Beruflich Dokumente
Kultur Dokumente
Group 2: Alison Hemy, Avril Hamilton, Gina Hummel, WaiSum Szeto, Saurabh Patel Date: June 17, 2011
Outline
Meet Christof Kottingheimer (CK) What is cellulitis?
Epidemiology Pathophysiology Risk Factors Microbiology Signs & Symptoms Complications Diagnosis Drug therapy problems and therapeutic alternatives Mild to moderate (uncomplicated) cellulitis Methicillin resistant Staphylococcus aureus (MRSA) treatments Severe (progressive/complicated) cellulitis Care plan/ monitoring/patient education Summary
invisibleparachute.com
Atrial fibrillation
alanderickson.com
Surgical History
1980 - motor vehicle accident and acquired large bump on forehead 1982 facial electrical burn requiring skin graft 2002- benign cyst removed from neck
Social History
Smokes 2 ppd x 20 years Occasional alcohol Denies illicit drug use
anguishedrepose.wordpress.com
Medications
Indication Cellulitis T2DM Atrial Fibrillation Medication Cephalexin 500mg po TID Metformin 500mg po BID Metoprolol 50mg BID Result to date Patient did not take Patient reports only taken a couple of doses Heart rate controlled
leanpowerfulfitness.com
What is Cellulitis?
Type of skin and soft-tissue infection
Acute Affects epidermis, dermis and subcutaneous layers
en.wikipedia.org
Cellulitis. PubMed Health. National Library of Medicine. 2009. Accessed June 15, 2011.
Epidemiology of Cellulitis
Not reportable in Canada
Difficult to determine incidence and prevalence
Incidence = 200 cases per 100 000 patient years More common in middle-aged and elderly Equally affects men and women
uptodate.com National Notifiable Diseases. Publich Health Agency of Canada. Accessed June 15, 2011. Baddour, LM. Cellulitis and erysipelas. UpToDate. Accessed June 15, 2011.
Pathophysiology of Cellulitis
Break to skin
Burn, trauma, ulcers, injections
Risk Factors
Co-morbidities
Diabetes (*** our patient ***) Immunodeficiency Cancer Peripheral artery disease
IV or SC drug use
invisibleparachute.com
Baddour, LM. Cellulitis and erysipelas. UpToDate. Accessed June 15, 2011.
Microbiology
80% of cases are gram positive:
-hemolytic streptococci (ex. Streptococcus pyogenes) Staphlococcus aureus.
Less common:
Streptococcus pneumoniae Haemophilus influenzae Gram-negative bacilli (pseudomonas, proteus, enterobacter) Anaerobes
biomarker.korea.ac.kr
equidblog.com
Baddour, LM. Cellulitis and erysipelas. UpToDate. Accessed June 15, 2011. Pendland SL, Fish DN, Danziger LH. Skin and soft tissue infections: In: DiPiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach, 6th ed. New York, McGraw-Hill, 2005:19771995
Cellulitis. PubMed Health. National Library of Medicine. 2009. Accessed June 15, 2011.
Cellulitis
Medicinenet.com
Cellulitis Complications
Osteomyelitis (bone infection) Lymphangitis (inflammation of lymph vessels) Meningitis Sepsis, shock Gangrene (tissue death)
wikinfo.org
Cellulitis. PubMed Health. National Library of Medicine. 2009. Accessed June 15, 2011.
