Evaluation of Empiric Oral Antibiotic Treatment for Outpatients with Cellulitis in a Community with a High Prevalence of CommunityCommunityassociated Methicillin-resistant

StaphylococcusMethicillinStaphylococcusaureus (CA-MRSA) Infections (CAThana Khawcharoenporn, M.D. ACP Associate Alan Tice, M.D., FACP (Advisor)

 Cellulitis is one of the most common skin and soft tissue infections, especially in ambulatory settings. Most common causative pathogens:
Streptococci Staphylococcus aureus

An increase in incidence of cellulitis caused by CACAMRSA.

Military personnel, team athletes, inmates, men who have sex with men (MSM)1,2
1Deresinski 2Weber

S. Clin Infect Dis 2005; 40: 562-73.

JT. Clin Infect Dis 2005; 41: S269-72.

Study of CA-MRSA infections in Hawaii1 CA July 2001 June 2003 4 study facilities (Kapiolani, Wilcox Memorial, Queens and Kaiser) The incidence of CA-MRSA infections: CA23% 23% in 2001 32% 32% in 2003

1Estrivariz

CF. J Infect 2007; 54: 349-357.

 Empiric oral antibiotics for cellulitis are generally determined by the common causative agents. Commonly prescribed oral antibiotics: beta-lactams, betaclindamycin and macrolides Microbiological data of cellulitis in areas with a high prevalence of CA-MRSA may be different. CA-

 To assess and compare clinical efficacy between oral antibiotics with and without activity against CACA-MRSA as empiric therapy for cellulitis in an ambulatory setting.

Study populations
Adult patients (age 18 years) Diagnosis of cellulitis (ICD 681 or 682) 682) The Queen Emma Clinic (QEC)
A teaching ambulatory clinic providing healthcare, especially to the underserved

1 January 2005 30 June 2007 (2.5 years) A retrospective cohort study

Exclusion criteria
Patients without follow-up data after treatment follow Patients who received at least 2 oral antibiotics at the same time

Study design
Primary outcome Treatment success
Documented clinical improvement or resolution of signs and symptoms of cellulitis within the follow-up time without the followneed for antibiotic change, surgical intervention or hospitalization

Secondary outcomes Predictors for treatment failure and hospitalization

Cellulitis severity score

Clinical/Lab characteristics
The largest lesions > 5 cm > 3 affected areas Concurrent ulcers and/or abscesses Fever and/or leukocytosis and/or leukopenia Hypotension

Score
1 1 1 1 1

Cellulitis severity score

Score
0-1 2-3 4-5

Severity
Mild Moderate Severe

 260 episodes of cellulitis were identified. 38 episodes were excluded due to no follow-up data followavailable. 222 episodes in the final cohort

aseline characteristics
Age (mean SD): Male: Homeless: Obesity (BMI 30): 30): DM: Cigarette smoker: Alcoholic drinker: Injection drug user: HIV infection: 48. 48.6 13.2 years (range; 18-86) 13. 18-86) 135 (60.8%) 60. 28 (12.6%) 12. 112 (50.5%) 50. 80 (36.0%) 36. 69 (31.1%) 31. 29 (13.1%) 13. 7 (3.2%) 6 (2.7%)

aseline characteristics
Ethnicity Pacific Islander Caucasian Asian African American Native American Hispanic 112 (50.5%) 64 (28.8%) 36 (16.2%) 6 (2.7%) 3 (1.3%) 1 (0.5%)

aseline characteristics
Cellulitis presentation Onset (mean SD) (range) 5.9 Data 5.5 days (1-30)

Involvement Head & neck Upper extremities Trunk Lower extremities Cellulitis only Cellulitis with ulcers Cellulitis with abscesses

19 (8.6%) 52 (23.4%) 58 (26.1%) 110 (49.5%) 73 (32.9%) 51 (23.0%) 103 (46.4%)

aseline characteristics
Severity of cellulitis

Moderate, 34.20%

Mild Moderate

Mild, 65.80%

aseline characteristics
Treatment at first encounter
Oral antibiotics only Oral antibiotics + I&D Hospitalization Topical antibiotics Oral antibiotics + Topical antibiotics + I&D Topical antibiotics + I&D Oral antibiotics + Topical antibiotics I&D only No treatment

Frequency
134 (60.4%) 55 (24.8%) 15 (6.8%) 9 (4.1%) 3 (1.3%) 2 (0.9%) 2 (0.9%) 1 (0.4%) 1 (0.4%)

Available cultures
Culture sources/results
Blood No growth Ulcers MRSA MSSA P. aeruginosa S. marcescens P. aeruginosa + -hememolytic streptococci MSSA + -hememolytic streptococci
MSSA = methicillin-susceptible Staphylococcus aureus

