Cellulitis

Valeria Fabre, M.D.

PATHOGENS

Streptococcus species: usually group A (S. pyogenes, responsible for most cases)
- Other Streptococcus groups: B, C, G (especially group G), possible
Staphylococcus aureus:
Dog/cat bite: Pasteurella multocida, Capnocytophaga canimorsus
Human bite: Eikenella corrodens, anaerobes, S. aureus
Salt water exposure: Vibrio vulnificus
- Other Vibrio species
Fresh or brackish water exposure: Aeromonas hydrophila, Plesiomonas shigelloides
Neutropenia: P. aeruginosa, other Gram negatives
Occasional causes (see individual pathogen modules): S. pneumoniae, H. influenzae, Legionella spp., Erysipelothrix rhusiopathiae (meat/fish exposure), fungal.
Immunosuppressed patients (mostly): Helicobacter cinaedi or other related species, coagulase-negative Staphylococci, Cryptococcus spp., Candida spp, other fungi, Nocardia, nontubercular mycobacteria

CLINICAL

Definition: Though a general term for inflammation, cellulitis in this module means a spreading bacterial infection of the skin.
- Erysipelas: superficial, sharply demarcated--nearly always group A Streptococcus.
- Cellulitis: deeper (subcutaneous) than erysipelas.
  - Group A Streptococcus causes the majority of cases, but other streptococci, such as group G, are occasionally implicated.
- Purulent cellulitis (often developing around a wound or furuncle, abscess, or carbuncle):
  - Differing from standard cellulitis, the pathogen is more likely to be Staphylococcus aureus.
Predisposing conditions: trauma, lymph or venous stasis (prior radiation, mastectomy, saphenous vein harvest), chronic edema, skin disorders (e.g., psoriasis), injection drug use, ulcers, wounds, dermatophytic infections, animal bites, neutropenia, chemotherapy, immunocompromise, immersion injuries.
Exam: red, hot, tender skin with edema [Fig 1] + fever and adenopathy.
- Bullae may develop [Fig. 2].
- Lymphangitis can develop in a small minority of patients.
Differential diagnosis: allergic reactions, gout, zoster, erythroderma, insect bite reactions, panniculitis, Lyme disease (erythema migrans), Sweet’s syndrome, pyoderma, fixed drug reaction, dermatitis, thrombophlebitis, and necrotizing fasciitis.
- Orbital cellulitis is a potentially severe condition that merits an ophthalmology consultation and a CT scan to exclude a preseptal infection.

DIAGNOSIS

Usually based upon a clinical diagnosis (appearance and symptoms).
Lab:
- Blood cultures are not routinely indicated due to low yield (positive in < 5%).
  - Blood cultures are indicated for extensive cellulitis, special populations (immunosuppressed, severe post-surgical wounds, etc.), and those who are severely ill.
- Can prove group A streptococcal infection with ASO and DNase B by serial titers; however, this is not helpful for acute management.
Imaging: useful in some cases.
- Ultrasound (rule out DVT)
- CT or MRI (if suspect a deeper infection, e.g., necrotizing fasciitis or pyomyositis)
  - A negative CT or MRI scan does not sufficiently exclude necrotizing fasciitis.
    - Obtain surgical consultation, especially if the patient is toxic, has severe pain, or has evolving bullae or skin discolorations.
      - Also, evaluate for compartment syndrome.
  - Refer to the relevant module for further details.

TREATMENT

Terms and General Principles

Classification (Based on 2014 IDSA Guidelines for Diagnosis and Management of Skin and Soft Tissue Infections)[3]
For infections for which culture information is derived, use results to help guide therapy.
Non-purulent cellulitis: without abscess, necrotizing fasciitis or erysipelas.
- Severe infection:
  - Failed oral antibiotics
  - Presence of SIRS (≥ 2 of the following: T > 38°C, P > 90, RR > 24, WBC < 4,000 cells/υL or > 12,000 cells/υL) and evidence of end-organ damage
  - Immunocompromised patients
  - Presence of skin sloughing or bullae
  - Hypotension
- Moderate infection:
  - Typical cellulitis or erysipelas + systemic signs of infection
- Mild infection:
  - Typical cellulitis or erysipelas
  - No evidence of purulence
Purulent-associated cellulitis: less common, associated with an abscess, carbuncle or furuncle.
- Severe infection:
  - Patients who have failed I&D plus oral antibiotics
  - Presence of SIRS (≥ 2 of the following: T > 38°C, P > 90, RR > 24, WBC < 4,000 cells/υL or > 12,000 cells/υL) and evidence of end-organ damage
  - Immunocompromised patients
- Moderate infection:
  - Purulent infection with signs of systemic inflammation
- Mild infection:
  - Purulent infection requires I&D (without the above)

