Session 5: Tumor, Infection and amputation
16. November
11:00 - 12:00
Lokale: Vingsal 2
Chair: Christina E. Holm and Christen Ravn
37. Rifampicin does not reduce moxifloxacin concentrations at the site of infection or improve treatment outcome of a one-stage exchange surgery protocol of implant-associated osteomyelitis lesions in a porcine model
Sofus Vittrup, Louise Kruse Jensen, Pelle Hanberg, Josefine Slater, Magnus Hvistendahl, Maiken Stilling, Nis Pedersen Jørgensen, Mats Bue
Department of Clinical Medicine, Aarhus University; Aarhus Denmark
Microdialysis Research (ADMIRE), Orthopedic Research Laboratory, Aarhus
University Hospital; Department of Orthopedic Surgery, Aarhus University
Hospital; Department of Infectious Diseases, Aarhus University Hospital;
Department of Veterinary and Animal Sciences, University of Copenhagen
Background: Rifampicin has for many years been considered
a cornerstone in implant-associated
osteomyelitis (IAO) treatment.
Aim: We conducted a randomised, one-stage
exchange surgery protocol with either one-week
treatment with moxifloxacin alone or co-
administered with rifampicin in IAO porcine
model to evaluate steady-state moxifloxacin
concentrations in infected bone and soft tissue
assess and the additive microbiological
treatment effect of rifampicin.
Materials and Methods: 16 female pigs were included. On day 0, IAO
was induced creating an implant cavity in the
right proximal tibia using a moxifloxacin and
rifampicin susceptible porcine Staphylococcus
aureus strain. On day 7, the pigs underwent
one-stage exchange surgery of IAO lesions and
were randomly allocated to receive seven days
of intravenous antibiotic treatment of either
rifampicin 450 mg twice daily combined with
moxifloxacin 400 mg once daily (Group RM) or
moxifloxacin 400 mg once daily (Group M).
Steady state concentrations were presumed for
both drugs after seven days. On day 14,
microdialysis was applied for continuous
sampling of moxifloxacin concentrations during
8 h in five compartments: the implant cavity,
cancellous bone in both the right (infected) and
left (non-infected) proximal tibia, and adjacent
subcutaneous tissue on both the right (infected)
and left (non-infected) side. Venous blood
samples were collected for reference.
Microbiological analyses were performed post-
mortem.
Results: Moxifloxacin AUC was lower in plasma in group
RM, (mean;95% CI) 407; 315–499 min µg/mL vs
Group M, 625; 536–724 min µg/mL (p=0.002).
For the implant cavity, there was a trend toward
a lower AUC in Group RM, 425; 327–524 min
µg/ml vs Group M, 297; 205–389 min µg/ml, but
not statistically different (p=0.06). For the other
compartments, the remaining calculated
pharmacokinetic parameters were similar
between the groups. Comparable cure rates
(sterilization of both implant and bone) were
observed with 5/8 pigs in Group RM compared
to 3/7 in Group M (p=0.62).
Interpretation / Conclusion: While moxifloxacin AUC was lower in plasma for
animals co-treated with rifampicin, both the
moxifloxacin concentrations at the site of
infection and treatment outcomes were
comparable between groups.
38. Piperacillin Bone Concentrations - a randomized porcine study comparing continuous infusion vs. short-term infusion
Hans Christian Rasmussen¹, Mats Bue¹, Andrea Jørgensen³, Pelle Hanberg4, Sara Tøstesen5, Martin Knudsen6, Maiken Stilling7
Department of Orthopaedic Surgery, Aarhus University Hospital ² 7
Orthopaedic Research Unit, Aarhus University Hospital ¹ ² ³ 4 5 6 7
Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital 4
Background: Osteoarticular infections caused by
Pseudomonas aeruginosa have seen an
increase in recent years. A central antimicrobial
choice in the treatment of pseudomonal
orthopaedic infections is piperacillin. Studies
have indicated higher cure rate of pseudomonal
infections with continuous infusion (CI) of
piperacillin compared to intermitted short-term
infusion (STI). However, due to practical reasons
STI is still commonly used.
Aim: The aim was to assess time above the minimal
inhibitory free concentration (f(T>MIC)) for
piperacillin at steady state in tibial cortical bone,
cancellous bone, the knee joint, and subcutaneous
tissue following STI and CI using microdialysis in a
porcine model.
