2 - Deutsche Kniegesellschaft

Was hat alles Einfluss auf die
Infektrate?
Andrej Trampuz
Center for Septic Surgery
Charité – University Medicine Berlin
Germany
Risk of implant-associated infection
Device
No. inserted in the US
per year
Rate of infection, %
Fracture fixation devices
2,000,000
5–10
Dental implants
1,000,000
5–10
Joint prostheses
600,000
1–3
Vascular grafts
450,000
1–5
Cardiac pacemakers
300,000
1–7
Mammary implants
130,000
1–2
Mechanical heart valves
85,000
1–3
Penile implants
15,000
1–3
700
25–50
Heart assist devices
Darouiche RO. Clin Infect Dis 2011;33:1567–1572
5-10%
Confirmed infection:
Mirror sign +
What now?
« Fistula check »
• No pain
• No swelling
• No warmth
• No redness
• No bad function
67-jährige Patientin
1-zeitiger Wechsel der KnieTEP wegen Lockerung (3
Jahre)
Punktat präop: Kultur
negativ
Histologie: negativ
2/5 Proben:
Propionibacterium acnes
Therapie: Levo/Rifa p.o.
12 Tage nach Beginn AB:
Rötung,
CRP 79, Kreatinin 2,4
MOP, MOM,
COC bearing
couples
Wear
particles
Acute or fatigue implant
fracture, oxidative
degredation, corrosion
Production errors,
improper materials or
design
Aggresive
activity - sports
Acute mechanical overload
Artifical joint
material failure Chronic mechanical overload
Infection
Bone to implant
interface failure
Periprosthetic
fracture
Osteolysis
Hypersensitivity,
mutagenicity?
Metal ion
release
ARTIFICIAL JOINT
FAILURE:
loosening, dislocation, neurovascular
deficits, tendon lesions, limb lenght
discrepancy, poor range of motion,
pain, sounds
Implant positioning,
poor approach
Poor surgical
technique
Sistemic
alterations
Excessive
micromotion
Bone to implant
toughness mismatch
Effective joint
space fluid
pressure
Stress shielding,
week bone
Excessive
rigidity
Unnatural force transfer
complication
rate
Preoperative
diagnosis
poor
education,
low
surgical
volume
Factors influencing the infection rate
1. Risk factors for infection (…)
2. Definition criteria
20% missed infections
3. Diagnostic procedure
30% missed infections
4. Registries
•
Septic vs. aseptic revisions
5. Preventive measures
50% reduction of infections
Definition
Klassifikation
Zeit
Typ der
Infektion
Pathogenese
Zeichen
Erreger
<1 Monat
3–24 (36) Monate
Jederzeit
Früh
postoperativ
Verzögert
(low grade)
Hämatogen
Perioperativ
Akut: Fieber,
lokale
Symptome
S. aureus
Streptococci
Enterococci
Chronisch:
Persistierende
Schmerzen, Fistel
Koagulase-neg.
Staphylokokken
P. acnes
Hämatogen
Akut oder
subakut
S. aureus
E. coli
2
Normal microbiota of the skin
100.000 bacteria/cm2
Staphylococci
- Staphylococcus epidermidis
Anaerobes
- Propionibacterium acnes
Microbiology
Microorganism
Frequency Resistant
Coagulase-negative staphylococci
(e.g. Staphylococcus epidermidis)
30%
70-90% (Oxacillin)
Staphylococcus aureus
20%
10-30% (Oxacillin)
Streptococci & enterococci
10%
5-10% (Penicillin)
Gram-negative bacilli (e.g.
Escherichia coli)
10%
10-30% (Ciprofloxacin)
Anaerobes (e.g.
Propionibacterium acnes)
10%
0-3% (Penicillin)
Mixed infections
Fungi (e.g. Candida albicans)1
Culture negative
1 Often
10-30%
1-3%
10% (Fluconazol)
10-20%
after VAC-therapy or fistula (with antibiotic therapy).
