REVIEW

Cellulitis: Definition, Etiology, and Clinical Features

Craig G. Gunderson, MD
Department of Internal Medicine, Yale University School of Medicine, Veterans Administration Health Care System, West Haven,
Conn.

ABSTRACT
Cellulitis is a common condition seen by physicians. Over the past decade, skin and soft tissue infections
from community-associated methicillin-resistant Staphylococcus aureus have become increasingly common. In this article, the definition, etiology, and clinical features of cellulitis are reviewed, and the
importance of differentiating cellulitis from necrotizing soft tissue infections is emphasized. Empiric
antimicrobial recommendations are suggested, including the most recent recommendations from the
Infectious Disease Society of America.
Published by Elsevier Inc. The American Journal of Medicine (2011) 124, 1113-1122
KEYWORDS: Cellulitis; Community-associated methicillin-resistant Staphylococcus aureus; Necrotizing fasciitis;
Soft tissue infections

Cellulitis is a common form of skin and soft tissue infection resulting in more than 600,000 hospitalizations per
year,1 and along with cutaneous abscess, more than 9
million office visits.2 Traditionally, -hemolytic streptococci and Staphylococcus aureus have been considered
the primary causative agents, and empiric therapy with
-lactam antibiotics has been the mainstay of therapy.
Over the past decade, however, numerous reports have
detailed the widespread emergence of methicillin-resistant S. aureus (MRSA). Previously, MRSA infections
had been limited to hospital-acquired infections or to
community cases with nosocomial exposures. Over the
past decade, however, an increasing proportion of outpatient S. aureus isolates has been found to be methicillinresistant. MRSA infections that occur in outpatients or
within 48 hours of hospitalization and lack nosocomial
exposures such as an indwelling device, recent hospitalization, surgery, dialysis, or residence in a long-term care
facility, have been termed community-acquired or community-associated methicillin-resistant S. aureus (CA-

MRSA).3 Recent studies have concluded that the majority of S. aureus skin and soft tissue infections are now
methicillin-resistant,4 and that CA-MRSA is the most
common isolate from purulent skin and soft tissue infections in the United States.5
Although CA-MRSA has become commonly recognized as a major cause of culturable skin and soft tissue
infections, its role in nonpurulent cases of cellulitis remains uncertain.6,7 Some authors have recommended that
all cases of cellulitis8 be treated for MRSA, while others
have recommended that therapy against CA-MRSA
should be limited to cases that are severely ill or fail
empiric -lactam therapy,7,9 or when local rates of
MRSA are 10% of isolates.10 In February 2011, the
Infectious Disease Society of America (IDSA) published
its first guideline for the treatment of MRSA,6 including
in cellulitis, which, along with the IDSA guideline from
2005 for the management of skin and soft tissue infections,11 forms the basis of the treatment recommendations for this review.

Funding: None.
Conflict of Interest: None.
Authorship: The author is solely responsible for writing this manuscript.
Requests for reprints should be addressed to Craig G. Gunderson, MD,
Department of Internal Medicine, Yale University School of Medicine,
Veterans Administration Health Care System, 950 Campbell Avenue,
West Haven, CT 06516.
E-mail address: craig.gunderson@va.gov

DEFINITIONS

0002-9343/$ -see front matter Published by Elsevier Inc.

doi:10.1016/j.amjmed.2011.06.028

The terminology used to describe different types of skin and

soft tissue infections is complicated because of the use of
terms to describe different forms of infection (cellulitis,
abscess, erysipelas), clinical scenarios (Fournier gangrene,
Ludwig angina), and etiologic agents (clostridial myonecrosis, streptococcal necrotizing fasciitis).

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The American Journal of Medicine, Vol 124, No 12, December 2011

The main types of adult skin and soft tissue infections

include:
1.

2.

3.

