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–Recurrent cellulitis is seen in immunocompromised patients (HIV/AIDS), steroids and TNF-α inhibitor therapy, diabetes, hypertension, cancer, peripheral arterial or venous diseases, chronic kidney disease, dialysis, IV or SC drug use (3)[A].

GENERALPREVENTION

Good skin hygiene

Support stockings to decrease edema

Maintain tight glycemic control and proper foot care in diabetic patients.

DIAGNOSIS

Primarily a clinical diagnosis

HISTORY

Previous trauma, surgery, animal/human bites, dermatitis, fungal infection are portals of entry for bacterial pathogens.

Pain, itching, and/or burning

Fever, chills, and malaise

PHYSICALEXAM

Localized pain and tenderness with erythema, induration, swelling, and warmth

Peau d’orange appearance

Regional lymphadenopathy

Purulent drainage (from abscesses)

Orbital cellulitis: proptosis, globe displacement, limitation of ocular movements, vision loss, diplopia

Facial cellulitis: malaise, anorexia, vomiting, pruritus, burning, anterior neck swelling

DIFFERENTIALDIAGNOSIS

Toxic shock syndrome, venous stasis dermatitis (commonly mistaken as cellulitis), bursitis, acute dermatitis or intertrigo, herpes zoster or herpetic whitlow, deep vein thrombosis or thrombophlebitis, acute gout or pseudogout, necrotizing fasciitis or myositis, gas gangrene, osteomyelitis, erythema chronicum migrans or malignancy, drug reaction, sunburn, or insect stings. Spider bites and MRSAcellulitis can present similarly.

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DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

If there are signs of systemic disease (fever, heart rate >100 bpm, or systolic blood pressure <90 mm Hg): blood cultures, CPK, CRP. Consider serum lactate levels.

WBC has 84% specificity and 43% sensitivity; CRPhas a sensitivity of 67% and specificity of 95% (PPV 95% and NPV 68%).

Aspirates from point of maximum inflammation are more sensitive (45% positive culture) than aspirates from leading edge (5% positive culture).

Blood cultures: pathogens isolated in <5% of patients. Blood cultures in children are more likely to show a contaminant than true positive.

Swab open cellulitis wounds for culture.

Plain radiographs, CT, or MRI are useful if osteomyelitis, fracture, necrotizing fasciitis, retained foreign body, or underlying abscess is suspected.

Gallium-67 scintigraphy helps detect cellulitis superimposed on chronic limb lymphedema.

Diagnostic Procedures/Other

Consider lumbar puncture in children with H. influenzae type B or if meningeal signs and facial cellulitis.

TREATMENT

GENERALMEASURES

Immobilize and elevate involved limb to reduce swelling.

Sterile saline dressings or cool aluminum acetate compresses for pain relief

Edema: compression stocking, pneumatic pumps; diuretic therapy for CHF patients

Mark the area of cellulitis to monitor progression.

Tetanus immunization if needed, particularly if there is an open (traumatic) wound

MEDICATION

First Line

Target treatment if known pathogen and with certain exposures (animal bites). Empiric antibiotic selection:

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–Nonpurulent cellulitis

With nonpurulent drainage, target treatment toward β-hemolytic streptococci and MSSA.

Outpatient: treatment duration of 5 to 10 days

■Oral: for mild cellulitis

■Cephalexin 500 mg PO q6h; children: 25 to 50 mg/kg/day in 3 to 4 doses

■Dicloxacillin 500 mg PO q6h; children: 25 to 50 mg/kg/day in 4 doses

■Clindamycin 300 to 450 mg PO q6–8h; children: 20 to 30 mg/kg/day in 4 doses

■IV: for rapidly progressing cellulitis

■Cefazolin 1 to 2 g IV q8h; children: 100 mg/kg/day IV in 2 to 4 divided doses

■Oxacillin 2 g IV q4h; children: 150 to 200 mg/kg/day IV in 4 to 6 doses

■Nafcillin 2 g IV q4h; children: 150 to 200 mg/kg/day IV in 4 to 6 doses

■Clindamycin 600 to 900 mg IV q8h; children: 25 to 40 mg/kg/day IV

in 3 to 4 doses

Purulent cellulitis (probable CA-MRSA)

–Culture all purulent wounds and follow up in 48 hours.

