Merck Manual

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Cellulitis

By

Wingfield E. Rehmus

, MD, MPH, University of British Columbia

Reviewed/Revised Jun 2023
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Topic Resources

Cellulitis is acute bacterial infection of the skin and subcutaneous tissue most often caused by streptococci or staphylococci. Symptoms and signs are pain, warmth, rapidly spreading erythema, and edema. Fever may occur, and regional lymph nodes may enlarge in more serious infections. Diagnosis is by appearance; cultures may help, but treatment with antibiotics should not be delayed pending those results. Prognosis is excellent with timely treatment.

Etiology of Cellulitis

The most common causes of cellulitis are

  • Streptococcus pyogenes

  • Staphylococcus aureus

Cellulitis is most often caused by group A beta-hemolytic streptococci (eg, S. pyogenes) or S. aureus. The skin barrier is usually compromised.

Streptococci cause diffuse, rapidly spreading infection because enzymes produced by the organism (streptokinase, DNase, hyaluronidase) break down cellular components that would otherwise contain and localize the inflammation.

Manifestations of Streptococcal Cellulitis

Methicillin-resistant S. aureus (MRSA-USA300) is the predominant community strain of MRSA in the United States (community-associated MRSA [CA-MRSA]) (1 Etiology reference Cellulitis is acute bacterial infection of the skin and subcutaneous tissue most often caused by streptococci or staphylococci. Symptoms and signs are pain, warmth, rapidly spreading erythema... read more Etiology reference ). If S. aureus is suspected, MRSA infection should now be considered the most probable etiology. Patients who are exposed to MRSA in a hospital or nursing facility may have a MRSA strain that has a different pattern of resistance from that of MRSA-USA300.

Less common causes of cellulitis are

  • Group B streptococci (eg, S. agalactiae) in older adults with diabetes

  • Gram-negative bacilli (eg, Haemophilus influenzae) in children

  • Pseudomonas aeruginosa in patients with diabetes or neutropenia, hot tub or spa users, and patients who are hospitalized

Animal bites Human and Mammal Bites Human and other mammal bites (mostly dog and cat bites, but also squirrel, gerbil, rabbit, guinea pig, and monkey bites) are common and occasionally cause significant morbidity and disability... read more may result in cellulitis and are often polymicrobial; Pasteurella multocida is often the cause in cat bites, and Pasteurella or Capnocytophaga species are typically responsible in dog bites.

Immersion injuries in fresh water may result in cellulitis caused by Aeromonas hydrophila. Immersion injuries in warm salt water may result in cellulitis caused by Vibrio vulnificus Noncholera Vibrio Infections Noncholera vibrios include the gram-negative bacteria Vibrio parahaemolyticus, V. mimicus, V. alginolyticus, V. hollisae, and V. vulnificus; they may cause... read more .

Patients who are immunocompromised may become infected by opportunistic organisms, including gram-negative bacteria (such as Proteus Proteeae Infections The Proteeae are normal fecal flora that often cause infection in patients whose normal flora have been disturbed by antibiotic therapy. The Proteeae constitute at least 3 genera of gram-negative... read more , Serratia Klebsiella, Enterobacter, and Serratia Infections The gram-negative bacteria Klebsiella, Enterobacter, and Serratia are closely related normal intestinal flora that rarely cause disease in normal hosts. Diagnosis is by... read more , Enterobacter Klebsiella, Enterobacter, and Serratia Infections The gram-negative bacteria Klebsiella, Enterobacter, and Serratia are closely related normal intestinal flora that rarely cause disease in normal hosts. Diagnosis is by... read more , or Citrobacter), anaerobic bacteria Overview of Anaerobic Bacteria Bacteria can be classified by their need and tolerance for oxygen: Facultative: Grow aerobically or anaerobically in the presence or absence of oxygen Microaerophilic: Require a low oxygen concentration... read more , and Helicobacter Helicobacter pylori Infection Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more and Fusarium Miscellaneous Opportunistic Fungi Many yeasts and molds can cause opportunistic, even life-threatening infections in patients who are immunocompromised. These infections only rarely affect immunocompetent people. Yeasts tend... read more species. Mycobacteria Nontuberculous Mycobacterial Infections There are over 170 recognized species of mycobacteria, mostly environmental. Environmental exposure to many of these organisms is common, but most exposures do not cause infection and many infections... read more may rarely cause cellulitis.