4.

patients with cellulitis appear to support the primary role of streptococci.15-23 Although the reported rates of positive cultures are
low, ranging from 1% to 18%, streptococcal species account for
Cellulitis: any spreading infection involving the dermis and
51% of reported isolates, while S. aureus was isolated in only
subcutaneous tissues.12 Purulent cellulitis is defined as celluli15%. Surprisingly, a broad range of gram-negative organisms
tis with associated purulent drainaccounted for another 25%.
age or exudate in the absence of a
The recent guideline on the
drainable abscess.6 This distincmanagement of infections by
tion is significant because purulent
CLINICAL SIGNIFICANCE
MRSA by the IDSA clarifies the
cases are more likely to be due to
relative contributions of strepto Cellulitis is one of the most common
S. aureus.5,6,13
cocci and S. aureus by emphasinfections seen by primary care and hosErysipelas: a specific type of
izing the distinction between
pital-based physicians.
cellulitis involving more superpurulent and nonpurulent types.6
ficial dermal structures distin Cellulitis that is associated with puruCiting a large study of purulent
guished clinically by raised
lent drainage is most commonly due to
soft tissue infections in emergency
borders and clear demarcation
departments across the US, which
Staphylococcus aureus, including combetween involved and uninfound that 76% of cases were due
munity-associated methicillin-resistant
volved skin.11 The distinction
to S. aureus, including 59% by
S. aureus (CA-MRSA). Empiric antimicrois significant because erysipeCA-MRSA,5 the guideline states
bial therapy in these cases should be
las is thought to be predothat in cases with purulence, therdirected against CA-MRSA, and modified
minantly due to -hemolytic
apy should be directed at CAbased on cultures.
streptococci.11
MRSA. In cases of nonpurulent
Abscess: any collection of pus
More commonly, cellulitis is nonpurucellulitis, on the other hand, the
within the dermis or subcutaguideline cites a recent study that
lent. Antimicrobial therapy in such caneous tissues. 11 Clinically,
assessed for evidence of streptoses should be directed at -hemolytic
patients present with nodules
cocci using acute and convalesstreptococci and methicillin-sensitive
with surrounding erythema and
cent serologies of antistreptolysin
S. aureus.
fluctuance. The distinction beO and anti-DNase-B antibodies.7
tween abscess and cellulitis is
This study found that 73% of
significant because abscesses
cases of nonpurulent cellulitis had
are more likely to be due to S.
positive serology, supporting the traditional teaching of the
13
aureus, and are treated primarily by incision and drainage.
predominant streptococcal origin for nonpurulent cellulitis.
Necrotizing soft tissue infections: a necrotizing infection involving any of the soft tissue layers, including the dermis,
subcutaneous tissue, superficial or deep fascia, and muscle.14
CLINICAL PRESENTATION

ETIOLOGY
As noted in the 2005 guideline from the IDSA, traditional
teaching is that most cases of cellulitis are due to -hemolytic
streptococci, often group A, but also groups B, C, or G. S.
aureus also is noted to cause cellulitis, especially when associated with furuncles, carbuncles, or abscesses.11 Nevertheless,
the exact frequency of specific pathogens and the relative
proportion of streptococci and S. aureus remain uncertain,
largely because of the difficulty in culturing most cases of
cellulitis. Potential sources for culture include peripheral
blood, needle aspirates, skin biopsies, and surgical specimens
in cases with purulence, abscess, or necrosis. Unfortunately,
cultures from blood, needle aspirate, and skin biopsy have a
relatively low yield, and many cases of cellulitis are
nonpurulent.7
A recent review of studies of cellulitis that used needle aspiration or punch biopsy for diagnosis questions the traditional
teaching that most cases of cellulitis are due to streptococci. These
authors found that S. aureus accounted for 51% of positive cultures, compared with only 27% from group A streptococcus.8 On
the other hand, studies reporting the results of blood cultures in

Patients with cellulitis typically present with a brief history

of pain, redness, and swelling of the involved skin.24 Commonly there is a history of a predisposing condition for
cellulitis, including obesity, edema, prior saphenous vein
removal, prior radiation therapy, or any skin disorder that
causes a potential portal of entry, including ulcers, wounds,
dry skin with fissuring, chronic skin diseases, and venous
stasis.22 Toe web intertrigo also has been shown to be a risk
factor for cellulitis25, especially if it is complicated by
bacterial colonization with pathogenic bacteria.22,26
The history also should include assessing for risk factors
associated with specific pathogens (Table 1).5,10,12,13,27-30
Risk factors for MRSA include a range of nosocomial
exposures, as well as putative risk factors for CA-MRSA.
Importantly, these MRSA risk factors are derived from
retrospective studies, and have not been prospectively
shown to be clinically useful in discriminating between
MRSA and non-MRSA infections.27
The physical examination should be focused on characterizing the area of cellulitis and assessing for evidence of
abscess or necrotizing infection. Most commonly, cellulitis
involves the lower extremities but may involve the upper

