1. Andrea Guyot MD FRCPath MSc DTM&H DipHIC
Educational Workshops 2013
Bone and Joint Infections
Severe back pain after a fall
Andrea Guyot MD FRCPath MSc
DTM&H DipHIC

2. Presentation 78 y old female
Comorbidities: Type II diabetes, infrarenal AAA, on warfarin for FAF, CRF
In November 2010 leg ulcers infected with S. aureus and admission for cellulitis

3. Presentation
fall on back and admission with severe lower back pain and fever (T 38.9 C)
WBC 17, CRP 129

4. Which investigations are useful foR the diagnosis of discitis?

5. Facilitator Slide Diagnosis
90% ESR or CRP elevated
30% leukocytosis
60% Blood culture positive (5)
X-ray spine 30% sensitive
90% Bone scan with Gallium 67 scintigram spots
MRI 100% sensitive for bone marrow oedema (T1 dark and T2 signal bright)
MRI with gadolinium can distinguish degenerative Modic type 1 abnormalities and shows paravertebral abscesses

6. X-rays

7. Weeks 1-3
X-ray of lower spine was interpreted as scoliosis with degenerative changes
Blood culture - no growth
Tazocin was given for PUO from
UTI with enterococcus and cellulitis over toe ulcer
MRI for severe lower back pain, CRP 111, WBC 10

8. T1 T2
MRI interpreted as lumbar scoliosis with foraminal narrowing in L5/S1 and L2/L3 with impingement of roots. Incomplete canal stenosis at L2/L3 and T2 signals due to degenerative changes in endplates

9. Weeks 3-5
MRI interpreted as lumbar scoliosis with foraminal narrowing in L5/S1 and L2/L3 with impingement of roots. Incomplete canal stenosis at L2/L3 and T2 signals due to degenerative changes in endplates
Oral flucloxacillin from for cellulitis on foot
Still severe back pain and CRP 93 on 2.12.
Review of MRI concludes now possible discitis L2/L3

10. What is the differential radiological diagnosis of pyogenic discitis?

11. Facilitator Slide T1 and T2 weighed signal for bone marrow oedema in pyogenic spondylodiscitis

12. Facilitator Slide

13. Facilitator Slide Differential diagnosis: Modic 1 abnomalities

14. Facilitator Slide Osteochondrosis (Modic 1 abnormality)can mimic pyogenic spondylodiscitis

15. Facilitator Slide
Degenerative Modic type 1 abnormality = disruption of the endplate and vascularized fibrous tissue in the adjacent marrow cause hyperintensity in the endplate on T2-weighted images and enhancement after the administration of gadolinium, but often disc is not enhancing on T2 images
T1 T2

16. How can pyogenic discitis be confirmed?

17. Facilitator Slide CT guided biopsy
Sensitivity 50-77%
Repeat if negative
French guidelines for management of discitis suggest 6 biopsy samples for histology and culture (120)

18. Disc aspiration on

19. What are the common bacterial aetiological agents of spondylodiscitis?

20. Facilitator Slide Bacterial aetiology for haematogenous infections
Adults
Children
50% S. aureus
30% Coliforms
10% Streptococci (GBS)
<5% Candida
Brucella
MTb
80% S. aureus
10% Kingella
MTb
Bartonella henselae
Nocardia

21. Weeks 6-8 14.12.12 L2 disc aspirate grows S. aureus res: fusidic acid
sens: fluclox, ceftriaxone, teicoplanin, clindamycin, doxycycline, rifampicin

22. Which antibiotic regimen would you choose for this patient, who is not fit for home discharge?

23. Weeks 6-8
Flucloxacillin 2g 6hrly x 6-12 weeks or ceftriaxone 2g od as OPAT
Transfer to community hospital for rehabilitation on flucloxacillin iv via PICC line

