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>5>
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.
Antimicrobial Therapy for Impetigo and for Skin and Soft-Tissue Infections
Antibiotic therapy, by disease
Some strains of Staphylococcus aureus and Streptococcus pyogenes may be resistant
For patients with a limited number of lesions
Nafcillin or oxacillin
Parental drug of choice; inactive against MRSA
For penicillin-allergic patients, except those with immediate hypersensitivity reactions
Bacteriostatic; potential of cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in MRSA
Oral agent of choice for methicillin-susceptible strains
For penicillin-allergic patients, except those with immediate hypersensitivity reactions
Bacteriostatic; limited recent clinical experience
Bactericidal; efficacy poorly documented
For penicillin-allergic patients; parenteral drug of choice for treatment of infections caused by MRSA
Bacteriostatic; limited clinical experience; no cross-resistance with other antibiotic classes; expensive; may eventually replace other second-line agents as a preferred agent for oral therapy of MRSA infections
Bacteriostatic; potential of cross-resistance and emergence of resistance in erythromycin- resistant strains; inducible resistance in MRSA
Bactericidal; possible myopathy
Bacteriostatic, limited recent clinical experience
Bactericidal; limited published efficacy data
Note: MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus; SSTI, skin and soft-tissue infection; TMP-SMZ, trimethoprim-sulfamethoxazole.
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. Patients not allergic to penicillin should receive treatment with oral amoxicillin-clavulanate or with intravenous ampicillin-sulbactam or ertapenem (B-II), because agents such as dicloxacillin, cephalexin, erythromycin, and clindamycin have poor activity against Pasteurella multocida. Although cefuroxime, cefotaxime, and ceftriaxone are effective against P. multocida, they do not have good anaerobic spectra. Thus, cefoxitin or carbapenem antibiotics could be used parenterally in patients with mild penicillin allergies. Patients with previous severe reactions can receive oral or intravenous doxycycline, trimethoprim-sulfamethoxazole, or a fluoroquinolone plus clindamycin.
Human bites may occur from accidental injuries, purposeful biting, or closed fist injuries. The bacteriologic characteristics of these wounds are complex but include infection with aerobic bacteria, such as streptococci, S. aureus, and Eikenella corrodens, as well as with multiple anaerobic organisms, including Fusobacterium, Peptostreptococcus, Prevotella, and Porphyromonas species. E. corrodens is resistant to first-generation cephalosporins, macrolides, clindamycin, and aminoglycosides. Thus, intravenous treatment with ampicillin-sulbactam or cefoxitin is the best choice (B-III).
Infections Associated with Animal Contact
Infections associated with animal contact, although uncommon, are frequently severe, sometimes lethal, and diagnostically challenging. The potential use of Bacillus anthracis, Francisella tularensis, and Yersinia pestis for bioterrorism has generated great interest in rapid diagnostic techniques, because early recognition and treatment are essential. Doxycycline or ciprofloxacin therapy is recommended in standard doses for nonpregnant adults and children 18 years of age, pending identification of the offending agent (B-III).
Adults and children who receive a diagnosis of tularemia should receive an aminoglycoside, preferably streptomycin or gentamicin, for 7-10 days. In mild cases, doxycycline or tetracycline for 14 days is recommended (B-III) (comments regarding treatment of children <8>
Data regarding antibiotic efficacy for treatment of cat-scratch disease are inconclusive, although 1 small study demonstrated more-rapid lymph node regression in patients receiving azithromycin, compared with patients receiving no treatment. Cutaneous bacillary angiomatosis has not been systematically studied, but treatment with erythromycin or doxycycline in standard doses for 4 weeks has been effective in very small series (B-III).
On the basis of very incomplete data, erysipeloid is best treated with oral penicillin or amoxicillin for 10 days (B-III). E. rhusiopathiae is resistant in vitro to vancomycin, teicoplanin, and daptomycin (E-III).