–Incise and drain abscess and start empiric antibiotic therapy. Modify based on culture results; tailor duration based on clinical response (4)[B]:

Oral

■Clindamycin 300 to 450 mg PO; children: 40 mg/kg/day in 3 to 4 doses

■Trimethoprim-sulfamethoxazole (TMP-SMX) 1 DS tab PO BID; children: dose based on TMPat 8 to 12 mg/kg/day divided in 2 doses

■Doxycycline 100 mg PO BID; children >8 years of age: ≤45 kg: 4 mg/kg/day divided in 2 doses; >45 kg: 100 mg PO BID

■Minocycline 200 mg PO once and then 100 mg PO BID; children >8 years old: 4 mg/kg PO once and then 4 mg/kg PO BID

■Linezolid 600 mg PO BID; children <12 years: 10 mg/kg/dose (max 600 mg/dose) PO TID; ≥12 years: 600 mg PO BID

■Tedizolid 200 mg PO once daily; children: Dosing is not established.

IV

■Vancomycin 15 to 20 mg/kg/dose IV every 8 to 12 hours

■Daptomycin 4 mg/kg/dose IV once daily; if bacteremia is present or suspected: 6 mg/kg IV once daily

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■Linezolid 600 mg IVBID

■Tedizolid 200 mg IV once daily

■Ceftaroline 600 mg IV q12h

■Tigecycline 100 mg IV once, thereafter 50 mg IV q12h

Necrotizing cellulitis: requires broad-spectrum coverage to cover clostridial and anaerobic species: ampicillin-sulbactam 1.5 to 3.0 g q6–8h IV or piperacillin-tazobactam 3.37 g q6–8h IV plus ciprofloxacin 400 mg q12h IV plus clindamycin 600 to 900 mg q8h IV; have a low threshold for consultation and intensive care

Freshwater exposure: penicillinase-resistant: penicillin plus gentamicin or fluoroquinolone; in salt water exposure: doxycycline 200 mg IV in 2 divided doses

Bites: The combination of amoxicillin and clavulanic acid is recommended for human and dog bites. Ticarcillin and clavulanic acid or the combination of a 3rd-generation cephalosporin (i.e., ceftriaxone) plus metronidazole provides adequate parenteral therapy for animal or human bites. If allergic to penicillin, use fluoroquinolone plus metronidazole.

Facial cellulitis in adults: ceftriaxone IV

Diabetic foot infection: ampicillin/sulbactam or imipenem/cilastatin or meropenem; alternative: combinations of targeting anaerobes as well as grampositive and gram-negative aerobes

If severe infection, toxicity, immunocompromised patients, or worsening infection despite empirical therapy, admit for empiric antibiotic therapy covering MRSA.

Recurrent streptococcal cellulitis: penicillin 250 mg BID, or if penicillinallergic, use erythromycin 250 mg BID

Pediatric Considerations

Avoid doxycycline in children ≤8 years old and during pregnancy.

Second Line

Mild infection

Penicillin allergy: erythromycin 500 mg PO q6h

Cephalexin remains a cost-effective therapy for outpatient management of cellulitis at current estimated MRSAlevels.

SURGERY/OTHER PROCEDURES

Débridement for gas and purulent matter

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Intubation or tracheotomy may be needed for cellulitis of the head or neck.