Non-purulent Infections

Unless there are unusual risk factors, bites, or exposures, therapy assumes a streptococcal infection.
Duration of therapy:
- Typically, 5 days.
- It may extend in severe cases or result in a slow clinical response.
Severe:
- Assess for potential necrotizing infection (clinical exam or gas on x-ray).
  - Emergent surgical consultation, consideration for debridement.
    - Vancomycin 15 mg IV q 12h IV PLUS piperacillin/tazobactam 3.375 g IV q 4-6h plus clindamycin 900 mg IV q 8 (or linezolid)
  - Microbiology/special associations — pathogen-specific: see specific modules for details.
    - Necrotizing group A streptococcal or clostridial infection: PCN G + clindamycin 900 mg IV q 8 or linezolid 600 mg IV q 12h.
      - Anti-toxin abx (clindamycin or linezolid) is added for suspected or documented GAS or clostridial infection (gram stain or culture).
      - Consider IVIG if the patient has criteria for toxic shock syndrome.
    - Vibrio vulnificus: ceftriaxone 1g IV Q24H + doxycycline 100mg PO Q12H OR doxycycline + ceftazidime
    - Aeromonas hydrophila: doxycycline + ciprofloxacin
    - Polymicrobial: vancomycin + piperacillin/tazobactam
Moderate: intravenous therapy
- Adult:
  - Cefazolin 1-2 g IV q 8h
  - Nafcillin 1-2 g IV q 4-6h
  - Ampicilin-sulbactam 1.5g IV q6H
- Alternatives: for severe beta-lactam allergy
- Pediatric
  - PCN G 60-100,000 units/kg IV q 6h
  - Clindamycin 10-13 mg/kg IV q 8 h
  - Nafcillin 50 mg/kg IV q 6h
  - Cefazolin 33 mg/kg IV q 8h
Mild: oral therapy
- Adult:
  - PCN Vk 250-500 mg PO four times daily
  - Amoxicillin is often preferred due to better bioavailability: 250-500 mg PO three times daily
  - Cephalexin 500 mg PO four times daily
  - Dicloxacillin 500 mg PO four times daily
- Pediatric
  - Amoxicillin 25-50 mg/kg/d divided into twice or thrice daily doses (500 mg max per dose)
  - Cephalexin 50 mg/kg/day PO divided four times daily
  - Dicloxacillin 25-50 mg/kg/day PO divided four times daily
  - Clindamycin 25-30 mg/kg/day PO divided three times daily

Purulent Infections

For all infections, perform thorough incision and drainage (I&D).
Severe: obtain culture from I&D; use IV abx--may convert to oral when stable/improved.
- Adult
  - Empiric to cover MRSA
    - Vancomycin 15 mg/kg IV q 12h
    - Linezolid 600 mg every 12h IV
    - Daptomycin 6-8 mg/kg IV q 24h
    - Telavancin 10 mg/kg IV once daily (infuse over 1 hr)
    - Ceftaroline 600 mg IV q 8-12h (consider only if other options are not available)
    - Ceftibiprole 667 mg IV q 8h
  - MSSA:
    - Nafcillin or oxacillin 2 g IV q4h
    - Cefazolin 2g IV q8h
- Pediatric
  - Empiric
    - Vancomycin 40 mg/kg/d in four divided doses
    - Linezolid 10 mg/kg IV q 12h (children < 12 yrs)
  - MSSA:
    - Nafcillin or oxacillin 100-150 mg/kg/d IV in four divided doses IV
    - Cefazolin 50 mg/kg/d IV in three divided doses
    - Clindamycin 25-40 mg/kg/d IV in three divided doses
Moderate: obtain culture from I&D. May use IV above or oral selection below based on clinical judgment.
- Adult:
  - MSSA: IV from above or oral from below
    - Dicloxacillin 500 mg PO four times a day
    - Cephalexin 500 mg PO four times a day
  - MRSA: IV, same options as in severe (above)
    - Linezolid 600mg PO q12h
    - TMP/SMX 1-2 DS tabs twice daily PO
- Pediatric:
  - Empiric: IV from above or oral from below.
    - TMP/SMX 8-12 mg/kg/d (based on TMP) PO in two divided doses
  - MSSA: IV from above or oral from below
    - Dicloxacillin 25-50 mg/kg/d PO in four divided doses
    - Cephalexin 25-50 mg/kg/d PO in four divided doses
  - MRSA: IV from above or oral from below.
    - TMP/SMX 8-12 mg/kg/d (based on TMP) PO in two divided doses
Mild: no culture required.
- TMP/SMX 1-2 DS tabs PO twice daily
- Doxycycline 100 mg PO twice daily
Antibiotics can be avoided for small abscesses (< 2cm) in immunocompetent patients who are clinically stable.
Studies have shown a benefit in recurrence for those who received antibiotics after I&D, although they also suffered more adverse events related to antibiotics than patients who received a placebo.
Omadacycline could be considered for adult patients intolerant or with a contraindication to linezolid for treatment of moderate infections in the outpatient setting (two once-daily 450mg doses on days 1 and 2 followed by once-daily 300 mg for the rest of the course)., although GI side effects more common than with linezolid [6].

