flow pharma edura presentation slide share
Post on 01-Nov-2014
546 Views
Preview:
DESCRIPTION
TRANSCRIPT
Instrumented Spine Surgical Site Infections (SSI)
source: AAOS orthopaedic knowledge online
Contents
• Risk Factors for SSI• Economic impact of SSIs• SSI Isolates• Presentation of SSI• Current methods of prophylaxis• Novel approaches for prophylaxis• The Edura gentamicin advantage
Not statistically significant: age group (p = 0.16 – 0.60); smoking (p = 0.83); PVD (p = 0.17)
Risk FactorsAmy Cizket al. Bone and Joint, 2012.
Retrospective analysis of 1532 pts over 1 yearInclusion: > 18yo, no prior SSI, invasiveness index > 0
Risk FactorsAmy Cizket al. Bone and Joint, 2012.
Retrospective analysis of 1532 pts over 1 yearInclusion: > 18yo, no prior SSI, invasiveness index > 0
Risk Factors Summary
• Primary Impact Factor on SSIs:–Surgical invasiveness
• Secondary Impact Factors on SSIs:–Treating pre-existing disease –Not operating on “high risk” patients
Economic Impact
• About 300,000 US spine fusion surgeries/year1
• SSI rate about 6% overall2
• Cost per SSI about $24,0002
• Total annual spine fusion SSI cost = – 0.06 X 300,000 X $24,000 = $432,000,000
• Spine fusion SSI now an HAC for IPPS hospitals – CMS bulletin May 2012– The hospitals pay
Analysis of SSI isolatesPullter Gunne et al. Spine, 2010.
Retrospective cohort analysis of 3174 pts over 9 years
Culture yields
• Diagnosed SSI: 132 (4.2%)– Deep component: 84
(64%)– Superficial only: 48
(36%)__________________________________________________________________________________________________________________________________________________________
• Culture (+): 83 (63%)• Culture (-): 38 (29%)__________________________________________________________________________________________________________________________________________________________
• Monomicrobial: 63 (77%)• Polymicrobial: 20 (24%)
Isolated organisms*
• Gram(+): 82 (68%)• Gram(-): 27 (22%)__________________________________________________________________________________________________________________________________________________________
• S. aureus: 63 (76%)– MSSA: 54
(86%)– MRSA: 9
(14%)
• E. faecalis: 12 (14%)• E. coli 9 (11%)• K. pneumoniae 6 (7%)
* Percentages calculated as a function of the number of patients with culture growth
Analysis of SSI isolatesPullter Gunne et al. Spine, 2010.
Retrospective cohort analysis of 3174 pts over 9 years
Culture yields
• Diagnosed SSI: 132 (4.2%)– Deep component: 84
(64%)– Superficial only: 48
(36%)__________________________________________________________________________________________________________________________________________________________
• Culture (+): 83 (63%)• Culture (-): 38 (29%)__________________________________________________________________________________________________________________________________________________________
• Monomicrobial: 63 (77%)• Polymicrobial: 20 (24%)
Isolated organisms*
• Gram(+): 82 (68%)• Gram(-): 27 (22%)__________________________________________________________________________________________________________________________________________________________
• S. aureus: 63 (76%)– MSSA: 54
(86%)– MRSA: 9
(14%)
• E. faecalis: 12 (14%)• E. coli 9 (11%)• K. pneumoniae 6 (7%)
* Percentages calculated as a function of the number of patients with culture growth
Presentation of SSI
Median Time to Diagnosis (d)
• Deep SSI: 15 (6 - 730) • Superficial SSI: 18 (5 - 85)
Signs & Symptoms
• ESR ↑ 94.4%• CRP ↑ 98.0%• WBC ↑ 44 - 58%__________________________________________________________________________________________________________________________________________________________
• Drainage 88 (67%)• Pain 36 (27%)• Fever 34 (26%)• Erythema 24 (18%)
Microbial trends
• Gram(-) isolates 4X as frequent in deep vs superficial SSI
Pullter Gunne et al. Spine, 2010. Retrospective cohort analysis of 3174 pts over 9 years
Current methods of prophylaxis
• IV 1st gen cephalosporin– IV vanco non-superior3
• Antiseptic prep – Chlorahex / betadine /
isopropanol
• Ioban dressing
• Laminar flow systems
• Limited room traffic
Discectomy < 1%
Decompression 1.5 – 2%
Fusion 1 – 5%
Instrumentation 3 – 9%
Trauma 8 – 13%
Agency for Healthcare Research and Quality, 2004
Current methods of prophylaxis
• The economic impact of SSI is large• Big spine surgeries are high risk for SSI• Current methods are not effective• The hospitals are paying for SSI care
Novel methods for SSI prophylaxis
Intrawound Application of Vancomycin Powder
Sweet et al. Spine, Nov. 2011. Retrospective cohort study of 1732 consecutive pts over 11 years
Vancomycin Powder – Sweet et al.