Materials and Methods: 16 female Danish landrace pigs were randomized to
either CI or STI of piperacillin/ tazobactam. Group
STI received a bolus of 4g/0.5g every 6h and Group
CI received 16g/2g daily. Microdialysis catheters
were placed for sampling in the tibial cortical bone,
cancellous bone, the knee joint, and subcutaneous
tissue. Steady state was assumed at 12h and data
collection of dialysates and blood samples preceded
for the following 6h. The piperacillin f(T>MIC) was
evaluated at MIC targets of 4 µg/mL, 8 µg/mL and
16 µg/mL.
Results: At steady state, with exclusion of cortical bone, CI
resulted in a mean f(T>MIC) (4 µg/mL) target
attainment of =99% across all compartments
compared to =67% for group STI. Similar results
were found for targets of 8 µg/mL (=93%, =53%) and
16 µg/mL (=64%, =35%). Mean f(T>MIC) in cortical
bone was generally lower in group CI compared to
group STI for all targets, but only statistically
significant for the 8 µg/mL target (p=0.049).
Interpretation / Conclusion: For all tissue targets, except cortical bone, CI
administration resulted in higher steady state
piperacillin concentrations compared to STI
administration. To obtain sufficient piperacillin
concentrations in cortical bone, higher or more
frequent dosing is needed.
39. Surgical offloading procedures for patients with non-healing diabetic foot ulcers. A National Clinical Guideline
Tue Smith Jørgensen
Department of Orthopedics, Amager and Hvidovre University Hospital
Background: Patients with diabetes have a higher risk of
developing a foot deformity or malposition in the
foot due to bone collapse, neuropathy, tendon
contracture and insufficient muscle strength.
Deformities and misalignments can result in an
increased local pressure load on the foot, and
significantly increased risk of developing a
diabetic foot ulcer. To promote wound healing, it
is essential to offload the wound with insoles,
footwear or a offloading bandage. If the external
offloading (standard treatment) does not have an
effect, or the misalignment of the foot and toes is
too extensive, offloading surgery may be
appropriate.
Aim: To review the litterature on surgical offloading
procedures for patients with foot or toe malalignment
and non-healing diabetic foot ulcers.
Materials and Methods: The study is a systematic review and metaanalysis,
and the systematic litterature search was performed
the 31. Of january 2020. The evidens consists of
three randomised clinical trials (4 publications), one
non randomised controlled trial and 4 case control
studies. The intervention in the studies consisted of
achilles tendon lengthening or metatarsal osteotomy.
Patients in the control groups were treated with a
non-removable cast or a specially made foot
orthosis.
Results: Nine out of 63 patients in the surgical offloading
group had a recurrent ulcer compared with 29 out of
60 patients who received standard wound care. The
meta-analysis showed a lower risk of recurrence of
wounds in patients who received offloading surgery,
the relative risk was 0.30 (95% CI: 0.15, 0.58). None
of the 52 patients in the group who received surgical
offloading had a lower extremity amputation,
whereas 2 out of 53 patients had an amputation in
the group that received standard wound treatment.
The meta-analysis showed a relative risk of 0.34
(95% CI: 0.04, 3.12)
Interpretation / Conclusion: Clinicians should consider surgical offloading with
achilles tendon lengthening or metatarsal osteotomy
in patients with foot or toe malalignment and non-
healing diabetic foot ulcers.
40. Role of Sonication in Diagnosis of Orthopaedic Implant Associated Infections
Diana Salomi Ponraj¹, Thomas Falstie-Jensen², Nis Pedersen Jørgensen³ , Christen Ravn², Holger Brüggemann4, Jeppe Lange ¹,5
Department of Clinical Medicine, Aarhus University¹; Department of Orthopaedic
surgery, Aarhus University Hospital²; Department of Infectious diseases, Aarhus
University Hospital³; Department of Biomedicine, Aarhus University4; Department
of Orthopaedic surgery, Horsens Regional Hospital5
Background: Orthopaedic implant associated infections
(OIAI) have high morbidity and mortality. In
addition to aerobic bacteria like
Staphylococcus aureus, slow growing Gram-
positive anaerobic bacteria (SGAB) like
Cutibacterium acnes are increasingly
associated with OIAI. SGAB infections are
difficult to diagnose because of their
prolonged cultivation times as well as non-
specific clinical, laboratory and radiologic
features. Sonication of implants can help in
the diagnosis of SGAB infections.
Aim: To identify the different bacteria, especially
SGAB, isolated from sonication fluid of
orthopaedic implants removed during revision
surgeries.
