Cellulitis medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2], Mugilan Poongkunran M.B.B.S [3]

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Overview

The treatment for cellulitis consists of oral or intravenous antibiotics. The usual drug of choice are beta-lactam antibiotics, as most of the cases of cellulitis are caused either by Staphylococcus aureus or Streptococcus. Bed rest and elevation of the affected limbs are recommended as adjuvant therapy. In patients with edema of the extremities, compressive stockings may be beneficial in treating the fluid accumulation. If a small abscess is surrounding the affected tissue, it can be treated with a simple incision and drainage of the fluid.

Empiric Therapy Adapted from Clin Infect Dis. 2011;52(3):e18-55 and Guidelines for Skin and Soft-Tissue Infections CID 2005

• Empiric therapy depends on the clinical presentation of the cellulitis.

• • Non-purulent cellulitis refers to the infection without purulent drainage or exudate and not associated with an abscess.
  • Purulent cellulitis is associated with purulent drainage or exudate in the absence of a drainable abscess, and it is associated to Staphylococcus aureus.
  • Complicated cellulitis refers to a deeper soft-tissue infection and/or the association significant coexisting diseases (including diabetes mellitus, immunocompromised patients, and obesity), the need for significant surgical intervention or the involvement of the perianal area.
• Patients with complicated cellulitis also present with surgical site infection, necrotizing soft-tissue infection, and signs of systemic toxicity.
• For patients with purulent cellulitis, cultures are recommended and empirical therapy for Community Associated-MRSA (CA-MRSA) should be started.
• For patients with non-purulent cellulitis, empirical therapy for β-hemolytic streptococci should be started; if the patient does not respond to B-lactam antibiotics, empirical coverage for CA-MRSA should be initiated. Per 2014 clinical practice guidelines, antibiotics for outpatients should be "an antimicrobial agent that is active against streptococci...For patients whose cellulitis is associated with penetrating trauma, evidence of MRSA infection elsewhere, nasal colonization with MRSA, injection drug use, or SIRS (severe nonpurulent; Figure 1), vancomycin or another antimicrobial effective against both MRSA and streptococci is recommended (strong, moderate)".

• The duration of the therapy should be individualized for the clinical response of each patient; 5-10 days is usually recommended.
• The treatment of cellulitis in neonates usually requires hospitalization and parenteral therapy. Oral therapy is given for completion of the treatment when the pathogen is unknown.

• The optimal dose should be based on determination of serum concentrations and patients with renal insufficiency may require dose adjustment in case of cephalosporins.
• Clindamycin is an alternate therapy for patients at risk of severe hypersensitivity reaction to penicillins and cephalosporins.
• Doxycycline is not recommended for children <8 years of age.

• Studies have shown an increase in treatment failure with TMP-SMX compared to other agents for cellulitis in children, reflecting a decreased efficacy of TMP-SMX against Group A streptococcus.

▸ Click on the following categories to expand treatment regimens.

Non-Purulent Cellulitis   ▸  Adults   ▸  Children age >28 days Purulent Cellulitis   ▸  Adults   ▸  Children age >28 days