Risk factors include skin abnormalities (eg, trauma, ulceration, fungal infection, other skin barrier compromise due to preexisting skin disease), which are common among patients with chronic venous insufficiency Chronic Venous Insufficiency and Post-Thrombotic Syndrome Chronic venous insufficiency is impaired venous return, sometimes causing lower extremity discomfort, edema, and skin changes. Post-thrombotic (postphlebitic ) syndrome is symptomatic chronic... read more Chronic Venous Insufficiency and Post-Thrombotic Syndrome or lymphedema Lymphedema Lymphedema is edema of a limb due to lymphatic hypoplasia (primary) or to obstruction or disruption (secondary) of lymphatic vessels. Symptoms and signs are brawny, fibrous, nonpitting edema... read more Lymphedema . Scars from saphenous vein removal for cardiac or vascular surgery are common sites for recurrent cellulitis, especially if tinea pedis is present. Frequently, no predisposing condition or site of entry is evident.

Etiology reference

  • 1. Lakhundi S, Zhang K: Methicillin-resistant Staphylococcus aureus: Molecular characterization, evolution, and epidemiology. Clin Microbiol Rev 31:e00020-18, 2018. doi: 10.1128/CMR.00020-18

Symptoms and Signs of Cellulitis

The major findings are local erythema and tenderness and, in more severe infections, often lymphangitis and regional lymphadenopathy. The skin is warm, erythematous, and edematous, often with surface appearance resembling the skin of an orange (peau d’orange). The borders are usually indistinct, except in erysipelas Erysipelas Erysipelas is a type of superficial cellulitis with dermal lymphatic involvement. Diagnosis is clinical. Treatment is with oral or parenteral antibiotics. (See also Overview of Bacterial Skin... read more Erysipelas (a type of cellulitis with sharply demarcated margins). Petechiae are common; large areas of ecchymosis are rare.

Vesicles and bullae may develop and rupture, occasionally with necrosis of the involved skin.

Cellulitis may mimic deep venous thrombosis but can often be differentiated by one or more features (see table ).

Table

Differentiating Cellulitis and Deep Venous Thrombosis

Feature

Cellulitis

Deep Venous Thrombosis

Skin temperature

Warm

Normal or warm (rarely cool unless limb ischemia present due to extensive venous disease causing arterial insufficiency)

Skin color

Erythematous

Normal or erythematous but blanchable (infrequently cyanotic)

Skin surface

Peau d’orange

Smooth

Lymphangitis and regional lymphadenopathy

Frequent

Nonexistent

Fever, chills, tachycardia, headache, hypotension, and delirium (usually indicating severe infection) may precede cutaneous findings by several hours, but many patients do not appear ill. Leukocytosis is common. Cellulitis with rapid spread of infection, rapidly increasing pain, hypotension, delirium, or skin sloughing, particularly with bullae and fevers, suggests life-threatening infection.

Diagnosis of Cellulitis

  • Examination

  • Sometimes blood cultures

  • Sometime tissue cultures

Diagnosis of cellulitis is by examination. Contact dermatitis Contact Dermatitis Contact dermatitis is inflammation of the skin caused by direct contact with irritants (irritant contact dermatitis) or allergens (allergic contact dermatitis). Symptoms include pruritus and... read more Contact Dermatitis and stasis dermatitis Stasis Dermatitis Stasis dermatitis is inflammation, typically of the skin of the lower legs, caused by chronic edema. Symptoms are itching, scaling, and hyperpigmentation. Ulceration can be a complication. Diagnosis... read more Stasis Dermatitis are often misdiagnosed as cellulitis, thus leading to unnecessary antibiotic use. Contact dermatitis can often be differentiated by the presence of itching, limitation of lesions to the site of contact, absence of systemic signs, and sometimes unilateral location. Stasis dermatitis can sometimes be differentiated by features of dermatitis itself (eg, scaling, eczematous findings, lichenification), evidence of venous stasis, and bilateral location. Other disorders to consider include cutaneous T-cell lymphoma Cutaneous T-cell Lymphomas (CTCL) Mycosis fungoides and Sézary syndrome are uncommon chronic T-cell non-Hodgkin lymphomas primarily affecting the skin and occasionally the lymph nodes. (See also Overview of Lymphoma and Non-Hodgkin... read more Cutaneous T-cell Lymphomas (CTCL) , nummular dermatitis Nummular Dermatitis Nummular dermatitis is inflammation of the skin characterized by coin-shaped or discoid eczematous lesions. Diagnosis is clinical. Treatment may include topical corticosteroids and phototherapy... read more Nummular Dermatitis , and tinea infection Tinea Corporis (Body Ringworm) Tinea corporis is a dermatophyte infection of the face, trunk, and extremities. Diagnosis is by clinical appearance and by examination of skin scrapings on potassium hydroxide wet mount. Treatment... read more Tinea Corporis (Body Ringworm) .

