Cellulitis/Erysipelas Management

Choice of Route of Administration for Empiric Treatment

Oral Antibiotics

If lymphadenopathy, fever and other constitutional signs are not present (eg white blood cell [WBC] <15,000), may typically treat the patient with oral antibiotics on an outpatient basis. This may be given for uncomplicated cellulitis.  If symptoms do not improve or if the disease progresses significantly within the first 24-48 hours, parenteral therapy may be needed.

Parenteral Antibiotics

Parenteral antibiotics should be considered in the presence of the following: The presence of signs of toxicity (fever >100.5°F/38°C, tachycardia, hypotension); rapid progression of erythema or extensive erythema; unresponsive/intolerant to oral antibiotic therapy with significant disease progression after 2 days of initiation; the presence of indwelling medical device (eg prosthesis, stents); and high-risk neutropenia (Please see Febrile Neutropenia disease management chart for further information). Parenteral antibiotics may also be considered in patients with complicated cellulitis and comorbidities (eg DM, peripheral vascular diseases). Consider switching to oral therapy after 48 hours if possible.

Choice of Antibiotic

The choice of antibiotics is tailored according to known pathogen, comorbid condition (eg DM) and special situations like water (salt or freshwater) exposure or animal bites. Treatment should also address underlying predisposing conditions. Empiric therapy may start pending culture results. For patients with purulent cellulitis, treatment is directed towards Methicillin-resistant S aureus since it is the dominant pathogen in this type of cellulitis; therapy for beta-hemolytic streptococci is likely not needed. For patients with non-purulent cellulitis, treatment is directed towards Methicillin-sensitive S aureus (MSSA) and beta-hemolytic streptococci. Empiric therapy for Methicillin-resistant S aureus may be needed if the patient has signs of systemic infection, is unresponsive to initial therapy, has recurrent infection, has a previous episode of or is at high risk for MRSA infection, or has an indwelling medical device in close proximity to the location of the lesion. An increased use of biocides (eg antiseptics and disinfectants) during the coronavirus disease (COVID-19) pandemic has led to the emergence of antimicrobial-resistant organisms. Empiric antimicrobial stewardship should be guided by the local resistance patterns of pathogens. Recent studies show the potential use of antimicrobial fatty acids in developing antibacterial agents to reduce antibiotic resistance.

Aminopenicillin/Beta-lactamase Inhibitors 





Example drugs: Amoxicillin/clavulanic acid, Ampicillin

Aminopenicillin/beta-lactamase inhibitors are recommended as a first-line therapy for patients with cellulitis or erysipelas near the eyes or nose. These are considered second-line alternatives for patients with severe infection. These are effective and especially useful in the presence of bone or joint infection.

Cephalosporins - First Generation 







Example drugs: Cefadroxil, Cefalexin, Cefazolin

First generation cephalosporins are usually sufficient for mild, non-purulent uncomplicated cellulitis and are a treatment option for erysipelas. These are active against streptococci and MSSA. Cefalexin may be used in patients with erysipelas with beta-lactam allergy.

Cephalosporins - Second and Third Generation (Parenteral)

Example drugs: Ceftriaxone, Cefuroxime

Second and third generation cephalosporins are treatment alternatives for patients with moderate non-purulent cellulitis or severe infection. These are usually used empirically in DM patients who have early mild cellulitis. These are active against streptococci and MSSA. Aminoglycosides may be added if needed.

Cephalosporins – Other Generations

Example drugs: Ceftaroline, Ceftobiprole

Other generations of cephalosporins may be considered for patients with Methicillin-resistant S aureus infections.

Clindamycin 







Clindamycin is used in patients allergic to Penicillin and cephalosporins. This is an alternative therapy for patients with non-purulent or purulent cellulitis caused by MSSA or MRSA infection or severe infection.

Co-trimoxazole

Co-trimoxazole is used for non-purulent cellulitis and moderate purulent cellulitis. This is a treatment option for patients with erysipelas with beta-lactam allergy. This has very good activity against community-acquired Methicillin-resistant S aureus but not to streptococci.

Glycopeptide Antibacterials

Example drugs: Dalbavancin, Oritavancin, Telavancin

Lipoglycopeptide antibacterials with properties similar to Vancomycin may be considered for complicated cellulitis caused by Gram-positive organisms including Methicillin-resistant S aureus.