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

Severe infection, suspicion of deeper or rapidly spreading infection, tissue necrosis, or severe pain

Marked systemic toxicity or worsening symptoms that do not resolve after 24 to 48 hours of therapy

Patients with underlying risk factors or severe comorbidities

ONGOING CARE

FOLLOW-UPRECOMMENDATIONS

Patient Monitoring

Repeat relevant labs (blood culture, CBC, potentially LP) if patient is toxic or not improving.

Consider deep vein thrombosis prophylaxis.

Cutaneous inflammation may worsen in the first 24 hours due to release of bacterial antigens. Symptomatic improvement usually occurs in 24 to 48 hours, but visible improvement may take 72 hours.

DIET

Glucose control in diabetics

PATIENT EDUCATION

Good skin hygiene

PROGNOSIS

With adequate antibiotic treatment, prognosis is good.

Low-dose penicillin prophylaxis in patients with recurrent cellulitis decreases recurrence (5)[A].

COMPLICATIONS

Local abscess or bacteremia, sepsis

Superinfection with gram-negative organisms Lymphangitis, especially if recurrent

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Thrombophlebitis or venous thrombosis

Bacterial meningitis

Gangrene

REFERENCES

1.Raff A, Kroshinsky D. Cellulitis: a review. JAMA. 2016;316(3):325–337.

2.Figtree M, Konecny P, Jennings Z, et al. Risk stratification and outcome of cellulitis admitted to hospital. J Infect. 2010;60(6):431–439.

3.Tay EY, Fook-Chong S, Oh CC, et al. Cellulitis recurrence score: a tool for predicting recurrence of lower limb cellulitis. J Am Acad Dermatol. 2015;72(1):140–145.

4.Champion AE, Goodwin TA, Brolinson PG, et al. Prevalence and characterization of methicillin-resistant Staphylococcus aureus isolates from healthy university student athletes. Ann Clin Microbiol Antimicrob. 2014;13(1):33.

5.Thomas KS, Crook AM, Nunn AJ, et al; for U.K. Dermatology Clinical Trials Network’s PATCH I Trial Team. Penicillin to prevent recurrent leg cellulitis. N Engl J Med. 2013;368(18):1695–1703.

ADDITIONALREADING

Gunderson CG. Cellulitis: definition, etiology, and clinical features. Am J Med. 2011;124(12):1113–1122.

Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillinresistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011;52(3):285–292.

Oh CC, Ko HC, Lee HY, et al. Antibiotic prophylaxis for preventing recurrent cellulitis: a systematic review and meta-analysis. J Infect. 2014;69(1):26–34.

Phoenix G, Das S, Joshi M. Diagnosis and management of cellulitis. BMJ. 2012;345:e4955.

Quirke M, O’Sullivan R, McCabe A, et al. Are two penicillins better than one? Asystematic review of oral flucloxacillin and penicillin V versus oral flucloxacillin alone for the emergency department treatment of cellulitis. Eur J Emerg Med. 2014;21(3):170–174.

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CODES

ICD10

L03.90 Cellulitis, unspecified

H05.019 Cellulitis of unspecified orbit

L03.211 Cellulitis of face

CLINICALPEARLS

S. aureus and group AStreptococcus are the most common organisms causing cellulitis.

Consider MRSAif cellulitis does not respond to antibiotics within 48 hours. Rapid expansion of infected area with red/purple discoloration and severe pain may suggest necrotizing fasciitis, requiring urgent surgical evaluation.

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CELLULITIS, ORBITAL

Robert T. Carlisle, MD, MPH

BASICS

DESCRIPTION

Acute, severe, vision-threatening infection of orbital contents posterior to orbital septum. Preseptal (previously referred to as periorbital) cellulitis is anterior to the septum. Distinguishing location determines the appropriate workup and treatment.

Synonym(s): postseptal cellulitis

ALERT

Differentiating orbital from preseptal cellulitis is the critical diagnostic step. Preseptal cellulitis can be identified by exam or, if needed, by CT scan.

Both preseptal and orbital cellulitis present with a red, swollen painful eye or eyelid.

