AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Cellulitis is a term that describes the inflammatory response caused by bacteria in the skin below the epidermis. The immune system responds to invading bacteria with an inflammatory reaction in the dermis and subcutaneous tissues, resulting in signs of inflammation.

Pathophysiology

The integumentary system (ie, skin, glands, hair follicles) is the first defense against invasion by pathogenic organisms. Squamous epithelial cells with strong intercellular bonds form a physical barrier. When skin is damaged, this physical barrier is locally compromised. Compromise of this barrier allows bacteria to penetrate into the dermis. Typical pathogens include bacteria found on the external surface of the skin. Less commonly, bacteria in the environment adjacent to skin may infect the skin. In rare cases, hematogenous spread of bacteria causes cellulitis.

Frequency

United States

Cellulitis is a common disease. Because most patients do well with outpatient care, estimating the frequency of the disease is difficult.

International

The frequency is unknown.

Mortality/Morbidity

Most patients recover from cellulitis without sequelae. Healthy people without systemic symptoms respond well to oral antibiotics. Over the past several years, the incidence and severity of cellulitis has increased. Most of this increase can be attributed to the high prevalence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA).

• Cellulitis is more serious in individuals with underlying diseases such as diabetes, cancer, or immunodeficiency. Patients with diabetes often have impaired microcirculation, which decreases the number of white blood cells and the amount of antibiotic delivered to infected sites. Patients who are immunodeficient or have cancer may not be able to mount an effective inflammatory response because of neutropenia or a defect in the function of neutrophils.
• Occasionally, bacteria enter the circulatory system by direct invasion or passage through lymphatic tissue to the blood (bacteremia). If the invading bacteria have the necessary virulence factors, bacteremia can develop into sepsis and/or seeding of internal organs and prosthetic devices.
• Even when infection is localized in healthy patients, some strains of gram-positive bacteria, such as group A beta-hemolytic Streptococcus (GABHS) and S aureus, may produce systemic toxins. Toxin-mediated disease is a serious infection causing septic shock, hypotension, and organ failure. In adults, the mortality rate of toxin-mediated disease is approximately 50%.

Race

Cellulitis has no predilection for any racial or ethnic group.

Sex

Cellulitis has no predilection for either sex.

Age

The vast majority of cases have no age-group predilection. Historically, children younger than 3 years were predisposed to buccal cellulitis from Haemophilus influenzae type B. Introduction of a conjugate vaccine against this organism has almost completely eliminated buccal cellulitis in children who have been immunized and live in the industrial world.

• Facial cellulitis is more common in adults older than 50 years.
• Perianal cellulitis, usually with GABHS, occurs in children younger than 3 years.
• Group B Streptococcus cellulitis occurs in infants younger than 6 months. Physicians must exclude underlying osteomyelitis or septic arthritis in these infants.
• Elderly patients with cellulitis are predisposed to thrombophlebitis.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients may provide a history of skin injury caused by surgery, trauma, bites, or puncture. Patients are typically unaware of any predisposing injury. Microscopic tears from scratching can serve as a portal of entry. The infection usually develops slowly over days, but certain organisms cause rapidly progressing cellulitis in a matter of hours.

• If a specific injury is known, query the patient for details about the environment in which the injury occurred (eg, water, animal bite, garden). While cellulitis almost always is the result of infection with Gram-positive bacteria, Gram-negative and anaerobic organisms may also cause the condition.
• Query the patient about bite wounds. The oral flora of dogs and cats includes Pasteurella multocida, an organism known to cause cellulitis with rapid onset.
• Skin breakdowns from minor abrasions, bedsores, or local fungal infections (tinea pedis) commonly serve as entry portals for cellulitis, especially in patients with vascular compromise such as diabetes.
• Foreign bodies can serve as a nidus for cellulitis. These include intravenous catheters or external orthopedic pins.
• Patients with a history of lymph node dissection (eg, patients with cancer, patients who are postvenotomy) are at increased risk for cellulitis in the area of surgery. Infection may occur years after surgery.

Physical

Infection in the skin triggers the immune system to respond with neutrophils and other inflammatory mediators. These mediators are responsible for the 4 cardinal signs of infection: erythema, pain, swelling, and warmth. Because the infection occurs underneath the epidermis in the dermis and subcutaneous tissue, the margins of infection are not precise and are difficult to observe. Areas of edema and erythema often gradually blend into the surrounding skin. Systemic symptoms (eg, fever, malaise) may occur.

