XIV SIMIT CATANIA 2015

LE INFEZIONI IN ORTOPEDIA

Silvio Borr
U.O.C. MALATTIE INFETTIVE
- VERCELLI -

Osteomieliti
post-traumatiche

Infezione
mezzi
osteosintesi

Pseudoartrosi
infette

ORTOPEDICO

Osteomieliti
ematogene

Spondilodisciti

Artriti
Piede
diabetico

Infezione di protesi
articolare

INFETTIVOLOGO

Mortalit 4.7%
Costo stimato : 257.000.000

Direction generale de la sante 2012

Interaction of staphylococci with bone

J. A. Wright et al Int J Med Microbiol. 2010 February; 300(2-3): 193204.

Pseudoartrosi
focolaio frattura
Mobilizzazione
protesi

Estensione area necrosi

ossea sequestro TNF IL-1 IL-6 *

Schematic of how the

inflammasome pathway is
centrally involved in the pathology
of implant debris-induced local
cytokine responses

Stefan Landgraeber et al.,The pathology of orthopedic implant failure is mediated by innate immune system cytokines.
Mediators Inflamm. 2014: 185150.

 La grande percentuale di successi

ottenuti con la terapia antibiotica
nella maggior parte delle malattie
ad eziologia batterica
contrasta decisamente con la
elevata percentuale di fallimenti nel
trattamento delle infezioni
osteoarticolari
Waldvogel F.A. et al.: Osteomyelitis Lancet Vol. 364, Issue 9431, 369 - 379, 24 July 2004

INTRACELLULAR SURVIVAL

Evidence of an
intracellular reservoir
in osteocytes (A,B),
osteoblasts (C)
bone matrix ( D)
of a patient with
recurrent osteomyelitis

Bosse et al., J Bone Joint Surg Am. 2005; 87:1343-7

Antibiotic activity against biofilms- MRSA

Bauer, Siala et al., AAC 2013; Epub PMID: 23571532

Penetration of Antibacterials into Bone

Pharmacokinetic, Pharmacodynamic and Bioanalytical
Considerations
passaggio attraverso capillari

peso molecolare
legame proteico
lipofilia
caratteristiche acido / base

legame con il calcio ( chinoloni,tetracicline)

legame con idrossiapatite (fosfomicina)
distribuzione corticale / midollare
distribuzione in corso di infezione
Assenza di Linee guida per: manipolazione / preparazione del campione
modalit rilevazione concentrazione antibiotico
risultati discordanti tra diversi studi stesso antibatterico
Landersdorfer C B. et al.: Clin Pharmacokinet 2009; 48 (2): 89-124

Penetration of Antibacterials into Bone

Pharmacokinetic, Pharmacodynamic and Bioanalytical
Considerations

Landersdorfer C B. et al.:

Clin Pharmacokinet 2009; 48 (2): 89-124

Penetration of Antibacterials into Bone

Pharmacokinetic, Pharmacodynamic and Bioanalytical
Considerations

Landersdorfer C B. et al.:

Clin Pharmacokinet 2009; 48 (2): 89-124

100 Pz con diagnosi clinica di osteomielite cronica

La coltura di prelievi di osso nel focolaio osteomielitico ha permesso
lidentificazione dell'agente nel 94% dei casi, compresi i batteri
anaerobi (14%). Colture di campioni non-osso e osso diedero
risultati identici nel 30% dei pazienti, (>concordanza in osteomielite
cronica causata da Staphylococcus aureus -42%- rispetto a tutte le
altre specie batteriche -22%-).

Ldentificazione dellagente eziologico di

osteomielite cronica richiede la cultura
dell'osso infetto

Frattura chiusa
(integrit delle parti molli)

Frattura esposta 1 grado

Frattura chiusa con parti molli gravemente

contuse
Corpi estranei ritenuti
Frattura esposta di 2 o di 3 grado
Amputazione traumatica

dopo 9 mesi
Il trasporto viene terminato e il fissatore esterno rimosso.

