Transcript Gentamicin collagen fleeces

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
40 patients undergoing abdominoperineal resection for
rectal cancer after
short-course radiotherapy
Patients underwent complete closure of the pelvic peritoneal floor,
sacral drainage and multiple layer wound closure with or
without Garacol®
postoperative deep
wound infection or abscess
p=0.05
Patients with postoperative deep
wound infection or abscess (%)
30
•Superficial perineal wound
complications occurred in 11% of the
Collatamp® group and 29% of the
control group (p=0.15)
29%
20
•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)
10
5%
0
Control
Collatamp®
De Bruin AFJ et al. Tech Coloproctol 2008 Dec.
Gentamicin collagen fleeces
• Aminoglycoside:
• Gram negative:
• Gram positive:
Strong bactericide
Pseudomonas, Entrobacter, Klebsiella
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
Fibrinolysis: thrombin cleaves
fibrinogen allowing fibrin
polymerisation
Polymerised fibrin fibres
(clot)
Thrombin
Binding of the platelet
collagen receptor to
collagen leads to
activation of platelets
Activation of surface glycoprotein
Aggregation of platelets
Initiation of haemostasis by tissue factor
receptors in renatured collagen
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
Gentamicin tissue
concentration (mg/L)
2000
After implantation of 3 units
(total gentamicin sulphate dose
600 mg) into a postoperative
abdominal wound
Minimum inhibition concentration (MIC)
0
1
2
3
Day
4
5
6
7
Adapted from Ruszczak Z & Friess W. Adv Drug Deliv Rev 2003;55:1679–1698
Low serum levels of gentamicin
Gentamicin serum
concentration (µg/mL)
4
Minimum inhibition concentration (MIC)
After implantation of 3 units
(total gentamicin sulphate dose
600 mg) into a postoperative
abdominal wound
2
0
1
2
3
Day
4
5
6
7
Adapted from Ruszczak Z & Friess W. Adv Drug Deliv Rev 2003;55:1679–1698
Microscopy collagen matrix pictures
Collatamp
Gentafleece
x200
Collatamp’s Collagen Matrix Carrier has a highly
cross-linked Fine-Fibril-Matrix compared to Gentafleece
x200
Diptest data – impact of soaking
Gentamicin Content Lost (%)
120
100
80
60
40
20
0
0
50
100
150
200
250
300
Immersion time (min)
Andrew M Lovering, Julie Sunderland; Antimicrobial Reference Laboratory,
North Bristol NHS Trust, Bristol, BS10 5NB, United Kingdom
350
400
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
Patients with postoperative
wound infection (%)
30
20
•3-fold decrease in wound
infection rates; (p<0.01)
p<0.01
•Significantly shorter hospital
stay
(13.8 days vs
16.3 days; p=0.015)
18.4%
10
5.6%
•No adverse events related to
Collatamp®
0
Systemic
antibiotics
only
Collatamp® +
systemic antibiotics
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®
Postoperative perineal wound
infection
P=0.01
•Eradication of enterobacteria,
staphylococci and
Pseudomonas aeruginosa in
84% of Genta patients versus
60% controls
(P 0.013).
Patients with postoperative
perineal wound infection (%)
30
25%
20
12 %
10
•4% Deep wound infection
treatment group versus 10%
control group
0
Systemic
antibiotics
only
Collatamp® +
systemic antibiotics
Gruessner, et al. 2001
Collatamp vs PMMA Chains
local concentrations of gentamicin in the wound (mg/L)
Gentamicin tissue
concentration (mg/L)
MIC for resistent pathogens (300 mg/L)
small PMMA Chains
MIC for sensitive pathogens(4 mg/L)
PMMA Chains
Collatamp®
Time 
Adapted from Swieringa, et al..(2008)Acta Orthopaedica,79:5,637 —642
Biomaterial-associated infection of
gentamicin-loaded PMMA beads in
orthopaedic revision surgery
Daniëlle Neuta,b, Hilbrand van de Belta et al.
Journal of Antimicrobial Chemotherapy (2001)
• 20 patients with prosthesis-related infections
• Gentamicin loaded beads in two-stage
orthopaedic revision surgery
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
p=0.0001
Revision operations(%)
100
50
0
67%
• Local wound healing
criteria p=0.34
20 %
GCCI
PMMA beads
D. Bettin et al. J Bone Joint Surg Br 2009
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
90 %
80%
The number of re-operations
was significantly group I
1.1 vs 1.9
complete resolution of osteomyelitis(%)
100
50
• 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
GCCI
PMMA beads
Letsch et al. Actualle traumatol 1993
Cardiothoracic surgery
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
Sternal wound infections at 2 months
Infection rate (%)
10
• Re-operation rate for
infection(p=0.021):
9
8
6
4,3
4
2
– 3,9% control
– 2,1 % GCCI(gentamicin
collagen fleeces
p<0.001
0
Systemic antibiotics (n=967)
COLLATAMP G + systemic
antibiotics (n=983)
Friberg O et al. Ann Thorac Surg 2005;79:153-161.
Collatamp® and orthopaedic surgery
Therapy with gentamicin-PMMA beads, gentamicincollagen 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 osteomyelitis
150 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:
Cefalozine:
Gentamicin PMMA
Gentamicin collagen
106 CFU/g
104 CFU/g
102 CFU/g
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
p<0.001
Primary healing rate (%)
100
90%
•Mean time to wound healing Group I: 10 days vs Group II: 50
days (p<0.001)
90
80
70
60
•LOS: There was no difference
seen between the two groups in
length of hospital stay
50
40
30
13%
20
10
0
Collatamp®
•No difference long-term
recurrence rate
No antibiotics
Milind M. Rao &Wojtek Zawislak; Int J Colorectal Dis 2009
Turkey the place to be for a hairy ass
Results
20%
5%
Vascular surgery
Jorgensen et al Eur J Vasc Surg 5 1991
Treatment of groin wound graft infections
• 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 reoperations
• Bacteriology:
• 6 Staph aureus
• 2 Pseudomonas aeruginosa
• 1 non-haemolytic Streptococcus (not sensitive to
gentamicin)
• 5 sterile cultures
34
2. Jørgensen LG et al. Eur J Vasc Surg 1991;5:87-91.
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