Vancomycin mixed with calcium sulphate beads provide a 2-3 week sustained local high antibiotic release elution profile which may impede the formation of a recurrent calpular contracture in conjunction with capsulotomy open and or capsulectomy as well as implant change.

1. Vancomycin Calcium Sulphate Beads in the Prevention of
Recurrent Capsular Contracture of The Breast - A Pilot Study
Olivia Jackson B. Sc., U C Davis & Rex Moulton-Barrett, MD, FACS
Plastic & Reconstructive Surgery, Alameda, California

2. Are the previous concepts on
prevention, causation & treatment
of capsular contractures:
evidence based or ‘ medical fashion ’ ?

3. U.S. Breast Implantation Statistics 2016U.S. Breast Implantation Statistics 2016
ASPS 2016 Plastic Surgery StatisticsASPS 2016 Plastic Surgery Statistics
• 290,567 Augmentations: no. 1 cosmetic surgery290,567 Augmentations: no. 1 cosmetic surgery
• 89,000/109,256 (89,000/109,256 ( 81%81% ) Breast Reconstructions) Breast Reconstructions
• 2011-20162011-2016 rate increaserate increase by +/-by +/- 3% / yr3% / yr
• 28,467 (28,467 ( 10%10% ) Augmentation) Augmentation implantsimplants removedremoved

4. Relevance of Capsular ContractureRelevance of Capsular Contracture
After Breast AugmentationAfter Breast Augmentation
• The most common complication & reason for removal / reoperation
• >10 x more common than explantation for acute infection / extrusion
• Incidence after Breast Augmentation 3-29%: >= to Grade III +/-r II
• Headon, Kasem & Mokbel, 2015: ‘Overall incidence’ 10.6%

5. Definition of Capsular ContractureDefinition of Capsular Contracture
Baker Classification, 1976: Breast Augmentation
I- Natural
II- Minimal: palpable firmness noticed by surgeon only
III- Moderate: Firmness noticed by patient
IV- Severe: Obvious distortion of breast shape
Spear and Baker, 1995: Prosthetic Breast Reconstruction
Ia- Natural
Ib- soft detectable by physical examination only
II- mildly firm by examination, may be visibly detectable
III- moderately firm, readily detectable visually, may be acceptable
IV- severe, symptomatic, unacceptable esthetically, needs surgery

6. 1. Older patient vrs young
2. Smooth vrs textured
3. Silicone elastomer vrs polyurethane shell
4. Subglandular vrs submuscular
5. Silicone vrs saline
6. Previous XRT vrs no XRT
7. Implantation < 6 -12 months after pregnancy / breast feeding
8. Incision: transglandular: mastopexy>periareola>= transaxillary
vrs inframammary incision
9. Touch technique vrs no touch technique +/- nipple shields
10. Talc / Lap packing vrs talc-free gloves & no packing
11. No irrigation triple antibiotic +/- betadine 5-10%
12. Delayed replacement: deflated saline / ruptured silicone implant
13. Blood / hematoma in pocket vrs dry pocket dissection +/ -drain
14. No IV antibiotics vrs IV Vancomycin & Ancef +/-orals
Clinical Factors Associated With Capsular
Contractures after Primary Augmentation
( no randomized, controlled, blinded studies to date )

7. 1. The Same Factors as for Primary Augmentation
2. Replacement of implant in the same pocket vrs neo-pocket
3. Neo-pocket adjacent vrs change to trans-pectoral :
sub-muscular  sub-glandular
4. Capsulotomy vrs sub total / total capsulectomy
5. No prolonged vrs prolonged oral antibiotics
6. No ADM vrs ADM grafting
7. Replace with same implant vrs new implant
8. No steroid injection vrs injection into the capsular bed
9. No BoTox injection vrs injection into the capsular bed
10. No fat grafting vrs peri-capsular fat grafting & capsulotomy
11. Prior reconstructive implantation vrs esthetic augmentation
Clinical Factors Associated With
Recurrent Capsular Contractures
( no randomized, controlled, blinded studies to date )

