Gentamicin collagen fleeces (Collatamp/Garacol®)

A.F.J. De Bruin

Abdominalperineal resection (APR).

•Ernest Miles 1908

•Perineal infection up to 70%

Wound infection after APR + RTX

Author Journal APR APR + Rtx

p-value

Marijnen et al J Clin Oncol 2002

18% 29% 0.008

Vallero et al. Int J Colorectal Dis 2003

26% 45% -

Bullard et al. Dis Colon Rectum 2005

23% 47% 0.005

Preoperative radiotherapy multiplies perineal morbidity !

Local gentamicin reduces perineal wound infection after radiotherapy and

abdominoperineal resection

De Bruin AFJ et al. Tech Coloproctol 2008 Dec

Patients underwent complete closure of the pelvic peritoneal floor, sacral drainage and multiple layer wound closure with or

without Garacol®

40 patients undergoing abdominoperineal resection for rectal cancer after

short-course radiotherapy

postoperative deep wound infection or abscess

•Superficial perineal wound complications occurred in 11% of the Collatamp® group and 29% of the control group (p=0.15)

•Only 5% of patients developed a deep wound infection or abscess in Collatamp® group compared with 29% of patients in control group (p=0.05)

0

10

20

30 29%

5%

p=0.05

Control Collatamp®

De Bruin AFJ et al. Tech Coloproctol 2008 Dec.

Pati

ents

wit

h p

ost

opera

tive d

eep

woun

d in

fect

ion o

r ab

scess

(%

)

Gentamicin collagen fleeces• Aminoglycoside: Strong bactericide • Gram negative: Pseudomonas, Entrobacter, Klebsiella• Gram positive: Staphylococci

• NO effect on osteoblasts

• Gentamicin fleeces (Collatamp®=Garacol®): – Collagen impregnated with Gentamicin– Concentration exsudaat stays high during short period and diminish

fast.– Re-absorbable– Measurements; 5x5 cm(32,gmg) or 10x10cm(130mg) – No biofilm formation

Collagen fleeces

Initiation of haemostasis by tissue factor receptors in renatured collagen

Thrombin

Binding of the platelet collagen receptor to

collagen leads to activation of platelets

Activation of surface glycoprotein

Aggregation of platelets

Polymerised fibrin fibres(clot)

Fibrinolysis: thrombin cleaves fibrinogen allowing fibrin

polymerisation

Hakim NS & Canelo R. (2007) Haemostasis in Surgery. Imperial College Press; Stemberger A et al. Eur J Surg 1997;Suppl 578:17–26

Microbial resistence

3. Stemberger A. Eur J Surg Suppl 1997;578:17-26.

High local concentrations of gentamicin

Adapted from Ruszczak Z & Friess W. Adv Drug Deliv Rev 2003;55:1679–1698

Day

Minimum inhibition concentration (MIC)

After implantation of 3 units (total gentamicin sulphate dose

600 mg) into a postoperative abdominal wound

0

2000

Genta

mic

in t

issu

e

conce

ntr

ati

on (

mg

/L)

1 2 3 4 5 6 7

Low serum levels of gentamicin

2

1 2 3 4 5 6 7

Minimum inhibition concentration (MIC)4

Genta

mic

in s

eru

m

conce

ntr

ati

on (

µg/m

L)

Adapted from Ruszczak Z & Friess W. Adv Drug Deliv Rev 2003;55:1679–1698

Day

After implantation of 3 units (total gentamicin sulphate dose

600 mg) into a postoperative abdominal wound

0

Microscopy collagen matrix pictures

Gentafleece Collatamp

x200 x200

Collatamp’s Collagen Matrix Carrier has a highly

cross-linked Fine-Fibril-Matrix compared to Gentafleece

Diptest data – impact of soaking

0

20

40

60

80

100

120

0 50 100 150 200 250 300 350 400

Immersion time (min)

Gen

tam

icin

Co

nte

nt

Lo

st (

%)

Andrew M Lovering, Julie Sunderland; Antimicrobial Reference Laboratory, North Bristol NHS Trust, Bristol, BS10 5NB, United Kingdom

Collatamp® and gastrointestinal (GI) surgery

•Prevention of wound infection in elective colorectal surgery by local application of a gentamicin-containing collagen implant