Non-Purulent Cellulitis - Adults Preferred Regimen ▸ Cephalexin 500 mg PO q6h x5-10 days OR ▸ Dicloxacillin 500 mg PO q6h x5-10 days OR ▸Clindamycin 300-450 mg PO q8h OR ▸ Amoxicillin 500 mg PO q8h OR ▸ TMP-SMX 80-160 mg/400-800 mg PO q12h OR ▸Doxycycline 100 mg PO q12h OR ▸ Linezolid 600 mg PO q12h Non-Purulent Cellulitis - Children Preferred Regimen ▸ Cephalexin 25 mg/kg/day PO divided q6h x 5-10 days OR ▸ Dicloxacillin 25 mg/kg/day PO divided q6h x 5-10 days OR ▸ Clindamycin 10-13 mg/kg IV q6-8h (max:40 mg/kg/day) OR ▸ TMP-SMX 4-6 mg/kg PO q12h (TMP component) OR ▸Doxycycline¶ 2 mg/kg PO q12h† OR ▸ Linezolid 10 mg/kg PO q8h (max: 600mg/dose) ¶ Not recommended for children < 8 years of age † For children ≤45 kg. Children >45 kg receive adult dosing. Purulent Cellulitis - Adults Preferred Regimen ▸ Linezolid 600 mg PO q12h OR ▸ Clindamycin 300 - 450 mg PO q8h OR ▸ Minocycline 200 mg PO 1 dose, then 100 mg PO q12h OR ▸ Doxycycline 100 mg PO q12h OR ▸ TMP-SMX 80-160 mg/400-800 mg PO q12h Purulent Cellulitis - Children Preferred Regimen ▸ Linezolid 10 mg/kg PO q8h (max: 600mg/dose) OR ▸ Clindamycin 10-13 mg/kg IV q6-8h (max:40 mg/kg/day) OR ▸ Minocycline 4 mg/kg PO 1 dose, then2 mg/kg/dose PO q12h OR ▸ Doxycycline¶ 2 mg/kg PO q12h† OR ▸ TMP-SMX 4-6 mg/kg PO q12h (TMP component) ¶ Not recommended for children < 8 years of age † For children ≤45 kg. Children >45 kg receive adult dosing. Complicated Cellulitis - Adults Preferred Regimen ▸ Vancomycin 15-20 mg/kg IV q8-12h OR ▸ Linezolid 600 mg IV/PO q12h OR ▸ Daptomycin 4mg/kg IV q24h OR ▸ Telavancin 10mg/kg IV q24h Alternative Regimen ▸ Clindamycin 600 mg IV/PO q8h Complicated Cellulitis - Children Preferred Regimen ▸ Vancomycin 15 mg/kg IV q6h OR ▸ Linezolid 10 mg/kg IV/PO q8h (max: 600mg/dose) Alternative Regimen ▸ Clindamycin 10-13 mg/kg IV/PO q6-8h (max:40 mg/kg/day)

Special Considerations Adapted from N Engl J Med 2004;350:904-12.

• For the certain anatomical locations (buccal, facial and periorbital) a specific therapy should be given due to the predisposition of certain bacteria.
• For certain conditions, such as salt or fresh water wound exposure, or if the patient is a butcher, fisherman or veterinarian, an additional antibiotic therapy should be added to the usual regimen in order to cover specific pathogens associated to those circumstances.

▸ Click on the following categories to expand treatment regimens.

Special Considerations   ▸  Buccal Cellulitis   ▸  Facial Cellulitis   ▸  Orbital Cellulitis   ▸  Salt Water Wound Exposure   ▸  Fresh Water Wound Exposure   ▸  Butcher, Fisherman, Veterinarian

