SI’s Mysterious Cellulitis

1. SI’s Mysterious Cellulitis Sandra Katalinic – Pharmacy resident July 13, 2009 Pharmaceutical Care rotation

2. Presentation Outline • Our patient • Her diagnosis • Cellulitis pathophysiology • CC, social history, PMH etc. • ROS, labs, current treatment • Drug related problems • Clinical question • Literature review • Plan and outcomes

3. Learning Objectives • Cellulitis vs necrotizing fasciitis – differences in presentation and causative agents • Cellulitis vs. necrotizing fasciitis – differences in treatment • Recommended monitoring of vancomycin serum levels

4. Our Patient: SI • 73 y/o Caucasian female • c/c rapidly spreading cellulitis on her right leg • Erthythmatous rash to mid thigh • Large 10 x 4cm blister on back of calf • Blistering to lateral malleolus • Source: cracked callous (?) • ? cellulitis or necrotizing fasciitis

5. Cellulitis • Dermis & epidermis  superficial fascia • Serious b/c can get into lymphatic / CV system (bacteremia in 30%) • Pathogens: • S. pyogenes, S. aureus, • 1st line (empiric) nafcillin / oxacillin, cefazolin x5-10 days • MRSA • TMP-SMX (CA-MRSA), Vancomycin (10-14 days)

6. Necrotizing Fasciitis • Rapidly spread (hours), gas production, muscle involvement • Erythmatous, hot, swollen, shiny, ++ tender, bullae filled with clear fluid, maroon colour after several days • Fever, chills, leukocytosis • Clostridium perfringens aka “gas gangrene” • Gm + anaerobe • 1st line tx = Pen G + clindamycin x 10-14 days

7. Past Medical History

8. Social History • Previous smoker • 25 pk/yr hx; quit 40 yrs ago • Well balanced diet • 1.5 espresso sized cups coffee / day • Drinks occasionally • No previous flu or pneumococcal vaccine • No recreational drug use • Codeine intolerance  “violently ill”

9. Goals of therapy • Cure disease • Cure SI’s cellulitis infection • Prevent resistance of causative microorganism • Tailor abx therapy to diagnosis / cultures when available

10. In the Hospital… • Admitted to Emergency Dept: • Vanco 1.5g IV load • Pen G 4mu q4h • Clindamycin 900 mg q8h • Transferred to SS: • Same abx as above • MgSO4 2gm IV q8h • Gravol 25-50mg IV/PO q4h prn • Morph 5-10mg q4h prn • APAP 1-2 tabs q4h prn * HOME MEDS NOT ORDERED**

11. In the Hospital • Logic: • Vancomycin = MRSA, Gm + • Penicillin G = Gm + • Clindamycin = anaerobes • *Clindamycin + Penicillin G = first line for gas gangrene • Aka necrotizing fasciitis • Clostridium (Gm + anaerobe)

12. Review of Systems

13. Review of Systems cont’d

14. Drug Related problems

15. The Plan • Maintain pt on 3 abx’s • Until infectious agent identified • Calculate vancomycin kinetics and adjust dose accordingly

16. The Plan • Other recommendations • KCl 40 mEq, monitor K+ daily • Monitor reaction if morphine given • Monitor for UTI symptoms (BUF) • Start sennosides • Counsel on adequate calcium + Vit D intake (1500mg Ca, 800 IU vit D)

17. Monitoring • Vancomycin Levels 10-15 mg/L • Kidney function : SrCr, GFR, urine output • SrCr 3x weekly while on vancomycin • SE’s: ototoxicity, neutropenia, phlebitis, • Cellulitis:  erythema / edema,  blistering, regressing margins • Ø systemic symptoms (fever, nausea, chills) •  WBC’s

18. 8? Or 10? • Dr. Ensom Says: target 8-10mg/L for cellulitis • Northern Health says: target 10-15mg/L • What are the current recommendations?

19. The Evidence • Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society Of Infectious Diseases Pharmacists • Michael Rybak, Ben Lomaestro, John C. Rotschafer, Robert Moellering Jr., William Craig, Marianne Billeter, Joseph R. Dalovisio, and Donald P. Levine

20. The Evidence • Pub med search from 1958-2008 of all relevant peer reviewed studies in English • Search terms: vancomycin pharmacokinetics, pharmacodynamics, efficacy, resistance, and toxicity.

21. The Evidence • Vancomycin MIC’s required to kill bacteria are on the rise • Vancomycin kills in a time dependant manner (i.e. exposure to levels >MIC affect killing) • Target 5-10mg/L may not achieve desired exposure in higher (but susceptible) MIC bugs • Always maintain vancomycin levels above 10 mg/L to avoid resistance.

22. What this means to us? • Target doses for 10-15 mg/L • Higher serum vancomycin levels prevent resistance without an increase in nephrotoxicity • Vancomycin nephrotoxicity found to be due to impurities from processing / manufacturing • Today’s product very unlikely to have this impurity and occurrence of nephrotoxicity is very low

23. What really happened… • Patient was given1500mg load • Pharmacist dosed 1000mg q12h • Level done prior to 3rd dose = 9.5 • Patient rapidly improving, margins regressing • Blood culture –’ve after 48 hrs

24. What really happened… • Kinetics calculations done: • CrCl = 68.8 ml/min; K = 0.6h-1 • T½ = 11hours; VD = 44.1L • 4-5 t½’s required to reach SS (44-55hours) • Level prior to 3rd dose (36hrs = too early) • Expect level to increase • Maintain dose at 1g q12h

25. What really happened • Requested pk and tr levels, for kinetic monitoring • July 9th trough = 8.5, peak = 22.7 • Kinetics calculations done w/ pk/tr levels •  dose to 1500mg q12h • Expect trough 11.3

26. What really happened • Vanco D/C’s by internal med later that day • necrotizing fasciitis and MRSA ruled out • patient recovering quickly

27. Update • Today: Pt progressing, mobilizing regularly • Erythema only affecting lower leg • Bullae / blistering ↓, WBC 5.5x109/L • Regular BM’s • Stable lytes (including K+) • Chest clear • No s/s of UTI (BUF) • MD considering switch to PO clindamycin

28. References • Dipiro JT, et al. Pharmacotherapy: A pathopysiologic approach.7th ed. New York. 2008: p. 1801-10. • Hill-Blondel. Bugs and Drugs 2006. Edmonton. 2006: p.181-3. • Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2009;66:82-98. • Vancomycin dosing and monitoring in adults. Pharmacist’s Letter/Prescriber’s Letter 2009;25(2):250215.