Incidence of infection, %
Route of implant infection
2
Perioperative (60-70%)
- During surgery: 100 bacteria sufficient
Hematogenous (30-40%):
- Distant urinary, skin, gut and
respiratory infections
- Dental procedure
- Endocarditis, IV device (port, PM)
1
1
Time, years
2
A definite diagnosis of PJI (MSIS criteria)
• Sinus tract communicating with the prosthesis; or
• Pathogen isolated from two separate samples; or
• Presence of 4 of 6 criteria:
• Elevated ESR or CRP
• Elevated synovial white blood cell (WBC) count
• Elevated synovial neutrophil percentage (PMN%)
• Isolation of a microorganism in one culture
• Positive histology
• (Presence of purulence in the affected joint)
136 patients with hip & knee revision
Implant Pus Leuk
age (y)
count
Neut
%
Histo ESR/
CRP
Tissue Sonic Pathogen
ation
ATB MSIS IDSA
Zimmerli
1.1
Yes
ND
ND
-
ND
1 Pos
-
E. coli
Yes
AF
PJI
PJI
4.7
Yes
ND
ND
-
ND
Neg
+
S. epidermidis
No
AF
PJI
PJI
2.4
No
Elev
Norm -
ND
1 Pos
-
S. epidermidis
Yes
AF
AF
PJI
1.1
No
Norm
Elev
-
+
Neg
-
No growth
Yes
AF
AF
PJI
0.4
Yes
Elev
Elev
-
ND
Neg
-
No growth
Yes
AF
PJI
PJI
0.4
No
Norm
Norm ND
-
Neg
+
C. albicans
No
AF
AF
PJI
0.1
Yes
Elev
Elev
+
Neg
-
No growth
Yes
AF
PJI
PJI
32
35
ND
7 of 35 (20%) missed by MSIS
3 of 35 (9%) missed by IDSA
No. infections: 28
Portillo ME et al. (CORR 2016)
Conclusion
About 20% of PJI are missed by MSIS criteria.
About 10% of PJI are missed by IDSA criteria.
The ostrich effect
Ostriches: bury their heads in
the sand to avoid danger
(legend).
In humans: Avoid an
apparently risky situation by
pretending it doesn’t exist
(not legend).
Definition
Diagnosis of periprosthetic joint infection is confirmed if at least 1 criteria is fulfilled:
Sensitivity
Criteria
Clinical
Sinus tract (fistula) or visible purulence
features
around the prosthesis
Histology
Acute inflammation in periprosthetic tissue
Specificity
20-30%
100%
95-98%
98-99%
96%
98%
60-80%
97%
70-85%
92%
85-95%
95%
(>10 neutrophils per HPF nach Morawietz &
Krenn)
Cytology
>2000/µl leukocytes or
Microbiology
Microbial growth in:
70% granulocytes
- Synovial fluid
-
2 periprosthetic tissue samples*
- Sonication fluid ( 50 CFU/ml)
*For highly virulent organisms (e.g. S. aureus, E. coli) 1 positive tissue sample is sufficient.
Diagnostic procedure
AAOS Clinical Practice Guidelines
Diagnosis of PJI
Dogmas, personal opinions and misleading
information
www.aaos.org/research
AAOS Clinical Practice Guidelines
Diagnosis of PJI
Dogmas, personal opinions and misleading
information
x
www.aaos.org/research
Conclusion
Every patients with painful or loose prosthesis
within 2-3 years after implantation should…
…get joint aspiration (cell count & culture).
Joint puncture
Operating procedure for joint aspirations
If aspirated synovial fluid volume <5 ml distribute the obtained synovial fluid according to
the priority column (otherwise vials can be completely filled up)
Sonication of implants
Removed implants
Vortex, 30 s
Sonication, 1 min, 40 kHz
May 2005–Feb 2007
Tissue
Standard method
( 3 tissue biopsies)
Trampuz A et al. N Engl J Med 2007;357:654–663
Sonicate
Figure 1. Time to diagnosis of 39 IAI cases.