8. Incidence of Recurrent Capsular Contracture (CC)Incidence of Recurrent Capsular Contracture (CC)
Wan & Rohrich, 2016 PRS: 137:826-841Wan & Rohrich, 2016 PRS: 137:826-841..
Incidence of recurrent CC %
•24/461 articles up to 4/2015: 0-54%
•Capsulotomy vrs Capsulectomy conflicting data
•Partial vrs total Capsulectomy conflicting data
•
•Site change Neo +/- Trans Muscle 0-12 % vrs no site change: 0-54%
•
•Implant Exchange 0-26% vrs same implant 33-54%
vrs No ADM
•6 articles using ADM 0-2.6% +site change 3/6: 50%
0% + no site change 1/6: 16%

9. 1. Early massage and superior compression
2. Closed capsulotomy- Dan Baker 1975: 75% resolution at 2 yrs
3. Ultrasound / Aspen – randomized clinical study 2017-2018
4. Low Dose Laser – randomized study: conclusions not helpful
5. Medication:
• Accolate – Zafirlukast: leukotrine receptor antagonist: check LFT’s
• Singulair – Montelukast: minimal results at most
• Tamoxifen – Myofibroblast: Block Er - receptors⍺
⚠︎
Post Operative Factors: Prevention & / 0r
Treatment of Capsular Contractures

10. Peri-Prosthetic Inflammation
•Fibroblast ‘transient immortalization’– loss p53 senescence
•Macrophages
•TGF- β
•Myofibroblasts: estrogen receptors ( Er - , 1/⍺ )β
stimulated by mechanical stress / tension
•Fibroblast collagen parallel layering – texturing reduces
Bacterial Colonization
•Bacterial Colonization – also without capsular contracture
•Bacterial Biofilms - also without capsular contracture
Multifactorial Pathophysiological
Causes of Capsular Contractures

11. • Implant Colonization with bacteria:
Staphylococcus epidermidis 56%with CC vrs 18% with no CC
Virden, et al, 1992. Aesthetic Plast Surg 16:173-179
• Endogenous Bacterial Flora Cultured from Breast Tissue:
■ Benign: not the same as skin flora & also different from malignancy
(Bacillus>Acinetobacter,>Enterbacteriaeae>Pseudomonas,>Staphlococcus>Proprionibact)
■ Malignant: Fusobacterium, Atopbium,Gluconacterobacter, Hydrogenophaga
Lactobacillus
■ Early Acute Infection: Staphloccus aureus, streptococcus, gram-negatives
■ Late infection: Coagulase negative staph., Propionibacterium spp.
• Biofilm Producing bacteria from the capsule
Propionbacterium acnes
Staphylococcus epidermidis: 80% oxacillin resistant
• Bacteria cultured from textured implants associated with ALCL
Ralstonia spp: in the water reservoirs
Capsular Contracture and Bacterial Colonization

12. • 65 - 80% of human infections associated with biofilms
• 5 stages of a Biofilm
• Composition of Biofilms < = 97% water
2% microbial cells
2% Extracel Polymeric Substances ie protein enzymes
1-2% Polysaccharides –adhesion + immune barrier
1-2% DNA / RNA
Calcium Sulphate Beads with
Vancomycin
planktonic eradicate
• MRSA and Staph epidermidis biofilm formation prevention
mature biofilm may reduce
• Biofilm of IV Staph Aureus requires a 4 X increase in antibiotic MIC (50)
• Rough surfaces and or foreign bodies are more susceptible to biofilms
• Nutrient / O2 / waste dormancy =↓ ↓ ↑ → reduced antibiotic susceptibility
Relevance of Biofilms in Medicine

13. PMMA filler / beads: do not dissolve & beads need to be removed
• high levels of antibiotics 2-3 days surface area diffusion∝
• prolonged release below MIC may support biofilms
Bioceramic Beads: dissolve and beads do not need to be removed
• Calcium Phosphate: Monocalcium: mono or anhydrous
Dibasic calcium: anhydrous, hemihydrous
Tricalcium: simple, and⍺ β
Hydroxyapatite: & calcium deficient
Biphasic Tricalcium
Tetracalcium
Octacalcium
• Calcium Sulphate Anhydrous = anhydrate
Dehydrate = gypsum = Plaster of Paris
Hemihydrate: and⍺ β
Antibiotic Beads in Medicine