Diplopia, proptosis, vision loss, and fever suggest orbital involvement.

Contrast CT is the imaging method of choice and must be done for suspicion of orbital cellulitis.

Treat with immediate IV antibiotics, hospital admission, and ophthalmology referral.

Monitor frequently for vision loss, cavernous sinus thrombosis, abscess, and meningitis.

EPIDEMIOLOGY

No difference in frequency between genders in adults

More common in children; mean age of surgical cases: 10.1 years; medical pediatric cases: 6.1 years

Much less common than preseptal cellulitis

Incidence

Orbital cellulitis has declined since Haemophilus influenzae type b (Hib) vaccine was introduced. Haemophilus is no longer the leading cause of orbital cellulitis (1,2)[B].

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ETIOLOGYAND PATHOPHYSIOLOGY

Sinusitis is classically associated with orbital cellulitis. Local skin conditions are typically associated with preseptal cellulitis.

The ethmoid sinus is separated from the orbit by the lamina papyracea (“layer of paper”), a thin bony separation, and is often the source of contiguous spread of infection to the orbit.

The orbital septum is a connective tissue barrier that extends from the skull into the lid and separates the preseptal from the orbital space.

Cellulitis in the closed bony orbit causes proptosis, globe displacement, orbital apex syndrome (mass effect on the cranial nerves), optic nerve compression, and vision loss.

Cultures of surgical specimens in adults often grow multiple organisms. In over 1/3 of cases, no pathogen is recovered (3)[B].

Most common organisms (1,2)[C]:

–Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus anginosus

Less common organisms:

–Moraxella catarrhalis, H. influenzae, group Aβ-hemolytic Streptococcus,

Pseudomonas aeruginosa, anaerobes, phycomycosis (mucormycosis),

aspergillosis, Mycobacterium tuberculosis, Mycobacterium avium complex, trichinosis, Echinococcus

There are increasing cases of methicillin-resistant S. aureus (MRSA).

Genetics

No known genetic predisposition

RISK FACTORS

Sinusitis present in 80–90% of cases (1)[C]

Orbital trauma, retained orbital FB, ophthalmic surgery

Dental, periorbital, skin, or intracranial infection; acute dacryocystitis (inflammation of the lacrimal sac) and acute dacryoadenitis (inflammation of the lacrimal gland)

Atopy and HSV can lead to recurrent episodes (2).

Immunosuppressed patients are at increased risk of adverse outcomes.

GENERALPREVENTION

Routine Hib vaccination

Appropriate treatment of bacterial sinusitis

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Proper wound care and perioperative monitoring of orbital surgery and trauma

Avoid trauma to the sinus and orbital regions.

High index of suspicion in febrile patients presenting with periocular pain, swelling, and erythema

COMMONLYASSOCIATED CONDITIONS

Trauma and intraorbital FB

Preseptal cellulitis

Adverse outcomes of orbital apex syndrome, vision loss, ophthalmoplegia, abscess, meningitis, or cavernous sinus thrombosis

DIAGNOSIS

HISTORY

Complaints of acute onset red, swollen, tender eye or eyelid, and pain with eye movements

History of surgery, trauma, sinus or upper respiratory infection, dental infection

Malaise, fever, stiff neck, mental status changes Specific signs of orbital cellulitis include:

–Proptosis, double vision, ophthalmoplegia, vision loss (or decreased field of vision), pain with eye movement, decreased color vision

ALERT

Septic appearance, mental status changes, contralateral cranial nerve palsy, or bilateral orbital cellulitis may indicate CNS involvement.

MRSAorbital cellulitis may present without associated upper respiratory infection.

PHYSICALEXAM

Vital signs

Assess visual acuity (with glasses if required).

Lid exam and palpation of the orbit

Pupillary reflex for afferent pupillary defect

Extraocular movements; assess for pain with eye movement—if present, concerning for orbital cellulitis.

Red desaturation: Patient views red object with one eye and compares to the

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