Profylax med antibiotika mot infektion i kirurgin

Profylax med antibiotika
mot infektion i kirurgin
Per-Olof Nyström
Gastrocentrum kirurgi
Karolinska
Antibiotikaförsäljning, slutenvård i Sverige under perioden 2001 - 2007.
Sverige
Stockholm
DDD per 650
1000 inv.
600
550
500
450
400
350
300
2001
2002
2003
2004
2005
2006
2007
GCK Karolinska
Antibiotika
Kostnader
2011
1
Antifungala medel
2
1603921
70,5%
Carbapenem, Pip-Tazo
317363
14%
3
Vankomycin, Zyvoxid
101053
4%
4
Kinoloner
53484
5
Cefalosporiner
43868
6
Tetracyklin, Tigecyklin
35051
7
Erytromycin m fl
31066
8
Aminoglykosider
19465
9
Penicillinas stabila
18952
10
Penicilliner
18686
11
Antivirala medel
17085
Totalt
2259994
99%
Duration of intravenous antibiotic treatment in 29 patients
with postoperative complication (n=25) or primary infection (n=4)
29/141 = 20.6 percent
20
18
16
Mean 7.2 days, median 6 days.
Antal dagar
14
12
10
8
6
4
2
0
1
3
5
7
9
11
13
15
17
19
21
23
25
27
29
Patient
NAK (H) Sep 2009 – Mar 2010
Indications for intravenous antibiotic treatment in 29 patients
with postoperative complication (n=25) or primary infection (n=4)
Primary infection or extended prophylaxis
4
Anastomotic leakage
6
Abscess
5
Wound healing problems
5
SIRS
4
Pneumonia or respiratory problem
3
Peritonitis
2
6/29 had follow-up treatment with oral antibiotics
K73 Data Sept 2009 to March 2010
Trauma
Infektion
SIRS
Brännskada
Pankreatit
Akut
kolit
Postoperativ
Systemic inflammatory response syndrome
Cancer
Bone et al. Chest 1992
Explanation models for surgical infection
Hygiene
Hygiene
Surgery
Surgery
Physiology
Physiology
National Inpatient Sample database (US) for elective colon resection and cholecystectomy
Davis et al. SIS annual meeting 2011
The Surgical Care Improvement Project, SICP,
does not prevent surgical site infection in colorectal surgery.
Period A
n=238
Period B
n=258
SSI rate
19 %
19 %
Superficial
12 %
13 %
Deep wound
2 %
0.5 %
Organ space
5 %
5 %
Pastor et al. DCR2010;53:24-30
Surgical Site Infection
Incision
Organ space
Over all
Laproscopy
12,3
7,5
19,8
Open 13,2
12,1
25,3
605 colorectal procedures requiring a resection and anastomosis.
Operated between 2001 – 2008 at NY Presbytarian Hospital.
94 % Clean-contaminated, 71 % ASA II, mean Age 60 years.
Ho et al. Surgical Infections 2011;12:255-60.
Duration of intravenous antibiotic treatment in 29 patients
with postoperative complication (n=25) or primary infection (n=4)
29/141 = 20.6 percent
20
18
16
Mean 7.2 days, median 6 days.
Antal dagar
14
12
10
8
6
4
2
0
1
3
5
7
9
11
13
15
17
19
21
23
25
27
29
Patient
NAK (H) Sep 2009 – Mar 2010
Medicare database 2005 & 2006, (269 911 patients);
Incidence of complication
Best
0
2
4
6
Worst
8
10
12
14 %
Respiratory
Pneumonia
MI
DVT/PE
Renal
GI bleed
Haemorrhage
SSI
Ghaferi et al. Ann Surg 2009;250:December
How common is SWI in colorectal surgery ?
Test arm
No. of 24
trials
22
Control arm
No. of 24
trials
22
Median 9.9%
IQR 9.7
20
20
18
18
16
16
14
14
12
12
10
10
8
8
6
6
4
4
2
2
0
0
0
5
10
15
20
Percent SWI
After Song et al. BJS 1998
25
30
Median 9.7%
IQR 8.9
35
40
0
5
10
15
20
Percent SWI
25
30
35
40
Sir (Arnold) Ashley Miles (1904-1988)
Professor of Experimental Pathology
Director, Lister Institute of Preventive Medicine in London
John F. Burke
Hiram C. Polk
Harvard, Boston
Louisville, Kentucky
Mechanism of
Antibiotic prophylaxis
1961
Första randomiserade
profylaxstudien 1969
Miles, Miles, Burke. The value and duration of defence reactions of the skin to the primary lodgement
of bacteria. Br J Exp pathol 1957;38:79-96.