• Red lines streaking away from a cellulitic area represent progression of the infection into the lymphatic system. Localized adenopathy is commonly observed with lymphangitis.
• Crepitus is a sign of infection most commonly observed with anaerobic organisms.

Causes

The most common bacteria that cause cellulitis in patients with a normal immune system are GABHS (Streptococcus pyogenes) and S aureus. Rarely, Gram-negative organisms, anaerobes, or fungi may cause cellulitis.

Community-acquired MRSA causes recurrent abscesses and cellulitis. This is epidemiologically associated with production of the Panton-Valentine leukocidin, which inhibits function of neutrophils and monocytes. MRSA that produces this toxin has been identified in community outbreaks of cellulitis or abscesses.

• Vibrio vulnificus may infect skin that is injured in brackish water by scraping against rocks or stepping on organisms with hard shells. Patients infected with this organism, especially those with chronic liver disease, develop rapidly progressing cellulitis with systemic symptoms of illness.
• Skin injuries or exposure of damaged skin in fresh or brackish water may be infected by gram-negative bacilli such as Aeromonas species.
• Cellulitis that complicates bite wounds from cats and dogs may be the result of P multocida infection.
• Cellulitis in infants is usually caused by hematogenous spread of group B Streptococcus. These patients often have additional sites of infection such as the blood, joints, bone, kidneys, or central nervous system.
• Individuals who are immunocompromised may have gram-negative or fungal cellulitis.
• Cellulitis occurring around surgical wounds less than 24 hours postoperatively may result from GABHS or Clostridium perfringens. C perfringens produces gas, which is appreciated on examination as crepitus.
• Puncture wounds, especially through the bottom of sneakers, may cause Pseudomonas osteomyelitis and/or cellulitis, particularly in young people.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Arthropod envenomation
Partial thickness burns
Septic joints
Osteomyelitis
Dermatitis
Erysipelas
Ecthyma
Gas gangrene

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Most patients with cellulitis do not require laboratory studies. Consider the following laboratory tests in patients with moderate-to-severe cellulitis (ie, patients requiring admission, patients requiring parenteral antimicrobials).
• • CBC counts often show leukocytosis greater than 13,000 WBC/µL. In patients with toxin-mediated disease, CBC counts often show profound leukopenia.
  • Blood cultures are not cost-effective or necessary in most patients. Obtain a blood culture only if the patient is admitted with significant systemic symptoms or if concern for bacteremia exists.
  • Gram stains are usually unnecessary. They show the presence of neutrophils, but observed bacteria may represent skin flora instead of the pathogenic organism. Gram stains of bullous fluid may be helpful in diagnosing group A Streptococcus or V vulnificus.
  • Consider a baseline BUN and creatinine (Cr) study in patients receiving nephrotoxic antimicrobials.
• Obtain a culture in all patients with cellulitis that requires admission or parenteral antibiotics.

Imaging Studies

• Imaging studies are usually unnecessary.
• Crepitus is diagnosed by physical examination and does not require confirmation by radiography. Any patient with crepitus should be promptly evaluated by a surgeon for debridement of the wound.
• If concern for the presence of a foreign body exists, consider obtaining radiographs providing 2 different views of the affected area.

Procedures

• Leading-edge cultures have no utility.
• Aspiration from the point of maximal induration for culture has less than a 20% yield of an organism. Aspiration without saline is preferable to injecting nonbacteriostatic saline followed by aspiration.
• If bullae or abscesses form, culturing the fluid from inside these lesions yields an organism in more than 90% of cases.

Histologic Findings

Tissue stains and microscopy reveal WBC infiltration, particularly of neutrophils, bacteria, and cellular debris.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Patients with mild local symptoms and no systemic symptoms can be treated as outpatients with a 10-day course of an appropriate oral antimicrobial. Outpatients must be reevaluated within 48 hours to ensure that the infection is improving. Progression of infection or the absence of improvement requires intravenous antimicrobial treatment and admission.
• No evidence supports administration of an intravenous or intramuscular dose of an antibiotic before starting outpatient oral therapy. An oral dose of the antibiotic administered before discharge is appropriate for patients unable to promptly fill a prescription.
• All patients with lymphangitis or systemic symptoms require admission for intravenous antibiotics. Progression of infection into the lymphatic system indicates that the infection is spreading. As lymph fluid eventually reaches the blood, these patients are at risk for bacteremia. If present, hypotension and tachycardia indicate that the patient requires treatment in a critical care unit.
• No literature supports any benefit from using heat applications to improve symptoms or to facilitate treatment.

