Management of Cellulitis in the Immunocompromised Patient

Authors: Marvinia Charles, MD & Jill R. Ripper, MD, MS (Rutgers University-New Jersey Medical School, Newark NJ) / Editor: Alex Koyfman, MD (@EMHighAK) & Justin Bright, MD (@JBright2021)


Cellulitis comes from a Latin derivation literally meaning “inflammation of the cell”. Cellulitis is a spreading infection of the skin and its underlying tissues associated with leukocyte invasion and localized capillary dilatation.


Primary cellulitis usually follows a breach in the skin’s integrity but occasionally occurs from hematogenous or lymphangitic spread from more distal sources.  Micro-damage can cause the opening to be non-visible on physical exam. Predisposing conditions to cellulitis commonly include trauma, venous stasis, obesity, lymphedema, pre-existing dermatitis, co-morbid conditions, burns, and surgical wounds.

In primary cellulitis, the natural bacterial skin flora of S. aureus and S.pyogenes are the usual causative agents.  Secondary cellulitis occurs when pathogens infect larger wounds or areas of pre-existing dermatitis. Conditions surrounding the occurrence may dictate the pathogen especially in the immunocompromised patient such as fresh water (Aeromonas hydrophilia), sea water (Vibrio vulnificans), fish tanks (Mycobacterium marinum), soil (Clostridium perfringens), plants (Sprorothrix schenickii) and human bites (Eikenella corrodens). Physical sites also may dictate different pathogens for example peri-anal infections have more of a mixed flora than peripheral body parts. A wide variety of atypical pathogens can invade the skin of immunocompromised patients including fungi, mycobacteria, pseudomonas, aspergillus, and cryptococcus. MRSA should always be considered due to its increasing frequency in both healthy and immunocompromised populations.

Clinical features

Cellulitis usually exhibits the classic signs of inflammation – rubor, calor, dolor, and tumor. Cellulitis presents clinically with local warmth, edema, tenderness, and erythema.  The area may be swollen but typically does not exhibit a sharp demarcation from uninvolved skin.  Lymphangitis – linear red streaks – may accompany cellulitis, but often skips adjacent areas.  However, swollen lymph nodes are characteristic and tend to have the normal expected distribution patterns.  Petechiae are common; large areas of ecchymosis are rare. Vesicles and bullae may develop and rupture with occasional necrosis of the involved skin. Deeper dermal infections can manifest as “shiny skin”.  In more lengthy courses, edema can occur around the hair follicle and cause dimpling, the “peau d’orange” sign.  S. aureus infections cause leg and foot cellulitis in about 80% of cases with the face being the next most typically affected area.

Progression to systemic symptoms may occur particularly in immunocompromised patients. As a result of their diminished capacity to mount an immune response, these patients may present with deceptively minimal symptoms and local erythema may be subtle.  Pain out of proportion may be a sign of a severe underlying infection. Conversely, immunocompromised patients may not notice their infection and have relatively little care of the affected area. Symptoms tend to be progressive over days.  Systemic signs of fever, leukocytosis, and bacteremia are more typical in the immunocompromised patient. Cellulitis tends to recur much more frequently in the immunocompromised patient and may incur a secondary fungal infection concomitantly with the recurrence.

Care should be taken in the immunocompromised host to rule out the life-threatening condition of necrotizing fasciitis, which indicates that the infection has progressed to muscle.  Warning signs on physical exam include any rapidly spreading erythema and violaceous bullae.  Necrotizing fasciitis can be deceptive as some cases have a reddish-purple hue to the skin while a more subtle sign can be a pale appearance to the affected area.  Any incision and drainage yielding thrombosed vessels or a lack of resistance to the tissue should warrant a high level of suspicion. Early and rapid surgical debridement is required.

Diagnosis: Cellulitis is a clinical diagnosis. A high degree of suspicion should be maintained in the immunocompromised population due to subtle or absent typical exam findings from decreased systemic inflammatory systems. A complete medical history and physical examination are important and can be helpful in determining the potential cause of infection. Cellulitis over a joint must be distinguished from the more concerning septic arthritis and pain with range of motion is the best clinical indicator.  A simple fingerstick should be considered to rule out diabetes or poor glycemic control. Laboratory testing is usually not indicated except when systemic symptoms are present. Blood work includes: CBC with differential, BMP, creatine phosphokinase, C-reactive protein, and lactate levels.  The role of these laboratory results in the diagnosis of cellulitis is to help the physician narrow antibiotic choices and determine if admission to the hospital is warranted. Results of wound and blood cultures are of low yield, although wound cultures are recommended in immunocompromised patients. The offending pathogen is determined in less than 5% of all blood cultures.  Needle aspirates have less than a 50% correct result and drop precipitously low when the leading edge of the cellulitis is tested.  Tissue and deep wound cultures may be beneficial in the deep necrotic skin infections.