Gunderson

Cellulitis
Table 1

1115
Risk Factors for Associated Pathogens in Cellulitis5,10,13

Reported risk factors for MRSA

Previous history of hospitalization or surgery within the past year
Residence in a long term care facility within the past year
Hemodialysis
Previous MRSA infection or colonization
Recent antibiotic use
Contact sports
Patient report of spider bite
Purulent soft tissue infections
Crowded living environments, including homeless shelters, prisons, soldiers
Intravenous drug users
Men who have sex with men
Household contacts with MRSA infection
Risk factors associated with other
pathogens12,13,27-30
Diabetic foot infections
Often polymicrobial, including gram-positive and gramnegative aerobes and anaerobes
Neutropenia
Gram-positive, gram-negative including Pseudomonas
aeruginosa
Cirrhosis
Gram-negatives, also Campylobacter fetus, Vibrio vulnificus,
Capnocytophaga canimorsus
Intravenous drug use
Staphylococcus aureus, P. aeruginosa
Human bites
Polymicrobial mixture of oral anaerobes and aerobes
(Streptococci, S. aureus, Eikenella corrodens)
Dog and cat bites
Polymicrobial mixture of pathogens derived from the animal
(mixed aerobic and anaerobic bacteria, including
Pasteurella species) and host skin flora, including
staphylococci and streptococci. Capnocytophaga canimorsus
potential severe pathogen for hosts with asplenia or
cirrhosis.
Fresh water lacerations
Aeromonas hydrophila
Salt water lacerations
Vibrio vulnificus
Fish fin or bone injuries
Vibrio vulnificus, streptococci, S. aureus, gram-negatives.
MRSA methicillin-resistant Staphylococcus aureus.

extremities, trunk, perineum, or head and neck.20,24 The

rash is almost universally found to be warm, red, tender, and
swollen,24,31 and there may be associated lymphangitis or
lymphadenopathy.24 In erysipelas, the rash is well demarcated, whereas in cellulitis the borders are less well defined.
There may be associated vesicles and bullae, although if
present, bullae generally are filled with clear fluid as opposed to the hemorrhagic or violaceous fluid found in necrotizing infections.11
Fever and constitutional symptoms are often mild or
absent in uncomplicated cellulitis. In published series, fever
is reported in only 26%-67% of cases.15,16,24,32 Hypotension
is rare, reported in one series of hospitalized patients as
present in 2.7%.32 Leukocytosis and elevated sedimentation
rate are present in approximately one half of cases.16

DIFFERENTIAL DIAGNOSIS
A broad range of conditions may masquerade as cellulitis,
including infections such as necrotizing fasciitis, varicella

zoster, herpetic whitlow, and erythema migrans; inflammatory conditions such as acute arthritis, gout, or bursitis; or
dermatologic conditions such as contact dermatitis, hypersensitivity reaction, fixed drug reaction, and venous stasis
disease33 (Table 2). As previously described, cutaneous
abscesses are important to distinguish from cellulitis because of the necessity of drainage.
One common practice for patients with lower-extremity
cellulitis is to rule out deep venous thrombosis with duplex
ultrasound. Data on this practice are mixed, however.
Glover and Bendick34 reviewed 241 patients with a clinical
diagnosis of cellulitis who were referred for ultrasound, and
found no cases of proximal deep venous thrombosis (2 cases
had isolated calf thrombosis). On the other hand, Rabuka et
al35 retrospectively reviewed all duplex scans ordered in the
emergency department with the question of cellulitis versus
deep venous thrombosis. In this study, 17% had a deep
venous thrombosis.35 Based on these studies, it seems that
the yield for routine lower extremity ultrasound in patients
with readily apparent cellulitis is very low, but for patients

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The American Journal of Medicine, Vol 124, No 12, December 2011

Table 2

Differential Diagnosis of Cellulitis12,13,33

Characteristics

Infectious
Necrotizing fasciitis

Erysipelas
Cutaneous abscess

Herpetic whitlow
Erythema migrans
Inflammatory
Acute arthritis (gout, septic)
Acute bursitis
Dermatologic
Stasis dermatitis
Hypersensitivity reaction
Fixed drug reaction