14. Calcium Sulphate: • used since 1892, initially used as a bone graft
• gypsum: impure, acidic, inflammatory
( self limiting synovitis and post-op drainage )
• hemihydrate with water exothermic reaction
• hemihydrate dissolves in 3-6 weeks soft tissue
• Medical Grade alpha hemi-hydrate 1997:
■ Prevention & treatment osteomyelitis
■ Preventive & treatment of infection in joint replacement
■ Treatment of prosthetic vascular graft infections
■ Deep diabetic foot infections
■ Deep neck infections adjacent to the carotid artery
Calcium Phosphate: • longer resorption time 1 / water solubility⍺
• resorption may be 6 months to 10 years
• can be made into a strong cement
Polyphasic Ceramics: • + Potassium Sulphate short & longer release
Use of Antibiotic Bioceramics in Medicine

15. Commercially Available Antibiotic Beads Kits
of Calcium Sulphate Hemi- Hydrate∝
3mm 4.8mm
OsteoSet ( Wright Medical ) Gypsum derived: less hydrophilic
510(k) 2001: bone void filler 2 size beads 3, 4.8mm
No 510(k) for + antibiotics 5ml rapid 5 min and 20 minute cure
$1,100
Stimulan ( Biocomposites ) synthetic: hydrophilic mix
510(k) 2015: bone void filler 3 size beads 3, 4.8, 6mm
No 510(k) for + antibiotics 5ml rapid 4 min and 12ml 8 min cures
$1,000

16. 1. 12mls of OsteoSet powder to bowl from kit
1.Add 500mg Vancomycin powder to the bowl
2. Add diluent from small bottle in kit, makes 5mls in total
3.Alow to sit for 1 minute without touching
4.Mix thoroughly with plastic spatula in kit for 45 seconds into paste
5.Press paste into the mold 3mm smaller side: makes 200 x 3mm beads
6.Fast Cure allow to sit 3-5 minutes ( regular kit = 15-20 minutes )
7.Flex mold to remove beads
How to Make Vancomycin OsteoSet Fast Cure 3mm Beads

17. • Severe vascular or neurological disease
• Uncontrolled diabetes
• Severe degenerative bone disease
• Pregnancy
• Hypercalcemia
• Renal compromised patients
• Patients with a history of or active Pott’s disease
• Where intra-operative soft tissue coverage is not planned or possible
Contraindications for the use of OsteoSet Beads

18. • Hypercalcaemia: 2 case reports
Kaliiala & Hadda, 2015: 15 pts s/p revision hip / knee surgery
all 15 peri-prosthetic infections
Stimulan 10mls + 1g vancomycin
+ 240mg gentamicin
‘radiological absorption’: 21-45 days
3/15 developed transient hypercalcemia
maximum POD#5: 1/3 was symptomatic
Carlson, et al, 2015: single case report
hip replacement infection
Osteoset beads – unspecified amount
+ 2g Vancomycin, 3.6 g Tobramycin
POD#6: 14.7 mg/dl max
Returned to normal POD# 8
Potential Complications Related To Calcium Sulphate Beads

19. • Increased Volume and Duration of Drainage: acidic elution
Stimulan purported 0-3.2% drainage rates ( > 30mls beads )
Osteoset purported* 23-50% drainage rates
* unsubstantiated competitor data
• Heterotopic Ossification: no reported cases for soft tissue
1-2%: avascular bed ( > 33mls beads )
Potential Complications Related To Calcium Sulphate Beads

20. Elution Profile of Calcium Sulphate / Vancomycin Beads
Aiken et al, 2015: 900 mg Vancomycin bead immersed in 4ml saline
3mm Stimulan Beads
Peak conc. 13.5 mg/L at 48 hrs
42 days later : 0.67 mg/L
6mm Stimulan Beads
Peak conc. 10.4 mg/L at 48 hrs
42 days later : 0.59 mg/L
MIC 90: planktonic MRSA is 1mg/L Vancomycin∝
MIC90+: biofilm MRSA:15mg/L but only if + rifampicin or tigecycline