Frequency
n=8 8 (100%) n = 19 10 (52.6%) 5 (26.2%) 1 (5.3%) 1 (5.3%) 1 (5.3%) 1 (5.3%)

Available cultures
Culture sources/results
Abscesses MRSA No growth MSSA E. coli P. mirabilis K. pneumoniae P. acnes -hemolytic streptococci

Frequency
n = 72 39 (54.2%) 12 (16.6%) 11 (15.2%) 2 (2.8%) 2 (2.8%) 1 (1.4%) 1 (1.4%) 1 (1.4%)

MRSA susceptibility profile Antibiotics

Erythromycin Clindamycin Levofloxacin Tetracycline TMP-SMX Gentamicin Rifampicin Vancomycin

Susceptibility (%)
41 96 88 96 100 100 100 100

Oral antibiotics
Prescribed oral antibiotics
Cephalexin Trimethoprim-sulfamethoxazole Clindamycin Amoxicillin-clavulinic acid Dicloxacillin Ciprofloxacin Azithromycin Tetracycline Doxycycline

Frequency (n= 194)

87 (44.8%) 77 (39.7%) 13 (6.8%) 9 (4.6%) 2 (1.0%) 2 (1.0%) 2 (1.0%) 2 (1.0%) 2 (1.0%)

 Episodes treated with cephalexin vs.TMP-SMX were vs.TMPcompared ( n = 87 vs. n = 77). 77). Baseline characteristics of both treatment groups were similar (P 0.05). (P 05).
Age, Ethnicity, gender, homelessness, obesity, underlying conditions, cellulitis presentations, follow-up time, severity of followcellulitis and concurrent treatment (I&D and/or topical antibiotics).

Success rate by treatment group

Patient

All groups

TMP-SMX group (n=77) 87%

Cephalexin group (n=87) 71%

Odds ratio (95% CI)

2.70 (1.22-5.99) 0.02

Success rate by treatment group

Patient
Age < 50 Male Pacific Islanders DM Ulcers +MRSA Oral Abx only

TMP-SMX group
90% 91% 91% 89% 90% 84% 83%

Cephalexin group
70% 74% 68% 59% 56% 14% 66%

Odds ratio (95% CI)

4.07 (1.28-12.77) 3.76 (1.19-11.76) 4.76 (1.46-15.28) 5.65 (1.46-21.41) 7.00 (1.32-35.63) 31.50 (5.38-177.85) 2.56 (1.07-6.15)

P
0.02 0.04 0.01 0.02 0.04 <0.001 0.04

Secondary outcomes
Characteristics of episodes with treatment success and episodes with treatment failure were compared (n = 162 vs. n = 45) 45) Characteristics of episodes that did not require hospitalization and episodes that did require hospitalization were compared (n = 207 vs. n = 15) 15) Logistic regression analysis was used to identify independent predictors of treatment failure and hospitalization.

Secondary outcomes: Predictors of treatment failure

Logistic regression analysis Moderate cellulitis

B 1.22

Standard Error 0.39

Odds ratio (95% CI) 3.40 (1.59-7.28)

P 0.002

Secondary outcomes: Secondary outcomes Predictors of hospitalization

Logistic regression analysis
DM Lower extremity involvement Moderate cellulitis

Standard Error
0.78 0.87 3052.83

Odds ratio (95% CI)

4.77 (1.04-22.03) 5.58 (1.02-30.57) ---

1.56 1.72 19.57

0.04 0.04 <0.001

Adverse reactions:
2/77 (2%) episodes in TMP-SMX group TMPN/V (1%) and Itchiness (1%) (1 (1 1/87 (1%) episodes in cephalexin group Diarrhea (1%) (1

 There was a high incidence of cellulitis caused by MRSA in the ambulatory setting in Hawaii (54%). (54%). TMP-SMX appeared to be more effective than TMPcephalexin as empiric treatment for outpatients with cellulitis Substantial benefit of TMP-SMX treatment was TMPobserved in specific populations:
Age < 50 years, male, Pacific Islanders, DM, presence of ulcers, positive culture for MRSA

 MRSA (CA-MRSA) is likely to be the predominant (CApathogen causing cellulitis. Active empiric antibiotic therapy against CACAMRSA should be considered as the first-line firsttreatment for cellulitis in areas with a high prevalence of CA-MRSA infections, especially in CAthe high-risk patients. high Prospective study is needed to compare other CACAMRSA sensitive antibiotics (clindamycin, doxycycline, minocycline).

 Early and frequent follow-up appointments are followrequired for patients with moderate cellulitis. Hospitalization and aggressive treatment should be considered in patients with moderate cellulitis, DM and lower extremity involvement.