Miscellaneous
Deep venous thrombosis
Rare
Familial Mediterranean fever

Pyoderma gangrenosa
Sweets syndrome

Triad of severe pain, swelling, and fever. Pain out of proportion,

severe toxicity, hemorrhagic or bluish bullae, gas or crepitus,
skin necrosis or extensive ecchymosis, rapid progression.
A form of cellulitis with well demarcated borders.
Early abscess may appear similar to cellulitis. Eventually
distinguishable by appearance of a nodule with fluctuance
and drainage.
Vesicular. Characteristic location on fingers.
Often not painful, not typically located on lower extremities,
ovoid appearance. Tick exposure.
Essential feature is involvement of joint, with disproportionate
pain with joint movement.
Characteristic locations such as over the patella or olecranon,
often with palpable fluid collection.
Distinguishable from cellulitis by lack of fever, less pain, heme
deposition, and circumferential pattern.
Pruritis instead of pain, absence of fever.
Typically occurring soon after drug ingestion, usually not painful
unless erosions occur, characteristic locations on genitalia,
face, trunk; less commonly, lower extremities.
Typically not associated with skin redness or fever.
Patients may get erysipelas-like erythema during episodes.
Distinguished from true erysipelas by recurrent nature,
positive family history, and occurrence in Sephardic Jews and
persons from the Middle East.
Often on the anterior shin, ragged ulcers with undermined
borders. Often in patients with inflammatory bowel disease.
Occasionally mistaken for cellulitis. Typical lesions are papules
that coalesce into plaques. Commonly on upper extremities
and face. Treated by corticosteroids.

for whom the diagnosis is in doubt, ultrasound may be

useful.

RULING OUT NECROTIZING SOFT

TISSUE INFECTION
Although uncommon, necrotizing soft tissue infections are
important to diagnose, given their high mortality without
surgery, and are usually either streptococcal or polymicrobial in origin.14 Most patients with necrotizing soft tissue
infections present with the clinical triad of severe pain,
swelling, and fever.36 Possible physical examination findings include severe toxicity, hemorrhagic or bluish bullae,
skin necrosis or ecchymosis, gas or crepitus, cutaneous
anesthesia, edema that extends beyond the margin of erythema, and rapid progression. Unfortunately, these so-called
hard signs of necrotizing soft tissue infection often are
absent at presentation.37

Laboratory tests may be useful for assessing the risk of

necrotizing soft tissue infections. Wall et al37 found that the
combination of a white blood cell count of 15,500 cells/
mm3 and a serum sodium concentration of 134 mmol/L
effectively ruled out necrotizing soft tissue infection, although their presence was not effective at ruling in the
diagnosis. Similarly, Wong et al32 described a risk score
based on admission laboratory values to predict the likelihood of necrotizing soft tissue infection,32 wherein a low
risk score had a 96% negative predictive value and moderate to high risk scores had a 92% positive predictive value.
Both authors then outlined approaches to necrotizing soft
tissue infection using their algorithms (Figure 1).
Diagnostic imaging also may be useful in assessing possible necrotizing soft tissue infections. Plain films may
show subcutaneous gas, a relatively specific but insensitive
finding of necrotizing infection. Computed tomography is

Gunderson

Cellulitis

1117

Figure 1 Proposed approach to evaluating patients for necrotizing soft tissue

infections (modified from Wall et al37 and Wong et al32).

more sensitive at showing soft tissue gas, and may additionally show deep fascial thickening or associated deep
tissue abscesses.38 Magnetic resonance imaging has been
touted as the imaging study of choice for differentiating
necrotizing infections from cellulitis.39-41 Reported findings
include deep fascial involvement with thickening and inflammation, and the absence of gadolinium contrast enhancement on T1-weighted images, which may reflect tissue necrosis.42 Because studies of diagnostic imaging for
necrotizing fasciitis have generally been retrospective case
series that have lacked meaningful comparison groups,14
data on sensitivity and specificity are unknown.11
Ultimately, the only way to definitively diagnose necrotizing soft tissue infections is by surgical exploration, which
is recommended urgently for any case with substantial concern. Operative findings diagnostic of necrotizing soft tissue
infection include the presence of necrotic fascia, lack of
resistance of normally adherent muscular fascia to blunt

dissection (positive finger test), lack of bleeding of fascia

during dissection, and the presence of foul-smelling dish
water pus.36

DIAGNOSTIC STUDIES
Most cases of cellulitis are managed empirically. According
to the IDSA guideline, cultures of blood, needle aspirates,
and skin biopsies are optional. Given the relatively low
yield in culturing cellulitis and risk of contaminants, cultures are generally not pursued other than the common
practice of obtaining blood cultures for admitted patients.
Purulent infections, on the other hand, should be debrided
and cultured.
The IDSA does recommend that needle aspiration or skin
biopsies should be considered in patients who are immunocompromised or have an abnormal exposure history, such as
bite wounds. These tests also should be considered in pa-

