SI’s Mysterious CellulitisSandra Katalinic – Pharmacy resident

July 13, 2009Pharmaceutical Care rotation

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

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

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

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)

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

Past Medical History

Condition Drug

Osteoporosis Alendronate 10mg O.D. x 10 years

Ca+ + vit D (dose unknown)

Shingles Lysine 100mg 1 tab daily (per pt)

Aging Q10 100mg 1 tab daily (per pt)

1* prevention ASA 81mg O.D.

Anemia? *pt doesn’t know*

Folic acid 5mg O.D.

Vitamin B12 (dose unknown)

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”

Goals of therapy

Cure disease Cure SI’s cellulitis infection

Prevent resistance of causative microorganism

Tailor abx therapy to diagnosis / cultures when available

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**

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)

Review of Systems

System Comments

CNS Ø confusion, dizziness, etc; hx of shingles

Temp: 37 (36.5)

HEENT Ø changes in hearing, sight, smell etc.

RESP Ø, no complaints

CO2 = 16 mmol/L (17 ,17 )

RR = 18 (16); O2= 94% RA

CVS EKG – possible left ventricular hypertrophy

WBC = 13.8 (15.5 , 12.9 ); BP = 97/60mmHg; HR = 100

Neutrophils =12.3 (14.6 ,12.3 )

Lymphocytes = 1.0 (0.3 , 0.5 )

GI/GU Ø, no complaints, passing flatus, No BM x 3 days

Review of Systems cont’d

System Comments

Liver/

Kidney

No hx of liver or renal failure

SrCr = 64 (57,55); GFR = 79;

Endocrine No concerns; no family hx of diabetes or thyroid disease

Msk/Extr/ Skin Cellulitis, red rash, blister on calf, and malleolus; osteoporosis (hip = 2.1; spine 2.9); No pain

Fluid status No complaints as per pt.

Na = 133 mmol/L (133,138);

K= 3.1 mmol/L (2.7 ,2.9 );

Cl = 108 mmol/L (107,109 );

Mg = 0.79

Drug Related problems

At risk of ineffective antibiotic therapy and possible microbial resistance

At increased risk for abx induced side effects (C. diff)

Currently experiencing low potassium & at risk of arrhythmias / muscle cramps

Currently experiencing constipation (drug indicated, not given)

At risk of experiencing cross sensitivity to morphine 2˚ to codeine intolerance (morphine ordered prn, not yet requested by pt)

Risk of UTI 2˚ foley catheter

Currently not receiving adequate Ca+ / Vit D intake

No known indication for folic acid and B12

The Plan

Maintain pt on 3 abx’s Until infectious agent identified

Calculate vancomycin kinetics and adjust dose accordingly

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)

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

8? Or 10?

Dr. Ensom Says: target 8-10mg/L for cellulitis Northern Health says: target 10-15mg/L

What are the current recommendations?

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

Pub med search from 1958-2008 of all relevant peer reviewed studies in English

Search terms: vancomycin pharmacokinetics, pharmacodynamics, efficacy, resistance, and toxicity.

The Evidence

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.

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

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

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

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

What really happened

Vanco D/C’s by internal med later that day necrotizing fasciitis and MRSA ruled out patient recovering quickly

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

References

1) Dipiro JT, et al. Pharmacotherapy: A pathopysiologic approach.7th ed. New York. 2008: p. 1801-10.

2) Hill-Blondel. Bugs and Drugs 2006. Edmonton. 2006: p.181-3.

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.

4) Vancomycin dosing and monitoring in adults. Pharmacist’s Letter/Prescriber’s Letter 2009;25(2):250215.