Portillo et al. JCM 2015
Suppression with antibiotics
•
Long-term antibiotic therapy is splitted in treatment phases with
different antibiotics instead of a single drug
4 weeks
cotrimoxazol
•
Changement of substance every 2-4 weeks
•
Indications:
• No anti-biofilm-active agent available
• Intolerance of antibiotics/side effects
4 weeks
drug
holidays
4 weeks
doxycyclin
4 weeks
clindamycin
•
Benefits:
• Bacteria are getting confused prevention of emergence of
resistance
• Antibiotic tolerance is better, adverse effects are less
Outlook: New diagnostic methods
Microcalorimetry
Molecular methods (PCR)
MALDI-TOF
Corvec S, Portillo ME et al. IJAO 2012
Registries
Year 2014
(n = 11,251)
www.dhr.dk
2 years
16%
Kaplan-Meier Analyse von
112 Prosthesen
69%
Portillo ME et al. CORR 2013
Orthopädische Implantat Register
Unterschätzte Infektions-Raten
PPI Qualitätsindikator zu kurzfristig
Hip-TEP
1 Jahr post-OP: 3%
Dale et al. Acta Orthop 2011
Knee-TEP
1 Jahr post-OP: 0,5 % Zmistowski et al. CORR 2011
Männer < 1%,
Frauen < 0,3 %
Swedish knee arthroplasty
registry, Report 2011
Direkt postoperativ
bis Entlassung: 0,1 %
Memtsoudis et al. CORR 2008
Shoulder-TEP 1 Jahr post-OP: 9%
Rasmussen et al. Acta Orthop. 2012
„Wahre“ Inzidenz für Infektion ist deutlich höher
In the Danish national registries, the 1- and 5-year cumulative incidences of
surgically treated prosthetic joint infection were approximately 0.50% and
0.60%. The corresponding 1- and 5-year cumulative incidences estimated by
the algorithm were 0.86% (0.77–0.97) and 1.03% (0.87–1.22). Thus, the use of
multiple data sources for estimation of the “true” incidence of surgically treated
PJIs led to a 40% higher estimate than reported by national arthroplasty and
patient registries alone.
Register und Patienten-MiBi Daten
“It is intriguing that only about 66% of
periprosthetic joint infections were detected in
the registry and you could improve it by linking
the registry with a microbiology database.”
Validation of the Diagnosis Prosthetic Joint Infection in the Danish Hip Arthroplasty
Register
Gundtoft PH, Schønheyder HC, Kjærsgaard-Andersen P, Pedersen AB, Overgaard S
Presented at:
- IX th annual conference «Vreden's Readings» October, 8-10 2015, St. Petersburg
- EBJIS 2015
- Under 2nd review in BJJ
European
Prosthetic Joint
Infection Cohort
(EPJIC)
www.pro-implant-foundation.org
www.epjic.org
Preventive measures
Timing of perioperative prophylaxis
Classen DC, NEJM 1992; 326: 281-286
Clinical relevance of antibiotics
Varianten Erläuterung
1
2
A
B
Prä-stionäres Screening auf
S.aureus (nicht nur auf
MRSA) und Dekolonisation
aller S.aureus-Patienten
(prä stationär oder
unmittelbar bei Aufnahme)
Kein prä-stationäres
Screening,
Dekolonisation aller
Patienten unmittelbar bei
Aufnahme
Anwendung von Mupirocin
für die Nase und
Chlohexidin für die Haut
Anwendung von OctenidinNasen-Gel und OctenidinWaschlappen
Vorteil
Nachteil
Weniger Kosten für
DekolonisationsSubstanzen
Geringere
Resistenzentwicklung
Schwieriger zu
organisieren
Der protektiver Effekt
für den Erwerb von
MRE ist limitiert
Einfacher zu
organisieren
Der protektive Effekt
auf den Erwerb von
MRE ist umfänglich
Entspricht den
Bedingungen der
publizierten Studien
Höhere Kosten für
Dekolonisation
Höhere
Resistenzentwicklung
Preiswerter
(16 € vs > 50 €)
Keine Resistenzentwicklung
Höhere Kosten
Risiko der Resistenzentwicklung gegen
Mupirocin
Unklar, ob der Effekt
ebenso gegeben ist
wie bei Mupirocin
Skin/nose decolonization
(5 days before surgery)
Orthopedic surgery
Heart surgery
No.