2013
168.487 protesi impiantate
1 MILIONI DI ITALIANI SONO PORTATORI DI
PROTESI ARTICOLARI
Prima
In aumento
le revisioni
edizione: novembre
2015
2015 Il Pensiero Scientifico Editore

Aumentate le protesi di spalla

5853

0.8 - 1.9%

2.2 %*

0.3 - 1.7%

2.2 %*

* Tande A.J. Et al:Prosthetic Joint Infection Clin. Microbiol. Rev. 2014, 27(2):302.DOI:10.1128/CMR.00111-13.

Infezione di Endoprotesi
-in frattura femore-

6.9 %
*Merrer J. Et al Infect Control Hosp Epidemiol 2007;28:1169-74.

Infezione dopo procedure di revisione

Fino 20%
Barberan J. Management of infections of osteoarticular prosthesis.
Clin Microbiol Infect 2006; 12 Suppl 3: 93101.

The management of infection in arthroplasty of the shoulder

infection of 1.8%

for primary and 4% for revision

procedures.
J. S. Coste et al J Bone Joint Surg Br. 2004 Jan;86(1):65Peri-prosthetic Infections after Shoulder Hemiarthroplasty
9 -2008: 1,349 patients 1,431 primary hemi-arthroplasties 14
1976
infections 1%
J Shoulder Elbow Surg. Oct 2012; 21(10): 13041309.
Periprosthetic infections after total shoulder arthroplasty: a 33-year perspective
1976 -2008 : 2,207 patients 2,588 primary TSAs
J Shoulder Elbow Surg. Nov 2012; 21(11): 15341541.

46 infections

1.7%

Diagnosis of Periprosthetic Infection After Shoulder Arthroplasty A Critical

Analysis Review
primary shoulder arthroplasty

0.7% and 4% for revision

surgery
Eric T. Ricchetti et al.: JBJS Reviews, 2013 Nov;1

CLASSIFICAZIONE
* Le classificazioni sono necessarie per creare gruppi omogenei di pazienti
permettere di confrontare i risultati ottenuti/pubblicati
e definire linee guida di trattamento

Su un unico punto vi totale accordo in letteratura:

il risultato terapeutico fortemente condizionato

dal tempo intercorso tra infezione ed inizio terapia
adeguata
Acuta
Cronica
. Per il clinico, acuta se segni di flogosi locali e/o generali + dolore insorto
recentemente; cronica se presenta anche segni radiologici suggestivi,
. Per il microbiologo, il biofilm (entit dinamica ) e il polimorfismo delle colonie
isolate da campioni profondi che definiscono la cronicit
. Per il chirurgo, l infezione acuta quella che pu guarire senza rimozione del
materiale protesico.
27

Early
1st month
Delayed 2nd-6th months
Late
> 6th months

Buller et al. Irrigation/Debridement With Polyethylene Exchange for PJIs.

Journal of Arthroplasty 2012 : 27 No. 6

Buller et al. Irrigation/Debridement With Polyethylene Exchange for PJIs.

Journal of Arthroplasty 2012 : 27 No. 6

New Definition for Periprosthetic Joint Infection.

From the Workgroup of the Musculoskeletal Infection Society
fistola comunicante con la protesi;
o
1 patogeno viene isolato da coltura di almeno due campioni
di tessuto o fluido separati ottenuti dalla articolazione protesizzata;
o quattro dei seguenti sei criteri presenti:
VES e PCR elevati,
> leucociti liquido sinoviale ,
> percentuale PMN% liquido sinoviale ,
presenza di pus nel tessuto periprotesico,
isolamento di un microrganismo da 1 coltura di tessuto o fluido
periprotesico,
o
istologico estemporaneo con > cinque neutrofili per campo a 400 X
in cinque campioni di tessuto periprotesico
PJI pu essere presente anche se sono soddisfatti < quattro di questi criteri.
Parvisi et al. Clin Orthop Relat Res (2011) 469:29922994.

