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Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial

BMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l5654 (Published 16 October 2019) Cite this as: BMJ 2019;367:l5654

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Re: Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial

We strongly support the notion that antibiotics should be prescribed carefully, especially in potentially non-infective conditions and therefore welcome trials which attempt to provide more robust evidence about their use in areas of clinical uncertainty. As a group of infectious diseases specialists, we would like to mention some additional points.

The authors mention in their hypothesis that signal changes in the vertebral bone marrow in a subgroup of patients with chronic lower back pain – Modic changes – may be caused by low grade bacterial discitis from Cutibacterium acnes. This bacterium is generally susceptible to a range of antibiotics. Amoxicillin is associated with Clostridioides difficile infection as well as the development of antibiotic resistant genes in the gut microbiome.(1) In acne vulgaris caused by the same bacteria for example, first line treatment is usually with doxycycline or lymecycline, which are less associated with the development of C. difficile infections.(2) Additionally, doxycycline also has well known anti-inflammatory effects and is often prescribed for other chronic inflammatory conditions such as bronchiectasis and inflammatory dermatoses.

In this study, amoxicillin was required to be taken three times a day for 3 months, which will have been significantly challenging for patients to adhere to, which was identified in 15 participants (supplementary data) although this number can be expected to be higher given the limitations of self-reporting of compliance to treatment. Other antimicrobials, including doxycycline and lymecycline, allow for less frequent dosing, which can potentially improve adherence to therapy. We consider, therefore, that amoxicillin may not, for all these reasons, have been the ideal antibiotic to select.

Future studies should first focus on acquiring more evidence of the nature of the relationship between C.acnes and chronic lower back pain. The literature so far suggests that C acnes are present in discs with Modic changes, suggesting that they are colonisers at most.(3) There may also have been a missed opportunity to compare antimicrobial therapy to current gold standard care which is a combination of exercise therapy in addition to analgesia.

We continue to advocate an approach whereby clinicians should make every effort to confirm the presence of C acnes first, through microbiological culture, with corroborative histology, before commencing antibiotics. In real world clinical practise, blind treatment may delay the diagnosis of other conditions presenting in an indolent fashion, such as tuberculosis/brucella discitis or even malignancy, which would require entirely different management approaches. We therefore call for a more systematic approach for future studies that investigate the use of antimicrobials for non-infective indications, including compulsory microbiological sampling and perhaps even monitoring of the gut microbiome.

References
(1) Zaura et al. Same exposure but two radically different responses to antibiotics: resilience of the salivary microbiome versus long-term microbial shifts in feces. mBio Nov 2015, 6(6). e01693-15; DOI: 10.1128/mBio.01693-15
(2) Tariq et al. Low risk of primary Clostridium difficile infection with tetracyclines: a systematic review and meta-analysis. Clin. Infect Dis. 2018 Feb 1;66(4):514-522. doi: 10.1093/cid/cix833
(3) Urqygart et al. Could low grade bacterial infection contribute to low back pain? A systematic review. BMC Med. BMC Med. 2015 Jan 22;13:13. DOI: 10.1186/s12916-015-0267.

Competing interests: No competing interests

29 October 2019
Daniel K Pan
NIHR Academic Clinical Fellow in Infectious Diseases
Ryan Hamilton, Thomas C. Morris, Helena White
Department of Respiratory Sciences
College of Life Sciences, University Rd, University of Leicester, Leicester LE1 7RH