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The American Journal of Medicine, Vol 124, No 12, December 2011

tients who fail to improve with empiric antibiotics.11 Various methods have been described for needle aspiration,43-45
but the most common is using a 22-gauge needle to aspirate
fluid from the advancing edge of the cellulitis after the area
is cleaned with povidone-iodine solution. The average microbiologic yield reported in studies using needle aspiration
or skin biopsy for culture is 24%,8 although rates have
varied from 0-40%. An alternative to needle aspirate is
using a punch biopsy for culture, although it is unclear
whether this increases diagnostic yield.46
Studies of patients with cellulitis with associated open
wounds or ulcers that have used swabs for culture have
reported high yields of potential pathogens, but distinguishing between causative agents and contaminants may be
difficult.47
A summary of possible diagnostic tests to consider in
patients with cellulitis is found in Table 3.

TREATMENT
Traditionally, cellulitis has been managed empirically with
antibiotics chosen to cover -hemolytic streptococci and
methicillin-sensitive S. aureus. Over the past decade, with
the widespread emergence of CA-MRSA as a potential
pathogen, many clinicians have chosen to treat cellulitis
Table 3

with therapy directed at MRSA. A recent study from Denver, for example, reported that 85% of hospitalized patients
with cellulitis were treated with vancomycin or other antiMRSA therapy, whereas only 20% were treated with cefazolin and 8% with nafcillin. At discharge, 48% were discharged on trimethoprim-sulfamethoxazole, compared with
only 6% on cephalexin and 3% on dicloxacillin.48
The recent guideline from the IDSA on the treatment of
MRSA substantially changes prior recommendations about
the treatment of cellulitis. For outpatients with purulent
cellulitis, empiric therapy for CA-MRSA is now recommended, pending culture results. Empiric therapy for -hemolytic streptococci is considered unnecessary (class A-II
recommendation). Listed options include clindamycin, trimethoprim-sulfamethoxazole (TMP-SMZ), a tetracycline
such as doxycycline or minocycline, or linezolid (Table 4).
For outpatients with nonpurulent cellulitis, on the other
hand, empirical therapy for infection due to -hemolytic
streptococci and methicillin-sensitive S. aureus is still recommended (A-II), whereas therapy for CA-MRSA is reserved for patients who fail -lactam therapy or who are
severely ill. Listed options include cephalexin, dicloxacillin,
and clindamycin. If therapy for both CA-MRSA and -hemolytic streptococci is desired, options include a -lactam

Tests to Consider in Patients with Cellulitis

Laboratory tests:
CBC, chemistries, ESR, CRP
CK

Imaging:
Plain films
Ultrasound
CT

MRI

Bacterial cultures:
Blood cultures
Associated wounds or ulcers

Needle aspiration
Culture from punch biopsy
Culture from fluid-filled bullae
Culture of drainage

Generally nonspecific. Can be used for LRINEC score and Wall

criteria if necrotizing infection is suspected.
May be useful to screen for muscle involvement of infection,
which can be seen in necrotizing infections and bacterial
myositis.
Presence of gas strongly suggests necrotizing soft tissue infection.
Specific but insensitive sign.
Test of choice if suspect underlying abscess.
Possible role for evaluating for necrotizing soft tissue infections.
Reported signs include soft tissue gas, deep fascial thickening,
and associated deep tissue abscess.
Possible role for evaluating for necrotizing soft tissue infections or
osteomyelitis. Deep fascial involvement evidenced by fascial
thickening and enhancement, gas, and fluid collections.
Generally low yield, commonly obtained for hospitalized patients.
High yield, uncertain pathogenic significant unless done from
debribed base. Obtain specimens by biopsy or curettage, or
potentially needle aspiration. Avoid swabbing undebrided ulcers
or wound drainage.
Generally modest yield, consider in immunocompromised patients
or patients who fail empiric treatment.
Not clearly superior to above, potentially scarring.
Possibly high yield, easy to do.
Possibly high yield but swabs risk contamination. If purulent
wound should generally be debrided before culturing.