Macrolides

Cellulitis Erysipelas_Management 5

Example drugs: Clarithromycin, Erythromycin, Roxithromycin

Macrolides may be used if a patient is allergic to Penicillin. Macrolide resistance among Group A Streptococci has increased and has become a concern in some countries. Erythromycin is the main macrolide used unless Erythromycin resistance is widespread in the community. This is an alternative therapy for patients with cellulitis or erysipelas near the eyes or nose. This is also used for prophylactic treatment against recurrent cellulitis. Studies showed that the efficacy of Roxithromycin for erysipelas was comparable to that of Benzylpenicillin.

Oxazolidinones

Example drugs: Linezolid, Tedizolid

Oxazolidinones may be used in patients allergic to Penicillin and for complicated cellulitis and erysipelas, or MRSA infections.

Penicillins (Beta-lactamase Resistant) 

Cellulitis Erysipelas_Management 6

Example drugs: Dicloxacillin, Flucloxacillin, Nafcillin, Oxacillin

Penicillins are recommended as first-line therapy for patients with erysipelas, moderate non-purulent and purulent cellulitis, and MRSA infection. These are recommended antibiotics against mild non-purulent cellulitis caused by group A Streptococcus or S aureus. Some authorities recommend antistaphylococcal penicillin alone while others advocate antistaphylococcal penicillin + Penicillin or Amoxicillin. The combination may increase adverse effects. These are recommended for initial treatment of neonates with moderate to severe cellulitis and are also recommended for recurrent cellulitis.

Penicillin G (IV)

Intravenous penicillin C is used for erysipelas and moderate non-purulent uncomplicated cellulitis. This is a treatment option for patients with recurrent cellulitis. This is usually sufficient for uncomplicated cellulitis of an extremity caused by streptococci.

Quinolones 

Cellulitis Erysipelas_Management 7

Example drugs: Ciprofloxacin, Delafloxacin, Levofloxacin, Moxifloxacin, Ofloxacin

Quinolones are those that have enhanced activity against Gram-positive bacteria and have been shown to be effective. This is used in combination with other antibiotics for Methicillin-resistant S aureus and other Gram-positive or Gram-negative organisms and anaerobes.

Teicoplanin

Teicoplanin is an alternative to Vancomycin for patients with cellulitis caused by Gram-positive organisms including Methicillin-resistant S aureus. This is used for cellulitis caused by Vibrio vulnificus.

Tetracyclines

Example drugs: Doxycycline, Minocycline, Omadacycline, Tigecycline

Tetracyclines may be considered for moderate-severe purulent cellulitis, MSSA, and MRSA infections. This may be used in patients with allergies to Penicillin. Tigecycline may be used for the treatment of complicated skin infections. The clinical efficacy is comparable with standard treatment.

Vancomycin

Vancomycin is a treatment option for patients allergic to Penicillin. A combination with Ampicillin/sulbactam, Piperacillin/tazobactam, Ticarcillin/clavulanate, or Ceftriaxone/ Ciprofloxacin/Levofloxacin plus Metronidazole is recommended for patients with purulent cellulitis caused by MRSA infection and other Gram-positive or Gram-negative organisms and anaerobes. A combination with Cefotaxime or Gentamicin is recommended as first-line parenteral treatment for neonates with MRSA infections. This is also used for patients with penetrating trauma, nasal colonization with Methicillin-resistant S aureus, and IV drug use. Daptomycin is an alternative option if Vancomycin is unavailable.

Length of Therapy

Uncomplicated/Purulent/Non-purulent Cellulitis and Erysipelas

Patients may be treated with antibiotics for 5 to 14 days depending on clinical response. Extension of therapy (up to 14 days) may be warranted in case severe infection, slow response to therapy or if the patient is immunocompromised.

Complicated Cellulitis

It is typically recommended that once erythema, warmth and edema have subsided significantly, the patient may be treated for an additional 10 days with oral antibiotics. Patients with peripheral vascular disease, chronic venous stasis, DM or alcoholic cirrhosis may take 1-2 weeks to improve and often require 3-4 weeks of treatment.

Adjunct Therapy

Corticosteroids

Cellulitis Erysipelas_Management 8

Example drugs: Prednisolone, Prednisone

Studies showed that when used in combination with antibiotics, the healing time of lesions is reduced. These should be considered in non-diabetic patients. 

Advise good personal hygiene and wound care. Cover draining wounds with a clean bandage. Regularly bathe and wash hands after coming in contact with a wound. Avoid sharing or reusing items that come in contact with infected skin. Inspect interdigital toe spaces regularly, especially with lower extremity cellulitis. Immobilization and elevation of affected limb may be done. This may help decrease swelling and pain especially if done early in the course of treatment and may also shorten time to recovery. A cool sterile saline dressing may be applied. This may help remove purulent exudate from ulcers or infected abrasions and decrease local pain. Compression stockings may also help with edema.