Treatment of prosthetic joint infection - Alex Soriano Department of Infectious Diseases Hospital Clínic of Barcelona - Infektion.net
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Treatment of prosthetic joint infection Alex Soriano Department of Infectious Diseases Hospital Clínic of Barcelona
Barret L, et al. The clinical presentation of prosthetic joint
infection. J Antimicrob Chemother 2014; 69: suppl 1: i25-i27
debridement, antibiotic
treatment and implant
retention (DAIR)
“planktonic” bacteria
bactericidal antibiotic (5-10 d)
“adapted” bacteria
anti-biofilm antibiotic (2-6 m)
“persistent” bacteria
“suppresive” antibiotic (???)
Lora-Tamayo J, et al. A Large Multicenter Study of MS and MR
Staphylococcus aureus Prosthetic Joint Infections Managed
With Implant Retention. Clin Infect Dis 2013; 56: 182–94
retrospective & multi-centric study including
345 episodes of acute PJI
MSSA: i.v. cloxacillin
MRSA: i.v. vancomycin
1m
Tornero E, et al. KLIC-score for predicting early failure in
acute prsothetic joint infections treated with DAIR
Clin Microbiol Infect 2015; 21: 786
Tornero E, et al. KLIC-score for predicting early failure in
acute prsothetic joint infections treated with DAIR
Clin Microbiol Infect 2015; 21: 786
5%
Tornero E, et al. KLIC-score for predicting early failure in
acute prsothetic joint infections treated with DAIR
Clin Microbiol Infect 2015; 21: 786
N=114 N=54 N=36
% remission / failure
(56%) (26%) (18%)
C-reactive protein before debridement (mg/dL)
Tornero E, et al. KLIC-score for predicting early failure in
acute prsothetic joint infections treated with DAIR
Clin Microbiol Infect 2015; 21: 786
high planktonic
bacterial load
Dastgheyb S, et al. Staphylococcal Persistence Due to Biofilm
Formation in Synovial Fluid Containing Prophylactic Cefazolin.
Antimicrob Agents Chemother 2015; 59:2122–2128
Staphylococcus aureus
x10 PIA/PNAG 3D- confocal
staining laser microscopy
Dastgheyb S, et al. Effect of Biofilms on Recalcitrance of
Staphylococcal Joint Infection to Antibiotic Treatment.
J Infect Dis 2015; 211: 641-50Dastgheyb S, et al. Effect of Biofilms on Recalcitrance of
Staphylococcal Joint Infection to Antibiotic Treatment.
J Infect Dis 2015; 211: 641-50Thompson JM, et al. Oral-Only Linezolid-Rifampin Is Highly Effective
Compared with Other Antibiotics for Periprosthetic Joint Infection
J Bone Joint Surg (Am) 2017; 99:656-65
1. inoculum 103 CFU of bioluminiscent MRSA
2. After a 2-week incubation period to allow biofilm
formation on the Kirschner
3. Antibiotic treatment (or sham treatment with saline
solution) was initiated for 6 weeks with doses that
approximate human-exposure doses according to the
AUC and differences in serum drug protein binding
between mice and humansThompson JM, et al. Oral-Only Linezolid-Rifampin Is Highly Effective
Compared with Other Antibiotics for Periprosthetic Joint Infection
J Bone Joint Surg (Am) 2017; 99:656-65
1. inoculum 103 CFU of bioluminiscent MRSA
2. After a 2-week incubation period to allow biofilm formation on the
Kirschner
3. Antibiotic treatment (or sham treatment with saline solution) was
initiated for 6 weeks with doses that approximate human-exposure
doses according to the AUC and differences in serum drug protein
binding between mice and humansThompson JM, et al. Oral-Only Linezolid-Rifampin Is Highly Effective
Compared with Other Antibiotics for Periprosthetic Joint Infection
J Bone Joint Surg (Am) 2017; 99:656-65
culture results after 6 weeks of treatmentAchermann Y, et al. Factors associated with rifampin
resistance in staphylococcal periprosthetic joint infections
(PJI): a matched case–control study.