Surgical Site Infections
Surgical soft-tissue infections include those occurring postoperatively and those severe enough to require surgical intervention for diagnosis and treatment. The algorithm presented in the original guideline document clearly indicates that surgical site infection rarely occurs during the first 48 hours after surgery, and fever during that period usually arises from noninfectious or unknown causes. In contrast, after 48 hours, surgical site infection is a more common source of fever, and careful inspection of the wound is indicated. For patients with a temperature <38 .5=".5">38.5 degrees C or a heart rate >110 beats/minute generally require antibiotics as well as opening of the suture line. Infections developing after surgical procedures involving nonsterile tissue, such as colonic, vaginal, biliary, or respiratory mucosa, may be caused by a combination of aerobic and anaerobic bacteria. These infections can rapidly progress and involve deeper structures than just the skin, such as fascia, fat, or muscle (see table below entitled "Antibiotic Choices for Incisional Surgical Site Infections").
Antibiotic Choices for Incisional Surgical Site Infections (SSIs).38>
Antibiotic Therapy for SSIs, By Site of Operation
Intestinal or genital tract
Facultative and aerobic activity
Penicillin agent plus beta-lactamase inhibitor Nonintestinal
Trunk and extremities away from axilla or perineum
Axillary or perineum
Other single agents as described above for intestinal and genital operations
Infections in the Immunocompromised Host
Skin and soft tissues are common sites of infection in compromised hosts and usually pose major diagnostic challenges for the following 3 reasons: (1) infections are caused by diverse organisms, including organisms not ordinarily considered to be pathogens in otherwise healthy hosts; (2) infection of the soft tissues may occur as part of a broader systemic infection; and (3) the degree and type of immune deficiency attenuate the clinical findings. The importance of establishing a diagnosis and performing susceptibility testing is crucial, because many infections are hospital acquired, and mounting resistance among both gram-positive and gram-negative bacteria makes dogmatic empirical treatment regimens difficult, if not dangerous. In addition, fungal infections may present with cutaneous findings.
Immunocompromised patients who are very ill or experiencing toxicity typically require very broad-spectrum empirical agents that include specific coverage for resistant gram-positive bacteria, such as MRSA (e.g., vancomycin, linezolid, daptomycin, or quinupristin/dalfopristin). Coverage for gram-negative bacteria may include monotherapy with a cephalosporin possessing activity against Pseudomonas species, with carbapenems, or with a combination of either a fluoroquinolone or an aminoglycoside plus either an extended-spectrum penicillin or cephalosporin.
Infections in patients with cell-mediated immunodeficiency (such as that due to Hodgkin disease, lymphoma, human immunodeficiency virus [HIV] infection, bone marrow transplantation, and receipt of long-term high-dose immunosuppressive therapy) can be caused by either common or unusual bacteria, viruses, protozoa, helminths, or fungi. Although infection may begin in the skin, cutaneous lesions can also be the result of hematogenous seeding. A well planned strategy for prompt diagnosis, including biopsy and aggressive treatment protocols, is essential. Diagnostic strategies require laboratory support capable of rapid processing and early detection of bacteria (including Mycobacteria and Nocardia species), viruses, and fungi. The algorithm presented in the original guideline document provides an approach to diagnosis and treatment. The empirical antibiotic guidelines are based on results of clinical trials, national surveillance antibiograms, and consensus meetings. Because antimicrobial susceptibilities vary considerably across the nation, clinicians must base empirical treatment on the antibiograms in their own location.
Microbiologic cultures are important in establishing a specific diagnosis, and testing the drug susceptibility of organisms is critical for optimal antimicrobial treatment. This guideline offers recommendations for empirical treatment of specific community-acquired and hospital-acquired infections. Nonetheless, therapy may fail for several reasons: (1) the initial diagnosis and/or treatment chosen is incorrect, (2) the etiologic agent from a given locale is resistant to antibiotics, (3) antimicrobial resistance develops during treatment, and (4) the infection is deeper and more complex than originally estimated.
Neutropenia - Initial infection
Bacteria: Gram negative
Type of therapy: Monotherapy or antibiotic combination
Duration of Therapy: 7-14 days
Fredquency or reason for surgery: Rare