Materials and Methods: Between August 2019 and September 2020,
100 implants that were removed during
revision surgery at the Department of
Orthopaedic surgery, Aarhus university
hospital were collected and processed by the
vortex-sonication method. The resultant
sonication fluid (SF) was cultured aerobically
and anaerobically. All isolated bacteria were
identified by 16S rRNA sequencing. Bacterial
growth >50 or >200 CFU/ml of uncentrifuged
or centrifuged SF respectively was
considered significant. In case of C. acnes,
significance of the isolates was based on
whole genome sequencing and amplicon
based next generation sequencing. Relevant
clinical details including tissue culture results
were obtained from patients’ records.
Results: SF from 21 implants showed significant bacterial
growth. Only 11 of these implants had a prior
diagnosis or suspicion of infection. C. acnes
(n=8), S. aureus (n=4) and Staphylococcus
epidermidis (n=2) were the most commonly
isolated bacteria. Tissue culture were either not
sent or had no bacterial growth in 33% (7/21) of
implants.
Interpretation / Conclusion: Routine sonication of orthopaedic implants
removed during revision surgeries can help to
identify cases of OIAI that might otherwise be
overlooked.
41. Hip Joint Stability After Hip Replacement Surgery due to Metastatic Bone Disease - A retrospective cohort study evaluating different hip joint options
Afrim Iljazi¹, Michala Skovlund Sørensen¹, Thea Hovgaard Ladegaard, Michael Mørk Petersen¹
¹Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet,
Denmark
Background: Joint stability after hip replacement in patients
with metastatic bone disease (MBD) is of special
importance. Dislocation is the second leading
cause of all-time implant revision. Expected
survival after surgery among these patients is
very poor, why avoidance of hospital re-
admissions has a significant impact on end-of-life
quality. Selecting the right joint solution is
therefore paramount. Few studies have
investigated the dislocation rate across different
hip joint options in MBD patients. We therefore
conducted a retrospective study on primary hip
replacements for patients with MBD conducted at
Rigshospitalet.
Aim: To evaluate the 1-year post-operative joint
dislocation rate by type of hip joint.
Materials and Methods: We included patients =18 years with MBD who
received hemiarthroplasty (HA), regular total hip
arthroplasty (THA) or THA with a constrained
liner (CL) at Rigshospitalet in 2014-2020. We
excluded patients with dual mobility joints, partial
pelvic reconstruction, total femoral replacement
and endoprosthesis revision surgeries. Risk of
dislocation was assessed by competing risk
analysis (cumulative incidence function) with
death and implant removal as competing risks.
Only the first surgery was included in the
analysis in case of bilateral surgery. The Kaplan-
Meier estimator was used to assess the
probability of survival.
Results: We identified 266 patients who received 277 joint
replacements. Mean age was 68(SD:11) years.
Median follow-up was 176(IQR: 54-503) days. The
patients were treated with 101(36%) HA, 88(32%)
THA and 88(32%) CL. Major bone resection (MBR)
was performed in 75% of THAs, 64% of CLs and
55% of HAs. The 1-year patient survival was 44%
(CI-95: 33-55) for THA, 29% (CI-95: 20-38) for HA
and 38% (CI-95: 27-48) for CL. The 1-year
dislocation risk was 8% (CI-95: 2-14) for THA, 5%
(CI-95: 1-10) for HA and 6% (CI-95: 1-11) for CL
(p=0.19). The 1-year dislocation rate by MBR was
5% (CI-95: 1-10) for non-resection and 7% (3-11) for
resection (p=0.33).
Interpretation / Conclusion: Our study suggests a higher tendency for dislocation
in THA. However, the finding was not statistically
significant. Interpretation might be confounded by
MBR and lower survival for HA. Further studies are
needed.
42. Solitary vs. Multiple Bone Metastases in The Extremities: Are There Any Differences?
Thea Hovgaard Ladegaard, Michala Skovlund Sørensen, Michael Mørk Petersen
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet,
University of Copenhagen
Background: Patients with solitary metastatic bone disease in
the extremities (MBDex) is believed to have
better survival than patients with multiple MBDex.
Metastasectomy is known to improve patient
survival for renal cell cancer and maybe breast
cancer in selected cohorts.
Aim: To evaluate 1-year survival for metastasectomy
in patients treated surgically for MBDex.
Materials and Methods: We conducted a retrospective study including all
MBDex-lesions treated surgically at orthopedic
departments in the Capital Region (CR) 2014-
2016. We excluded patients with unknown status
of bone metastases and unknown resection
margin. Patients were followed until end of study
(30 September 2021) or death. Kaplan-Meier
analysis (with log-rank test) evaluated patient
survival.