24. What are the antibiotic concentrations in bone?

25. Facilitator Slide Which antibiotic bone concentrations are achieved?
Breakpoint MICs (BSAC)
Flucloxacillin
Clindamycin
Ceftriaxone
Teicoplanin
Levofloxacin
Ciprofloxacin
Rifampicin
Ertapenem
S. aureus
2mg/l
4mg/l
2 mg/l
1 mg/l
0.5 mg/l
0.12 mg/l
Strep. pyogenes
1mg/l
Data on serum/bone ratio from Penetration of Antibacterials into bone. Clin Pharmakokinetics 2009;48:89-124
Antibiotic
dose
serum peak
serum trough
serum/bone ratio
cancellous bone peak
bone trough
reference
Flucloxacillin
25mg/kg iv qds
125mg/l
10mg/l
0.16
20mg/kg
1.6mg/kg
Frank 1988
500mg po qds
15mg/l
2 mg/l
2.4mg/kg
0.34 mg/kg
Kropec 1979
Clindamycin
600 mg iv
12mg/l
1.4mg/l
0.3
3.4mg/kg
0.4mg/kg
Mueller 1999
450 mg po
8 mg/l
0.9 mg/l
3 mg/kg
0.3 mg/kg
Teicoplanin
10mg/kg iv/od
50mg/l
20mg/l
15 mg/kg
7 mg/l
Nehrer 1998
Ceftriaxone
25mg/kg iv od
250mg/l
0.15
5mg/l
Martin 1996
Ciprofloxacin
750mg bd
3.7 mg/l
0.6 mg/l
0.6
1.8mg/kg
0.1mg/l
Massias 1992
Ertapenem
1g iv od
155 mg/l
1mg/l
0.19
30mg/kg
0.2mg/l
Boselli 2007
Rifampicin
4 mg/kg po bd
4 mg/l
1.3mg/l
Sirot 1983

26. What are the CURE RATES?

27. Facilitator Slide Antibiotic trials on osteomyelitis
For S. aureus osteomyelitis in adults   
Antbiotic
Dose
Duration
Trial size
Trial type
OM type
Follow up period (m)
Cure rate
Adverse effect rate
Reference
Nafcillin iv
6 w 8
RCT 6m
87%
Norden 1983
Flucloxacillin iv
continous 11
cohort
15m
82%
Leder 1999
Flucloxacillin po
24w 14
17m
64%
2 hepatotoxic
Hodgkin 1975
Ceftriaxone
2g iv od 4w 50
haematogenous
27m
73.00%
Tice 2003
Flucloxacillin
2g iv qds 56
hamatogenous
72.00%
Vancomycin
1g bd iv
4 w
40%
Tice 2004
Teicoplanin
6-12mg/kg/d 6w 90 3m
90%
30% rash or neutropenia
Lefrock 1999, J In Chemo
Rifampicin +
ciprofloxacin
450mg bd
>3m 18
prosthetic joints
35m
100%
6/18 hepatotoxic
Zimmerli 1998
Ciprofloxacin
750mg bd
8 W 31 1y
77%
Gentry 1990
Clindamycin
30-50mg/kg/d 8w 29
 12m
Rodriguez 1977, AmJ Dis Child

28. Weeks 9-10
Transfer back to acute hospital on for hypokalaemia, CRP 40
On still back pain and CRP 22

29. how long would you give antbiotics for spondylodiscitis?

30. Facilitator Slide Antibiotic therapy
Antibiotics <4w has treatment failure of 40% and Antibiotics >4 w has treatment failure of 4% Sapico Rev Infect Dis 1979;1:754)
French guidelines suggest 6-12 weeks of antibiotics
After 10 d iv ABX oral switch possible to antibiotic with high bioavailability: clindamycin, quinolones, fusidic acid, rifampicin (Beronius, Scand J Inf Dis 2001; 33:527)

31. Facilitator Slide Antibiotics for discitis
High concentrations in discs for clindamycin, glycopeptides (teicoplanin at 10mg/kg)
Lower concentrations for beta-lactams
Monotherapy with flucloxacillin has recurrence of 20% and Combination therapy with flucloxacillin + fusidic acid has recurrence of 5%
First trials with daptomycin promising
Linezolid and tigecycline not licensed for osteomyelitis
Cure rate of linezolid 4/8 for vertebral osteomyelitis

32. WHICH MARKERS ARE USEFUL FOR MONITORING CURE?

33. Facilitator Slide Monitoring of Rx response
ESR should reduce by 50% within 4 weeks , otherwise treatment failure (108)
CRP reduces weekly by 50% and normalises after 3 months of treatment (132)
MRI changes worsen at 2-3 months in-spite of response
Fusion of vertebral bodies requires months

34. Facilitator Slide Diagnostic yield of follow up MRIs
At follow-up MR imaging, resolution of soft-tissue change and deposition of fat in the bone marrow are reliable signs of healing. Bone or disc changes may progress despite clinical improvement

36. Weeks 11-12
MRI reported as increased fluid in the intervertebral disc space L2/L3 and also in L1/L2, absence of psoas abscess and spinal stenosis. Worsening irregularity of vertebral endplates
Home discharge plan and change to ceftriaxone on
On unfit for discharge and change to iv flucloxacillin
On CRP and WBC rising, fever and hypotension

37. Week 13
On onset of diarrhoea: oral vancomycin started for CDI and iv gentamicin for sepsis
GDH positive and Vidas CD toxin equivocal
septic shock, AKI, unsuitable for ITU
End of life care pathway