Transcript 11.30-5-P-acnes-Discitis

BRITSPINE DEBATE
Should antibiotics be given for back pain?
Propionibacter acnes related discitis –
proposals for further investigations
Jeremy Fairbank
Modic change and infection
Albert H, Lambert P, Rollason J, Sorensen J, Worthington T, Pedersen M, et al.
Does nuclear tissue infected with bacteria following disc herniations lead to Modic changes in the
adjacent vertebrae?
European Spine Journal. 2013 Apr;22(4):690-6
• In this study, 46 % of the 61 patients with a lumbar disc
herniation were found to have microorganisms present in
extruded nuclear tissue. The microorganism most
frequently cultured was the anaerobic bacterium, P. acnes.
• The discs from which anaerobic bacteria were isolated
were statistically significant (P= 0.0038) more likely to
develop MC than those in which no bacteria or aerobic
bacteria were detected.
• The findings of this study could be interpreted as a support
to the theory that the occurrence of Modic Changes (MCs)
Type 1 in the vertebrae adjacent to the previously
herniated disc might the reactive oedema surrounding an
infected disc.
Modic changes and back pain
•
Modic changes (MCs) are signal changes in the vertebral
bodies adjacent to discs – attributed to bone oedema in
vertebrae and commonly observed and associated with low
back pain
– Jensen TS, Karppinen J, Sorensen JS, Niinima¨ki J, Leboeuf-Yde C (2008)
Prevalence of vertebral endplate signal changes and their association with
non-specific low back pain - A systematic literature review. Eur Spine J
17:1407–1422
– Albert HB, Manniche C (2007) Modic changes following lumbar disc
herniation. Eur Spine 16:977–982
• Jensen et al systematic review -MC prevelance in patients
with CLBP was 46 % as opposed to 6 % in the general
population
• A positive association between MC and non-specific LBP was
found in 70 % of studies with odds ratios ranging from 2.0 to
19.9
Modic changes and back pain
BUT…
• Peul et al 379 disc prolapse patients
considered for RCT reported in 2008 found
severe back pain at baseline predictive of poor
outcome. However they could not link this
with MC seen in ~40% cases (submitted for
publication)
• so we should consider possibility the MC is
not absolute biomarker…
100 days Co-amoxyclav vs placebo
Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes):
a double-blind randomized clinical controlled trial of efficacy
Hanne B. Albert • Joan S. Sorensen • Berit Schiott Christensen • Claus Manniche
Eur Spine J 2013; 22:690–696. DOI 10.1007/s00586-013-2675-y
• Problems concerning Albert et al trial:
– Very high treatment effect vs no benefit at all in placebo arm
– Arguments about placebo masking (patients can detect whether or
not they are receiving antibiotics)
– Probably underpowered as 2 different antibiotic doses tested
– No evidence of culture positive infection at baseline – so a Koch
postulate not fulfilled
– Is this optimum antibiotic regime – should we focus on P. acnes or
other microflora as well?
– Precisely equal numbers in each group weakens case for complete
blinding
– No description of skin prep regime of culture from wound edges
– COI over potential income from MAST
Koch's postulates
1.
2.
3.
4.
•
The microorganism must be found in abundance in all organisms
suffering from the disease, but should not be found in healthy
organisms. (fails for asymptomatic carriers)
The microorganism must be isolated from a diseased organism
and grown in pure culture. (Fails if no known means of culturing
organisms eg Prions)
The cultured microorganism should cause disease when
introduced into a healthy organism. (fails since injection does not
necessarily precipitate infection)
The microorganism must be re-isolated from the inoculated,
diseased experimental host and identified as being identical to the
original specific causative agent.
In summary, a body of evidence that satisfies Koch's postulates is
sufficient but not necessary to establish causation.
Power calculation to repeat Danish study
• …we will include a 20%
inflation for loss to follow up,
rendering a final sample size
of 462.
100 days of antibiotics
• OK if we are treating discitis
• Not so OK if are treating unconfirmed
infection
• Many public health/safety issues attending
extended courses of antibiotic
History
Positive cultures from discectomy specimens 2001
•
Stirling A, Worthington T, Rafiq M, Lambert P, Elliott T. Association between sciatica and
Propionibacterium acnes. Lancet. 2001;357(9273):2024-5.
– nuclear tissue removed under strict sterile conditions during surgery for lumbar
herniated discs, to be infected with low virulent anaerobic organisms
(Proprionibacterium acnes and Corynebacterium propinquum ) in 53 % of the patients
• Replicated by others
– Stirling et al. 2002
• 207 patients with lumbar disc herniation and 27 patients with other spinal disorders such
as scoliosis, fracture and tumors, all patients had nucleus material removed. In 37 % of
the patients with lumbar disc herniation bacteria were identified, mainly P. acnes .
Conversely, no (0 %) bacteria were found in the extracted nuclear material in the group
with other spinal disorders.
– Corsia et al. 2003
• 30 lumbar disc herniations: 71 % were infected, 36 % with Staphylococcus and 18 % with
P. acnes ; and in 30 cervical disc herniations they found 59 % were infected, 37 % with P.
acnes .
– Agarwal et al. 2010
• cultured material from 52 patients, 10 (19 %) of them were infected and in 7 (70 %) of
those, P. acnes was the sole organism isolated.
Vote NO!
• Should antibiotics be given for back pain?
• Not yet!
– We need proper replicatory trials
– We need a different trial design to establish
causation (Koch #2)
• NIHR have rejected well-written applications
x2 – want more evidence of +ve culture
– HTA
– EME