Adjunctive Therapy

For limb infections, elevate the affected area.
Treat associated conditions (especially if recurrent infection):
- Tinea pedis
  - Dermatophytic infections: topical terbinafine or clotrimazole
    - May consider systemic therapy if severe, e.g., oral terbinafine
- Venous stasis
- Lymphedema
  - Use compression stockings for prevention.
- Eczema
- Trauma sites
Erysipelas, especially if severe: Consider prednisone 30mg with a taper over 8 days to assist with the inflammatory reaction (may want to avoid in patients with diabetes).
Leg elevation

Prevention

Prevent edema by using diuretics, maintaining limb elevation, wearing compression stockings, and undergoing decongestive therapy.
Keep skin hydrated using emollients.
Treat dermatophytic infections, particularly in the interdigital spaces of the feet.
Prevention of recurrent cellulitis, especially with lymphedema (consider if > 3-4 episodes/ year and correction of underlying risk factors have been addressed already):
- Penicillin Vk 250-500mg PO twice daily
- Amoxicillin 250-500mg PO twice daily
- Erythromycin 250mg PO once or twice daily
Topical antibiotics are not effective.

For recurrent S. aureus abscesses, consider

a) Decolonization with twice-daily intranasal mupirocin for 5 days

b) Daily chlorhexidine washes for 5-7 days, then taper

c) Daily decontamination of personal items such as towels, sheets, and clothes.

Selected Drug Comments

Drug	Recommendation
Penicillin	Pen G IV or pen Vk PO is probably the drug of choice for streptococci.
Amoxicillin	Not effective against Staphylococcus aureus, ex., for the rare isolate that remains penicillin-susceptible, but good coverage against Group A Strep. Group A Streptococcus is always sensitive to penicillin and amoxicillin. Inexpensive oral medication.
Amoxicillin/clavulanate	Good oral drug for Group A Streptococcus and Staphylococcus aureus (MSSA but not MRSA).
Cephalexin	Effective against group A Streptococcus and MSSA but not MRSA.
Dicloxacillin	Additionally, it is a suitable option for covering both group A Streptococcus and methicillin-sensitive Staphylococcus aureus in patients with mild to moderate disease that can be treated with oral antibiotics.
Doxycycline	Along with minocycline, it is often considered an oral alternative to TMP/SMX for community-acquired MRSA.
Vancomycin	For severe purulent or non-purulent cellulitis to cover MRSA
Linezolid	It may favor patients with previous vancomycin-associated nephropathy or at high risk for nephrotoxicity. Also, consider patients who may clear Vanc very quickly and might be challenging to achieve adequate therapeutic levels. Oral dosing makes conversion from IV vancomycin attractive. Some now favor using linezolid for severe GAS infections instead of clindamycin due to rising rates of resistance among S. pyogenes.
Clindamycin	Used with severe GAS infections, such as toxic shock or necrotizing fasciitis. Rising resistance among GAS > 30% in the US warrants consideration of alternatives, such as linezolid, for inhibiting toxin production. Would not use as monotherapy for cellulitis. An additional concern is C. difficile infection.
TMP/SMX	Remains a usually effective agent for MRSA, with ~ 90% of isolates susceptible. Typically not a favored agent for streptococcal infection, with beta-lactams advocated by many. However, two studies have found that for uncomplicated, non-purulent cellulitis, TMP/SMX had similar outcomes to cephalexin (Palin CID 2013; Bowen OFID 2017 meta-analysis).