• Objective: To examine safety, drug levels, efficacy
• Inclusion: Thoracic / lumbar posterior instrumented fusions
• Control: 2g IV Ancef: 2000 – 2006, (n = 821)
• Tx: 2g vancomycin powder adjunct: 2006 – 2011, (n = 911)
• Average follow-up: 2.5 years (1 – 7 year range)
Vancomycin Powder – Sweet et al.Results – drug levels
• Local drug levels, POD 0 – 3 (n = 178, consecutive)
• Serum drug levels: – Day 1: 20% detection, average level 1.6 µg/mL (range 0.7 – 5.9)– Days 2 – 3: 6% detection, serum levels not reported
– ISDA guideline: Keep trough above 10 µg/mL to avoid resistance 4
– S. aureus in vitro MIC commonly ranges from <0.5 – 2 µg/mL 5
Post op day 0 1 2 3Drug level (µg/mL) 1457 (263-2938) 462 (97-2258) 271 (48-732) 128 (37-311)
Vancomycin Powder – Sweet et al.Results – drug levels
• Local drug levels, POD 0 – 3 (n = 178, consecutive)
• Serum drug levels: – Day 1: 20% detection, average level 1.6 µg/mL (range 0.7 – 5.9)– Days 2 – 3: 6% detection, serum levels not reported
– ISDA guideline: Keep trough above 10 µg/mL to avoid resistance 4
– S. aureus in vitro MIC commonly ranges from <0.5 – 2 µg/mL 5
Post op day 0 1 2 3Drug level (µg/mL) 1457 (263-2938) 462 (97-2258) 271 (48-732) 128 (37-311)
Vancomycin Powder – Sweet et al.Results – infection rate
• Control: 21 infections (2.6%) – 71% Staph spp.
• Treatment: 2 infections (0.2%)– Clostridium septicum, 6 wks post-op, 1 wk s/p diverticulitis– E. coli, 4 weeks post-op, immediately s/p E. coli urosepsis
• Statistical Analysis: Fisher exact test, power analysis– Rates significant, with P < 0.0001, α: 1%, power: 95%
Vancomycin Powder Issues • No coverage of Gram(-) species
• Increased vancomycin resistance – Systemic absorption in 20% of post-op pts (0.7 - 5.9 µg/mL)– Trough level ideally kept >10 µg/mL to avoid resistance 4
• “MIC creep” in S. aureus spp. 9
– 17% increase in MIC from 2001 – 2009 in one institution 10
• Unpublished case reports:– Vancomycin powder coagulating around nerve roots – Localized red man syndrome c/ skin exfoliation
Novel methods for SSI prophylaxis
Edura Gentamicin Microspheres
Stall et al. Spine, 2009. Animal study (rabbit spinal implant model)Proof of concept, pharmacokinetic profile
Gentamicin Microspheres – Stall et al.• Biodegradable PLGA gentamicin
microspheres
• Rabbit model of spinal fusion6
• 3 sites per rabbit– 1 control, 2 treatment– 106 CFU S. aureus inocculation– All animals given IM ceftriaxone
• Exploration on POD 7
• Endpoint: S. aureus present on
implanted rod and 1 other local
tissue sample
Hematoma Pharmacokinetic profile5
*Edura = gentamicin microspheres
*
Results – Stall et al.One Million CFU S. aureus inocculation
20mg/Kg Ceftriaxone pre-Rx
50% infection suppression in animal model
Vancomycin Powder
• Efficacy Profile– Significant benefit in preventing instrumented spine SSIs– No gram negative coverage
• 2/3 of spine SSIs are deep– Deep infections are 4x more likely to be gram negative
• Safety Profile– Very high dose to obtain duration of action– Systemic absorption demonstrated– Local toxicity reported– Worsening drug resistance reported
Vancomycin Powder
• Opportunity– Address Safety and Efficacy issues• Need gram positive and gram negative coverage• Need long duration of action without high dosing• Need to minimize systemic absorption• Need to minimize local toxicity• Need to reduce concerns RE creating resistance
Edura Gentamicin Advantage
• Gram(-) and gram(+) including MRSA10
• Longer duration above MIC7
• No systemic absorption8
• Dampened peak levels reducing toxicity7
• Eliminates vancomycin resistance concern
Edura Gentamicin AdvantageMultiple Issued US
Patents
• 8,138,157• 7,293,559• 7,059,319• 6,792,940• 6,595,202• 6,554,202• 6,386,463
• 6,357,670• 6,241,159• 6,196,525• 6,174,469• 6,119,953• 6,116,516
Edura Gentamicin Advantage
Edura Gentamicin Advantage
Blocking Method Patent Issued
References1. J Neurosurg Spine 2011 Jun;14(6):771-82. http://www.cms.gov/HospitalAcqCond3. J Thorac Cardiovasc Surg. 2002 Feb;123(2):326-32.4. Clinical Infectious Diseases 2009; 49:325–75. Clin Biochem Rev. 2010 Feb;31(1):21-4.6. Spine. 2000 Feb;25(4):406-10.7. Poelstra et al. 53rd ORS Meeting; Feb10–14, 20078. Spine. 2009 Sept;34(5):479-83.9. Surg Infect. 2011 Jun;12(3):191-203.10. J Microbiol Immunol Infect. 2012 May 7.11. Clin Infect Dis. 2008 Jun 1;46(11):1637-46.
top related