RR (CI95)
No.
RR (CI95)
Randomized
studies
2
0,48 (0,18-1,28)
4
0,59 (0,38-0,90)
Non-randomized
studies
5
0,59 (0,42-0,82)
3
0,30 (0,17-0,54)
All studies
7
0,57 (0,42-0,79)
7
0,45 (0,32-0,63)
Staphylococcus aureus 4-antigen vaccine
Indication
Adults undergoing elective posterior
instrumented lumbar spinal fusion procedures
Study
A phase 2b, randomized, double-blind,
placebo-controlled study
Intervention
Single-Dose 10-60 days before surgery
Where is the evidence?
Conclusion
Frequency of periprosthetic infections is largely
underestimated.
The cumulative “true” infection rate is 2-3x higher:
• Diagnosed with improved registries, diagnostic and
definition criteria.
• Reduced with improved systemic and local preventive
measures (antibiotic prophylaxis, implant design,
decolonization, possibly vaccination).
Renz N & Trampuz A.
Orthopädie & Rheuma 2015
Der Orthopäde. November 2015
Deutsche Med Wochenschrift 2013
Interdisziplinäre Behandlung
www.PRO-IMPLANT-foundation.org
February 11-12
March 21-22
June 13-14
October 10-11
November 24-25
Pocket Guide: Management of PJI
Interdisciplinary team
Werner Zimmerli
Olivier Borens
Carsten Perka
Thank you
[email protected]
Focus on implant, bone and joint-associated infections:
• Surgery: New concepts (retention, 1-stage, 2-stage short interval)
• Diagnosis: Fast innovative methods
• Antibiotics: Active against biofilms
Moving forward with optimized concepts
Treatment algorithm
Acute PJI
Chronic PJI
Intention to cure?
- DTT-organism?
- Bad bone/soft tissue?
- Instable prosthesis?
No
Yes
Long-term suppressive
antibiotic therapy, permanent
arthrodesis/girdlestone
No
Yes
Prosthesis exchange
- DTT (if known)?
- Bad bone/soft tissue?
- Fistula?
- Multiple revisions?
Yes
No
Débridement & retention
One-stage exchange
Two-stage exchange
- DTT-organism?
- Bad bone/soft tissue?
DTT = difficult-to-treat microorganisms
- Rifampin-resistant staphylococci
- Ciprofloxacin-resistant gram-negative
bacteria
- Fungi (Candida)
No
Short interval
(2-3 weeks)
Yes
Long interval
(6-8 weeks)
Unsatisfactory
course?
Three-stage exchange
Aspiration of prosthetic knee joints, underlying inflammatory disorders excluded
97%
94%
Trampuz A. Am J Med 2004; 117: 556
Joint aspiration: Leukocyte count
Value
Normal
Group 1
Group 2
(degenerative) (inflammatory)
Group 3
(infectious +
crystals)
Leukocytes
L
<200
200 - 2,000
2,000 – 20,000
>20,000
Neutophils,
%
<25%
25 – 70%
70 - 90%
>90%
Psoriasis
Rheumatoid arthritis
Reactive arthritis
Collagenosis (SLE)
Low-grade PJI
Leukozyten-Esterase
Parvizi et al. JBJS 2011
Synovasure™ Test
95% CI
Sensitivity
97.4%
86.1% - 99.6%
Specificity (excluding cases of metallosis)
97.1%
93.0% - 99.7%
Specificity (including cases of metallosis)
95.8%
90.5% - 98.6%