Buccal Cellulitis (H. influenzae) Preferred Regimen ▸ Ceftriaxone 1-2 g IV q24h Alternative Regimen ▸ Meropenem 0.5-1 g IV q8h (infuse over 15-30 min or in bolus over 3-5 min) OR ▸ Imipenem/cilastatin 250-1000 mg IV (max: 50mg/kg/day) Facial Cellulitis Preferred Regimen ▸ Vancomycin 15-20 mg/kg IV q8-12h (trough 15—20 μg/mL) Alternative Regimen ▸ Daptomycin 4 mg/kg IV q24h OR ▸ Linezolid 600mg IV q12h Orbital Cellulitis Preferred Regimen 1 ▸ Vancomycin 15-20 mg/kg IV q8-12h (trough 15—20 μg/mL) PLUS ▸ Ceftriaxone 2g IV q24h PLUS ▸ Metronidazole 1g IV q12h Preferred Regimen 2 ▸ Vancomycin 15-20 mg/kg IV q8-12h (trough 15—20 μg/mL) PLUS ▸ Piperacillin-tazobactam 4.5g IV q8h Alternative Regimen (if penicillin or cephalosporin allergic) ▸ Vancomycin 15-20 mg/kg IV q8-12h (trough 15—20 μg/mL) PLUS ▸ Levofloxacin 750 mg IV q24h Salt Water Wound Exposure (Vibrio vulnificus) Preferred Regimen ▸ Doxycycline 200 mg IV initial dose, then 50-100 mg IV q12h Alternative Regimen ▸ Cefotaxime 1-2 g IV/IM q8-12 (up to 2 g q4-6h) OR ▸ Ciprofloxacin 400 mg IV q8-12h x 7-14 days OR ▸ Ciprofloxacin 500-750 mg PO q8-12h x 7-14 days Fresh Water Wound Exposure (Aeromonas spp) Preferred Regimen ▸ Ciprofloxacin 400mg IV q12h OR ▸ Ceftazidime 0.5 -2 g IV q8h PLUS ▸ Gentamicin 3-5 mg/kg/day IV/IM divided q6-8h or 4-7 mg/kg IV q24h Alternative Regimen ▸ Meropenem 0.5-1 g IV q8h (infuse over 15-30 min or in bolus over 3-5 min) OR ▸ Imipenem/cilastatin 250-1000 mg IV (max: 50mg/kg/day) Butcher, Fisherman, Veterinarian (Erysipelothrix rhusiopathiae) Preferred Regimen ▸ Amoxicillin 500 mg PO q8hr Alternative Regimen ▸ Cefotaxime 1-2 g IV/IM q8-12 (up to 2 g q4-6h) OR ▸ Ciprofloxacin 400 mg IV q8-12h x 7-14 days OR ▸ Ciprofloxacin 500-750 mg PO q8-12h x 7-14 days OR ▸ Imipenem-cilastatin 250-1000 mg IV (max: 50mg/kg/day)

Diabetic Foot Ulcer Adapted from Diabetes Care. 2013;36(9):2862-71. and Clin Infect Dis. 2012;54(12):e132-73.

Further information: [[:Mangement of Diabetic Foot Infection]]

• Appropriate wound care is essential for the management of all diabetic foot ulcers.
• Uninfected diabetic ulcers do not require antibiotic therapy.
• For acutely infected wounds, empiric antibiotic with efficacy against Gram-positive cocci should be initiated after obtaining a post-debridement specimen for aerobic and anaerobic culture.
• Infections with antibiotic-resistant organisms and those that are chronic, previously treated, or severe usually require broader spectrum regimens.

Empiric Therapy

▸ Click on the following categories to expand treatment regimens.

Uninfected (Grade 1)   ▸  No Evidence of Infection     Mild (Grade 2)   ▸  Acute Infection Without Recent Antibiotic Use   ▸  High Risk for MRSA     Moderate to Severe (Grade 3–4)   ▸  Chronic Infection or Recent Antibiotic Use   ▸  High Risk for MRSA   ▸  High Risk for Pseudomonas aureuginosa   ▸  Polymicrobial Infection