FOLLOW UP

Symptoms typically dissipate within the first few days of antibiotic therapy. Still, they may take longer, especially in limbs with poor circulation or chronic edema, even though the constitutional symptoms may disappear earlier.
Cellulitis may appear to worsen in the first 24-48+ hrs despite antibiotics. This may be due to toxins and/or bacterial lysis that drive inflammation, despite the antibiotic achieving a bactericidal effect.
- Also, consider whether a deeper process is present, e.g., necrotizing fasciitis.
Severe cellulitis may predispose to repeated bouts[11]: "cellulitis begets cellulitis."

OTHER INFORMATION

S. aureus: including MRSA, leading cause of soft tissue abscesses -- easy to find and to culture.
S. pyogenes: the major cause of cellulitis, but it is unusual to culture in the setting of routine cellulitis.
- Always sensitive to penicillin, which is the drug of choice.
- A most common form of cellulitis afflicts the leg (tibial area) with a breach in the skin, sometimes due to intertrigo.
Treatment: always cover streptococci, which are always sensitive to beta-lactams.

Pathogen Specific Therapy

Pathogen	First-Line Agent	Second-Line Agent
Group A Streptococci	Penicillin	Amoxicillin Ampicillin Cephalexin Cefadroxil Cefprozil Cefpodoxime Cefazolin Cefuroxime Cefotaxime Ceftriaxone Clindamycin Linezolid
Staphylococcus aureus (methicillin-sensitive)	Cephalexin, cefuroxime, cefazolin, cefadroxil, Oxacillin, nafcillin dicloxacillin	Amoxicillin/clavulanate TMP/SMX
Staphylococcus aureus (methicillin-resistant)	Vancomycin	Linezolid Tedizolid Ceftaroline Ceftibiprole Dalbavancin Oritavancin Omadacycline Non-severe infections TMP/SMX Doxycycline
Hemophilus influenzae	Amoxicillin clavulanate, ampicillin/sulbactam Cefuroxime TMP/SMX Cefotaxime, ceftriaxone	Ciprofloxacin Moxifloxacin,
Vibrio vulnificus	Doxycycline	Cefotaxime, ceftazidime Ciprofloxacin, levofloxacin, moxifloxacin
Pasteurella multocida	Penicillin Ampicillin, amoxicillin, amoxicillin/clavulanate	Doxycycline Cefotetan, cefoxitin, cefuroxime, cefotaxime, ceftriaxone, ceftazidime TMP/SMX
Aeromonas hydrophila	Ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin TMP/SMX	Doxycycline Cefotaxime, ceftriaxone, Ceftazidime
Erysipelothrix rhusiopathiae	Penicillin Ampicillin, amoxicillin	Erythromycin Ciprofloxacin, levofloxacin, moxifloxacin

Basis for recommendation

Gottlieb M, DeMott JM, Hallock M, et al. Systemic Antibiotics for the Treatment of Skin and Soft Tissue Abscesses: A Systematic Review and Meta-Analysis. Ann Emerg Med. 2019;73(1):8-16. [PMID:29530658]
Comment: This meta-analysis examined the benefits of antibiotics in managing cutaneous abscesses after incision and drainage (I&D). Four studies (n = 2,406 participants) were identified. There were 89 treatment failures (7.7%) in the antibiotic group and 150 (16.1%) in the placebo group. There was also a decreased incidence of new lesions in the antibiotic group (risk difference -10.0%, 95% CI -12.8% to -7.2%; odds ratio 0.32, 95% CI 0.23 to 0.44) and a mildly increased risk of minor adverse events (risk difference 4.4%, 95% CI 1.0% to 7.8%; odds ratio 1.29, 95% CI 1.06 to 1.58).
Raff AB, Kroshinsky D. Cellulitis: A Review. JAMA. 2016;316(3):325-37. [PMID:27434444]
Comment: Excellent review article including diagnosis and treatment with some key points: 1) diagnosis is clinical but often incorrect. Up to 30% of cases are misdiagnosed. 2) Streptococci are the primary pathogens if non-purulent cellulitis presents, and 3) recurrent cellulitis is frequent, occurring in perhaps 30% primarily with risk factors such as obesity, lymphedema or tinea infections.
Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-52. [PMID:24973422]
Comment: Foundation for recommendations presented in this module.