Diagnosis of Cellulitis
Must be distinguished from other infections
Herpes zoster Necrotizing fasciitis Erysipelas Impetigo
Diagnosis often based on clinical manifestations Blood cultures, needle aspirations or biopsies not useful for mild infection
Positive 5-40% of the time Should be performed with serious disease (systemic toxicity, extensive skin involvement, comorbidities (lymphedema, malignancy, neutropenia, diabetes))
Back to CK
Vitals:
BP 129/74 HR 96 RR 16 T 38.3C BMI 35
invisibleparachute.com
CV:
Irregularly irregular heart beat
CrCl= 77 mL/mins
joetri-tthardt.blogspot.com
Back to CK
Normal 3.2-9.8 x 10^3/mm3 40-70% 0-10% 22-44% 4-11% 4-7 mmol/L (FBG) 5-10 mmol/L (PPG) 136-145 mmol/L 3.5-5 mmol/L 98-106 mmol/L
21-30 mEq/L
26.3 x 10^3/mm3
Kratz A, Ferraro M, Sluss, P, Lewandrowski KB. Laboratory Reference Values. N Engl J Med. 2004. 1548 -1564. .
Medical Conditions
Type 2 diabetes mellitus Atrial Fibrillation
Mr. CK is at risk of stroke due to atrial fibrillation and requires anticoagulant therapy.
Additional DRPs
Mr. CKs metoprolol may not be efficacious as his heart rate is 96bpm and irregularly irregular.
Mr. CK smokes two packs of cigarettes per day and would benefit from smoking cessation education. Mr. CK is at risk of a cardiovascular event, and may require and ACEI and statin (lipid panel unknown). Mr. CKs is at an increased risk of cardiovascular events due to BMI of 35, and requires lifestyle education.
Objective:
swelling (pitting edema), warm, red left forearm decreased range of motion in right shoulder fever tachycardia increased WBCs High neutrophils count, high bands, low lymphs, low monos negative for left upper extremity (LUE) DVT
1. Pendland SL, Fish DN, Danziger LH. Skin and soft tissue infections: In: DiPiro JT, Talbert RL,Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach, 6th ed. New York, McGraw-Hill, 2005:19771995 CREST. Guidelines on the Management of Cellulitis in Adults. 2005
Goals of Therapy
Cellulitis rapid eradication of infection relief of pain and tenderness in left forearm, left upper extremity, right shoulder, and return of range of motion resolution of fever prevention of further complications prevent recurrence
Goals of Therapy
T2DM FBS 4-7mmol/L, PPBS 7-10mmol/L, HbA1c ~ 8 % Prevent complications
microvascular: neuropathy, retinopathy, nephropathy, foot ulcers/wounds, macrovascular: CV disease
Goals of Therapy
Atrial Fibrillation control atrial fibrillation
< 100 bpm
Non-drug Therapies
Local care of cellulitis: elevation and immobilization of the area involved to decrease swelling. Drainage of edema and inflammatory substances Ensure proper wound care and dressing changes Skin should be hydrated
Avoid dryness, cracking but also maceration
Lowy FD, Sexton DJ, Baron EL. Up-to-date: Cellulitis and erysipelas. UpToDate INC, 2010. (Accessed June
Moderate - Severe
administration of semisyntheitic penicillin (nafcillin or oxacillin 1-2g IV q 4-6hrs) administration of 1 st gen cephalosporin (cefazolin) clindamycin both have activity against strep and staph usual duration of therapy 5-10d
Streptococci: mild:
oral penicillin VK 0.5g q 6 hrs OR IM procaine penicillin G 600 000U q 8-12hrs
severe:
Penicillin G 1 2 million U IV q 4-6hrs OR IV ceftriaxone 50-100mg/kg as single dose
if allergic to penicillin:
oral or parenteral clindamycin OR 1st gen cephalosporin w/ caution (cefazolin 1-2g IV q 6-8hrs)
Pendland SL, Fish DN, Danziger LH. Skin and soft tissue infections: In: DiPiro JT, Talbert RL,Yee GC, et al., eds. Pharmacot herapy: A Pathophysiologic Approach, 6th ed. New York, McGraw-Hill, 2005:19771995 Kish TD, Chang MH, Fung HB. Treatment of skin and soft tissue infections in the Elderly: A review. Am J Geriatr Pharmacother. 2010 Dec;8(6):485-513.