Burke. The effective period of preventive antibiotic action in experimental incisions and dermal lesions.
Surgery 1961;50:161-8.
Polk, Lopez-Mayor. Postoperative wound infection: a prospective study of the determinant factors
and prevention. Surgery 1969;66:97-103.
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The Epidemiology and Other Problems
of Wound Infection
Sir Arthur Ashley Miles
University of Cambridge 1952
0
1
2
3
4 timmar
12 mm
10
8
6
4
2 mm
105 avdödade eller levande S.aureus
Decisive period = Effective period ≈ 4 tim
8
E. coli
B. fragilis
7
Log. Conc. per ml
6
5
4
3
2
1
0
4
8
12
Hours
16
20
24
Pure bacterial contamination
Bacterial/faecal contamination
9
8
E. coli
E. coli
b1
B. fragilis
7
B. fragilis
6
Log. Conc. per ml
Log. Conc. per ml
8
5
4
3
7
b2
6
2
a2
a1
5
1
0
4
8
12
16
Hours
20
24
0
4
8
12
Hours
16
20
60
Surgical 50
Wound
Infection 40
(%)
wet wound placebo,
wound Hct > 8%
dry wound
placebo
30
20
10
dry wound
with antibiotic
0
0
1
2
3
4
5
6
Log wound bacteria
After Polk & Lopez Mayor 1969
Kirurgiska infektionens patogenes (kortformen)
Hematomet är den kirurgiska infektionens kuvös.
Antibiotika i hematomet är profylaxens mekanism.
Varje sår med läkningsstörning blir sekundärt infekterat
American Society of Health-System Pharmacists
Therapeutic Guidelines for Antimicrobial Prophylaxis in Surgery
Cardiothoracic
Cefazolin
Gastrointestinal
Cefazolin
Biliary
Cefazolin
Colorectal
Neomycin+Erytromycin base or Cefoxitin
Head & neck
Cefazolin
Craniotomy
Cefazolin
Obstetric, Gyn
Cefazolin
Orthopedic
Cefazolin
Vascular
Cephazolin
Urology
Sulphamethoxazole
Transplant
Cefazolin
Cefazolin: Eli Lilly 1964
Am J Health-Syst Pharm. 1999; 56:1839–88.
Timing of antibiotic prophylaxis
Type of surgery
Number of cases
Optimal time
Clean‐contaminated
2847
Within 2 hrs
Elective
9195
1 or 2 hrs
Colorectal
3836
30 – 60 min
Colorectal 605
30 min
Classen et al. NEJM 1992;326:281-86.
Hawn et al. JACS 2006:203:803-11.
Weber et al. Ann Surg 2008;247:918-26.
Steinberg et al. Ann Surg 2009;250:10-16.
Ho et al. Surgical Infections 2011;12:255-60.
Två inställningar:
1. Ab profylax skall bara ges till kirurgi med bevisad effekt på infektioner?
2. Ab profylax är en generell behandlingsprincip i kirurgin.
Is Antibiotic Prophylaxis in Surgery a Generally Effective Intervention?
Meta-analyses published between1990 and 2006 of
randomized controlled trials that looked at the
effectiveness of prophylactic antibiotics versus no antibiotic or placebo
The hypotheses to be assessed were:
1. antibiotic prophylaxis is an effective intervention for preventing
wound infection over a broad range of different surgical procedures,
2. there is a substantial difference in the effectiveness of antibiotic
prophylaxis between “clean” and “contaminated” surgical procedures.
Bowater et al. Ann Surgery 2009;249:551
The hypotheses to be assessed were:
1. antibiotic prophylaxis is an effective intervention for preventing
wound infection over a broad range of different surgical procedures:
2. there is a substantial difference in the effectiveness of antibiotic
prophylaxis between “clean” and “contaminated” surgical procedures.
Hypothesis #1: Effectiveness over 23 types of surgery
was significant and similar, all RR <1.
Hypothesis #2: No evidence of a difference with wound class.
Bowater et al. Ann Surgery 2009;249:551
Antibiotic prophylaxis for surgery for proximal femoral and
other closed long bone fractures.