•Rutten HJ & Nijhuis PH. Eur J Surg Suppl 1997;578:31–35

221 patients undergoing elective colorectal surgery

Systemic antibiotic cover with (n=107) or without (n=114) the use of Collatamp®

Clinically proven efficacy of Collatamp® in GI surgery

•3-fold decrease in wound infection rates; (p<0.01)

•Significantly shorter hospital stay (13.8 days vs 16.3 days; p=0.015)

•No adverse events related to Collatamp®

18.4%

5.6%

p<0.01

0

10

20

30

Systemic antibiotics

only

Collatamp® + systemic antibiotics

Pati

ents

wit

h p

ost

opera

tive

woun

d in

fect

ion (

%)

Rutten HJ & Nijhuis PH. Eur J Surg Suppl 1997;578:31–35

Gentamicin collagen Fleeces and gastrointestinal (GI) surgery

• Improvement of perineal wound healing by local administration of gentamicin-impregnated collagen fleeces after abdominoperinealexcision

of rectal cancer

• Gruessner and Clemens, et al. The American Journal of Surgery 2001

97 patients undergoing elective abdominal perineal resection

Systemic antibiotic cover with (n=49) or without (n=48) the use of Collatamp®

•Eradication of enterobacteria, staphylococci and Pseudomonas aeruginosa in 84% of Genta patients versus 60% controls (P 0.013).

•4% Deep wound infection treatment group versus 10% control group

25%

12 %

P=0.01

0

10

20

30

Systemic antibiotics

only

Collatamp® + systemic antibiotics

Pati

ents

wit

h p

ost

opera

tive

peri

neal w

oun

d infe

ctio

n (

%)

Gruessner, et al. 2001

Postoperative perineal wound infection

Collatamp vs PMMA Chains

local concentrations of gentamicin in the wound (mg/L)

Adapted from Swieringa, et al..(2008)Acta Orthopaedica,79:5,637 —642

MIC for resistent pathogens (300 mg/L)

MIC for sensitive pathogens(4 mg/L)

PMMA Chains

small PMMA Chains

Time

Gen

tam

icin

tiss

ue

conc

entr

ation

(mg/

L)

Collatamp®

Biomaterial-associated infection of gentamicin-loaded PMMA beads in

orthopaedic revision surgery

• 20 patients with prosthesis-related infections

• Gentamicin loaded beads in two-stage orthopaedic revision surgery

Daniëlle Neuta,b, Hilbrand van de Belta et al. Journal of Antimicrobial Chemotherapy (2001)

Gentamicin loaded beads

Cocci

• Presence of bacteria on gentamicin loaded beads in 18 of the 20 patients

• 12 of these 18 patients considered free of infection

• 9 cultures MIC >256mg/l

COMPARATIVE EVALUATION OF RESULTS AFTER LOCAL ANTIBIOTIC THERAPY WITH GENTAMYCIN IN FORM OF

BEADS AND FLEECE

D. Bettin et al. J Bone Joint Surg Br 2009

Chronic osteomyelitis

108 patients undergoing debridement and local application of gentamicin

Prospective serie:54 patients PMMA beads group and 54 patient in GCCI group

revision operations

• Local wound healing criteria p=0.34

0

50

100

20 %

67%

p=0.0001

GCCI PMMA beads

D. Bettin et al. J Bone Joint Surg Br 2009

Rev

isio

n o

pera

tions

(%)

Local antibiotic administration in osteomyelitis treatment--a comparative study with two different

carrier substances

Letsch et al. Actualle traumatol 1993

osteomyelitis of long bones

20 patients undergoing debridement and local application of gentamicin

Prospective serie:10 patients PMMA beads group and 10 patient in GCCI group

complete resolution of osteomyelitis

The number of re-operations was significantly group I 1.1 vs 1.9

• Release characteristics: – Group I: Local levels of 1400 mg/l at 6

hours post-insertion & non-therapeutic levels in plasma

– Group II: Local levels of 100 mg/l at 3 hrs post-insertion.

0

50

100

90 % 80%

GCCI PMMA beads

Letsch et al. Actualle traumatol 1993

com

plet

e re

solu

tion

of o

steo

mye

litis

(%)

Evaluation of the impact of COLLATAMP on the incidence of post-operative sternal wound infections

Friberg et al, Ann Thorac Surg 2005

Prospective, randomised, double blind trial (recruited 2000-02)

1950 patients analysed (73% CABG, 14% valves)

Primary outcome: all sternal wound infections occurring within 2 months of surgery

Friberg O et al. Ann Thorac Surg 2005;79:153-161

Cardiothoracic surgery

Sternal wound infections at 2 months

• Re-operation rate for infection(p=0.021):– 3,9% control– 2,1 % GCCI(gentamicin

collagen fleeces

Friberg O et al. Ann Thorac Surg 2005;79:153-161.