21. Albright, et al, 2016: • Pilot Study, Retrospective
n=14 • Debridement of infected pocket +IV antibiotics
• PMMAplates/beads:2g Vancomycin+1.2gTobramycin
• Immediate Expander placed + drain
• Exchange for implant & removal plates / beads
• No reoperations for capsular contractures
• Mean follow-up 8.2 months
Sherif, et al, 2017: • Infected implant removed, partial capsulectomy
n=12 • 6/12 culture +: Staph epidermidis, Staph aureus
Enterobacter, yeast & Rhodococcus
• Stimulan + 1g Vancomycin, 1.2g Tobramycin
• Immediate new implant or expander replaced
• 75%,n=9 patients successful ‘salvage’ of implant
Off label Use of Antibiotic Beads in Breast Surgery
2016-2018

22. Kenna, et al, 2018: • Preventive Study to Reduce Expander Infection
• 3 years: 127 submuscular breast reconstructions
n=68 • Retrospective, non randomized, 68 / 127 + beads
• 5ml Stimulan beads + 500mg vancomycin
+ 240mg gentamicin
• all patients with Alloderm : IMF to Pect Major
• drains kept up to 4 weeks
• infections: + Beads: Pseudomonas (1)
No Beads: Pseudomonas (3), Staph epi (3), Escherichia coli (1)
• infections 1.5% +beads group vrs 11.9 %
• now using beads for all implant exchanges
• no mention of capsular contractures at all
Off label Use of Antibiotic Beads in Breast Surgery
2016-2018

23. Can peri & intra - capsular placement of 5mls of OsteoSet
3mm Beads + 500mg Vancomycin prevent recurrent
capsular contracture ?
In conjunction with:
• IV antibiotics and 10 days of post-operative oral antibiotics
• Capsulectomy, partial capulectomy & or open capsulotomy
• Early superior compression and breast massage
• In office closed capsulotomy if indicated: Baker Grade II-III
Purpose of Current Pilot Study

24. • Pearl IRB re Study No. 17-RMB-101: ‘IRB Exempt’ 10/18/17
• Retrospective case review: chart and structured interview
• n = 14 implants & 10 patients
• Original Implantation: esthetic augmentation or reconstruction
• Indications for surgery: capsular contracture Baker III-IV
• Same surgeon and one post graduate student
• Follow-up to > 6 years: 2011-2018
Methods: Pilot Study CC with Antibiotic Beads

25. Methods: Pilot Study CC with Antibiotic BeadsMethods: Pilot Study CC with Antibiotic Beads
Data collected included:Data collected included:
Prior Procedure(s)Prior Procedure(s) Current SurgeryCurrent Surgery
• age, gravida, para
• date of last breast feeding
• esthetic or reconstructive
• surgical details: incisions, pocket
• numbers of surgery since then
• complications associated
• pre and final post op grade capsule
• date of surgery, follow up dates
• implants, incisions, drains / duration
• surgical details: capsulectomy/otomy
• use of simultaneous ADM
• complications of surgery

26. • + Retrospective review 50 primary augmentations ( 25 patients )
• document post-operative Baker grade
duration of follow-up
implant texture and silicone vrs saline
incision(s) used
• + Retrospective review 17 CC surgeries without antibiotic beads
• document Baker grade before vrs after surgery
Methods: Additional Information

27. • Surgery: outpatient
• IV Ancef was given within 30 minutes prior to surgery + 10 days po Keflex
• Incisions preexisting or new: inframammary, mastectomy, periareola,
mastopexy
• Explantation followed by capsulotomy, partial / complete capsulectomy
• Pocket irrigations 5% betadine then triple: Vanco/Bacitracin/Gentamicin
• Osteoset 5ml rapid 3mm beads 500mg vancomycin in peri-capsule / pocket
• All pts received new implants and no lap packing in the pocket
• All cases s/p capsulectomy were drained with a 7-10mm Jackson Pratt
• No: transposition of the pocket to opposite side of pectoralis
implant funnels , no-touch technique, nipple guards were utilized
Methods: Operative Details