CBC complete blood count; CK creatine kinase; CRP C-reactive protein; CT computed tomography;
ESR erythrocyte sedimentation rate; LRINEC Laboratory Risk Indicator for Necrotizing Fasciitis; MRI magnetic
resonance imaging.

Gunderson
Table 4

Cellulitis

1119

Recommended Antimicrobial Therapy for Patients with Cellulitis6,11

Erysipelas
Penicillin
Outpatient purulent cellulitis
Clindamycin

A-I*

Drug of choice for erysipelas. 100% sensitivity of Streptococcus pyogenes.

A-II

Bacteriostatic. Highly effective against Streptococci. Good efficacy data

in SSTI; 3%-24% CA-MRSA resistance.49 Also, potential for inducible
resistance in susceptible strains during treatment if erythromycinresistant.
Bactericidal. Limited published data on SSTI. Uncertain efficacy against
S. pyogenes.10 CA-MRSA rarely resistant.49
Bacteriostatic. Little recent efficacy data;10 5% CA-MRSA resistance.49
Bacteriostatic, expensive, numerous potential side effects
(myelosuppression, peripheral neuropathy, optic neuritis, nausea,
vomiting, diarrhea, lactic acidosis). Weekly CBC for monitoring. Highly
effective against HS, CA-MRSA.

TMP-SMZ

A-II

Doxycycline
Linezolid

A-II
A-II

Outpatient nonpurulent cellulitis

-lactam (cephalexin or
dicloxacillin)
Clindamycin
-lactam plus TMP-SMZ or a
tetracycline
Linezolid
Hospitalized patients with cellulitis
Vancomycin

A-II

Bactericidal, highly effective against HS, MSSA.

A-II
A-II

See above.
Highly effective against both HS and CA-MRSA. Recommended for
patients who fail -lactam therapy and may be considered in all with
systemic toxicity.
See above. Recommended for patients who fail -lactam therapy and
may be considered in all with systemic toxicity.

A-II

A-I

Linezolid
Daptomycin

A-I
A-I

Telavancin
Clindamycin
Nafcillin or oxacillin

A-I
A-III
A-II

Cefazolin

A-II

Necrotizing soft tissue infections

Type 1, polymicrobial
Ampicillin-sulbactam/piperacillintazobactam clindamycin
ciprofloxacin
Type 2, monomicrobial (S. pyogenes,
MRSA, V. Vulnificus, others)
Clindamycin plus penicillin for
S. pyogenes

A-III

Traditional parenteral therapy for MRSA infections. Concerns over its

slow bactericidal activity. Less effective against Staphylococcus aureus
than -lactams for susceptible strains.6
See above.
Bactericidal, expensive. Risk of myopathy and rhabdomyolysis. Weekly CK
for monitoring. Avoid administering with HMG-CoA reductase
inhibitors.
Bactericidal. Nephrotoxicity, monitor creatinine levels.
See above; A-III recommendation for hospitalized patients.
Bactericidal. Inactive against MRSA. A-II recommendation for
hospitalized patients with nonpurulent cellulitis.
Bactericidal. Inactive against MRSA. A-II recommendation for
hospitalized patients with nonpurulent cellulitis.

Preferred per IDSA

Pathogen directed.
A-II

Clindamycin appears to be superior to penicillin as monotherapy, but

rarely, S. pyogenes may be resistant, hence addition of penicillin.

HS beta-hemolytic streptococci; CA-MRSA community-acquired S. aureus; MSSA methicillin-susceptible S. aureus; MRSA methicillin-resistant
S. aureus; SSTI skin and soft-tissue infection; TMP-SMZ trimethoprim-sulfamethoxazole.
*All grading of recommendations per the Infectious Disease Society of America (IDSA) guidelines.6,11 Grade A Good evidence to support a
recommendation for use; should always be offered. Quality of evidence I Evidence from at least one randomized, controlled trial; II Evidence from at
least one well-designed nonrandomized clinical trial or cohort or case-controlled study, or multiple time-series, or from substantial results from
uncontrolled experiments; III Evidence from opinions of respected authorities.

such as amoxicillin plus either TMP-SMZ or a tetracycline,

or linezolid alone. Monotherapy with TMP-SMZ or a tetracycline for nonpurulent cellulitis is not recommended
given limited published efficacy data and concerns about
effectiveness against streptococci.49,50