Surgical Care

• Any patient with crepitus, circumferential cellulitis, or necrotic-appearing skin requires rapid surgical intervention.
• • Necrotic skin requires examination of fascial planes to exclude necrotizing fasciitis.
  • Crepitus requires immediate debridement of tissue. Circumferential cellulitis may impede blood flow or increase pressure distally, resulting in a compartment syndrome.
• In the past 15 years, the incidence of necrotizing fasciitis from GABHS has increased. Pain disproportional to the physical examination or severe pain on passive movement of the extremities requires prompt evaluation by a surgeon.

Consultations

• Consider surgical consultation as described under Surgical Care.
• Consider consulting an infectious disease specialist for patients not responding to treatment or patients infected with unusual pathogens.
• • Patients with chronic illnesses have increased risk factors for resistant bacteria.
  • Some unusual organisms are life-threatening and require various antibiotics.
• Patients with severe, life-threatening disease associated with hemodynamic instability require a critical care setting with invasive monitoring and administration of intravenous fluids, vasopressors, and broad-spectrum antimicrobials.

Diet

No dietary restrictions exist.

Activity

No restrictions on activity exist. Patients may choose not to move an affected area secondary to pain.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.

Historically, beta-lactam agents (ie, penicillins, cephalosporins) have been the antibiotics of choice for treatment of cellulitis. In the last 5 years, the number of S aureus isolates resistant to beta-lactam agents has dramatically increased. These strains of methicillin-resistant S aureus (MRSA) require treatment with alternative agents. MRSA is no longer limited to so-called high-risk populations, and strains are often cultured from patients without medical problems. All GABHS is susceptible to penicillin.

In many areas of the country, community-acquired MRSA is more common than methicillin-susceptible S aureus. Empiric treatment of cellulitis must cover MRSA and GABHS. Macrolides are no longer adequate empiric therapy for cellulitis, as many MRSA and GABHS strains are resistant to the class. While clindamycin covers most GABHS, it is not as effective against MRSA. In central Ohio, 13% of MRSA is resistant to clindamycin; another 17% is intrinsically resistant. The Infectious Disease Society of America estimates that 50% of MRSA has intrinsic or constitutive resistance to clindamycin.

Many strains of community-acquired MRSA are susceptible to trimethoprim-sulfamethoxazole and the tetracyclines. However, these drugs do not cover GABHS. Use of these agents combined with penicillin would cover MRSA and GABHS well. Of the tetracyclines, minocycline is thought to have the best activity against MRSA. Doxycycline is thought to be more effective than tetracycline.

Evidence is insufficient to support using clindamycin, trimethoprim-sulfamethoxazole, or tetracyclines to treat severe or systemic S aureus infections. Vancomycin is the drug of choice for serious MRSA infections. Alternatives to vancomycin include daptomycin, linezolid, and the combination of quinupristin/dalfopristin (Synercid). These newer agents are much more expensive than vancomycin. Their use should be limited to severe infections where vancomycin is indicated but contraindicated in a particular patient (eg, anaphylaxis).

Physicians must know local antibiotic resistance rates. This information helps guide successful empiric therapy. Local infectious diseases specialists, hospital epidemiologists, or microbiology laboratories can provide this information.

Once culture results show an organism and antibiotic susceptibility, therapy should be changed to a more narrow agent.

Drug Category: Antimicrobials

Used to treat infections by killing bacteria or inhibiting bacterial growth. The goals of treatment are to eradicate the infection and to prevent sequelae. When selecting an antibiotic, choose the drug that provides appropriate empiric coverage. Antibiotics with the narrowest spectrum of activity are more appropriate than broad-spectrum agents.