Results: We identified 506 MBDex-surgeries (459
patients), 22 surgeries were revisions. 122
surgeries (118 patients) were oligo metastatic
and 384 surgeries (343 patients) were known
with multiple metastases. Of the 122
surgeries, 72 surgeries (71 patients) had
no/unknown status of visceral metastases
(solitary-group) and 50 surgeries had visceral
metastases. In the solitary-group, 44
surgeries had wide resection (44
patients).The most common primary cancer in
this group was renal (15) and breast (9). 24
patients in the group had intralesional
resection (24 patients). The most common
primary cancer in this group was breast (6),
lung (5), lymphoma (5) and myelomatosis (5).
The 1-year patient survival was 48% (CI-95:
40-58) for the oligo MBDex and 34% (CI-95:
29-38) for the multiple MBDex (p<0.001). The
1-year patient survival was 65% (CI-95: 55-
77) for solitary MBDex without/unknown
visceral metastases and 23% (CI-95: 14-39)
for solitary MBDex with visceral metastases
(p<0.001). The 1-year patients survival was
75% (CI-95: 63-89) for the solitary-group with
wide resection and 42% (95% CI: 26-67) for
the solitary-group with intralesional resection
(p<0.001).
Interpretation / Conclusion: Our study suggests that aggressive treatment of
solitary MBDex-lesions with wide resection
improve patient survival regardless of primary
tumor. Further, surgical treatment of patients with
oligo metastatic disease results in better 1-year
survival than patients with multiple metastatic
disease.
43. Surgical treatment of metastatic bone disease in the extremities: a population-based epidemiologic study
Thea Hovgaard Ladegaard¹, Celine Sørensen¹, Rasmus Nielsen², Anders Troelsen³, Dhergam AA. Al-Mousawi4, Rikke Bielefeldt5, Michael Mørk Petersen¹, Michala Skovlund Sørensen¹
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet,
University of Copenhagen¹; Department of Orthopedic Surgery, Herlev and Gentofte
Hospital²; Department of Orthopedic Surgery, Amager and Hvidovre Hospital³;
Department of Orthopedic Surgery, Nordsjællands Hospital4; Department of Orthopedic
Surgery, Frederiksberg and Bispebjerg Hospital5
Background: Population-based studies of patients with metastatic
bone disease in the extremities (MBDex) requiring
surgery for complete or impending fracture is
meagerly known.
Aim: We sought to determine possible time-related
changes of the incidence of MBDex-surgery and
examine differences between patients treated at
different centers in a population-based cohort.
Materials and Methods: We examined a population-based cohort consisting
of all MBDex patients treated in the Capital Region
(CR) 2014–2019. Procedures were performed at 5
secondary surgical centers (SSC) or 1 tertiary
referral Musculoskeletal Tumor Center (MTC).
Patients were followed until end of study (Sep 30
2021) or death. No patients were lost to follow-up.
Logistic regression was used to describe
associations. Kaplan-Meier analysis was used for
survival analysis.
Results: Four-hundred-fifty-seven patients (493 primary
MBDex lesions, 482 procedures) were included.
Annual incidence of MBDex-surgery was 46
MBDex lesions/million inhabitants/year. MTC-
patients had a significant better preoperative
status than SSC-patients considering factors
known for survival. Patients with complete
fracture experienced longer surgical delay when
treated at MTC compared to SSC: 4 (1-9) and 1
(1-3) days (p<0.001), respectively. Overall
survival for the entire cohort was 37% and 11%
at 1 and 5 years (MTC and SSC 1- and 5-year
respectively: 44% and 15% vs. 29% and 5%,
p<0.001). In patients with debut or relapse of
cancer, 8% and 9% had insufficient biopsies, and
21% and 12% had no biopsy, respectively. The
majority of patients with insufficient/no biopsies
were treated at SSC. Comparison showed no
change over time.
Interpretation / Conclusion: Current study highlights the low awareness on
treating MBDex at SSC and emphasizes the
importance of caution in interpretation of studies
not representing an entire population thus
introducing selection bias. A need for more
awareness of atypical fractures, concern of MBD
and securing proper biopsies for
histopathological examinations is essential,
especially at SSC, since the majority of lesions
without any biopsy were found here. Biopsies are
valuable to exclude a second malignancy and as
material for targeted oncological treatment
postoperatively.