Hospitalized patients with cellulitis have, by definition,

complicated skin and soft tissue infection, which also includes patients with deep soft tissue infections, surgical and
traumatic wound infections, major abscesses, and infected
ulcers and burns.6 For these patients, the IDSA states that

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therapy for CA-MRSA should be considered pending culture data. Listed options include vancomycin, linezolid,
daptomycin, and telavancin (all A-I). Clindamycin also is
listed as an option, but with a lower level of evidence
(A-III). For hospitalized patients with nonpurulent cellulitis,
however, the IDSA guideline states that -lactam therapy
remains an acceptable option, with reservation of MRSAactive therapy for patients who fail to respond.
Of note, the IDSA does not recommend different antibiotics for diabetics with cellulitis than it does for nondiabetics, except in cases of chronic diabetic foot infections.28
Antimicrobial medications based on IDSA recommendations, including for necrotizing soft tissue infections, are
listed in Table 4. The overall approach to cellulitis is shown
in Figure 2.

Adjuvant Treatments for Cellulitis

Although not specifically studied, treatment of patients
edema when present may hasten recovery and prevent recurrent cellulitis. This may be done with compression dressings or stockings, leg elevation, and potentially, diuretics
when indicated.
Another potential adjuvant treatment is corticosteroids.
Given the difficulty culturing microbes in cellulitis, some
authorities have surmised that many of the manifestations of

cellulitis are inflammatory in nature. This led to at least one

trial of adjuvant corticosteroids, which found that patients
given 8 days of prednisolone had a significantly shorter
duration of illness and decreased length of hospitalization.51
Although not a widespread practice, the IDSA recommends
that clinicians consider the addition of corticosteroids for
the treatment of cellulitis.

Duration of Therapy and Failure to Respond

The optimal duration of antibiotics for cellulitis is unknown.
Most authorities comment that durations of 5-10 days are
commonly needed,6 or longer, depending on clinical response.12 The Sanford Guide to Antimicrobial Therapy52
recommends that therapy be continued until 3 days after
acute inflammation disappears. This common practice of
continuing antibiotics until erythema has resolved has been
questioned by at least one study, which randomized a group
of patients with uncomplicated cellulitis who were improving after 5 days of standard therapy to either placebo or an
additional 5 days of antibiotic.53 These authors found that
98% of both groups of patients had complete clinical
resolution of their cellulitis, suggesting that at least for
patients with uncomplicated cellulitis who are already
improving after 5 days of treatment, additional antibiotic
is unnecessary.

Figure 2 Suggested approach to cellulitis.6

MSSA methicillin-susceptible Staphylococcus aureus; CA-MRSA communityassociated methicillin-resistant S. aureus; TMP-SMZ trimethoprim-sulfamethoxazole.

Gunderson

Cellulitis

For patients who fail to respond to empiric therapy,

options include adding anti-MRSA therapy, adding gramnegative coverage, searching for a drainable focus with
imaging, and needle aspiration for culture. Even with appropriate diagnosis and therapy, some patients are slow to
respond.11 For hospitalized patients, the average length of
stay for cellulitis in the US is 4.5 days,1 but some patients
remain hospitalized for prolonged periods.54,55 One study
found that independent predictors of prolonged lengths of
stay included edema, prior use of diuretics, and absolute
neutrophil counts 10 109/L,55 indicating that edema and
possibly disease severity were the primary determinants of
duration of therapy. Although unproven, this suggests that
aggressive therapy for coexisting edema may be a useful
adjuvant therapy.

CONCLUSIONS
Cellulitis is a common cause of infection for adult patients.
Until the past decade, empiric treatment using -lactam
antibiotics has been standard. Specific microbiologic diagnosis was rarely pursued or found. Over the past decade,
however, community isolates of S. aureus have been found
to be increasingly resistant to even extended-spectrum
-lactams. Studies of skin and soft tissue infections during
this time, particularly purulent infections, have found a
large proportion to be due to CA-MRSA. It remains unknown, however, how much of nonpurulent cases are due to
CA-MRSA. High-quality randomized, controlled trials
comparing different antibiotic regimens for nonpurulent cellulitis are needed. Lastly, studies to evaluate duration of
therapy and preventive strategies also are overdue.

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