severe:
aminoglycoside IV cephalosporin (1st or 2nd gen depending on severity/susceptibility)
Severe:
Aminoglycoside + clindamycin OR metronidazole monotherapy with 2nd or 3rd gen cephalosporin monotherpay with imipenem, meropenem, ertapenem, piperacillin/tazobactam,
tigecycline
Pendland SL, Fish DN, Danziger LH. Skin and soft tissue infections: In: DiPiro JT, Talbert RL,Yee GC, et al., eds. Pharmacot herapy: A Pathophysiologic Approach, 6th ed. New York, McGraw-Hill, 2005:19771995 Kish TD, Chang MH, Fung HB. Treatment of skin and soft tissue infections in the Elderly: A review. Am J Geriatr Pharmacother. 2010 Dec;8(6):485-513.
Empiric antibiotic therapy for management of cellulitis should include activity against betahemolytic streptococci and S. aureus.
Penicillinase is a specific type of lactamase, which hydrolyses the -lactam ring. Pennicillinase producing bacteria are still susceptible to cloxacillin
and methicillin, oxacillin Ortho-dimethoxyphenyl group produces steric hindrance around the amide bond.
Autiero I, Costantini S, Colonna G. Modeling of the bacterial mechanism of methicillin-resistance by a systems biology approach. PLoS One. 2009 Jul 13;4(7):e6226. Stapleton PD, Taylor PW. Methicillin resistance in Staphylococcus aureus: mechanisms and modulation. Sci Prog. 2002;85(Pt 1):57-72. Review.
Antibiotic use throughout the years resulted in multiresistant MRSA strains due to mutations in genes coding for target proteins (such as PBPs) and acquisition of various other resistance-coding genes S. aureus can become resistant to methicillin through expression of PBP2a
still has the same functions as PBP but is resistant to methicillin
Autiero I, Costantini S, Colonna G. Modeling of the bacterial mechanism of methicillin-resistance by a systems biology approach. PLoS One. 2009 Jul 13;4(7):e6226. Stapleton PD, Taylor PW. Methicillin resistance in Staphylococcus aureus: mechanisms and modulation. Sci Prog. 2002;85(Pt 1):57-72. Review.
Evidence
- No definitive evidence in terms of which antibiotic is the best for mild-to-moderate cellulitis - Decision really depend on culture results, host factors, common organisms in the local area, resistance patterns, severity, and cost & convenience - Our recommendations are based on following resources:
- Infectious Diseases Society of America guideline(IDSA) Diagnosis and Management of Skin and Soft-tissue infections1 - Sanford Antimicrobial guideline2 - Evidence-based Infectious disease book3 - Essential Evidence Plus Cellulitis4 - Up-To-Date Cellulitis5
1. Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger P, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan EL, Montoya JG, Wade JC. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 2005 Nov 15;41(10):1373-406 2. Gilbert DN., Moellergin RC, Eliopoulos GM. Sandford Guideline to Antimicrobial Therapy. 40th Edition. Virginia, Sandford: Antimicrobial Therapy Inc. 2010: 1-219 3. Loeb M, Smaill Fiona, Smieja M. Cellulitis and Erysipelas. IN: Evidence-based infectious diseases. 2nd edition. NJ: John Wiley & Sons, Inc., 2009: 11-15 4. Carek PJ, Steyer TE. Essential Evidence Plus: Cellulitis. John Wiley & Sons, Inc., 2011. (Accessed June 12, 2011 at: www.essentialevidenceplus.com/content/eee/724) 5. Lowy FD, Sexton DJ, Baron EL. Up-to-date: Cellulitis and erysipelas. UpToDate INC, 2010. (Accessed June 12, 2011 at: www.uptodate.com)
Empiric antibiotic therapy for management of cellulitis should include activity against betahemolytic streptococci and S. aureus.