References

Cross ELA, Jordan H, Godfrey R, et al. Route and duration of antibiotic therapy in acute cellulitis: A systematic review and meta-analysis of the effectiveness and harms of antibiotic treatment. J Infect. 2020;81(4):521-531. [PMID:32745638]
Comment: A meta-analysis could not find any evidence to support a difference between shorter and longer durations of therapy, although only two trials used the same drug as a comparator.
Webb E, Neeman T, Bowden FJ, et al. Compression Therapy to Prevent Recurrent Cellulitis of the Leg. N Engl J Med. 2020;383(7):630-639. [PMID:32786188]
Comment: A small trial showed that regular use lowered risk by about 80% in analysis with up to three years of follow-up.
O'Riordan W, Cardenas C, Shin E, et al. Once-daily oral omadacycline versus twice-daily oral linezolid for acute bacterial skin and skin structure infections (OASIS-2): a phase 3, double-blind, multicentre, randomised, controlled, non-inferiority trial. Lancet Infect Dis. 2019;19(10):1080-1090. [PMID:31474458]
Comment: Double-blind, randomised, non-inferiority study of adults with SSTI at 33 sites in the USA randomly assigned (1:1) to receive omadacycline (450 mg orally every 24 h over the first 48 h then 300 mg orally every 24 h) or linezolid (600 mg orally every 12 h) for 7-14 days. While Omadacycline was non inferior in early clinical response (defined as survival with at least 20% reduction in lesion size 48–72 h after the first dose of study drug without rescue antibacterial therapy) and post-treatment response (defined as infection being sufficiently resolved such that further antibacterial therapy was not needed at both end of treatment and post-treatment evaluations at 7-14 days) it was associated wtih more nausea and vomiting than linezolid.
Rating: Important
Daum RS, Miller LG, Immergluck L, et al. A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses. N Engl J Med. 2017;376(26):2545-2555. [PMID:28657870]
Comment: Adults and children with a single skin abscess 5 cm in diameter or smaller were randomly assigned to receive oral clindamycin, TMP-SMX, or placebo in addition to incision and drainage. In patients with S. aureus infections, patients in the abx groups had a higher cure rate and were less likely to have a recurrent infection at 1 month. Adverse events were common in the abx groups.
Rating: Important
Obaitan I, Dwyer R, Lipworth AD, et al. Failure of antibiotics in cellulitis trials: a systematic review and meta-analysis. Am J Emerg Med. 2016;34(8):1645-52. [PMID:27344098]
Comment: According to the literature review, cellulitis failure rates vary widely (6-37%). The author speculates that this reflects many cases that mimic cellulitis.
Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372(12):1093-103. [PMID:25785967]
Comment: Comparative trial of 524 patients with cellulitis, cutaneous abscess, or both using TMP/SMX vs clindamycin x 10 days. Abscesses were drained. Outcomes of the two groups were similar (cure rates of 90% vs. 88%; P=0.8).
Baang J. Antibacterial Treatment for Uncomplicated Skin Infections. N Engl J Med. 2015;372(25):2459. [PMID:26083211]
Comment: The letter to the editor noted that 30% of each group had abscesses that may only need drainage without antibiotics. The authors respond that this query was not addressed, so their trial could not provide an answer.
Chlebicki MP, Oh CC. Recurrent cellulitis: risk factors, etiology, pathogenesis and treatment. Curr Infect Dis Rep. 2014;16(9):422. [PMID:24980389]
Comment: Recurrent cellulitis may strike patients, especially those with predisposing factors, in limbs or around breast tissue and elsewhere.
van Bijnen EM, Paget J, den Heijer CD, et al. Evidence-based primary care treatment guidelines for skin infections in Europe: a comparative analysis. Eur J Gen Pract. 2014;20(4):294-300. [PMID:24456348]
Comment: Review of 13 guidelines for skin infections from 9 European countries. Conditions included erysipelas, folliculitis, cellulitis, impetigo and furuncle. All recommended beta-lactam agents, mainly those with a limited spectrum. Seven also recommended topical fusidic acid. The beta-lactam recommended for adults varied, including penicillin (2), flucloxacillin (4), and oxacillin (1); the duration was typically 7-14 days, with a median of 10 days.