Infection 2013; 41: 431-7
variable P-value
male 0.02
≥3 prior revision surgeries 0.006
rifampin treatment“planktonic” bacteria
bactericidal antibiotic (5-10 d)
• debridement + PE exchange
• C-RP < 10 mg/dL: cloxacillin / linezolid / daptomycin /ceftaroline
• C-RP ≥ 10 mg/dL: association of ≥2 atb (fosfomycin)
• Local antibiotics ?: gentamicin beads have been associated
with a worse outcome (Lowik C, et al. J Arthroplasty 2018)
“adapted” bacteria
anti-biofilm antibiotic (2-6 m)Otero LH, et al. How allosteric control of Staphylococcus aureus penicillin
binding protein 2a enables methicillin resistance and physiological
function. PNAS 2013; 110: 16808-16813
PBP2A (MRSA)
ß-lactams bind in a
distal site
(alosteric site)
Mahasenan KV, et al. JACS 2017; 139; 2102-2110Saravolatz LD, et al. Ceftaroline: A Novel Cephalosporin with
Activity against Methicillin-resistant Staphylococcus aureus
Clinical Infectious Diseases 2011;52(9):1156–1163
MIC90 (µg/mL)
MIC90 (µg/mL). For GNB, has an activity similar to ceftriaxoneRemission rates with different oral antibiotic regimens in
staphylococcal prosthetic joint infections
Senneville CID Tornero IJAO
2011 N=98 (%) 2012 N=106 (%)
Surgical treatment: DAIR or Ex DAIR
Microorganims: S. aureus S. aureus & CoNS
Oral options*:
FQ+Rif 37/39 (94.8) 44/50 (88)
LNZ (+/-Rif) 9/11 (81.8) 26/32 (81)
others 31/48 (64.5) 22/28 (78.5)
v
* after 1 week of intravenous antibiotic with vancomycin and a ß-lactamViale P, et al. Treatment of pyogenic (non-tuberculous)
spondylodiscitis with tailored high-dose levofloxacin plus
rifampicin
Int J Antimicrob Agents 2009; 33: 379-82
Levo (750 mg/24h) + rifa 600 mg/24hZeller V, et al. Continuous Clindamycin Infusion, an
Innovative Approach to Treating Bone and Joint Infections
Antimicrob Agents Chemother 2010; 54: 88-92
Continuous infusion 30-40 mg/kg/24h (2-3 g/24h for 70 kg)
30-40%Ribera E, et al. Rifampin Reduces Concentrations of Trimethoprim
and Sulfamethoxazole in Serum in HIV-Infected Patients.
Antimicrob Agents Chemother 2001; 45: 3238-41
Serum concentration of trimethroprim
decreased 47% and sulfametoxazol 23%Gandelman K, et al. Unexpected Effect of Rifampin on the
Pharmacokinetics of Linezolid: In Silico and In Vitro
Approaches to Explain Its Mechanism.
J Clin Pharm 2011; 52: 229-236
Linezolid 600 mg Linezolid 600 mg +
Rifampicina 600 mgTornero E, et al. Importance of selection and duration of
antibiotic regimen in prosthetic joint infections treated with
debridement and implant retention
J Antimicrob Chemother 2016; 71:1395-1401
grampositives
Lev+Rif Lin+Rif LinPushkin R, et al. A Randomized Study Evaluating Oral Fusidic Acid (CEM-102)
in Combination with Oral Rifampin Compared with Standard of Care
Antibiotics for Treatment of Prosthetic Joint Infections: A Newly Identified
Drug-Drug Interaction. Clin Infect Dis 2016; 63: 1599-1604.
FA (1200-1500 mg/24) +
RIF (450 mg/12h) n= 7
Stopped RIF
2 failures
1 MRSA – RIF-R“planktonic” bacteria
bactericidal antibiotic (5-10 d)
• debridement + PE exchange
• C-RP < 10 mg/dL: cloxacillin / linezolid / daptomycin /ceftaroline
• C-RP ≥ 10 mg/dL: association of ≥2 atb (fosfomycin)
• Local antibiotics ?: gentamicin beads have been associated
with a worse outcome (Lowik C, et al. J Arthroplasty 2018)
“adapted” bacteria
anti-biofilm antibiotic (2-6 m)
• levofloxacin (500 mg/24h) + rifampin (600 mg/24h)
• cotrimoxazol, clindamycin, linezolid, minocycline? +/- rifampinCheng M, et al. Anti-cooperative ligand binding and dimerisation
in the glycopeptide antibiotic dalbavancin.