Blood cultures are useful to detect or rule out bacteremia Bacteremia Bacteremia is the presence of bacteria in the bloodstream. It can occur spontaneously, during certain tissue infections, with use of indwelling genitourinary or IV catheters, or after dental... read more in patients who are immunocompromised and in patients who have signs of systemic infection (eg, fever and leukocytosis).

Culture of involved tissue may be required in patients who are immunocompromised if they are not responding to empiric therapy or if blood cultures do not isolate an organism as well as in patients with cellulitis at the site of certain injuries (eg, animal bite wounds, penetrating injuries).

Skin and wound cultures (when wounds are present) are generally not indicated in cellulitis because they rarely identify the infecting organism.

Treatment of Cellulitis

  • Antibiotics

Antibiotics are the treatment of choice, and selection is based on the presence or absence of purulence and other risk factors for serious and/or resistant infection (1 Treatment reference Cellulitis is acute bacterial infection of the skin and subcutaneous tissue most often caused by streptococci or staphylococci. Symptoms and signs are pain, warmth, rapidly spreading erythema... read more Treatment reference ). Treatments are usually not given for a fixed interval but are continued until there is satisfactory clinical response—but typically for not less than 1 week.

Immobilization and elevation of the affected area help reduce edema; cool, wet dressings relieve local discomfort.

Compression therapy can help prevent repeat episodes of leg cellulitis in patients with recurrent cellulitis who have chronic lower extremity edema.

Nonpurulent, uncomplicated cellulitis

For most patients with nonpurulent cellulitis, empiric therapy effective against both group A streptococci and S. aureus is used.

Oral therapy is usually adequate for mild infections, typically with dicloxacillin 250 mg or cephalexin 500 mg 4 times a day. In patients allergic to penicillin, clindamycin 300 to 450 mg 3 times a day is an alternative.

Patients with mild cellulitis caused by mammalian bites can be treated as outpatients with amoxicillin/clavulanic acid 875/125 mg orally every 12 hours. In patients allergic to penicillin, clindamycin 300 to 450 mg 3 times a day plus either an oral fluoroquinolone (eg, ciprofloxacin 500 mg every 12 hours) or double-strength sulfamethoxazole/trimethoprim (800 mg sulfamethoxazole/160 mg trimethoprim) orally 2 times a day may be used.

Cellulitis that develops after exposure to fresh or brackish water should be treated with a 1st-generation cephalosporin such as cephalexin 500 mg orally 4 times a day or cefazolin 1 g IV every 8 hours in addition to a fluoroquinolone. If cellulitis develops after exposure to brackish or salt water, doxycycline 100 mg orally 2 times a day should also be added.

Likely infecting organisms tend to be similar in brackish and fresh water (eg, Vibrio species, Aeromonas species, Shewanella species, Erysipelothrix rhusiopathiae, Mycobacterium marinum, Streptococcus iniae).

Cellulitis can recur in patients with risk factors such as tinea pedis, obesity, venous insufficiency, edema, and atopic dermatitis. These disorders should be identified and treated to decrease the likelihood of recurrent cellulitis. Prophylactic antibiotics such as benzathine penicillin 1.2 million units IM monthly or penicillin V or erythromycin 250 mg orally 2 times a day for 1 to 12 months may be considered for patients who have 3 to 4 episodes of cellulitis per year despite treatment of risk factors. Patients taking prophylactic antibiotics should be assessed regularly to monitor for adverse effects and efficacy of treatment. Antibiotics should be continued until risk factors also have been managed. If these regimens prove unsuccessful, tissue culture may be required.

MRSA and purulent or complicated cellulitis

Purulent cellulitis and other risk factors predispose to complicated (serious, eg, deeper, invasive, systemic) infection. Affected patients should receive coverage for MRSA.

Risk factors for MRSA and complicated infection include the following:

  • Penetrating trauma

  • Surgical wounds

  • Recent hospitalization or nursing home exposure

  • Illicit IV drug use

  • Proximity of infection to an implanted medical device such as a prosthetic joint

  • Previous MRSA infection

  • Known nasal colonization with MRSA

  • Clinical features suggestive of serious infection

Clinical features suggestive of MRSA or complicated infection (high-risk symptoms) include the following:

  • Pain disproportionate to physical findings

  • Cutaneous hemorrhage

  • Bullae

  • Skin sloughing

  • Skin anesthesia

  • Rapid progression

  • Tissue gas

  • Signs of systemic toxicity (fever or hypothermia, tachycardia, hypotension, delirium)

For suspected MRSA without features suggesting complicated infection, empiric outpatient treatment is reasonable using double-strength sulfamethoxazole/trimethoprim (800 mg sulfamethoxazole/160 mg trimethoprim) orally 2 times a day, doxycycline 100 mg orally 2 times a day, linezolid 600 mg orally 2 times a day, or clindamycin 300 to 450 mg orally 3 times a day (however, resistance to clindamycin is becoming more prevalent).