- Cellularit
- Colturale
- Biomarker
- Esterasi leucocitaria
- -defensina

LA STORIA D
EL
PAZIENTE

GB VES PCR
- PCT IL-6

Rx
+++ colturali
- Scintigrafia Tc Es.istologico
Leu N.C.
- ECO TC RM

LA CLINI
CA

VES e PCR aumentati sembrano fornire la miglior sensibilit e

specificit diagnostica (A-III).
Una
semplice
radiografia
deveinessere
eseguita
in tutti
pazienti con
Plain
radiographs
should
be performed
all cases
of suspected
PJI. iMagnetic
sospettaimaging
PJI (A-III).
di imaging
come
scintigrafia
resonance
(MRI), Studi
computed
tomography
(CT),laand
nuclear imaging currently
doossea/leucociti+,
not have a direct role
in theRNM
diagnosis
of PJI
but dovrebbero
may be helpfulessere
in the richiesti di
TAC,
e PET
non
identification
other causes of joint
pain/failure. Strong (93)
routine perofdiagnosticare
PJI (B-III).
International Consensus on Periprosthetic Joint Infection 2013
Una artrocentesi diagnostica dovrebbe essere eseguita in tutti i Pz
- con sospetta PJI acuta
- con protesi dolorosa cronica anche senza > VES e/o PCR (A-III)
Analisi del liquido sinoviale:
- N totale GB e % PMN,
- Coltura per microrganismi aerobi ed anaerobi (A-III).
La sospensione della terapia antibiotica per almeno 2 settimane prima
della raccolta liquido sinoviale > la probabilit di identificare
organismo (B-III)

Methods
We performed a prospective study of 133 patients in whom synovial fluid specimens were collected before
total knee arthroplasty revision between January 1998 and December 2003. Patients with underlying
inflammatory joint disease were excluded.
Results
Aseptic failure was diagnosed in 99 patients and prosthetic joint infection was diagnosed in 34 patients. The
synovial fluid leukocyte count was significantly higher in patients with prosthetic joint infection (median,
18.9 103/L; range, 0.3 to 178 103/L) than in those with aseptic failure (median, 0.3 103/L; range,
0.1 to 16 103/L; P <0.0001); the neutrophil percentage was also significantly higher in patients with
prosthetic joint infection (median [range], 92% [55% to 100%] vs. 7% [0% to 79%], P <0.0001). A leukocyte
count of >1.7 103/L had a sensitivity of 94% and a specificity of 88% for diagnosing prosthetic joint
infection; a differential of >65% neutrophils had a sensitivity of 97% and a specificity of 98%.
Staphylococcus aureus was the only pathogen associated with leukocyte counts >100 103/L.
Conclusion
A synovial fluid leukocyte differential of >65% neutrophils (or a leukocyte count of >1.7 103/L) is
a sensitive and specific test for the diagnosis of prosthetic knee infection in patients without
underlying inflammatory joint disease.

Diagnosis and management of prosthetic joint infection

Matthews et al. BMJ.2009; 338: b1773

Reported cutoff values for diagnosis of periprosthetic joint infection

Bedair H. et al: Diagnosis of Early Postoperative TKA Infection Using Synovial Fluid Analysis
Clin Orthop Relat Res (2011) 469:3440

The Mark Coventry Award: diagnosis of early postoperative TKA infection using synovial fluid analysis.

> 27.000 G.B / ml nelle prime 6 settimane

sensibilit 84%, specificit 99%,
valore predittivo positivo 94%,
valore predittivo negativo 98%
L'uso di valori di cutoff standard per questo
parametro (~ 3.000 cellule / microlitro) avrebbe
comportato reinterventi inutili.
Bedair H. et al: Diagnosis of Early Postoperative TKA Infection Using Synovial Fluid
Analysis Clin Orthop Relat Res (2011) 469:3440

Diagnosis of Periprosthetic Joint Infection:

The Utility of a Simple Yet Unappreciated
Methods: Between May 2007 and April 2010,Enzyme
synovial fluid was obtained preoperatively from the knees
of patients with a possible joint infection and intraoperatively from the knees of patients undergoing
revision knee ESTERASI
arthroplasty. The LEUCOCITARIA
aspirate was tested for thesu
presence
of leukocyte
esterase with use of
liquido
articolare:
a simple colorimetric strip test. The color change (graded as negative, trace, +, or ++), which
corresponded to the level of the enzyme, was noted after one or two minutes.
Results: On the basis
of clinical,
serological, and operative criteria,
of the 108 knees undergoing
80.6
% sensibilit
100%thirty
specificit
revision arthroplasty were infected and seventy-eight were uninfected. When only a ++ reading was
considered positive, the leukocyte esterase test was 80.6% sensitive (95% confidence interval [CI],
61.9% to 91.9%) and 100%VPP
specific
(95% CI, 94.5% to 100.0%),
a positive predictive value of
: 100%
VPN : with
93.3%
100% (95% CI, 83.4% to 100.0%) and a negative predictive value of 93.3% (95% CI, 85.4% to
97.2%). The leukocyte esterase level correlated strongly with the percentage of polymorphonuclear
leukocytes (r = 0.7769) and total white blood-cell count (r = 0.5024) in the aspirate as well as with the
erythrocyte sedimentation rate (r = 0.6188) and C-reactive protein level (r = 0.4719) in the serum.
Risultato
in tempo
reale
a bassissimo
costo
Conclusions: The
simple colorimetric
strip test
that detects
the presence of
leukocyte esterase in
synovial fluid appears to be an extremely valuable addition to the physician's armamentarium for the
diagnosis of periprosthetic joint infection. The leukocyte esterase reagent strip has the advantages of
providing real-time results, being simple and inexpensive, and having the ability to both rule out
and confirm periprosthetic joint infection. However, additional multicenter studies are required to
substantiate the results of our preliminary investigation before the reagent strip can be used confidently in
the clinic or intraoperative setting.

Javad Parvizi et al.: J Bone Joint Surg Am, 2011 Dec 21;93(24):2242-2248.

Leukocyte esterase analysis in the diagnosis of joint infection:

Can we make a diagnosis using a simple urine dipstick?

Our test results confirm that the leukocyte esterase test can accurately detect PJI and that
it can be used as a part of the traditional PJI workup.
In the assessment of native joints, its high negative predictive value suggests that it is a
valuable tool in excluding native joint septic arthritis.

Otis C. Colvin et al.:Skeletal Radiol (2015) 44:673677

Diagnosing Periprosthetic Joint Infection:

Biomarker Arrived?

Has the Era of the

Parvizi J. et al. Clin Orthop Relat Res. Nov 2014; 472(11): 32543262. Published online Mar 4, 2014.
doi: 10.1007/s11999-014-3543-8

The Synovasure PJI Test is the first and only test specifically
designed and validated for the diagnosis of
Periprosthetic Joint Infection (PJI).
The Synovasure Test achieves 97% sensitivity and 96% specificity by measuring synovial
fluid alpha defensin (antimicrobial peptide released by neutrophils in response to pathogens )
Superior ease of use- rapid results visible within 10 minutes

The Alpha-defensin Test for Periprosthetic Joint Infection

Responds to a Wide Spectrum of Organisms

Deirmengian C. et al.:Clin Orthop Relat Res (2015) 473:22292235

DIAGNOSI INTRAOPERATORIA DI PJI

- Esame istopatologico di campioni di tessuto periprotesico:
test diagnostico altamente affidabile con patologo esperto per
dirimere il sospetto di infezione periprotesica revisione 1 o 2
tempi (B-III).
infezione in atto
Se presenza di 5 o pi polimorfonucleati
per campo microscopico -400 x in almeno 5 distinti campi microscopici

Identificazione microbiologica
- Almeno 3 - meglio 5 o 6 -,campioni di tessuto o la stessa protesi
inviati per coltura(B-II).
- sospendere eventuale terapia antibiotica per almeno 2
settimane prima dei prelievi intraoperatori (A-II).