Cellulitis
Mild to moderate/uncomplicated
Severe /progressive/complicated
Start Cloxacillin or Cephalexin Therapeutic Failure Obtain blood/tissue sample/pus for culture Modify based on the C&S results Start TMP-SMX or Clindamycin
Therapeutic failure
Daptomycin or Linezolid
Cloxa/Cepha lexin
HC-MRSA
TMPSMX/Clinda
Severe
Vancomycin
Daptomycin/ linezolid
Vancomycin
Answer
Yes, cephalexin was appropriate
Will see this clearer in the next few slides!
Cellulitis
Mild to moderate/uncomplicated
Severe /progressive/complicated
Start Cloxacillin or Cephalexin Therapeutic Failure Obtain blood/tissue sample/pus for culture Modify based on the C&S results Start TMP-SMX or Clindamycin
Therapeutic failure
Daptomycin or Linezolid
Therapeutic alternatives
Most commonly recommended
Cephalexin Cloxacillin Clindamycin Trimethoprim-Sulfamethoxazole Fluoroquinolones
ESC
Drug Product Efficacy Safety NV, C.diff colitis, headache, confusion, BUN/Scr, LFT NVD, rash NVD, headache C. diff colitis, rash, fever, neutropenia, eosinophilia, thrombocytopenia NVD, confusion, fever, rash, photosensitivity, neutropenia, eosinophilia, thrombocytopenia NVD, photosensitivity, dizziness, light headedness, tendenitis, transient increase in LFTs, intestinal nephritis, hypoglycemia Cost/Convenience Cephalexin ++++ $ 0.45/500mg tab
Cloxacillin
++++
$0.35/500mg capsule
Clindamycin
++
$0.44/300mg capsule $0.40/ (400mg & 80mg tablet) $0.55-$1.4/tab depending on tluoroquinilone you choose
TMP-SMX
++
Fluoroquinol ones
++
TMP-SMX
7-14 days
7-14 days
* Depends on the clinical response (until 3 days after the acute inflammation disappears)
Care Plan
Indication: Cellulitis Drug Product Cephalexin (Keflex) Dosage instructions Note changes 500 mg four times a Initiate day for 7 days
Monitoring Plan
Effectiveness Parameter Clinical symptoms: Redness, edema, tenderness, warmth, pain, range of motion in affected area Temperature (38.3 C) Pulse (96 bpm) WBC count (26.3 x 10 3/mm3 ) Bands (10%) Neutrophils (81%) Prevent complications (sepsis)
Change Timeframe
Improved
24-48 hours
Reduced to 37.5 C Return (decrease) to normal (60-80 bpm) 3.54 to 9.06 x 10 3/mm3 0-5% 40-70% None
24-48 hours 24-48 hours Improve in 3-4 days Normal in 1 week Improve in 3-4 days Normal in 1 week Improve in 3-4 days Normal in 1 week Continuously
Lowy FD, Sexton DJ, Baron EL. Cellulitis and erysipelas. Uptodate 2010. Retrieved June 15th, 2011.
Monitoring Plan
Safety Parameter GI symptoms (nausea, diarrhea, vomiting) Mild skin rash Headache/confusion Change None to minimal Timeframe 2 days and during therapy
Rogers SH, Cavazos JE. Chapter 114 Skin and soft-tissue infections. In: Dipiro JT, Talbert TL, Yee GC, Matzke GR, Wells BG, and Posey ML. Pharmacotherapy: A pathophysiological approach, 7th edition. NY: The McGraw-Hill Companies,. 2008:1807-09
Therapeutic Failure
What is an alternative treatment if cephalexin fails?
Therapeutic Failure
Cellulitis Mild to moderate/uncomplicated Severe /progressive/complicated
Start Cloxacillin or Cephalexin Therapeutic Failure Obtain blood/tissue sample/pus for culture Modify based on the C&S results Start TMP-SMX or Clindamycin
Therapeutic failure
Daptomycin or Linezolid
ER visit 3
MRI done to rule out compartment syndrome Two blood cultures drawn Orthopedics consulted for potential incision and drainage of the left arm cellulitis Admitted for complicated/progressive cellulitis and possible MRSA Started on Cefazolin 1g IV x one dose given in ED
Questions
Severity? Appropriate drug of choice?