Patients who have more serious infections, with high-risk symptoms with suspected or confirmed MRSA, or whose oral therapy failed are hospitalized and typically are given one of the following:

  • Vancomycin 15 mg/kg IV every 12 hours (drug of choice; see Antibiotic resistance Antibiotic resistance Antibiotic resistance )

  • Linezolid 600 mg IV every 12 hours for 10 to 14 days, usually for highly resistant MRSA

  • Daptomycin 4 to 6 mg/kg IV once/day

  • Teicoplanin 6 mg/kg IV every 12 hours for 2 doses, followed by 3 or 6 mg/kg IV or IM once a day to achieve targeted trough concentration (mechanism of action similar to that of vancomycin; commonly used outside the United States to treat MRSA)

The use of alternative medications for severe acute bacterial skin and skin structure infection (ABSSSI) with S. aureus (including MRSA) are based on availability, ease of administration, adverse effect profile, and cost. Alternatives include:

  • Linezolid or tedizolid (IV or oral)

  • Delafloxacin (IV or oral)

  • Omadacycline (IV or oral)

  • Ceftaroline and ceftobiprole (which is only available in Canada and Europe) (IV)

  • Dalbavancin, oritavancin, and telavancin (IV)

Cellulitis in a patient with neutropenia requires broad-spectrum antibiotic coverage. Vancomycin plus cefepime or meropenem is recommended until blood culture results are available to guide therapy. Tissue culture should be strongly considered for identification of the causative organism because of the increased risk of fungal infection. Culture should be considered for patients who are immunocompromised if they are not responding to empiric therapy or if blood cultures do not isolate an organism and for patients with cellulitis at the site of certain injuries (eg, animal bite wounds, penetrating injuries).

Treatment reference

Prognosis for Cellulitis

Recurrences in the same area are common, sometimes causing serious damage to the lymphatics, chronic lymphatic obstruction, and lymphedema.

Key Points

  • The most common pathogens causing cellulitis overall are S. pyogenes and S. aureus.

  • Methicillin-resistant S. aureus (MRSA) should be considered in the presence of certain risk factors (eg, purulent cellulitis, penetrating trauma, wound infection, nasal colonization), particularly if there is a known outbreak or local prevalence is high.

  • Differentiate leg cellulitis from deep vein thrombosis by the presence of skin warmth, erythema, peau d'orange quality, and lymphadenopathy.

  • Consider obtaining tissue culture in patients who are immunocompromised if they are not responding to empiric therapy or if blood cultures do not isolate an organism and in patients with cellulitis at the site of certain injuries (eg, animal bite wounds, penetrating injuries).

  • Direct antibiotic therapy against the most likely pathogens in specific clinical situations.

Drugs Mentioned In This Article

Drug Name Select Trade
Amphadase, Hydase, Hylenex , Vitrase, Wydase
Dynapen
Biocef, Daxbia , Keflex, Keftab, Panixine
Cleocin, Cleocin Ovules, Cleocin Pediatric, Cleocin T, CLIN, Clindacin ETZ, Clindacin-P, Clinda-Derm , Clindagel, ClindaMax, ClindaReach, Clindesse, Clindets, Evoclin, PledgaClin, XACIATO
Amoclan , Augmentin, Augmentin ES, Augmentin XR
Cetraxal , Ciloxan, Cipro, Cipro XR, OTIPRIO, Proquin XR
Primsol, Proloprim, TRIMPEX
Ancef, Kefzol
Acticlate, Adoxa, Adoxa Pak, Avidoxy, Doryx, Doxal, Doxy 100, LYMEPAK, Mondoxyne NL, Monodox, Morgidox 1x, Morgidox 2x , Okebo, Oracea, Oraxyl, Periostat, TARGADOX, Vibramycin, Vibra-Tabs
Beepen VK, Veetids
A/T/S, Akne-mycin, E.E.S., Emcin Clear , EMGEL, E-Mycin, ERYC, Erycette, Eryderm , Erygel, Erymax, EryPed, Ery-Tab, Erythra Derm , Erythrocin, Erythrocin Lactobionate, Erythrocin Stearate, Ilosone, Ilotycin, My-E, PCE, PCE Dispertab , Romycin, Staticin, T-Stat
Zyvox, Zyvox Powder, Zyvox Solution
FIRVANQ, Vancocin, Vancocin Powder, VANCOSOL
Cubicin, Cubicin RF
SIVEXTRO
Baxdela
NUZYRA
Teflaro
DALVANCE
Kimyrsa, ORBACTIV
Vibativ
Maxipime
Merrem
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