- Cellularit
- Colturale
LA STORIA D
EL
PAZIENTE

LA CLINI
CA

- Esterasi leucocitaria
- -defensina

GB VES PCR
- PCT IL-6
Rx
- Scintigrafia Tc
Leu N.C.
- ECO TC RM

IDENTIFICAZIONE
DEL PATOGENO

+++ colturali
Es.istologico

sonicazione: interessante ..ma

We do not recommend routine sonication of explants.

Its use should be limited to cases of suspected or proven PJI (based upon
presentation and other testing) in which pre-operative aspiration does not
yield positive culture and antibiotics have been administered within the
two
weeks.
Laprevious
sensibilit
degli
esami Strong
colturali(86)
International
Consensus
on Periprosthetic Joint Infection 2013
del
liquido ottenuto
dopo
sonicazione stato > delle colture
del tessuto periprotesico( 78.5%
vs 60.8%, p < 0,001) con una
specificit del 99% anche prima
dei 14 gg di sospensione atb

Trampuz A. Sonication of Removed Hip and Knee Prostheses for

Diagnosis of Infection. N Engl J Med 2007;357:654-63

Prosthesis sonication

Polymicrobial infections reduce the cure rate in prosthetic joint

infections: outcome analysis with two-stage exchange
and follow-up two years

follow-up two years : OK

67,6 %

87,5%

Wimmer M.et al.: International Orthopaedics (SICOT) April 2015

p: 0,041

PJI :DIFFERENTI STRATEGIE MEDICHE E CHIRURGICHE

- debridement, sostituzione polietilene senza rimozione della protesi
- sostituzione in 1 o 2 tempi chirurgici
- rimozione senza reimpianto /artrodesi ginocchio
- amputazione/disarticolazione
-

terapia antimicrobica soppressiva cronica senza intervento chirurgico

L'obiettivo di ogni strategia chirurgica rimuovere tutto il tessuto infetto e
parte o tutto limpianto per diminuire carica batterica e biofilm permettendo alla
terapia antibiotica post-operatoria di eradicare la restante infezione .
Se la diagnosi eziologica certa lapproccio chirurgico potr essere eseguito
con Pz in trattamento antibiotico mirato
Se la diagnosi eziologica certa non stata ottenuta, non somministrare
antibiotici fino ad esecuzione di prelievi multipli intraoperatori

Tande A. J. Et al:Prosthetic Joint InfectionClin. Microbiol. Rev. April 2014vol. 27 no. 2 302-345

 Culture-negative infection was common among these chronic

infections treated by two-stage revision, but was not associated with
a worse outcome.

Cultures taken at reimplantation following an antibiotic-free

period did not predict outcome and clinical failure of treatment
was more often identified during antibiotic treatment than after
antibiotics were stopped.

Reimplantation may be considered without an antibioticfree period, with additional antibiotic prophylaxis before
reimplantation.
Where multiple reimplantation cultures are positive in the absence of clinical indicators of
ongoing infection, a limited course of oral antibiotics may be appropriate.
Beion P. et al., Two-stage revision for prosthetic joint infection: predictors of outcome and the role of
reimplantation microbiology J Antimicrob Chemother. 2010 Mar; 65(3): 569575.

Two-stage revision of prosthetic hip joint infections using

antibiotic-loaded cement spacers: When is the best time to
perform the second stage?

Vielgut I. International Orthopaedics (SICOT) (2015) 39:17311736

Lassociazione previene lemergenza di resistenza alla

rifampicina

Vergidis et al., AAC 2011; 55: 11826

.An essential component of the care of patients with PJI is strong

collaboration between all involved medical and surgical specialists
(eg, orthopedic surgeons, plastic surgeons, infectious disease
specialists, internists). It is anticipated that consideration of these
guidelines may help reduce morbidity, mortality, and the costs
associated with PJI. The panel realizes that not all medical
institutions will have the necessary resources to implement all the
recommendations in these guidelines.

Proper referral to specialty centers may need to occur

65

Tande A. J. Et al:Prosthetic Joint InfectionClin. Microbiol. Rev. April 2014vol. 27 no. 2 302-345

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Daptomycin efficacy in osteomyelitis

Seaton et al., JAC 2013 Epub PMID: 23515247