Gunderson CG, Martinello RA. A systematic review of bacteremias in cellulitis and erysipelas. J Infect. 2012;64(2):148-55. [PMID:22101078]
Comment: Literature review of patients hospitalized with cultures that were positive in 4.6% of 607 cases, of which Group A strep accounted for 65%, S. aureus for 14% and Gram-negative bacilli for 11%. The conclusion is that these results suggest that Group A streptococci are the primary cause of most cellulitis cases.
Rating: Important
Keller EC, Tomecki KJ, Alraies MC. Distinguishing cellulitis from its mimics. Cleve Clin J Med. 2012;79(8):547-52. [PMID:22854433]
Comment: The skin conditions that mimic cellulitis include stasis dermatitis, contact dermatitis, lymphedema, eosinophilic cellulitis, and papular urticaria.
Walraven CJ, Lingenfelter E, Rollo J, et al. Diagnostic and therapeutic evaluation of community-acquired methicillin-resistant Staphylococcus Aureus (MRSA) skin and soft tissue infections in the emergency department. J Emerg Med. 2012;42(4):392-9. [PMID:21524884]
Comment: Evaluation of sensitivity tests of 58 community-acquired MRSA isolates from soft tissue infections in an emergency room in Salt Lake City -- 51 (98%) were sensitive to TMP/SMX -- 50 (80%) sensitive to tetracycline -- 47 (81%) sensitive to clindamycin. Note that this sensitivity pattern is similar to that reported in many other studies over the past four years. TMP/SMX or clindamycin are usually "preferred."
Rating: Important
Khawcharoenporn T, Tice A. Empiric outpatient therapy with trimethoprim-sulfamethoxazole, cephalexin, or clindamycin for cellulitis. Am J Med. 2010;123(10):942-50. [PMID:20920697]
Comment: Evaluation of the treatment of cellulitis in 405 patients. The success rate was 91% with TMP/SMX vs. 74% (P < 0.001). Factors associated with treatment failure were: antibiotic inactive in vitro (OR=4.2) and cellulitis severity (OR=3.7). This report serves as testimony to the need for antibiotic treatment and the value of TMP/SMX for CA-MRSA infections.
Rating: Important
Jeng A, Beheshti M, Li J, et al. The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis: a prospective investigation. Medicine (Baltimore). 2010;89(4):217-226. [PMID:20616661]
Comment: This report describes 179 patients with diffuse, non-culturable cellulitis, for whom serology (ALSO and DNase B) was performed, yielding a positive result in 73%. A separate analysis of 73 showed 71 (97%) responded to a β-lactam. Group A Streptococcus typically causes cellulitis without pus and yields negative cultures.
Siljander T, Karppelin M, Vähäkuopus S, et al. Acute bacterial, nonnecrotizing cellulitis in Finland: microbiological findings. Clin Infect Dis. 2008;46(6):855-61. [PMID:18260753]
Comment: Review of 90 cases and 90 controls. The most common pathogen was Group G strep -- 26 (29%) cases. Additionally, in 7% of cases, 13% of household contacts, and no controls. Group A strep was detected in 7% of the samples. Recurrent infection in 7%.
Sebeny PJ, Riddle MS, Petersen K. Acinetobacter baumannii skin and soft-tissue infection associated with war trauma. Clin Infect Dis. 2008;47(4):444-9. [PMID:18611157]
Comment: The authors describe eight patients with A. baumannii infections associated with war wounds. The presentation was cellulitis with a "peau d’orange" appearance, characterized by vesicles that progressed to necrosis with bullae.
Rating: Important
McNamara DR, Tleyjeh IM, Berbari EF, et al. A predictive model of recurrent lower extremity cellulitis in a population-based cohort. Arch Intern Med. 2007;167(7):709-15. [PMID:17420430]
Comment: Mayo Clinic review of cellulitis in a population-based cohort. There were 209 cases of cellulitis, and 35 (17%) recurred within 2 years. The most common findings in the cellulitis group are tibial involvement, malignancy and dermatitis. These risks correlate with the risk of recurrence.
Rating: Important