Cochrane Database of Systematic Reviews 2010, Issue 3.
William J Gillespie & Geert HIM Walenkamp
Review included 23 trials, involving a total of 8447 participants.
Reduced incidence of deep infection: risk ratio 0.40, 95% CI 0.24 to 0.67
No added benefit of multiple dosing.
Economic modelling using data from one large trial indicated that
single dose prophylaxis with ceftriaxone is a cost-effective intervention.
Meta-analysis of the effectiveness of prophylactic antibiotics
in the prevention of postoperative complications after
tension-free hernioplasty.
Included 6 studies with 2235 patients
Infection rate 1,7 % vs 3,8 %
OR 0.45 (95% CI 0.26–0.77, p = 0.004),
number needed to treat 48
(cefazolin, cefuroxime, amoxicillin-clavulanic acid)
Jian-Fang Li et al. (China) Can J Surg, 2012;55:27-32
Systematic review and meta-analysis of the effectiveness of
antibiotic prophylaxis in prevention of wound infection after
mesh repair of abdominal wall hernia
Six studies of 2507 patients with femoral or inguinal hernia.
Infection rate 1,5 % versus 3,0 %.
odds ratio 0·54, 95 per cent CI 0·24 to 1·21
Number needed to treat was 74.
(cefazolin, cefuroxime, amoxicillin-clavulanic acid)
Aufenacker et al. BJS 2006; 93: 5–10
Systematic review of Ab prophylaxis in colorectal surgery
Favouring
intervention
+5 %
0
Favouring
control
-5 %
1968
1970
1980
year
Baum et al. NEJM 1981;305:795-9
Surgical Wound Infection in colorectal surgery ?
Test arm
No. of 24
trials
22
Control arm
No. of 24
trials
22
Median 9.9%
IQR 9.7
20
20
18
18
16
16
14
14
12
12
10
10
8
8
6
6
4
4
2
2
0
0
0
5
10
15
20
Percent SWI
After Song et al. BJS 1998
25
30
Median 9.7%
IQR 8.9
35
40
0
5
10
15
20
Percent SWI
25
30
35
40
Antimicrobial prophylaxis for colorectal surgery.
Nelson, Glenny & Song: Cochrane Systematic reviews 2009.
161 studies.
Ab prophylaxis vs. none
RR 0.3
Single dose vs. multiple dose
RR 1.06
Additional anaerobic coverage
RR 0.55
Additional aerobic coverage
RR 0.41
Different antibiotics vs. Gold standard
RR 0 (no difference)
Antibiotic Prophylaxis in Obstetric Procedures
1. All women undergoing elective or emergency Caesarean section
should receive antibiotic prophylaxis. (I-A)
2. The choice of antibiotic for Caesarean section should be a single
dose of a first-generation cephalosporin. (I-A)
3. The timing of prophylactic antibiotics for Caesarean section should
be 15 to 60 minutes prior to skin incision. (I-A)
4. If an open abdominal procedure is lengthy (> 3 hours) or estimated
blood loss is greater than 1500 mL, an additional dose of the
prophylactic antibiotic may be given 3 to 4 hours after the
initial dose. (III-L)
5. Prophylactic antibiotics may be considered for the reduction of
infectious morbidity associated with repair of third and fourth degree
perineal injury. (I-B)
Van Schalkwyk & Van Eyk JOGC September 2010
Gastrocentrums kirurgi Ab-program
Oral profylax för planerad kirurgi:
T. Bactrim forte eller Eusaprim forte 1 tabl.
T. Flagyl 3 tabl. à 400 mg = 1,2 g
Vid känd sulfa allergi kan Bactrim ersättas med T. Doxyferm 4 tabl
Antibiotika profylax i kirurgins praktik
1. Profylax är för elektiv patient utan aktuell infektion.
2. Single-dos som regel.
3. Kan upprepas vid lång operation > 4 tim.
4. Ingen profylaxdos efter avslutad op.
5. Intravenös dos 30 min före incision.
6. Oral dos 1 tim före incision.
7. Effekten är ca halvering av infektionerna.
8. Många olika antibiotika fungerar, välj något som inte
används för terapi.
Antibiotikaprofylaxen är ett endimensionellt sätt att se på
den kirurgiska infektionen.
Riskfaktorerna är många hos patienten.
Läkningsstörningar är vanliga.
Stor kirurgi och komplex kirurgi dubblar komplikationerna.