MRSA
MRSA emerged in the 1960s
Health care associated MRSA ( HA-MRSA) 1
Recently, MRSA infections without health care setting exposures is termed communityacquired MRSA (CA-MRSA) 1 CA-MRSA associated with primarily skin and soft-tissue infections 1
Sometimes associated with sepsis and necrotizing pneumonia 1
1) Rybak MJ, LaPlant KL. Community-associated methicillin-resistant Staypylococcus aureus: a review. Pharmacotherapy 2005;25:74-85
MRSA
Defined as an oxicillin minimum inhibitory concentration
(MIC) 4mcg/mL 1 If microorganism is resistant to oxicillin or methicillin, they are also resistant to beta-lactam agents such as dicloxacillin and cefazolin 1
CA-MRSA tend to be less resistant than HA-MRSA and
has different types of gene complexes known as staphylococcocal cassette chromosome mec (SCCmec) 2
1) Lowy FD, Sexton DJ, Baron EL. Treatment of skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus in adults. Uptodate 2010. Retrieved June 15th, 2011. 2) Rybak MJ, LaPlant KL. Community-associated methicillin-resistant Staphylococcus aureus: a review. Pharmacotherapy 2005;25:74-85
Severity?
Cellulitis Mild to moderate/uncomplicated Severe /progressive/complicated
Start Cloxacillin or Cephalexin Therapeutic Failure Obtain blood/tissue sample/pus for culture Modify based on the C&S results Start TMP-SMX or Clindamycin
Therapeutic failure
Daptomycin or Linezolid
Appropriate DOC?
Cellulitis Mild to moderate/uncomplicated Severe /progressive/complicated
Start Cloxacillin or Cephalexin Therapeutic Failure Obtain blood/tissue sample/pus for culture Modify based on the C&S results Start TMP-SMX or Clindamycin
Therapeutic failure
Daptomycin or Linezolid
Cloxa/Cepha lexin
HC-MRSA
TMPSMX/Clinda
Severe
Vancomycin
Daptomycin/ linezolid
Vancomycin
Answers
Very severe Cefazolin is an inappropriate drug of choice
Therapeutic Alternatives
- Vancomycin - Linezolid - Daptomycin
Bottom-line: Linezolid does not provide any significant advantages in terms of effectiveness over vancomycin. The unblinded nature of this study, post hoc subgroup analyses, and failure to describe criteria for initiating oral versus intravenous therapy are serious limitations. Any trends toward an advantage for linezolid should be interpreted very cautiously.
Weigelt J, Itani K, Stevens D, et al, for the Linezolid CSSTI Study Group. Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother 2005; 49:2260-66.
Bottom-line: There was no difference in the rate of resolution of cellulitis or erysipelas among patients treated with daptomycin or vancomycin. Daptomycin 4 mg/kg once daily appeared to be effective and safe for treating cellulitis or erysipelas.
Pertel et al. The efficacy and safety of daptomycin vs. vancomycin for the treatment of cellulitis and erysipelas. Int J Clin Prcact 2009; 3: 368-375
ESC
Drug Product Efficacy Safety Cost/Convenience
Vancomycin
+++++
Nausea, vomiting, nephrotoxicity(rare), neutropenia, C. Diff., red man syndrome, Ototoxicity Nausea, vomiting, diarrhea, vision disturbances, headache, body aches, fever, rash Vomiting, diarrhea, edema, numbness, tingling, headache, pneumonia, pain in throat, renal failure
$$$ IV
Linezolid
++++
$$$$ IV PO
Daptomycin
++++
$$$$ IV
Note: Local antibiotic resistance patterns and culture susceptibility results are absolutely critical in tailoring the treatment. This table is a tool in selecting therapy when local resistance data and culture susceptibility are not available.
