Study proposes antibiotics as possible new treatment for some types of chronic low back pain
BMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f2988 (Published 09 May 2013) Cite this as: BMJ 2013;346:f2988
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Why does the BMJ editor let 'bacteria' become a singular noun throughout this otherwise interesting report? Is the medium indeed the message?
Competing interests: No competing interests
Whilst the findings of the studies referred to in this news article by Wise are fascinating, what caught my eye was the picture accompanying the article in the print version (18th May). Unless I'm grossly mistaken, the articles in question are not proposing antibiotics as treatment for C6/7 cervical spinal cord compression, which is what the MRI scan shows. Whilst of course the two conditions may co-exist in the degenerate spine, the sight of a cerebellum only a few vertebrae higher than the 'back pain' hotspot did somewhat alarm me.
Yours Sincerely
Dr Trevor Pickersgill
Competing interests: No competing interests
The double blind RCT carried out by Albert and colleagues found that long term antibiotic therapy was significantly more efficacious than placebo[1]. A significant association of anaerobic bacteria Propionibacterium acnes was found with modic changes. The entrapment of anaerobic bacteria is understandable but what can be the reason for the requirement of such a long term antibiotic therapy? Is the bacteria is able to colonize in that area and they are becoming more resistant? P. acnes infections are reported to be resistant to many antibiotics and the continued treatment with antibiotics is reported to be in appropriate[2]. P. acnes is capable of forming biofilms both in vitro and in vivo. Therefore the involvement of sessile P. acnes cells in modic changes has to be studied before going for the mentioned antibiotic therapy.
References
1. Albert HB, Sorensen JS, Christensen BS, Manniche C. 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. European Spine Journal 2013:1-11
2. Cooper AJ. Systematic review of Propionibacterium acnes resistance to systemic antibiotics. The Medical Journal of Australia 1998;169(5):259
Competing interests: No competing interests
This study interesting as it seems raises a lot of questions;
A. Is modic change a stage in infective osteomyelitis or a non-specific response to mechanical stresses irrespective of causality.
B. If it is infective osteomyelitis, does propionibacter have exclusive eatiologic role or any other bacteria could be just as responsible in an unselected population
C. Is the role of propionibacter in this case related exclusively to its production of propionic acid and nerve root irritation or to broader range of infective inflammatory players/mediators.
D. If propionic acid is the causative mechanism for neuralgic symptons/signs, could there a role for chemical targeting of the acid other than use of antibiotics for this length of time.
E. Inspite of the association, to what extent is propionibacter an innocent bystander in a crime scene in which other 'hidden' or ignored players could be more culpable.
F. To what extent can modic change as described in this account be either a self limiting condition or one that could ameliorate with mere rest or reduction in physical activity whether or not antibiotics are deployed.
G. What was used in the study as outcome measure:
1 de-symptomatisation
2. Bacterial clearance
3. MRI changes
4 others
H. It would seem if propionibacter turns out to be the pathologic agent here rather than incidental bystander/associate, the clinical condition seems one of auto-infection from a skin commensal. How often is such an auto infective process to be expected in the general population, the subset of discopaths or the subsets of spondylitics or thesubset of herniations.
I. As an auto infective condition, what is the role of immune compromise as a facilitator in this case.
J. What about recurrence and what will be the antibiotic policy for recurrence
K.
1 the pathogenetic sequence seems to be explained as disc herniation, then neovascularisation, then haematogenous bacterial ingress, then symptoms.
2 Is a different pathogenetic sequence plausible; haematogenous bacterial localisation in the osseo-discal region/ annulus, inflammatory softening of osseo- discal intertace,or discal material, osseo- discal slip/disc rupture and clinical syndromes.
L. In the original trial of antibiotic vs placebo, would a third arm of mere rest(without intervention otherwise) have shed any light.
Competing interests: No competing interests
Re: Study proposes antibiotics as possible new treatment for some types of chronic low back pain
The study is an attempt to try an address a common problem with a new angle. It succeeds in raising more questions than answers and provides a good platform for a trial to take this research further. The balance of treatment must be considered in light of widespread abuse of broad-spectrum antibiotics and multi drug resistance amongst pathogens.
Specific ambiguities relevant to the paper are as follows:
• The explanation for the improvement is given as “treatment” of Proprionibacterium infection, even though neither the diagnosis, nor the treatment is confirmed by any cultures.
• In studies involving pain medicines, there is normally a placebo response of 20% - 30 %(Pollo, Martina, Arslanian, & Casadio, 2001). In the present study, there is no improvement in placebo group in any parameters over one year. This is a very unusual. If the placebo response in this study was similar to what is usually expected, than the treatment effect is unlikely to be significant.
• 1 in 5 patients had gastrointestinal side effects that were labelled as “mild”. There needs to be an estimate of the “numbers needed to treat” versus “numbers needed to harm” for such an intervention before it is put into practice.
• The study hypothesis relies on previous studies that indicate the presence of Proprionibacterium in cultures of discs taken out during surgery, which had adjacent modic changes. There is every chance of introduction of skin commensals like Proprionibacterium in the discs as these patients are exposed to procedures like discographies and transforaminal epidurals, which would not be the case in discs cultured from scoliosis surgery patients.
• A Study by Keeler et al (Keeler, Boyle, Skogg, & Kassidy, 2012) showed Modic type 2 changes to be most common amongst back pain patients and that Modic changes were not significant covariates for the clinical course of pain, function or fear avoidance beliefs. Education was a strong prognostic factor for recovery.
• The present study protocol advised participants not to engage in active exercise programme for the duration of trial. This is contrary to the usual management strategies in uncomplicated low back pain (Samanta & Kendall, 2003).
It is imperative that balance of treatment must be considered in light of widespread abuse of broad-spectrum antibiotics and multi drug resistance amongst pathogens.
It is perhaps also worth mentioning that the authors have offered to train the individuals in this treatment (called MAST) by charging between £100 - £200 for online accreditation.
References:
Keeler, A., Boyle, E., Skogg, T. A., & Kassidy, D. J. (2012). Are Modic changes prognostic for recovery in a cohort of patients with non-specific low back pain? Eur Spine J , 21, 418–424.
Pollo, A., Martina, A., Arslanian, A., & Casadio, C. (2001). Response expectancies in placebo analgesia and their clinical relevance. Pain , 93, 77 - 84.
Samanta, J., & Kendall, J. (2003). Chronic low back pain. BMJ , 326, 535.
Competing interests: No competing interests