Radiographs of the affected area may be warranted if foreign body, osteomyelitis, or tissue gas is suspected.  Glass may be visualized if the piece is large enough; however, wood is rarely detected. Ultrasound can play a role in the detection of occult abscesses, pyomyositis, and foreign bodies. CT imaging in a stable patient can sometimes be indicated if there is concern for necrotizing fasciitis, gas gangrene, or foreign body. Duplex scanning is the best modality to differentiate cellulitis from deep venous thrombosis as these entities can clinically present similarly.


Abscesses should be incised and drained except in the case of herpetic whitlow. Empiric antibiotic therapy in the immunocompromised patient should be quickly initiated and guided by patient-specific clinical parameters and the most likely pathogens. Familiarity with common pathogens and with local flora and resistance patterns is essential in choosing initial agents. For the immunocompromised patient, antimicrobial therapy should cover both gram-positive and gram-negative organisms (ceftazidime, cefepime, zosyn, meropenem, doripenem, or imipenem). Penicillin-allergic patients should receive fluoroquinolones or aztreonam. If considering MRSA, empiric addition of vancomycin, clindamycin, or daptomycin should be prescribed. Fungi should be considered as a cause and can be covered by amphotericin, echinocandin, or a triazole. There is a large variability and little agreement among clinicians on antibiotic regimens. Authors also disagree on the duration of therapy with some advocating 3-5 days of treatment while others 5-7 days.

The affected area should be immobilized and elevated above the level of the heart to reduce lymphedema. Cool wet dressing should be applied and changed frequently on large open infected areas.   Hyperbaric oxygen for diabetic wound treatment remains controversial.

Prevention of cellulitis is best accomplished by good hand hygiene, thorough cleansing of wounds, inspecting plantar surfaces of feet in diabetics, and early management of any lesions. Controlling edema with support stockings or compression devices may limit stasis and predisposing factors for cellulitis. In severe edema, diuretic therapy may be initiated.  In diabetics, keeping tight glycemic control decreases factors that cause infection.  A tetanus booster should be given when that patient is not up-to-date with recommended schedules.


Healthy patients without signs of systemic infection can be discharged home on oral antibiotics with follow-up and a list of warning signs for prompt return. Follow up intervals depend on initial presentation, but generally 2-3 days to evaluate success of treatment. Patients may need to come in to the hospital for IV antibiotics in an observation unit setting until they can be transitioned to a PO regimen and sent home. Observation patients who needed transitioning to inpatient admission typically had elevated blood lactate levels, documented fever, or cellulitis of the hand.

Pearls and Pitfalls

  1. Cellulitis that is associated with purulent drainage is commonly associated with Staphylococcus Aureus compared to non-purulent cellulitis that is more commonly β hemolytic streptococcus. Antimicrobial therapy should be directed at the organism in question.
  2. Cellulitis may not appear as red and can span the gamut from pale to violet coloration in deeper infections. Pain is not always present particularly in immunocompromised patients.
  3. Cultures from peripheral blood, needle aspirates, skin biopsies, and surgical specimens have a relatively low yield. They should be considered however in patients with purulent drainage, those who failed outpatient therapy, or immunocompromised patients.

References / Further Reading

– Breen, James. “Skin and Soft Tissue Infections in Immunocompetent Patients.” American Family Physician 81.7 (2010): 893-99. Print.

– Eron, Lawrence. “Cellulitis and Soft Tissue Infections.” Annals of Internal Medicine (2009): 1-16. Print.

– Herchline, Thomas. “Cellulitis.” Medscape. 19 Aug. 2014. Web. 25 Sept. 2014. <>.

– Tintinalli, Judith E. “Soft Tissue Infection.” Emergency Medicine: A Comprehensive Study Guide. 7th ed. McGraw-Hill Medical, 2011. 1014-1018. Print.

– Peterson D et al. Predictors of failure of empiric outpatient antibiotic therapy in emergency department patients with uncomplicated cellulitis. Acad Emerg Med 2014 May; 21:526.

– Gunderson CG. Cellulitis: definition, etiology, and clinical features. Am J Med 2011;124:111322.

Pulia MS, Calderone MR, Meister JR, Santistevan J, May L Update on management of skin and soft tissue infections in the emergency department. Curr Infect Dis Rep. 2014 Sep;16(9):418.

Volz KA, Canham L, Kaplan E, Sanchez LD, Shapiro NI, Grossman SA. Identifying patients with cellulitis who are likely to require inpatient admission after a stay in an ED observation unit. Am J Emerg Med. 2013 Feb;31(2):360-4. Epub 2012 Nov 15.

– Stevens DL 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 Jul 15; 59:e10.

Carey CF, Dall L. Diagnosis of cellulitis in the immunocompromised host. Can J Infect Dis. 1990 Winter;1(4):133-5

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