Uninfected Wound, No Evidence of Infection ▸ Uninfected wounds should be managed with appropriate wound care. ▸ Antibiotic therapy is not recommended. Mild DFI, Acute Infection Without Recent Antibiotic Use Preferred Regimen ▸ Dicloxacillin 125–250 mg PO qid OR ▸ Clindamycin 150–300 mg PO qid † OR ▸ Cephalexin 500 mg PO qid OR ▸ Levofloxacin 750 mg PO qd OR ▸ Amoxicillin-Clavulanate 500 mg PO bid (or 250 mg PO tid) ‡ † Usually active against community-associated MRSA, but check macrolide sensitivity and consider ordering a D-test before using for MRSA. ‡ Relatively broad-spectrum oral agent that includes anaerobic coverage. Mild DFI, High Risk for MRSA Preferred Regimen ▸ Doxycycline 100 mg PO q12h † OR ▸ TMP–SMX 80-160 mg/400-800 mg PO q12h † † Active against many MRSA & some gram-negatives; uncertain against streptococci. Moderate to Severe DFI, Chronic Infection or Recent Antibiotic Use Preferred Regimen ▸ Levofloxacin 750 mg IV/PO q24h OR ▸ Cefoxitin 1 g IV q4h (or 2 g IV q6–8h) OR ▸ Ceftriaxone 1–2 g/day IV/IM q12–24h OR ▸ Ampicillin–Sulbactam 1.5–3 g IV/IM q6h OR ▸ Moxifloxacin 400 mg IV/PO q24h OR ▸ Ertapenem 1 g IV/IM q24h OR ▸ Tigecycline 100 mg IV, then 50 mg IV q12h † OR ▸ Imipenem–Cilastatin 0.5–1 g IV q6–8h ‡ Alternative Regimen ▸ Levofloxacin 750 mg IV/PO q24h OR ▸ Ciprofloxacin 600–1200 mg/day IV q6–12h OR ▸ Ciprofloxacin 1200–2700 mg IV q6–12h (for more severe cases) PLUS ▸ Clindamycin 150–300 mg PO qid † Active against MRSA. ‡ Not active against MRSA; consider when ESBL-producing pathogens suspected. Moderate to Severe DFI, High Risk for MRSA Preferred Regimen ▸ Linezolid 600 mg IV/PO q12h OR ▸ Daptomycin 4 mg/kg IV q24h OR ▸ Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L) Moderate to Severe DFI, High Risk for Pseudomonas aeruginosa Preferred Regimen ▸ Piperacillin–Tazobactam 3.375 g IV q6–8h Moderate to Severe DFI, Polymicrobial Infection Preferred Regimen ▸ Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L) OR ▸ Linezolid 600 mg IV/PO q12h OR ▸ Daptomycin 4 mg/kg IV q24h PLUS ▸ Piperacillin–Tazobactam 3.375 g IV q6–8h OR ▸ Imipenem–Cilastatin 0.5–1 g IV q6–8h OR ▸ Ertapenem 1 g IV/IM q24h OR ▸ Meropenem 1 g IV q8h Alternative Regimen ▸ Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L) OR ▸ Linezolid 600 mg IV/PO q12h OR ▸ Daptomycin 4 mg/kg IV q24h PLUS ▸ Ceftazidime 2 g IV q8h OR ▸ Cefepime 2 g IV q8h OR ▸ Aztreonam 2 g IV q6–8h PLUS ▸ Metronidazole 15 mg/kg IV, then 7.5 mg/kg IV q6h

Neutropenic Patients Adapted from Guidelines for Skin and Soft-Tissue Infections CID 2005

• Patients with neutropenia require an antimicrobial therapy with a broader coverage.
• The duration of antimicrobial therapy should be individualized in accordance with patient's clinical response.

Recommended Duration of Antimicrobial Therapy Based on the Microorganism.

Microorganism	Duration of Therapy
▸ Gram-negative Bacteria	7-14 days
▸ Gram-positive Bacteria	7-10 days
▸ Fungi	Until clinical resolution

▸ Click on the following categories to expand treatment regimens.

