Thana Khawcharoenporn, M.D. ACP Associate Alan Tice, M.D., FACP (Advisor)

1. Evaluationof Empiric Oral Antibiotic Treatment for Outpatients with Cellulitis in a Community with a High Prevalence of Community-associated Methicillin-resistant Staphylococcus- aureus (CA-MRSA) Infections Thana Khawcharoenporn, M.D. ACP Associate Alan Tice, M.D., FACP(Advisor)

2. Background 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 CA-MRSA. Military personnel, team athletes, inmates, men who have sex with men (MSM)1,2 1Deresinski S. Clin Infect Dis 2005; 40: 562-73. 2Weber JT. Clin Infect Dis 2005; 41: S269-72.

3. Background Study of CA-MRSA infections in Hawaii1 July 2001 – June 2003 4 study facilities (Kapiolani, Wilcox Memorial, Queens and Kaiser) The incidence of CA-MRSA infections: 23% in 2001 32% in 2003 1Estrivariz CF. J Infect 2007; 54: 349-357.

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

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

6. Methods Study populations Adult patients (age ≥ 18 years) Diagnosis of cellulitis (ICD 681 or 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

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

8. Methods Study design Primary outcome Treatment success Documented clinical improvement or resolution of signs and symptoms of cellulitis within the follow-up time without the need for antibiotic change, surgical intervention or hospitalization Secondary outcomes Predictors for treatment failure and hospitalization

9. Methods Cellulitis severity score

10. Methods Cellulitis severity score

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

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

13. Results Baseline characteristics Ethnicity

14. Results Baseline characteristics

15. Results Baseline characteristics

16. Results Baseline characteristics

17. Results Available cultures MSSA = methicillin-susceptible Staphylococcus aureus

18. Results Available cultures

19. Results MRSA susceptibility profile

20. Results Oral antibiotics

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

22. Results Success rate by treatment group

23. Success rate by treatment group Results

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

25. Results Secondary outcomes: Predictors of treatment failure

26. Results Secondary outcomes Secondary outcomes: Predictors of hospitalization

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

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

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

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

31. Thank you for your attention