Empiric oral therapy should cover GABHS and S aureus. If the infecting agent may be a water organism, treatment with parenteral piperacillin/tazobactam or doxycycline may be necessary.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients admitted for intravenous therapy who show significant improvement may be discharged on an oral agent to complete a minimum of 10 days of antimicrobial therapy.
• If a patient does not respond to therapy with an intravenous antibiotic, the organism may be resistant to the drug. Also, consider unusual organisms that may require combinations of antibiotics.

Further Outpatient Care

• Reevaluate all outpatients within 48 hours. Progression of illness or lack of improvement necessitate parenteral therapy.

In/Out Patient Meds

• Antibiotics to treat cellulitis should provide coverage against Gram-positive bacteria such as S aureus and GABHS.
• • Clindamycin is a reasonable choice for outpatient therapy. Vancomycin should be started if severe infection necessitates admission because of the prevalence of MRSA.
  • If a patient is allergic to all of the above-mentioned antibiotics (see Medication), linezolid or Synercid is effective for treating cellulites caused by gram-positive bacteria.
• If cellulitis progresses or does not improve on oral therapy, start parenteral therapy with the same or a similar drug, using the highest end of the recommended dosing range.
• • Lack of improvement or progression may indicate that the pathogenic organism is not susceptible to the antibiotic used. In these cases, consider resistance to the antibiotic or infection with an unusual organism(s).
  • Infectious disease specialists should evaluate patients who are not responding appropriately to antibiotics.

Complications

• Bacteremia with seeding of bone, joints, or the brain
• Abscesses
• Superinfection
• Lymphangitis
• Thrombophlebitis
• Gas-forming cellulitis
• Toxin-mediated disease
• Thrombophlebitis
• Necrotizing fasciitis

Prognosis

• Uncomplicated cellulitis has an excellent prognosis. Outpatient regimens are effective in far more than 90% of patients. Of those in whom outpatient therapy is unsuccessful or those who require admission initially, intravenous antibiotics are effective.

Patient Education

• Cellulitis is an infection of the bottom layers of the skin and is not contagious.
• • Symptoms include redness, warmth, and tenderness.
  • Discerning the exact border of the infection is difficult because the edge gradually blends with surrounding skin.
  • Bacteria that enter damaged skin cause cellulitis. Damage occurs by injuries such as scrapes, bites, puncture wounds, or cuts. Some skin damage is too small to see with the eye.
• In healthy people, cellulitis is rarely a serious illness, especially if treated early. Most patients take antibiotics by mouth.
• • Schedule a follow-up appointment within 2 days (48 h) for patients receiving oral antibiotics to ensure that the infection is improving.
  • Patients with severe cellulitis sometimes need a brief hospitalization to receive stronger antibiotics intravenously. When the infection improves, patients return home on oral antibiotics.
  • Patients with advanced HIV/AIDS or receiving cancer chemotherapy usually need hospitalization to treat cellulitis.
  • Long-term use of corticosteroids to reduce inflammation weakens the immune system. This group of patients also requires hospitalization.
• Depending on the location of the infected area, the patient may want to decrease physical activity.
• • For example, if the patient has cellulitis on a leg, walking may be uncomfortable.
  • The patient may take over-the-counter pain medication such as acetaminophen (Tylenol) or ibuprofen (Advil, Motrin).
• Patients should call their doctor's office immediately if they have any of the following symptoms:
• • Fever (>100.5°F), especially associated with chills
  • Cellulitis with a generalized feeling of aches and fatigue
  • A red streak from an area of cellulitis or a fast-spreading area of redness, which indicates that the infection may need a different antibiotic or an intravenous antibiotic
  • Significant pain not relieved by acetaminophen or ibuprofen
  • Inability to move an extremity or joint because of pain
• If patients have diabetes or cancer or if they are taking corticosteroids or chemotherapy, even very localized cellulitis may become serious.
• For excellent patient education resources, visit eMedicine's Diabetes Center. Also, see eMedicine's patient education article Cellulitis.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The most common pitfall is not admitting patients with lymphangitis or systemic symptoms who require parenteral therapy.
• Use caution when considering outpatient treatment for individuals who are immunocompromised. Consider the severity and mechanism of immunocompromise to decide if the patient is an appropriate candidate for outpatient therapy.
• Be sure to carefully examine patients for crepitus and other signs of deeper infection. Any suspicion of a gas-producing infection requires surgical consultation and admission.
• Document the patient's blood pressure and pulse. Hypotension and tachycardia in patients with cellulitis are signs of toxin-mediated disease or sepsis.
• Remember to ask patients if they have any medication allergies before prescribing antibiotics.
• Patients with cellulitis that inhibits range of motion of the joints should probably be admitted for therapy. In this scenario, the clinician must consider septic arthritis in addition to cellulitis.