Neutropenia   ▸  Gram-Negative Bacteria   ▸  Gram-Positive Bacteria   ▸  Fungi

Gram-Negative Bacteria Preferred Regimen ▸ Meropenem 0.5-1 g IV q8h (infuse over 15-30 min or in bolus over 3-5 min) OR ▸ Imipenem/cilastatin 0.5–1 g IV q6–8h(max: 50mg/kg/day) OR ▸ Ertapenem 1 g IV/IM q24h OR ▸ Cefepime 2g IV q8h OR ▸ Ceftazidime 2g IV q8h OR ▸ Piperacillin/tazobactam 3.375 g IV q6–8h Alternative Regimen 1 ▸ Amikacin 15 mg/kg/day IV/IM divided q8-12h (max: 15 mg/kg/day) OR ▸ Gentamicin 3-5 mg/kg/day IV/IM divided q6-8h OR ▸ Gentamicin 4-7 mg/kg/day IV q24h (adjust dosage based on serum concentrations) PLUS ▸ Cefepime 2g IV q8h OR ▸ Piperacillin/tazobactam 3.375 g IV q6–8h (max 24 g/day) Alternative Regimen 2 ▸ Piperacillin/tazobactam 3.375 g IV q6–8h (max 24 g/day) PLUS ▸ Ciprofloxacin 400mg IV q8h Gram-Positive Bacteria Preferred Regimen ▸ Vancomycin† 15-20 mg/kg IV q8-12h Alternative Regimen ▸ Linezolid 600 mg IV/PO q12h OR ▸ Daptomycin 4mg/kg IV q24h † Vancomycin should be discontinued if culture results remain negative after 72-96 hrs Fungi Preferred Regimen ▸ Liposomal Amphotericin B 3 mg/kg/day IV × 1-2 weeks OR ▸ Amphotericin B deoxycholate 0.7-1 mg/kg/day IV × 1-2 weeks OR ▸ Amphotericin B lipid complex 5 mg/kg/day IV × 1-2 weeks Alternative Regimen ▸ Voriconazole 6 mg/kg IV q12h x 1 day, then 3 mg/kg IV q12h OR ▸ Voriconazole 200 mg PO q12h OR ▸ Caspofungin 70 mg IV once, then 50 mg IV q24h x ≥ 14 days

Cellular Immune Deficient Patients Adapted from Guidelines for Skin and Soft-Tissue Infections CID 2005

• Patients with cellular immunodeficiency require a pathogen-specific antimicrobial therapy.
• The duration of antimicrobial therapy should be individualized in accordance with patient's clinical response.

Recommended Duration of Antimicrobial Therapy Based on the Microorganism.

Microorganism	Duration of Therapy
▸ Nocardia spp	3-12 months
▸ Atypical mycobacteria	6-12 months
▸ Cryptococcus spp	8-12 weeks
▸ Histoplasma spp	≥ 12 months
▸ Varicella-zoster virus	7-10 days
▸ Herpes simplex virus	7 days
▸ Cytomegalovirus	21 days

Bacteria   ▸  Nocardia spp   ▸  Atypical mycobacteria Fungi   ▸  Cryptococcus spp   ▸  Histoplasma spp Viruses   ▸  Varicella-zoster virus   ▸  Herpes simplex virus   ▸  Cytomegalovirus

Nocardia spp Preferred Regimen ▸ TMP-SMX x 3-12 months Alternative Regimen 1 ▸ Sulfadiazine 2-4 g PO 1 dose FOLLOWED BY ▸ Sulfadiazine 2-4 g/day PO q4-8h x 3-12 months Alternative Regimen 1 ▸ Imipenem 250-500 mg IV q6-8h x 3-12 months Atypical mycobacteria† Preferred Regimen ▸ Clarithromycin 500 mg PO q12h PLUS ▸ Ethambutol 15 mg/kg PO q24h WITH OR WITHOUT ▸ Rifabutin 300 mg PO q24h Alternative Regimen ▸ Azithromycin 500 mg PO q24h PLUS ▸ Ethambutol 15 mg/kg PO q24h WITH OR WITHOUT ▸ Rifabutin 300-450 mg PO q24h † Adapted from Am J Respir Crit Care Med Vol 175. pp 367–416, 2007 Cryptococcus spp Preferred Regimen Moderate Severe to Severe Disease ▸ Liposomal Amphotericin B 3 mg/kg/day IV × 1-2 weeks OR ▸ Amphotericin B deoxycholate 0.7-1 mg/kg/day IV × 1-2 weeks OR ▸ Amphotericin B lipid complex 5 mg/kg/day IV × 1-2 weeks FOLLOWED BY ▸ Itraconazole 200 mg PO q12h x ≥12 months Mild to Moderate Disease ▸ Itraconazole 200 mg PO q12h x ≥12 months Adapted from Clin Infect Dis. 2007;45(7):807-25. Histoplasma spp Preferred Regimen ▸ Liposomal Amphotericin B 3 mg/kg/day x 1- 2 weeks OR ▸ Amphotericin B lipid complex 5 mg/kg/day x 1- 2 weeks FOLLOWED BY ▸ Itraconazole 200mg q8h x 3 days FOLLOWED BY ▸ Itraconazole 200mg q12h x 6-12 months Varicella-zoster virus Preferred Regimen ▸ Acyclovir 10-12 mg/kg IV (infusion over 1 hour) q8h x 7-10 days Alternative Regimen ▸ Famciclovir 500 mg PO x 7-10 days OR ▸ Valacyclovir 500 mg PO x 7-10 days Herpes simplex virus Preferred Regimen ▸ Acyclovir 10 mg/kg IV (infusion over 1 hour) q8h x 7-10 days Alternative Regimen ▸ Famciclovir 500 mg PO x 7 days OR ▸ Valacyclovir 500 mg PO x 7 days Cytomegalovirus Preferred Regimen ▸ Ganciclovir 5 mg/kg IV q12h x 21 days Alternative Regimen ▸ Valganciclovir 900 mg PO q12h x 21 days