9

4,3

0

2

4

6

8

10

Systemic antibiotics (n=967) COLLATAMP G + systemicantibiotics (n=983)

Infec

tion

rate

(%)

p<0.001

Collatamp® and orthopaedic surgery

Therapy with gentamicin-PMMA beads, gentamicin-collagen sponge,and cefazolin for experimental osteomyelitis due to Staphylococcus aureus in

rats

V. Mendel et al. Arch Orthop Trauma Surg (2005)

Rat model for Staphylococcus aureus-induced osteomyelitis150 rats radiographic confirmed osteomyelitis undergoing debridement and

randomization in to four groups.

Gentamicin; PMMA chains versus Collagen(Collatamp®)

• Goups: – No treatment

– Cefazoline

– Gentamicine PMMA chains + Cefazoline

– Gentamicin collagen fleeces + Cefazoline

Mendel et al. Arch Orthop Trauma Surg 2005

Results after four weeks

• All rats in treatment groups stage 1 infection

• All rats in control group stage 3 en 4

• Bacteriën – Control group: 106 CFU/g– Cefalozine: 104 CFU/g– Gentamicin PMMA102 CFU/g– Gentamicin collagen in 81% no bacteria

Mendel et al. Arch Orthop Trauma Surg 2005

Collatamp® and Pilonidal sinus

•A prospective randomised study comparing two treatment modalities for chronic pilonidal sinus with a 5-year follow-up

•Milind M. Rao &Wojtek Zawislak; Int J Colorectal Dis 2009

60 patients undergoing excision and primary suture of pilonidal sinus

Surgical procedure with (n=30) or without (n=30) the use of Collatamp®

Pain scores

patients healed after 4 weeks

•Mean time to wound healing - Group I: 10 days vs Group II: 50 days (p<0.001)

•LOS: There was no difference seen between the two groups in length of hospital stay

•No difference long-term recurrence rate

p<0.001

13%

90%

0

10

20

30

40

50

60

70

80

90

100

No antibiotics

Pri

mary

healin

g r

ate

(%

)

Collatamp®

Milind M. Rao &Wojtek Zawislak; Int J Colorectal Dis 2009

Turkey the place to be for a hairy ass

20%5%

Results

Treatment of groin wound graft infections

3434

• 10 months prospective follow up (range 6-15 months) of 14 cases of graft infection following vascular reconstruction

1 COLLATAMP® implant• Results:

• 13/14 (93%) healed, 1 case failed: required multiple re-operations

• Bacteriology:• 6 Staph aureus• 2 Pseudomonas aeruginosa• 1 non-haemolytic Streptococcus (not sensitive to

gentamicin)• 5 sterile cultures

2. Jørgensen LG et al. Eur J Vasc Surg 1991;5:87-91.

Vascular surgeryJorgensen et al Eur J Vasc Surg 5 1991

Jorgensen et al Eur J Vasc Surg 5 1991

Vaatstudie MUMC/ Atrium• ‘PREVENTION OF SURGICAL SITE INFECTION AT THE GROIN AFTER

FEMORAL• ARTERIAL EXPOSURE USING LOCAL GENTAMYCIN SPONGE• PROSPECTIVE, RANDOMISED, CONTROLLED TRIAL’

• drs. B.J. Telgenkamp (projectleider) Atrium• dr. J.W. Daemen (begeleider) MUMC• drs. A.G. Krasznai (begeleider) Atrium• dr. P. Boelens MUMC

Cost – benefit • Cost 10 cm x 10 cm = 90 €• Adverse impact of SSI

Median LOS without SSI (days)

Extra LOS with SSI*(days)

Extra costs due to SSI (€)

Limb amputation 13.2 21.0 6940

ORLBF 9.6 9.9 3270

Hip prothesis 11.1 11.5 3780

Knee prosthesis 10.3 10.9 3601

*Adjusted by age, sex, preoperative stay, ASA score, wound class, duration operation, multiple procedures, emergency, trauma

Coello et al. J Hosp Infect 2005;60:93-103