Special Concerns

• Elderly patients with cellulitis are at increased risk for thrombophlebitis.
• Rapidly progressing cellulitis may indicate a very virulent organism such as V vulnificus and those found in the oral flora of dogs and cats. Cellulitis developing within hours of surgery may be the result of Clostridium species or GABHS.
• Patients with nephrotic syndrome are immunodeficient because of proteinuria (including the loss of immunoglobulins). This population is at high risk for Escherichia coli cellulitis and sepsis.
• Consider unusual organisms, especially if the infection involves a postoperative incision or skin damaged in unusual environments such as water.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N Engl J Med. Jan 25 1996;334(4):240-5. [Medline].
• Brogan TV, Nizet V, Waldhausen JH. Streptococcal skin infections. N Engl J Med. May 30 1996;334(22):1478. [Medline].
• Brook I, Frazier EH. Clinical features and aerobic and anaerobic microbiological characteristics of cellulitis. Arch Surg. Jul 1995;130(7):786-92. [Medline].
• Chambers HF. Community-Associated MRSA - Resistance and Virulence Converge. NEJM. 2005;352:1487. [Medline].
• Darmstadt GL. Oral antibiotic therapy for uncomplicated bacterial skin infections in children. Pediatr Infect Dis J. Feb 1997;16(2):227-40. [Medline].
• Darmstadt GL. Skin and Soft Tissue Infections. In: Principles and Practices of Pediatric Infectious Diseases. New York, NY: Churchill Livingstone; 1997:476-85.
• File TM Jr, Tan JS. Treatment of skin and soft-tissue infections. Am J Surg. May 1995;169(5A Suppl):27S-33S. [Medline].
• Francis JS, Doherty MC, Lopatin U. Severe community-onset pneumonia in healthy adults caused by methicillin resistant Staphylococcus aureus carrying the Panton-Valentine leukocidid genes. Clin Infect Dis. 2005;40:100-7. [Medline].
• Fridkin SK, Hageman JC, Morrison M, et al. Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med. Apr 7 2005;352(14):1436-44. [Medline].
• Givner LB, Mason EO Jr, Barson WJ, et al. Pneumococcal facial cellulitis in children. Pediatrics. Nov 2000;106(5):E61. [Medline].
• Perl B, Gottehrer NP, Raveh D, et al. Cost-effectiveness of blood cultures for adult patients with cellulitis. Clin Infect Dis. Dec 1999;29(6):1483-8. [Medline].
• Pharmacist's Letter/Prescriber's Letter. Community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) on the rise. Pharmacist's Letter/Prescriber's Letter. 2004;20(11):Available at: www.prescribersletter.com.
• Sadow KB, Chamberlain JM. Blood cultures in the evaluation of children with cellulitis. Pediatrics. Mar 1998;101(3):E4. [Medline].
• Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger P, Goldstein EJ, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis. Nov 15 2005;41(10):1373-406. [Medline].
• Swartz MN. Cellulitis and subcutaneous tissue infections. In: Mandell: Principles and Practice of Infectious Diseases. 5^th ed. New York, NY: Churchill Livingstone; 2000:1042-45.
• Talan DA, Citron DM, Abrahamian FM, et al. Bacteriologic analysis of infected dog and cat bites. Emergency Medicine Animal Bite Infection Study Group. N Engl J Med. Jan 14 1999;340(2):85-92. [Medline].
• Thomas S, Cunha BA. Group B streptococcal toxic shock-like syndrome with fulminant cellulitis. Heart Lung. Nov-Dec 1996;25(6):497-9. [Medline].
• Traylor KK, Todd JK. Needle aspirate culture method in soft tissue infections: injection of saline vs. direct aspiration. Pediatr Infect Dis J. Sep 1998;17(9):840-1. [Medline].

Article Last Updated: Jan 8, 2007