BitesAdapted from Guidelines for Skin and Soft-Tissue Infections CID 2005

Further information: [[:Mangement of Bites]]

• All bite wounds should be cleaned profusely with iodide soap and water.

• Bites are contaminated by a polimicrobial flora and antibiotic prophylaxis treatment is recommended to avoid subsequent infection.

• The route of administration depends on the depth and severity of the wound, as well as the time that has passed since the bite.

▸ Click on the following categories to expand treatment regimens.

Antibiotic Prophylaxis   ▸  Any Type of Bite Specific Therapy   ▸  Cat Bite   ▸  Dog Bite   ▸  Human Bite

Antibiotic Prophylaxis Preferred Regimen ▸ Amoxicillin-clavulanate 500-875/125 PO q8-12h Alternative Regimen ▸ Clindamycin 300 mg q8h OR ▸ Metronidazole 500 mg PO q8h PLUS ▸ Doxycycline 100 mg q12h OR ▸ TMP-SMX 160/800 mg PO q12h OR ▸ Penicillin VK 500 mg PO q6h OR ▸ Cefuroxime 500 mg PO q12h OR ▸ Moxifloxacin 400 mg PO q24h Human Bite Preferred Regimen ▸ Ampicillin sulbactam 1.5 g IV q6h OR ▸ Cefoxitin 2 gm IV q8h OR ▸ Ticarcillin clavulanate 3.1 g IV q6h OR ▸ Piperacillin-tazobactam 3.375 g IV q6-8h Alternative Regimen (beta-lactam allergy) ▸ Clindamycin 300 mg PO q8h PLUS ▸ Ciprofloxacin 500-750 mg IV q12h OR ▸ Moxifloxacin 400 mg IV q24h OR ▸ TMP-SMX 160/800 mg q12h Dog Bite Preferred Regimen ▸ Amoxicillin-clavulanate 500-875/125 PO q8-12h Alternative Regimen (beta-lactam allergy) ▸ Clindamycin 300 mg PO q8h PLUS ▸ Ciprofloxacin 500-750 mg IV q12h OR ▸ Moxifloxacin 400 mg IV q24h OR ▸ Gatifloxacin 400 mg q24h Cat Bite Preferred Regimen ▸ Amoxicillin-clavulanate 500-875/125 PO q8-12h Alternative Regimen (beta-lactam allergy) ▸ Cefuroxime 500 mg q12h OR ▸ Doxycycline 100 mg q12h

Non-Antibiotic Therapy

• Elevation of the affected area facilitates gravity drainage of edema and inflammatory substances. Compressive stockings and diuretic therapy may help patients with edema.
• The skin should be sufficiently hydrated to avoid dryness and cracking without maceration.