28. Frequency Capsular Contracture after Primary Augmentation
n = 50 implants (25 patients)
14 Silicone: 4 Smooth & 10 Textured
36 Saline: 36 Smooth & 0 Textured
Incision:
50 Superior peri-areola
Final Grade: (48) I-II, (2) III, (0) IV
Mean follow-up: 10.2 months
CC rate (III-IV): 4%
Results: Primary Augmentations

29. n = 14 implants (10 patients)
Ages: (36-69) mean = 53
Para: (0-4) mean = 2.3
Prior Surgery
Indication for first surgery: 9 esthetic, 5 reconstruction
Prior XRT: 1/14
14 Implant used: 8 saline of which 5 textured, 6 silicone of which 4 textured
Incision: 1 mastectomy, 0 anchor, 4 transaxillary, 4 periareola, 5 inframammary
Number of previous surgeries for CC: 0-24, most common 0 (7/14)
Baker Grade: 7 III, 7 IV
Months from last surgery to current surgery: 4-396
Current Surgery
Capsular work done: 5 open capsulotomy, 5 partial, 4 total capsulectomy
Implants: 4 saline of which all 4 textured, 10 silicone of which 8 textured
Drain & Duration in days: 14/14, (5-34) mean = 16
Incision: 1 mastectomy, 3 anchor, 0 transaxillary, 5 periareola, 5 inframammary
Use of ADM- Alloderm: 1/14
Follow-up duration in months : (4-75) mean = 20.5 months
Final Grade: (10) I-II, (1) III, (3) IV
Complications: none
Results: Antibiotic Beads Pilot Study Prior + Current Surgical Details

30. Case example: 62 yr lady 33 yr after silicone augmentation Mexico
10/16 1/17 2/18
• Infra-mammary incision
• Bilateral total capsulectomy + 7mm JP
• 500mg Vancomycin in 200 3mm beads of 5mls OsteoSet
• implant replacement using Natrelle Inspira TRF 450

31. Implants Grade
+ Bead therapy _______ (I) ________ (II)______ _(III-IV)____
Prior to Surgery (n=14) 0 0 14
Bead Therapy (n=14 ) 10 0 4
71% improvement with surgery + beads
Implants
No Bead therapy _______ (I) ________ (II)_________(III-IV)____
Prior to Surgery (n=17) 0 0 17
After Surgery (n=17) 3 8 6
64% improvement with surgery + no beads
Surgery & Beads versus no Bead Therapy Fisher’s Exact one tailed Test (p= 0.497)
Results: Statistical Evaluation of Success of Antibiotic Bead Therapy

32. Summary Of ResultsSummary Of Results
• A Pilot Study was performed to determine the efficacy
of OsteoSet & Vancomycin Beads with replacement
of implant + capsulotomy / capsulectomy to prevent
recurrent capsular contracture
• While 71% showed an improvement with the use of the
beads so did 64% without using beads
• There was a 4% Grade III-IV capsular contracture rate
for primary breast augmentation

33. 1. The current results did not reach statistical significance, n= low sample size
• unable to show a difference between surgery with antibiotic beads vrs no beads
2. The surgical techniques used are in keeping with other current standards based on
a 4% rate of capsular contracture after primary augmentation
3. Symptomatic hypercalcemia has been reported with 10mls of Ca Sulphate beads
4. The inflammatory reaction to a biofilm may be individual including
the susceptibility of the biofilm to local immunity and antibiotic therapy
5. The 29% failure rate of surgery with Vancomycin beads may be a reflection of the
inadequate dosage of Vancomycin +/- need for an additional anti-staphlococcal agent
for biofilm producing bacteria, such as rifampicin ?
6. The results support further work, (n) & a prospective, randomized study↑
Conclusions

34. “Rejoice while we are young”