Care Plan
Drug Product Cefazolin Vancomycin Dosage instructions 1g IV daily 1g every 12 hour, infused over two hours for 10 days Note changes Discontinue Initiate
Monitoring Plan
Effectiveness Parameter Clinical symptoms
Change
Timeframe
Left arm -pain, redness, tenderness, increased swelling Right shoulder pain, tenderness, right axilla pain, and swelling; and swollen lymph nodes
Pain radiating to lower extremities Pain, redness, tenderness, swelling
Shoulder motions
24-48 hours
24-48 hours
Decrease in severity of pain and radiation of pain subsides to the lower extremities Complete resolution
Improve and normal
24-48 hours
10-14 days
Improve within 48 hours and normal within a week
BP/HR/temperature WBC/Neutrophils
Monitoring Plan
Safety Parameter GI symptoms (nausea, diarrhea, vomiting)
Mild skin rash Change Timeframe
None to minimal
None to minimal
24-48 hours
24-48 hours
Muscle pain or tightness Hearing C. Difficile infection (severe diarrhea, abdominal cramp, and fever) SCr Serum trough concentration of vancomycin time dependent
Normal to prevent renal failure Ongoing Therapeutic range At least 10mcg/mL 15mcg/mL 30 mins before 3rd or 4th dose Every 3 days once concentration is therapeutic
Rogers SH, Cavazos JE. Chapter 114 Skin and soft-tissue infections. In: Dipiro JT, Talbert TL, Yee GC, Matzke GR, Wells BG, and Posey ML. Pharmacotherapy: A pathophysiological approach, 7th edition. NY: The McGraw-Hill Companies,. 2008:1807-09
Therapeutic Failure
What to do if vancomycin does not work (improvement within 48 hour of effectiveness parameters) or the patient experiences serious side effects?
Start Cloxacillin or Cephalexin Therapeutic Failure Obtain blood/tissue sample/pus for culture Modify based on the C&S results Daptomycin or Linezolid Start TMP-SMX or Clindamycin
Start Vancomycin
Therapeutic failure
Therapeutic failure
Cellulitis Mild to moderate/uncomplicated Severe /progressive/complicated
Start Cloxacillin or Cephalexin Therapeutic Failure Obtain blood/tissue sample/pus for culture Modify based on the C&S results Start TMP-SMX or Clindamycin
Therapeutic failure
Daptomycin or Linezolid
Therapeutic failure
Drug Product Vancomycin Dose/frequency 1g twice q 12 hour 600 mg q 12 hour 4mg/kg IV Tablet/oral suspension/IV injection IV Dosage form Duration of Therapy* 7-14 days 7-14 days
Linezolid
Daptomycin
7-14 days
Consider either linezolid or daptomycin if vancomycin does not improve symptoms within 2 days or severe side effects occur
Patient Education
Elevation of affected area
Improves draining of edema and inflammatory substances
Patient Education
Adherence to antibiotics in the future
Explain importance of full duration of treatment
Effectiveness and resistance
Summary
Cellulitis is a type of skin and soft tissue infection, affecting epidermis, dermis, and subcutaneous layers CK diagnosed with LUE cellulitis, but lost prescription for cephalexin,
returned 5 days later with progressing cellulitis
given cephalexin
CK took cephalexin as prescribed, but came back to ER again with progressing cellulitis (severe)
admitted for complicated/progressive cellulitis and possible MRSA
given vancomycin
CK also had multiple other drug therapy problems needing to be addressed at a later date
education regarding his conditions and medications CV disease prevention
Start Cloxacillin or Cephalexin Therapeutic Failure Obtain blood/tissue sample/pus for culture Modify based on the C&S results Start TMP-SMX or Clindamycin
Therapeutic failure
Daptomycin or Linezolid
QUESTIONS?