Gabillot-Carré M, Roujeau JC. Acute bacterial skin infections and cellulitis. Curr Opin Infect Dis. 2007;20(2):118-23. [PMID:17496568]
Comment: Leg erysipelas/cellulitis is common, affecting approximately 1 in 1,000 persons per year. Group A strep remains the most common, and foot intertrigo is a significant risk.
Leclerc S, Teixeira A, Mahé E, et al. Recurrent erysipelas: 47 cases. Dermatology. 2007;214(1):52-7. [PMID:17191048]
Comment: Review of recurrent erysipelas in 47 Patients. The average was 4.1 recurrences, most had cutaneous disruption (81%), usually due to intertrigo (60%). Antibiotic prophylaxis was given to 68% - no recurrences were noted in 72% at two years.
Swartz MN. Clinical practice. Cellulitis. N Engl J Med. 2004;350(9):904-12. [PMID:14985488]
Comment: Group A Strep: lymphedema, early post-op wound infections, perianal cellulitis; Crepitant cellulitis: Clostridia and other anaerobes; Bites: Human - anaerobes, Eikenella, S. aureus, cats/dogs - Pasteurella; Diabetic foot: GNB and anaerobes; Blood cultures: Usually Group A strep.
Rating: Important
Stevens DL, Herr D, Lampiris H, et al. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis. 2002;34(11):1481-90. [PMID:12015695]
Comment: Randomized trial of linezolid vs. vancomycin for soft tissue infections involving MRSA. Clinical cure rates were 73% in both groups.
Eriksson BK. Anal colonization of group G beta-hemolytic streptococci in relapsing erysipelas of the lower extremity. Clin Infect Dis. 1999;29(5):1319-20. [PMID:10524984]
Comment: Anal colonization with Group G and possibly Group A, as well as other Beta-hemolytic streptococci, may serve as a reservoir for the pathogen in recurrent erysipelas. In recurrent cases, it may be beneficial to educate patients about this potential source of infection.
Perl B, Gottehrer NP, Raveh D, et al. Cost-effectiveness of blood cultures for adult patients with cellulitis. Clin Infect Dis. 1999;29(6):1483-8. [PMID:10585800]
Comment: A retrospective review of 757 patients admitted with community-acquired cellulitis over 41 months shows that the yield of blood cultures is very low (2%), has a marginal impact on clinical management and is not cost-effective for most patients with cellulitis.
Bergkvist PI, Sjöbeck K. Relapse of erysipelas following treatment with prednisolone or placebo in addition to antibiotics: a 1-year follow-up. Scand J Infect Dis. 1998;30(2):206-7. [PMID:9730318]
Comment: Placebo-controlled trial of antibiotic with or without prednisolone for erysipelas. Steroid treatment hastened the response.
Klempner MS, Styrt B. Prevention of recurrent staphylococcal skin infections with low-dose oral clindamycin therapy. JAMA. 1988;260(18):2682-5. [PMID:3184334]
Comment: A controlled trial demonstrated the benefit of prophylactic clindamycin (150 mg/d) in preventing recurrent S. aureus skin infections.
Hook EW, Hooton TM, Horton CA, et al. Microbiologic evaluation of cutaneous cellulitis in adults. Arch Intern Med. 1986;146(2):295-7. [PMID:3947189]
Comment: Microbiology studies in 50 patients hospitalized with cellulitis revealed a pathogen in blood in 5 (10%) cases, by needle aspirate in 5, but with a higher yield by skin punch biopsy in 10 (20%) cases; however, the latter is rarely performed.
Hepburn MJ, Dooley DP, Skidmore PJ, et al. Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med. 2004;164(15):1669-74. [PMID:15302637]
Comment: A randomized trial comparing five versus ten days of treatment showed that uncomplicated cellulitis can be treated effectively in five days.

Media

Cellulitis with bullae

Descriptive text is not available for this image

Cellulitis developing after an immunization (for smallpox with vaccinia!). There is spreading erythema and swelling as well as bulla.

Source: CDC/A. W. Mathies, MD

Cellulitis of the leg

Typical cellulitis of the left leg with line drawn at time of evaluation. Despite effective antibitoics, erythema may extend somewhat in the first day or two but not reflect lack of therapeutic effect.

Source: John Campbell

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Last updated: July 12, 2025