Org. Biomol. Chem 2014; 12: 2568
dalbavancin (derivative of teicoplanin)Mature PG
Trans-
peptidation
Trans-
GP (dalbavancin) glycosilation
Nascent PG
C55 PBP
MIC90 (mg/L) for MIC90 (mg/L) for
Antibiotic Staphylococcus spp Enterococcus spp
dalbavancin 0.06 0.06-0.12
vancomycin 2 2
daptomycin 0.5 2Dorr MB et al. Human pharmacokinetics and rationale for once-
weekly dosing of dalbavancin, a semi-synthetic glycopeptide
J Antimicrob Chemother 2005;55 (Suppl2):25-30
Renal adjustment:
300
- GF20 mg/L, PBS frente a SARM*
0
0 8 14 days
1000 mg (30’) 500 mg (30’)
1500 mg (30’) * Leighton, et al. AACh 2004Dunne MW, et al. Extended duration dosing and distribution
of dalbavancin into bone and articular tissue.
Antimicrob Agents Chemother 2015; 59:1849 –1855
1000 mg DLBRappo U, et al. Long-term outcomes of dalbavancin for the
treatment of osteomyelitis in adult patients.
28th ECCMID 2018, Madrid, Spain. Abst 697
* implant-associated infections were excludedRappo U, et al. Long-term outcomes of dalbavancin for the
treatment of osteomyelitis in adult patients.
28th ECCMID 2018, Madrid, Spain. Abst 697
1500 mg day 1
1500 mg day 7Rappo U, et al. Long-term outcomes of dalbavancin for the
treatment of osteomyelitis in adult patients.
28th ECCMID 2018, Madrid, Spain. Abst 697Barret L, et al. The clinical presentation of prosthetic joint
infection. J Antimicrob Chemother 2014; 69: suppl 1: i25-i27
debridement, antibiotic treatment and implant retention
(DAIR)Wouthuyzen-Bakker, M et al. Late acute prosthetic joint infections
treated with DAIR; outcome and risk factors for failure (ESGIAI).
340 patients (27 centers) Definition:
< 3 weeks of symptoms
> 3 months after the index surgery
a prior history of normal function
60%
% survival
45%
27%
Failure:
related death
Prosthesis removal
Suppressive therapyWouthuyzen-Bakker, M et al. Late acute prosthetic joint infections
treated with DAIR; outcome and risk factors for failure (ESGIAI).
Variables OR P-value
Fracture as indication for prosthesis 5.4 0.01
Rheumatoid arthritis 5.1 0.04
Chronic obstructive pulmonary disease 2.9 0.05
Age above 80 years 2.6 0.02
Male Gender 2.0 0.04
C-reactive protein > 150 mg/L 2.0 0.04
Exchange of mobile components 0.35 0.002
340 patients (27 centers)Wouthuyzen-Bakker, M et al. Late acute prosthetic joint infections
treated with DAIR; outcome and risk factors for failure (ESGIAI).
19
% failure
56
124
68 340 patients
18 (27 centers)Wouthuyzen-Bakker, M et al. Late acute prosthetic joint infections;
should the imlant be removed? (ESGIAI).
Implant removal (n=105)
75%
% survival
55%
Implant retention (n=340)
A propensity-matching score analysis (81:81)
confirm these results (48% vs. 74%, P=0.001) 445 patients
(27 centers)Wouthuyzen-Bakker, M et al. Late acute prosthetic joint infections;
should the imlant be removed? (ESGIAI).
Late acute PJI (n=395) % of FAILURE
CRIME80 ≥ 3 n=107 CRIME80 < 3 n=288
(retention 83% vs. removal 31%)
S. aureus (n=125) other (n=163)
(retention 45% (retention 29%
vs. removal 25%) vs. removal 23%)
No RA
PE exchange
CRPKunutsor SK, et al. One- and two-stage surgical revision of peri-
prosthetic joint infection of the hip: a pooled individual participant
data analysis of 44 cohort studies.
Eur J Epidemiol 2018; 97: 1368
Reinfection rates per 1000 person-years of
follow-up were 16.8 (95% CI 13.6–20.7) and
32.3 (95% CI 27.3–38.3) for 1-stage and 2-
stage strategies respectively.EUROPEAN BONE AND JOINT INFECTION SOCIETY 6-8 SEPTEMBER 2018 - HELSINKI, FINLAND The conference will be held in the white marble and granite faced Finlandia Hall. The congress venue is situated beautifully in a park near the sea in the centre of Helsinki, in the vicinity of several hotels- DEADLINES ABSTRACT SUBMISSION: 20 APRIL 2018 EARLY REGISTRATION: 1 JULY 2018 We look forward to welcoming you to Helsinki!
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