrosis. In patients who become increasingly ill or experience increasing toxicity, necrotizing fasciitis, myonecrosis, or toxic shock syndrome should be considered, an aggressive evaluation initiated, and antibiotic treatment modified, on the basis of Gram stain results, culture results, and antimicrobial susceptibilities of organisms obtained from surgical specimens. Necrotizing infections. Necrotizing fasciitis may be monomicrobial and caused by S. pyogenes, Vibrio vulnificus, or Aeromonas hydrophila. Recently, necrotizing fasciitis was described in a patient with MRSA infection . Polymicrobial necrotizing fasciitis may occur following surgery or in patients with peripheral vascular disease, diabetes mellitus, decubitus ulcers, and spontaneous mucosal tears of the gastrointestinal or gastrourinary tract (i.e., Fournier gangrene). As with clostridial myonecrosis, gas in the deep tissues is frequently found in these mixed infections. Gas gangrene is a rapidly progressive infection caused by Clostridium perfringens, Clostridium septicum, Clostridium histolyticum, or Clostridium novyi. Severe penetrating trauma or crush injuries associated with interruption of the blood supply are the usual predisposing factors. C, perfringens and C. novyi infections have recently been described among heroin abusers following intracutaneous injection of black tar heroin. C. septicum, a more aerotolerant Clostridium species, may cause spontaneous gas gangrene in patients with colonic lesions (such as those due to diverticular disease), adenocarcinoma, or neutropenia. Necrotizing fasciitis and gas gangrene may cause necrosis of skin, subcutaneous tissue, and muscle. Cutaneous findings of purple bullae, sloughing of skin, marked edema, and systemic toxicity mandate prompt surgical intervention. For severe group A streptococcal and clostridial necrotizing infections, parenteral clindamycin and penicillin treatment is recommended (A-II). A variety of antimicrobials directed against aerobic gram-positive and gram-negative bacteria, as well as against anaerobes, may be used in mixed necrotizing infections (B-II). Infections following animal or human bites. Animal bites account for 1% of all emergency department visits, and dog bites are responsible for 80% of such cases. Although Pasteurella species are the most common isolates, cat and dog bites contain an average of 5 different aerobic and anaerobic bacteria per wound, often including S. aureus, Bacteroides tectum, and Fusobacterium, Capnocytophaga, and Porphyromonas species. The decision to administer oral or parenteral antibiotics depends on the depth and severity of the wound and on the time since the bite occurred. © 2005 by the Infectious Diseases Society of America. All rights reserved.